Organic Chemistry 1

If a compound rotates light clockwise it is called ?

(+) or d (dextrorotary)

If a compound rotates light counterclockwise it is called ?

(-) or l (levorotary)

Rank the following according to decreasing bond length: a) triple bonds b)double bonds c)single bonds

Single > Double > Triple [bond length]

IUPAC nomenclature

Met-, eth-, prop-, but-, pent-, hex-, hept-, oct-, non-, dec- (sec-butyl, isopropyl, isobutyl, tertbutyl)

Huckels Rule

To be aromatic, a ring system must have 4n + 2 pi electrons. The number of pi electrons is set equal to = 4n +2 and if n is 0, 1, 2, 3 the rule is met.

Remember the following regarding geometric isomers

a) Cis isomers often have a dipole moment, but trans isomers usually do NOT (ex, cis 1,2-dichloroethene vs. trans-1,2-dichloroethene). b) Cis isomers often experience "steric hindrance", resulting in a higher energy molecule, but trans do NOT.

Remember the following regarding enantiomers

a) They have opposite R/S configuration at every chiral carbon (mirror images). b) They rotate plane polarized light to the same degree, but in different directions. c) They have all the same physical properties (boiling points, reactivity, etc) EXCEPT for: a) how they rotate plane polarized light and b) the products they form when reacted with another chiral compound.

NaBH4 can only reduce...

aldehydes and ketones to an alcohol.

LiAlH4 and H2/pressure can reduce

aldehydes, ketones, carboxylic acids and esters to alcohols.

Electrophilicity

are ALWAYS electron poor. They will always have a full or partial positive charge. Electrophiles always get attacked by electron rich species, NOT the other way around!

The second bond or third bond to be formed between two elements...

are ALWAYS pi bonds and involves side to side overlap of two p-orbitals. Because pi bonds require side-to-side overlap, the atoms must be fairly close to one another.

Hybridization

sp= linear (180) sp2 = Trigonal planar or bent (120) sp3 = Tetrahedral, trigonal pyramidal, or bent (109.5) sp3d= Trigonal bipyramidal, seesaw, T-shaped, or linear (90, 120, or 180) sp3d2= Octahedral, square pyramidal, or square planar (90)

Relative Configuration

Two molecules have the same relative configuration if their spatial arrangement is identical, but they have one and only one non-identical substituent.

Enantiomers

Two molecules with the same formula and the same bond-to-bond connectivity that are non-identical, non-superimposable mirror images. They contain at least one chiral center.

Important Classifications of Resonance

1) Resonance is a "snapshot" of differing electron arrangements of electrons that contribute to the "actual structure". 2) The actual structure is a weighted average (ex. hybrid) of all the contributors and does NOT look exactly like any of the individual resonance structures. 3) Individual resonance structures contribute differently; The most stable structures contribute the most to the actual structure and the least stable structures contribute the least. 4) The actual structure DOES NOT resonate back and forth between forms, it is a PERMANENT weighted hybrid of the contributing structures.

Steps in grignard synthesis

1). Due to the very low electronegativity of Mg, the R group in RMgBr gains significant electron density and more or less acts as if it were a carbanion (R-), attacking the electrophilic carbonyl carbon. This occurs in a single step, kicking the electrons in the C=O bond up onto the oxygen. 2). The negatively charged oxygen is protonated, yielding an alcohol.

Shape and bond angle are determined by?

1). Hybridization 2). Lone pairs of electrons

Coordinate covalent bonds

A covalent bond in which both electrons shared in the bond are donated by one atom. Usually more than one of these "donor" molecules (ex. Lewis bases) surround and bind a single "recipient" molecule (ex. Lewis acid; usually a metal). For the MCAT, if a molecule does not have a lone pair of electrons it will NOT participate in a coordinate covalent bond. The complex formed by the metal and the molecules forming coordinate covalent bonds with that metals, is called a "coordination complex".

Alcohol Acidity

-Alcohols are less acidic than water. -Alcohol acidity increases from tertiary to secondary to primary.

Characteristics of oxidation of alcohols

1 Alcohols → Aldehydes → Carboxylic Acids 2 Alcohols → Ketones 3 Alcohols → They CANNOT be oxidized further!!!!!!!!!!! Secondary alcohols can only form ketones, and tertiary alcohols cannot be oxidized at all.

Rules when drawing resonance structures

1) Atoms can NEVER be moved 2) Single bonds can NEVER be moved 3) All structures must obey the octet rule 4) All structures must have the same number of valence e's (ex. the number of electrons in bonds plus the number of electrons in lone pairs). This is NOT to say that individual atoms will not change their valence. In one structure they may have a formal charge and in another they may not, but in all structures the total number of valence electrons for the structure as a whole must be constant. 5) Tail of an arrow showing electron flow during resonance can only start from a lone pair, a double, or a triple bond.

Predicting Reactions and Products:

1) Carbocations: The mechanism will always proceed through the most stable carbocation (unless peroxide is present). Carbocation stability =tertiary>secondary>primary 2) Steric Hindrance: If more than one mechanism, intermediate, electrophile, or nucleophile is possible, the one that involves the LEAST steric hindrance will be favored. 3) Count your Carbons: Be sure that the product has the correct number of carbons. Pay special attention to those reactions that a add to, or take away from, the length of the carbon chain (eg grignard synthesis, Hofmann degradaton, aldol condensation, acetoacetic ester synthesis)

What are exceptions to the octet rule?

