Ch 21 Carboxylic Acids and their Derivatives

Question 1

How do you name a carboxylic acid?

Answer 1

monocarboxylic acids,compounds containing one carboxylic acid group, are named with the suffix “-oic acid”

the parent chain includes the carbon atom of the carboxylic acid, that carbon is always assigned number 1 when naming the parent

when a carboxylic group is connected to a ring, the compound is named as an alkane carboxylic acid.

diacids,compounds containg two carboxylic acids groups ,are named with the suffix “dioic acid

Question 2

oxalic acid

Answer 2

Question 3

malonic acid

Answer 3

Question 4

succinic acid

Answer 4

Question 5

Glutaric acid

Answer 5

Question 6

What is the hybridization, geometry and bond angle of carbon atom of a carboxylic acid?

Answer 6

sp²

Trigonal planar

120º

Question 7

Why do carboxylic acids have higher boiling points than other compounds with OH groups?

Answer 7

carboxylic acid can form two hydrogen bonding interactions, allowing molecules to associate with each other in pairs. Stronger intermolecular forces.

Question 8

Treatment of a carboxylic acid with strong base yields _____

Answer 8

Treatment of a carboxylic acid with a strong base yields a carboxylic salt

Question 9

Carboxylate salts are ____ and are therefore more water soluble than their corresponding carboxylic acids.

Answer 9

Carboxylic salt are ionic and are therefor more water soluble than their their corresponding carboxylic acids

Question 10

The pKa of most carboxylic acids is between __ and __.

Answer 10

The pKa of most carboxylic acids is between 4 and 5

Question 11

Physiological pH

Answer 11

our blood is buffered to a pH of approximately 7.3

Question 12

Explain the effects of electron withdrawing substituents on the acidity of a carboxylic acid.

Answer 12

Electron with drawing groups increase the acidity (decrease he pKa) of carboxylic acids.

The inductive effects can stabilize the conjugate base.

The effect of the EWG depends on its proximity to the carboxlic acid group.

the effect is most pronounced when the EWG is located at the alpha position. as the distance increase the effect becomes less pronounced

Question 13

What happens when a carbon carbon triple bond(alkynes) is treated with 1).O₃ the 2). H₂O

Answer 13

Oxidative cleavage will break a triple bond froming two carboxylic acids

Question 14

What happens when a primary alcohol is treated with Na₂Cr₂O₇/H₂SO₄,H₂O.

Answer 14

oxidation will occur and a carboxylic acid will be formed( a variety of strong oxidazing agens can be used to oxidize primary alcohols and produce carboxylic acids)

Question 15

What happens when a alkyl benzen is treated with Na2Cr2O7/H2SO4,H2O

Answer 15

an alkyl group on an aromatic ring will be completely oxidized to give benzylic acid, provided that the benzylic postion has at least one hydrogen atom

Question 16

When treated with aqueous acid and a nitrile ( a compound with a cyano group) can be converted into a ________

Answer 16

Carboxylic acid , this process is called hydrolysis

Question 17

Give a two step process for convering an alky halide to a carboxylic acid. Via hydrolysis

Answer 17

The first step is an S_N2 reaction in which a cyanide acts as a nucleophile. The resulting nitrile is then hydrolized to yield a carboxylic acid hat has one more carbon atom than the original alkyl halide.

the reaction cannot occur with tertiary alkyl halides

the 1).nitrile replace the halide and then hydroized with 2).H₃O⁺/heat

Question 18

Carboxylic acids can be prepared by treating a Grignard reagent with ______ and ____

Answer 18

Carboxylic acids can be prepared by treating a Grignard reagent with carbon dioxide and a proton source.

In the first step, the grinard reagent attacks the eletrophilic center of carbon dioxide, generating a carboxylate ion. Treating the carboxylate ion with a proton source affords a carboxylic acid.

The two step must occur separately becaue the proton source is not caompatible with the Grignard reagent

Question 19

Give a two step process for converting an alkyl ( or vinyl or aryl) halide to a carboxylic acid

Answer 19

1. Grinard reaction
2. treatment with CO₂

Adds a carbon atom

Question 20

Carboxylic acids are reduced to alcohols upon treatment with _____

Answer 20

Carboxylic acids are reduced to alchols upon the tretmant of LAH and a H₃O⁺ (proton source)

Or BH₃ •THF, reduction with borane is often preferred over the reduction with LAH, beacuse borane reacts selectively with carboxylic acids in the presence of another carbonyl group

Question 21

What are some common carboxylic acid derivatives?

