Orgo Exam 3

what are: alkyl halide, hydroxy group, mercapto group/sulfhydryl group, ethers, and sulfides, and alpha-carbon

- Alkyl halide: halogen is bound to the C of an alkyl group - Hydroxy group: -OH, bound to C of an alkyl group makes an alcohol - Mercapto group/sulfhydryl group: (-SH), bound to C of alkyl group makes a thiol (mercaptan) - Thio: "sulfur in place of oxygen" - thiol is alcohol in which S replaces O Alpha-carbon: C bonded to the halogen in an alkyl halide, or the O in an alcohol or ether - Alkyl halides and alcohols are classified by the # of alkyl groups attached to the alpha-carbon

what are the classifications for bi/polycyclic compounds and how does the nomenclature work

- Bicyclic compound: 2 rings share 2+ common atoms - Spirocyclic compound: 2 rings have a single common atom - Polycyclic compounds: contain many rings joined at common atoms. Some have shapes of regular geometric solids: docane, tetrahedrane, etc. - Bridgehead C's: atoms at which 2 rings are joined in bicyclic compound - Fused bicyclic compound: when bridgehead C's are adj - Bridged bicyclic compound: When bridgehead C's are not adjacent Example of nomenclature: - Bicyclo[3.2.1]octane: bicyclic compound, has 8 C's. #'s in brackets represent the # of C atoms in the respective bridges, in order of decreasing size. - Start numbering at bridge C. When you number C's, go from larger bridge to smaller bridge. Must say if substituents are R or S, NOT just say cis/trans for ring But SPIRO goes from small to large!!! [4.5] And start numbering ADJACENT to the bridgehead C. Seems like u can choose which way you go on the second ring based on functional group priority. (Priest wants you to number C's on ring to make it easier for TAs to see) (Note you HAVE to put 0 at the end of brackets if there's only 2 on either side of bridge)

what's in common b/w dehydration and rxns of alcohols w/ hydrogen halides

- Both take place in very acidic solution; in both rxns, the acid converts the -OH group into a good LG - For substitution rxns, if acid were not present, the halide ion would have to displace -OH to form the alkyl halide. This doesn't take place because -OH is a much stronger base than any halide ion, and strong bases are poor LG. - Remember: substitution and elimination rxns of alcohols require the -OH group to be converted into a better LG! - Formation of secondary and tertiary alkyl halides and the dehydration of secondary and tertiary alcohols have the same initial steps: protonation of the alcohol O and formation of a carbocation - They differ in the fate of this carbocation, governed by conditions of the rxn. In presence of hydrogen halide, halide ion is present in excess and reacts w/ carbocation. In dehydration, no halide ion is present, and when the alkene forms by loss of a beta-proton from the carbocation, the conditions of the dehydration rxn force the removal of the alkene product and the water by-product from the rxn mixture. - So, alkyl halide formation and dehydration to alkenes are alternative branches of a common mechanism.

fun priest notes

- More step reaction are more likely than fewer step reactions - bc things have to come together at the very same time - Ketone is not a stereocenter bc O means there's no way it can be switched to make a diff enantiomer

what is bredt's rule

- Trans-cyclooctene is the smallest trans-cycloalkene that can be isolated under ordinary conditions. However, is less stable than its cis isomer - Closely related: instability of any small bridged bicyclic compound that has a double bond at a bridgehead atom. Bredt's rule: In a bicyclic compound, a bridgehead atom contained solely within small rings cannot be part of a double bond. (Small ring: 7 or fewer atoms) - Basis: double bonds at bridgehead C's within small rings are twisted - CANNOT lie in the same plane. (but priest said someone made it lol) - But those with larger rings are more stable and can be isolated

summary of conversion of alcohols into alkyl halides

1. Rxn with hydrogen halides 2. Formation of sulfonate esters followed by Sn2 rxn with halide ions 3. Rxn with thionyl chloride or triphenylphosphine dibromide Method depends on alcohol structure and type of alkyl halide to be prepared. Primary alcohols: - Alkyl bromides are prepared from primary alcohols by the rxn of the alcohol with concentrated HBr or with Ph3PBr2. HBr often chosen for convenience. Rxn with Ph3PBr2 is quite general, but is particularly useful when alcohol contains another functional group that would be adversely affected by the strongly acidic conditions of the HBr rxn. - Primary alkyl iodides can be prepared with HI, which is usually supplied by mixing an iodide salt such as KI with a strong acid such as phosphoric acid. - Thionyl chloride for primary alkyl chlorides bc the rxns of primary alcohols with HCl are slow. - Sulfonate ester methods r good but require 2 separate rxns (formation of sulfonate ester, then rxn of ester with halide ion). - Bc all methods have an Sn2 mechanism as their basis, alcohols with several beta-alkyl substitutions do not react under the usual conditions. Tertiary alcohols: - React rapidly with HCl or HBr under mild conditions to give the corresponding alkyl halides. - Sulfonate ester method is not used with tertiary alcohols because tertiary sulfonates, like tertiary alkyl halides, do not undergo Sn2 rxns. Secondary alcohols: - If secondary alcohol has no beta-alkyl substitution, the thionyl chloride method can be used to prepare alkyl chlorides. - To avoid rearrangements completely, the alcohol can be converted into a sulfonate ester, which in turn can be treated with the appropriate halide ion in a polar aprotic solvent. This type of solvent provides the enhanced nucleophilicity of the halide ion necessary to overcome the relatively low SN2 rxn rate of a secondary sulfonate ester. - Less reactive secondary alcohols can be converted into triflates, which are much more reactive than tosylates or mesylates toward halide ions in polar aprotic solvents. - HBr method makes rearrangements, so Ph3PBR2 method can be used if primary/secondary alcohols have significant beta-alkyl substitution. Summary: - -OH group cannot act as a LG because far too basic. Need to convert into good LG. 2 strategies 1. Protonation: protonated alcohols are intermediates in both dehydration to alkenes and the rxn with hydrogen halides to give alkyl halides 2. Conversion into sulfonate esters, inorganic esters, or related LGs: sulfonate esters, to a useful approximation, react like alkyl halides. That is, the principles of alkyl halide reactivity are equally applicable to sulfonate esters. Thionyl chloride and triphenyl phosphine bromide are additional examples of this approach in which the reagent converts -OH into a good LG and provides the displacing nucleophile.

what are the 2 important situations of rxns involving enantiomers, and general summary

1. Rxns w/ chiral compound as starting material 2. Rxns w/ achiral compound as starting material, that form enantiomers as products - Enantiomers react at identical rates w/ achiral reagents/catalysts and at diff rates w/ chiral reagents/catalysts. How different depends on the specific case and can't be predicted generally without more info. With ENZYMES as catalysts, the difference is in most cases so large that only one enantiomer reacts. - When enantiomers are formed from achiral starting materials, the product is racemic UNLESS the rxn is carried out under the influence of a chiral environment such as a chiral catalyst. In that case, the predominance of one enantiomer can be expected. Which enantiomer is preferred can't be predicted. With enzymes as catalysts, however, it's usually just 1 that's formed.

summary of Sn1 and E1 rxns

1. Tertiary and secondary alkyl halides undergo solvolysis rxns by the Sn1 and E1 mechanisms; tertiary alkyl halides are much more reactive 2. If an alkyl halide has beta-H's, elimination products formed by the E1 rxn accompany substitution products formed by the Sn1 mechanism 3. Both Sn1 and E1 rxns of a given alkyl halide share the same rate-limiting step: ionization of the alkyl halide to form a carbocation 4. The Sn1 and E1 rxns are first order in the alkyl halide 5. Sn1 and E1 rxns differ in their product-determining steps. The product-determining step in the Sn1 rxn is a reaction of a nucleophile with the carbocation intermediate, and in the E1 rxn, loss of a beta-H from the carbocation intermediate 6. Carbocation rearrangements occur when the initially formed carbocation intermediate can rearrange to a more stable carbocation 7. The best LG's are those that give the weakest bases as products 8. The rxns are accelerated by polar, protic, donor solvents 9. Sn1 rxns of chiral alkyl halides give largely racemized products, but some inversion of configuration is also observed

describe cis and trans ring fusion

2 stereoisomers for decalin (2 cyclohexanes fused) - There's a cis and trans stereoisomer Each cyclohexane in cis-decalin can undergo chair interconversion. But in trans-decalin, they cannot change into them. (Can assume twist-boat conformations tho). - Equatorial would have to become both axial, and this is impossible cuz the distance is too great Trans-decalin is more stable because it has fewer 1,3-diaxial interactions. Trans ring fusion, however, is not the more stable way of joining rings in all fused bicyclic molecules. In fact, if both of the rings are small, trans ring fusion is virtually impossible. In summary - 2 rings can in principle be fused in a cis or trans arrangement - When the rings are small, only cis fusion is observed bc trans fusion introduces too much ring strain - In larger rings, both isomers are known, but trans-fused ones are more stable bc 1,3-diaxial interactions are minimized - Effects 2 and 3 are about equally balanced in cyclohexane and cyclopentane fusion (hydrindane). Trans barely more stable than cis isomer

describe the acidity of alcohols and thiols

Alcohols and thiols are weak acids. Similarity b/w structures of water and alcohols, so acidities are about the same. - Conjugate bases of alcohols are generally called alkoxides - Common name: delete final -yl from name of alkyl group and add -oxide - Sodium ethoxide -Substitutive: suffix ate is added to name of the alcohol - Sodium ethanolate Thiols, though weak acids, are much more acidic than alcohols - Relative acidities are a reflection of the element effect - Conjugate base common name: mercaptide - Sodium methyl mercaptide - Substitutive: thiolates - Sodium methanethiolate Alcohols/thiols containing electronegative substituents groups have enhanced acidity. - Polar effects are more important when groups are closer to -OH group

describe the basicity of alcohols and thiols

Alcohols and thiols can be protonated to form positively charged conjugated acids. Alcohols do not differ greatly from water in basicities; thiols are much less basic. - All have neg pKa values, which reflect the charge effect on pKa, and means they are very strong acids - neutral conjugate bases are rather weak. Nevertheless, the ability of alcohols and thiols to accept a proton plays a very important role in many rxns, particularly those that take place in acidic solutions - Alcohols and thiols, like water, are amphoteric: can either gain or lose a proton 2 acid-base equilibria are associated with an alcohol: loss and gain of a proton - Acidity of an alcohol (loss of proton) occurs only in presence of strong bases, since is weak acid - Basicity of alcohols (gain of proton) occurs only in presence of strong acids, bc weak base Thiols also act as both acids and bases. Much more acidic than alcohols bc of element effect. Conjugate acids of thiols are also more acidic than conjugate acids of alcohols for same reason. Thiols are less basic than alcohols.

describe rxns of alcohols w/ hydrogen halides

Alcohols react w/ hydrogen halides to give alkyl halides Tertiary/secondary alcohols: protonation of alcohol O is followed by carbocation formation. - Carbocation reacts w/ halide ion, which is formed by ionization of strong acid HCl, and which is present in great excess. NOTE: once alcohol is protonated, the rxn is an Sn1 rxn with H2O as the LG! Primary alcohol: the rxn occurs as a concerted displacement of water from the protonated alcohol by halide ion. Rxn is an Sn2 rxn in which water is the leaving group. Notice: initial step in both mechanisms is protonation of the -OH group Rxns of tertiary alcohols with hydrogen halides are much faster than the reactions of primary alcohols. Tertiary alcohols react w/ hydrogen halides rapidly at room temp, whereas the reactions of primary alcohols require heating for several hours. - Rxns of primary alcohols with HBr and HI are satisfactory, but rxns w/ HCl are very slow. Other methods for preparing primary alkyl chlorides are better. Rxns of secondary alcohols w/ hydrogen halides tend to occur by the Sn1 mechanism. This means that carbocations are involved as reactive intermediates; consequently, rearrangements can occur in many cases.

what are alkylating agents

Alkyl halides, alkyl tosylates, and other sulfonate esters are reactive in nucleophilic substitutions rxns. In a nucleophilic substitution, an alkyl group is transferred from the LG to the nucleophile. - The nucleophile is said to be alkylated by the alkyl halide or the sulfonate ester in the same sense that a Bonsted base is protonated by a strong acid. - For this reason, alkyl halides, sulfonate esters, and related compounds containing good LGs are sometimes referred to as alkylating agents. To say that a compound is a good alkylating agent means that it reacts rapidly with nucleophiles in Sn2 or Sn1 rxns to transfer an alkyl group

describe cyclobutane and cyclopropane

Angles constrained to be much smaller than optimum tetrahedral angle of 109.5. Energy raised! Excess energy is called angle strain. For cyclobutane, puckering avoids complete eclipsing b/w H's. 2 puckered conformation in rapid equilibrium 3 C's define a plane, so cyclopropane is planar; neither angle strain nor eclipsing interactions can be relieved by puckering. Least stable of cyclic alkanes - Bonds bent in banana shape. Slightly more like tetrahedral, but at the cost of less effect C-C overlap

general notes about any condensed state of matter, and what boiling point is. order of importance of intermolecular attractions

Any condensed state of matter (solid or liquid) owes its existence to noncovalent intermolecular attractions. If there were none, the substance would be a gas. (We are using the ideal-gas model). - Interactions are noncovalent bc no chemical rxn occurs when we convert a liquid to a gas or a solid to a liquid. That is, chemical bonds are not broken. Therefore, these attractions are much weaker than the attractions that hold atoms together in covalent bonds. - We can learn about these attractions by studying the conversion of a liquid to a gas. Specifically, we can use the boiling point as a crude measure of noncovalent attractions. Boiling point: temp required to raise the vapor pressure of a liquid to atmospheric pressure. - Boiling point is a measure of the E required to bring a liquid to the state in which all of the molecules want to escape from the liquid into the gas. As the boiling point increases, then, more energy is required to break the intermolecular attractions in the liquid state. Order of importance of intermolecular attractions 1. h-bonding 2. permanent dipoles 3. van der Waals force a. molecular surface area b. molecular shape c. polarizability

rate law and mechanism of the e2 rxn

Base-promoted beta-elimination is a dominant rxn of tertiary alkyl halides in the presence of a strong base, and it competes with the Sn2 rxn in the case of secondary and primary alkyl halides. Typically follows a rate law that is second order overall and first order in each reactant - E2 mechanism: concerted removal of a beta-proton by a base and a loss of a halide ion - E2 means: elimination, bimolecular (2 molecules involved in rate-limiting step) why is it concerted? - Beta-C acts simultaneously as a leaving group and as a nucleophile that reacts at the alpha-C. That is, the e- pair that departs from the beta-H is donated to the alpha-C to expel the bromide ion. - This could happen in 2 distinct steps. The concerted mechanism avoids the formation of a very unstable, strongly basic, carbon-anion intermediate. Concerted mechanism brings about a net transfer of e-'s from the O of ethoxide to bromine to form the much weaker base bromide ion. This is why middle curved arrow doesn't "pause" at C as e- pair and "hang around" before it reacts at the alpha-C - We will later learn about beta-eliminations that DO involves carbon-anion intermediates. But these only take place if carbon anion is stabilized in some way. To say it is more stable is to say that the beta-proton is much more acidic. So stepwise beta-elimination mechanisms will only be observed w/ compounds in which the beta-proton is unusually acidic.

