Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
UNIT 10
CARBOXYLIC ACID DERIVATIVES
Structure 10.1 Introduction 10.6 Carboxylic Acid Esters
Objectives Preparation of Carboxylic Acid Esters 10.2 Structure and Reactivity of Carboxylic Acid Reactions of Carboxylic Acid Derivatives esters
10.3 Physical Properties of Reformatsky Reaction Carboxylic Acid Derivatives 10.7 Amides 10.4 Carboxylic Acid Halides Preparation of Amides Preparation of Carboxylic Acid Reactions of Amides Halides 10.8 Summary Reactions of Carboxylic Acid Halides 10.9 Terminal Questions 10.5 Carboxylic Acid Anhydrides 10.10 Answers
Preparation of Carboxylic Acid Anhydrides
Reactions of Carboxylic Acid Anhydrides
10.1 INTRODUCTION
In the last unit, you have studied about the chemistry of carboxylic acids. There, in Sec. 9.5 under the reactions of carboxylic acids, you came across the formation of derivatives of carboxylic acids.
A functional derivative of carboxylic acid is a compound which results on replacement of the hydroxyl group of the carboxylic acid by some other group, L. A characteristic feature of these derivatives is that they regenerate the carboxylic acid on hydrolysis, i.e. 28
Unit 10 Carboxylic Acid Derivatives
O O
RCL + H2O RCOH + HL Carboxylic acid Water Carboxylic Conjugate derivative acid acid of L
Various functional derivatives of carboxylic acids are possible depending upon the nature of L. The functional derivatives which you will study in this unit include carboxylic acid halides also called alkanoyl halides, anhydrides, esters and amides. The general structures of carboxylic acid and these functional derivatives can be represented as follow:
O O O O R C OH R C X R C O C R' a carboxylic acid an alkanoyl an anhydride halide
O O
R C R' R C NH2 an ester an amide O R C You can see that all of these derivatives contain a or alkanoyl group in their structure. While studying this unit, you will realise that there is not only a structural similarity among carboxylic acids and their derivatives but also a close relationship in their chemistry. Expected Learning Outcomes
After studying this unit, you should be able to:
define carboxylic acid derivatives;
give examples of various carboxylic acid derivatives;
comment on the acidic and basic behavior of various carboxylic acid derivatives;
correlate the reactivities of carboxylic acid derivatives with their structures;
outline the synthesis of various carboxylic acid derivatives;
explain the reactions of various carboxylic acid derivatives;
compare the behavior of various carboxylic acid derivatives, reaction conditions required in various nucleophilic addition-elimination reactions like hydrolysis, formation of amides, etc., and the nature of products obtained;
describe the reactions of various carboxylic acid derivatives with organometallic reagents; and
explain the reduction reactions undergone by carboxylic acid derivatives. 29
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds 10.2 STRUCTURE AND REACTIVITY OF CARBOXYLIC ACID DERIVATIVES
Similar to the structure of carbonyl compounds and carboxylic acids, the derivatives of carboxylic acids have trigonal geometry, i.e., all the bonds to the carbonyl carbon are in the same plane. This is shown in Fig. 10.1.
O L C R
Fig. 10.1: Planar arrangement of bonds to the carbonyl carbon in carboxylic acid derivatives.
An important structural feature of carboxylic acid derivatives is that the atom O R attached to the C group bears an unshared pair of electrons which is capable of interacting with the π electrons of the carbonyl group. This is shown in Fig. 10.2.
Individual p orbitals in carboxylic acid Extended orbital system in carboxylic derivatives acid derivatives
Fig. 10.2: The extended π electron system in carboxylic acid derivatives.
This electron delocalisation can be represented by the following resonance structures.
O: : :O: : R C R C + : L L I II
The extent of this electron delocalisation depends on the electron donating properties of L. Thus, a less electronegative L will donate the electrons more easily than a more electronegative L. The electron release from L reduces the polarisation of the carbonyl group, thereby, decreasing its electrophilic character. Thus, the greater the electron release from L, the greater is its stabilising effect. Consequently, when L is more electronegative, the extent of resonance decreases and the reactivity increases. Thus, the reactivity of carboxylic acid derivatives towards nucleophilic substitution reactions follows 30 the following order:
Unit 10 Carboxylic Acid Derivatives
O O O O O A derivative higher in RCCl > RCOCR > RCOR > RCNH this order can be 2 converted to the one alkanoyl halide anhydride ester amide lower but not vice-
versa.
You will study the nucleophilic substitution reactions of carboxylic acid derivatives in detail in the later sections of this unit.
The degree of resonance stabilisation is also reflected in the structural parameters and spectral characteristics of carboxylic acid derivatives about which you will study in the next section.
But before that let us understand the reactivity of carboxylic acid derivatives as acids and bases. Basicity and Acidity of Carboxylic Acid Derivatives
Carboxylic acid derivatives are weakly basic at the carbonyl oxygen which can be protonated using strong acids. This property is particularly useful in some of the acid-catalysed reactions of esters and amides.
...... H H H ...... +
O .. O O O H+ C C + C .. .. C .. R L R L R L R L+
pKa values of the The pKa values for the conjugate acids of carboxylic acid derivatives show that conjugate acids of alkanoyl halides are the weakest bases as their conjugate acids have the carboxylic acid derivatives. lowest pKa and are, therefore, strongest acids. Esters are about as basic as
: H : H + + + : H carboxylic acids whereas amides are the most basic. O O O
: :
: RCCl : < RCOR ' < RCNH The acidity of the -hydrogens next to the carbonyl group shows the following : : 2 pKa ~ 9 ~ 10 ~ 0 order amongst carboxylic acid derivatives.
O O O CH CCl < CH COCH < 3 3 3 CH3CN(CH3)2
pK ~ 16 pK ~ 25 pK ~ 30 a a a Primary and secondary amides are deprotonated at nitrogen to give an amidate ion which is resonance stabilised in the same way as the carboxylate
ion...... .. .. O .. O O
C H+ + C C .. .. .. R R NH2 NH R NH
pK ~ 15 an amidate ion a
31
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds 10.3 PHYSICAL PROPERTIES OF CARBOXYLIC ACID DERIVATIVES
It was pointed out in the earlier section that the extent of resonance is reflected in the structural parameters. This can be understood when we compare the C-L bond lengths in various carboxylic acid derivatives with the C-L bond lengths in the compounds of the type R-L. These bond lengths are listed in Table 10.1.
