question

Carboxylic acid + LiAlH4

answer

Ether (diethyl ether of THF) and H3O+. Reduces carboxyl group to primary alcohol.

question

NaBH4

answer

Selectively reduces ketone to primary alcohol. Leaves carboxylic acid alone. MeOH. No mechanism.

question

Pt, H2

answer

Selectively reduces ketone to primary alcohol. Leaves carboxylic acid alone. No mechanism.

question

Fischer esterification

answer

Carboxylic acid + alcohol with strong acid (usually H2SO4, ArSO3H, or gaseous HCl) ---> ester. R-COOH + HO-R' --> R-COO-R'

question

Reactions with diazoalkanes

answer

With diazomethane have mild conditions and very high yield. Usually under ether. Gives ester. RCOOH + CH2N2 --->(ether) R-COO-CH3. CH3 replaces H on hydroxyl if using diazomethane.

question

Decarboxylation

answer

Regular carboxylic acids need heat (400C). Carboxylic acids with beta ketone need mild heat (150C)

question

Carboxylic acid derivative reactivity

answer

Acid chlorides > acidic anhydrides > esters > amides. Reactivity from leaving group ability (less basic = better leaving group) and electrophilicity of carbonyl carbon (resonance structures stabilize).

question

Acid halide naming

answer

-ic acid --> -yl halide

question

Acid anhydride naming

answer

acid --> anhydride. COC with two balls.

question

Ester naming

answer

-ic acid --> -ate. Cyclic esters --> lactones

question

Amide naming

answer

-ic acid --> -amide

question

Nitrile naming

answer

-oic acid --> -nitrile

question

Leaving ability of carboxylic acid derivatives

answer

X- (from acid halide) > RCOO- (from anhydride) > RO- (from ester) > R2N- (from amide)

question

Basicity of carboxylic acid derivatives

answer

X- < RCOO- < RO- < R2N-

question

Hydrolysis of acid chloride

answer

Just need water. Most reactive.

question

Hydrolysis of anhydrides

answer

Just need water. Sometimes need acid/base catalyst if too big, because less reactive than acid chlorides.

question

Hydrolysis of esters

answer

Reverse of Fischer esterification. Need acid as catalyst.

question

Hydrolysis

answer

Makes carboxylic acids!

question

Hydrolysis of esters with base

answer

Saponification. Need hot aqueous base, usually NaOH or KOH.

question

All acid derivatives with base

answer

React like in saponification.

question

Hydrolysis of amides

answer

Either acid or base, different mechanisms for both. Both require heating.

question

Hydrolysis of nitriles

answer

In aqueous acid, like H2SO4. Get amide, then do hydrolysis of amide to get carboxylic acid. (Acid + heat)

question

Acid halides + alcohols

answer

Give ester! Very reactive, don't need catalyst. Typically add base, either pyridine or triethylamine.

question

Acid anhydrides + alcohols

answer

Gives one mole ester and one mole carboxylic acid!

question

Esters + alcohols

answer

Acid-catalyzed. Called transesterification. If have methanol and kept slightly above methanol BP, methanol distills from rxn mixture shifting the equilibrium to favor product ester. If have large excess of methanol (byproduct), shifts in favor of reactant ester.

question

Amides + alcohols

answer

Does not make ester, not reactive enough to react with alcohols.

question

Acid halides + amines

answer

Gives amides. Need 2 equivalents of amine. Only react with primary and secondary amines and ammonia.

question

Acid anhydrides + amines

answer

React with primary and secondary amines and ammonia to make amides. Two moles required.

question

Esters + amines

answer

React with primary and secondary amines and ammonia to makes amides. One mole required. Less reactive, often requires heating or high concentrations of amine (or both).

question

Amides + amines

answer

Do not react with ammonia or primary/secondary amines.

question

Esters + Grignard

answer

Ester of formic acid gives secondary alcohol. Ester of any other acid gives tertiary alcohol. 2 moles of Grignard for either. Need acid after adding Grignard (HCl, H2O). Can't use to just create ketone; intermediate ketone more reactive than ester itself.

question

Esters + organlithium

answer

2 moles of R'Li, then H2O, HCl. Gives secondary and tertiary alcohols like with Grignard. Often gives higher yields.

question

Acid chlorides + lithium diorganocuprates

answer

Gives unsymmetrical ketone. In ether (diethyl or THF) at -78C. Only reacts with acid chlorides; if have some other functional group and acid chloride, only acid chloride will turn to ketone.