describe the formation of alkoxides and mercaptides

Because pKa of a typical alcohol is about same as water, CANNOT be converted completely into its alkoxide conjugate base in an aqueous NaOH solution. Relative pKa values for ethanol and water are nearly the same. Hydroxide is not a strong enough base to convert an alcohol completely into its conjugate-base alkoxide - Alkoxides can be formed irreversibly w/ stronger bases. 1 convenient base used for this purpose is sodium hydride, NaH, which is a source of the hydride ion, H:-. - Is a very strong base; pKa of conjugate acid H2 is about 37. Hence, its rxns with alcohols go essentially to completion. In addition, when NaH reacts with an alcohol, the rxn cannot be reversed because the by-product, H2 gas, simply bubbles out of the solution. Solutions of alkoxides in their conjugate-acid alcohols find wide use in organic chem. Rxn used to prepare such solutions is analogous to this rxn in water: - Sodium reacts w/ water to give an aqueous sodium hydroxide solution, H2 gas leaves - Analogous reaction occurs w/ many alcohols. Sodium metal reacts w/ alcohol to afford a solution of the corresponding sodium alkoxide, H2 leaves. Rate of this rxn depends strongly on the alcohol. Rxns of sodium with anhydrous (water-free) ethanol and methanol are vigorous, but not violent. However, rxns of sodium with some alcohols, such as tert-butyl alcohol, are rather slow. Alkoxides of such alcohols can be formed more rapidly with the more reactive potassium metal Bc thiols are more acidic than water/alcohols, they can be converted completely into conjugate-base mercaptide anions by rxn with 1 equivalent of hydroxide or alkoxide. Common method of forming alkali-metal mercaptides is to dissolve them in ethanol containing 1 equivalent of sodium ethoxide - Although alkali-metal mercaptides are soluble in water and alcohols, thiols form insoluble mercaptides with many heavy-metal ions, such as Hg, Cu, and Pb (only goes to the right in the rxn) - Insolubility of heavy-metal mercaptides is analogous to the insolubility of heavy-metal sulfides, which are among the most insoluble inorganic compounds known. 1 reason for toxicity of lead salts is that the lead forms very strong (stable) mercaptide complexes with the thiol groups of important biomolecules

how do you form grignard reagents and organolithium reagents?

Both are formed by adding the corresponding alkyl or aryl halides to rapidly stirred suspensions of the appropriate metal. Anhydrous ether solvents must be used for the formation of Grignard reagents. - Solubility of Grignard reagents in ether solvents plays a crucial role in their formation. Reagents are formed on the surface of the magnesium metal. As they form, these reagents are dissolved from the metal surface by the ether solvent. As a result, a fresh metal surface is continuously exposed to the alkyl halide. Grignard reagents are soluble in ether solvents bc the ether solvates the metal in a Lewis acid-base interaction - Mg of Grignard reagent is 2 e- pairs shorts of an octet, and the O of each ether molecule can donate an e- pair to the metal. Organolithium reagents are soluble in hydrocarbons. Grignard and organolithium reagents react violently with O2 and vigorously with water. For this reason, these reagents must be prepared under rigorously O2-free and moisture-free conditions. priest: grignard: metal-halogen insertion organolithium: metal-halogen exchange makes these incredibly strong nucleophiles! the C behaves like a carbanion bc through formation, we reduce 2 e-'s to give C an oxidation state of -1 as opposed to +1. bases so strong they cause E2 rxns!

describe the stereochemistry of addition rxns

Can have syn-addition or anti-addition Sides of the plane which a double bond is on are called faces - Side of plane nearest observed: top face - Other side: bottom face Syn-addition: 2 groups add to double bond from same face - Notice the 2 directions of syn-addition are enantiomeric Anti-addition: 2 groups added to double from opposite faces - These 2 directions are also enantiomeric Also conceivable that an addition might occur as a mixture of syn and anti modes - In such a rxn, the products would be a mixture of all of these products Note: syn- and anti-additions give different products only when BOTH C's of a double bond become C stereocenters in the product. The question is the relative stereochemistry at BOTH C's, and the relative stereochemistry is meaningless if both aren't stereocenters

describe the stereochemistry of substitution rxns

Can occur in 2 stereochemically different ways 1. Retention of configuration: Y replaces X and they have same relative stereochemical positions 2. Inversion of configuration: X and Y have diff relative stereochemical positions - Y group must form a bond to asymmetric C from the side opposite the departing X. To make room for Y and to maintain tetrahedral configuration of C, the 3 R groups must move in a way that resembles amine inversion - Implies that if X and Y have same relative priorities, C must have opposite configurations in reactant and product As w/ addition, possible that a rxn might occur so both retention + inversion occur at comparable rates in a substitution rxn. Both products would be formed. - Also note, if C is not a stereocenter, stereochemistry cannot be determined Stereoselective rxn: particular stereoisomers of the product are formed in significant excess.

what is the common and substitutive nomenclature of alkyl halides, what's haloform

Common Nomenclature - Name of alkyl group followed by name of halide as a separate word - Ethyl chloride, methylene bromide, isopropyl iodide Haloforms: methyl trihalides. Chloroform is commonly used organic solvent - Chloroform (HCCl3), bromoform, iodoform (HCI3) Substitutive Nomenclature - Halogens treated as substituents; fluoro, chloro, bromo, or iodo. Double bonds have precedence in numbering.

what is common and substitutive nomenclature for ethers and sulfides

Common Nomenclature Ether: cite as separate words the 2 groups attached to the ether oxygen in alphabetical order, followed by the word ether - Diethyl ether, ethyl methyl ether Sulfide in similar manner Ethyl methyl sulfide, diisopropyl sulfide Substitutive Nomenclature Ethers and sulfides are never cited as principal groups! - Alkoxy groups (RO-) and alkylthio groups (RS-) always cited as substituents - C2H5O- group named by dropping yl from the name of the alkyl group and adding the suffix oxy. Thus = ethoxy group. - RS- group means adding thio to the end. The final yl is not dropped. Thus: 2-(methylthio)hexane. Parentheses indicate "thio" is associated with "methyl" rather than with "hexane."

what are organometallic compounds, and what are the 2 we know

Compounds that contain C-metal bonds: organometallic compounds - most often formed from alkyl and aryl halides Grignard reagent: compound of the form R-Mg-X, where X = Br, Cl, or I Organolithium reagent: compounds of the form R-Li - Are often aggregates of several molecules (RLi repeated) and aggregation state depends on solvent

what is the simmons-smith rxn?

Cyclopropanes w/o halogen atoms can be prepared by allowing alkenes to react with methylene iodide (CH2I2) in the presence of a copper-zinc alloy called a zinc-copper couple. Called the Simmons-Smith rxn. - Role of copper is not understood, but active reagent is believed to be an alpha-halo organometallic compound, a compound with a halogen and a metal on the same C. Can be formed by a rxn analogous to the formation of a Grignard reagent. (I-CH2-Zn-I) The Simmons-Smith reagent can be conceptualized as methylene that is coordinated (loosely bound) to the Zn atom. This is reasonable because 1) the C-Zn bond polarity is the same as the C-Mg bond polarity in a Grignard reagent, and 2) bc an alpha-halo carbanion loses halide ion to give a carbene. - Rxn of this "coordinated methylene" w/ the alkene double bond gives a cyclopropane. Bc they show carbenelike reactivity, alpha-halo organometallic compounds are sometimes called carbenoids. Carbenoid: reagent that is not a free carbene but has carbenelike reactivity. - Priest; note that Zn adds only b/w one C-I bond, not between both of them, just bc of statistics. Then intramolecular action more likely to happen - Zn-I leaves rather than another Zn joining. Always do intramolecular reaction! It's always faster and easier! Alkene reacts with carbon just as Zn-I leaves, and other I leaves too.s And make ZnI2 precipitate Addition rxns of methylene from Simmons-Smith reagents to alkenes, like the rxns of dichloromethylene, are stereospecific syn-additions. If cis/trans, stays cis/trans. - Addition of carbenes or carbenoids to alkenes to yield cyclopropanes is a rxn that forms new C-C bonds. Rxns that form C-C bonds are especially important in orgo bbc they can be used to build up larger C skeletons from smaller ones.

notes about stereochemistry for rxns involving diastereomers

Diastereomeric compounds in general have diff reactivities toward ANY reagent, whether chiral or achiral. Reason: both starting materials and transition states are diastereomeric, and diastereomers have diff free energies. Thus, standard free energies of activation, hence rxn rates, differ. Can't predict. All we know is they're not equally reactive. When rxns form diastereomeric products, products are formed at diff rates and therefore in diff amounts. Without knowing more about the rxn, can't predict. - Why? Bc they are formed through diastereomeric transition states. In general, one transition state has a lower standard free energy than the other. Remember: - When starting materials are achiral, each diastereomer of product will be formed as a pair of enantiomers (the racemate) - Drawing convention: sometimes people only draw one enantiomer of each product, but it is understood that each of these diastereomers MUST be racemic.

explain the mechanism for free-radical halogenation of alkanes

Direct halogenation of alkanes produces simple alkyl halides. When an alkane is treated with Cl2 or Br2 in the presence of heat or light, a mixture of alkyl halides is formed by successive chlorination rxns. Formed in a series of substitution rxns. Substitute H atom with Cl. - Relative amounts of the various products can be controlled by varying the rxn conditions, but mixtures of them are formed, and each compound must be isolated by fractional distillation. - Conditions of rxn (initiation by heat or light) show involvement of free-radical intermediates. Initiation: small # of halogen molecules absorb E from heat or light and dissociate homolytically into halogen atoms. - Ensuing chain rxn has following steps: Cl takes H, CH3 becomes free radical. CH3 free radical takes Cl. - Cl radical formed reacts with another Ch4, and chain rxn continues. - Termination steps result from the recombination of radical species after the methane and Cl2 concentrations are depleted. - Example of free-radical substitution rxn: substitution rxn that occurs by a free-radical chain mechanism. Free-radical halogenations w/ Cl and Br proceed smoothly. F is violent (too exothermic), and I does not occur (too endothermic). Correlate with delta H values.

priest's notes about E1/E2/Sn1/Sn2

E1: polar protic (h2o, methanol, ethanol) E2: polar aprotic If you want to favor E1/E2 rxns, raise the temp (because it's increasing amount of molecules, so delta S raises, and as we increase T it makes that whole value more and more negative so delta G becomes more and more negative). For substitution - lower the temp!!!! E1/E2: delta, or 100 deg C Sn1/Sn2: room temp, 20-40 deg C SO: look at temp and solvent! Note: you CAN use both types of solvents for E2, but not both for E1! NOTE: - if conditions are acidic, can b Sn1/E1 bc carbocation is formed - if conditions are basic, is Sn2/E2 NOTE: intramolecular always happens over intermolecular! bc probability! proximity! HIS CHART: primary - primarily sn2 unless steric hinderance - no sn1/e1 secondary - both sn2/e2; stronger base and higher temp, greater % e2 - both sn1/e1; higher temp, greater % of e1 tertiary - no sn2/e2 - both sn1/e1; higher temp, greater % of e1 PA: sn2/e2 PP: sn1/e1 low temp: sn1, sn2 high temp: e1, e2

what is an example of ester derivatives of strong inorganic acids

Esters of strong inorganic acids exemplify another type of alkylating agent. Like tosylates and mesylates, these compounds are derived conceptually by replacing the acidic H of a strong acid (in this case an inorganic acid) with an alkyl group. - Example: sulfuric acid becomes dimethyl sulfate when H's replaced with C's Alkyl esters of strong inorganic acids are typically very potent alkylating agents bc they contain LGs that are very weak bases.

describe stereochemistry malic acid to fumaric acid - alcohol dehydration (alkene hydration reversed)

Example of when starting material is chiral - Enantiomers react at identical rates w/ an achiral reagent - The principle of enantiomeric differentiation states that enantiomers behave differently only in the presence of a chiral agent So when rxn is catalyzed by enzyme fumarase, 2 enantiomers behave differently - S-malic acid reacts rapidly, and enzyme does not catalyze reaction of R-malic acid Why? - Fumarase and all other enzymes are enantiomerically pure chiral molecules - So 2 enantiomers of malate react differently w/ the enzyme - In terms of free energies, bc the transition state for the rxn of water and malate includes the chiral enzyme, then the R and S transition states, which are enantiomers in the absence of the enzyme, are diastereomers in the presence of the enzyme, and their free energies are different. The faster reaction (S) has the transition state of lower free energy - Principle of enantiomeric differentiation is operating here exactly as it does in enantiomeric resolution. We can think of enzyme as a chiral resolving agent In the presence of an enzyme catalyst, only (S)-malate reacts to give fumarate. Therefore, in the reverse rxn, fumarate reacts in the presence of the enzyme to give only (S)-malate. The basis of this selectivity is the free energies of diastereomeric transition states. In general, enantiomers are formed at different rates from achiral starting materials in the presence of a chiral catalyst - But we can't predict which enantiomer is more reactive without more info.

describe cyclopentane

Exists in puckered conformation called the envelope conformation. Undergoes rapid conformational changes in which each carbon alternates as the "point" of the envelope - Somewhat higher energy than cyclohexane. Due mostly to eclipsing b/w H atoms - Substituted cyclopentanes exist, substituents assume equatorial to minimize van der Waals repulsions w/ neighboring groups.

priest: how is iodide the best nucleophile AND electrophile? shouldn't nucleophile have localized charge?

