Primary amines reactions with esters

Primary amines react with esters to yield amides RCO-7R + R"NH9 — RCONHR" + R OH. Propose a mechanism for the following reaction of an a,/3-unsaturated ester. 

Pyrrolinones are best obtained by cyclizative condensation of y-keto esters with ammonia or a primary amine (reaction 195). Alternatively, the 2-pyrrolinones may be obtained by cyclization of preformed a-keto amides as shown in reaction (196) (71CC346). Preexisting lactones (2H- or 5H-furanones) also react with amines to give pyrrolinones (reaction 197). Jones and Bean give references to specific examples of these methods as well as to more specialized examples (B-77MI30610). 

King and Gill have been studying the reaction of alkyl 2,2,2-trifluoroethanesulfonate esters (tresylates) (308) in aqueous base (pFI>9) in the presence of a primary or secondary amine. Reaction with hydroxide is foimd to be a reversible ElcB process and reaction with water is the normal sulfonic ester hydrolysis. 

Action of Hydrogen and of Ammonia.— Another reaction of aceto acetic ester should be mentioned. When hydrogen (sodium amalgam), ammonia or alkyl primary amines react with aceto acetic ester, crotonic acid (p. 173) CHs—CH = CH—COOH, or derivatives of it are obtained. The fact that crotonic acid contains a double bond seems to indicate the presence of a double bond in aceto acetic ester, and would be evidence for the enol form. 

An aqueous, green, simple, and direct synthetic procedure was reported by our group in 2009 for the synthesis of rhodanine derivatives via the three-component method, which began with the reaction of carbon disulfide, primary amines, and acetylenic esters under neutral conditions [44] to give rhodanine 50. This procedure was completely a green and eco-friendly method (Scheme 9.22). 

Another important reaction of diketene derivatives is the Hant2sch pyridine synthesis (101). This synthesis is the preparation of 1,4-dihydropyridines (14) starting either from two acetoacetic esters, which react with an aldehyde and ammonia or a primary amine or from 3-aminocrotonates and 2-alkyhdene acetoacetic esters, both diketene derivatives. Several such dihydropyridines such as nifedipine [21829-25-4] (102), nimodipine [66085-59-4] and nicardipine [55985-32-5] exhibit interesting pharmaceutical activity as vasodilators (blood vessel dilation) and antihypertensives (see Cardiovascularagents). 

Fabric Softeners, Surfactants and Bleach Activators. Mono- and bisamidoamines and their imidazoline counterparts are formed by the condensation reaction of one or two moles of a monobasic fatty acid (typically stearic or oleic) or their methyl esters with one mole of a polyamine. Imidazoline formation requires that the ethyleneamine have at least one segment in which a secondary amine group Hes adjacent to a primary amine group. These amidoamines and imidazolines form the basis for a wide range of fabric softeners, surfactants, and emulsifiers. Commonly used amines are DETA, TETA, and DMAPA, although most of the polyethylene and polypropane polyamines can be used. 

The diester (429) has been cyclized with ammonia or primary amines to give the esters (430) (72AP2), whilst the related diester (431) has likewise been converted to (432). Similar reactions starting with TV-substituted o-phenylenediamines have been used as the basis of a synthesis of deazariboflavins (433) (77TL2551). 

The carboxyl groups of amino acids undergo all the simple reactions common to this functional group. Reaction with ammonia and primary amines yields unsubstituted and substituted amides, respectively (Figure 4.9a,b). Esters... 

While mechanistically this reaction is related to the Robinson-Schopf reaction for the generation of the tropinone skeleton, it also has similarities to the Hantzsch reaction. Here the heterocyclic ring 75 is assembled by the condensation of an equivalent of acetonedicarboxylic ester 72 with 2 equivalents of aldehyde 73 in the presence of ammonia or primary amine 74. 

Preparation of the key tropine is achieved by any one of several variations on the method first developed by Robinson, which involves reaction of a primary amine with dihydroxyacetone and glyoxal. Reduction of the carbonyl group in the product (86) followed by acylation affords the aminoester (88). Transesterification with ester aldehyde 89... 

The chemistry of acid anhydrides is similar to that of acid chlorides. Although anhydrides react more slowly than acid chlorides, the kinds of reactions the two groups undergo are the same. Thus, acid anhydrides react with water to form acids, with alcohols to form esters, with amines to form amides, and with UAIH4 to form primary alcohols. Only the ester and amide forming reactions are much used, however. 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

This procedure, which is based on the work of Ishii and co-workers, affords a mild and general method for converting a wide variety of esters to primary, secondary, and tertiary amides (Table 1). While the preparation of the tertiary amide, N,N-dimethylcyclohexanecarboxamide, described here is carried out in benzene, aluminum amides derived from ammonia and a variety of primary amines have been prepared by reaction with trimethylaluminum in dichloromethane and utilized for aminolysis in this solvent. Although 1 equivalent of the dimethylaluminum amides from amines was generally sufficient for high conversion within 5-48 hours, best results were obtained when 2 equivalents of the aluminum reagent from ammonia was used. Diethyl-aluminum amides can also effect aminolysis, but with considerably slower rates. 

When the -OH of a carboxylic acid is replaced by an -NH2, the compound produced is an amide. Amides are neutral to mildly basic compounds. They can be made from acids, acid chlorides, acid anhydrides, and esters by reaction with ammonia or primary and secondary amines. The amide linkage is found in polyamide resins such as nylon. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Less is known about unequivocal reactions of the POf ion with amines. This is partly because the phosphate esters examined undergo direct SN2(P) reaction with amines via oxyphosphoranes or can at least react in the boundary area between SN1 (metaphosphate mechanism) and SN2(P)37) or because the reaction actually occurs at another part of the molecule (simple primary and secondary amines react with 2,4-dinitrophenylphosphate to give 2,4-dinitroanilines " ). 

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