question

Reduction of esters to alcohol

answer

With LiAlH4 gives two alcohols, the only from the acyl group usually primary (LiAlH4, ether then HCl, H2O). Usually not with NaBH4 because so slow, so possible to reduce aldehyde/ketone but not ester with NaBH4 (and ethanol/methanol).

question

Reduction of esters to aldehyde

answer

Use DIBALH in toluene or hexane at -78C, then warming to room temp and adding aqueous acid. If carried out at room temp, reduces to primary alcohol so need to control temp.

question

Reduction of amides

answer

With LiAlH4 get primary, secondary or tertiary amines depending on the substitution of the amide. So therefore lose =O.

question

Reduction of nitriles

answer

LiAlH4 then H2O. Reduces to a primary amino group only.

question

NaBH4 as reduction agent

answer

Doesn't react to reduce most of these.

question

Aldol reaction

answer

Nucleophilic addition of enolate to carbonyl group of another molecule. Gives beta-hydroxyaldehyde or beta-hydroxyketone. Base catalysis more common. Products racemic unless one of reactants is chiral and only in one enatiomer.

question

Good aldehydes for crossed aldol

answer

Formaldehyde, benzaldehyde, furfural, 2,2-dimethylpropanal. No a-hydrogens.

question

Retrosynthetic analysis help

answer

If have beta-hydroxy carbonyl or alpha,beta-unsaturated carbonyl, an aldol reaction probably occurred.

question

Claisen condensation

answer

Product a beta-ketoester. Requires nonaqueous base like sodium ethoxide in ethanol and sodium methoxide in methanol. Need an ester with two alpha-hydrogens.

question

Dieckmann condensation

answer

Intramolecular Claisen. In presence of one equivalent sodium ethoxide. Same mechanism as Claisen, but intramolecular.

question

Crossed Claisen

answer

Use an ester without alpha-hydrogens in excess. Some of these are ethyl formate, diethyl carbonate, diethyl oxalate and ethyl benzoate.

question

Retrosynthesis analysis help

answer

If have beta-ketoester, probably had a Claisen. If beta-ketoester in ring, probably had a Dieckmann.

question

Alkylation of enamines

answer

Need a secondary amine (commonly pyrrolidine or morpholine) with an aldehyde or ketone. Here the enamine reacts with methyl and primary alkyl halides, alpha-haloketones and alpha-haloesters to give a double bond. Need HCl/H2O workup at end. Retro: makes carbonyl with alpha-carbon having group on it that could come from SN2 (methyl, primary, maybe secondary but not tertiary). This can be gotten from a carbonyl reactant with alpha-hydrogen + secondary amine (usually pyrrolidine) + new group R bonded to Lv.

question

Acylation of enamines

answer

Get new carbonyl off of beta-carbon. Can get from carbonyl reactant with an alpha-hydrogen, a secondary amine (usually pyrrolidine), and the acid chloride that gives the correct R group.

question

Alkane C-H peaks

answer

0.8-1.5

question

Next to electronegative atom

answer

2.4-4.5

question

Alkene

answer

4.5-6.5

question

Aromatic

answer

6.5-8.5

question

Aldehyde

answer

9.5-10.5

question

Carboxylic acid

answer

10.5-13

question

Alcohol (OH), Amine (NH)

answer

1-5

question

Esters

answer

3.7-4 if closer to double bonded; 2-2.2 if closer to single bonded

question

Ethers

answer

3.3-4

question

Carbonyl

answer

2-2.7

question

Acetoacetic ester synthesis

answer

Makes monosubstituted or disubstituted acetones. Retrosynthesis: makes carbonyl compound with alpha carbon possessing one or two groups. Good way to make complex ketones. Derive complex ketone from beta-ketoester and alklyating agent (R-Lv). Pg. 766

question

Acidity of carboxylic acids

answer

Most unsubstituted aliphatic and aromatic carboxylic acids within 4-5 pKa.

question

Carboxylic acids + bases

answer

Form water-soluble salts with metal hydrixides, carbonates, bicarbonates, and with ammonia and aliphatic/aromatic amines. Under H2O. R-COOH + NaOH --> R-COO-Na+ + H2O; R-COOH + NH3 --> R-COO-NH4+

question

Carbonation of Grignard Reagent

answer

Grignard + CO2 then HCl/H2O gives carboxylic acid + Mg2+.