F surrounded by solvent molecules so it can't reach the orbitals it wants to get into. It's a tight hard small molecule. As solvent becomes less polar, F becomes better nucleophile

what is the rate law and overall kinetic order

For molecules to react, must collide. Bc molecules at higher concentrations are more likely to collide, the rate of a rxn is a function of the concentration of the reactants. Mathematical statement of how a rxn rate depends on conc is called: rate law - Determined experimentally by varing the conc of each ractant (including catalysts) independently and measuring the resulting effect on the rate. Each rxn has its own characteristic rate law - Example = rate k[A][B] - only if those molecules conc affects the reaction rate (conc terms indicate which species are present in the transition state of the rate-limiting step!!!!) - Conc are at any time during the rxn, and rate is velocity of the rxn at that same time Constant of proportionality k: rate constant. Is different for every rxn, and is a property of each rxn under particular conditions of temp, pressure, solvent, and so on. - Is numerically equal to the rate of the rxn when all reactants are present under the standard conditions of 1 M conc. The rates of 2 rxns are compared by comparing their rate constants!!!! Important aspect of rxn: kinetic over. Overall kinetic order for a rxn is the sum of the powers of all the concentrations in the rate law. The kinetic order in each reactant is the power to which its concentration is raised in the rate law. - Second-order rxn, overall kinetic order of 2: rate = k[A][B] - First-order rxn, overall kinetic order of 1: rate = k[D] - Units of rate constant depend on the kinetic order of the rxn. W/ conc in moles per liter, and time in seconds, the rate of any rxn has the units M s^1. For a second-order rxn then, dimensional consistency requires that the rate constant have units of M^-1 s^-1. For a first-order rxn, has units of s^-1. Take second-order and look at it like this: M s^-1 = M^-1 s^1 x M x M

what are sulfonate esters, how do you prepare and what's the point

If alcohol molecule contains a group that might be sensitive to strongly acidic conditions, or if milder or even non acidic conditions must be used, different ways of converting the -OH group into a good LG are required. Important method: convert them into sulfonate esters: derivatives of sulfonic acids, which are compounds of the form R-SO3H. - Sulfonate ester: compound in which the acidic H of a sulfonic acid is replaced by an alkyl or aryl group. - Mesylates (R-OMs): esters of methanesulfonic acid - Tosylates (R-OTs): esters of p-toluenesulfonic acid

monosubstituted cyclohexane conformational analysis

If substituent is equatorial or axial on one C, these are diastereomers! And when they interconvert, a down methyl remains down and an up methyl remains up! Bc it's such a rapid process, methylcyclohexane is a mixture of 2 conformational diastereomers. Since they have diff energies, one form is more stable than the other. Equatorial is more stable than axial. Why? - Van der Waals repulsions occur b/w methyl H's and 2 axial H's on the same face of the ring. Call 1,3-diaxial interactions. Destabilize the axial conformation relative to the equatorial conformation, where these repulsions are absent - Each methyl-hydrogen 1,3-diaxial interaction in a cyclohexane derivative raises the enthalpy by the same amount - Basically the same as gauche butane interaction, and for this reason the cyclohexane derivatives are often called gauche-butane interactions - So we will see that methylcyclohexane contains very little of the axial conformation at equilibrium Priest: - t-butyl means cyclohexane ring is locked and does not flip! - higher delta G (energy difference) b/w axial and equatorial, more it favors equatorial. Halogens have very small, bc compact?

explain intermolecular repulsion and intermolecular attraction

In HBr free-radical addition to alkene, interaction of Br atom w/ alkyl branches on a double bond is an energetically unfavorable noncovalent interaction- that is, an intermolecular repulsion - Intermolecular repulsions raise the energy of the interacting species Energetically favorable - intermolecular attraction: the attractions between ions in the crystal structure of a salt, which we often call an ionic bond. - Intermolecular attractions lower the energy of the interacting species.

what is the competition b/w nucleophilic substitution and beta-elimination rxns

In the presence of a strong base such as ethoxide, the nucleophilic rxn is typical for primary alkyl halides, and a beta-elimination rxn is observed for tertiary alkyl halides. Typical secondary alkyl halide under same conditions undergoes both reactions. - Occur at comparable rates- in other words, they are in competition. For ALL alkyl halides, even primary and tertiary - Under some conditions, the result of the competition can be changed.

describe the different cation-binding molecules

Ionophores: molecules that form strong complexes with ions. Crown ethers: heterocyclic ethers containing a number of regularly spaces O atoms. - [18]-crown-6 complex (18 atoms, 6 O's) - O's of "host" crown ether wrap around the "guest" metal cation, complexing it within the cavity of the ether using donor and charge-dipole interactions - Can think of crown ether as "synthetic solvation shell" for a cation - Bc metal ion must fit within the cavity, the crown ethers have some selectivity for metal ions according to size Cryptands: nitrogen-containing analogs of crown ethers. Presence of N allows for a bicyclic structure that provides an additional pair of O's to assist in binding metal ion. More snug than crown ether- like a catcher's mitt - Complexes of metal ions and cryptands: cryptates More info about them - Bc contain hydrocarbon groups, they have significant solubilities in hydrocarbon solvents such as hexane or benzene. - They can cause inorganic salts to dissolve in solvents in which these salts ordinarily have little or no solubility. - Stabilization of ion by crown ether compensates for fact that the anion is "naked" or unsolvated Ionophore Antibiotics - Antibiotic: compound that interferes with the growth or survival of microorganisms - Example: nonactin. Strong affinity for ion. Contains cavity. Has outside hydrocarbonlike region that provides a natural barrier into the passage of ions. However, allows it to enter readily into, and pass through, membranes. Binds and transports ions! Ion balance is crucial to proper cell function, so cell dies. Ion channels: provide passageways for ions into and out of cells. Large protein molecule imbedded in cell membrane. Can be opened/closed to regulate conc of ions inside cell. - Ions dont diffuse passively. Open channel contains regions that bind a specific ion. - The structures of ion-binding regions of these channels have much in common with the structures of ionophores such as nonactin. Outside is hydrocarbons, interacts with bilayer. Entrance has binding sites for 2 K+ ions, which are O-rich, just like nonactin. Structure is such a way that it only fits K+. Selectivity filter! O's in selectivity filter provide "solvation" for potassium ion.

summary of e2 rxn

Is promoted by strong bases. Key points: 1. Rates of E2 rxns are second order overall: first order in base and first order in alkyl halide 2. E2 rxns normally occur with anti stereochemistry 3. E2 rxn is faster w/ better LG - those that give the weakest bases as products 4. The rates of E2 rxns show substantial primary deuterium isotope effects at the beta-H atoms 5. When an alkyl halide has more than 1 type of beta-H, more than one alkene product can be formed; most stable alkenes (w/ greatest # of alkyl substituents at double bonds) are formed in greatest amount 5. E2 rxns compete with Sn2 rxns. Elimination is favored by alkyl substitution in the alkyl halide at the alpha or beta-C atoms, by alkyl substituents at the alpha-C of the base, and by highly branched bases.

heterocyclic nomenclature

Many important ethers and sulfides contain an O or S atom within a ring. Cyclic compounds with rings that contain at least 1 atom other than C are called heterocyclic compounds. Oxirane is a parent compound of a special class of heterocyclic ethers: epoxides. 3-membered rings that contain an O atom. - Some are named traditionally as oxides of corresponding alkenes bc that's how they're prepared. - Ethylene oxide, styrene oxide However, most are named substitutively as derivatives of oxirane. Atoms of epoxide ring are numbered consecutively, w/ O receiving number 1 regardless of the substituents present.

give summary of sn2 rxn

Most primary and some secondary alkyl halides 1. Rxn rate is second order overall: first order in nucleophile and first order in alkyl halide 2. Mechanism involves opposite-side substitution rxn of nucleophile w/ alkyl halide and inversion of stereochemical configuration 3. Rxn rate is decreased by alkyl substitution at both the alpha and beta-C atoms; alkyl halides with 3 beta-branches are unreactive 4. Nucleophilicity depends on the basicity and polarizability of the nucleophile, and the solvent - Sn2 rxns are much faster in polar aprotic solvents than in protic solvents provided that the nucleophile is soluble enough for the rxn to be practical. Protic solvents are useful if the rxn is fast enough - Nucleophiles in which the nucleophilic center is from periods > 3 have enhanced nucleophilicity bc they are highly polarizable - In PA solvents, nucleophilicity increases with the basicity of the nucleophile - In protic solvents, nucleophilicity increases with the basicity of the nucleophile if the nucleophilic atom is the same - In protic solvents, nucleophilicity is significantly reduced when the nucleophilic atom is a good H-bond acceptor. For this reason, nucleophiles with period-2 nucleophilic atoms are less reactive in protic solvents than nucleophiles in which the nucleophilic atoms come from higher-numbered periods within the same group. 5. The fastest Sn2 rxns involve leaving groups that gives the weakest bases as products

describe cell membranes and drug solubility

Need to get to sites of action - for many drugs, means they must enter cells. Only way is to get through the cell membrane. - The ability of a molecule to penetrate a cell membrane is a solubility issue. Cell membranes - Consist primarily of molecules called phospholipids - Lipid: compound that shows significant solubility in apolar solvents. Significant hydrocarbon character - Phospholipids: lipids that contain phosphate groups. - Membrane phospholipids: have specialized structures. Structural features - Polar head group; Well solvated by water and counterions. Hydrophilic groups: have stabilizing interactions with water - Nonpolar tails: long, unbranched hydrocarbon portions of molecules. Hydrophobic group. - Amphipathic molecules: has hydrophilic and hydrophobic regions When added to water... - They undergo a process called self-assembly in which they spontaneously form a phospholipid bilayer. - Many molecules in a double layer. Nonpolar tails interact w/ each other on the interior of the layer, and the polar head groups interact with water on the outside of the layer. - Is it violation of tendency toward increasing entropy? No, this is hydrophobic bonding! Releasing the solvent provides a highly positive and dominating entropic contribution to the self-assembly process. - Form phospholipid vesicles: closed, more or less spherical structures in which a phospholipid bilayer encloses an inner aqueous region. Polar heads interact both on the inside and outside of the vesicle. Phospholipid bilayer generally impermeable to ions - Can't penetrate any more than ions can dissolve in gasoline - Insolubility of ionic compounds in hydrocarbons is crucial to the cell's ability to retain proper ion balance. Transport requires special carriers - proteins imbedded in the membrane A number of uncharged molecules diffuse readily through the cell membrane (O2!) - Drugs that are insoluble in hydrocarbons do not pass through membranes. Drugs that are highly soluble don't either; they move into the bilayer and stay there. Those that pass through have moderate solubility in hydrocarbons. Soluble enough in water to leave the membrane! - Simple solubility measurements have value in predicting the effectiveness of drug candidates. Potency of many drugs can be correlated with their relative solubilities in 1-octanol and water. - Ratio of concentrations of neutral molecule in 1-octanol and aqueous phases is called: the octanol-water partition coefficient. Hydrophobic molecules have larger partition coefficient than hydrophilic ones. There is an optimum value for a given drug class!

what are the 3 broad categories of solvents, and describe them

Not mutually exclusive! 1) Protic or aprotic - H-bonding 2) Polar or apolar - polar has high dielectric constant, attractions b/w ions is small, so polar solvents better at dissolving ionic compounds 3) Donor or nondonor - donate unshared e- pairs, like Lewis bases Protic solvent: consists of molecules that can act as H-bond donors - Water, alcohols, and carboxylic acids Aprotic solvents: cannot act as H-bond donors - Ether, dichloromethane, and hexane Polar has two meanings. 1) Individual molecule of solvent has significant dipole moment - Dipoles b/w solvent and solute molecules can have significant effects on solubility. - Dipolar solvents: consisting of molecules w/ significant dipole moments 2) Has to do with dielectric constant (epsilon) - Polar solvent: has high dielectric constant (epsilon >= 15) - Water, methanol, formic acid - Apolar solvent: has low dielectric constant - Hexane, acetic acid - Dielectric constant: defined by electrostatic law. Shows that when the dielectric constant is large, the magnitude of E (energy of interaction b/w the ions) is small. Means that both attractions b/w ions of opposite charge and repulsions b/w ions of like charge are weak in a polar constant. Thus, a polar solvent effectively separates, or shields, ions from one another. Therefore, the tendency of oppositely charged ions to associate is less in a polar solvent than it is in an apolar solvent. Dielectric constant contributes significantly to the ability of a solvent to dissolve ionic compounds. POLAR SOLVENTS BETTER AT DISSOLVING! - Dielectric constant is the property of many molecules of a solvent acting together, whereas the dipole moment is a property of individual molecules. Fortunately, all polar solvents consist of dipolar molecules; so, when we say "polar solvent" we can assume that the solvent molecules have a significant dipole moment. However, the converse is not true. A number of apolar solvents also contain dipolar molecules. Donor solvents: consist of molecules containing Os or Ns that can donate unshared e- pairs - that is, molecules that can act as Lewis bases - Ether, THF, and methanol Nondonor solvents: cannot act as Lewis bases - Pentane, benzene - Chlorines have unshared pairs, but are poor Lewis bases and considered to be nondonor

give info about the boat and twist-boat conformations of cyclohexane

Not stable conformation; 2 sources of instability 1. Certain H's are eclipsed 2. 2 H's on the "bow" and "stern" of the boat (flagpole H's) experience modest van der Waals repulsion - For these reasons, the boat undergoes very slight internal rotations that reduce both the eclipsing interactions and the flagpole van der Waals repulsions. The result is another stable conformation of cyclohexane called a twist-boat conformation - Simply nudge one flagpole higher than the other and vice versa - Twist-boat conformation is an intermediate in the chair interconversion. Energy minimum, but less stable than chair conformation. - Boat conformation itself is the transition state for the interconversion of 2 twist-boat conformations

describe the geometry of alkyl halides, alcohols, thiols, ethers, and sulfides

Of all these, bond angles at C are very nearly tetrahedral, and alpha-C's are sp3-hybridized. The bond angle at O or S further defines the shape of the molecule. We can think of unshared e- pair as a bond without an atom at the ended. This means that O or S has four "groups": 2 e- pairs and 2 alkyl groups or H's. These molecules are therefore bent at O and S. Angle at S is generally found to be closer to 90 than the angle at O. Why? Unshared e- pairs on S occupy orbitals derived from quantum level 3 that take up more space than those on O, which are from quantum level 2. Repulsion b/w these unshared pairs and the e-'s in the chemical bonds forces the bonds closer together than they are on O. Lengths of bonds trends - Within a column, bonds to atoms of higher atomic number are longer. C-S longer than C-O. - Within a row, lengths decrease toward higher atomic number. C-O is longer than C-F, and C-S is longer than C-Cl.