Table 10.1: C-L Bond lengths of some carboxylic acid derivatives and compounds of R-L type
O L R C L (pm) R L (pm)
Cl 179 178
OCH3 136 143
NH2 136 147
The bond lengths shown in Table 10.1 indicate that as we go from the most reactive alkanoyl halides to the much less reactive esters and amides, the C-L bond becomes shorter as compared to the normal C-L single bond. Thus, in amides, the contribution of the dipolar structure II as discussed earlier, is strong enough to impart some double bond character to the carbon-nitrogen bond. The double bond character is also indicated by a barrier of 75 to 84 kJ mol1 to the rotation of the carbon-nitrogen bond.
O R' R R' C N C N R R" O R"
The other physical properties for various carboxylic acid derivatives are briefly stated below.
Alkanoyl Halides and Anhydrides
The lower members of these derivatives are dense, water-insoluble liquids with piercing odours. Their boiling points are not very different from those of other polar molecules of similar weight and shape. Some examples are given below:
O O O CH3 O C C C C CH CH CH C Cl O CH CH3 3 3 CH3 3 b.p. 413 K b.p. 403 K b.p. 324 K
O O O CH CH C Cl C OCH CH3 C O 2 3 3
b.p. 330 K b.p. 470 K b.p. 486 K 32
Unit 10 Carboxylic Acid Derivatives
Esters: The lower members of this class are volatile, fragrant liquids having lower density than water. Most esters are not soluble in water.
Amides: The lower members are water-soluble, polar in nature and have high boiling points. Primary and secondary amides associate to form hydrogen bonded dimers or higher aggregates in solid and liquid state.
O C
CH3 NH2 ethanamide m.p. 355 K O b.p. 494 K CH3 HCN CH3 A number of amides have high dielectric constants. N, N-Dimethylmethanamide (commonly known as N, N-dimethylfomamide, N,N-Dimethylmethanamide abbreviated as DMF) is widely used as a polar aprotic solvent.
SAQ 1 Which carboxylic acid derivative is least a) reactive towards nucleophilic substitution reactions? b) basic?
10.4 CARBOXYLIC ACID HALIDES
Carboxylic acid halides are important class of compounds belonging to carboxylic acid derivatives. In this section, we will be dealing with the preparation and the reactions of this class of carboxylic acid derivatives.
10.4.1 Preparation of Carboxylic Acid Halides
Carboxylic acid halides can be prepared from carboxylic acids using the acid chlorides of inorganic acids such as PCl5 (acid chloride of phosphoric acid),
PCl3 (acid chloride of phosphorous acid) and SOCl2 (acid chloride of sulphurous acid). The general reactions can be represented as shown below:
O O
RCOH + PCl5 RCCl + POCl3 + HCl phosophrous pentachloride
O O
3 RCOH + PCl3 3 RCCl + H3PO3 phosophrous trichloride
O O
RCOH + SOCl2 RCCl + SO2 + HCl thionyl chloride 33
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
Carboxylic acid fluorides, bromides and iodides are prepared from carboxylic acid chlorides by reaction with HF, HBr or HI, respectively.
O O HX = HF, HBr or HI RCCl + HX RCX + HCl
10.4.2 Reactions of Carboxylic Acid Halides
The reactions of carboxylic acid halides are listed in Table 10.4.
Table 10.4: Reactions of Carboxylic Acid Halides
A. Reactions with Nucleophiles
O O
RCL + Nu RCNu + L
where NuH = H2O, RCOOH, ROH, ArOH,NH3, NR2 and organometallic reagents.
B. Reduction
O O H /catalyst 2 RCH RCL or hydride aldehyde reduction
C. Friedel-Crafts reactions (discussed in Unit 11, Block-3 of BCHCT-135 Course).
A. Reactions with Nucleophiles
The reactions of carboxylic acid halides and carboxylic acid derivatives with nucleophiles proceed via addition–elimination steps which lead to the
nucleophilic substitution at the carbonyl carbon. This is shown below: ...... .. .. O O .. O
RCL + :Nu R C L RCNu + L
Nu
Thus, the nucleophile: Nu has substituted the group L in the carboxylic acid derivative. This reaction has little synthetic value Carboxylic acid halides react with a variety of nucleophilic reagents such as because acid halides water, carboxylic acids, alcohols and phenols, amines and organometallic are themselves reagents. Let us study each of these reactions in detail using the examples of usually prepared from carboxylic acid chlorides as these are the most readily accessible among the the acids. halides.
1. Reaction with Water
It was pointed out earlier that carboxylic acid derivatives, on hydrolysis, yield carboxylic acids. Thus, carboxylic acid halides react with water to 34 give carboxylic acids. For example,
Unit 10 Carboxylic Acid Derivatives
O O
CH3CH2CCl + HOH CH3CH2COH + HCl propanoyl propanoic acid chloride (100%)
2. Reaction with Carboxylic Acids
Carboxylic acid halides on reaction with carboxylic acid yield acid anhydrides, i.e.
O O O O Pyridine acts both as RCCl + R'COH + RCOCR' + Cl a catalyst as well as a + N N base to neutralise the .. H hydrogen chloride alkanoyl carboxylic pyridine carboxylic acid pyridinium formed in the chloride acid anhydride chloride reaction. Salts of carboxylic acids also react with a carboxylic acid halides to yield the acid anhydrides. For example,
O O O O
+ : C H CCl + Na :O C CH C H C O C CH3 + NaCl 2 5 : 3 2 5 propanoyl (excess) ethanoic propanoic chloride sodium ethanoate anhydride
3. Reaction with Alcohols and Phenols
The reaction of carboxylic acid halides with alcohols and phenols yields esters. A base is usually added to neutralise the hydrogen chloride formed as by-product. Usually pyridine, amines or alkali metal hydroxides are used as bases.