question

Preparation of Acetic Acid by Carbonylation of Methanol

answer

CO + 2H2 --->(catalyst) CH3OH --->(CO,rhodiumIII,Hi,H2O) ---> CH3COOH

question

Conversion to Acid Halides

answer

Under ether. R-COOH + SOCl2 --->(ether) R-COCl + SO2 + HCl. Hydroxyl replaced by Cl.

question

Decarboxylation of beta-ketoacids

answer

Upon heating (warm). Gives CO2 and enol of a ketone (which tautomerizes to give ketone).

question

Decarboxylation of beta-dicarboxylic acids

answer

Same as above, but need hotter heat.

question

Acidity of Imides

answer

pKa 8-10. Dissolve in aqueous NaOH by forming water-soluble sodium salts. RNH +NaOH --> RN-Na+ + H2O

question

Acidity of Sulfonamides

answer

pKa 9-10. Dissolve in aqueous NaOH by making water-soluble salts.

question

Hydrolysis of Acid Chloride

answer

Low-MW acid chlorides react vigorously with water. Higher MW react less rapidly. Replaces Cl with OH, making carboxylic acid. RCOCl + H2O ---> CH3COOH

question

Hydrolysis of Acid Anhydride

answer

React readily with H2O. Cleaves at O in between each sad, adding -OH groups where O was giving two carboxylic acids. CH3COOCOCH3 + H2O ---> CH3COOH + HOOCCH3

question

Hydrolysis of Ester

answer

Only hydrolyzed in presence of acid or base. Acid is catalyst, base is required in equimolar amount. In acid, protonate acyl oxgen, attack by H2O to make tetra addition intermediate, transfer of proton to oxygen of -OR, and departure of leaving alcohol. In base, direct addition of OH- to give tetra intermediate, collapse to give carboxylic acid and alkoxide, which transfers proton from carboxylic acid to alkoxide to give carboxylate ion & alcohol as final prod. CH3COOR + NaOH --->(H2O) CH3COO-Na+ + HO-R

question

Hydrolysis of Amide

answer

Either acid or base required in amount equivalent to amide amount. Acid, just like ester but departing amine reacts with proton to give ammonium ion prod. Base have initial attack by HO-, deprotonation to give dianionic tetra intermediate, loss of amide ion, which protonates to give amine product. Pg. 724

question

Hydrolysis of Nitrile

answer

Acid or base required in amount equivalent to that of nitrile. Acid, initial protonation of nitril N followed by attack of H2O to give imidic acid that tautomerizes to gives amide. Rest the same as amide. In base, initial attack of HO- on nitrile C to form anion of imidic acid, which gets proton to give imidic ion intermediate that tuatomerizes to amide. Rest the same for amide. Pg. 725

question

Acid Chloride + Alcohol

answer

Gives an ester plus HCl. CH3COCl + HOR --> CH3COOR

question

Acid Anhydride + Alcohol

answer

Gives one mole ester (w/ tail of alcohol) and one mole carboxylic acid. CH3COOCOCH3 + HOEt ---> CH3COOEt + CH3COOH

question

Ester with Alcohol Transesterification

answer

Needs acid catalyst and excess of alcohol. CH3COOCH3 + HOR --->(HCl) CH3COOR + CH3OH

question

Acid Chloride + Ammonia or Amine

answer

Two moles of ammonia or amine, one to form amide and one to neutralize HCl. Nucleophilic addition of ammonia or amine to carbonyl, proton transfer to give tetra addition intermediate which directly eliminates chloride and loses proton. RCOCl + 2NH3 ---> RCONH2 + NH4Cl. Replace Cl with NH2.

question

Acid Anhydride + Ammonia or Amine

answer

Need two moles of ammonia or amine, one to form amide and one to neutralize carboxylic acid byproduct. Same as acid chloride. CH3COOCOCH3 + 2NH3 ---> CH3CONH2 + CH3COO-NH4+

question

Ester + Ammonia or Amine

answer

Adding ammonia, primary or secondary amine gives amide. Nucleophilic addition of ammonia/amine to carbonyl, proton transfer to give tetra addition intermediate, directly eliminates alkoxide and lose proton to alkoxide to get prod. RCOOEt + NH3 --> RCONH2 + EtOH. Replaces OEt (or OR) group with NH2.