describe rxn b/w alcohol and triphenylphosphine dibromide

Ph3PBr2 - a triphenylphosphine dibromide - Is actually an ionic compound. So usually see as PBr2 - First step: Lewis acid-base association rxn in which the O of the alcohol acts as a nucleophilic center and phosphorus as the electrophilic center. (can form 5 bonds). - Br ion of reagent acts then as a base to bring about a beta-elimination of HBr and form a resonance-stabilized intermediate w/ pos formal charge - Br ion that was displaced then acts as a nucleophile at the alpha-C to displace (-)O-(+)PPh3 (triphenylphosphine oxide) as a LG Occurs very rapidly for 3 reasons 1) Triphenylphosphine oxide is a VERY weak base and therefore a good LG 2) Rxn is typically carried out in polar aprotic solvents such as acetonitrile or DMF, which accelerate Sn2 rxns -3) The rxn of the bromide ion nucleophile is essentially intramolecular (That is, the Br LG reacts as a nucleophile before it can diffuse away) - Rxn is so fast it can even be carried out successfully with neopentyl alcohol. Recall that its derivatives are very unreactive in Sn2 rxns. - Particularly useful for the preparation of secondary bromides. - An analogous reagent, triphenylphosphine dichloride, can be used for the preparation of alkyl chlorides. -NOTE: causes in inversion of stereochemistry -NOTE: must be in ANHYDROUS conditions!!! at least PBr3

what are phenol and enol

Phenol: -OH group bound to C of an aryl group (like benzene ring) Enol: -OH group bound to C that's part of a double bond Specifically, in an alcohol, OH is bound to C NOT part of double/triple bond Phenols, enols, and alcohols have very different properties

cis-trans isomerism in disubstituted cyclohexanes

Planar-ring structure: cyclohexane ring is drawn as planar hexagon - Compound w/ 2 diff substituents has 2 asymmetric C's and therefore 4 stereoisomers - 2 diastereomeric sets of enantiomers - When both substituents have same relative orientation (both up or down) substitution pattern is cis. When diff relative orientations, pattern is called trans - Note this has nothing to do with absolute (R, S) configurations Note: planar-ring structure does not tell you about conformation, and the up and down positions carry from the chair to the planar-ring - The 2 ways of showing it (like if either is a dash or a wedge) are conformational diastereomers. Diff energies and the diequatorial form is favored!

describe the rxn of alcohol w/ thionyl chloride

Preparation of primary alkyl chlorides from alcohols with HCl is not as satisfactory as the preparation of the analogous alkyl bromides with HBr. Better method is the rxn of alcohols with thionyl chloride. - Advantage: faster + no separation problems Involves the conversion of -OH into a good LG. When alcohol reacts with thionyl chloride, a chlorosulfite ester intermediate is formed. This reacts readily with nucleophiles because the chlorosulfite group -O-SO-Cl is a very weak base and thus a very good LG. Reacts with chloride ion to give the alkyl chloride. Displaced ion is unstable and decomposes to SO2 and Cl-. Although thionyl chloride method is most useful with primary alcohols, can also be used with secondary alcohols, although rearrangements have been known to occur. Avoid rearrangements by using Sn2 conditions: reaction of a halide ion with a sulfonate ester in a polar aprotic solvent. Priest: -OH w/ SOCl2: inversion -OH w/ SOCl2 and pyridine: retention. In Sni rxn

describe the preparation of sulfonate esters

Prepared from alcohols and other sulfonic acid derivatives called sulfonyl chlorides. Point is to get sulfonate thing on the O! Example: 1-decanol, tosyl chloride, pyridine (used as solvent). Pyridine is base - catalyzes rxn and neutralized HCl that would otherwise form in the rxn. Nucleophilic substitution rxn is where O of alcohol displaced Cl ion from tosyl chloride.

what is the principal group, and explain substitutive nomenclature of alcohols and thiols

Principal group: chemical group on which the name is based, and it is always cited as a suffix in the name. In a simple alcohol, -OH group is the principal group, and its suffix is ol. - Ethane -> ethanol. (Final e is dropped if the suffix begins with a vowel. Otherwise, retained For simple thiols, -SH group is principal group, suffix is thiol. Add suffix to parent alkane. - Ethane -> ethanethiol To name an alcohol containing more than one -OH group, suffixes diol, triol, and so on are added WITHOUT dropping the final e. - 2,3-pentanediol Rules for substitutive naming 1. Identify principal group - CEAKAA - can every aldo kill alcoholic americans - carboxylic, ester, aldehydes, ketones, alcohol, amine 2. Identify principal C chain - Chain w/ greatest # of principal groups, chain w/ greatest # of double and triple bonds, chain of greatest length, chain with the greatest number of other substituents 3. Number C's of principal chain consecutively from one end - Lowest numbers for principal groups, then for multiple bonds, with double bonds having priority over triple bonds in case of ambiguity, then for lowest numbers for other substituents, then lowest number for the substituent cited first in the name 4. Begin construction of the name with the name of the hydrocarbon corresponding to the principal chain - Cite principal group by its suffix and number; it's number is the last one cited in the name. If there is no principal group, name the compound as a substituted hydrocarbon. Cite the names and numbers of the other substituents in alphabetical order at the beginning of the name

describe a rxn of an achiral compound to give enantiomeric product

Principle of microscopic reversibility requires that a rxn and its reverse must have identical transition states. Therefore, if 2 enantiomers of malic acid undergo dehydration at the same rate, then the reverse rxn, hydration of fumaric acid, must give the 2 enantiomers of malic acid at the same rate In general, when chiral products are formed from achiral starting materials, both enantiomers of a pair are always formed at identical rates. That is, the product is always the racemate. Optical activity never arises spontaneously in the rxns of achiral compounds

deuterium kinetic isotope effects in the e2 rxn

Proton is removed in transition state of E2 rxn. This aspect of mechanism can be tested. When H transferred in rate-limiting step of rxn, a compound in which the H is replaced by its isotope deuterium will react more slowly in the same rxn. - Effect of isotopic substitution on reaction rates: primary deuterium kinetic isotope effect - Primary deuterium kinetic isotope effect is the ratio of the rates for the 2 rxns: that is, kH/kD. Ranges from 2.5-8. Effect of big magnitude shows that the bond to a beta-H is broken in the rate-limiting step of this rxn. Theoretical basis for effect lies in comparative strengths of C-H and C-D bonds - In starting material, bond to heavier isotope D is slightly stronger (and thus requires more energy to break) than bond to H. However, in transition states for both rxns, the bond from H or D to C is partly broken, and the bond from H or D to the base is partly formed. To a crude approximation, the isotope undergoing transfer is not bonded to anything - it is "in flight" - Bc there is no bond, there is no bond-energy difference b/w the isotopes in the transition state. Therefore, the compound with the C-D bond starts out at a lower energy than the compound with the C-H bond and requires more energy to achieve the transition state. Energy barrier for compound w/ C-D bond is greater - rate of rxn is smaller - This effect is observed only when the H that is transferred in the rate-determining step is substituted by deuterium. Substitution of other H's with deuterium usually has little or no effect on the rate of the rxn.

describe the reactivity of dichloromethylene and an important rxn it undergoes

Reactivity of dichloromethylene follows from its electronic structure. C atom bears 3 groups (2 Cl's and the lone pair) and therefore has approx trigonal planar geometry. Bc sp2-hybridized, the Cl-C-Cl bond angle is bent rather than linear, unshared pair occupies an sp2 orbital, and the 2p orbital is vacant. - Bc it lacks an electronic octet, it is an e-deficient compound and can accept an e- pair; it is a powerful electrophile. On the other hand, an atom with an unshared e- pair can react as a nucleophile. It fits into this category as well. So the divalent C of a carbene can act as a nucleophile and an electrophile at the same time!!! Important rxn that fits this analysis is cyclopropane formation. When dichloromethylene is generated in the presence of an alkene, a cyclopropane is formed. In general, rxn of a haloform with base in the presence of an alkene yields a 1,1-dihalocyclopropane. - Mechanistically, the rxn is a concerted syn-addition. The empty 2p orbital of the carbene is e-deficient and therefore acts as an electrophile. The pi e-'s of the alkene are donated to this orbital and a bond is formed b/w the carbene and 1 C of the alkene. This nucleophilic rxn produces e- deficiency at the other alkene C. This e- deficiency is satisfied by a simultaneous rxn with an unshared e- pair of the carbene, which acts as a nucleophile, forming the other bond to the alkene. (Priest: you don't know if it's single or double-headed arrows bc we don't actually know) - This rxn is stereospecific. Methyls are either cis or trans in both starting material and product.

describe the difference b/w relative rates of sn2 rxns and bronsted acid-base rxns

Recall close analogy b/w nucleophilic substitution rxns and acid-base rxns. Equilibrium constants are very similar, curved-arrow notation for Sn2 rxn and acid-base analog are identical. - However, it's important to understand that their RATES are very different - Most ordinary acid-base rxns occur instantaneously! Nucleophilic substitutions are MUCH slower than the analogous acid-base rxns. - If an alkyl halide and a Bronsted acid are in competition for a Bronsted base, the Bronsted acid reacts much more rapidly. It always wins!!!

do a conformational analysis of disubstituted cyclohexanes

Relative stability of 2 chair conformations is determined by comparing the 1,3-diaxial interactions in each conformation - When 2 groups on substituted cyclohexane conflict in their preference for the equatorial position, the preferred confirmation can be predicted from the relative conformational preferences of the 2 groups - Tert-butyl group is so large that van der Waals repulsions control the conformational equilibirum. Hench, chair conformation is favored where tert-butyl group assumes equatorial position, methyl group forced into axial position

what are the rate-limiting and product-determining steps of sn1 and e1 rxns

Sn1 and E1 rxns have a common rate-limiting step. Rate at which alkyl halide disappears as it undergoes both competing rxns is determined by its rate of ionization - rate at which it forms the carbocation. - The relative amounts of substitution and elimination products are determined by the relative rates of the steps that follow the rate-limiting step - Because the relative rates of these steps determine the ratio of products, they are said to be product-determining steps. Notice that the relative rates of the product-determining steps have nothing to do with the rate at which the alkyl halide dissociates into ions. Competition b/w them is different from competition b/w Sn2 and E2. Those share nothing in common but starting materials; they follow completely separate reaction pathways with no common intermediates. - In contrast, Sn1 and E1 rxns of alkyl halide share not only common starting materials, but also a common rate-limiting step, and hence a common intermediate - the carbocation - In E1 rxn, the proton is not removed from the alkyl halide, but from the carbocation. Bc the carbocation is a strong acid, a strong base is not required for the E1 rxn as it is for the E2 rxn

stereochemistry of sn1 rxn

Sn1 rxn results in a racemic mixture AND an inverted product. How can this be if a free carbocation is a reactive intermediate? - A mechanism that can account for this result assumes that the first reactive intermediate in the Sn1 rxn is an ion pair - carbocation intimately associated with its counterion. The ion pair is still a chiral species. Counterion blocks the access of solvent to the front side of the carbocation. Solvation of the carbocation in this ion pair occurs from the opposite side only; opposite side-substitution by the solvent molecule involved in this interaction results in inversion. - However, the counterion might also escape from the carbocation into the surrounding solvent, leaving the carbocation solvated on both sides by solvent. This symmetrically solvated carbocation is achiral and can, with equal probability, react at either face w/ solvent to give racemic product. - Occurrence of both racemization and inversion shows that both types of carbocations - ion pairs and free ions - are important in determining the products of Sn1 reactions. Exact percentages of which comes from which varies from case to case. - Occurrence of some inversion also shows that the lifetime of a tertiary carbocation is very small! The carbocations that undergo inversion don't last long enough for the counterion to fully escape!

what is the rate law and mechanism of the sn2 rxn

Sn2 mechanism: e-pair donation by a nucleophile to an atom (usually C) displaces a leaving group from the same atom in a concert manner (in one step, without reactive intermediates) - called "pentavalent transition state" - Sn2 meaning: substitution, nucleophilic, bimolecular (2 species) Reminder: the conc terms of the rate law indicate which species are present in the transition state of the rate-limiting step. - Mechanisms that are inconsistent with the rate law are ruled out - Of the chemically reasonable mechanisms consistent with the rate law, the simplest one is provisionally adopted - Mechanism is modified or refined if required by subsequent experiments - Rate law gives info about which species are present, but not how they are arranged! Could be same-side substitution or opposite-side substitution.

