Unit 3: Chem/Phys

A steric number of _____ corresponds to sp hybridization.

2

The following compound is an (acid/base): TsOH

ACID! Explanation: tosylic acid

Besides water, what are some other examples of amphoteric molecules?

Al(OH)₃ HCO₃⁻ HSO₄⁻ H₂PO₄⁻ AMINO ACIDS

If the carbon containing the leaving group is secondary or tertiary, you can definitely rule out which reaction mechanism?

CANNOT be SN2 ⟶ too hindered Depending on the type of nucleophile/base, it will either proceed with concerted elimination [E2] or through carbocation formation [SN1/E1]

Which is a better electrophile CH₃OCH₃ or CH₃OH?

CH₃OH Explanation: Even though OH⁻ is a terrible leaving group, CH₃O⁻ is even worse, so methanol is the better electrophile in this case

elimination of 1° alcohols

E2 ￫ just like E1, an alkene forms

Which is a stronger nucleophile RO⁻ or HO⁻?

RO⁻ Explanation: the alkyl group donates additional electron density, making the lone pair less tightly held and more reactive.

How are amides named?

Replace "-oic acid" with "-amide" in the name of the parent carboxylic acid. Any alkyl groups are placed at the beginning of the name with prefix "N-"

Racemization is characteristic of which substitution reaction?

SN1

Carbocations are hallmarks of which reaction mechanism?

SN1 (or E1)

True or False: Carboxylic acids are always terminal groups.

True

diol + HIO₄

aldehyde

diol + NaIO₄

aldehyde

alkene + O₃ followed by H₂O₂

carboxylic acid and ketone reaction is called "ozonolysis with oxidative workup"

potentiometry

carrying out a redox titration with a *voltmeter* present to get precise readings of the reaction's emf (voltage) to determine the endpoint. *no indicator used*

enolate

conjugate bases/anions of enols (like alkoxides are the anions of alcohols) and can be prepared using a base. a much stronger nucleophile than the enol too!

If a lens has a positive power, that means it is ____________.

convex (converging)

aldehyde/ketone + HCN (base-catalyzed)

cyanohydrin (NC-C-OH) after reprotonation! stable because of the newly-formed C-C bond ✴︎ reaction needs base to create the cyanide anion, which is the actual nucleophile

lactams

cyclic amides

lactone

cyclic ester

Nucleophile versus base

depends on the type of bond it is forming in the reaction. Take a species like NaOH. It's both a strong base and a good nucleophile. ￫ When it's forming a *bond to hydrogen*, e.g. in an elimination reaction, we say it's acting as a *base*. ￫ When it's forming a *bond to carbon* (as in a substitution reaction) we say it's acting as a *nucleophile*.

pH meter

determines the pH of a solution by measuring the voltage between the two electrodes that are placed in the solution used to carry out an acid-base titration to get precise reading for plotting a titration curve

What type of reaction will automatically have no net ionic equation (in other words, the two are the same)?

double-displacement reactions where *both reactants and both products are aqueous* it's also not redox either

Why are dicarboxylic acids more acidic than regular carboxylic acids?

each -COOH group influences the other -COOH group, and these groups are electron-*withdrawing*, which increases acidity

Adding acid makes -OH a better leaving group, favoring a ___________ reaction.

elimination

thermodynamic enolate

favored by slower, reversible reactions at higher temperatures with weaker, smaller bases

deprotection (of carbonyls)

final step when using alcohols as protecting groups, where the acetal that was formed is converted back to a carbonyl and a diol by treatment with catalytic *aqueous acid*

deprotection of alcohols converted to silyl ethers

final step when using silyl ethers as protecting groups on alcohols, where the O-Si bond is broken and the alcohol is reformed using *TBAF* or strong acid

Common names for carboxylic acids

follow trends for aldehydes methanoic acid = formic acid ethanoic acid = acetic acid propanoic acid = `propionic acid

1,2,3-propanetriol

glcyerol

pimelic acid

heptanedioic acid

What happens to the acidity of a dicarboxylic acid after the first proton is removed and it becomes a dicarboxylate anion?

immediate *decrease* in acidity Explanation: we don't want two negative charges on the same molecule (repulsion), so it's harder to get rid of this second proton

Electron-withdrawing groups ___________ acidity of carboxylic acids

increase weaken O-H bond

2° alcohol + PCC

ketone

What is a trick to naming the class of lactams/lactones by greek letters?

n - 2 count up the total # of members in the ring, then subtract 2 This accounts for the carbonyl carbon and the nitrogen, so the rest will be all the carbons relative to the carbonyl (α, β, ɣ, δ, etc.) Note, the smallest possible lactam is a β-lactam (4-membered ring)

I × t = ...

n × F

What is the common convention for naming ketones?

name the 2 alkyl groups alphabetically followed by *"-ketone"*

How do anhydrides react with water?

nucleophilic acyl substitution: reverts them to carboxylic acids or dicarboxylic acids (if cyclic) ✷ anhydride should be symmetrical to avoid mixture of products

Which molecules have higher boiling points, carboxylic acids or anhydrides?

often anhydrides Explanation: solely based on their much greater weight (both can hydrogen bond)

Carboxylic acid + LiAlH₄ (in ether) followed by H₂O

primary alcohol

Aldehyde + LiAlH₄ (in ether) or NaBH₄ (in ethanol)

primary alcohol ✴︎ LiAlH₄ reacts violently with water and alcohols, so it must be carried out in ether

Amide + LiAlH₄ (in ether) followed by H⁺/H₂O

primary amine *reduction*!!!!

The carbon in carbon dioxide has what hybridization?

sp Explanation: 2 of carbon's p orbitals remain unhybridized while the third hybridizes with the s orbital to form 2 sp hybridized orbitals. The sp orbitals create the σ bonds between the C and each O. Note, the O's have sp² hybridization and the pi bond configuration is strange because it is horizontal to allow for this linear shape.

stereospecificity

the stereochemistry of the substrate *determines* the stereochemistry of the product the stereochemical information is KEPT considering either direction. If you got the Z-alkene, you KNOW the stereochemistry at the center of the original substrate ✷ often seen in SN2 and E2

How do you name an aldehyde attached to a hydrocarbon ring?

use the suffix *"-carbaldehyde"*

TMS (tetramethylsilane)

used as the standard in NMR and also as a protecting group for alcohols it is symmetrical and inert, since all H atoms share the same environment

annhydrous

without water

What reagents can be used to convert an alkene into a vicinal diol?

① OsO₄ ② dilute KMnO₄, NaOH, cold

What is the purpose of acid catalyst in esterification?

① it makes the carbonyl carbon a better electrophile (Setting up step 2) ② allows for the loss of H₂O as a leaving group (much better leaving group than HO-) ✷ tsOH is the acid here

quinone

2,5-cyclohexadiene-1,4-diones formed when phenols are treated with oxidizing agents resonance-stabilized *electrophiles* due to the conjugated ring system serve as electron acceptors biologically ❗️not always aromatic though (structure can be slightly off)

A steric number of _____ corresponds to sp² hybridization.

3

What is the functional group on an anhydride?

-OCOR

What groups are attached to a hemiacetal?

-OR, -OH, -R, -H

What groups are attached to a hemiketal?

-OR, -OH, -R, -R'

What groups are attached to a acetal?

-OR, -OR, -R, -H ✴︎ R and H are from the original aldehyde ✴︎ each -OR is from either the diol or 1 from each equivalent of alcohol

What groups are attached to a ketal?

-OR, -OR, -R, -R' ✴︎ R and R' are from the original ketone ✴︎ each -OR is from either the diol or 1 from each equivalent of alcohol

What is the purpose of electrolytes in electrochemical cells?

often serve as salt bridges that dissociate into ions, which increase the conductivity of water (which in pure form conducts ZERO electricity) they also improve efficiency because the release of ions prevents charge buildup on both electrodes, which would presumably halt the reaction from going any further

Rank the carboxylic acid derivatives from most reactive to least reactive

anhydrides > carboxylic acids and esters > amides ✷ electrophilicity follows the same trend ✴︎ the most reactive will form derivatives of lower reactivity, like strong acids and bases ❗️ but not vice versa (i.e. less reactive derivatives form similarly low reactive conjugates, just like with weak acids and bases)

How does induction contribute to the reactivity of anhydrides?

anhydrides have 2 electron-withdrawing groups, which leaves a significant δ+ charge on the electrophilic carbon

What are some examples of Lewis bases?

anions, π bonds, atoms with lone pairs

α-racemization

any aldehyde or ketone with a chiral α-carbon will rapidly become a racemic mixture as the keto and enol forms interconvert

What reagents can be used to convert a primary alcohol to a carboxylic acid?

any equivalent chromic acid (H₂CrO₄) or KMnO₄

alkene + mCPBA

epoxide

Ketone + mCPBA

ester

isopropyl-2-iodobutanoate

ester included to show how the substituents are named: keep parent carboxylic acid together (everything to the left of the ester O), and then add the rightmost substituent as the prefix

triacylglycerols are...

esters of fatty acids (long chain carboxylic acids) + glycerol storage form of fatty acids

The reduction of aldehydes and ketones to primary and secondary alcohols is a _____________ reaction.

exergonic so spontaneous, but it is *very slow* without a catalyst

Nucleophilicity ___________ with increasing polarizability.

increases (size) ❗️opposite of basicity ❗️❗️ as long as the solvent is *protic*. They follow the same trends if solvent is aprotic...

How are quinones named?

indicate position of the carbonyls numerically and add "-quinone" to the name of the parent phenol

tautomerization

interconversion of two isomers in which a hydrogen and a double bond are moved

How are lactones formed?

intramolecular esterification of the corresponding *hydroxy*carboxylic acids, which takes place spontaneously when the ring that is formed is five- or six-membered

What aspect of carboxylic acid structure allows them to form dimers?

intramolecular hydrogen bonding between the hydroxyl H and carbonyl O

decarboxylation

intramolecular nucleophilic attack of the hydroxyl O on the carbonyl carbon, resulting in the complete loss of a carboxyl group as carbon dioxide, replaced by a hydrogen proceeds through a 6-member *cyclic transition state enol that initially forms (kinetic) tautomerizes to the keto (thermodynamic) Δ Heating is required because the reaction is less favorable at low temperatures

What are the acidic hydrogens on an aldehyde?

on the α-carbon Explanation: the negative charge is delocalized by resonance. As you can see, it's a stronger acid than a ketone because the ketone has an extra R" group that is electron-donating which destabilizes conjugate base (anion) because there's less room for the negative charge to delocalize

allylic position

one carbon away from the double bond

reduction of a carboxylic acid to a primary alcohol (mechanism)

nucleophilic addition of *hydride* (from LiAlH₄ only) proceeds through aldehyde intermediate, which will also be reduced to the alcohol

stereoselectivity

occurs in reactions where one configuration of product is more readily formed due to product characteristics stereoisomers "selective" indicates a preference, i.e. there's a choice of which way it can go and one is favored ✷seen in many different types of reactions, and the major product will generally be determined by differences in strain or stability

Factor #3: *Solvent* Nucleophilicity is hindered by _____________ solvent.

protic Explanation: protonation of the nucleophile or hydrogen bonding "slows down" the nucleophile In this case, nucleophilicity increases down a column (opposite trend of basicity) https://ibb.co/j3xGfL

Aldehyde + H₂CrO₄

carboxylic acid chromic acid is a *strong* oxidizing agent

Aromatic alkane + KMnO₄

carboxylic acid ❗️The reaction only works if there is a hydrogen attached to the carbon (see bottom pic)

Acids with a pKa below ______ are considered strong acids.

-2 almost always dissociate completely in aq solution

Weak organic acids have pKa values between...

-2 and 20

oxime

a type of imine, so there's a C=N, but the group attached to the nitrogen is an -OH. generally formed via reaction of *hydroxylamine* (NH₂OH) w/ aldehydes or ketones makes sense because it forms the same type of product as when 1° amines react with carbonyl compounds (product = imine), but this substrate has that OH group. Subtypes: ￫ If there is one R group and a hydrogen attached to the carbon, it's a *aldoxime* ￫ If there are two R groups attached to the carbon, it's a *ketoxime*

1° Alcohol + CrO₃/pyridine

aldehyde

1° Alcohol + PCC

aldehyde

Alkene + O₃, followed by Zn

aldehyde and ketone

Condition #3 For Aromaticity: Hückel's Rule

"n" is *NOT* a property of the molecule! 4n+2 is not a formula that you apply to see if your molecule is aromatic. It is a formula that tells you what numbers are in the "magic series" (2, 6, 10, 14, etc.) . If your π electron value matches any number in this series then you have the capacity for aromaticity. In other words, you count the π electrons in your molecule and then see if this matches up with Hückel's rule using some integer, n. ✷ hint: the # of π electrons is equal to an odd-numbered *pair* What counts as π electrons? - on another flash card

steric number

# of σ bonds + # of lone pairs determines *hybridization* Ex: CO₂ ::O=C=O:: Carbon's SN is 2 Oxygen's SN is 3 (2 lone pairs + bonded to 1 other atom)

β-dicarboxylic acids

1,3-dicarbonyl i.e. two carboxylic acid FGs separated by a single carbon - have α-hydrogen that is very acidic - note that the hydroxyl hydrogens are much more acidic, and have only been left protonated for illustration purposes

A steric number of _____ corresponds to sp³ hybridization.

