Acylation derivatives

Note. PRIMARY ALIPHATIC AMINES. The lower amines are gases or low-boiling liquids (b.ps. CHjNH, 7 CiHjNH, 17 CH,(CH2,>,NH 49 (CHg)jCHNHa, 34 ) but may be encountered in aqueous or alcoholic solution, or as their crystalline salts. They are best identified as their benzoyl, or toluene-/>-sulphonyl derivatives (c/. (C) above), and as their picrates when these are not too soluble. This applies also to benzylamine, CjHsCHjNH, b.p. 185 also to ethylenediamine, usually encountered as the hydrate, NHj (CHj)j NH2,HjO, b.p. 116 , for which a moderate excess of the reagent should be used to obtain the di-acyl derivative. (M.ps., pp. 55 55 )... 

Azlactones (anhydrides of a-acylamino acids) are formed by the condensation of aromatic aldehydes with acyl derivatives of glycine in the presence of acetic anhydride and anhydrous sodium acetate. Thus beiizaldehyde and acetyl-... 

The Lassaigne procedure for detecting nitrogen in organic compounds frequently gives unsatisfactory results with explosive compounds (diazonium salts, polynitro compounds and the like) and with certain volatile nitrogenous substances, such as bases, their acyl derivatives or their salts. These difficulties... 

It will be observed that the reaction involves two equivalents of the amine and produces, in addition to the substituted amide, an equivalent quantity of the amine hydrochloride. Acetic anhydride, on the other hand, converts the amine quantitatively into the acyl derivative, for example ... 

Acylated derivatives of 2-imino-3-alkyl-4-thiazoIines are reduced to 2-alkylimino-3-alkyl-4-thiazolines by the action of LiAlH4 (477). The acyl... 

Aminothiazolium hydroxide inner salts (2) (X = NR) are only known as N-phenyl (29) or acyl derivatives. (6. 34) or as hydrochlorides (35). 

Mercapto-imida2oliuin inner salts have been reported to rearrange under the influence of hydrochloric acid, producing S-aminothiazolium chlorides (Scheme 25) (36). Their N-acylated derivatives are obtained by cyclization of N-thiobenzoyl alkylaminoacetonitriles, effected with acyl or sulfonyl halides (Scheme 26) (34, 35). 

The 5-amino-THISs are very strong bases (35). The hydrochlorides, therefore, have not yet been deprotonized successfully. However, the decreased basicity of the N-acylated derivatives makes these readily accessible from their hydrochlorides (Scheme 28). 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

Acyl derivatives, RCO—NH—OH and HjN—O—CO—R, are named as A-hydroxy derivatives of amides and as O-acylhydroxylamines, respectively. The former may also be named as hydroxamic acids. Examples are A-hydroxyacetamide for CH3CO—NH—OH and O-acetylhydrox-ylamine for HjN—O—CO—CH3. Further substituents are denoted by prefixes with O- and/or A-locants. For example, C5H5NH—O—C2H5 would be O-ethyl-A-phenylhydroxylamine or A-ethox-ylaniline. 

Ketenes. Derivatives of the compound ketene, CH2=C=0, are named by substitutive nomenclature. For example, C4Hc,CH=C=0 is butyl ketene. An acyl derivative, such as CH3CH2—CO—CH2CH=C=0, may be named as a polyketone, l-hexene-l,4-dione. Bisketene is used for two to avoid ambiguity with diketene (dimeric ketene). 

Reaction with esters of strong acids, such as formates or oxalates, yields the acyl derivatives of ethyleneimine dimer (238,239). 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

Most derivatives of aniline are not obtained from aniline itself, but ate prepared by hydrogenation of their nitroaromatic precursors. The exceptions, for example, /V-a1ky1ani1ines, /V-ary1ani1ines, sulfonated anilines, or the A/-acyl derivatives, can be prepared from aniline and have been discussed. Nitroanilines are usually prepared by ammonolysis of the corresponding chloronitroben2ene. Special isolation methods may be requited for some derivatives if the boiling points are close and separation by distillation is not feasible. Table 6 Hsts some of the derivatives of aniline that are produced commercially. 

The resulting acetyl compound is usually hydrolyzed with aqueous alkaU to give the free amine. Other A/-acyl derivatives may be used, particularly for the less soluble succinyl and phthaloyl products. The use of -nitrobenzenesulfonyl chloride, followed by reduction of the nitro to an amino function, is much more expensive and is rarely used. A/-Acetylsulfanilyl chloride [121 -60-8] is obtained by the chlorosulfonation of acetanilide [103-84-4] which is the basic material for most of the sulfonamides. 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Bischler-ISlapieralski Reaction. This synthetic method involves the cyclodehydration of N-acyl derivatives of p-phenethjlamines (26) to... 

Acetylsucrose [63648-81-7] has been prepared in 40% yield by direct acetylation of sucrose using acetic anhydride in pyridine at 40° C (36). The 6-ester has subsequently been obtained in greater than 90% yield, by way of 4,6-cycHc orthoacetate. Other selective methods for the 6-acylated derivatives include the use of alkyl tin reagents such as dibutyl tin oxide (37) and of dibutyl stannolane derivatives (38). Selective acetylation of sucrose by an enzymic process has also been described. Treatment of sucrose with isopropenyl acetate in pyridine in the presence of Lipase P Amano gave, after chromatography, 6-0-acetylsucrose (33%) and 4/6-di-O-acetylsucrose (8%). The latter compound has been obtained in 47% yield by the prolonged treatment (39). 

Alkoxy titanium acylate derivatives coordinated with a phosphite diester (phosphonate diester) can be prepared by reaction of a tetraalkyl titanate and an equal molar amount of a carboxyUc acid, such as methacrylic acid or isostearic acid, and a phosphite or phosphonate diester, such as dibutyl hydrogen phosphite (103). These materials reduce the viscosity of a composite system, improve... 

The maridomycin complex of seven factors (40), Type II in Table 5, was obtained from culture broths of S. hjgwscopims (182—188). The principal difference from the leucomycins is a 12,13-epoxide. Confirmation of stmcture was obtained from x-ray crystallography and spectroscopy of 9-0-acyl derivatives of maridomycin III (188,189). 

Semisynthetic Derivatives. No significant improvements in activity have resulted from modifications of the 3-, 9-, 2and/01 4"-hydioxyl groups (314). 3 -0-Acyl derivatives have not been found via fermentation, but chemical acylation of the 3 -hydroxyl group yields products having good antibiotic activity and better pharmacokinetics than the patent macroHdes. Two such compounds have been developed (315,316) ... 

The enhanced activity from acylation of the 3- and 4 -hydroxyl groups of leucomycin prompted analogous studies of tylosin. Bioconversion of tylosin by S. thermotokrans yielded 3- and/or 4 -0-acyl derivatives possessing increased activity against certain resistant microorganisms and higher... 

The main type of hydrolysis reaction is that of halogenoaryl compounds to hydroxyaryl compounds, eg, the aqueous caustic hydrolysis of 0- and /)-chloronitrobenzene derivatives to nitrophenols. Another important reaction is the hydrolysis of A/-acyl derivatives back to the parent arylamine, where the acyl group is frequently used to protect the amine. 

Dimethylisoxazol-5-amine is easily acylated to its formyl derivative (697) which, on catalytic hydrogenation, undergoes ring cleavage and recyclization to yield 5,6-dimethyl-pyrimidin-4(3H)-one (698) other acyl derivatives give analogous 2-substituted pyrimidines... 

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