O O N(CH CH ) + 2 3 3 CH3CCl + HOCH2CH2CH3 CH3COCH2CH2CH3 + HN(CH2CH3)3Cl ethanoyl propanol propyl ethanoate triethylammonium chloride hydrochloride O
OH O C CH3 O ether CH CCl 3 + pyridine + HCl CH CH3 CH3 3 CH3 (75%)
4. Reaction with Ammonia and Amines
Ammonia, primary and secondary amines react with carboxylic acid halides to yield amides. The reaction with ammonia yields a primary amide as shown below:
O O + CH3(CH2)8C Cl + 2 NH3 CH3(CH2)8C NH2 + NH4Cl (73%) 35
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
The reaction with primary amines yields a secondary amide whereas the reaction with secondary amines gives tertiary amide.
O O .. .. Ph C Cl + PhCH2CH2NH2 + Ph C NHCH2CH2Ph + + N N .. pyridine H Cl
O O
+ .. Ph C Cl + N H + NaOH Ph C .. N + H2O + Na Cl
(77-81%)
What about the tertiary amines? Do they react with carboxylic acid halides? Before finding an answer to these questions, let us first try to
understand the mechanism of the amide formation which is given below:
......
......
O .. O O H O
...... H NR + 2
.. R C Cl .. R C Cl R C NH R R C NH R + H NR Cl
.. .. + 3 ..
+ .. .. NH R .. NH2 R 2 + Cl..
The last step in the mechanism involves loss of a proton from nitrogen which is not possible when the reaction is carried out with tertiary amines.
O O + + H R C Cl No amide + (CH3)3N: RCN(CH3)3Cl
a tertiary alkanoyl amine ammonium chloride
An important aspect of amide formation is that, for each equivalent of the amide formed, an additional equivalent of base is required to neutralise the hydrogen chloride formed. When the amine used in the reaction is cheap and readily available, it is used in excess to serve as a base also. When the amine used to form the amide is expensive and, hence, cannot be used in excess, a tertiary amine, which does not interfere with the reaction, can be used as a base.
5. Reaction with Organometallic Reagents
Carboxylic acid halides react with a number of organometallic compounds to yield ketones. When a Grignard reagent is used, the best results are obtained if the reaction is carried out at low temperature using one equivalent of the Grignard reagent.
O O R C X + R' MgBr R C R' + X Mg Br 36
Unit 10 Carboxylic Acid Derivatives
If an excess of the Grignard reagent is used, the ketone obtained reacts further to yield an alcohol as shown below:
+ O O OMgX OH R' MgX R' MgX H O R C Cl R C R' R C R' 2 R C R' R' R' a tertiary alcohol
Thus, to synthesise a ketone from a carboxylic acid halide, the organometallic reagent used should be so chosen that it reacts much faster with the starting halide than it does with the product ketone. Two types of organometallic reagents which satisfy this requirement are lithium organocuprate reagents and organocadmium reagents.
Lithium organocuprate reagents such as lithium dialkyl-and diaryl cuprates are prepared through the reaction of an alkyl or aryllthium reagent with a cuprous salt.
ether 2 RLi + CuX LiCuR2 + LiX alkyllithium cuprous lithium lithium halide dialkylcuprate halide
The reaction of a carboxylic acid halide with lithium diorganocuprate yields a ketone.
O O ether LiCuR R' CCl+ R' CR + RCu + LiCl 2 195 K lithium alkanoyl ketone alkyl lithium dialkylcuprate halide copper chloride
Organocadmium reagents such as dialkylcadmium and diarylcadmium are prepared by treating Grignard reagents with cadmium chloride.
CdCl 2 CH CH MgBr 2 (CH CH ) Cd 3 2 ether 3 2 2 ethylmagnesium diethylcadmium bromide CdCl 2 C H MgBr 2 (C H ) Cd 6 5 ether 6 5 2 phenylmagnesium diphenylcadmium bromide
The desired ketone can be prepared by the reaction of the suitable organocadmium reagent with a suitable carboxylic acid halide.
O O
R2Cd R' CX+ R' CR organocadmium carboxylic ketone reagent acid halide 37
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
Secondary and tertiary lithium alkylcuprates and also the secondary and tertiary alkylcadmium reagents are not stable and decompose readily and hence, cannot be employed for ketone synthesis. This then limits the synthetic utility of these reactions employed for ketone synthesis. To primary alkyl and arylcuprates and to primary dialkyl or diarylcadmium reagents.
B. Reduction
Carboxylic acid halides can be reduced to aldehydes by either of two methods: the first method involves catalytic hydrogenation and the second involves hydride reduction.
In catalytic reduction, the carboxylic acid halide is hydrogenated using a special catalyst such as palladium deposited on barium sulphate poisoned with an amine such as quinoline. The poisoning of the catalyst moderates its effectiveness and hence inhibits the subsequent reduction of the product aldehyde to alcohol. This reaction is called the Rosenmund reduction.
O O
CH2CCl CH2CH + HCl H2, Pd-BaSO4, quinoline
(71%)
O O CCl CH
H2, Pd/BaSO4 xylene, heat
naphthalene-2- carbonyl naphthalene-2-carbaldehyde chloride (74-81%)
H CO H3CO 3 O O H2, Pd/BaSO4 H CO CCl H CO CH 3 xylene, 423 K 3
H CO H3CO 3 3,4,5-trimethoxybenzoyl chloride 3,4,5-trimethoxybenzaldehyde (71%)
The hydride reduction using ordinary reducing hydrides, such as sodium borohydride or lithium aluminum hydride, coverts the aldehydes obtained initially in the reaction to alcohols. This over reduction can be prevented by using a modified lithium aluminium hydride namely, lithium tri(tert-butoxy) aluminium hydride which is obtained by the reaction of lithium aluminium hydride with three equivalents of 2-methyl-2-propanol (tert-butanol).
+ + LiH Al[O C(CH ) ] + 3 H Li AlH4 + 3 (CH3)3C O H 3 3 3 2
2-methyl- 2-propanol lithium tri(tert- butoxy) aluminium hydride 38
Unit 10 Carboxylic Acid Derivatives
In lithium tri(tert-butoxy) aluminium hydride, three of the reactive hydride groups of lithium aluminium hydride are replaced with alkoxy groups and hence, the one remaining hydride reduces only the most reactive functional groups. Because acid halides are more reactive towards nucleophiles than aldehydes, the reagent preferentially reduces the carboxylic acid halide rather than the product aldehyde
O O 1. ether RCCl + LiAl[OC(CH ) ] H RCH + LiCl + Al[OC(CH ) ] 3 3 3 2. H+, H O 3 3 3 2 C. Friedel-Crafts Reactions
The Friedel-Crafts alkanoylation (acylation of aromatic compounds using alkanoyl halides was dealt with in Unit 11, Block 3 of BCHCT-133 Course.