Answer 21

acid halide

acid anhydride

ester

amide

any compound with a carbon atom that has three bonds to heteroatoms will be classified as a carboxylic acid derivative. (i.e nitrile)

Question 22

how are acid are acid halides named?

Answer 22

acid halides are named as derivatives of carboxylic acids by replacinf the “ic acid” with “yl halide”

benzoic acid—> benzoyl chloride

when an acid halide group is connected to a ring, the suffix “carcoxylic acid” is replaced with “carbonyl halide”

cyclohexanecarboxylic acid ——>cyclohexanecarbonyl chloride

Question 23

how are acid anhydrides named?

Answer 23

acid anhydrides are named as derivatives of carboxylic acids by replacing the suffix “acid “ with anhydride.

Succinic acid—-> succinic anhydride

Unsymmetrical anhydrides are prepared from two different carboxylic acids and are named by indicating
both acids alphabetically followed by the suffix “anhydride

Acetic benzoic anhydride

Question 24

List the carboxylic acids in order of decreasing reactivity

Answer 24

OH>Cl>OOR>OR>NH₂

cloride

anhydride

ester

nitrile

Question 25

Explan the difference in reaivtiy of an acid cloride and a nitrile?

Answer 25

The third resonance(three lone pair on oxygen and a double bond on Cl) structure does not contribute much character to the overall resonance hybrid because the p-orbital overlap required for a C=Cl bond is not effective. As a result, the chlorine atom does not donate much electron density to the carbonyl group via resonance. The net effect of the chlorine atom is to withdraw electron density, rendering the carbonyl group extremely electrophilic. Nitrogen is less electronegative than chlorine or oxygen and is not an effective electron-withdrawing group. The nitrogen atom does not withdraw much electron density from the carbonyl group, and inductive effects are not significant. However, resonance effects are substantial. Unlike an acid halide, the third resonance structure of an amide contributes significant character to the overall resonance hybrid. The p orbital on the carbon atom effectively overlaps with a p orbital on the nitrogen atom, and the nitrogen atom can easily accommodate the positive charge.

Question 26

What is the major difference between carboxylic acid derivatives and aldehydels/ketones

Answer 26

carboxylic acid derivatives possess a heteroatom that can function as a leaving group, while aldehydes and ketones do not. When a nucleophile attacks a carboxylic acid derivative, a reaction can occur in which the nucleophile replaces the leaving group.

Question 27

What are the two core step of a nucleophilic acyl substitution

Answer 27

1. The carbonyl group is attacked by a nucleophile,forming a tetrahedral intermediate 2. A leaving group is expelled, and the carbonyl group is re-formed In the first step, a nucleophile attacks the carbonyl group, during which the hybridization state of the carbon atom changes. In both the starting material and product, the carbon atom is sp2 hybridized with trigonal planar geometry, but the same atom in the intermediate is sp3 hybridized with tetrahedral geometry. In recognition of this geometric change, the intermediate is often called a tetrahedral intermediate. In the second step, the carbonyl group is re-formed via loss of a leaving group. Re-formation of the CRO double bond is a powerful driving force, and even poor leaving groups (such as RO-) can be expelled under certain conditions.

Question 28

Why do proton trasfers occur?

Answer 28

In acidic conditions, avoid formation of a strong base. In basic conditions, such as hydroxide or methoxide, avoid formation of a strong acid. This rule dictates that all participants in a reaction (reactants, intermediates, and leaving groups) should be consistent with the conditions employed. The tetrahedral intermediate exhibits an oxygen atom with a localized negative charge, which is strongly basic and therefore inconsistentwith acidic conditions. To avoid formation of this intermediate, the acid catalyst is first employed to protonate the carbonyl group (just as we saw in the previous chapter with ketones and aldehydes). A protonated carbonyl group is significantly more electrophilic, and now when water attacks, no negative charge is formed. This step is now consistent with acidic conditions Formation of a strong base must only be avoided in acidic conditions. The story is different under basic conditions. protonationof the carbonyl group would involve formation of a strong acid, which is not consistent with basic conditions. Under basic conditions, hydroxide attacks the carbonyl group directly to give a tetrahedral intermediate.

Question 29

When do proton transfers occur?