1) Hydrogen and Helium: stable with two electrons in their valence shells (ex. H2) 2) Boron and Be: stable with only six electrons in their valence shells (ex. BF3) 3) Atoms from the 3rd, 4th, 5th or higher periods can accept more than eight electrons (PCl5, SF6, PO4 3- and SO2 2-)

To determine if a group is electron donating or withdrawing:

1) Look at the first atom from the point of attachment. Compare its electronegativity to the atoms bound to it. If it is more electronegative, it will bear a partial negative charge and if it is less electronegative, it will bear a partial positive charge. 2) Atoms with full or partial positive charges withdraw from whatever they are attached to. Atoms with full or partial negative charges donate to whatever they are attached to. 3) Hydrogen is considered neither electron donating or withdrawing. 4) Alkenes are weakly electron withdrawing.

Leaving groups

Atoms or molecules that leave the parent molecule during a reaction and take both electrons from the bond with them. The best leaving groups are those that are the most stable after they leave.

How do you find the maximum number of optically active sterioisomers?

2^n n= the number of chiral centers

Benzene (C6H5)

A benzene ring is a six-membered ring with alternating double and single bonds. (Note: of course, the bonds don't really alternate; they form a conjugated pi system often drawn as a circle.) Three representations: −−Ph, −−C₅H₆, and sometimes−Ar −−Ar is any aromatic ring system which would include phenyl.

Describe the forces responsible for the strength of a bond. What is the relationship between potential energy and bond length?

A chemical bond is a balance of electrostatic forces. We know that species with opposite charges (i.e., nuclei and electrons) will be attracted to each other with a force given by Coulomb's Law: F = Kqq/r2. However, remember that there are also repulsive forces between the two nuclei and between electrons. The bond is formed at a sort of "sweet spot" where potential energy is lowest. Increasing bond length or decreasing it would raise the energy of the bond and therefore weaken it.

Most alcohols are highly soluble in water. Explain why?

Alcohols can hydrogen bond with water, creating a very strong solvent-solute attraction. The only thing that will reduce alcohol solubility is the presence of long non-polar alkyl chains.

Mesyl/ Tosyl

Alcohols: there are times you need to get rid of them. Except there's one problem. They're terrible leaving groups. Remember that good leaving groups are weak bases? Hydroxide ions are strong bases, and therefore very poor leaving groups. However there's a way to turn the OH group into a good leaving group - if you can convert it into a weaker base. One practical way this is done is with the sulfonates p-toluenesulfonylchloride (TsCl) and methanesulfonylchloride (MsCl). Treatment of an alcohol with TsCl or MsCl, usually in the presence of a weak base such as pyridine, results in the sulfonate esters. Conversion to the sulfonate esters does one thing: the conjugate bases - toluenesulfonate and methanesulfonate are now extremely weak bases, since they're heavily stabilized by resonance. Weak bases, you say? That makes them great leaving groups. And you are right. The sulfonate esters participate easily in reactions such as substitution and elimination reactions.

synthesis of an alkane from an alkene

Alkanes can be formed by reducing an alkene with H2 in the presence of a metal catalyst. The reaction is an example of syn addition, where both new bonds are formed on the same side . In anti addition, the new bonds are formed on opposite sides. CH2=CH2 + H2/Pd(catalyst) → CH3CH3

Label each of the following as electron donating or electron withdrawing Alkyl group, nitro groups, cyano groups (nitriles), sulphones, amines, carboxylic acids, esters, alcohols, and quaternary amines?

Alkyl groups are weakly electron donating; nitro groups are strong withdrawing groups; cyano groups are electron withdrawing; sulphones are electron withdrawing (assuming connection to the sulfur); amines are electron donating; carboxylic acids are electron withdrawing, esters are electron withdrawing (assuming connection to the carbonyl; if connected to the oxygen of the -OR group, an ester is electron donating); alcohols are electron donating; quaternary amines are strong electron donators.

Alkene stability

Alkyl substituents (R-groups) increase alkene stability. Thus, tetrasubstituted > trisubstituted > disubstituted > monosubstituted > unsubstituted

Acidity

Always look at the stability of the conjugate base! This stability or lack thereof, will often be affected by electron donating or withdrawing groups (alcohols are weaker acids than water due to the donating effect of the -R group). Resonance Stabilization: This explains why the alcohol group on a carboxylic acid is more acidic than other hydroxyl groups and why alpha hydrogens are acidic.

How can you tell which is the most stable species between two that have resonance?

Among similar species that both experience resonance, the more stable species will be the one with the most possible resonance structures. (ex. CLO4- is more stable than CLO3- because perchlorate has four resonance forms and chlorate has only three).

Hybridization definition

Atoms, when bonded, hybridize (mix) their higher and lower energy valence orbitals to form "hybrid" orbitals with intermediate energy. Carbon has 2 e's in s and p orbitals. However, Carbon will form 4 orbitals with sp3 energy.

Alcohols

An alcohol is any species with an --OH functional group. Alcohols behave as either nucleophiles (the lone pair on oxygen acts as a Lewis base) or as Lewis acids when they are oxidized to carbonyl groups (ex. the oxygen accepts a pair of electrons from the O-H bond as the proton is abstracted). Alcohols are named with the -ol suffix (ex. butanol, cyclohexanol, 1,3 - hexanediol).

Alkenes

An alkene is any species with a double bond. Alkenes are NUCLEOPHILES. The pi electrons in the double bond will attack electrophiles forming a new bond to one of the carbons and leaving a carbocation on the other. The carbocation is then quenched by a nucleophile. When located one carbon away from another atom, alkenes are weakly electron withdrawing.

Alkynes

An alkyne is any species with a triple bond. Alkynes are almost identical in how they react to alkenes.