4

β-lactams are ______-membered rings.

4

d-orbital

4 symmetrical lobes and has 2 nodes

imine

A double bond between a carbon and a nitrogen formed from a 1° amine or ammonia reacting with an aldehyde/ketone under acidic conditions ✷ the Y atom attached to the nitrogen is either H or an alkyl group (R) ✷ can be referred to as a *Schiff base* if the Y is an alkyl group (R) Derivatives: ❗️if the Y is an OH, then it's an *oxime* (on another flashcard) ❗️if the Y is NH₂ or NHR", then it's a *hydrazone* (on another flashcard) ❗️if the Y is NHC(=O)NH₂, then it's a *semicarbazone* (on another flashcard)

cyanohydrin

A functional group containing a nitrile and a hydroxyl group (NC-C-OH) formed when an aldehyde/ketone reacts with HCN in base it's a stable compound

E1 reaction

A two-step reaction in which the alkyl halide dissociates, forming a carbocation intermediate, then a base removes a proton from a carbon adjacent to the positively charged carbon - unimolecular rate law (depends on substrate only): rate = k[R-L] - big barrier: carbocation intermediate 3° > 2° >> 1° - does not require strong base - no requirements for stereochemistry - product will follow Zaitsev's rule - favored by heat

enamine

An amino group attached to a carbon that is double-bonded to another carbon. formed by: ① tautomerization of an imine analogous to keto-enol tautomerization OR ② synthesis from a *2°* amine with aldehyde/ketone

carbinolamine

An intermediate in the formation of an imine, having an amine and a hydroxyl group bonded to the same carbon atom.

retro-aldol reaction

As the name suggests, retro-aldol is exactly the reverse of an aldol reaction. Here, a carbon-carbon bond is broken to form two fragments, forming either two aldehydes, two ketones, or one of each

If trying to determine whether a reaction is SN1 or E1, how can heat help you decide?

At low temperatures SN1 products tend to dominate over E1 products At higher temperatures, E1 products become more prominent

3-hydroxybutanal can be formed by the reaction of: A. Methanol in diethyl ether B. Ethanal in base, then in acid C. Butanal in strong acid D. Methanal and ethanal in catalytic base

B Clues: 3-hydroxybutanal is an aldol, which is an intermediate in the aldol condensation. The whole reaction is often base-catalyzed, so adding acid would halt the reaction at the aldol. Also, aldol condensations are most effective when the two molecules are the same. Since we end up with a four carbon product, it's likely that we started off with 2 two-carbon reactants ("eth") A and C are clearly wrong, but you can also eliminate D because this combination would form 3-hydroxy*prop*anal and since this answer choice does not include the acid, the whole reaction would continue and the aldol would dehydrate to form propenal (an enal).

A patient hears a beeping sound from ten meters away and decides to go closer to examine the source. If the patient is now one meter away, what is the ratio of the original intensity of the sound to the new intensity of the sound? A. 1:1 B. 1:10 C. 1:100 D. 1:1000

C Explanation: I = P/A A in this case is the area of a sphere: 4πr² (because it represents sound waves emanating from a single source) So if you decrease r by 10: 4π(1/10r²) this increases the intensity by 100 (inversely related)

succinic anhydride

CYCLIC "closed" acetic anhydride

phthalic anhydride

CYCLIC forms from intramolecular condensation or dehydration of dicarboxylic acids

aldol

Contains both aldehyde and alcohol functional groups. also called a *β-hydroxy ketone*

What reagents can be used to convert a secondary alcohol to a ketone?

PCC CrO₃/pyridine

Which conversion between carboxylic acid derivatives is NOT possible by nucleophilic reaction? A. Carboxylic acid to ester B. Ester to carboxylic acid C. Anhydride to aminde D. Ester to anhydride

D Explanation: remember the hierarchy (from most to least reactive): anhydride > carboxylic acid > ester > amide This means that practically derivatives of lower reactivity cannot form derivatives of higher reactivity, which is what D claims and is therefore false.

What type of mechanism is the following reaction? 2° or 3° alcohol ⟶ alkene with H₂SO₄ and heat

E1 Explanation: ✷ key parts to recognize: ① H₂SO₄ (or H₃PO₄ or tosic acid) as the acid produces elimination products, whereas HCl, HBr, and HI give substitution products ② heat - tends to favor elimination reactions ③ 2° or 3° alcohol ✴︎ Note, it can occur w/ primary alcohols too, but much more likely thru E2 since 1° carbocations are not stable in E1

elimination of 2° or 3° alcohols

E1 ￫ require heat ￫ alkene formed ￫ proceed through carbocation intermediate ￫ H₂SO₄, H₃PO₄, or p-TsOH as acid (because the conjugate bases are poor nucleophiles and are resonance-stabilized. This is useful when we just want the alkene to form, and don't want the nucleophile to react with our intermediate [which would result in *substitution* products instead of elimination products]). ￫ may see rearrangements (e.g. hydride shifts): *if you see that a more stable carbocation could be formed through migration of an adjacent H or alkyl group, expect that to happen!*

inductive effect

Electron donation (+I) or withdrawal (-I) through the sigma bonds of a molecule. has different effects on carbocation and carboanion stability +I stabilizes carbocations -I stabilizes carboanions

Esterification reaction

Formation of esters from carboxylic acids and alcohols. ￫ water is a byproduct ￫ slow ￫ in equilibrium ￫ improved with acid catalyst in excess, protonation activates carbonyl carbon

chromic acid

H2CrO4 is a strong acid and is a reagent for oxidizing alcohols to ketones and carboxylic acids It does this through the addition of the alcohol oxygen to chromium, which makes it a good leaving group; a base (water being the most likely culprit) can then remove a proton from the carbon, forming a new π bond and breaking the O-Cr bond 📸many different forms (equivalents) to chose from, but they all do the same thing

hydrogen cyanide

HCN classic nucleophile - triple bonds and super electronegative atom hydrogen dissociates and the cyanide anion can attack the electrophile/ carbonyl carbon

What reagents can be used to convert a diol into an aldehyde?

HIO₄ NaIO₄ Pb(OAc)₄

What reagents can be used to convert an aldehyde to a carboxylic acid?

H₂CrO₄, KMnO₄, H₂O₂

semicarbazide

H₂N-NH-C(=O)NH₂ urea derivative used to synthesize semicarbazones with aldehydes/ketones

Acetal/ketal formation

In acidic conditions, an aldehyde or ketone will react with two molecules of alcohol to form an *acetal* via SN1 absolutely REQUIRES acid otherwise it will stop at hemiacetal/hemiketal

aldol reactions in biochemistry

It is important to emphasize that aldol reactions are *highly reversible* in nature: in most cases, the energy levels of reactants and products are not very different. Thus, depending on the metabolic conditions, *aldolases* can also catalyze retro-aldol reactions (i.e. the reverse of aldol reactions, in which a carbon-carbon bond is broken). As a typical example; fructose 1,6-bisphosphate aldolase is involved in two divergent pathways. - the sugar synthesis (gluconeogenesis) pathway, - the sugar breakdown (glycolysis) pathway

What reagent can be used to convert an aromatic alkane into a carboxylic acid?

KMnO₄

LiAlH₄

Lithium aluminum hydride is a very strong reducing agent. It will reduce aldehydes, ketones, esters, and carboxylic acids to alcohols, and amides and nitriles to amines. It will also open epoxides. Disadvantages: reacts violently with water, so must be delivered in an anhydrous solution of diethyl-ether, Et₂O, and then neutralized by water and acid to isolate the product/s

Do alkanes make good leaving groups?

NO they form reactive anions

Which reducing reagent is preferred when milder conditions are needed: LiAlH₄ or NaBH₄?

NaBH₄ Explanation: LiAlH₄ is a powerful reducing agent NaBH₄, since the Al-H bond is weaker and thus less stable than B-H bond. LiAlH₄ is used only when you need to reduce all the way from very oxidized compounds (ex: carboxylic acids) Since NaBH₄ can reduce aldehydes and ketones, it is preferred since it won't react violently with water and you can avoid all those steps that are required when using LiAlH₄ ❗️NaBH₄ only works reduces aldehydes and ketones

Are hybridized orbitals molecular orbitals?

Not until they actually bond with another orbital Hybridized orbitals are atomic orbitals (s, p, etc.) that have combined and hybridized so that the resulting orbitals are all equivalent.

What is the oxidation state of both elements in the following compound? OF₂

O: +2 F: -1 Explanation: this is one of the few exceptions where oxygen does not have a -2 oxidation state. This is because it is bonded to a more electronegative element. ✴︎Use the convention that cations are written first followed by anions to determine which one has the + and - oxidation state. Another example: NaH Na (left) has +1 H (right, second) has -1

Oxidation number vs formal charge

Oxidation # assumes *unequal* sharing of electrons in bonds, awarding e⁻ to the most electronegative element • Formal charge assumes *equal* sharing of electrons in bonds, awarding one e⁻ to each atom in the bond. In reality, it lies between these two extremes

What reagents can be used to convert a primary alcohol to an aldehyde?

PCC CrO₃/pyridine

When you see a diol as a reagent with alcohols and ketones, think...

PROTECTING GROUP diols are nucleophiles

Amides have what general formula?

RCONR₂ R's attached to N can be H's too

When you see an "acidic workup", especially at the end of the reaction, think...

REMOVAL OF PROTECTING GROUP

If the carbon containing the leaving group is methyl or primary, you almost certainly have what type of reaction?

SN2 Explanation: Since the SN2 proceeds through a backside attack, the reaction will only proceed if the empty orbital is accessible. The more groups that are present around the vicinity of the leaving group, the slower the reaction will be. i.e. less steric hindrance = faster this reaction ❗️unless the base itself is super bulky, which will give elimination products instead

How are esters named?

Same manner as salts, they are based on the names of the parent alcohol and carboxylic acid: place alcohol group as a prefix + carboxylic acid chain (ex: ethan) + "-oate" example: ethyl acetate (ethyl ethanoate)

What is the shortcut formula for formal charge?

Should have - Has Ex: CN C should have 4 VE, but it has 5 (3 bonded to N and 2 as part of 1 lone pair) FC = 4 - 5 = -1

Describe the activation of a carbonyl carbon.

Sometimes, the electrophilic carbonyl carbon is still not positive-looking enough to attract a weak nucleophile (like water). So it requires *protonation* of the carbonyl oxygen by an acid, which makes the oxygen more positive and thus more motivated to steal even more electron density from the carbonyl carbon, making it more positive-looking. Now, the weak nucleophile is more motivated to attack. ✴︎ so whenever you see an acid in the reaction mechanism, think, what's being protonated?!

nucleophilic acyl substitution

Step 1: Nucleophilic Addition, opening the carbonyl and forming a tetrahedral intermediate Step 2: Reformation of the carbonyl and leaving group is kicked off ✷ in effect, nucleophile replaces the leaving group of an *acyl derivative* (carboxylic acid, ester, amide, acyl halides, etc.)

TMSCI

TMSCl is a protecting group for alcohols. When added to alcohols, it forms a silyl ether, which is inert to most reagents except for fluoride ion and acid. Note that the reagent can be written two ways (CH3)3SiCl and TMSCl.

True or False: Charges at the allylic position are ALWAYS the most stable, no matter if it's a carbocation, carbanion, or radical.

TRUE Explanation: no matter what charge it is, this position allows for delocalization

True or False: The carbonyl group can participate in conjugation

TRUE Explanation: the C=O is a π acceptor ex: α,β-unsaturated carbonyls (enones or Michael acceptor)

Zaitsev's Rule

The most substituted alkene is formed preferentially

transesterification

The process that transforms one ester to another when an *alcohol acts as a nucleophile* and displaces the alkoxy group ("esterifying group") on an ester: ester + alcohol ⟶ ester + alcohol

esterification

The reaction of an alcohol with a carboxylic acid to produce an ester and water.

enol

The tautomer of a carbonyl that has a carbon-carbon double bond (ene) and an alcohol (-ol)

True or False: The carbonyl in a ketone is never a terminal group.

True

True or False: The carbonyl in an aldehyde is always a terminal group.