SAQ 2
How will you convert butanoyl chloride into the following products.
O a) CH CH CH COH 3 2 2 O O b) CH CH CH COCCH 3 2 2 3 O c) CH3CH2CH2CO
O d) CH CH CH CN(CH ) 3 2 2 3 2 O e) CH CH CH CCH CH 3 2 2 2 3
O f) CH3CH2CH2CH
10.5 CARBOXYLIC ACID ANHYDRIDES
Carboxylic acids anhydrides are another important group of carboxylic acids derivatives. In this section, you will study about the preparation and important reactions of carboxylic acid anhydrides. 10.5.1 Preparation of Carboxylic Acid Anhydrides
Carboxylic acid anhydrides can be prepared using the methods listed in Table 10.5. 39
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
Table 10.5: Methods of Preparation of Carboxylic Acid Anhydride
1. From carboxylic acid halides and carboxylic acids pyridine RCOOH + R'COCl RCO O COR' + HCl
2. From Ketene and carboxylic acids
CH2 C O + RCOOH RCO O COCH3
(used in commercial preparation of ethanoic anhydride) 3. Using other anhydrides P O 2 R COOH 2 5 R CO O CO R or ethanoic anhydride
Let us now study these methods in detail.
1. From carboxylic acid halides
A general method of It was pointed out in the last section (sub-Sec.10.4.2) that carboxylic acid preparation of halides react with carboxylic acids or carboxylate salts to give carboxylic acid substituted ketenes is anhydrides. This reaction can be used prepare both the simple and the mixed based on the dehydrohalogenation anhydrides. of alkanoyl halides or the dehalogenation of 2. From ketene and carboxylic acids 2-halo-alkanoyl halides. Carboxylic acid anhydrides can also be prepared by the reaction of ketene with carboxylic acids. O N(CH CH ) RCH2CCl 2 3 3 O O O
+ RCH C O+HN (CH2CH3)3Cl CH2 C O + RCOH R C O C CH3 O ketene carboxylic anhydride Zn acid RCH 2CCl Br RCH C O + ZnClBr The commercial production of ethanoic anhydride, based on the above reaction, involves the use of ethanoic acid as the carboxylic acid.
3. Using other anhydrides
Most anhydrides may themselves be used to form other anhydrides. Examples
given below illustrate the use of P2O5 (an inorganic anhydride) and ethanoic anhydride.
O O O C OH + complex phosphates 2 CF3 P2O5 2 CF3 C O C CF3 + trifluoroethanoic phosphorus trifluroethanoic acid pentoxide anhydride (74%)
O O O O O CH C CH2 C OH 2 CH CH O2 CH+ 3 C OH CH3 CH + CH3 C O C CH3 3
CH2 C CH2 C OH O O (>90%) 40 a cyclic anhydride
Unit 10 Carboxylic Acid Derivatives
Cyclic anhydrides containing five- and six-membered rings can also be readily prepared just by heating the dicarboxylic acid. For example, 1,2-benzenedicarboxylic acid gives 1,2-benzenedicarboxylic anhydride on heating. O O C OH C fuse (melt) O + H2O sublimes C OH C
O O 1,2-benzenedicarboxylic acid 1,2-benzenedicarboxylic (phthalic acid) anhydride (phthalic anhydride)
10.5.2 Reactions of Carboxylic Acid Anhydrides
Table 10.6 lists the reactions exhibited by carboxylic acid anhydrides.
Table 10.6: Reactions of Acid Anhydrides
A. Reactions with nucleophiles 1. Hydrolysis
O O R C
O + H2O 2 R C OH R C
O 2. Reaction with alcohols
O O O R C O + R'OH R C OR' + R COH R C
O 3. Reaction with ammonia and amines O O O R C R' O + HN R CN R' + R COH R" R C R" O B. Friedel-Crafts alkanoylations
O O C R O R C AlCl O + 3 + R COH R C O 41
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
A. Reactions with Nucleophiles
The reactions of carboxylic acid anhydrides with nucleophiles are analogous to those of the carboxylic acid halides which you have studied in the last section. The difference here is that the leaving group is a carboxylate ion instead of the halide ion in the case of carboxylic acid halides. The reactions of carboxylic acid anhydrides with water, alcohols and amines are given below:
1. Hydrolysis
O O O
RCOCR + H2O 2 RCOH carboxylic acid carboxylic acid anhydride
2. Reaction with alcohols
O O O O RCOCR + R'OH RCOR ' + RCOH
carboxylic acid alcohol ester carboxylic anhydride acid
3. Reaction with ammonia and amines
O O O O + RCOCR + 2 NH3 RCNH 2 + RCO NH4 carboxylic acid ammonia amide ammonium anhydride carboxylate salt
O O O O + RCOCR + 2 R2'NH RCNR 2' + RCO H2NR2' carboxylic acid amine amide ammonium anhydride carboxylate salt
The products in this reaction are amide and carboxylic acid. The carboxylic acid reacts with ammonia or amine to form a salt. Therefore, two moles of ammonia or amines are required. Another alternative, as you have studied in the case of carboxylic acid halides is to use one equivalent of a tertiary amine.
The general nucleophilic addition-elimination of anhydrides is shown below:
: :O: :O: O:: :O: :O: :O: :O: :O: :: : + : RC O CR + :NuH RC OCR RC NuH + :OCR RCNu + HOCR : : + NuH
The nucleophilic reactions which you have just studied can be used to synthesise one carboxylic acid derivative from another, as you will study in the later sections.
If you recall the order of relativities of various carboxylic acid derivatives given 42 in Sec. 10.2, then you will realise that the less reactive carboxylic acid
Unit 10 Carboxylic Acid Derivatives derivatives can be synthesised from the more reactive ones but the reverse is usually difficult and requires special conditions or a catalyst.
B. Friedel-Crafts Alkanoylations
Carboxylic acid anhydrides also serve as sources of alkanoyl cations and can be used in Friedel-Crafts alkanoylations as shown below.