Ethers

An ether is an oxygen bonded to two- R groups (R-O-R). Nomenclature: On the MCAT simple ethers are sometimes referred to by common names wherein each -R group is named separately (ex. methyl ethyl ether, diethylether, methyl propyl ether, etc). IUPAC rules call for the standard naming of the longer of the two -R groups as the parent chain, and naming of the other -R group as a substituent with the suffix "-oxy" added. (ex. 1-ethylheptane) 1. VERY NON-REACTIVE. 2. Weakly polar 3. With short R groups ethers are slightly soluble in water. 4. Most non-polar species are soluble in ethers. 5. Low boiling point (no H-bonding) 6. All of these characteristics make ethers EXCELLENT SOLVENTS. Unlikely to see an ether in a rection on MCAT, almost always solvents. If they do react, its after protonation by a strong acid, the resulting unstable intermediate can be attacked by a nucleophile.

Dipole Moment

Any time charge is not evenly distributed within a bond (ex. when the two atoms have non-identical electonegativities) that bond will have a dipole moment, μ. The dipole moment can be calculated using μ= δ × d; where δ represents charge and d represents distance between charges. (Note: observe that δ is also the symbol often used to denote partial positive and partial negative charges; ex. +δ — δ). You may recall seeing the dipole moment represented on paper as an arrow with a plus sign on its tail. When this convention is used, the arrow points in the direction to which electrons in the bond will be pulled by the more electronegative atom.

Aromaticity

Aromatic compounds are conjugated, unsaturated, ring systems that exhibit greater stability than one would expect based on either resonance or conjugation alone. For example, benzene shows far greater stability than other unsaturated compounds with three bonds and two resonance forms. Conjugated systems are always very stable, but benzene is far MORE stable than a conjugated straight-chain alkene.

What is the Octet Rule?

Atoms of low (<20) atomic number tend to gain or lose electrons to obtain exactly eight electrons in their valence shell. Highly stable "noble gas" configuration. This is why sodium forms the ion Na+ and not Na2+.

What do bases do and describe them (electrons)

Bases abstract protons (hydrogens). They are electron dense and have a full or partial negative charge. The strongest base forms the strongest, most stable bond with hydrogen. In other words, for a strong base the acid/base equilibrium favors the conjugate acid, NOT the base. Basicity is a function of thermodynamics- it quantifies the stability of the reacted base (BH) compared to the unreacted base (B-). Basicity says nothing about how quickly the base will react. Put another way, basicity describes how much the molecule " wants" to react, but nothing about how quickly it will do so.

Provide five examples each of bases, nucleophiles, electrophiles, and leaving groups.

Bases: NH2-- ; OH-- ; RO-- ; H:-- ; RC:-- ; R3N ; H2O ; NH3 ; Nucleophiles: NH3 ; RC=CR ; H2O ; RMgBr ; X-- ; RCO2-- ; CN-- ; Electrophiles: H+ ; R2C=O ; RX ; X2 ; HX ; R3C+ ; Leaving Groups:- X ; -OCOR ; -H2O+ ; -Tosyl ; -NH3+ ; -N2+ (diazonium). These are NOT complete lists. Listed in no particular order (It would be a good exercise to have your students attempt to rank the lists according to strength). There are several species that can be placed in multiple categories. Hydroxide, for example, will usually be seen acting as a base on the MCAT, but will also act as a nucleophile if there are not acidic protons. For the MCAT focus on the function: if a species abstracts a proton it is acting as base and if it attacks a carbon it is acting as a nucleophile.

Provide a conceptual explanation for the two acidity trends describe above. Predict the acidity of carboxylic acids compared to alcohols and water.

Both trends are explained by the fact that alkyl substituents are weak electron donating groups. When we look at the conjugate base of water there are no alkyl groups donating electron density to destabilize the oxygen with additional negative charge. With primary, secondary and tertiary alcohols there are one, two and three donating groups respectively. Therefore, tertiary alcohols are the least stable because the conjugate base in that case is destabilized to the greatest degree by induction. Carboxylic acids experience the exact opposite effect because the carbonyl is a strong electron withdrawing group. Further (and even more importantly) the conjugate base in the case of a carboxylic acid is stabilized by resonance.

What is an example of two atoms with different electronegativites having NO NET dipole?

CCl4 Molecules with two or more dipole moments can still have no NET dipole when their geometric orientation causes the dipole moments to cancel each other out. This concept explains why carbon tetrachloride is non-polar even though carbon and chlorine clearly have different electronegativities.

What does this tell us about the relative reactivity of the carbons in a C=O vs. a C=N bond?

Comparing electronegativity, we see that the partial positive charge on the carbon in a C=O bond is greater than the partial positive charge on the carbon in a C=N bond. This indicates that carbonyls are more reactive than comparable imines.

Alkanes

Compounds made entirely of carbon-carbon or hydrogen single bonds (ex. gasoline, tar, crude oil, butane, methane, etc.) Alkanes are named with the -ane suffix.

How do you determine Hybridization?

Count the number of sigma bonds and add the number of lone PAIRS (of unbonded electrons). This number will equal the sum of the superscripts on one of the following hybridizations: sp, sp2, sp3, sp3d, sp3d2 (Note: no superscript indicates a superscript of one).

Cyclic compounds: ring strain

Cycloalkanes create ring strain because they force bond angles to deviate from the optimum tetrahedral angle of 109.5°. Cyclohexane in chair conformation has zero ring strain. Cycloalkanes with more or less than six carbons exhibit increasing ring strain as one moves away from six. Very large rings (ex. 10+ carbons) have enough freedom to again approximate the tetrahedral angle. Bycyclic rings are more strained than monocyclic rings.

Epimers

Diasereomers that differ at only one chiral center. Many pairs of carbohydrates are epimers (ex. glucose and galactose).

