Chloride, benzoyl reaction with amines

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

Nitration of hydroxypropiophenone (7-1) followed by conversion of the phenol to its methyl ether by means of methyl iodide provides the intermediate (7-2) the nitro group is then reduced to the corresponding amine (7-3) by catalytic reduction. The newly introduced amine is then replaced by a nitrile group by successive conversion to the diazonium salt by means of nitrous acid followed by treatment with cuprous cyanide (7-4). Reaction with aluminum chloride removes the methyl ether to afford the ortho acylphenol (7-5). This is converted to the chromone (7-6) as above by reaction with benzoyl chloride and sodium benzoate. The nitrile is next hydrolyzed to the carboxylic acid (7-7) by means of sulfuric acid. The acid is then converted to its acid chloride by means of thionyl chloride and that treated with 2-(A -piperidyl)ethanol (7-8). There is thus obtained flavoxate (7-9) [8], a muscle relaxant whose name reflects its flavone nucleus. 

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

The procedure may be adapted for the preparation of other acyl isocyanates (i.e., dichloroacetyl, trichloroacetyl, phenyl-acetyl, diphenylacetyl, benzoyl, etc) and is generally more convenient than the reaction of acid chlorides with silver cyan-ate3 4 Acyl isocyanates react with amines, alcohols, and mer-captans to yield acyl ureas, carbamates, and thiocarbamates. 

It should be noted that aliphatic and aromatic primary and secondary amines may be distinguished from tertiary amines by their reaction with acetyl chloride, benzoyl chloride and benzenesulphonyl chloride. In the latter case a primary amine yields an alkali-soluble derivative which distinguishes it from a secondary amine when the derivative is neutral and insoluble in acid and alkali. 

Baddiley and associates232 have prepared tri-O-benzoyl-D-ribofuranosyl-amine (LXX) by treatment of tri-O-benzoyl-D-ribofuranosyl chloride (LII) with sodium azide in acetonitrile to yield the intermediate 2,3,5-tri-O-benzoyl-/S-D-ribofuranosyl azide, which was reduced catalytically to LXX. Shaw and his associates233 have prepared 5 -cyanouridine by reaction of LXVII (R = H) with LXX in ethyl acetate in the presence of triethyl-... 

The diazepinone (127) reacted with benzoyl chloride to give the A,Ar -dibenzoyl derivative137 and was brominated in acetic acid at 20°.138 Compounds 127 and 128 undergo the bis-semidine inversion when heated with 3% hydrochloric acid.117 The thione (128) is converted in high yield into the methylmercapto diazepine (126, R = SCH3) by reaction with methyl iodide in tetrahydrofuran.129 The thione does not react with amines, but the 6-methylmercapto compound on heating with amines or amine hydrochlorides gave rise to the 6-amino compounds (126, R = NR R")120 A number of these amino derivatives have exhibited some medicinal activity. With -butanol the 6-methylmercapto compound is quantitatively converted into 127.120... 

Fluoro-l-phenylpyrazole-4-carboxamides 304 have been formed by condensation of the 5-fluoro-l-phenylpyrazole-4-carboxylic acid 303 with amines (Equation 58) <2000EJ0823>. 4-Benzoyl-l-(4-nitrophenyl)-5-phenyl-l//-pyrazole-3-carboxylic acid 305 was converted via reactions of its acid chloride with alcohols or N-nucleophiles, into the corresponding ester or amide derivatives 306 (Equation 59) <2004CHE1039>. Resin-bound pyrazole-4-carboxylic... 

Acetyl derivatives of primary and secondary amines are usually solids suitable for melting point characterization and are readily prepared by reaction with acetic anhydride, even in the presence of water. Benzoyl and benzenesulfonyl derivatives are made by reaction of the amine with the appropriate acid chloride in the presence of alkali, as in Section 2 (the benzenesulfonamides of aniline and of A-methylaniline melt at 110°C and 79°C, respectively). 

We must keep in mind that ions II and III, which contain a free —NH2 or —COOH group, are in equilibrium with dipolar ion I consequently, amino acids undergo reactions characteristic of amines and carboxylic acids. As ion II is removed, by reaction with benzoyl chloride, for example, the equilibrium shifts to supply more of ion II so that eventually the amino acid is completely benzoylated. 

Benzamides (N-Bz) are formed by the reaction of amines with benzoyl chloride in pyridine or trimethylamine. The group is stable to pH 1-14, nucleophiles, organometallics (except organolithium reagents), catalytic hydrogenation, and oxidation. It is cleaved by strong acids (6N HCl, HBr) or diisobutylaluminum hydride. ... 

Delayed-action catalysts have been made successfully. Buffered amine catalysts, where the activity of the amine has been reduced by the presence of an acid, have also been used. Acidic materials can be used to retard the urethane reaction. Hydrogen chloride and benzoyl chloride have been used in combination with amine-type catalysts to control reaction rates. A small percentage of acid can increase foaming time from 2.2 to 6 minutes (20). 

Acyloxaziridines are easily obtained from compounds unsubstituted at nitrogen by reaction with acid chlorides or isocyanates. Acylation proceeds so smoothly that, in the amination of carbonyl compounds, oxaziridine compounds are obtained in better yields on addition of acid chlorides than in the absence of the acylating agent. With aliphatic aldehydes, amination does not succeed at all except in the presence of benzoyl chloride. Proof of structure comes from reduction by iodide to give the acid amide and carbonyl compound. 

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