describe solute, solvent, and process of forming solution

Solute: small amount of liquid A added to larger amount Solvent: larger amount of liquid S, to which is being added - We assume they do not react w/ each other - If they persist as separate phases, even when in contact, we say that A is insoluble in S - If they form a single, clear, liquid phase, we say A has formed a solution in S, and that A is soluble in S - We have then dissolved A in S Process of forming a solution involves the interplay of noncovalent intermolecular interactions. - When solution is formed, some interactions b/w S molecules and ALL interactions b/w A molecules are replaced by interactions b/w A and S - Molecules of solvent S in direct contact w/ solute molecules A are called collectively the solvent shell, or solvent cage. - Solvent structure is very dynamic, w/ molecules in solvent and solvent shell moving around and exchanging places rapidly

what are the rate laws and mechanism of sn1 and e1 rxns

Solvolysis of tert-butyl bromide follows a first-order rate law: - Rate = k [(CH3)3CBr] - Any involvement of solvent in the rxn cannot be detected in the rate law bc the concentration of the solvent cannot be changed. However, the nature of the solvent does play a critical role in this rxn. - The solvolysis rxns of tertiary alkyl halides are fastest in polar, protic, donor solvents such as alcohols, formic acid, and mixtures of water with solvents in which the alkyl halide is soluble (for example, aqueous acetone). Notice that these solvents are the ones that are best at solvating ions. Occurrence of both substitution and elimination products shows that 2 competing rxns are involved. - First step in both rxns involves the ionization of the alkyl halide to a carbocation and a halide ion. This is a Lewis acid-base dissociation, and is the rate-limiting step of both the substitution and elimination rxns. - The carbocation then rapidly reacts to give both substitution and elimination products. They arise from competing rxns of the carbocation Sn1 product: - Product formed by Lewis acid-base association of a solvent molecule with the carbocation. Even though solvent is poor nucleophile, the reaction occurs rapidly because the solvent is present in very high concentration, and bc the carbocation is a very powerful Lewis acid. - The nucleophile that reacts with the carbocation is ethanol, NOT ethoxide ion; such a strong base is NOT present in a solvolysis rxn; further, if significant amounts of such a base were added, elimination by the E2 mechanism would be observed exclusively. - Final step: protonated ether loses a proton to solvent to give ether and conjugate acid of solvent. - Bronsted base involved in this rxn is ethanol, not ethoxide ion. Protonated ether is a strong acid, so no ethoxide ion is needed. - Notice: protonated solvent plus bromide ion is the form of ionized HBr in ethanol solvent, just as H3O+ Br- is the ionized form of HBr in water. - Sn1: substitution, nucleophilic, unimolecular (single molecule, alkyl halide, involved in rate-limiting step) Elimination product: - Loss of a beta-proton gives the alkene - The base that removes a beta-proton from the carbocation is typically a solvent molecule. Although ethanol is a very weak base, the rxn occurs readily because ethanol, as the solvent, is present in very high concentration and the carbocation is a VERY STRONG Bronsted acid. - Beta-elimination mechanism that involves carbocation intermediates: E1 mechanism E1 = elimination, unimolecular note: these take several steps, unlike sn2/e2. when molecule that attacks the carbocation has H that needs to be removed, that atom has a pos charge and is another intermediate

common nomenclature of alcohols and thiols

Specify the alkyl group to which the -OH group is attached, followed by the separate word alcohol. - Methyl alcohol, isopropyl alcohol, etc. Compounds that contain 2+ hydroxy groups on different C's are called glycols. - Ethylene glycol, propylene glycol, glycerol (3 of em) Thiols are named in the common system as mercaptans - Ethyl mercaptan

describe the chair conformation of cyclohexane

Stability data requires that bond angles in cyclohexane must be same as in an alkane - 1) Very close to ideal 109.5 tetrahedral angle - If significantly distorted from tetrahedral, would see greater heat of formation - C's of cyclohexane are sp3-hybridized - 2) must have staggered conformation about each C-C bond because otherwise, eclipsing interactions (torsional strain) would also inc the heat of formation - 2 geometrical constraints can only be met if the C skeleton of cyclohexane assumes a nonplanar, "puckered" conformation: chair conformation C at vertex of V: down C's. C at vertex of inverted D: up C's - Axial hydrogens: perpendicular to plane of table. Drawn vertically - Equatorial hydrogens: point outward along periphery of the ring - Pairs of equatorial bonds are parallel to pairs of nonadjacent ring bonds All bonds are staggered, without compromising the tetrahedral C geometry - Up and down H's of a given type are completely equivalent (see this by turning ring over) - Causes up C's to exchange places with down C's, up-axial to exchange places with down-axial, up-equatorial with down-equatorial - Also: if H is up on 1 C, 2 neighboring H's are down, and vice versa

what is a stereospecific rxn?

Stereospecific reaction: different stereoisomers of a starting material give different stereoisomers of a product - All stereospecific reactions are stereoselective, but not all stereoselective reactions are stereospecific. - All stereospecific reactions are a subset of all stereoselective reactions

stereochemistry of catalytic hydrogenation

Stereospecific syn-addition. Delivered from the catalyst to the same face of the bond.

what r steroids

Steroid: compound w/ a structure derived from the following tetracyclic ring system: 3 cyclohexanes and a cyclopentane - Have a special numbering system 2 structural features common in naturally occuring steroids: 1. In many cases all ring fusions are trans. All-trans ring fusion causes a steroid to be conformationally rigid and relatively flat. 2. Many steroids have methyl groups, called angular methyls, at C's 10 and 13, so-called bc each is located at the vertex of the angle at a bridgehead C

describe the equilibria in nucleophilic substitution rxns

TLDR: equilibrium of substitution rxn - seen as acid-base, strong acid wins How do we know whether the equilibrium for a given substitution is favorable? - We can look at it like Bronsted acid-base rxn, if alkyl group of alkyl halide is replaced with H. - This comparison is useful because it can be used to predict whether the equilibrium is favorable. Determine whether equilibrium for Bronsted acid-base rxn is favorable. - The equilibrium in any nucleophilic substitution rxn, as in an acid-base rxn, favors release of the weaker base. Some equilibria that aren't too unfavorable can be driven to completion by applying Le Chatelier's principle - Alkyl chlorides normally don't react to completion with iodide ion bc iodide is a weaker base than chloride. Equilibrium favors the formation of the weaker base, iodide. - But in solvent acetone, it happens that potassium iodide is relatively soluble and potassium chloride is relatively insoluble. Thus, when an alkyl chloride reacts with KI in acetone, KCl precipitates, and the equilibrium compensates for the loss of KCl by forming more of it, along with more alkyl iodide.

explain the mechanism of dehydration of alcohols

Strong acids such as H2SO4 and H3PO4 catalyze a beta-elimination rxn in which water is lost from a secondary or tertiary alcohol to give an alkene. (primary carbocation not allowed) - Dehydration: elements of water are lost from starting material. Cyclohexanol is dehydrated to cyclohexene Role of acid catalyst in dehydration is to convert the -OH group, a poor LG, into the -OH2 group, a good LG (bc H2O is a weak base). Alcohol dehydration: 3-steps, entirely acid-base rxns, involves a carbocation intermediate. 1. -OH is activated as a LG by acting as a Bronsted base to accept H from catalyzing acid - Basicity of alcohols is important to the success of the dehydration rxn 2. C-O bond of alcohol breaks in a Lewis acid-base dissociation to give water and a carbocation 3. Conjugate base of catalyzing acid removes a beta-H from the carbocation in another Bronsted acid-base rxn - This step generates the alkene product and regenerates the catalyzing acid H3PO4. Alternatively, the H2O by-product generated in the second step can serve as the base that removes a beta-proton from the carbocation, and the H3O+ formed can also serve as an acid catalyst in the dehydration - NOTE: hydroxide ion doesn't exist here NOTES: - Important principle of acid-base catalysis: an acid and its conjugate base always act in tandem in a mechanism. If H3O+ is a catalyzing acid, its conjugate base H2O will act as a base. - Alcohol dehydration is an E1 rxn. - Dehydration of alcohols is the reverse of the hydration of alkenes. They are the forward and reverse of the same rxn. Principle of microscopic reversibility: must have same intermediates and same rate-limiting transition states. 1) Loss of proton from carbocation intermediate is rate-limiting step. 2) Also, requires that if a catalyst accelerates rxn in 1 direction, also accelerates reverse. So both hydration and dehydration are catalyzed by acids - Involvement of carbocation intermediates explains several experimental facts about alcohol dehydration - Relative rates of alcohol dehydration are in order tertiary > secondary >> primary. Hammond's postulate - If alcohol has more than 1 type of beta-H, a mixture of alkene products can be expected. As in the E1 rxn of alkyl halides, the most stable alkene - greatest # of branches at the double bond - is the alkene formed in greatest amount. - Alcohols that react to give rearrangement-prone carbocation intermediates yield rearranged alkenes Priest note: can't use HCl bc might be a substitution product then, since it's such a good Nu-. H2SO4 isn't bc charge is delocalized

describe the reactivity of sulfonate esters

Sulfonate esters are useful bc they have approximately the same reactivities as the corresponding alkyl bromides in substitution and elimination rxns. Can think of them as a "fat" bromo group. - Reason for this similarity is that sulfonate anions, like bromide ions, are good leaving groups. In general, good LGs are weak bases. Sulfonate esters prepared from primary and secondary alcohols, like primary and secondary alkyl halides, undergo Sn2 rxns in which a sulfonate ion serves as the LG. - Similarly, secondary and tertiary sulfonate esters also undergo E2 rxns with strong bases, and they undergo Sn1-E1 solvolysis rxns in polar protic solvents. Occasionally we'll need a sulfonate ester that's much more reactive than a tosylate or mesylate. In such case a trifluoromethanesulfonate is used. Nicknamed triflate, abbreviated -OTf. A VERY good LG. Exceptionally weak base. Highly reactive. - OTf prepared in the same manner as tosylate esters, except that triflic anhydride is used instead of tosyl chloride E2 rxns of sulfonate esters can be used to prepare alkenes. This rxn is especially useful when the acidic conditions of alcohol dehydration lead to rearrangement or other side rxns, or for primary alcohols in which dehydration is not an option. To summarize: an alcohol can be made to undergo substitution and elimination rxns typical of the corresponding alkyl halides by converted it into a good LG such as sulfonate ester.

describe melting point trends

TLDR: - 1) in homologous series, there's saw tooth pattern. unbranched alkanes w/ odd #'s of C's lie on lower curve of MP than those with even #, due to inefficient crystal packing - 2) symmetrical compounds have higher MP - increases probability of forming crystal Melting point: temp above which a solid is spontaneously transformed into a liquid. Solid and its liquid are in equilibrium. Reflection of noncovalent intermolecular attractions. - Reflect the effects of noncovalent interactions in both the liquid state and the crystalline solid state. So isn't possible to interpret melting points in terms of interactions within a single state of matter. 2 observations 1) Within a homologous series, we often find a "sawtooth" pattern when melting points are plotted against # of C's. - Due to efficiency of crystal packing. Unbranched alkanes w/ odd #'s of C's lie on a lower curve of melting points vs. C # than those w/ an even # of C's. - Crystal packing of "even-C" alkanes is more efficient, van der Waals attractions in the solid state are somewhat great, and melting points are higher 2) Symmetrical compounds tend to have considerably higher melting points than less symmetrical isomers. (More amount of ways its symmetrical the better). Increases probability of forming the crystal. In a crystal, molecules have a regular, repeating arrangement. - There is an inherent statistical preference for crystallization of symmetrical compounds. Symmetry increases the entropy of the crystal. - Can also pack more closely than unsymmetrical ones. When closer, noncovalent attractions are stronger - energy of noncovalent attractions is reduced. Lower enthalpy. - Therefore, free energy is decreased by symmetry - stabilized. More energy must be expended to convert crystal into liquid.

describe the solubility of hydrocarbons in water: hydrophobic bonding

TLDR: - Don't dissolve bc solvent shell around the solute is actually unfavorable Hydrocarbons (apolar, aprotic, nondonor) are not at all like water (polar, protic, donor); therefore, they don't dissolve in water. Let's nitpick - Hydrocarbons DO have a VERY SMALL solubility in water. Is very unfavorable energetically. - Unfavorable standard free energy for dissolving pentane in water is due to the large, negative entropy associated with intermolecular interactions. - Let's understand: consider how solvent water changes when pentane molecules are introduced. Solvent shells of dissolved molecules must come from the solvent water. Turns out that water molecules in the solvation shell of a pentane molecule are different from those in ordinary water. Specifically, the water molecules at the water-pentane interface have reduced motional freedom relative to solvent water. Reduced motional freedom lowers entropy! Therefore, water in the hydrocarbon solvent shell has lower entropy than ordinary water. The energy decrease for the solvent is much greater than the positive entropy of mixing of pentane and water. - Also goes in reverse. Driving force for hydrocarbons to associate. Called hydrophobic bonding. Hydrocarbons aren't afraid of water tho- the enthalpy of solution of hydrocarbons in water is relatively favorable, so not really "hydrophobic." Major reason for this behavior is the entropy change of the solvent water. When hydrocarbon groups associate w/ e/o, low-entropy solvation water is released to become ordinary, higher-entropy water. Resulting delta S is highly positive, and this is why delta G is negative for hydrocarbon association. - Basis of much of biology: protein folding and enzyme binding and membrane formation

how to determine solvent for a liquid covalent compound

TLDR: - Like dissolves like - Solubility in water: better if accept/donate H-bond, then if one, then if neither - But large alkyl groups make alcohols more like alkanes Like dissolves like! Good solvent usually has some of the molecular characteristics of the compound to be dissolved - Example: apolar aprotic solvent likely to be good solvent for another apolar aprotic liquid - Why? Imagine dissolving pentane in hexane. Pentane-pentane and hexane-hexane attractions replaced by hexane-pentane. In both pure liquids, major type of intermolecular attraction is van der Waals attractions. In solution, major type of attraction should also be van der Waals, since both molecules are of the same type. We find that delta G inter is close to zero. Pentane and hexane are miscible (mixable) - form a solution when mixed in any proportions. - We can confidently predict that when the attractions b/w molecules in the pure liquids are similar to the attractions b/w the solvent and solute in the solution, then delta G inter will be small, delta G s will be dominated by the free energy of mixing, and a solution will be formed - Another example: smaller alcohols miscible in water. Major noncovalent interaction in pure substances is H-bonding. - Another example: hydrocarbons and chlorinated solvents are miscible. Pure pentane: van der Waals forces. Dichloromethane: dipole-dipole attractions and van der Waals forces. When 2 solvents are mixed, dipoles of dichloromethane can INDUCE temporary dipoles in nearby pentane molecules, and this interaction results in attractions as well. (dipole-induced dipole attractions). Such interactions are merely variations of van der Waals forces. Fundamentally the same interactions! One of most important practical considerations is solubility in water. Trends: - Alcohol is miscible with water. Is protic. Can both donate and accept an H-bond, an important factor in water solubility. - Ether can accept H-bonds, but can't donate. Some water-like characteristics, but less like water than the alcohol. - Alkyl and alkyl halide can neither donate nor accept H-bonds. Least water-soluble. Balance of "waterlike" and "hydrocarbonlike" - Alcohols w/ long hydrocarbon chains (large alkyl groups) are more like alkanes than are alcohols containing small alkyl groups. - Alkanes are more soluble in other apolar aprotic solvents, including other alkanes. Rule of thumb: compounds containing 1 -OH group for every 5 C's usually have significant water solubility. Solubility important in metabolism of xenobiotics - Xenobiotic: any substance that's not a normal constituent of a living organism. Environmental pollutants and drugs. - When an organism encounters one, usually routes substance into a pathway by which it can be eliminated. If it has low water solubilities, one of the most widely used strategies is to couple the xenobiotic to another group that increases its water solubility. This can then be routed to kidneys, where it can be excreted as urine. Called phase II metabolism. - Glucuronidation is an example. Like-dissolves-like is useful in nature!