Basicity

Electron donating groups increase basicity, while electron withdrawing groups decrease basicity.

Electron Flow

Electrons flow from high concentration to low concentration during reactions. In other words, they flow from a species with a full or partial negative charge to a species with a full or partial positive charge. Electron dense species, such as bases and nucleophiles, always attack electron poor species; which are called electrophiles.

Electrophiles

Electrophiles are electron poor species with a full or partial positive charge. They accept electrons from either nucleophiles or bases.

Rotation of plane-polarized light in enantiomers

Enantiomers rotate plane-polarized light. R and S enantiomers rotate this light to the same degree but in opposite directions. R enantiomers can rotate this light in a clockwise or counterclockwise direction, as can S enantiomers.

Epoxides

Epoxides are cyclic ethers involving one oxygen and two carbons in a there - member ring.

Substitution of an epoxide

Epoxides suffer from severe ring strain, making them highly reactive. Acid catalyzes the reaction by protonating the oxygen and making it a better leaving group.

Hydrogen bond donors/ acceptors

F, O, N bonded to a hydrogen can act as BOTH a hydrogen bond donor and a hydrogen bond acceptor. F, O, N atoms with lone pairs that are NOT attached to a hydrogen (i.e., ROR, RCOR, etc.) can act as hydrogen bond acceptors.

Ranking Resonance structures

If determining the relative contribution of various resonance structures to the actual structure, the individual structure that contributes the MOST to the actual structure is the one that: 1) Allows the most atoms to have a full octet (unless atom is a common exception for the octet rule). 2) Has the least formal charge (ex. no charge is better than some charge and one formal charge is better than multiple formal charges) 3) Places formal charge on atom most receptive to that charge (ex. it is preferable to have a negative formal charge on oxygen than on carbon because oxygen is more electronegative).

What is the Hybridization of BeCl2?

Linear BeCl2 is going to have: Be has a sigma bond with each of the chlorines. Which gives it a linear Hybridization. Be --> 2 valence e- Cl --> 7 valence e- (2x) Total = 16 valence e- Each chlorine has 6 valence electrons (nonbonding) and 2 valence electrons (bonding with the Be). Formal Charge = (valence e-) - (nonbonding e-) - (bonding e- / 2) Each Cl and Be has a formal charge of 0, which lets me know that this is the correct structure.

Use the principles of electron donation and withdrawal to explain why the alpha hydrogens on the methyl side of a methyl-ethyl ketone are more acidic than those on the ethyl side.

Looking at the stability of the conjugate base, we see that a carbanion on the alpha carbon of a methyl would experience electron withdrawal due to the carbonyl, but no additional inductive effects. However, if we examine ethyl side we see that the same carbanion on that alpha carbon would experience withdrawal due to the carbonyl, but also induction by a weakly donating methyl group (i.e., the beta carbon). This would destabilize the carbanion.

Geminal/Visinal

Geminal- comes from latin meaning twins. Two atoms or groups identical on a carbon eg CH2CH2CHBr2, the bromines are geminal Vicinal- comes from latin meaning neighbors. Two atoms or groups being identical and are on neighboring carbons: eg CH2BrCH2Br, the bromines are vicinal.

Absolute Configuration (R and S)

How two enantiomers are distinguished. Assign priority to all four substituents based on molecular weight, with higher molecular weight atoms receiving higher priority. Rotate the LOWEST priority substituent to the back motion, the absolute configuration is R; if proceeding in order from one to three requires a counter-clockwise motion, the absolute configuration is S.

Polarity results in?

In partial positive and partial negative charges, which are clues when trying to identify the nucleophile and electrophile in a reaction. To be a base or nucleophile, a molecule must have a full or partial negative charge. To act as an electrophile, it must have a full or partial positive charge.

Rank the bonds listed above according to increasing reactivity.

In this case, reactivity is measured in terms of how readily a species will react in the presence of a nucleophile or electrophile. You should definitely know that alkanes are very unreactive, and that alkenes are far more reactive. However, it is perhaps surprising that alkenes are actually slightly MORE reactive than alkynes. Still, alkynes are far more reactive than alkanes. The higher reactivity of alkenes is accounted for by the fact that the pi electrons in an alkyne are slightly more stable than the pi electrons in an alkene. One potential explanation is that the sp hybridized carbons in the alkyne have more s character and pull more tightly on those pi electrons, making them more centralized and therefore lower energy than the pi electrons in an sp2 hybridized alkene. In increasing order of reactivity they would be ranked: single < triple < double.

Physical structures of alkanes

Insoluble in water; very low density; non-polar; most are oils or gases. Melting and boiling point trends: these general principles apply not only to alkanes, but to most other functional groups. 1) Boiling point increases with INCREASING chain length and molecular weight. 2) Boiling point DECREASES with increased branching. 3) Melting point INCREASING with increasing chain length and molecular weight. 4) Straight- chain alkanes have the highest melting points. Among branched alkanes, however, INCREASING branching increases melting point.

Draw both chair conformations of cyclohexane. In which position, axial or equatorial, would a large substituent be most stable?

Large substituents are more stable (i.e., lower energy) when in the equatorial position. cis-1,2- dichlorocyclohexane cannot exist with both chlorines in the equatorial position. For neighboring carbons, two equatorial substituents would be trans to one another. Two neighboring substituents can be cis to one another, but one must be in the axial position and one in the equatorial position. Below is drawing of the two chair conformations of cyclohexane.

