Amides acyl chlorides conversion

Acylation (Section 12 7 and Chapter 20) Reaction in which an acyl group becomes attached to some structural unit in a molecule Examples include the Fnedel-Crafts acylation and the conversion of amines to amides Acyl chloride (Sections 4 1 and 20 1) Compound of the type... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

FIGURE 20.1 Structure, reactivity, and carbonyl-group stabilization in carboxylic acid derivatives. Acyl chlorides are the most reactive, amides the least reactive. Acyl chlorides have the least stabilized carbonyl group, amides the most. Conversion of one class of compounds to another is feasible only in the direction that leads to a more stabilized carbonyl group that is, from more reactive to less reactive. 

The procedure for synthesizing sulfanilamide (a sulfa drug) is a multistep procedure as illustrated in Figure 13-50. The first step also works if you substitute an acyl chloride for the acid anhydride. The conversion of the amine to an amide converts the strong activator into a medium activator, limiting multiple attacks. The last step converts the amide back into an... 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

Carboxylic acids with strongly electron-withdrawing groups, for example trifluoro-acetic or 2,4,6-trinitrobenzoic acid [22], are readily converted into esters or amides. The products can, however, be unusually sensitive toward attack by nucleophiles and can readily undergo hydrolysis, transesterification, or transamidation. 2,4,6-Tris(trifluoromethyl)benzoic acid has been reported to undergo conversion into the acyl chloride or esters only with difficulty [23]. 

This same polyamide can be prepared by reaction of the diacyl chloride of adipic acid with hexamethylenediamine. In Section 19.6 we saw that the conversion of the salt of a carboxylic acid and an amine to an amide could be accomplished by heating but that this method was not often used in the laboratory because of the rather vigorous conditions that must be employed. However, in an industrial setting, cost is a more important factor. Because the reaction starting only with the diacid and the diamine is much less expensive than first converting the diacid to its acyl chloride, the former method is the one used to prepare nylon 6,6. 

For a carboxylic acid and an amine to form an amide, the carboxylic acid usually must be activated that is, it must be converted to a more reactive functional group. Conversion to an acyl chloride is a common way to accomplish this for normal organic reactions (see Chapter 19). However, acyl chlorides are quite reactive and do not give high enough yields in peptide synthesis because of side reactions. Therefore, milder procedures for forming the amide bond are usually employed. In one method the carboxylic acid is reacted with ethyl chloroformate (a half acyl chloride, half ester of carbonic acid) to produce an anhydride. Treatment of this anhydride with an amine results in the formation of an amide ... 

Final purification by use of metal complexes was also applied in the syntheses of the ligands XS4—H4. These ligands exclusively contain thiolate donors and were prepared by Hahn et al. (23) using 2,3-dimercaptobenzoic acid as starting material (Scheme 8). Isopropyl or benzyl protection of the thiol functions, conversion into the acyl chlorides, reaction with a,oo-diamines, and deprotection of the sulfur atoms enabled the connection of two 1,2-benzene-dithiol units via carboxylic acid amide bonds. 

Cyanuric chloride has been used for the preparation of acyl chlorides, amides, and peptides. Conversion of cyanuric chloride into 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) leads to a reagent that upon reaction with carboxylic acids produces the highly reactive 2-acyloxy-4,6-dimethoxy-l,3,5-triazines.P l The resulting active ester is a powerful acylating agent for alcohols and amines. The activation is performed in presence of a base, preferentially NMM, which leads to intermediate formation of 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 7)P l (Scheme 5). This addition product is readily prepared from the commercially available CDMT (6) and NMM in THF and can be stored as solid compound in the cold.P P l It offers the advantage that it can be used in a one-... 

Sarcosinate specialty surfactants are currently made by acylation of naturally occurring amino acids with an acyl chloride. The use of a secondary amide for amidocarbonylation has been reported to give poor yields of amido acid since the corresponding oxazolone intermediate cannot be formed. Lin has demonstrated, however, that the amidocarbonylation of A-methylamine gives excellent yields of A-acyl sarcosinates (eq. (11)) when conducted in the presence of dicobalt octacarbonyl at 120°C with CO/H2 = 3 1. Sarcosinate selectivity is typically 95 %, at 92 % A-methylamine conversion. 

Primary phosphorothiosulphenamides may be acylated, and with sodium ethoxide they are converted into trialkyl phosphorothionates. Other reactions of phosphorothiosulphenamides include the loss of sulphur upon treatment with sodium, and translocation of the amino-function when treated with thiophosphoryl halides. Treatment of the acyl chloride (71) with ethyleneimine gives an amide which undergoes ready conversion into the isocyanate (72). ... 

Later, Venkataraman and Wagle <1979TL3037> reported the use of TCT as a useful reagent for the conversion of carboxylic acids into chlorides, esters, amides, and peptides the authors proposed the formation of the acyl chloride as shown in Scheme 44. 

Phenyl-1,4-benzoxazepin-5-one (36) was readily acylated with mesyl and benzenesulfonyl chlorides to give the corresponding IV-acylated derivatives. Conversion of the amide to thione (37) was also carried out by the use of Lawesson s reagent (Scheme 14) <93AP(326)73>. 

Carboxylic acids can be converted to the corresponding acyl chlorides, which react with an amine containing chromophore. A few methods have been developed for conversion of acids to acyl chlorides. Hoffman and Liao [107] used a mixture of triphenylphosphine and carbon tetrachloride or polystyryldiphenylphosphine to prepare acyl chlorides of fatty acids. The reaction was carried out at 80 °C for 5 min. The intermediate acyl chlorides were then converted to amides with p-nitroaniline or p-melhoxyaniline. Thionyl chloride [108] and oxalyl chloride [109] were also applied to prepare acyl chloride. The conversion with oxalyl chloride was quantitative in 30 min at 70 °C. The commonly used amines were 1-naphthylamine [109] and p-chloroaniline [110]. The final derivatives were separated by RP-HPLC with either gradient [108] or isocratic elution [109,110]. 

Often the best synthetic route to an anhydride, an ester, or an amide is synthesis of an acyl chloride from the carboxylic acid and then conversion of the acyl chloride to the desired acyl derivative. 

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