Answer 29

A proton transfer can occur (1) before the nucleophilic attack, (2) before loss of the leaving group, or (3) at the end of the mechanism. Some mechanisms will have proton transfers at all three points,while other mechanisms might only exhibit one proton transfer step at the end of the mechanism

Question 30

reactions performed under acid-catalyzed conditions commonly have proton transfer steps at ______ possible points

Answer 30

reactions performed under acid-catalyzed conditions commonly have proton transfer steps at all three possible points

Question 31

Acid chlorides can be formed by treating carboxylic acids with \_\_\_\_\_\_

Answer 31

SOCl₂

Question 32

Mech for the prepartion of acid chlorides via thionyl chloride.

Answer 32

The first part of the mechanism converts the OH group into a better leaving group, which is accomplished in three steps. Each of these three steps should seem familiar if we focus on the chemistry of the S=O bond. In the three steps, the S=O bond behaves very much like a C=O bond of a carboxylic acid derivative (as described in the previous section). First, the S=O bond is attacked by a nucleophile, then it is re-formed to expel a leaving group, and finally a proton transfer is used to remove the charge. Part 2 of the mechanism is a typical nucleophilic acyl substitution, which is accomplished in two steps: nucleophilic attack followed by loss of a leaving group. In this case, the leaving group further degrades to form gaseous SO2. Formation of a gas (which leaves the reaction mixture) forces the reaction to completion.

Question 33

When treated with ___ acid chlorides are hydrolyzed to give carboxylic acids

Answer 33

water

Question 34

Mech for the hydrolysis of an acide chloride

Answer 34

Question 35

When treated with alchols (and pyridine),acid chlorides can be converted into \_\_\_\_

Answer 35

esters pyrindine is used as a base to neutralize the HCl that is produced

Question 36

Why is pyridine used?

Answer 36

Pyridine is a base that reacts with HCl to form pyridinium chloride. This process effectively traps the HCl so that it is unavailable for any other side reactions.

Question 37

When treated with \_\_\_\_\_, acid chlorides are converted into amides

Answer 37

ammonia pyridine is not used in this reaction because ammona itself is a sufficiently strong base to neutralize the HCl produced For this reaction, two equivalents of ammonia are necessary: one for the nucleophilic attack and the other to neutralize the HCl. This reaction also occurs with primary and secondary amines to produce N-substituted amides

Question 38

When treated with Excess LAH and water , acid chlorides are reduced to give \_\_\_\_\_

Answer 38

alcohols 1) . Excess LAH 2) . H₂O

Question 39

When treated with LiAl(OR)₃H and water , acid chlorides are reduced to give \_\_\_\_\_

Answer 39

aldehydes

Question 40

When treated with Excess Grignard and water , acid chlorides are reduced to give \_\_\_\_\_

Answer 40

teretary alcohols

Question 41

When treated with a Gilman reagent (R₂CuLi) , acid chlorides are reduced to give \_\_\_\_\_

Answer 41

Ketone

Question 42

Carboxylic acids can be converted in to acid anhydrides with\_\_\_\_\_\_

Answer 42

excessive heating water is relased this method is only practical for acetic acid, as most other acids do not survive the heat

Question 43

When acid chlorides are treated with a carboxylate ion\_\_\_\_ are produced

Answer 43

acid anhydrides NaCl is relased this method can be used to prepare symmetrical or unsymmetrical anhydrides

Question 44

The reactions of anhydrides are directly analogous to the reactions of acid chlorides. The only difference is in the identity of the \_\_\_\_\_\_

Answer 44

leaving group With an acid chloride, the leaving group is a chloride ion, and the by-product of the reaction is therefore HCl. With an acid anhydride, the leaving group is a carboxylate ion, and the by-product is therefore a carboxylic acid. As a result, it is not necessary to use pyridine in reactions with acid anhydrides, because HCl is not produced.

Question 45

Acetic anhydride can be used to acetylate an alcohol or and \_\_\_\_\_

Answer 45

Amine

Question 46

When treated with a strong base followed by an alkyl halide, carboxylic acids are converted into

Answer 46

esters via Sn2 rections

Question 47

What is the mech for the preparation of esters via Sn2 reactions

Answer 47

The carboxylic acid is first deprotonated to yield a carboxylate ion, which then functions as a nucleophile and attacks the alkyl halide in an SN2 process. The expected limitations of SN2 processes therefore apply. Specifically, tertiary alkyl halides cannot be used.