reactivity and product distributions in sn1-e1 rxns

TLDR: - Sn1 + E1: prefer tertiary, sumtimez secondary - Sn1 + E1: prefer PP donor solvents (ion dissociation) - E1 favored when >2 alkyl substituents at double bonds - Rearrangements occur - Mixtures of both are always formed, unless no beta-H's Sn1-E1 rxns are most rapid with tertiary alkyl halides, they occur more slowly with secondary alkyl halides, and are never observed with primary alkyl halides. - This reactivity order is expected from the relative stability of the corresponding carbocation intermediates. Rate-limiting transition state by Hammond's postulate suggests it resembles a carbocation - Reactivity order of alkyl halides in Sn1-E1 rxns is I>Br>Cl>F. Same as in Sn2 and E2. Expected bc LG has same role. Bond to halide is breaking in rate-limiting step Sn1-E1 rxns are fastest in polar, protic, donor solvents. This is the result expected in a rxn for which the rate-limiting step is a dissociation of a neutral molecule into ions of opposite charge. Ionic dissociation is favored by solvents that separate ions (polar solvents - solvents with a high dielectric constant). Rate-limiting step is not very different conceptually from dissolution of an ionic compound; both processes hinge on stabilization of ionic species by the solvent. - Sn1 and E1 cannot truly be unimolecular processes. In the transition states of these rxns, solvent molecules must be actively involved in solvating the developing ions When alkyl halide contains 1+ beta-H, more than 1 type of elimination product can be formed. As in E2, alkene with the greatest # of alkyl substitutions at double bond is usually formed in greatest amount, and the ratio of alkene (E1) to substitution product (Sn1) is greater when the alkene formed contains more than 2 alkyl substituents at the double bond. Otherwise, Sn1 wins. - Also, rearrangements are observed in certain solvolysis rxns. Are a telltale sign of carbocation intermediates. Note: mixtures of products are invariably formed (unless alkyl halide has no beta-H's). This rxn is not useful, but lays groundwork for future useful rxns

explain nucleophilicity impacts on sn2 rxn

TLDR: - in period, nuc inc with basicity - in column, nuc inc w/ dec basicity - due to H-bonding w/ solvent! we use PP - don't use PA bc need to dissolve ions and separate products - weak bases can be good nuc bc of their polarizability - diff b/w nuc and basicity: 1) nuc involves bond formation to atoms other than H, 2) nuc measured w/ relative rates, + polarizability has greater effect on nuc Nucleophiles differ significantly in their reactivities. Relative reactivity of a nucleophile: nucleophilicity. What factors govern nucleophilicity in Sn2 rxn? 1) Bronsted basicity of nucleophile 2) Solvent in which the rxn is carried out 3) Polarizability of the nucleophile Basicity and Solvent Effects are interdependent. - We expect some correlation b/w nucleophilicity and Bronsted basicity bc both are aspects of Lewis basicity: in either role a Lewis base donates an e- pair. Trends for nucleophilic anions in PP solvents such as water/alcohols: 1. In series from same period, there is rough correlation of nucleophilicity w/ basicity 2. In series from same column, less basic nucleophiles are more nucleophilic The interaction of the nucleophile w/ solvent is the most significant factor that accounts for these generalizations. - Generalization 2 - H-bonding occurs b/w protic solvent molecules and nucleophilic anions. The strongest Bronsted bases are the best H-bond acceptors. F ion forms much stronger H bonds than iodide ion. When e- pairs of nucleophile H-bonding, they are unavailable for donation to C in an Sn2 rxn. For Sn2 rxn to take place, H-bond b/w the solvent and nucleophile must be broken. More energy is required to break a strong H-bond to F ion than to break a relatively weak H-bond to iodide ion. Extra energy reflected in greater energy barrier, and reaction of F ion is slower. - Generalization 1 - F ion is a worse nucleophile than an O anion with the same basicity. (i don't get this) - Sn2 rxns is considerably accelerated if they are carried out in solvents in which H-bonding is not possible. Effect on rate is due mostly to solvent proticity - whether the solvent is protic. Fluoride ion is by far the most strongly H-bonded halide anion - consequently, the change of solvent has the greatest effect on its rates of Sn2 rxns. Why not use polar aprotic solvents for all such Sn2 rxns? - Element of practicality. For Sn2 rxn in solution, must find a solvent that dissolves a salt that contains the nucleophilic anion of interest. Must also remove solvent from products when rxn is over. Protic solvents dissolve significant quantities of salts. - Solubility of salts in polar aprotic solvents is much more limited bc they lack the protic character that solvates anions. - However, for less reactive alkyl halides, polar aprotic solvents are in some cases the only practical alternative. Polarizability Effects on Nucleophilicity - Why should weak bases be good nucleophiles? - Nucleophilic atoms from higher-numbered periods of periodic table are very polarizable. Polarizability is a measurement of how easily an e- cloud is distorted by an external charge - how "squishy" an e- cloud is. Valence e- clouds are polarizable bc they are screened from nucleus by nonvalence e-'s and are easily pulled away from nucleus. Distortion forms a partial bond to the electrophile in a transition state; more bonding can occur at longer distances if nucleophile is polarizable, leads to transition state of lower energy. - Summary: weak bases can be good nucleophiles if the nucleophilic atom is highly polarizable. Nucleophiles and bases both donate e-'s in rxns. However, there are important differences b/w them 1. Nucleophilicity involves bond formation to atoms other than H, whereas basicity involves bond formation to H 2. Nucleophilicities are measured with relative rates, but basicities are measured with equilibrium constants- that is, pKa values. Polarizability has a greater effect on nucleophilicity than on basicity. priest: OH- is a better nucleophile than COO- bc COO- is stabilized thru resonance, so really has -1/2 charge on it. want a point localized charge for a good nucleophile!

describe attractions b/w permanent dipoles

TLDR: - molecules w/ permanent dipoles have higher BP than alkanes of same size/shape - polarizability is offset by attraction b/w dipoles - but for ethers, BP are not v diff from alkanes, bc van der waals attractions become dominant source at modest size - still, very polar molecules have much higher BP points, even at larger masses - tradeoff b/w size and polarity is apparent in alkyl halides: alkyl Cl has same BP as alkanes (equal tradeoff), alkyl Br and I both have lower bc alkanes so much larger Molecules with permanent dipoles can have higher boiling points than the alkanes of the same size and shape. - Results from greater attractions between molecules in the liquid state. Molecules with permanent dipoles are attracted to each other because they can align part of the time in such a way that the negative end of one dipole is attracted to the positive end of the other. Molecules are constantly moving in the liquid state, but on average, this attraction exists and raises the boiling point of a polar compound. - Electronegativity of O reduces its polarizability, but this reduction in polarizability is more than offset by the attraction b/w the permanent dipoles. However! Except at very small molecular masses, boiling points of ethers and alkanes are not very different - This is because van der Waals attractions between alkyl groups, and the resulting induced dipoles, become the dominant source of intermolecular attractions even in molecules of modest size. - However, very polar molecules show significantly higher boiling points than alkanes, even at large molecular masses. - Nitriles have particularly high boiling points. Unusually large dipole moments. Tradeoff b/w molecular size and polarity is apparent in boiling points of alkyl halides - Alkyl chlorides have about the same BPs as alkanes of the same molecular mass - Alkyl bromides and iodides have lower BPs than alkanes of same mass - ALL alkyl halides have significant dipole moments. Although Br and I are considerably less electronegative than Cl, the longer C-halogen bond lengths increase the dipole moment, which is a product of charge separation and bond length - So why? - Relatively high densities show that alkyl halide molecules have large masses within relatively small volumes. Thus, for a given molecular mass, alkyl halide molecules have smaller volumes than alkane molecules. Attractive forces b/w molecules are greater for larger molecules. - The effects of molecular volumes and polarity oppose each other. They nearly cancel in the case of alkyl chlorides, which have about the same BP as alkanes. However, alkane molecules are so much larger than alkyl bromide and alkyl iodide molecules of the same molecular mass that the size (surface area) effect trumps polarity.

describe hydrogen-bonding :)

TLDR: - reason why alcohols have high BP - donor: atom which gives H (Bronsted acid) - best: O, N, X, bronsted acids - acceptor: accepts H (Bronsted base) - best: O, N, anions, bronsted bases - to bond b/w identical molecules, must have both - results from 1) weak covalent interaction and 2) electrostatic attration b/w partial charges BPs of alcohols (especially of lower molecular mass) are unusually high when compared with those of other organic compounds. - Hydrogen bonding: association of a H on one atom with an unshared e- pair on another. Can occur within the same molecule, or b/w molecules. Is a weak association. - Requires 2 partners: the H-bond donor and the H-bond acceptor. - Donor: atom to which the H is fully bonded (analogous to Bronsted acid) - Acceptor: atom bearing the unshared pair to which H is partially bonded (analogous to Bronsted base) - Can serve both roles! But since networks are not static, are rapidly breaking and re-forming (for H-bonding to occur b/w identical molecules, must contain BOTH a donor and an acceptor) - Results from combo 2 factors: 1) weak covalent interaction b/w a H on the donor atom and unshared e- pairs on the acceptor atom; 2) electrostatic attraction b/w oppositely charged ends of 2 dipoles. Relative importance unknown - Best H-bond donor atoms in neutral molecules are O, N, and halogens. Also, all strong Bronsted acids are also good H-bond donors. - Best H-bond acceptors in neutral molecules are the electronegative first-row atoms O and N. Most anions with unshared pairs and all strong Bronsted bases are also good H-bond acceptors. H-bonding accounts for unusually high BPs of alcohols - To vaporize liquid, H-bonds b/w molecules must be broken, and breaking H-bonds requires E. E is manifested as an unusually high BP - In gas phase, H-bonding is much less important Also important in other ways - Affects water solubility of organic compounds - Important phenomenon in biology. Critical roles in maintaining the structures of proteins and nucleic acids

describe the solubility of solid covalent compounds

TLDR: solids with high MP are less soluble Dissolving solid in liquid solvent is not as simple as dissolving liquid. Must become liquid, then dissolve. - Melting a solid is part of the solution process and the energy required for melting adds an additional free-energy increment to the process. - Have to take into consideration not only like-dissolves-like, but also how easy or difficult it is to melt the solid. - Solids with high melting points should have greater delta G fusion,298 and therefore be less soluble in a given solvent than isomers of a similar structure with a much lower melting point Examples: - Recall that symmetrical compounds have higher melting points. Should have lower solubilities in any solvent than their less symmetrical isomers. Flipside of solubility is ease of crystallization - Can be a challenge to crystallize solid with low melting point. Solids with high melting points are generally easier to crystallize

describe the solubility of ionic compounds

TLDR: - Better ability of solvent to separate ions: high dielectric constant - Donor interaction - solvent acts as Lewis base to donate unshared e- pair. - Charge-dipole interaction - solvent interacts electrostatically w/ charge of ion - (These happen in solvation of both anion and cation) - H-bond interaction: If solvent is protic and anion can accept H-bonds Ionic compounds in solution can exist in several forms. - Ion pair: each ion closely associated w/ an ion of opposite charge - Dissociated ion: moves more or less independently in solution and is surrounded by several solvent molecules, called collectively the solvation shell or solvent cage - Solvation: favorable interaction of a dissolved molecule with solvent - When solvent molecules interact favorably with an ion, said to solvate the ion Most ionic inorganic compounds are solids. Ones we are most familiar with have high melting points. Shows that unlike van der Waals or H-bonds, forces b/w ions in a crystal of sodium chloride are very strong. Attractions b/w ions: electrostatic attractions. Energies of these attractions governed by electrostatic law - For a solvent to dissolve an ionic compound, the solvent must provide significant energetically favorable solvation to replace the large attraction b/w the ions in the crystal. Fact that sodium chloride can be dissolved shows that the noncovalent forces involved in solvating ions must be considerable. Let's examine the factors - Ion separation and ion solvation are mechanisms by which ions are stabilized in solution. Ionic compounds are relatively soluble in solvents in which ions are well separated and well solvated. What solvent properties contribute to this? - Ability of solvent to separate ions is measured by its dielectric constant epsilon. E of attraction of 2 ions is reduced in a solvent w/ a high dielectric constant. Hence, ions of opposite charge have a reduced tendency to associate in solvents w/ high dielectric constants, and thus a greater solubility in those solvents. - Solvent molecules solvate dissolved ions in various ways. Donor solvent can act as a Lewis base to donate unshared e- pair to a cation, which acts as Lewis acid. Called donor interaction. In addition, dipole moments of solvent molecules can interact electrostatically with the charge of the ion. Means water molecule is oriented so that the neg end of its dipole moment vector is pointing toward the positive ion - charge-dipole interaction. Can be considered 2 aspects of same interaction. - For solvation of anion, a favorable charge-dipole interactions can occur in opposite ways. Finally, if solvent is protic and the anion can accept H-bonds, solvent can solvate a negative ion by a H-bond interaction. - Solvation is dynamic. Remember it's a snapshot! These points show why water is the ideal solvent for ionic compounds. It's polar (large dielectric constant) - effective in separating ions of opposite charge. It's protic (good H-bond donor) - readily solvates anions. Is a Lewis base (e- pair donor) - can solvate cations by a donor interaction. Finally, significant dipole moment enables it to provide ion-dipole attractions to both cations and anions. The effective solvation of ions by water can lead to significant solubility changes as a result of acid-base reactions. Benzoic acid has small solubility. When base ionizes it, it dissolves. Bc it becomes an ionic compound! Can be reversed too.

what is the stereochemistry of bromine addition?