True

True or False: Conjugation in a molecule can also serve to stabilize positive charge

True electron delocalization in a conjugated system can stabilize both positive and negative charges, enhancing its stability for negative, simply take that negative charge and bounce it around so it's not sitting too long on any one atom ("hot potato") for positive, still move electrons around, but this time it's to give each atom an equal share of negative charge, so that it's not just one lonely atom that's positive ("rationing")

steric protection

Useful tool in the synthesis of desired molecules and the prevention of the formation of alternative products

Are acyl halides reactive?

YES Explanation: because they have a good leaving group attached to the carbonyl carbon so in a reaction where you start with an acyl halide as a reactant, it is quite unlikely that you're at risk for the reverse reaction (reformation of the acyl halide), because of the fact that it is so reactive!

Show the generic reaction of alkali metals with water. Is this a favorable reaction?

YES, alkali metals (Group I) react *very* readily with water.

What type of reaction could convert an imine back to an aldehyde/ketone and primary amine?

hydrolysis under acidic conditions

E2 reaction

a concerted elimination reaction involving a transition state where the base is abstracting a proton at the same time that the leaving group is leaving. - bimolecular rate law (depends on substrate and base): rate = k[B⁻][R-L] - big barrier: none - *requires* strong base - stereochemistry: anti-coplanar transition state i.e. the leaving group *must* be anti to the hydrogen removed. - Zaitsev orientation is usually preferred unless the base or the leaving group is unusually bulky. - favored by heat

Condition #2 For Aromaticity: "Every atom in the ring must be conjugated."

a continuous ring of p-orbitals around the ring that build up into a larger cyclic "π system" We can also say: • "Every atom in the ring must have an available p orbital", or • "Every atom in the ring must be able to participate in resonance". ✷✷✷Remember that the "available p orbital" condition applies not just to atoms that are part of a π bond, but also atoms bearing a lone pair, a radical, or an empty p orbital (e.g. carbocations). ❗️The key thing that "kills" conjugation is an sp³ hybridized atom with four bonds to atoms. Such an atom cannot participate in resonance

Lewis acids are electron pair ____________.

acceptors (LUMO) ✴︎ in the form of a covalent bond - electrophiles

hydration of carbonyls

aldehyde/ketone reacts with water to form geminal diols (*hydrates*) slow, but can be sped up using small amounts of catalytic acid or base Mechanism: ① Carbonyl is hydrated when the nucleophilic :O: in water attacks the electrophilic carbonyl carbon. The π electrons are kicked off, and the carbonyl O happily accepts them as a lone pair, acquiring a -1 formal charge ② proton transfer to protonate O⁻ and get rid of +1 formal charge on the newly-added O atom (from water) result is a geminal diol

____________ orbitals can hybridize into sp, sp², or sp³ orbitals.

atomic

Ligands are Lewis ___________.

bases Explanation: Ligands are ions or neutral molecules that bond to a central metal atom or ion. Ligands act as Lewis bases (electron pair donors), and the central atom acts as a Lewis acid (electron pair acceptor).

Water can only act as an acid in ____________ solution.

basic

When in ___________ solutions, α-hydrogens will easily deprotonate.

basic Explanation: copious base molecules around to abstract the easily-abstractable proton

succinic acid

butanedioic acid

acetic anhydride + butanol

butyl acetate Explanation: anhydride + alcohol ⟶ ester + carboxylic acid It's named this way because butanol will attack the anhydride (so it keeps the "acetate" high priority name) and butyl is the substituent IUPAC name: butyl ethanoate

Show how you can rule out certain reactions based on the substitution of the substrate

can easily narrow it down if it's 1° or 3°, but if you have secondary, you need to look at other factors

Which enolate tautomer is the most reactive?

carbanion

keto form of enolate

carbanion

β-keto acid

carbonyl at β position from a carboxyl group

soap

carboxylate anion with a large hydrocarbon tail

protecting group

chemical modification of a func. group to "protect" it from reacting can be used to temporarily mask a reactive leaving group with a sterically bulky group during synthesis ex: Reduction of a molecule with both carboxylic acids and aldehydes/ketones can result in reduction of all FGs. To prevent this, the aldehyde/ketone is first converted to a nonreactive acetal/ketal which serves as the *protecting group*, and the reaction can proceed

ozonolysis

cleaves double bond in half, it only oxidizes the carbon to an aldehyde under reducing conditions. if oxidizing conditions, aldeyde is rapidly converted to carboxylic acid (same products as KMNO₄)

valeraldehyde

common name for pentanal

How are anhydrides formed?

condensation of two carboxylic acids notice the *zwitterion* intermediate

Tautomers are ___________ isomers.

constitutional (structural) Explanation: differ by movement of a H atom

Mesylate (⁻OMs)

contains functional group -SO₃CH₃ ￫ derived from methanesulfonic acid ￫ prepared using methylsulfonyl chloride and an alcohol in presence of a base, converting it into an ester (-*ate*) ￫ mesyl and tosyl groups can serve as protecting groups when we don't want alcohols to react bc they will not react with many of the other reagents that would attack alcohols ￫ they are also much better leaving groups than the alkoxide ion

tosylate (⁻OTs)

contains functional group -SO₃C₆H₄CH₃ ￫ derived from toluenesulfonic acid ￫ prepared using p-toluenesulfonyl chloride and an alcohol in presence of a base, converting it into an ester (-*ate*) ￫ mesyl and tosyl groups can serve as protecting groups when we don't want alcohols to react bc they will not react with many of the other reagents that would attack alcohols ￫ they are also much better leaving groups than the alkoxide ion ⁂ also used to protect *amines*

How are cyclic carboxylic acids named?

cycloalkane + suffix "carboxylic acid"

Electron-withdrawing substituents ______________ basicity.

decrease Explanation: electron density on the nucleophilic center is lessened, making the lone pair less effective

What effect does branching have on boiling point?

decreases Explanation: This is another byproduct of the surface-area dependence of Van der Waals dispersion forces - the more rod-like the molecules are, the better able they will be to line up and bond. To take another intuitive pasta example, what sticks together more: spaghetti or macaroni? Spaghetti. The more sphere-like the molecule, the *lower its surface area* will be and the fewer intermolecular Van der Waals interactions will operate (lower BP)

Alkyl groups are electron...

donating unless they have an electronegative atom attached (e.g. CF₃)

Lewis bases are electron pair ______________.

donors (HOMO) ✷ in the form of a covalent bond - nucleophiles

What counts as π electrons for Hückel's rule?

double bonds and lone pairs AS LONG AS the lone pairs are not on an atom already participating in a double bond The bottom line: each ring atom can contribute a maximum of one p orbital toward the π system because the other will not be in the plane of the π system (90° to it) So an atom with two lone pairs *can only contribute one of them* And an atom participating in a double bond that also has a lone pair *cannot* contribute its lone pair of electrons ✴︎ lone pairs contribute 2 electrons ✴︎ double bonds contribute 2 electrons (1 in each p orbital of each atom participating in the double bond)

Quinones are (electrophiles/nucleophiles)

electrophiles resonance-stabilized electron *acceptors*

Methanol is oxidized in the body to __________.

formic acid

What intermediate is formed when oxidizing aldehydes to carboxylic acids with strong oxidizing agents?

geminal diol ("hydrate") the formation of this hydrate is the key to the E2 mechanism at work. ✷ this explains why PCC can't oxidize past the aldehyde stage because it lacks the water necessary to hydrate the aldehyde and form this *hydrate* intermediate and also explains why water is essential in reactions such as the Jones Oxidation ("*dilute* sulfuric acid")

The more electronegative-containing groups in a carbonyl-containing compound, the ___________ its reactivity.

greater Explanation: EW groups steal even more electron density from the carbonyl carbon, making it more electrophilic this is why amides are less reactive than esters, carboxylic acids and anhydrides: N < O (electronegative)

What is the effect of charge on electrophilicity?

greater the positive charge = more electrophilic so a carbocation (C+) is more electriphilic than a carbonyl carbon (δ+C=O)

Ubiquinone contains polar functional groups (ketones). So how is it able to act as an electron carrier *within* the phospholipid bilayer?

has a very long alkyl chain which allows it to be lipid soluble indicated by [-------]₁₀

Which hydrogen is more acidic on a dicarboxylic acid, the α-hydrogens or the hydroxyl hydrogens?

hydroxyl, of course, because they're directly attached to O but α-hydrogens are very acidic compared to other C-H bonds!

Flip for a chart of electron-donating and electron-withdrawing groups.

in this chart, activating is ED because in this mechanism, we have carbocations deactivating is EW because in this mechanism, we have carbocations ❗️If the intermediate was instead carbo*anions*, it would be opposite: activating groups would be EW and deactivating groups would be ED.

3-hydroxylcycloheptane carboxylic acid

included to emphasize that when naming cyclic carboxylic acids, always name the ring as an ALKANE (in this case, NOT with the alcohol as the highest priority)

Electron-donating substituents ______________ basicity.

increase Explanation: electron density on the nucleophilic center is enhanced, making it more willing to donate its lone pair.

The addition of an electronegative atom to an alcohol would have what effect on its acidity?

increase Explanation: electron-withdrawing groups stabilize the conjugate base - the more stable the conjugate base, the stronger the acid

What effect would removing water have on the formation of acetal?

increase (shift right) Explanation: it's a product

Factor # 1: *Charge* Nucleophilicity ___________ with increasing electron density.

increases Explanation: more negative charge = more likely to give some up

To say that a fluid has a constant density is another of saying what?

it is incompressible!

What product is obtained when aldehydes or ketones are treated with alcohols under basic conditions?

it will stop at the "halway" step (hemiacetal/hemiketal) because they are stable in base NO acetal/ketal formed without acid! Acid is required for all the protonation steps that increase the reactivity of the substrates and *creates water as a leaving group* so that you can get a second nucleophilic attack (by the alcohol) and get two -OR groups.

What happens to the Eustachian tube upon swallowing?

it's normally closed except during swallowing, when it temporarily opens to equalize external pressure and pressure in the middle ear

Why is the keto tautomer more thermodynamically stable than the enol tautomer?

keto tautomer puts more electron density around the oxygen than the enol tautomer

2° alcohol + CrO₃/pyridine

ketone

elimination reactions

part of a reactant is lost and a new multiple bond is formed

What are "soft" Lewis bases?

larger and polarizable ex: organophosphines, thioethers, carbon monoxide, iodide

If there is no strong/charged nucleophile/base, e.g. just water or alcohol, what is the likely reaction mechanism?

likely looking at carbocation formation ⟶ SN1 or E1

Nucleophiles tend to have...

lone pairs or π bonds (HOMO)

fatty acids are...

long chain carboxylic acids

Reducing agents have ____________ electronegativity and ionization energy.

low

boiling point of esters

lower than carboxylic acids and alcohols because they lack hydrogen bonding

Nucleophilic attack will only occur if the reactants are _________ reactive than the products.

more ￫ nuc must be more reactive than the leaving group ("battles" it for the position). ✴︎ just like acid-base reactions

glutaric acid

pentanedioic acid

What is the requirement for the substrate in SN1/SN2/E1/E2 reactions?

must be an *alkyl* group attached to the leaving group ❗️very likely that no reaction will occur if the leaving group is attached directly to an alkene or alkyne Why are alkenyl and alkynyl halides so bad? Well, the SN1, SN2, and E1 mechanisms all involve considerable build-up of positive charge on the carbon bearing the leaving group, and the stability of sp² and sp hybridized carbocations is much lower than that for sp³ hybridized carbocations [for the same reason that sp and sp² *anions* are more stable than sp³ carbanions - a vinyl or aryl carbocation carries the positive charge on an sp² or sp carbon, which puts the charge closer to the nucleus (repulsion for carbocation + [high energy, unstabe] and attraction for carbanion - [low energy, stable]) than a carbon of an alkyl carbocation where the charge is further from the nucleus]. Plus, the + charge decreases the ability for π conjugation due to geometrical restraints of the hybridization E2 reactions are also more difficult due to the stronger C-H bonds of alkenes (harder to break bond)

An aldehyde or ketone acts as a _____________ in its enol form.

nucleophile i.e. does the attacking on another aldehyde/ketone in the keto form, especially in catalytic base because it will deprotonate it so that it now has a lone pair of electrons

What compounds can NaBH₄ be used to reduce?

only ketones and aldehydes and also used in second step of oxymercuration (out of scope MCAT) Explanation: it's weaker than LiAlH₄

heterolytic reactions

opposite of *coordinate covalent bond* formation: a bond is broken and *both* electrons are given to *one* of the two products. this is how leaving groups detach

conjugation

overlapping of p orbitals that allow a delocalization of π electrons across all the adjacent aligned p orbitals. ✴︎ The π electrons do not belong to a single bond or atom, but rather to a group of atoms 📸 Note that only one of the oxygen lone pairs participates in conjugation in a p orbital, while the other lone pair is in an sp² hybridized orbital in the plane of the molecule and not part of the π system. The participation of six electrons in the π system makes furan aromatic

What is the smallest dicarboxylic acid?

oxalic acid (2-carbons) IUPAC name: ethanedioic acid

SN1/E1 reactions are best carried out in what type of solvent?

polar protic Explanation: nucleophiles form hydrogen bonds with the -O*H* hydrogen atom, stabilizing them carbocations form hydrogen bonds with the -*O*H oxygen atom, also getting stabilized

E1 reactions do best with what type of solvent?

polar protic Explanation: the polar protic solvent is stabilizing the nucleophile, and also has the ability to stabilize any carbocations formed during the reaction. The lone pair of electrons on the solvent can donate electron density to the carbocation, making the carbocation more stable. A weaker nucleophile and a stabilized carbocation mean that polar protic solvents are evidence for SN1 and E1 reactions 📸 #3

SN1 reactions do best with what type of solvent?

polar protic such as water, alcohols, and carboxylic acids. ✴︎ These also tend to be the nucleophiles for these reactions as well Explanation: 📸 #4

What does "-ium" indicate in a compound?

positive charge ex: hydron*ium* ion (H₃O⁺), iminium ion, oxonium ion, etc.