The difference in strength between LiAlH4 and NaBH4

LiAlH4 produces 2 hydride equivalents NaBH4 produces 1 hydride equivalent

Alcohols melting and boiling point

Like alkanes, boiling point goes up with increasing molecular weight and down with increased branching. Melting point also goes up with increasing polarity and H-bonding. Because alcohol substituent's can be considered as branching, the effect of branching on the melting points of an ROH is variable.

Describe the difference between methyl, primary, secondary, tertiary and quaternary carbons.

Methyl: CH4 Primary: RCH3 Secondary: R2CH2 Tertiary: R3CH Quaternary: R4C

Anomers

Molecules that differ only in their spatial orientation at the anomeric carbon of a ring structure . If the anomeric OH/OR group and the CH2OH group are on the same side the ring = Beta, if they are on the opposite side = alpha.

Meso Compounds

Molecules with two or more chiral centers that contain a place of symmetry. This symmetry cancels out their optical activity. To recognize them, look for a center of symmetry. However, NOT all molecules with a plane of symmetry are meso compounds. Next, check for mirror chiral centers across the plane of symmetry (NOT between TWO molecules; remember that a meso compound is ONE molecule).

Are meso compounds diastereomers? Are they enantiomers? Why or why not?

No. Diastereomers are PAIRS of compounds that have the same formula, the same bond-to-bond connectivity, are non-identical, and are NOT mirror images. A meso compound is a SINGLE molecule with a mirror plane. Therefore a meso compound clearly cannot be a diastereomer (or an enantiomer) with itself.

Nucleophiles

Nucleophiles attack carbons (or other central atoms). They are electron dense and have a full or partial negative charge. Best nucleophile reacts fastest with an available electrophile. Nucleophilicity is kinetics. How "easily" or "readily" a molecule will react, but nothing about how stable the new bond will be.

Common oxidizing agents of alcohols

O3, Cr2O7, Cr2O7, CrO4, KMnO4, Jones, Collins, PCC, PDC, etc.

Provide a conceptual definition for each of the following: observed rotation, specific rotation, polarimeter, plane-polarized lights, optically active vs. optically inactive, and racemic mixture.

Observed rotation is simply the degree to which a sample rotates plane polarized light. However, that rotation is not a universal constant for a particular molecule. Rather, it varies depending on concentration, length of the tube, etc. Specific Rotation takes these factors into account by dividing observed rotation by the length of the tube and the concentration. Specific rotation could therefore be described as "observed rotation per length, per concentration unit." A polarimeter is an apparatus that measured the rotation of plane-polarized light as it passes through a sample. Plane- polarized light is light that exist in only a single plane. Normally, light waves are oriented in an infinite number of planes from zero to 360°. A polarizer can sift out all of these leaving, for example, only vertically oriented waves. To be optically active means that a substance does rotate plane- polarized light. Optically inactive compounds do not rotate plane-polarized light. A racemic mixture is a 50/50 mix of the two absolute configurations of a compound (i.e., R and S).

Chirality

Often referred to as "handedness". Any atom attached to four DIFFERENT substituents must be chiral. Any atom with less than four substituents cannot be chiral (and therefore cannot be an enantiomer). Double or triple bonds count the same as if that atom were bonded to the other atom two or three different times. Sot it would have more weight, so higher priority.

Cyclic compounds: axial vs. equatorial

On the chair conformation of cyclohexane the axial substituents rise vertically from the ring and the equatorial substituents extend horizontally.

Difference between a phenyl group and a benzyl group

Phenyl = −−Ph, Benzyl = −−CH₂−Ph

Important Note on Pi Bonds

Pi bonds themselves are weaker associations than are sigma bonds. However, a double bond (one sigma bond plus one pi bond ) is stronger together than a single bond (one sigma bond only). Also, triple bonds are much shorter, stronger bonds than are single bonds, but are also more reactive. Reactivity has to do with the tendency of the third bond (a pi bond) to react. Bond strength is at measure of the energy needed to completely break the two atoms apart (ex. break all three bonds)

Grignard synthesis

Production of an alcohol with extension of the carbon chain. Produces an alcohol by adding RMgBr (called an organometallic) compound to a carbonyl. Results in an INCREASE in the # of carbons. The Grignard Reaction will also work with C=N, cyano groups, S=O and N=O.

Things that can be used to protect an alcohol:

Protection with TMS: ROH + TMS → RO-Si(CH3)3 Protection by MOM (Methoxy-methyl ether): ROH + Base → RO- + CH3OCH2Cl (MOMCl)→ROCH2OCH3 (RO-MOM) Acidification will remove either protecting group to restore the alcohol.

Reaction with SOCl2 and PBr3

ROH + SOCl2 → RCl ROH + PBr3 → RBr

SN1 (Nucleophilic Substitution, Unimolecular)

Rate depends on concentration of ONE species and is thus FIRST ORDER. Involves TWO STEPS: 1) The dissociation of the leaving group, resulting in formation of a carbocation [SLOW STEP] 2) Attack of the carbocation by the nucleophile [FAST STEP] yes methyl or hydride shifts

E2 reaction steps (Elimination, BImolecular)

Rate depends on concentration of two species and is thus SECOND ORDER. Involves ONE STEP only: 1) The single-step abstraction of a proton with collapse of the electrons to form a double bond and ejection of the leaving group. no methyl or hydride shifts

SN2 reaction steps (Nucleophilic Substitution, Bimolecular)

Rate depends on concentration of two species and is thus a SECOND ORDER. Involves ONE STEP: 1) The single-step "back side attack" of the electrophile with simultaneous ejection of the leaving group. no methyl or hydride shifts

E1 reaction steps (Elimination, UNImolecular)

Rate depends on the concentration of one species and is thus FIRST ORDER. Involves TWO STEPS: 1) The dissociation of the leaving group, resulting in formation of a carbocation [SLOW STEP] 2) The abstraction of a proton with collapse of the electrons to form a double bond (which quenches the carbocation) [FAST STEP] yes, methyl or hydride shifts

Mechanisms SN1/SN2 and E1/E2

Realize that SN1 competes with E1 and SN2 competes with E2. SN1 does NOT compete with SN2, nor does E1 compete with E2. Remember that as far as the MCAT is concerned a 3 carbon must react via an SN1 or E1 mechanism.