TLDR: - cis alkene make enantiomers - trans alkene makes meso compound When cis-2-butene reacts with Br2, the product is 2,2-dibromobutane - 3 stereoisomers of the product are possible: enantiomers and meso compound - Meso compound and enantiomeric pair should be formed in diff amounts because they are diastereomers. If enantiomers are formed, should be formed as the racemate bc the starting materials are achiral - BUT When carried out in lab, only product is the racemate. - Br addition to trans-2-butene, in contrast, exclusively gives the meso compound - Highly stereoselective! The Br addition to most simple alkenes occurs exclusively with anti stereochemistry. Br addition is therefore a stereoselective anti-addition reaction Why is Br addition a stereospecific anti-addition? - One of the main reasons why the bromonium-ion mechanism was postulated! - Bromonium ion can form at either face. - Suppose that bromonium ion reacts with the bromide ion by opposite-side substitution: bromide ion, acting as a nucleophile, donates an e- pair to a C at the face opposite to the bond that breaks, which is the C-Br bond. - This type of reaction MUST occur with inversion of configuration, because as the substitution takes place, the methyl and H must swing upwards to maintain the tetrahedral configuration of C - Reaction of bromide ion at 1 C yields one enantiomer, reaction at the other C yields the other enantiomer - In general, when a nucleophile reacts at a saturated C atom in any substitution rxn, opposite-side substitution is observed If there were to be a carbocation intermediate, Br could add from either plane. Both diastereomers of the product would be formed! Reaction would not be stereoselective. Also would be rearrangements, duh.

competition b/w e2 and sn2 rxns

TLDR: - more substituted alkyl halide: E2 - no beta-H: no E2 - more substituted base: E2 - weak base, good nuc: Sn2 Lewis base acts as nucleophile: Sn2 rxn (substitution) Lewis base acts as a Bronsted base: E2 rxn (elimination) Competition is a matter of relative rates: rxn pathway that occurs more rapidly predominates 2 variables determine which rxn will be major process observed 1) Structure of alkyl halide - More # of alkyl substituents at both alpha and beta-C's, E2 more likely - For Sn2 rxn to occur on alkyl halide with alpha or beta-substituents, the nucleophile must approach through a thicket of interfering H atoms on the substituents that impede its access to the alpha-C. Resulting van der Waals repulsions create energy barrier to Sn2 rxn that decreases its rate - When Bronsted base initiates the E2 rxn, it reacts with a beta-proton that lies near the periphery of the molecule. Much less affected by steric repulsions than rxn at the alpha-C atom - Also: standard free energy of the E2 transition state is lowered by alkyl substitution. So rate of E2 rxn is increased by alkyl substitution - 2 effects of alkyl substitution favor E2 rxn: rate of Sn2 rxn is decreased, and rate of E2 rxn is increased. - Seen not only in tertiary, but also in secondary and even primary alkyl halides. (It seems secondary alkyl halides favor E2, and beta-substituents favor even more! As for primary, every additional beta-substituent favors E2 more, and it becomes actually more favorable when we get to 2 beta-substituents. 2) Structure of base - Highly branched based (tert-butoxide) inc the proportion of E2 relative to Sn2. - When highly branched base reacts at alpha-C to give substitution product, alkyl branches of base suffer van der Waals repulsions w/ the surrounding H's in the alkyl halide molecule. - When such a base reacts at a beta-proton to give the elimination product, the base is further removed from the offending H's in the alkyl halide, and van der Waals repulsions are less severe. - Sn2 is retarded more than E2 rxn by branching in the base, and E2 becomes the predominant rxn. - Also: species w/ nucleophilic atoms from higher periods of periodic table are excellent nucelophiles even though they are relatively weak Bronsted bases. Greater fraction of Sn2 rxn is observed in the rxns of such nucleophiles. Let's summarize: 1. Structure of alkyl halide - Alkyl halides w/ greater # of alkyl substituents at alpha-C give greater amounts of elimination. Consequently, tertiary alkyl halides give more elimination than secondary alkyl halides, which give more than primary - Alkyl halides w/ greater #'s of alkyl substituents at the beta-C give greater amounts of elimination. - Alkyl halides that have no beta-H's cannot undergo beta-elimination. 2. Structure of the base - In comparison of alkoxide bases w/ similar strengths, tertiary alkoxide bases such as tert-butoxide give a greater fraction of elimination than primary alkoxide bases - Weaker bases that are good nucleophiles give a greater fraction of substitution

stereochemistry of hydroboration-oxidation

TLDR: - overall: stereospecific syn-addition - hydroboration: stereospecific syn addition - oxidation: stereospecific substitution w/ retention of configuration Involves 2 distinct rxns, so stereochemical outcome is consequence of stereochemistry of both rxns Hydroboration: stereospecific syn-addition - 2 enantiomers made - This as well as absence of rearrangements provides evidence for concerted mechanism of the reaction Oxidation of organoboranes: stereospecific substitution rxn that occurs with retention of stereochemical configuration Hydroboration-oxidation of an alkene brings about the net syn-addition of the elements of H-OH to the double bond

describe the interconversion of chair conformations

Undergo internal rotations! Since constrained w/in a ring, several internal rotations must occur at the same time. A change in the ring conformation occurs. - 1 chair conformation converted into another, completely equivalent, chair conformation. - Intermediate: boat conformation (1 and 4 both rotate as up as they can, either corner). Not a TRUE intermediate, but handy for models - Involves simultaneous internal rotations about all C-C bonds except those to C-1. - Then after this, same thing except no rotations around carbon 4. - Thus, upward movement of leftmost C and downward movement of rightmost C changes 1 chair conformation into another, completely equivalent, chair conformation - In this process: equatorial H's have become axial, and axial have become equatorial. And all up C's have become down C's and vice versa Interconversion of 2 chair forms of cyclohexane: chair interconversion or chair flip - Energy barrier is low enough that interconversion is very rapid - In any one chair conformation, the axial H's are stereochemically different from the equatorial. Averaged over time, the axial and equatorial hydrogens of cyclohexane are equivalent and indistinguishable

describe energetics of solution formation in GREAT detail :(

TLDR: - there is always statistical driving force of formation of the solution called the entropy of mixing. Is just statistically more probable. - but noncovalent interactions also make a contribution. might be strong enough to overpower desire to dissolve Free E change = free E of "products" (solution) - free E of "reactants" (pure liquids) - When solute A dissolved in a liter of solvent S, free-energy change, delta G, is called the free energy of solution - Delta G = G(solution) - [G(pure solute) + G(pure solvent)] - When delta G < 0, the solution is favorable, and vice versa. Magnitude tells us how favorable/unfavorable process is First aspect of solution formation: regardless of intermolecular interactions involved, there is a statistical driving force for formation of the solution, called the entropy of mixing (delta S mixing): quantitative description of the probability of solution formation that is completely independent of any intermolecular interactions that may be involved - Entropy: measure of probability. If a system goes from a less probable to a more probable state, the entropy of the system has increased. - Example: box of 10 blue balls and another of 1000 red balls. Shake. Would blue balls stay together? No! Would disperse, and odds are each blue ball is surrounded by only red balls. Huge number of possible arrangements of balls that can give this result, but only 1 (or few) where blue balls could stay together. Dispersed state is much more probable. - So, if we squirt water-soluble blue ink into beaker of water, it will spontaneously disperse because in the dispersed state there are many more ways the ink molecules can be located relative to when they stay together. Result of entropy! If free energy of mixing were the only free-energy change involved in solution formation, every liquid would dissolve in every other liquid! But we know this isn't the case. - Reason: noncovalent interactions also make a contribution to the free energy! - Forming a solution involves replacing some S-S interactions and all of the A-A interactions with S-A interactions. - Delta G s (overall free energy of solution) = delta G inter (associated w/ these interactions) + delta G mixing - So overall free energy results from balance of interactions and always-favorable free-energy of mixing - Example: 10 blue balls contain embedded bar magnet. If we mix them with 1000 red balls and shake, they would not disperse if the magnets were strong enough. In this case, the attractions b/w the blue balls overcome the tendency toward spontaneous mixing. Separating the blue balls would require energy! Similarly, if solute/solvent molecules have significant intermolecular attractions for each other that are not replaced by compensating S-A interactions in solution, then delta G inter > 0. If it's large enough, it overcomes the entropy of mixing, and delta G s > 0. As it increases, the amount of A that dissolves in S decreases. - Let's suppose solute and solvent are so similar the intermolecular interactions are exactly the same. In this gase, delta G inter = 0 and the overall delta G s equals the delta G mixing.

describe van der Waals (dispersion) forces and polarizability

TLDR: (also called LDFs) - Liquids exist bc of them - they are the interaction you overcome to vaporize a liquid - Larger molecules have more surface area so higher BP. BP increase w/ molecular size. Branching decreases surface area, so lower BP - More polarizable (squishy e- cloud) the molecule, the higher the BP. More e-negative = less polarizable BP increase regularly w/ molecular size w/in a homologous series. - Inc about 20-30 deg C per C atom Why do liquids exist? - E-'s in bonds are not confined b/w nuclei, but rather reside in bonding MOs that surround the nuclei, in "e- cloud." These clouds are squishy and undergo distortions. Such distortions occur rapidly and at random, and when they occur, they result in the temporary formation of regions of local positive and negative charge. Cause a temporary dipole moment within the molecule. - When a second molecule is located nearby, its e- cloud distorts to form a complementary dipole, called an induced dipole. The positive charge in one molecule is attracted to the negative charge in the other. The attraction between temporary dipoles - called a van der Waals attraction, or a dispersion interaction- is the cohesive interaction that must be overcome to vaporize a liquid. - Alkanes don't have permanent dipole moments. These are TEMPORARY, and the presence of a temporary dipole in one molecule induces a temporary dipole in another. They come and go. But over time, "nearness makes the molecules grow fonder." - The time scale of these attractions is extremely small. Can form and dissipate many times during a molecular collision. Form "flickering dipoles." However, if one molecule changes its e- distribution, the other instantly follows suit so as to maintain a net attraction. Why do larger molecules have higher BP? - Van der Waals attractions increase with the surface areas of the interacting e- clouds. The larger the interacting surfaces, the greater the magnitude of the induced dipoles. - Note: it's surface area, NOT volume. The more a molecule approaches spherical proportions, the less surface area it presents to other molecules (3D object with the minimum surface-to-volume ratio). - So boiling points tend to be lower for highly branched molecules, because they have less molecular surface available for van der Waals attractions. Polarizability: direct measure of how easy it is energetically for an external charge (or dipole) to alter the e- distribution in a molecule or atom. More polarizable molecules have "squishier" e- clouds. - Molecules that contain very electronegative atoms are typically not very polarizable, because their e-'s are held tightly and pulled closer to the nuclei. - Molecules with atoms of lower electronegativity are typically more polarizable. - F is very e-negative, so e-'s are difficult to pull away from the nucleus. Valence e-'s in iodine lie in level-5 orbitals, which are easily deformed by external charges because they are held less strongly - Therefore: a liquid consisting of more polarizable molecules should have a higher boiling point than one consisting of less polarizable molecules, because the van der Waals attractions are stronger between more polarizable molecules. - Perfluorohexane, despite considerably greater molecular mass and size, has lower boiling point than hydrocarbon hexane - Teflon (polytetrafluoroethylene) is slippery because it does not adhere to other molecules, including surfaces. Weak noncovalent attractions with practically everything. - Helium has the lowest polarizability of any element. Basically never a liquid

explain regioselectivity of free-radical halogenation

TLDR: Br selective, Cl is not When it takes place on a hydrocarbon with more than 1 type of H, more than 1 product can be obtained. For example, bromination of isobutane could give both tertiary and primary alkyl bromides. But it almost entirely gives tertiary! - There are 9 primary H's and only 1 tertiary H. On a statistical basis, we would expect 1/9 of tertiary product. But no. - Is a consequence of relative stabilities of 2 possible free-radical intermediates. Rate-limiting step is the first propagation step - step that forms the C radicals. Only difference is the free-radical intermediate. Tert-butyl is much more stable. - Hammond's postulate: bc tertiary radical is more stable than primary, it's transition state has lower energy. So it is formed more rapidly. Chlorination is much less selective than bromination. Light-promoted chlorination of isobutane actually gives a little more of the primary alkyl chloride. Why is bromination so much more selective? - The H abstraction step is exothermic for Cl but endothermic for Br. Is a direct consequence of the much greater BDE of the H-Cl bond than the H-Br bond. Bromination goes to completion only bc the second propagation step, and thus the overall reaction, is very exothermic. - In addition, the exothermic reaction (chlorination) is much faster than the endothermic one (bromination). Cl is MUCH more reactive with hydrocarbons than Br is. - In effect, isobutane and Cl free radical are the "unstable intermediates" in chlorination. It has very little C-radical character, so C-radical stability is not very important in determining the position of the rxn. - Priest: it means that the bond is not really broken, bc otherwise primary radical would not do well. Transition state is more like starting material. Molecule doesn't know it's making primary radical. A more reactive species (Cl) is less selective, and a less reactive species (Br) is more selective. Inverse relationship is called the reactivity-selectivity principle. This is often observed.

what is the stereochemistry of the E2 rxn

TLDR: anti-elimination bc 1) staggered, 2) no steric hindrance, 3) MO stuff Tetrahedral alpha and beta-C's become trigonal when the beta-proton is removed and the halide leaves. The R-groups on these 2 C's move into a common plane that also contains the alkene C's. Syn-elimination: dihedral angle b/w C-H and C-X bonds is 0 deg: the H and X groups leave from the same side of the reference plane. Anti-elimination: dihedral angle is 180 deg. Leave from opposite sides of the reference plane. Only these 2 eliminations are possible because only these geometries result in the planar alkene geometry required for pi-orbital overlap. Investigation of stereochemistry of elimination rxn requires the alpha and beta-C's to be stereocenters in both the starting alkyl halide and the product alkene. It is found experimentally that most E2 rxns are stereoselective anti-eliminations! 3 reasons why 1) syn-elimination occurs through a transition state that has an eclipsed conformation, whereas anti-elimination occurs through a transition state that has staggered conformation. As consequence, anti-elimination is faster 2) base and LG are on opposite sides of molecule, out of each other's way. If on same side, can interfere sterically w/ e/o 3) anti-elimination involves all-opposite-side e- displacements, as in Sn2 rxn. Some sort of MO theory transition-state energy thing Sapling note: for rings, make sure that the bond you're making is possible to make - must be anti-elimination!!!

what are LG effects in the sn2 and e2 rxns

TLDR: better LG, weaker base. F useless When alkyl halide is used as starting material in Sn2 rxn, choice of LG is possible. Halide that reacts most rapidly is usually preferred. - Can be predicted from close analogy b/w Sn2 rxns and Bronsted acid-base rxns. Recall, ease of dissociating H-X bond depends mostly on H-X bond energy, and for this reason H-I is the strongest acid. Likewise, Sn2 reactivity depends primarily on C-halogen bond energy, which follows same trend: alkyl iodides are the most reactive alkyl halides, alkyl fluorides are the least reactive - Best LGs in Sn2 rxns are those that give the weakest bases as products. Alkyl F's are useless as LG's. All other halides are acceptable. priest: LG more stable if resonance!