KH

potassium hydride, a strong base (actually a *superbase*) that can form enols by deprotonation of the α-carbon

regioselectivity

preferential formation of one *constitutional* isomer over another

How is an aldol isolated?

reaction conditions must be mild: ￫ *low* temp ￫ carefully-controlled amount of acid (used to protonate the alkoxide ion intermediate) ❗️If too much acid is added, or if the temperature is too high, the aldol will dehydrate to form a conjugated alkene

iodometric titration

redox titration that relies on the titration of free iodine radicals. 2 steps: first oxidizing analyte (e.g. IO₃⁻) is tested for the presence of iodine: It's titrated until converted to a colorless solution that requires a starch indicator for the remainder of the titration. second, the ions produced in the first are then reduced in the presence of sodium thiosulfate to determine its concentration You can use the stoichiometry from the two balanced half-reactions, the initial volumes, and the known molarity of the oxidizing analyte to calculate the thiocyanate concentration. ❗️different from iod*i*metric titration (which occurs in only one step and uses a reducing analyte)

CO is a ___________ agent.

reducing

Carbon is a ___________ agent.

reducing

Zn(Hg) is a ____________ agent.

reducing (Zinc Amalgam) *Clemmensen reduction*: takes ketones adjacent to aromatic rings down to the alkane Mechanism: addition of acid protonates the ketone, and electrons from the Zn(Hg) are delivered to the carbon; the new hydrogens come from the acid, while the oxygen is eventually expelled as water

Pure metals are ___________ agents.

reducing e.g. Sn²⁺

Hydrazine is a __________ agent.

reducing ✷ hydrazine = H₂N:-:N₂H

What conditions are required to convert an acetal/ketal back to an aldehyde/ketone?

same as before: acid and heat, but... ✷ this reverse reaction will be hydrolysis, so with water as a reactant, you want an excess of water, whereas for the forward reaction, you want to remove water since it's a product.

If you do decide to use a mixture of aldehydes or ketones in your aldol condensation, how can you control which will act as the nucleophile and which as the electrophile?

select a molecule that has no α-hydrogens, because the α-hydrogens are quaternary ex: benzaldehyde that way, it will necessarily have to be the electrophile and your other molecule can be deprotonated at it's α-carbon and become the nucleophile

How are electrochemical cells arranged so that undesired cross-reactions are prevented?

separating the two half-cells ❗️only necessary for galvanic cells, because electrolytic cells are nonspontaneous anyway

protection of alcohols with silyl ethers

silyl ether + alcohol under basic conditions to form O-Si bond. ✴︎ silyl ether commonly used is *TMSCl* and forms *TMS* since it is the simplest (least bulky) and therefore makes it easy to cleave the O-Si bond ✴︎ removal with TBAF or strong acid

Redox titrations vs. Acid-Base titrations

similar setup, but different focus: ￫ acid-base: follow transfer of *protons* to reach equivalence point ￫ redox: follow transfer of *electrons* to reach the equivalence point

Describe the boiling points of amides

since amides may or may not participate in hydrogen bonding (depends on the number of alkyl groups they have bonded), their boiling points may be *lower* or on the *same* level as carboxylic acids

Why would you ever use a less strong base in an aldol condensation?

since you are using the same molecules, you don't want them all to turn into enolates. You need some to stay as the aldehyde/ketone so that they can be attacked by the enolate ex: use NaOH in this case

What are "hard" Lewis bases?

small, highly charged, and nonpolarizable ex: ammonia and amines, water, carboxylates, fluoride and chloride

In the following reaction, nitrate is a ____________. Cu(s) + 2AgNO₃ (aq) ⟶ Cu(NO₃)₂ (aq) + 2Ag (s) Write the net ionic equation.

spectator ion Explanation: it doesn't participate in the reaction and is therefore unchanged, so it's not included in the net ionic equation

stereoselectivity vs. stereospecificity

stereochemical information in the substrate is lost, e.g. when forming the carbocation you could have had the opposite stereochemistry at the C with the OH and still gotten the same mixture of products. stereospecific: the stereochemical information in the substrate is PRESERVED because of the mechanism. It *determines* the product.

The weaker the bond strength, the __________ the acid.

stronger Explanation: H+ is more easily donated (BL) ✷ this trend takes precedence if there is opposition between bond strength and electronegativity i.e. if there's low bond strength but the atom is not very electronegative, it will still be acidic.

All else being equal, polar aprotic solvents favor ___________.

substitution (SN2) Explanation: such as acetone, DMSO, acetonitrile, or DMF that are polar enough to dissolve the substrate and nucleophile but do *not* participate in hydrogen bonding with the nucleophile!

Esterification is a nucleophilic (addition/substitution).

substitution (acyl, not traditional SN1 or SN2)

aldol reaction (detailed mechanism)

technically two separate reactions - first you form the aldol, then the enal/enone is formed from that ① Aldol formation ￫ α-carbon of an aldehyde/ketone is deprotonated at the α-carbon by a base, generating the enolate (has resonance structures called carbanion and oxyanion [more stable], both constitute the same product). This enolate can then attack another aldehyde or ketone at the carbonyl carbon, pushing the π electrons off onto the oxygen. IMPORTANT: Now we have a new *carbon-carbon bond*. Next, the alkoxide intermediate is protonated by water, generating the *aldol* ✴︎*the key is that both species are in the same flask!* This step will occur at high temperatures!!!! ② Aldol dehydration/condensation ￫ *you can form different products depending on reaction conditions* aldol also has acidic α-hydrogens, so the base again strips off a proton and forms another enolate. The lone pair on the carbon move in and form a double bond between the two carbons, kicking off the electrons to form hydroxide as a leaving group (E1 or E2 mechanism). This double bond is between the α- and β-carbons, so the molecule is an *α,β-unsaturated carbonyl*, and the major product formed is the *trans* product (less steric hindrance) Variables: - Choice of aldehyde or ketone, both are still aldol reactions, so product can be *enal* or *enone* - Base-catalyzed/acid-catalyzed (usually shown as base catalyzed) - Strong base vs. weak base (strong base = kinetic product; weak base = thermodynamic product) - Heat (cold = kinetic product; heat = thermodynamic product) ✴︎For each case, there will be 2 structures (a kinetic oxyanion & a kinetic carbanion; a thermodynamic oxyanion & a thermodynamic carbanion) - Depending on whether the carbanion resonance structure reacts (described above) or the oxyanion reacts, you will get a slightly different product

What is the focal length of the human eye?

the distance between the *lens* and the *retina* when an object is in focus general definition: the distance between the center of a lens/mirror and its focus (focal point). Here the retina is the focal point and the lens is the crystalline lens generally agreed upon to be 17 mm

focal length

the distance between the center of a lens or curved mirror and its focus.

polarizability

the ease with which the electron distribution in the atom or molecule can be distributed greater for bigger atoms: increases *down* a group and from *left to right* ex: Group: I > F (bigger) Row: M > F (electrons held less tight, bigger cloud)

Why is cyclooctatetraene not aromatic?

violates rule #3 ([4n+2] π electrons) if you count, it has 8 π electrons, which cannot ever fit Hückel's rule with any integer "n" ex: n = 1, 4(1) + 2 = 6 n = 2, 4(2) + 2 = 10

Fischer esterification

the formation of an ester from a carboxylic acid and an alcohol through condensation under *acidic* conditions

Why are phenols so acidic?

the hydroxyl hydrogens are particularly acidic due to *resonance* between the phenol ring and the resulting lone pairs on the O atom after donating its proton.

How do β-lactam antibiotics work?

the ring strain and non-planar configuration of the N make it very reactive (carbonyl carbon is super electrophilic, so it attracts the bacterial transpeptidase enzyme that builds cell walls) the O: on transpeptidase is the nucleophile and attacks the carbonyl carbon on the antibiotic, and with this new attachment we've disabled the bacterial enzyme.

Why is it difficult to isolate hemiacetals and hemiketals?

they are unstable because the hydroxyl group is rapidly protonated and lost as water under acidic conditions, leaving behind a reactive carbocation hence, they usually go all the way to acetals and ketals when there's enough alcohol (nuc) that will attack that carbocation

Why are conjugated carbonyl-containing compounds more reactive?

they can stabilize their transition states through electron delocalization

Why do tertiary amines have lower boiling points than primary and secondary amines of similar weight?

they cannot hydrogen bond!

Why is nitrous oxide (N₂O) stored at high pressures and cool temperatures?

to promote a phase change (liquid) when it's stored so that the proper concentration can be measured when dosing. Much easier to measure concentration as a liquid, rather than trying to use the ideal gas law and figure out the moles because nitrous oxide is NOT like an ideal gas (polarity, large, has IMF's) It's DEADLY when not dosed properly

Where does the equilibrium lie between a carboxylic acid and its carboxylate anion?

towards carboxylate anion Explanation: carboxylic *acid* donates a proton and the resulting anion is resonance stabilized, so it's favored at equilibrium even more so if there are electron-withdrawing groups!!

ortho

two groups on adjacent carbons

Jones oxidation

uses chromium trioxide (CrO₃) dissolved in dilute sulfuric acid and acetone (stronger oxidizing agent) to oxidize 1° alcohols all the way to carboxylic acids or 2° alcohols to ketones

How can carbonyls act as nucleophiles?

using either the lone pairs on the oxygen or the electrons in the π bond to attack other electrophilic molecules in either case you get the same result because the products are resonance structures and thus identical. ex: carbonyl condensation

alkene + OsO₄

vicinal diol syn addition - same side

Why should esterification reactions NOT be carried out in water?

water is a byproduct of the forward reaction, and this reaction is in equilibrium If there is an abundance of water, Le Chatelier's Principle states that the reaction will shift left (towards the reactants), and that would ↓ synthesis of our desired products (ester) Mechanism for reverse reaction: water acts as the nucleophile and attacks the ester's carbonyl carbon to reform the carboxylic acid reactant.

_____________ bases make the best leaving groups.

weak Explanation: they're more stable (unreactive) with that extra set of electrons low pKas ex: I⁻, Br⁻, Cl⁻

At high temperatures and with a _________ base in a protic solvent, the thermodynamic enolate will be favored.

weak ex: NH₃ Explanation: the reaction proceeds slowly with a weak base, giving the kinetic enolate (which forms very fast, but is less stable) time to interconvert to the more stable thermodynamic enolate.

An acid-base reaction will only proceed if the products that will be formed (conjugate base of the acid and conjugate acid of the base) are ____________ than the original reactants.

weaker Explanation: that means that the reactants are way more reactive, so the products will be at a lower energy and will continue to spontaneously form

Why is acyl chloride particularly reactive?

you have an electronegative halide, but also the Cl⁻ is a great leaving group so it's even more reactive than anhydrides!

enone

α,β unsaturated carbonyl formed via aldol condensation of ketones

What is the product of the aldol condensation?

α,β-unsaturated carbonyl or enone/enal

Spontaneous decarboxylation upon heating occurs with what kind of acids?

β-keto acids and β-dicarboxylic acids Explanation: these can form a *cyclic transition state* which permits simultaneous hydrogen transfer and loss of CO₂

What factors affect electrophilicity?

① Charge ② Presence of empty orbitals - no need for a leaving group to "make room" ③ Nature of the leaving group in species without empty orbitals - *requires* a leaving group because there's no vacancy, will go through an intermediate/transition state where both are bonded and then kick off the leaving group

When analyzing a mechanism and you see that a carbonyl is opened via nucleophilic attack, one should always ask...

"Can I reform the carbonyl?" ￫ If there is a good leaving group present (as w/ carboxylic acids and their derivatives), then the carbonyl *can* reform, pushing off the leaving group ￫ If no good leaving group is present (as w/ aldehydes and ketones), the carbonyl will *not* reform and instead, the O⁻ will accept a proton from the solvent to form an -OH group.