O
H O O CCH 3 O AlCl + CH COCCH 3 + CH COH 3 3 313 K 3 ethanoic ethanoic acid anhydride benzene 1-phenylethanone (76-83%) (acetophenone)
SAQ 3 Write the products of the following reactions: O O H2O a) CH3COCCH 3 ethanoic anhydride
O O CH3OH b) CH3CH2COCCH 2CH3 propanoic anhydride
O O CH3 COC CH CH CH NH c) 3 2
cyclohexanecarboxylic anhydride
Esters have pleasing 10.6 CARBOXYLIC ACID ESTERS odors.
Carboxylic acid esters constitute a very important class of carboxylic acid CH2OH derivatives. Some examples of naturally occurring esters are given below. CHOH O CH O CH 3 3 CH2OH 1,2,3-propanetriol CH3COCH 2CH2CHCH 3 CH3CH2CH2CH2COCH 2CH2CHCH 3 (glycerol) 3-methylbutyl ethanoate 3-methylbutyl pentanoate O (component of banana flavour) (component of apple flavour) CH2OCR O O HCOCR' COCH 3 O
CH2OCR'' 1,2,3-propanetriol OH triester (Triglyceride) methyl 2-hydroxybenzenecarboxylate (principal component of oil of wintergreen) 43
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
Triesters of 1,2,3 -propanetriol (glycerol) constitute the oils and fats found in plants and animals.
As the esters contain alkyl and alkanoyl (acyl) groups, they are named as alkyl alkanoates. The alkyl group is cited first, followed by the name of the alkanoyl (acyl) portion which is named by replacing the ic ending of the carboxylic acid by the suffix ate. Some more examples are given below: O O O CH CH COCH CH3COCH3 CH3COCH2CH3 3 2 3 methyl ethanoate ethyl ethanoate methyl propanoate
The systematic names of cyclic esters, i.e., lactones are illustrated by the following examples.
O 1 1 3 1 2 2 O 2 O H C O O 3 O 2-oxacyclobutanone 2-oxacyclopentanone 2-oxa-3-methylcyclo- (-propiolactone) (-butyrolactone) pentanone (-valerolactone)
Let us now study the methods of preparation of carboxylic acid esters. 10.6.1 Preparation of Carboxylic Acid Esters
Let us first list the methods of ester formation which you have already studied.
1. From the reaction of carboxylic acids and alcohols (Fischer esterification): It was dealt with in detail in Sec. 9.5, Unit 9.
2. From carboxylic acids using diazomethane: It was also dealt with in Sec. 9.6, Unit 9.
3. From carboxylic acid halides: The reaction of carboxylic acid halides with alcohols and phenols also yields esters. It involves the use of a weak base. It was discussed in Sub-Sec. 10.4.2.
4. From carboxylic acid anhydrides: Carboxylic acid anhydrides react with alcohols in the presence of acid catalysts to give esters. This reaction was discussed in sub-Sec. 10.5.2.
In addition to the above methods, esters can also be prepared by ester interchange which is discussed below.
5. Ester interchange: Esters can also be obtained by ester interchange. When an ester reacts with an alcohol under acidic conditions or with an alkoxide ion under basic conditions, a new ester is formed. This is called transesterification. The general reaction can be represented as shown below: O O
RCOR ' + R"OH RCOR " + R'OH Transesterification will be discussed in detail under the reactions of 44 esters in the next sub-section.
Unit 10 Carboxylic Acid Derivatives
10.6.2 Reactions of Carboxylic Acid Esters
The reactions of esters are listed in Table 10.7 followed by their detailed discussion. Table 10.7: Reactions of Esters 1. Hydrolysis
O O + H ' R C OH + R' RCOR + H2O OH
O O RCOR' + OH RCO + R' OH H O 2 2. Conversion to amides
O O R" R" RC O OR' + HN R-C-N + R' OH R"' R"' R" and/or R''' may be H
3. Conversion to other esters: transesterification
O O + H RCOR' + R'' OH RCOR" + R' OH 4. Reaction with Grignard reagents O OMgX ether R C OR' + 2 R" MgX R C R" + R'OMgX R"
H+
OH R C R"
R" 5. Reduction
O RCOR' + H Ni R CH OH + R' OH 2 2 O RCOR' + LiAlH R CH OH + R' OH 4 2 O C H OH R C OR' + Na 2 5 R CH OH + R' OH 2 6. Formation of enolates
O O RCH 2COR' + :B RCH C + BH OR' ester ester enolate
45
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
1. Hydrolysis
In contrast to the hydrolysis of carboxylic acid halides and anhydrides, esters Base catalysed do not react with water unless a catalyst is present. Both acid catalysed and hydrolysis of esters is base catalysed hydrolysis reactions are possible. called saponification because it was The acid catalysed hydrolysis is just the reverse of acid catalysed formation of initially used in the esters which was discussed in detail in Sec. 9.5, Unit 9 .You studied in manufacture of soaps from fats. This term is Sec. 9.5 that esterification is an equilibrium reaction, i.e., now sometimes used to refer to base- O O + catalysed hydrolysis H RCOH + R'OH RCOR ' + H O of any acid derivative. 2 acid alcohol ester Base catalysed hydrolysis of esters is In esterification, either excess of the starting alcohol is used or water produced faster than acid- is removed from the reaction mixture to shift the equilibrium in the forward catalysed hydrolysis. direction. But when ester hydrolysis is the objective, the reaction is carried out
using excess of water in the presence of a mineral acid. Remember that acid- catalysed hydrolysis is an equilibrium process.
In contrast to acid catalysed hydrolysis, base catalysed hydrolysis of esters is not an equilibrium process but is irreversible because the carboxylic acid produced on hydrolysis is converted to its anion under the basic conditions.
O O RCOR ' + HO RCO + R'OH ester hydroxide carboxylate alcohol ion ion
CH3 O CH3 O 1. KOH, H O, CH OH, CH CHCH COCH 2 3 CH CHCH COH + CH OH 3 2 3 + 3 2 3 2. H , H2O methyl 3-methyl- 3-methylbutanoic methanol butanoate acid
O OCH 3 O OH C C
1. 20% NaOH, 5-10 min. + HO + CH OH 2. HCl 3 NO 2 NO2
As shown in the above examples, a separate acidification step is required to get the free acid from the carboxylate ion.