describe the protonolysis of grignard reagents and organolithium reagents

TLDR: converts organometallic reagent into hydrocarbon All rxns of Grignard and organolithium reagents can be understood in terms of the polarity of the C-metal bond. Bc C is more electronegative than either Mg or Li, the neg end of the C-metal bond is the C! - Imagine carrying this to the extreme by breaking the C-metal bond so the metal becomes pos charged and e-deficient, and the pair of e-'s in the bond ends up on C. Such a C, bearing 3 bonds, an unshared e- pair, and a neg formal charge, is a carbon anion, or carbanion. Grignard and organolithium reagents react as if they were caranions. - They are not true carbanions bc they have covalent C-metal bonds. However, we can predict their reactivity by treating them conceptually as carbanions. This view predicts the outcome of simple Bronsted acid-base rxns. Carbanions are powerful Bronsted bases, bc their conjugate acids, the corresponding alkanes, are extremely weak acids, with pKa values in 55-60 range. Logic then is: 1. R-H is a very weak acid, therefore 2. R:- is a very strong base, therefore 3. R-MgX and R-Li are also strong bases They are such strong bases that they react instantaneously with even weak acids such as water or alcohols. The products of such a rxn are the hydrocarbon- the conjugate acid of the organometallic "carbanion"- and the conjugate base of the proton source - hydroxide ion (if acid is water) or alkoxide ion (if acid is alcohol) - (AND the magnesium-halide charged compound) These rxns are examples of protonolysis: any rxn w/ the proton of an acid that breaks chemical bonds. Example: C-metal bond of Grignard reagent is broken. - Is useful, because it provides a method for the preparation of hydrocarbons from alkyl halides. - It's particularly useful in preparing hydrocarbons labeled with H isotopes deuterium or tritium by rxn of a Grignard reagent with the corresponding isotopically labeled water.

what is the stereochemistry of the sn2 rxn

TLDR: inversion of configuration We can investigate stereochemistry only if C at which substitution occurs is a stereocenter in both reactants and products. A substitution can occur at stereocenter in 3 stereochemically different ways: 1) With retention of configuration 2) With inversion of configuration 3) With a combo of 1 and 2; mixed retention and inversion Retention of configuration: approach of the nucleophile and departure of the leaving group occur from the same direction (same-side substitution) Inversion of configuration: approach of nucleophile and loss of leaving group on asymmetric C occur from opposite directions (opposite-side substitution), the other 3 groups on C must invert or "turn inside out" to maintain the tetrahedral bond angle. - Products of first and second are thus enantiomers! The 2 types of substitution can be distinguished by subjecting 1 enantiomer of a chiral alkyl halide to the Sn2 rxn and determining which enantiomer of the product is formed. If both paths occur at equal rates, then the racemate will be formed. Experimental results: - Recall the opposite-side substitution observed for the rxn of bromide ion and other nucleophiles with the bromonium ion in the addition of bromine to alkenes. This is an Sn2 rxn. - Inversion of stereochemical configuration is generally observed in all Sn2 rxns at C stereocenters. - Calls to mind the inversion of amines. Central atom is turned "inside out" and is approx sp2-hybridized at the transition state. In amine inversion, the 2p orbital on the N contains an unshared e- pair during transition state. For Sn2 rxns on C, the nucleophile and leaving group are partially bonded to opposite lobes of the C 2p orbital. - Why is opposite-side substitution preferred in the Sn2 rxn? bc gives bonding overlap (doesn't matter)

what is the effect of alkyl halide structure on the sn2 rxn

TLDR: less substitution of beta and alpha C, Sn2 faster Sn2 rxn reaction rate varies with the structure of the alkyl halide. If it is very reactive, its Sn2 rxns occur rapidly under mild conditions. If unreactive, severity of rxn conditions must be increased. However, harsh conditions increase the likelihood of competing side rxns. Hence, if an alkyl halide is unreactive enough, the reaction has no practical value. Trends: - Increased alkyl substitution at the beta-C (and alpha-C but maybe to a lesser extent?) retards an Sn2 rxn. Methyl halide easily undergoes substitution, as approach of nucleophile and loss of LG are relatively unrestricted. But when neopentyl halide reacts w/ nucleophile, both nucleophile and LG experience severe van der Waals repulsions with H's of the methyl substituents. These repulsions raise the E of the transition state and therefore reduce the rxn rate. Example of a steric effect: any effect on a chemical phenomenon caused by van der Waals repulsions. - Explains why elimination rxns compete with the Sn2 rxns of secondary and tertiary alkyl halides: these halides react so slowly in Sn2 rxns that the rates of elimination rxns are competitive.

describe the relative stabilities of monocyclic alkanes

TLDR: more C's, more stable til cyclohexane! :) Monocyclic compound: compound that contains a single ring - Cyclohexane, cyclopentane, etc. Relative stabilities gives important clues ab their conformations Can be determined by heats of formation Have the same empirical formula, CH2 - Gives smallest whole-number proportions of the elements - When compounds have the same empirical formula, their heats of formation (and thus stabilities) can be compared on a per carbon basis! Divide heat of formation of each compound by its # of C's! Cyclohexane is the most stable! - Further insight comes from comparing to typical noncylic alkane - Pentane -> heptane, more stable - Data shows: heats of formation change regularly within a homologous series - Cyclohexane has the same stability as a typical unbranched alkane! Cyclohexane is the most widely occurring ring in compounds of natural origin - Prevalence is undoubtedly a consequence of stability, makes it most important

describe the role of solvent in alcohol acidity

TLDR: primary alcohols more acidic bc conjugate base is better solvated Acidities go methyl > primary > secondary > tertiary. - Not polar effect bc in gas phase (absence of solvent), order is reversed - Note: relative order changes. Alcohols are more acidic in solution than as gas - Branched alcohols are more acidic in gas phase bc alpha-alkyl substituents stabilize alkoxide ions more effectively than H's. (stabilization of a conjugate-base anion increases acidity). Stabilization occurs by a polarization mechanism: e- clouds of each alkyl group distort so that e- density moves away from the neg charge on the alkoxide O, leaving a partial pos charge on the central C. Anion is stabilized by its favorable electrostatic interaction with this partial positive charge. Bc tertiary alcohol has more substituents, is stabilized more. So tertiary more acidic in gas phase Same effect is present in solution, but order shows another more important effect is operating as well. Acidity order is due to effectiveness in which alcohol molecules SOLVATE their conjugate-base anions. Anions are solvated (stabilized in solution) by H-bonding with the solvent. Such H-bonding is nonexistent in the gas phase. It's thought that the alkyl groups of a tertiary alkoxide somehow adversely affect the solvation of the alkoxide O, mechanism is unclear (NOT a simple steric effect). Reducing solvation of tertiary alkoxide increases energy and increases basicity. Primary alkoxides have fewer alkyl branches, so solvation is more effective. To summarize: tertiary alkoxides are more basic in solution than primary alkoxides. Primary alcohols are more acidic in solution than tertiary alcohols. Solvent is not an idle bystander in the acid-base rxn; it takes an active role in stabilizing the molecules involved, especially the charged species

describe cyclic meso compounds

TLDR: same 2 substituents on 1,2 spots are ON AVERAGE meso. 1,3 are fr meso doe Cyclohexane with 2 same substituents going same way across plane is example of meso compound - Let's focus on cis-1,2-dimethylcyclohexane - Asymmetric C's and have chiral stereoisomers (the trans isomers) - Chair conformations show that each one is chiral, but each conformation is the enantiomer of the other - In other words, it is a mixture of conformational enantiomers. If we could isolate the individual conformations, each would be chiral and optically active. But because they interconvert rapidly, it cannot be isolated in optically active form. - Over any realistic time interval, we can think of it as the time-averaged, planar-ring structure, which is meso. Same is tru for any cis-1,2-disubstituted cyclohexane in which the substituents are identical Cis-1,3,-dimethylcyclohexane however consists of 2 chair conformations that are true meso compounds, because each one has an internal plane of symmetry - Are conformational diastereomers - Will never be optically active!

overview of what a nucleophilic substitution rxn is

When a methyl halide or a primary alkyl halide reacts w/ a nucleophile, such as sodium ethoxide, a reaction occurs in which the nucleophilic atom of the base, in this case oxygen, displaces the halogen, which is expelled as halide ion. In the simplest type of nucleophilic displacement rxn, a nucleophile donates an e- pair to an electrophile to displace a leaving group - In this chapter, the electrophile typically is a C and the LG will typically be a halide ion - In the example: base is conjugate base of ethanol. In general, conjugate bases of alcohols are called alkoxides. - Sodium ion plays role of a spectator ion: has no overt role in reaction. - For simplicity, we often write nucleophilic substitution rxns as net ionic equations: in which only the reacting ionic components are shown, and spectator ion is omitted - You can assume a spectator ion is present - often Na+ or K+ More notes - Although many nucleophiles are anions, others are uncharged. - Can be an intramolecular substitution rxn- happens w/in same molecule

what is the regioselectivity of the e2 rxn

When alkyl halide has 1+ type of beta-H, more than one alkene product can be formed. - When simple alkoxide bases such as methoxide/ethoxide are used, the predominant product of an E2 rxn is usually the most stable alkene isomer. Recall: most stable are those with most alkyl substituents at the C's of the double bond. - Then, statistics determine which one is formed in greater amount. Unless there are other factors... - The distribution of products must reflect the relative rates at which they are formed. Hence, we look for the explanation in transition-state theory Transition state can be visualized as structure that lies somewhere b/w alkyl halide and alkene (plus other species present). To extent that transition state resembles the alkene product, it is stabilized by the same factors that stabilize alkenes - alkyl substitution at the double bond. - Rxn that can give 2 alkene products is rly 2 rxns in competition, each with its own transition state. Reaction with transition state of lower E - one with more alkyl substitution at the developing double bond - is the faster rxn. - Zaitsev elimination: elimination rxn that forms predominantly the most stable alkene isomers. Describes regioselectivity of elimination rxns When alkyl halide has 1+ type of beta-H, a mixture of alkenes is generally formed. Formation of mixture means that the yield of the desired alkene isomer is reduced. Bc alkenes in such mixtures are isomers, they generally have similar boiling points and are therefore difficult to separate. Consequently, the greatest use of E2 elimination for the preparation of alkenes occurs when the alkyl halide has only 1 type of beta-H, and only 1 alkene product is possible. Sapling: strong bulky base is not able to deprotonate a H on a more highly substituted C as well as one that is sterically hindered. Results in Hoffman product: not more stable alkene (less substitution at the alkene C's) - only LARGE BULKY BASE like tert-butoxide

what is an alpha-elimination rxn and what undergoes this

When an alkyl halide contains no beta-H's but has an alpha-H, a diff sort of base-promoted elimination is sometimes observed. Chloroform (H-CCl3) undergoes this. - Chloroform, although a weak acid, is a much stronger acid than an alkane bc of the polar effect of the 3 Cl's. It's acidity is high enough that it can react as an acid with strong bases. Therefore, when its treated with an alkoxide base such as potassium tert-butoxide, a small amount of its conjugate-base anion is formed. - This anion can lose a chloride ion to give a neutral species called dichloromethylene. This is an example of a carbene: a species with a divalent C atom. It has only 6 valence e-'s on C; its C is 2 e-'s short of an octet. Carbenes are unstable and highly reactive species. Formation of dichloromethylene involves an elimination of the elements of HCl from the SAME C atom. Alpha-elimination: elimination of 2 groups from the same atom. - When an alkyl halide has beta-H's, beta-elimination occurs in preference to an alpha-elimination bc alkenes, the products of beta-elimination, are much more stable than carbenes, products of alpha-elimination.

overview of solvolysis and what undergoes it

When primary alkyl halide is dissolved in a protic solvent with NO added base, Sn2 rxn takes 2+ weeks, because a neutral, un-ionized alcohol is a weak base and therefore a poor nucleophile. When a tertiary alkyl halide such as tert-butyl bromide is subjected to the same conditions, however, both substitution and elimination rxns occur readily. - Rxn of an alkyl halide with a solvent in which no other base or nucleophile has been added is called a solvolysis (literally, bond breaking by solvent). - Substitution that occurs in solvolysis of tert-butyl bromide cannot involve an Sn2 mechanism because chain branching at the alpha-C retards the Sn2 rxn. (Primary alkyl halide sn2 solvolysis is slow, so tertiary should be even slower) - Elimination cannot occur by E2 bc a strong base is not present.

overview of a beta-elimination rxn

When tertiary alkyl halide reacts with a Bronsted base such as sodium ethoxide, a very different type of reaction is observed. - Elimination reaction: reaction in which 2+ groups (in this case H and Br) are lost from within the same molecule. In alkyl halide, C bearing the halogen is often referred to as the alpha-carbon, and adjacent C's are beta-carbons. Notice that the halide is lost from the alpha-C and a proton from a beta-C. - An elimination that involves loss of 2 groups from adjacent C's to form a double bond is called a beta-elimination. Most common type of elimination rxn. Conceptually the reverse of an addition to an alkene. - Strong bases promote the beta-elimination rxns of alkyl halides. Among most frequently used bases are alkoxides. Most common: ethoxide (as sodium ethoxide) and tert-butoxide (potassium tert-butoxide). - Often conjugate-acid alcohols of these bases are used as solvents. Just as -OH is used as a solution in its conjugate acid water, sodium ethoxide used as solution in ethanol and potassium tert-butoxide in tert-butyl alcohol. - If the reacting alkyl halide has 1+ type of beta-H atom, then more than 1 beta-elimination rxn are possible. When they occur at comparable rates, more than one alkene product are formed.

list the 9 apolar solvents

hexane 1,4-dioxane benzene diethyl ether chloroform ethyl acetate acetic acid THF dichloromethane

are methanol and tert-butoxide good bases?

methanol: poor nuc, poor base tert-butoxide: strong base

stereochemistry of oxymercuration-reduction

not stereoselective rxn - Oxymercuration is a stereospecific anti-addition. Occurs by cyclic-ion mechanism, like Br addition, so it works the same! - But the reaction with NaBH4 varies. Loss of stereochemical configuration! - Oxymercuration-reduction overall is NOT a stereoselective rxn. Still is highly regioselective, so useful in situations where stereoselectivity is not an issue