Reduction synthesis of an alcohol

Reducing agents such as NaBH4, LiAlH4 and H2/ pressure reduce a carbonyl to an alcohol.

Energy is always ________ when a bond is formed and ________ when a bond is broken.

Released ; required. One example that often confuses students is ATP. They have the general concept that breaking the phosphate bond in ATP releases energy. That is wrong. Breaking the ATP bond does require energy, but the new bonds formed—in particular the new -OH bond resulting from hydrolysis, releases more energy than was required to break the phosphate bond of ATP.

Diastereomers

Two molecules, with the same formula and the same bond-to-bond connectivity that are non-identical, but are NOT mirror images. There are three kinds of diastereomers you must be familiar with for the MCAT: geometric isomers, epimers and anomers.

Structural Isomers

Same formula, different bond-bond connectivity (For example: 2-methylpentane and 3-methylpentane are both C6H14)

Stereoisomers

Same formula, same bond-to-bond connectivity, but different in the 3-D arrangement of their substituents. There are two categories of stereoisomers: enantiomers and diastereomers.

Draw a mechanism for the formation of an alkyl halide from an alcohol via both SN1 and SN2.

See the diagram below. Note that the SN1 forms a planar intermediate and could result in a racemic mixture only if all three -R groups are different from one another.

Draw a mechanims for the formation of a tosylate or mesylate. Why would we want to form a tosylate or a mesylate anyway?

See the mechanism below. Mesylates and Tosylates are desirable because they make very good leaving groups that will react readily with almost any nucleophile.

Which is stronger, a sigma bond or a pi bond? Why?

Sigma bonds are significantly stronger than pi bonds. This is because sigma bonds allow for electron density to be concentrated to a much larger degree between the two nuclei. The lowest energy state for electrons—being electrostatically attracted to both nuclei simultaneously, is between those two nuclei and as close to each nuclei as possible. In a pi bond the p orbitals overlap above and below the atom, localizing the electrons above and below the plane of the bond—a higher energy state compared to the head-on overlap of a sigma bond. You can also conceptualize that pi bonds are weaker simply because we know those electrons are in a higher-energy state. It is universally true that when a bond is HIGHER in energy it will require LESS energy to break it.

Rank the bonds listed above according to increasing bond strength.

Single < Double < Triple

1) The H-O-H bond angle in water is measured experimentally to be 104.4°. The related angle H-N-H in ammonia is expected to be: A) larger due to the greater electron repulsion in ammonia B) larger due to the greater electron repulsion in water C) smaller due to the greater electron repulsion in water D) smaller due to the greater electron repulsion in ammonia

Solution: Both molecules are approximately tetrahedral in shape, but experience some distortion due to the repulsion of lone pairs of electrons. In water, two lone pairs push both hydrogen substituents away from the plane shared by the two lone pairs, decreasing the H-O-H bond angle. Ammonia has only one lone pair, so the same effect is observed, but to a lesser degree. Thus, the bond angle is larger in ammonia due to the greater repulsion in water than in ammonia, or answer B.

An unknown molecule has an absolute configuration of S and rotates plane-polarized light 15 degrees in the clockwise direction. Which of the following molecules is enantiomeric to the unknown? A) Absolute configuration is R; rotates plane-polarized light 15°; levorotary B) Absolute configuration is S; rotates plane-polarized light 15°; levorotary C) Absolute configuration is S; rotates plane-polarized light 15°; dextrorotary D) Absolute configuration is R; rotates plane-polarized light 15°; dextrorotary

Solution: Enantiomers must have opposite R/S configurations. You CANNOT predict dextrorotary or levorotary from R and S. However, if you know one enantiomer is dextrorotary, then the other enantiomer must be levorotary. In this case, the molecule was S and rotated light clockwise (dextrorotary), so its R equivalent must be levorotary, or Answer A.

N2 is one of the most stable molecules known; will it have a high or low heat of combustion? Rank cyclopropane, cyclobutane, cyclohexane and cycloctane according to increasing heat of combustion per -CH2 group.

Stable molecules have very low heats of combustion. The heat of combustion per -CH2 group increases with ring strain. From highest to lowest heat of combustion: cyclopropane, cyclobutane, cyclooctane, cyclohexane.

Basicity vs. Nucleophilicity

Steric hindrance favors basicity over nucleophilicity; nucleophiles must have very little hindrance. Primary nucleophiles are most common. Secondary atoms can often act as bases or nucleophiles, depending on conditions. However, tertiary atoms will ONLY act as BASES. Reactivity (low stability) favors basicity over nucleophilicity (NH₂⁻ vs RO⁻). If an atom has a full negative charge it will almost always act as a base (halide are notable exception).

Electronegativity

The greater the difference in the electronegativity of two atoms in a bond, the more polar the bond. This shows us that oxygen forms stronger hydrogen bonds than does nitrogen. It is worth knowing that carbon and hydrogen have similar, but not identical, electronegativities (carbon=2.5; hydrogen=2.2). Fluorine has the largest electronegativity (4.0) and Francium has the smallest (0.7). Beyond these general trends, if specific electronegativity figures are required they will always be given.