1,3-dicarbonyl

"active methylene compounds" because of the very acidic α-hydrogens, they often form an enol and this causes them to exhibit internal hydrogen bonding (creation of an -OH group allows the O in the carbonyl to hydrogen bond with the alcoholic H)

What is included in the net ionic equation? What is not? What compounds are split? Which stay together?

*IS*: species that participate (i.e. get reduced or oxidized) *NOT*: spectator ions (ex: Na⁺; SO₄²⁻) *Split*: compounds that are *aqueous* *Keep together*: solid salts & polyatomic ions (since the latter are often spectator ions, you should get rid of them anyway) ❗️exception: something like K₂Cr₂O₄ does get split into K⁺ and Cr₂O₄²⁻ but you keep the Cr₂O₄ together. It's not a spectator ion, and the whole thing acts as the oxidizing agent.

mnemonic for oxidizing and reducing agents

*LEORA* says *GEROA* Loses electrons, oxidation, reducing agent Gains electrons, reduction, oxidizing agent

Common names for dicarboxylic acids

*O*h *M*y *S*uch *G*ood *A*pple *P*ie oxalic acid = ethanedioic acid (2-carbons) malonic acid = propanedioic acid (3-carbons) succinic acid = butanedioic acid glutaric acid = pentanedioic acid adipic acid = hexanedioic acid pimelic acid = heptanedioic acid **very common biologically!

SN1 reaction

*S*ubstitution *N*ucleophilic *1* molecule in the rate determining step (*unimolecular*) • often a *weak* (neutral) nucleophile • racemization (mixture of retention and inversion since the nucleophile can attack from either face of the planar carbocation intermediate) • best substrate is most substituted: 3° > 2° > 1° > methyl because carbocation will be more stable • barrier: carbocation stability • two steps #1 (rate-limiting) spontaneous dissociation of leaving group, forming carbocation #2 nuc attack • best in polar protic solvent • unimolecular rate law (first-order): rate only depends on concentration of the the substrate rate = k[R-L] ✷R-L = alkyl substrate + leaving group

SN2 reaction

*S*ubstitution *N*ucleophilic *2* molecules in the rate determining step (*bimolecular*) • must be a *strong* nucleophile, minimal steric hindrance • barrier: steric hindrance • best substrate is least substituted: methyl > primary > secondary > tert carbon • one step (*concerted*) - back side attack • stereospecific reaction: configuration of the reactant determines the configuration of the product - product will inverted stereochemistry (R) ⟶ (S) if nuc and leaving group have the same priority in their respective molecules • best in polar aprotic solvent • bimolecular rate law: rate depends on concentrations of the the substrate and nucleophile rate = k[Nuc:][R-L] ✷R-L = alkyl substrate + leaving group

When nitrogen or nitrogen-containing derivatives react with aldehydes and ketones, what type of reaction happens, and what functional group is formed?

*condensation* reaction (small molecule is lost) and also a *nucleophilic substitution* reaction (lose C=O and gain C=N) results in the formation of an *imine* (or, for derivatives: oximes, hydrazones, or semicarbazones)

saponification

*reverse esterification*: ester + strong base ⟶ carboxylic acid + alcohol triacylglycerols (esters) react with lye (NaOH or KOH), resulting in soap (a salt)

What do E1 and E2 reactions have in common?

- in both cases, we form a new C-C π bond, and break a C-H bond and a C-(leaving group) bond in both reactions - a species acts as a *base* to remove a proton, forming the new π bond - both reactions follow Zaitsev's rule (where possible) - both reactions are favored by heat.

Which molecule has a higher boiling point, 1-pentanol or 3-pentanol?

1-pentanol Explanation: OH is more exposed, so more opportunities for hydrogen bonding, versus on 3-pentanol it is shielded by alkyl groups

An electron is known to be in the n = 4 shell and the l = 2 subshell. How many possible combinations of quantum numbers could this electron have?

10 Explanation: for l = 2: -2, -1, 0, +1, +2 so 5 possible orbital values for m₁ Then, electrons in each orbital can be ↑ or ↓. So 5 × 2 = 10

Molecular orbitals can contain a maximum of ______ electrons.

2 Explanation: key word is *orbitals*. Like atomic orbitals, molecular orbitals can only hold 2 electrons (with opposite spins) ❗️the 2n² rule is for max electrons in an energy level (shell).

Why is a 1,3-dicarbonyl particularly acidic? a/k/a β-carbonyl

2 carbonyl oxygens to delocalize negative charge ✷ often used to form enolate carbanions

alkyne + O₃ followed by H₂O₂

2 carboxylic acids

The reaction that converts ubiquinone into ubiquinol is a reduction reaction in which two ____________ are reduced to two ___________.

2 ketones ⟶ reduced to 2 hydroxyl groups

How are phenols converted into hydroxyquinones?

2 oxidation steps: ① Phenol (often a *hydro*quinone) ⟶ quinone (1st oxidation) ② Quinone ⟶ *hydroxy*quinone (2nd oxidation)

What lends to the acidity of carboxylic acids?

2 oxygen atoms to delocalize negative charge after donating a proton, so the anion (-ate) is very stable

aldol reaction

3 steps and an optional 4th step if proper conditions: ① A base abstracts a proton at the α-carbon of the aldehyde or ketone to generate an "enolate" carbanion. ② Nucleophilic attack by this enolate at the electrophilic carbonyl carbon of a second molecule of aldehyde or ketone. Look for a new *carbon-carbon bond*! ③ Protonation of the product formed. If heat is applied then an irreversible fourth step can take place: ④ A dehydration step to yield a α,β-unsaturated aldehyde or ketone. ✷✷Just a clarification, if the mechanism involves steps 1 - 3 only, then it is termed as an *aldol addition* reaction (or simply an aldol reaction). But if step 4 takes place, then it becomes an *aldol condensation* reaction (because a water molecule is lost in the event). ✷✷Aldol reactions can be base-catalyzed or acid-catalyzed. For our purposes, we will restrict ourselves to *base-catalyzed* aldol reactions. https://ibb.co/7XV8qx4

If propanamide were treated with water, what product(s) would be observed? A. Propanamide B. Propanoic acid C. Equal concentrations of proanamide and propanoic acid D. Propyl propanoate

A Explanation: amides are the *least* reactive of the carboxylic acid derivatives, so without strong acid or base (as is the case here, with just water), it cannot undergo nucleophilic acyl substitution no reaction ❗️even though the reverse reaction (carboxylic acid + ammonia ⟶ amide + H₂O) occurs, this reaction ("amide hydrolysis") needs that catalytic acid/base

When benzaldehyde is reacted with acetone, which will act as the nucleophile?

Acetone, after reaction with strong base Explanation: benzaldehyde lacks an α-proton, so it cannot be reacted with base to form the nucleophilic enolate carbanion. So this means acetone must be the nucleophile. A strong base is needed to extract the α-hydrogen off acetone and form the enolate anion, which can then act as the nucleophile.

An object is situated in front of a glass lens with a power of +5 diopters. The object is moved from a distance of 100 cm to a distance of 5 cm. What would be the associated change in the image's appearance? A. It would get smaller, then disappear, then get bigger. B. It would get bigger, then disappear, then get smaller C. It would get smaller. D. It would get bigger

B Explanation: f = 1/P f = 1/5 f = 20 cm The object started at a distance of 100 cm (far), and ends at a distance of 5 cm. That means it started outside the focal length, passes the focal point at some point, and then ends within the focal length. Therefore, the image appears larger until it reaches the focal point (F), at which time it will disappear (∞), and then once inside F, the closer it gets to the mirror, the smaller it gets. This matches B. See picture and this interactive: https://micro.magnet.fsu.edu/primer/java/lenses/converginglenses/index.html

Carboxylic acids can be reacted in one step to form all of the following compounds EXCEPT: A. esters B. amides C. alkenes D. alcohols

C Explanation: - esters are formed by *nucleophilic acyl substitution*: carboxylic acid + alcohol ⟶ ester + H₂O - amides are formed by *nucleophilic acyl substitution* with ammonia or an amine - alcohols are formed via *reduction* of a carboxylic acid with a strong reducing agent Conversely, converting a carboxylic acid to an alcohol takes 2 steps: COOH ⟶ reduced to -OH ⟶ alkene via *elimination*

If the reaction involves a really bulky base, what is most likely the mechanism?

E2 explanation: it will be a poor nucleophile due to its great steric hindrance, but still a strong base so it can easily abstract a proton (elimination) Use of a bulky base provides an advantage if the substrate is prone to substitution and you want the elimination product.

What is the product of the reaction of benzoic acid with 0.25 equivalents of lithium aluminum hydride?

Explanation: only 1 reductive process allowed (1 hydride), so only get to the aldehyde

Treating 2-methyl-1-propanol with methylsulfonyl chloride in base, followed by reaction with pyridinium chlorochromate, and a final step in strong acid, will give an end product of: A. 2-methyl-1-propanol B. 2-methylpropanal C. 2-methylpropanoic acid D. 2-methyl-1-propane

Explanation: treating the alcohol with methylsulfonyl chloride under basic conditions converts it into a mesylate. Since the alcohol is "disguised" (*protected*), reacting with this reagent before continuing with what would normally be oxidation (PCC) keeps the alcohol from reacting. The final step with strong acid gives another clue because this is how you remove the protecting group. So the resultant product is the same as the initial reactant.

True or False: Tautomers are resonance structures.

FALSE Explanation: in keto-enol tautomers, an H+ is moved from one group to another. For MCAT purposes, the definition of a tautomer is two substances that can interconvert by moving a hydrogen from one group to another. Resonance structures never have a moving proton, but rather are characterized by a non-integer distribution of electrons between bonds.

True or False: Nucleophilicity is an inherent property to a given species.

FALSE Explanation: it greatly depends on the medium it's in (polar protic, polar aprotic have big effects)

True or False: π bonds are stronger than σ bonds

FALSEEE Explanation: While double bonds are stronger than single bonds *overall*, individual π bonds are *weaker* than σ bonds (further from the nucleus). Breaking the π bond on a double bond is pretty easy, but breaking the remaining σ bond requires much more energy. So in increasing order of strength: π bond < σ bond < double bond < triple bond

True or False: Quinones are aromatic.

False Explanation: they are *conjugated* but not always aromatic

True or False: A carbocation is *always* more stable if it is highly substituted.

False Explanation: this is almost always true (top picture); however, if the groups are not electron-donating and instead are electron-withdrawing, this actually decreases the stability of the carbocation (see bottom picture how the less substituted is actually more stable because it's further from the EW group)

True or False: Resonance forms are in equilibrium

NO NO NO Explanation: they are just structures to show that the electron density is distributed throughout, making the true form a hybrid of all the possible resonance structures. ✷ If the stability of the various resonance forms varies, then the true electron density will favor the most stable form, e.g. no formal charge, have full octets on highly EN atoms, inductive effects, aromaticity, etc. ❗️Don't get confused by this ↔︎ seen between resonance structures. It is *NOT* the same thing as this ⇋ which is equilibrium

Is nucleophilic acyl substitution SN1 or SN2?

Neither, it's its own separate thing in a smaller context of molecules that have an acyl group (the electrophiles) and nucleophiles. There is an SN2 step involved, but there's more to it than that

Can tertiary alcohols be oxidized?

No

When are protic solvents not desirable?