Question 48

Carboxylic acids are converted into ____ when treated with an alcohol in the presence of an acid catalyst.

Answer 48

esters this process is called a fisher esterification

Question 49

What is the mech for a fisher esterification

Answer 49

Question 50

How do you prepare an ester from an acid chloride.

Answer 50

by teating the acid chloride with and alcohol and pyridine

Question 51

What happen when esters are treated irh sodium hydroxide then an acid?

Answer 51

the ester is converted into a carboxylic acid

Question 52

What is the mech for the saponification of ester?

Answer 52

Question 53

Esters can be hydrolized under\_\_\_\_ conditions

Answer 53

esters can be hydrlized under acidic conditions

Question 54

What is the mech for an acid catalyzed hydrolysis of esters?

Answer 54

Question 55

Esters react slowy with ___ to yield amides

Answer 55

esters react slowly with amines to yield amides

Question 56

When treated with excess LAH ,esters are reduced to \_\_\_\_\_\_

Answer 56

When treated with excess LAH esters are reduced to yield alcohols.

Question 57

What is the mech for the reduction of an ester with LAH

Answer 57

Question 58

An ester can be treated with 1).DIBAH/2).H₂O to produce \_\_\_\_\_\_.

Answer 58

Aldehydes

Question 59

What happens when an ester is treated with a Grignard reagent

Answer 59

When treated with a Grignard reagent, esters are reduced to yield alcohols with the introduction oftwo alkyl groups

Question 60

What is the mech for the reaction between an ester and a grignard reagent

Answer 60

Question 61

Amides can be prepared from _______ of the carboxylic acid derivatives. Which are the most efficient?

Answer 61

Amides can be prepared from any of the carboxylic acid derivatives discussed earlier in this chapter. Among these methods, amides are most efficiently prepared from acid chlorides. Acid halides are the most reactive of the carboxylic acid derivatives, so the yields are best when an acid chloride is used as a starting material.

Question 62

Amides are hydrolyzed to give _______ in the presence of aqueous acid aor base

Answer 62

amides can he hydrolyzed to give carboxylic acids in the presence of aqueous acid , but the process is slow and requires heating to occur at an appreaciable rate Amides are also hydrolyzed when heated in basic aqueous solutions, although the process is very slow. The mechanism for this process is directly analogous to the saponification of esters.

Question 63

What is the mech for the acid catalyzed hydrolysis of an amide?

Answer 63

The mechanism for this transformation (Mechanism 21.11) is directly analogous to the acid- catalyzed hydrolysis of esters (Section 21.11). In this reaction, notice that an ammonium ion (NH4+) is formed as a by-product. Since the ammonium ion (pKa = 9.2) is a much weaker acid than H3O+ (pKa = -1.7), the equilibrium greatly favors formation of products, rendering the process effectively irreversible

Question 64

What is the mech for a hydrolysis of amides under basic canditions?

Answer 64

Question 65

What happens when an alkyl halide is treated with a cyanide ion

Answer 65

Nitriles are produced , along with the salt of the halide this process proceeds via an Sn2 mech, so tertiary alkyl halides connot be used

Question 66

What happens when a amide is treated with SOCl₂

Answer 66

a nitrile is formed in this dehydration this process is useful fro preapring nitriles, which cannot be prepared via an Sn2 process

Question 67

In aqueous acidic conditions, nitriles are hydrolyzed to afford \_\_\_\_\_, which are then further hydrolyzed to yield carboxylic acids.

Answer 67

In aqueous acidic conditions, nitriles are hydrolyzed to afford amides,which are then further hydrolyzed to yield carboxylic acids.

Question 68

What happens when an nitriles are treated with 1)NaOH,H₂O/2)H₃O⁺

Answer 68

Carboxylic acids are produced

Question 69

What is the mech for an acid catalyzed hydrolysis of nitrile

Answer 69

Question 70

what is the mech for the base catalyzed hydrolysis of nitriles

Answer 70

Question 71

What happens when a nitrile is treated with a Grignad reagent,followed by aqueous acid

Answer 71

a ketome is formed the grignard reagent attacks the nitrile, much like it attaacks a carbonyl group the resulting anion is then treated with aquesous acid to give an imine, which is then hydrolyzed to a ketone under acidic conditons.

Question 72

Nitriles are conveted to ____ when treated with LAH(excess) then a proton source.

Answer 72

nitriles are converted to amines when treated with LAH