2. Reaction with ammonia and amines: Conversion to amides
Esters react with ammonia and amines to give an amide and an alcohol.
O O
RCOR ' + NH3 RCNH 2 + R'OH ester ammonia mide alcohol 46 a
Unit 10 Carboxylic Acid Derivatives
O O heat FCH2COCH 2CH3 + NH2 FCH2CNH + CH3CH2OH ethyl fluoroethanoate cyclohexylamine N-cyclohexyl- fluoroethanamide ethanol (61%)
The reaction of esters with azanol (hydroxylamine, :NH2OH) gives N-hydroxyamides. These compounds are known as hydroxyamic acids.
O O
R C OCH 2CH3 + :NH2OH R C NHOH + C 2H5OH ester azanol a hydroxamic ethanol (hydroxylamine) acid The hydroxamic acids form highly coloured complexes with ferric ion. This chemistry forms the basis of hydroxamic test used for the identification of esters. 3. Reaction with alcohols: Transeterification
It was pointed out in the last sub-section that a new ester can be syhthesised by the reaction of an ester with an alcohol by a process called transesterification. Transeterification is an equilibrium reaction and requires a large excess of the alcohol which is usually used in the form of solvent.
O O + H C H COCH CH + CH OH C H COCH + CH CH OH 17 35 2 3 3 or 17 35 3 3 2 _ ethyl octadecanoate solvent OCH thyl octadecanoate ethanol 3 me 4. Reaction with Grignard Reagents
Esters react with two equivalents of Grignard reagent to produce tertiary alcohols. O OH 1. ether RCOR ' + 2 R"MgX + RCR" + R'OH 2. H O ester 3 alcohol Grignard reagent R" ry alcohol a tertia A ketone is an intermediate in the reaction but as soon as it is formed, it reacts with the second equivalent of the Grignard reagent. O O ether RCOR ' + R"MgX RCR" + ROMgX ester ketone 1. R"MgX, ether + 2. H3O OH RRC " R" a tertiary alcohol 47
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
Obviously, methanoic esters on reaction with Grignard reagents yield a secondary alcohol. For example,
O OH 1. ether + C H OH HCOC 2H5 + 2 CH3CH2CH2CH2MgBr HC CH2CH2CH2CH3 2 5 + O 2. H , H2 ethanol ethyl n-butyl CH2CH2CH2CH3 methanoate magnesium bromide 5-nonanol (85%)
This reaction is a very important method for the synthesis of alcohols having two identical groups attached to carbon atom carrying the hydroxyl group.
5. Reduction
The hydrogenation of esters is accompanied by cleavage to yield two alcohols and is therefore, referred to as hydrogenolysis.
O hydrogenolysis RCOR' RCH2OH + R'OH ester primary alcohol alcohol
Hydrogenolysis is normally carried over a combination of copper-chromium oxides known as copper chromite at high temperature and pressure.
O
H2 (200 atm) COCH 2CH3 CH2OH + CH3CH2OH copper chromite 523 K ethanol cyclohexylmethanol ethyl cyclohexanecarboxylate (97%)
The reduction proceeds in two stages. The first stage involves the formation of on aldehydes which rapidly undergoes reduction to the primary alcohol.
O O H RC OR' 2 RCH + R'OH catalyst aldehyde alcohol (slow) H2, catalyst (fast) cleavage of this bond on first RCH 2OH hydrogenation (a primary alcohol)
Esters are also reduced by sodium in alcohol. This is a method of long standing and is known as Bouveault-Blanc reduction. It was the common laboratory method before the discovery of lithium aluminium hydride.
O Na CH (CH ) COCH CH CH (CH ) CH OH + CH CH OH 3 2 10 2 3 ethanol 3 2 10 2 3 2 ethanol ethyl dodecanoate dodecanol 48 (65-75%)
Unit 10 Carboxylic Acid Derivatives
Reduction of esters using lithium aluminium hydride requires only 0.5 equivalent of LiAIH4 because only two of the hydrogens are used per ester function.
O 1. LiAlH , ether 4 CH CH CH OH + CH OH 2 CH3CH2COCH3 + 3 2 2 3 2. H2O, H methanol methyl propanoate 1-propanol (92%) This reduction proceeds via the formation of an aldehyde which reacts rapidly with LiAlH4 and yields an alcohol after acidification.
6. Formation of Enolates You will study about the Claisen When esters are treated with strong bases at low temperature, ester enolates condensation are formed. This involves the abstraction of the acidic hydrogen from the involving ester carbon atom next to the ester function. enolates to yield 3- ketoesters such as O O ethyl 3-oxobutanoate Unit 8 of BCHET-147 RCHCOR ' + :B RCH C + H B OR' Course. H enolate ester ester Having studied the reactions of esters, answer the following SAQ. SAQ 4
Write the expected product(s) of the reaction between ethyl benzoate and the following reagents:
+ a) H , H2O, heat b) NaOH, H2O c) Aqueous NH3, heat d) i) LiAlH4
+ ii) H3O e) i) excess CH3CH2CH2MgBr
+ ii) H2O, H
10.7 AMIDES
The amides can be named by replacing the -ic or -oic acid suffix of the carboxylic acid with the suffix amide.
O O
CH3C-OH CH3C-NH 2 acetic acid acetamide 49
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
Thus, acetamide has the IUPAC name ethanamide. Having done this, can you give common and IUPAC names for the following amide?
O
HC NH2 These are formamide and methanamide, respectively. The IUPAC name for an amide is derived by appending the suffix amide to the parent hydrocarbon with the final e dropped. Thus, amides can be named as alkanamides.
Amides are also named as substituted carboxamides. According to this system, in
O R C NH 2 the name of the group R followed by the suffix carboamide gives the name of the amide; examples being benzenecarboxamide and cylcopentanecarboxamide.
O
O C NH2
C NH2
e cyclopentanecarboxamide benzenecarboxamid Amides can be classified as primary, secondary or tertiary according to the degree of substitution on the amide nitrogen.
RCONH 2 RCONHR ' RCONR 'R" ide a tertiary amide a primary amide a seconday am In the case of secondary and tertiary amides, the symbol N- must precede the name of each different group attached to the nitrogen.