Provide multiple examples of coordinate covalent bonds. Include a human-body example.

Students will see two types of coordinate covalent bonds. The first one is illustrated any time a nucleophile with a lone pair abstracts a proton: NH3 + HCl <--> NH4 + Cl-. The amine binds a fourth hydrogen, but the electron belonging to that hydrogen stays with the Chlorine. Both electrons that were part of the amine lone pair now form the new covalent bond between nitrogen and the fourth hydrogen. Another example, and the one we've seen most on the MCAT, is easily recognizable. It involves a metal coordinated with one or more molecules that have lone pairs. When you see something like Fe(NH3)4 or Co(NH3)3, these structures should stand out because they look almost like ionic compounds, but obviously the amine does not have a charge (so they cannot be ionic). This thought would lead one to wonder how the amines are attached to those metals? The answer is via coordinate covalent bonds. A common and very applicable example of coordinate covalent bonds in the human body is the binding of iron in the heme unit of hemoglobin (see below).

Substitution of an epoxide can proceed via an SN1 or an SN2 pathway. Use your knowledge of these two types of reactions to predict and draw a mechanism for both pathways.

Technically, epoxide ring openings can open via either an SN2 with good nucleophiles or an "SN1- like" reaction with poor nucleophiles. In SN2-like reactions the good nucleophile attacks the least substituted epoxide carbon and in SN1-like the nucleophile attacks the most substituted epoxide carbon.

How does rotational limitation of pi bonds relate to our previous study of proteins?

The amide functional group in a protein (created when the amino group of one amino acid attacks the carboxylic acid group of another amino acid) exhibits resonance and therefore both the C-O and C-N bonds have double-bond character. This prevents rotation—a key characteristic of peptide bonds.

Propose a mechanism for the pinacol rearrangement

The two hydroxyl groups must be in the vicinal (vic-) position and the carbons bearing those two hydroxyl groups must be tri- or tetra- substituted by -R groups. If tri-substitute, it will yield an aldehyde, and if tetra-substituted it will yield a ketone.

Which version of 2,3-dibromo-2-butene would have the higher heat of combustion, the cis isomer or the trans isomer? Which would have the higher boiling point?

The cis- version of this molecule would have a dipole moment and the trans- version would not. This would increase intermolecular forces and therefore boiling point (Bp-cis > Bp-trans). One might think that this dipole moment would also increase melting point, but the importance of stacking to melting point becomes more important. Trans- molecules can stack on top of one another closely. However, -cis molecules cannot fit inside of one another and therefore are limited in how closely they can stack. This has been hard to visualize for some students. Consider that the cis- molecules are all the same size. To stack inside of one another they would have to be like Russian dolls—each one smaller than the next. The closer stacking of the trans- molecules means that more energy is required to disrupt the Van der Waals forces between them (Mp-cis < Mp-trans).

Draw two energy coordinate diagrams demonstrating why the combustion of a less-stable molecule results in a heat of combustion than the combustion of a more-stable molecule.

The diagram below shows two RXN coordinate diagrams combined, one for combustion of Reactant1 and one for Reactant2. Both reactants are hydrocarbons and therefore the products of combustion are the same—carbon dioxide and water. That is the key to understanding why less stable molecules release more energy: the energy of the products is always going to be the same (i.e., the energy of CO2 + H2O). Therefore, the higher the energy of the reactants the greater will be the difference in energy between them. (Note: This diagram shows the energy of the transition state being the same for both reactions, but that is arbitrarily chosen. This is a path-independent process and so the only concern is the difference in energy between the reactants and the products).

Potassium dichromate is often used as an oxidizing agent. A solution of dichromate ions (Cr2O7 2-) is orange, but a solution of chromium ion (Cr3+) is green. If alcohol A is reacted with potassium dichromate and produces a green solution, and alcohol B is reacted with the same reagent and produces an orange solution, what can be inferred about the two alcohols, A and B?

The dichromate ions are becoming chromium ions as a result of the oxidation reaction. Because the UNREACTED dichromate is orange, alcohol B must not have reacted with the dichromate. This would allow us to infer that alcohol B is very likely tertiary because tertiary alcohols do not oxidize. Alcohol A did react, as indicated by the green solution. Therefore we can infer that it was either a primary or a secondary alcohol.

Formal Charge

The difference between the # of electrons in an atom's valence shell when it is in its ground/elemental state and the number assigned (lone-pair electrons and 1/2 of the bonding electrons) to it in a molecule. Formal charge= valence - assigned or FC = (valence e-) - (nonbonding e-) - (bonding e- /2 )

Describe to your tutor why each attribute is desirable in an organic solvent.

The fact that ethers are unreactive makes them desirable as a solvent because generally we do not want the solvent to react with the reactants or products of our reaction to form byproducts. The unique polarity of ethers allows them to dissolve many molecules, also desirable for a solvent. Finally, the low boiling point makes it easier to separate the product from the solvent via evaporation.

Which of the above models is the most accurate visual representation of an actual molecule?

The most conceptually-accurate representation in terms of what you would actually see if you could take an "Incredible Voyage" down to the molecular level would be the space-filling model. However, remember that those electron clouds would not be nicely color-coded for you. They are only math functions that predict where the electrons might be. If you were seeing a real methane molecule at that size and scale you would most likely see nothing. The first thing you could see would be the nucleus and you would need to have magnification many, many times that to see an electron.

Valence

The number of bonds an atom "normally" makes: carbon and its family are tetravalent; nitrogen and its family are trivalent; oxygen and its family are divalent and fluorine and its family are monovalent.

Draw all possible resonance structures for a) an amide (R-CONH2) and b) the phosphate ion (PO4 3-). In each case rank each structure in terms of its contribution to the actual structure.