SN2 reactions Explanation: they solvate the nucleophile, making it less likely to attack

Aldehyde + 2 equivalents of alcohol

acetal

Aldehyde + diol

acetal

acetal vs. ketal

acetal = *primary* carbon with 2 -OR groups ketal = *secondary* carbon with 2 -OR groups

The coupling of two acetic acid molecules would result in the formation of what product?

acetic anhydride (condensation)

How are fatty acids regenerated from soap?

acid

Why can both acids and bases increase the formation of hydrates and/or hemiacetals?

acid catalysts work by increasing the electrophilicity of the carbonyl group by protonating the O, making it more + and "motivated" to steal electrons from the carbonyl carbon. base catalysts, on the other hand, work by increasing the nucleophilicity of water or the alcohol by removing the OH proton making stronger nucleophiles before attack on the C=O group. In both cases the energy of the starting materials is raised (hence more likely to react): in the acid-catalyzed reaction the aldehyde is destabilized by protonation and in the base-catalyzed reaction the alcohol is destabilized by deprotonation https://www.khanacademy.org/science/organic-chemistry/aldehydes-ketones/reactions-aldehydes-ketones-jay/v/acid-and-base-catalyzed-formation-of-hydrates-and-hemiacetals

Water can only act as a base in ____________ solution.

acidic

Esterification is favored under ___________ conditions.

acidic (and with *primary* alcohols) Explanation: two purposes. First, it makes the carbonyl carbon a better electrophile (Setting up step 2) and also allows for the loss of H₂O as a leaving group (much better leaving group than HO-) note: reaction is actually in *equilibrium* so it's not always your best bet to produce carboxylic acids

Transesterification reactions are favored under ___________ conditions.

acidic or basic plus a large excess of alcohol to drive the reaction forward (since it's in equilibrium), so it's often used as the solvent as well (NOT water)

Why are thiols so acidic?

acidity increases down the periodic table ￫ the sulfur atom is larger than the oxygen atom so the negative charge will be borne on a larger atom and dispersed over a greater volume. Greater volume = more diffuse charge = greater stability of the conjugate base (weaker conjugate base = stronger acid)

What conditions favor retro-aldol reactions?

addition of aqueous base and heat

diol + Pb(OAc)₄

aldehyde

Alkene + O₃, followed by CH₃SCH₃

aldehyde and ketone

What functional groups act as acids?

aldehydes & ketones (at the α-carbon), carboxylic acids, most carboxylic acid derivatives, alcohols (weakly)

Why are ketones less reactive to nucleophiles than aldehydes?

aldehydes have less steric hindrance (only an H) the carbonyl-carbon has less partial-positive character on a ketone because the additional alkyl group can donate electron density, which decreases electrophilicity

3-hydroxybutanal is an example of an _____________.

aldol Explanation: hydroxy = -OH; al = aldehyde

In gluconeogenesis, the reaction between glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP), fructose 1,6-bisphosphate, catalyzed by *fructose 1,6-bisphosphate aldolase*, is what type of reaction?

aldol reaction Explanation: an aldehyde and a ketone, which are both 3-carbon molecules, come together and form a 6-carbon molecule (a new carbon-carbon bond) and a new stereocenter! https://ibb.co/7SBqjgF ✷ Extra credit: What type of reaction is the REVERSE reaction that occurs in glycolysis? answer: retro-aldol

What type of reaction is catalyzed by citrate synthase in the citric acid cycle?

aldol reaction Explanation: instead of an aldehyde or ketone, a thioester acts as the nucleophilic partner. This reaction leads to the generation of a *new carbon-carbon bond* and a new stereocenter. https://ibb.co/9VF3XPj

How are dicarboxylic acids named (IUPAC)?

alkane + "dioic acid" ex: hexanedioic acid

How are alcohols commonly named?

alkyl group + alcohol ex: ethane ⟶ ethyl alcohol

What four factors determine nucleophilicity?

also presence of π bond can make a species nucleophilic and size (polarizability)

When do nucleophilicity and basicity follow the same trend? When do the two follow opposite trends?

always same ACROSS a row on the periodic table and same down a column if in polar *a*protic solvent. opposite DOWN a column on the periodic table if in polar protic *only*

carboxylic acid + ammonia

amide + water

lactam

amide in a ring (cyclic amide) N cannot be planar (less stable, less donation of electron density). Carbonyl carbon is therefore more electrophilic Ring strain both make it very reactive (*antibiotics*)

What functional groups act as bases?

amines, amides, alcohols (act as both acid and base), sulfides

Why are amides the least reactive carboxylic acid derivative?

amino group is electron-donating, which makes the carbonyl carbon slightly less electrophilic it's also quite stable on its own, because N is less electronegative than O, so it doesn't react easily (it's happy how it is). i.e. inductive effect is less because the dipole is not as strong amide ion is a very *poor* leaving group ex: β-lactams are extremely reactive due to ring strain (torsional strain (eclipsing interactions and angle strain.) The nitrogen is no longer planar, and so it can't donate electron density to the carbonyl carbon, which makes the carbonyl carbon more reactive

enal

an aldehyde with an alkene between the α and β carbons formed via aldol condensation of aldehydes

Michael addition (conjugate addition)

an enolate carbanion attacks an α,β-unsaturated carbonyl, creating a bond

semicarbazone

an imine derivative, so there's a C=N, but the group attached to the nitrogen is NHC(=O)NH₂. generally formed via reaction of *semicarbazide* (H₂N-NH-C(=O)NH₂) w/ aldehydes or ketones ￫ For ketones H₂N-NH-C(=O)NH₂ + RC(=O)R → R₂C=NNHC(=O)NH₂ ￫ For aldehydes H₂N-NH-C(=O)NH₂ + RCHO → RCH=NNHC(=O)NH₂

hydrazone

an imine derivative, so there's a C=N, but the group attached to the nitrogen is NH₂ or NHR". generally formed via reaction of *hydrazine* (H₂N-NH₂) w/ aldehydes or ketones

hydroxyquinones

any derivative of any quinone where any number *n* of hydrogens have been replaced by *n* hydroxyls have 2 carbonyls and a variable number of hydroxyl groups ✷ named by indicating the position of the OH group with a number & indicating the total number of OH groups by a prefix (di-, tri-, etc.) with the substituent name "hydroxy-" (ex: 1,2-dihydroxyanthraquinone) ✷ To convert phenols to hydroxyquinones, they must be converted to quinones to an oxidation step first and then another oxidation is required to further oxidize the quinones (total of 2 oxidation steps) ✷ resonance ✷ used to synthesize many medications, and have biological activity

What is the relationship between nucleophilicity and basicity?

basicity is a *subset* of nucleophilicity *base* = a type of nucleophile that specifically attacks hydrogen *nucleophile* = a specifies that attacks any electrophilic atom i.e. all bases are also nucleophiles, but not all nucleophiles are bases

Why are α-hydrogens so acidic?

because the *enol* form of carbonyl-containing carbanions is stabilized by resonance, so these acidic hydrogens are easily lost

Why are phenols more acidic than other alcohols?

because the aromatic ring can delocalize the charge of the conjugate base this is supported by the fact that the conjugate base of a phenol is a weaker base than that of other alcohols: *the weaker the conjugate base, the stronger the acid*

How does conjugation improve electrophilicity?

being able to delocalize positive charge once the nucleophile has attacked and bonded increases stability of the intermediate and makes these molecules more susceptible to nucleophilic attack

Why do our ears "pop" as airplanes take off?

being at high altitudes causes a decrease in external pressure. the sudden shift in external pressure as the plane elevates occurs before the middle ear can equilibrate. since air will always move from a high pressure environment to a low pressure environment, the air will quickly rush out the middle ear upon swallowing

The position directly adjacent to an aromatic group is called the ___________ position.

benzylic ❗️The reaction only works if there is a hydrogen attached to this carbon

The lower the pKaH (pKa of the conjugate acid), the __________ the leaving group.

better Explanation: Strong acid (low pKa) have inert conjugate bases (stable). The best leaving groups are *stable*.

1° alcohol + KMnO₄

carboxylic acid

Aldehyde + H₂O₂

carboxylic acid

Aldehyde + KMnO₄

carboxylic acid

1° alcohol + H₂CrO₄

carboxylic acid CrO₃ is a chromic acid equivalent, so does the same thing

The reaction of formic acid with sodium borohydride will yield what final product? An aldehyde A carboxylic acid A ketone An alcohol

carboxylic acid Explanation: NaBH₄ is not strong enough of a reducing agent to reduce a carboxylic acid

In a molecule with an alcohol and a carboxylic acid, a nucleophile is more likely to act on which functional group?

carboxylic acid Explanation: nucleophile-electrophile reactions tend to occur at the highest-priority functional group

In a molecule with an alcohol and a carboxylic acid, a reducing agent is more likely to act on which functional group?

carboxylic acid Explanation: redox reactions tend to occur at the highest-priority functional group

Formation of an Amide by Nucleophilic Acyl Substitution

carboxylic acid + ammonia or amine condensation reaction: requires the loss of a H from nucleophile (combines with the -OH from the carboxylic acid to form water), so only *primary* and *secondary* amines will react here

alkene + KMnO₄, heat, H3O⁺

carboxylic acid and ketone reaction is called "ozonolysis with oxidative workup"

What reaction conditions favor amide hydrolysis?

catalytic acid or base Explanation: acid protonates the carbonyl oxygen, which increases the electrophilicity of the carbonyl carbon (an amide on its own is the least reactive of all c.a. derivatives). This allows water to serve as the nucleophile, attacking the bond and hydrolyzing the molecule into a carboxylic acid and an amine salt strongly basic conditions greatly increase the concentration of OH- (nucleophile) which directly attacks the carbonyl carbon, and then an amide anion (::NH₂⁻) is lost, which then abstracts a proton from the newly attached base (-OH), to form ammonia/amine as a leaving group and a carboxylate anion

How are salts of carboxylic acids named?

cation, followed by the name of the acid with the ending "-oate" replacing -oic acid.

indicators for redox titrations

change color at a particular *voltage* (emf) e.g. cool example is safranin, which is not only voltage-dependent but also pH dependent (good for acid-base titration too)

protection of alcohols with sulfonyl groups

combine p-toluenesulfonyl chloride or methylsulfonyl chloride and an alcohol in presence of a base, converting it into an ester (-*ate*) ￫ mesyl and tosyl groups can serve as protecting groups when we don't want alcohols to react bc they will not react with many of the other reagents that would attack alcohols ￫ same reaction also converts alcohols into better leaving groups

If a lens has a negative power, that means it is ____________.

concave (diverging)

Charged (strong) nucleophiles/bases will favor ___________ pathways

concerted (SN2/E2) ✴︎ no carbocation

Carboxylic acid derivatives are formed by what major reaction?

condensation Explanation: loss of water from the -OH on the carboxylic acid reactant and a H from the incoming nucleophile

Esterification is a ___________ reaction.

condensation loss of H₂O

Reduction of a carboxylic acid may also be classified as a _____________ reaction.

condensation very similar to nucleophilic acyl substitution requires strong RA (LiAlH₄) aldehyde may be produced, but will often keep going to the 1° alcohol

How are enamines formed?

condensation reaction b/w *2°* amine + aldehyde/ketone with acid catalyst Mechanism is same as with imine formation, up until the iminium ion (step #4) ① nuc attack by the amine on the carbonyl carbon, π electrons in the double bond are kicked off to form an anion ② proton transfer: since O has a -1 formal charge and N has a +1 formal charge, N will give O its proton and keep the lone pair of electrons ✷ this leaves us with an intermediate called a *carbinolamine* ③ protonation of the -OH group, forming water as a good leaving group ④ nitrogen's lone pair move in and form the C=N, water is kicked off. N has a +1 formal charge again, and this molecule is called an *iminium ion*. ❗️However, this time, the iminium ion cannot be deprotonated to get rid of the formal charge (two alkyl groups, but no more hydrogens left!). So for step #5, we can't deprotonate in the same place, we have to pick another spot... ⑤ deprotonate at an adjacent carbon with available base. That carbon is left with a lone pair of electrons, which it will contribute to form a C=C double bond, and this kicks off the π electrons in the C=N double bond. Now, the N is attached to 3 alkyl groups and has a lone pair (as it prefers)

How are imines formed?

condensation reaction of ammonia or a 1° amine with an aldehyde/ketone using catalytic acid optimal pH of ~ 5 so that you can use acid to protonate (step #3) but also have available conjugate base for the deprotonation step (#5) Mechanism ① nuc attack by the amine on the carbonyl carbon, π electrons in the double bond are kicked off to form an anion ② proton transfer: since O has a -1 formal charge and N has a +1 formal charge, N will give O its proton and keep the lone pair of electrons ✷ this leaves us with an intermediate called a *carbinolamine* ③ protonation of the -OH group, forming water as a good leaving group ④ nitrogen's lone pair move in and form the C=N, water is kicked off. N has a +1 formal charge again, and this molecule is called an *iminium ion* ⑤ deprotonate iminium ion (N is happy to get rid of the proton) with available base to form *imine* https://ibb.co/q5mzFDQ

What chemical properties of ubiquinone allow it to carry out its biological functions?

conjugated rings, which stabilize the molecule when accepting electrons long alkyl chain (R)₁₀ allows for lipid solubility, which allows it to function *within* the phospholipid bilayer as an electron carrier thus it can be rapidly reduced and reversely, ubiquinol can be rapidly oxidized which is very useful for photosynthesis and the ETC

Besides protonation, how else can alcohols be converted to better leaving groups?

converting them into organosulfonates *advantages*: no rearrangements, no alterations to stereochemistry, and sulfonyl groups are stable under both basic and acidic conditions *reagents*: mesyl chloride or tosyl chloride (basically equivalent) Why is protonation with strong acid sometimes problematic?: ① On certain 2° alcohols the reaction proceeds through an SN1 pathway, which can lead to *rearrangements* ② We can end up scrambling any stereocenters that are present. For instance, if we start with one enantiomer in the reaction pictured, we end up with some racemization of the final product

Factor #4: *Steric Hindrance* Nucleophilicity ______________ the more bulkier the molecule is.

decreases affects the *rate* of attack

In polar aprotic solvent, nucleophilicity ___________ down the periodic table.

decreases parallels trend for basicity ex: DMF, DMSO, acetone

pKa _____________ down the periodic table.

decreases therefore acidity *increases*

Across the periodic table, pKa ____________ as electronegativity increases.

decreases therefore acidity *increases* ❗️however, once you go *down* a group, acidity increases due to size, so in this case, as pKa decreases, electronegativity decreases.