O O H C CH3 C N CH CH NH 2 3 CH3
N-ethyl-N-methyl-methanamide N-phenylethanamide Cyclic amides are called lactams. The systematic names of some lactams are given below:
O
1 NH 2 1 2 O N H 2-azacyclopentanone 2-azacyclohexanone 50 (-butyrolactam) (-valerolactam)
Unit 10 Carboxylic Acid Derivatives
10.7.1 Preparation of Amides
The formation of amides from carboxylic acid halides, anhydrides and esters was discussed in Secs. 10.4.2, 10.5.2 and 10.6.2, respectively. General reactions of the above carboxylic acid derivatives with amines (or ammonia) can be represented as shown below:
O O H O
RCL + R'2NH CR L RCNR '2 + HL amide conjugate carboxylic acid amine NR' derivative 2 acid of the tetrahedral leaving intermediate group
You will recall that two molar equivalents of amine are required in case of carboxylic acid halide and anhydride.
O O + 2 R2NH + R'CCl R'CNR 2 + R2NHCl amine carboxylic amide hydrochloride acid halide salt of amine
O O O O + 2 R2NH + R'COCR ' R'CNR 2 + R2NH OCR' amine carboxylic acid amide carboxylate anhydride salt of amine But in the case of esters, no acid is formed. Therefore, the reaction is carried out using the ester and the amine in 1:1 molar ratio to yield the amide.
O O
R2NH + R'COCH3 R'CNR2 + CH3OH methyl ester amine amide methanol In addition to the above methods, amides can also be prepared from ammonium carboxylates. Ammonium carboxylates are prepared by the reaction of ammonia with carboxylic acids.
O O
: R C OH + NH3 R C ONH 4 an ammonium carboxylate When dry ammonium carboxylates are heated, dehydration takes place to yield an amide.
O O heat RCO NH4 R C NH2 + H2O (solid) A similar sequence of reactions can be carried out using amines instead of ammonia. 51
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
This is a poor method of preparing amides. A much better method is to convert the acid into the acid halide which can yield the amide as discussed above in sub-Sec. 10.4.2.
You may recall from sub-Sec. 18.4.1, Unit 18, Block 4 of BCHCT-135 Course
that ketones react with RNH2 compounds to yield condensation products.
When azanol (hydroxylamine, HO–NH2) reacts with ketones, an oxime is obtained as shown below. R R OH H+ C O + H2N OH CN H2O R' R' oxime Oximes on heating with a strong acid rearrange to give amides.
R OH O H2SO4 ' CN heat R C NHR R' amide oxime This reaction is known as Beckmann rearrangement. 10.7.2 Reactions of Amides
The reactions of amides are listed in Table 10.8.
Table 10.8: Reactions of Amides
1. Hydrolysis O O + + H2O R C NR' + H3O R C OH + R' NH2
R" R" O O H O R C NR' + OH 2 RCO + R' NH
R" R" R, R, and/or R may be H 2. Reduction
O
LiAlH4 R C NR'2 RCH 2NR'2 or B H 2 6 or 3. Dehydration O P O R CNH 2 5 RCN 2 heat (H O) 2 4. Hofmann rearrangement
O Br2, NaOH, H2O R C NH RNH + O C O 52 2 2
Unit 10 Carboxylic Acid Derivatives
Amides are the least reactive amongst the carboxylic acid derivatives discussed so far. Therefore, their nucleophilic addition-elimination requires relatively vigorous reaction conditions. Let us understand this by taking the example of hydrolysis.
1. Hydrolysis of Amides
Hydrolysis of amides occurs only on prolonged heating in strongly acidic or basic aqueous conditions to yield an amine and a carboxylic acid.
O R' O R' hydrolysis RC N + H2O RCOH + N H R" R" amide water acid amine When the hydrolysis is carried out in acidic medium, the amine obtained is protonated to yield ammonium ion, i.e.,
O O H + + R CNR' 2 + H3O RCOH + R' N R' H an ammonium ion But when the hydrolysis is done using a base, the carboxylic acid obtained is deprotonated to give a carboxylate ion, as shown below:
O O R'
H2O RCNR' 2 + OH RCO + R' N amide hydroxide carboxylate H amine ion ion The following examples illustrate hydrolysis of amides.
O
CH3CH2CHCNH 2 CH3CH2CHCOOH
SO + H2O, H2 4 + NH4HSO4 heat
2-phenylbutanamide 2-phenylbutannoic amonium acid (88-90%) hydrogen sulphate
O O OH, H2O, CH3CH2CH2CNHCH 3 CH3CH2CH2CO + CH3NH2 H+, H O 2 O CH3CH2CH2COH + CH 3NH3 butanoic acid (87%) 53
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
2. Reduction of Amides
Amides can be converted to the corresponding amines on reduction with lithium aluminum hydride. O
1. LiAlH4 R C NR' 2 + RCH 2NR' 2 2. H O, H amide 2 amine O
1. LiAlH4, ether (CH3)2CHCH 2CH2CN(CH 2CH3)2 + (CH3)2CHCH 2CH2CH2N(CH 2CH3)2 2. H2O, H N, N-diethyl-4-methylpentanamide N, N-diethyl-4-methylpentanamine
(85%)
Diborane, B2H6, may also be used for the reduction of amides. O
B2H6 (CH ) CCN(CH ) (CH ) CCH N(CH ) 3 3 3 2 THF 3 3 2 3 2 N, N, 2,2-tetramethylpropanamide N, N, 2,2-tetramethyl propanamine (79%)
3. Dehydration of Amides
Amides can be dehydrated, using a number of dehydrating agents like P2O5 or ethanoic anhydride, to the corresponding nitriles. For example, O P2O5 CH3CH2 C CH3CH2C N H2O NH2 propanenitrile (55-70%) propanamide 4. Hofmann Rearrangement
O
Primary amides RCNH 2 , on treatment with bromine in basic solution undergo an interesting reaction to yield amines.
O Br2,NaOH, H 2O
RCNH 2 RNH 2 + O C O The overall reaction appears as if the carbonyl group is expelled from the amide to give an amine with one carbon atom less than the amide. O
Br2, NaOH, H2O (CH3)3CCH 2CNH 2 (CH3)3CCH 2NH2 3,3-dimethylbutanamide 2,2-dimethylpropanamine (94%) The reaction proceeds via the following steps.