The possible resonance structures are drawn below. For the amide, the most stable structure is the one to the far left because there is no separation of charge. Next in line is the middle structure because it places a positive formal charge on carbon, whereas the structure to the right places that charge on nitrogen. Among the phosphate structures, the least stable will be the structure with a positive formal charge on the phosphorous because this has more formal charges and is the only one with both negative and positive formal charges. The other four structures will be equal contributors.

Lone pairs of electrons

The presence or absence of unpaired electrons determines the exact shape from among those choices. For example, an sp2 hybridized atom can take on the trigonal planar shape (no lone pairs) or the bend shape (one lone pair). Sp hybridized atoms are always linear.

Conformational isomers

These are NOT true isomers!!! They are the same exact molecule. When a molecule twists or rotates around its bonds these are considered "conformers" NOT isomers.

Dehydration of an alcohol: synthesis of an alkene

This is an equilibrium reaction *the alkene is favored by hot, concentrated acid; the alcohol is favored by cold, dilute acid* The major product is the most substituted, most stable alkene 1. alcohol protonated by acid 2. good leaving group water leaves 3. *methyl or hydride shift* can occur, but only if it makes a more stable carbocation. 4. water molecule abstracts a proton and electrons collapse to quench carbocation and form an alkene.

Formation of Tosylates/Mesylates

Tosyl-Cl + ROH → Tosyl-OR + HCl STEPS: 1) The alcohol attacks the tosyl or mesyl halide via SN2, kicking off a halide ion . 2) A hydrogen is taken by the halide ion, quenching the charge on the oxygen. -Mesylates and Tosylates are desirable because they make very good leaving groups that will react readily with almost any nucleophile.

Isomers

Two molecules are isomers if they have the same molecular formula but are actually different compounds.

What is VESPR?

Valence Shell Electron Pair Repulsion Theory. Predicts the shape molecules will take due to the repulsion of lone pairs of electrons. Hybridization state determines the possible shapes for the molecule.

Heat of Combustion

When molecules are combusted, all of the bonds are broken and then reformed via a radical reaction. The less stable bond, the greater the heat of combustion. The more stable the bond, the lower the heat of combustion.

What is the percent "s" character of the hybrid oxygen orbital in water?

When orbital hybridize they do so in a weighted manner such that the character of the hybrid orbital is an average of its contributors. Therefore, an sp hybrid orbital has 50% s character and 50% p character. By this same logic, the oxygen in water—which is sp3 hybridized, exhibits 25% s character and 75% p character. Mathematically, 1s orbital and 3p orbital's equal 4 orbitals (1s + 3p = 4 orbitals). 1 out of 4, 1⁄4 , or 25% is from the s orbital.

Rank the bonds listed above according to increasing stability.

When you see the term "stability" on the MCAT they mean "thermodynamic stability"—which in essentially every case will be reflected by the strength of the bond. Remember that strong bonds are a "lower-energy" state and weaker bonds represent a "higher-energy" state. Therefore, TRIPLE BONDS are the MOST thermodynamically STABLE, meaning it will require the most energy to break them apart. In increasing order of stability they would be ranked: single < double < triple. (Be careful not to confuse stability with reactivity.)

Can an optically inactive compound rotate plane-polarized light?

Yes. A compound with an even number of chiral centers could be said to be rotating light internally, but the net effect of say two R chiral centers plus two S chiral centers is zero net rotation. If we accept that chiral compounds really do rotate light, then it follows that they must actually be rotating light in this case. It would not be logical to assume that because a chiral center is near (even very, very near as in a molecule) another chiral center that rotates in the opposite direction, that this proximity actually stops that chiral center from rotating light.

Why can weaker reducing agents only reduce aldehydes and ketones?

You can think of LiAlH4 as producing two equivalents of hydride ions and of NaBH4 as producing only one equivalent of hydride ions. When a hydride ion attacks the carbon on an aldehyde or ketone the carbonyl double bond moves up onto the oxygen. Following protonation you have an alcohol— and only one hydride equivalent was required. In the case of the acid derivatives one equivalent of hydride ions will produce a similar result, but the hydroxyl or alkoxy group will still be present. Because we know that the reaction proceeds all the way to the alcohol, this group must be kicked off, which can be accomplished when a SECOND hydride equivalent attacks the carbonyl carbon. Therefore, the acid derivatives require two equivalents of hydride ions and NaBH4 can only provide one.

Combustion of an Alkane

a radical, exothermic chain reaction with oxygen; high energy of activation. CH₄ + 20₂ → C0₂ + 2H₂0 + Heat

Which is the weaker bond c=o or c=n?

c=n, because the radii are further apart. As the radius of either atom increases, the p orbitals are spread apart, resulting in less overlap and a weaker pi bond. Remember that atoms with smaller radius ( like Fluorine) will be able to hug other things more easily because of its small radius.

Geometric Isomers (cis/trans)

cis = same side ; trans= opposite sides The E/Z convention: prioritize the two constituents on each carbon by molecular weight, (as you do for R/S). If the two higher priority substituents are on the same side = Z. IF the two higher priority substituents are on opposite sides= E.

The first bond to form between two elements...

is ALWAYS a sigma bond (ex. a single bond, or the first bond or a double or triple bond) and involves head to head overlap of two atomic orbitals.

In relation to the boiling and melting points of hydrocarbons with similar molecular weights to alcohols, the alcohols have

much higher boiling points and melting points due to hydrogen bonding.

Aliphatic

non-aromatic compounds

The pinacol rearrangement (polyhydroxyl alcohols)

vic-diol + hot acid → ketone or aldehyde