A-substituted amide

By treatment of this oxime with phosphorus pentachloride or thionyl fhloride in ether solution, smooth conversion into benzanilide, m.p. 163°, results. The change of any oxime into a substituted amide under the conditions mentioned is usually termed the Beckmann rearrangement. The above example may be represented ... 

Hydrolysis of a substituted amide. A. With 10 per cent, sulphuric acid. Reflux 1 g. of the compound (e.g., acetanilide) with 20 ml. of 10 per cent, sulphuric acid for 1-2 hours. Distil the reaction mixture and collect 10 ml. of distillate this will contain any volatile organic acids which may be present. Cool the residue, render it alkaline with 20 per cent, sodium hydroxide solution, cool, and extract with ether. Distil off the ether and examine the ether-soluble residue for an amine. 

Acrylamide—acrylic polymers are made by free-radical polymerization of monomers containing the acryHc stmcture, where R is —H or —CH and is —NH2 or a substituted amide or the alkoxy group of an ester. 

Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

If primary or secondary amines are used, A/-substituted amides are formed. This reaction is called aminolysis. Hydra2ines yield the corresponding hydra2ides, which can then be treated with nitrous acid to form the a2ides used in the Curtius rearrangement. Hydroxylamines give hydroxamic acids. 

Primary amines (RNH2) yield A-substituted amides (R CNHR). 

In general, the Michael addition of a-substituted amide dienolates to a,/j-unsaturated esters is a method with great future potential for the diastereoselective construction of adjacent tertiary and quaternary stereogenic centers80. 

The treatment of acyl halides with ammonia or amines is a very general reaction for the preparation of amides.The reaction is highly exothermic and must be carefully controlled, usually by cooling or dilution. Ammonia gives unsubstituted amides, primary amines give A-substituted amides, and secondary amines give N,N-disubstituted amides. Arylamines can be similarly acylated. In some cases aqueous... 

The second step in this case, which is much slower than the first, is the attack of the amide nitrogen on the carboxylic carbon. Unsubstituted and A -substituted amides have been used instead of ammonia. Since the other product of this reaction is RCOOH, this is a way of hydrolyzing such amides in the absence of water. ... 

Secondary nitramides are relatively stable in highly acidic media and so their synthesis from the direct nitration of A -substituted amides with nitric acid and its mixtures is feasible. The synthesis of primary nitramides from the nitration of A -unsubstituted amides is usually not possible in acidic media, although this class of compounds have no practical value as explosives anyway. 

A substituted amide linkage between two amino acids in which the carbonyl group and/or the nitrogen is not... 

Compositions and functions of typical commercial products in the 2-alkyl-l-(2-hydroxyethyl)-2-imidazolines series are given in Table 29. 2-Alkyl-l-(2-hydroxyethyl)-2-imidazolines are used in hydrocarbon and aqueous systems as antistatic agents, corrosion inhibitors, detergents, emulsifiers, softeners, and viscosity builders. They are prepared by heating the salt of a carboxylic acid with (2-hydroxyethyl)ethylenediamine at 150—160°C to form a substituted amide 1 mol water is eliminated to form the substituted imidazoline with further heating at 180—200°C. Substituted imidazolines yield three series of cationic surfactants by ethoxylation to form more hydrophilic products quatemization with benzyl chloride, dimethyl sulfate, and other alkyl halides and oxidation with hydrogen peroxide to amine oxides. 

A new copper-catalyzed reaction involving imines, acid chlorides, and alkynes has been applied to the synthesis of propargyl amides 160 in a single operation by Arndtsen and co-workers. The same method allows the synthesis of N-carbamate-protected propargylamines [149]. a-Substituted amides 161 may also be prepared under palladium catalysis by substituting alkynes for vinyltin (Scheme 8.71) [150]. 

Iminobenzo-TA may also be obtained from A-substituted amides 77. Trifluoro derivatives 78 with fungicidal activity were obtained by a reaction... 