Step 1: Amidate formation
:O: :O:
: : :
RCNH + :OH RCNH + HOH :
: 54 2 :
Unit 10 Carboxylic Acid Derivatives
Step 2: Halogenation
:O: :O:
: : : : :
RCNH + : X X: RCNH + : X:
:
: :
: X: : Step 3: N-Halo amidate formation
:O: O
: : : :
RCNH + :OH RCN X : + HOH
:
: : N-haloamidate : X: : Step 4: Halide elimination
:O: :O:
:
: : :
RCN X: RCN + : X:
:
:
: :
Step 5: Rearrangement
:O:
: :
C OC N
: : R N: R an isocyanate Step 6: Hydrolysis to carbamic acid and decomposition
:O:
H
: : : H O
N OC 2 OHCN RNH + CO
: : 2 2 R R amine After studying the chemistry of amides, answer the following SAQ.
SAQ 5
Outline the synthesis of propanamine, CH3CH2CH2NH2 from butanoic acid.
10.8 SUMMARY
In this Unit, you have studied that
the functional derivatives of carboxylic acids are those derivatives which are formed by substitution of -OH of the carboxy group and can be hydrolysed to yield carboxy acids.
various carboxylic acid derivatives can be arranged according to their reactivity in the following order:
carboxylic acid > carboxylic acid > esters > amides
halides anhydrides 55
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
the electrophilic reactivity of the carbonyl carbon in carboxylic acid derivatives is weakened by good electron-donating substituents. This also explains the increasing basicity in the series: carboxylic acid halides < anhydrides < esters < amides.
carboxylic acid derivatives undergo nucleophilic substitution reactions by addition-elimination mechanism.
one carboxylic acid derivative can be converted into another by nucleophilic addition-elimination and the more reactive derivative can be converted to the less reactive derivative easily but the reverse requires special conditions and suitable catalysts.
carboxylic acid halides undergo nucleophilic substitution reactions with water, carboxylic acids, alcohols, amines and organometallic reagents.
reactions of carboxylic acid anhydrides with water, alcohol and amines are similar to carboxylic acid halides.
esters can be obtained from carboxylic acids, carboxylic acid halides and carboxylic acids anhydrides by reaction with alcohols.
esters can be hydrolysed both in acidic and basic conditions and they react with amines to yield amides and alcohols. Their catalytic
hydrogenation, reaction with Grignard reagents and LiAlH4, yield alcohols.
Amides can be prepared by the reaction of ammonia or amines with carboxylic acid halides, anhydrides and esters. Their important reactions include hydrolysis, reduction, dehydration and Hofmann rearrangement.
10.9 TERMINAL QUESTIONS
1. Benzenecarboxylic anhydride can be prepared by adding one molar equivalent of water to two molar equivalents of benzenecarbonyl chloride, i.e.,
O O O C Cl CO C 2 + H2O
benzenecarbonyl chloride benzenecarboxylic anhydride
Explain how this reaction takes place.
2. Write products of the following reactions
O
CH OH a) O 3 373 K
O butanedioic anhydride 56
Unit 10 Carboxylic Acid Derivatives O
H3C 2 NH b) O 3
H3C O 3,3-dimethylpentanedioic anhydride
3. The compound
O O
CH3COCH 2CHCH2CH2CH2OCCH 3
OCCH 3 O on hydrolysis in acidic medium gave a compound of molecular formula
C5H12O3. Write the structure of this compound. What other compound is formed in this reaction?
4. Suggest suitable starting materials for the following reactions.
O ? + ? (CH ) CHCNH a) 3 2 2 an acid halide
O ? + ? CH CNHCH b) 3 3 an acid anhydride
O ? + ? HCN(CH ) c) 3 2 a methyl ester
5. Write the products of hydrolysis of the following compounds. O CH2CH3 C N a) CH2CH3
CH 2 O C CH2 b) CH2 N H CH2 O HOOCCH NHC CHNH c) 2 2 CH2
CH3 57
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds 10.10 ANSWERS
Self-Assessment Questions
1. a) Amide
b) Alkanoyl halides
2. a) H2O
O
b) + CH3CO Na OH
c)
d) (CH3)2NH
e) (CH3CH2)2Cd or LiCu(CH3CH2)2
f) LiAl[OC(CH3)3]3H or H2, Pd–BaSO4, Quinoline
3. a) O
2 CH3COH ethanoic acid
O O
b) CH3CH2COCH 3 + HOCCH2CH3
methyl propanoic propanoate acid
O O
CNHCH(CH 3)2 HOC c) +
N-(1-methylethyl)- cyclohexanecarboxylic cyclohexanecarboxamide acid
4. O
C O CH2CH3
ethyl benzoate
COOH + H , H2O, heat a) + CH3CH2OH 58
Unit 10 Carboxylic Acid Derivatives O
+ C O Na NaOH, H O b) 2 + C2H5OH
O
C NH2 aq. NH , heat c) 3 + CH3CH2OH
CH2OH 1. LiAlH4 d) + + CH3CH2OH 2. H2O, H
1. excess CH3CH2CH2MgBr 2. H O, H+ 2 e) OH
C CH2CH2CH2CH3 + CH3CH2OH CH2CH2CH2CH3
O Br , NaOH 1. SOCl2 2 5. CH3CH2CH2COOH CH3CH2CH2CNH 2 CH3CH2CH2NH2 2. NH3 H2O butanoic acid butanamide propanamine
Terminal Questions
1. Benzenecarbonyl chloride on reaction with water yields benzenecarboxylic acid which further reacts with second molar equivalent of benzenecarbonyl chloride to yield benezenecarboxylic anhydride.
O O
2. a) HOCCH 2CH2COCH 3
O CH3 O + b) NH4 OCCH 2CCH 2CNH 2 CH 3
3. HOH 2CCHCH 2CH2CH2OH OH
(molecular formula C5H12O3)
The other product obtained is ethanoic acid. O
4. a) (CH3)2CHCCl and 2 NH3 O O
b) CH3COCCH3 and 2 CH3NH2 59
Block 3 Carboxylic Acids, their Derivatives and Amino Compounds
O
c) HCOCH3 and HN(CH3)2 O 5. a) COH
+ NH(CH 2CH3)2
b) H2NCH2CH2CH2CH2COOH c) HOOCCH 2 NH2 + HOOCCH NH2
CH2
CH3
60