Basicity ____________ down a column on the periodic table.

decreases (increasing polarizability) ❗️nucleophilicity *increases* So F⁻ is a stronger *base* but a weaker *nucleophile than I⁻

Factor #2: *Electronegativity* Nucleophilicity ___________ as electronegativity increases.

decreases, just like with basicity Explanation: less likely to share electron density ❗️only ACROSS a row. Down a row, it depends on the solvent

What type of reaction(s) is the aldol condensation?

dehydration and nucleophilic addition Explanation: Water is lost Nucleophilic enolate attacks and binds the the carbonyl carbon

resonance of amides

delocalization of electrons between O and N atoms

crossed aldol reaction

different nucleophile and electrophile ex: aldehyde and a ketone, or two diff ketones, or two diff aldehydes

induction

distribution of charge across σ bonds pretty weak in general, and gets weaker as you move further away from the EW/ED atom conjugation and resonance are much more powerful!

Possible reactions for alkyl halides based on substitution of substrate

does not include alkyl *fluorides* because they make bad leaving groups

Ethers are electron-__________.

donating R groups donate electron density

An aldehyde or ketone acts as a _____________ in its keto form.

electrophile i.e. it gets attacked

Secondary amines tautomerize to form _____________. Which is preferred at equilibrium?

enamines analogous to *keto-enol tautomerism*: In both cases, a hydrogen atom switches its location between the heteroatom (oxygen or nitrogen) and the second carbon atom the imine is preferred (C=N is more stable), and enamines are quite reactive

Why are *cyclic* hemiacetals stable whereas linear ones are not?

entropy Explanation: forming a linear hemiacetal results in a decrease in entropy (2 molecules consumed and create 1 product), but that's not the case for cyclic hemiacetals (intramolecular reaction, so 1 reactant and 1 product)

kinetic enolate

favored by fast, irreversible reactions at lower temperatures with strong, sterically hindered bases (poor nucleophiles)

deprotection of alcohols/amines converted to sulfonates

final step when using organosulfonates as protecting groups on alcohols/amines, where the organosulfonate formed is converted back to an alcohol and sulfonyl chloride by treatment with *strong acid* or one-electron *reductive* conditions (e.g. MeOH) 📸 top shows deprotection of alcohol with reductive conditions, bottom shows deprotection of amine with strongly acidic conditions

Anhydrides, particularly cyclic anhydrides, will spontaneously form from dicarboxylic acids when exposed to what conditions?

heat but only 5 or 6-membered rings are easily made, since the increased stability of the newly formed ring is what actually drives the reaction forward

adipic acid

hexanedioic acid

Which is more acidic, cyclohexanol or hexanol?

hexanol Explanation: the ring structure of cyclohexanol is slightly electron-donating (C steals electrons from H and donates them into the ring and the oxygen can soak them up), which makes its hydroxyl hydrogen slightly less acidic and phenol is more acidic than all other alochols!

Strong bases have _______ pKa values.

high

Food molecules, such as sugars, lipids, and proteins, are _________-enthalpy, __________-entropy compounds.

high enthalpy low entropy ✴︎ think about how forming them *requires* energy, which is not spontaneous (ΔH > 0; ΔS < 0). Explanation: so their breakdown (cell respiration, etc.) is an exergonic reaction (ΔG < 0), resulting in waste products that are low enthalpy, high-entropy compounds (CO₂ GAS!)

The more electronegative the atom, the __________ the acidity.

higher Explanation: being attached to an EN atom causes it to hog the electrons, and the H+ is more easily donated (BL) ✷ if there's opposition with bond strength, i.e. no electronegative atom but weak bond strength, the bond strength takes precedence and the molecule is still considered acidic

Why are alcohols quite soluble?

hydrogen bonding with the polar solvent (water) *assuming the solvent is polar! they would not be soluble in a nonpolar solvent...

hydroquinone vs. phenol

hydroquinone (benzene-1,4-diol) is a type of phenol that has 2 hydroxyl groups bonded to a benzene ring in a para position

How are anhydrides named?

if symmetrical, replace "acid" at the end of the name of a parent carboxylic acid with "anhydride" both if cyclic or linear if cyclic, it will have a unique prefix (oxalic, succinic, etc.) because they are often derived from a single parent acid w/ 2 carboxylic acid functional groups when they are asymmetrical, all you have to do is name the two chains alphabetically, followed by "anhydride"

Why is the thermodynamic enolate produced if the reaction is reversible?

if the reaction is reversible, the kinetic product that initially formed can revert to the original reactant and react again to form the thermodynamic product

If there are no reaction conditions listed, what determines how the reaction will proceed?

if there are no reagents other than the reactants, then the properties of the functional groups on the reactants themselves will determine the outcome ex: acid-base; nucleophile-electrophile, etc.

When are aldol condensations most useful?

if we only use one type of aldehyde or ketone If there are multiple kinds, we cannot easily control which will acts as the N:⁻ and which as the E⁺ and a mixture of products will results

Aldehydes and ketones react with ammonia and nitrogen-based derivatives to form ___________.

imines C=N Mechanism: condensation and substitution: ammonia or 1° amine added to the carbonyl, excess protons in solution result in the protonation of the -OH and elimination of water. Nitrogen contributes its lone pair to form a double bond b/w the C and the N, result is an imine ✷ needs acidic conditions (optimal pH 4.5)

In polar protic solvents, nucleophilicity ____________ down the periodic table.

increases Explanation: more opportunity to hydrogen bond at the top of the table, which creates a "crowd" around the nucleophile. F⁻, being the conjugate base of a weak acid (HF) will want to form bonds with protons *in solution* and be less able to access the electrophile, whereas I⁻, being the conjugate base of a strong acid (HI), will be essentially inert as a base and will not want to bond with protons in solution and so it's available to react with an electrophile ex of protic solvents: carboxylic acids (O-H), water/alcohols (O-H), ammonia/amines (N-H)

The reactivity of Group I metals ___________ as you move down a group.

increases So Li < Na < K < Rb Explanation: reactivity increases as electropositivity increases. All group 1 metals have one electron in its outer shell. As we go down the group, the atom gets bigger. The bigger the atom, the further away the last electron. Therefore, the attraction between the nucleus and the last electron gets weaker. This makes it easier for the atom to give up the electron which increases its reactivity *electropositivity* = tendency of atoms to *lose* electrons and form positive ion. In a group electropositivity increases because ionization energy decreases when we move down in a group

iodimetric vs. iodometric titration

io*di*metric: direct, one step, reducing analyte io*do*metric: indirect, multistep, oxidizing analyte (often iodine radicals) https://ibb.co/g2YYQL

Nucleophile strength is a ____________ property.

kinetic based on relative *rates* of reaction with an electrophile Explanation: Unlike bases, many reactions of nucleophiles are *not* reversible. A bond forms, a bond breaks, and that's the end of the reaction. The problem with this from a measurement standpoint is that we often can't determine an equilibrium constant for a reaction. And if we can't do that, then we can't develop a reactivity scale based on equilibria. If we can't measure equilibria, then what do we do? Well, we use the next best measurement available: to measure reaction rates. Factors: steric hindrance, solvent, etc.

PCC

mild oxidizing agent (mild version of chromic acid) will only go as far as to oxidize 1° alcohols ⟶ aldehydes or 2° alcohols ⟶ ketones (happens regardless of OA strength) but will *not* oxidize aldehydes to carboxylic acids

What makes a good leaving group?

molecules that are stable when they leave ￫ weaker bases (low pKa) ￫ (-I effect): electron withdrawing substituents since they stabilize resonance form ￫ polarizability ✴︎ bad leaving groups can be modified to become better leaving groups ex: OH⁻ is a terrible leaving group, but by protonating it to H₂O, you have created an excellent leaving group

Which is more acidic, a monocarboxylic acid or a dicarboxylic acid that has been deprotonated once?

monocarboxylic acid Explanation: carboxylate anion is electron-donating and destabilizes the product of the second deprotonation step (plus repulsion of 2 - charges on same molecule!!!) so acidity is decreased

Sp² and sp centers are ___________ electronegative than sp³.

more Explanation: they hold on tighter to electrons because they have more s character (closer to positively-charged nucleus) That's why hybridization state affects carbanions differently than carbocations/radicals

The more oxidized the functional group, the ___________ reactive it is.

more ✴︎ this applies to both nucleophile-electrophile reactions and redox reactions!

3° alcohol + PCC

no reaction!

Acetone is a (nucleophile/electrophile).

nucleophile donor atom: O in the reaction pictured, it's clear that the other species is more electrophilic. however, if the other species had been something like an amine, the carbon might act as an electrophile due to the polarized π bond.

Which is a stronger acid, oxalic acid or succinic acid?

oxalic Explanation: a dicarboxylic acid will be more acidic the closer the two -COOH groups are. As proof, oxalic acid has a lower pKa

Decarboxylation of a carboxylic acid may also be classified as a _____________ reaction.

oxidation Explanation: increasing bonds to O ✴︎ also note, since CO₂ is gaseous, it bubbles off and drives the reaction forward

Tollen's reagent

oxidizes aldehydes to carboxylic acids tests to distinguish b/w aldehyde and ketone: it exploits the fact that aldehydes are readily oxidized whereas ketones are not

HNO₃ (nitric acid) is a ____________ agent.

oxidizing

H₂SO₄ is a _____________ agent.

oxidizing

Compounds containing strongly electronegative elements (such as halogens) are likely ____________ agents.

oxidizing Ex: F₂, O₂, Cl₂, Br₂, I₂, NaClO

enol form of enolate

oxyanion

What reagents can be used to lyse an alkene into an aldehyde and a ketone?

ozonolysis w/ *reductive* workup: O₃ followed by reducing agent (such as Zn or CH₃SCH₃)

Lewis acids have vacant _________ into which they can accept an electron pair, or are positively polarized (δ+)/positively charged (+) atoms.

p-orbitals (signified by 𝟴) ✴︎ rehybridizes to a σ bond upon binding ex: BF₃ (𝟴) other types are... ￫ ones bonded to a good leaving group and have a δ+ center ￫ or have a polarized π bond & are susceptible to nuc attack (the all-famous carbonyl!)

chemoselectivity

preferential reaction of one functional group in the presence of other functional groups

Esterification occurs most rapidly with __________ alcohols.

primary Explanation: better nucleophiles (less bulky)

Rank the alcohols from most acidic to least acidic? Why?

primary > secondary > tertiary phenols & thiols are the most acidic of all cyclic alcohols are less acidic Explanation: the strength of alcohols as acids depends on the corresponding strength of its conjugate base, the alkoxide ion. A more stabilized alkoxide is a weaker conjugate base so the alcohol will be more acidic. Electronically, when there are more electron-donating alkyl groups attached to the hydroxyl carbon, the electron density on the O atom increases and the alkoxide is less stable. This is also why cyclic alcohols are less acidic, bc the ring structure is electron-donating For steric factors, more alkyl groups would mean that the alkoxide ion is more bulky and it would be harder for the solvent to stabilize the alkoxide thru *solvation*

What does a neutral nucleophile indicate?

probably SN1 or E1 mechanism

malonic acid

propanedioic acid

How can an alkene be formed from a carboxylic acid?

reduction to an alcohol, then elimination reaction on the alcohol

How are lactones named?

replace "-oic acid" with "-lactone"

How are lactams named?

replacing "-oic acid) with "-lactam" - or - by indicated the specific carbon that is bonded to nitrogen during cyclization of the compound (e.g. β, ɣ, δ)

The catalytic production of dihydroxyacetone (DHAP) and glyceraldehyde 3-phosphate from fructose 1,6-bisphosphate is what type of reaction?

retro-aldol reaction Explanation: discern that we are creating a ketone and an aldehyde from a single molecule. The hallmark of a reverse aldol condensation is the breakage of a carbon-carbon bond and the formation of 2 ketones, 2 aldehydes, or 1 of each https://ibb.co/7V7GLVh

amide hydrolysis

reverse condensation (hydrolysis) an amide is cleaved to produce a carboxylic acid and an amine or ammonia nucleophile: water (acid) or OH- (base) *requires strong acid or base* the central reaction in the digestion of proteins and the breakdown of proteins within cells ￫ acid: protonates carbonyl O, making carbonyl carbon more susceptible to attack by water ￫ base: similar, except no protonation and nucleophile is :::OH-, so now the product is a carboxylate anion.