An amide of the form R—CO—NH2 is called a primary amide because there is only one carbon atom bonded to the amide nitrogen. An amide with an alkyl group on nitrogen (R—CO—NHR ) is called a secondary amide or an A-substituted amide. Amides with two alkyl groups on the amide nitrogen (R—CO—NR2) are called tertiary amides or /V,/V-disubstituted amides. 

Potassium fluoride can be used to introduce fluorine in the a-position of A-substituted amides via substitution of tosyloxy groups. 2-Fluoro-A-phenylacetamide (mp 76 C) and 2-fluoro-A-phenylpropanamide (mp 62 C) are prepared by heating the corresponding tosyloxy derivatives with potassium fluoride in ethylene glycol at 100 C in 54 and 63% yield, respectively. This method is especially advantageous for the synthesis of higher a-fluoro acid derivatives, because in these cases the products cannot be distilled off from the reaction mixtures and side reactions of simple ester groups with the solvent become more important. 

A number of aromatic amidines have been readily obtained by boiling a primary or secondary amine with a substituted amide in a solution of phosphorus trichloride. Several aliphatic amides undergo a similar condensation with amines and phosphorus oxychloride. An imino chloride, RC(C1)=NR, is an intermediate in this process. N-Phenylbenzarnidine, CsHsC(NHC6Hs)= NH, is obtained by the action of methanolic ammonia on... 

Diastereoselective Alkylation of Chiral Amides Derived from Ephedrine. Chiral amides derived from ephedrine are converted to the corresponding dianion. The subsequent diastereoselective alkylation with alkyl iodides affords chiral a-substituted amides with >90% de. Acid hydrolysis affords optically active a-substituted acids with 78% ee as a result of racemization in the cleavage step (eq 2). 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

Amides. The spectra of amides and A -substituted amides characteristically contain three prominent bands near 1700, 1500, and 1250 cm These bands, called, respectively, the amide I, II, and III bands, are considered to involve C=0 stretching, C—N stretching, and N—H deformation. The controversy over the assignment of these bands is summarized well by Bellamy (188), and only notable recent contributions will be mentioned. 

With this assurance concerning the nature of these absorptions, we can investigate the effect of H bond formation. After extended studies of A -substituted amides, Miyazawa e( al. (1424), summarized their assignments of the three bands. For A-methylacetamide in dilute GCh solution they assigned the bands 1700 (I), 1500 (II), and 1260 cm (III). For the pure liquid these bands are found to be shifted by values of Ar/r of +0.028 (I), -0.045 (II), and -0.031 (III). 

The effect of the H bond on Vt is shown in the IR studies by Miyazawa of A -substituted amides (1420, 1421). The paper by Miyazawa, Shimanouchi, and Mizushima (1424) summarizes their assignments for a number of these amides. Table 3-XX lists a portion of their data pertaining to vt, the out-of-plane N—deformation [which they designate as amide V or 7t(N—H)]. 

Renilla (sea pansy) luciferin (and certain of its synthetic analogues) produces a brilliant blue chemiluminescence when dissolved in organic solvents such as dimethylformamide and involves the anion of 2-acetamido-3-benzyl-5-(p-hydroxy-phenyl)pyrazine (21) (1191). 5-Hydrazino-2-hydrazinocarbonylpyrazine is effective against mycobacterium tuberculosis and m. kansasii in vitro (1098). Aminonitro-pyrazines have been claimed as useful yellow dyes for wool (1180) and tetraamino-pyrazine (1180) and A -substituted amides of 2-carboxy-3,5-bismethylamino-6-(A -methylcarbamoyl)pyrazines (1192) as fluorescent brighteners (or optical bleaching agents) for textiles. 

A -Substituted amides can be prepared by direct attack of isocyanates on... 

A-Substituted amides can be converted to A-nitrosoamides, which are more easily hydrolyzable than the orginal amide. For example, see Rull, M. Serratosa, R Vilarrasa, J. Tetrahedron Lett. 1977,4549. For another method of hydrolyzing A-substituted amides, see Flynn, D.L. Zelle, R.E. Grieco, PA. J. Org. Ghent. 1983, 48, 2424. 

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