question

Acid Chloride with Carboxylic Acid Salt

answer

Gives mixed anhydride. CH3COCl + Na_-OCOR ---> CH3COOCOR

question

Ester with Grignard Reagent

answer

Formic ester with Grignard then hydrolysis gives secondary alcohol. Any other ester with Grignard then hydrolysis gives tertiary alcohol. Nucleophilic attack of Grignard on carbonyl to give tetra addition, collapses w/ departure of OH- to give ketone intermediate (aldehyde if formic ester), which reacts with 2nd mole of Grignard! R-COOMe ---->(2EtMgBr, H2O, HCl) R-COHEtEt

question

Acid Chloride with Lithium Diorganocuprate

answer

React readily at -78C under ether, then H2O/HCl to give ketones. Lose Cl.

question

Reduction of Ester

answer

By LiAlH4 gives two alcohols. Initial nucleophilic attack by hydride ion onto carbonyl to give tetra addition intermediate, which collapses through loss of alkoxide to give aldehyde, which reacts with second hydride to give alcohol. R-OOCH3 --->(LiAlH4, ether; H2O, HCl) R-COH + CH3OH By DIBALH at low temp gives aldehyde and alcohol, under toluene. R-COOCH3 ---> R-COH + CH3OH

question

Reduction of Amide

answer

By LiAlH4 gives amine. Initial nucleophilic reaction of hydride equiv. with carbonyl to give tetra addition intermediate, followed by acid-base rxn to give O-Al bond that rearranges electron pairs to eject Al-O species to give electrophilic iminium ion, which reacts with equiv. of hydride to give amine. Lose ketone.

question

Reduction of Nitrile

answer

By LiAlH4 gives primary amino group. R-CN --->(LiAlH4, ether; H2O) R-CH2NH2

question

Aldol

answer

Nucleophilic addition of enolate anion of one aldehyde/ketone to carbonyl of another aldehyde/ketone. Product is beta-hydroxyaldehyde of beta-hydroxyketone. Base catalyzed or acid catalyzed. Most times new chiral centers created giving racemic products, unless starting product is chiral and present in one enantiomer. Have alcohol where on carbonyl was, and ketone/aldehyde beta to that.

question

Dehydration of Product of Aldol

answer

Under acidic or basic conditions. Gives alpha,beta-unsaturated aldehyde or ketone. Turns the -OH above into double bond.

question

Claisen Condensation

answer

Product is beta-ketoester. Nucleophilic acyl substituion, where attacking nucleophile is enolate anion of an ester. Rxn of one ester molecule with base to get enolate anion, which reacts as nucleophile with another molecule of ester to give tetra addition, where RO- group is lost to give beta-ketoester, deprotonated at alpha position by RO-. Pg. 788

question

Dieckmann Condensation

answer

Intramolecular Claisen condensation.

question

Alkylation of Enamine followed by Hydrolysis

answer

Reactive with methyl and primary alkyl halides, alpha-haloketones, and alpha-haloesters. Replace -NR with =O, add R of RX alpha to where =O is.

question

Acylation of Enamine followed by Hydrolysis

answer

First add acyl group alpha to N, then replace N with =O.

question

Acetoacetic Ester Synthesis

answer

Synthesis of monosubstituted and disbustituted acetones. 1. EtO-Na+ 2. CH2=CHCH2Br 3. NaOH, H2O 4. HCl, H2O 5. Heat

question

Malonic Ester Synthesis

answer

Good for synthesizing monosubstituted and disubstituted acetic acids. 1. EtO-Na+ 2. CH2=CHCH2Br 3. NaOH, H2O 4. HCl, H2O 5. heat

question

Michael Reaction

answer

Addition of weakly basic nucleophile to C=C made electrophilic by conjugationg with carbonyl group of aldehyde, ketone or ester or with nitro/cyano group. Initial formation of enolate anion in base, attack of enolate nucleophile at beta-Carbon of Michael acceptor to make new resonance-stabilized enolate anion intermediate protonated on oxygen to create an enol and regenerate base, then tuatomerization to keto form. Base is catalytic. Pg. 789

question

Robinson Annulation

answer

Michael reaction followed by intramolecular aldol reaction and dehydration to give substituted 2-cyclohexenone. Pg. 790

question

Conjugate Addition of Lithium Diorganocopper Reagents

answer

Lithium diorganocopper reagents undergo conjugate addition to electrophilic double bond of alpha,beta-unsaturated aldehydes and ketones. Pg. 790

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