The more basic the nucleophile, the more reactive it is when comparing atoms in the same __________ on the periodic table.

row - it parallels basicity in this case i.e. nucleophilicity *decreases* across a row because electronegativity increases ❗️however, this does not suffice when proceeding *down a column* on the periodic table. In this case, the trend is *opposite* of basicity: nucleophilicity *increases* down a column In that case, you have to look at many factors: charge, electronegativity, size (polarizability), steric hindrance, and solvent effects

aldol dimerization

same nucleophile and electrophile i.e. both the same aldehyde or the same ketone

What factors stabilize free radicals?

same that stabilize carbocations! ① electron-donating groups (+I effect) more highly substituted = most stable ② conjugation (and therefore resonance) ￫ adjacent C-C double bonds ￫ or adjacent lone pairs

dismutation reaction

same thing as disproportionation reaction element undergoes both oxidation and reduction in producing its products Another biological example (bottom reaction📸) is *superoxide dismutase*, which quenches free radicals and produces peroxide and oxygen. ✷on the radical is 1 negative charge divided over 2 oxygen atoms

Ketone + LiAlH₄ (in ether) or NaBH₄ (in ethanol)

secondary alcohol ✴︎ LiAlH₄ reacts violently with water and alcohols, so it must be carried out in ether

Why are silyl ethers used over typical ethers to protect alcohols?

silyl ethers (O-Si) and regular ethers (O-C) share the property of being inert to other reaction conditions but typical ethers are super hard to cleave (remove) at the end of the desired reaction. Instead, the O-Si bond is easily cleaved because the Si-F bond formed by reaction with TBAF is even stronger than the O-Si, so it will be cleaved without affecting the rest of the molecule (versus removal of a typical ether which requires very strong acid and heat)

LDA

strong base, poor nucleophile (bulky) used to form *enolates*: ex: aldol condensation ￫ it converts an aldehyde or ketone with α-hydrogens into a better nucleophilic carbanion and enolate ion (both are resonance structures of the same product) ex #2: used to form Hoffman product in E2 reaction ✴︎using a strong base like this will form the *kinetic* enolate, since LDA will remove the proton selectively from the least substituted carbon and it works best in *cold temperatures* (to avoid forming the thermodynamic product)

Alcohol to tert-butyl ether

temporary reversible reduction of a molecule to "protect" the alcohol functional group so that another functional group can react, and then we remove the protective group selectively.

Why are alkynes so acidic?

the sp-hybridized orbitals of alkynes bear 50% s-character, and as the 2s orbital is closer to the nucleus than the 2p orbitals, the resulting lone pair of the conjugate base "feels" more of the positive charge from the nucleus than would a lone pair in a sp³ hybridized orbital (25% s-character). It's similar to why a lone pair is more stable on a more electronegative atom like fluorine than on a less electronegative atom like carbon.

Base strength is a _____________ property.

thermodynamic related to the *equilibrium position* of a reaction Explanation: We can measure acidity (and, by extension, basicity) through *pKa*, which reflects the position of equilibrium between an acid and its conjugate base, i.e. most acid-base reactions are *reversible*. Because we can measure the equilibrium constants for reversible acid-base reactions, we can get a fairly good idea of the relative strengths of acids and bases - the pKa table is our friend. It's a great "reactivity ladder" to hang our hats on.

Which is a better nucleophile, a thiol or alcohol?

thiol Explanation: sulfur is less electronegative than oxygen, so it holds onto its electrons less tightly and gives them up more readily as a result in general, (as long as solvent is polar *protic*) nucleophilicity *increases* going down the periodic table with the opposite being true for basicity

What is the geometry of the nitrogen in a β-lactam

trigonal pyramidal - no longer planar when ideal is sp² (trigonal *planar*) ✷ this reduces resonance, because the orbitals no longer overlap well enough. This makes hydrolysis more likely (i.e. ↑ reactive) because the carbonyl carbon cannot receive as much electron density from the nitrogen, so it's MORE reactive!

para

two groups on opposite sides of the ring

meta

two groups separated by 1 carbon

Ester + LiAlH₄ (in ether) followed by H₂O

two primary alcohols

The orbital that actually participates in the π bond is ____________.

unhybridized Explanation: In a carbon with a double bond, 1 s-orbital combines with 2 p-orbitals to form 3 sp² hybridized orbitals. Those hybridized orbitals form the sigma bonds (one of which is part of the double bond.) The third p-orbital of the carbon atom remains unhybridized and *participates in the π bond* ex: ethene Both carbons have 3 sp² orbitals. 1 from each forms the σ bond of the double bond. The other 2 sp² hybridized orbitals (on each) form σ bonds with the Hs' unhybridized s-orbitals. Finally, the unhybridized p-orbitals (1 from each carbon) form 1 π bond (top and bottom)

Are double displacement (metathesis) reactions redox reactions?

usually not ✴︎*single* replacement reactions usually are though!

alkene + dilute KMnO₄, NaOH, cold

vicinal diol (syn addition - same side) ❗️only works as long as it's kept cold and it has to be an alkene (alkyne gives no reaction)

molecular orbitals

when atomic orbitals overlap can be: ① *bonding* (σ) - same signs added head-to-head or tail-to-tail ② *antibonding* (σ*) - opposite signs added head-to-head or tail-to-tail ❗️don't get confused with opposite charges attract. These are orientations, not charges

methylsulfonyl chloride (MsCl)

when combined with alcohol in the presence of base, it is used to prepare *mesylates*, which are excellent leaving groups this converts the alcohol into a more suitable substrate for substitution reactions this reaction is often preferred compared to converting alcohols to alkyl halides because there can be rearrangements with that reaction. With MsCl (or TsCl), the stereochemistry is also conserved!

Is there any way that a ketone can become further oxidized?

yes, but rare (see pic) mCPBA converts ketones to esters

Rules for drawing resonance *hybrids*

① Draw the Lewis Structure & Resonance for the molecule (using solid lines for bonds). ② Where there *may* be a double or triple bond, draw a dotted line (-----) for a bond. ③ Draw only the lone pairs found in all resonance structures, do not include the lone pairs that are not on all of the resonance structures. https://ibb.co/dM2Kjf

What are the 6 steps for solving organic chemistry reactions?

① Know your nomenclature ② Identify functional groups - look at how they normally would react, how oxidized, etc. ③ Identify other reagents - could be solvent, catalyst, acid, base, indicative of a critical step (e.g. protonation), etc. ④ Identify the *most* reactive functional group(s) - most oxidized; also look for protecting groups ⑤ Identify the 1st step of the reaction ￫ if acid/base, first will likely be protonation or deprotonation ￫ if nucleophile, first step is usually nuc attack and bond formation ￫ if redox, most oxidized functional group will get ox/red then consider the subsequent steps ⑥ Consider stereospecificity/stereoselectivity (if applicable)

What makes one resonance structure preferable over another?

① Lack formal charge. If there is formal charge on all of them, the most stable will have the negative formal charge on the most electronegative atom, and the positive formal charge on the least EN atom ② Full octet on highly electronegative atoms ③ Inductive effect ④ Aromaticity ⑤ The greater the number of covalent bonds, the greater the stability since more atoms will have complete octets ⑥ The structure with the least separation of formal charge is more stable ✴︎Resonance forms that are equivalent have no difference in stability and contribute equally (eg. benzene)

Write out the steps of peptide bond formation

① Nucleophilic attack by the amino group of one AA on the electrophilic carbonyl carbon of another AA ② Carbonyl has to open up (can't have 5 bonds). Hydroxyl group on the carboxylic acid is a poor leaving group, so it rearranges protons to form water that gets kicked off What makes them react in the first place (no reagent, heat, manipulation, etc.)? The amino group closer to the carbonyl will react because the resulting product will be stabilized by resonance!

DELOCALIZATION AND RESONANCE STRUCTURES RULES

① Resonance structures should have the same number of electrons: do not add or subtract any electrons. (check the number of electrons by simply counting them). ② All resonance structures must follow the rules of writing Lewis Structures. ③ The hybridization of the structure must stay the same. ④ The skeleton of the structure can not be changed (only the electrons move). ⑤ Resonance structures must also have the same amount of lone pairs. ✴︎ formal charge on each atom definitely *can* change though, and this is what makes one more stable than others, but IT MUST ADD UP TO THE OVERALL CHARGE ON THE MOLECULE (*conservation of charge*)

What conditions favor nucleophilic acyl substitution?

① basic solution - makes nucleophile more nucleophilic by deprotonating it ② acidic solution - makes electrophile more electrophilic by protonating the oxygen, which makes it positive and steals more electron density from the electrophilic center ③ good leaving groups - weak bases

What are the two reactive centers of carbonyl-containing compounds?

① carbonyl-carbon (electrophilic) ② α-hydrogens (acidic)

Rules for aromaticity

① cyclic ② every atom in the ring must be conjugated. ③ molecule must have [4n+2] π electrons (on another flashcard what this means) ④ 📸 molecule must be flat (usually true if conditions 1-3 are met, but there are rare exceptions) as long as the π system are in the same, it is still aromatic even if there are some other weird bridges, etc. (see picture)

How is the tropylium ion aromatic? (flip to see)

① cyclic ✓ ② conjuagted π system ✓ Remember, this condition means that there must be an *available* p orbital, and in this case, the carbocation has an empty p orbital ③ [4n+2] π electrons ✓ It has 6 π electrons (count), which fulfills Hückel's rule ④ flat ✓ planar

Carbocations are stabilized by...

① electron-*donating* groups ￫ to donate e⁻ density to the positive carbon (*positive* inductive effect) ex: alkyl groups (more highly substituted) ❗️as long as the groups are electron-donating!!! ② *resonance* - delocalizes positive charge ex: *conjugation* - overlapping p orbitals (A.) adjacent carbon-carbon π bonds (B.) adjacent lone pairs ③ hybridization: less s character = more stable (opposite of carbanions) https://ibb.co/j9CBS0

How are carbanions stabilized?

① electron-*withdrawing* groups - to delocalize negative charge on the carbon (*negative* inductive effect) ✴︎ the LEAST substituted will be the most stable (least amount of electron-donating groups) ② conjugation & resonance - again delocalizes ⊖ charge if atoms all share it, versus just on one. ③ hybridization - more s character = more stable (e⁻ closer to the nucleus) ④ bonding to a element with a *d-orbital* - moving down the table, the more bonds to elements w/ d-orbitals = the more stable 📸 not shown, but e.g. is ⁻:C-S bond > ⁻:C-O bond. ❗️lone pairs destabilize carbanions because they donate e⁻ density

Types of enolates

① kinetic: less substituted, less stable, produced with strong base, forms more quickly has 2 tautomers: carbanion and oxyanion ② thermodynamic: more substituted, more stable, produced with weaker base, forms more slowly has 2 tautomers of its own: carbanion and oxyanion 📸 arrow represents equilibrium, NOT resonance (he used the wrong kind of arrow)

Negative charges are stabilized by...

① low charge densities ② high electronegativity ③ polarizability ④ resonance and conjugation ⑤ electron-*withdrawing* groups ⑥ greater hybridization (most s character) ⑦ aromaticity (again, conjugation) https://ibb.co/eLmGuf

What reagents can be used to lyse an alkyne into carboxylic acids?

① ozonolysis w/ *oxidative* workup: O₃ followed by oxidizing agent (such as H₂O₂) ② KMnO₄, heat, H3O⁺

What reagents can be used to lyse an alkene into a carboxylic acid and a ketone?

① ozonolysis w/ *oxidative* workup: O₃ followed by oxidizing agent (such as H₂O₂) ② hot acidic potassium permanganate (KMnO₄, heat, H₃O⁺)

ammonia + anhydride

⟶ carboxylic acid + amide it's both a substitution reaction and a *cleavage* reaction (anhydride split into 2) nucleophile: ammonia electrophile: 1 of the carbonyl carbons leaving group: 1 carboxylic acid ✷ and note that the carboxylic acid product may very well react with the leftover ammonia since they are still in the same environment, forming ammonia carboxylate (NH₄⁺COO⁻)

anhydride + alcohol

⟶ ester + carboxylic acid nucleophilic substitution & cleavage reaction nucleophile: alcohol electrophile: 1 of the carbonyl carbons leaving group: carboxylic acid use *pyridine* (a base) as solvent Mechanism: https://chem.libretexts.org/Textbook_Maps/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Anhydrides/Reactivity_of_Anhydrides/Acid_Anhydrides_react_with_alcohols_to_form_esters

If trying to determine whether a reaction is SN1 or E1, how can the type of acid help you decide?

￫ SN2: Use a strong acid with a conjugate base that's a strong nucleophile ￫ E1: Use a strong acid with a conjugate base that is a poor nucleophile so it won't attack the intermediate and you won't get substitution!

What effect does hybridization have on intermediate stability?

￫ for carbocations, LESS s character = more stable explanation: positive charge closer to nucleus ⟶ repulsion ❗️opposite for carbanions: ￫ the MORE s character = more stable explanation: negative charge closer to nucleus ⟶ attraction