Acetamides, trisubstituted

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Nitrolysis reactions employing l,3,5-trisubstituted-l,3,5-triazacyclohexanes have been explored as alternative routes to RDX. Some of the results are illustrated in Table 5.4 and show the difference in the efficiency of the three nitrolysis agents used, namely, absolute nitric acid, phosphorus pentoxide-nitric acid and trifluoroacetic anhydride-nitric acid. The acetamide derivative (81) (TRAT) undergoes incomplete nitrolysis on treatment with absolute nitric acid and trifluoroacetic anhydride-nitric acid to give a crude product containing some l-acetyl-3,5-dinitro-1,3,5-triazacyclohexane (TAX) (82) (Table 5.4, Entry 1) the latter can be preferentially formed in 93 % by suitably modifying the reaction conditions. Interestingly, the nitrolysis of... 

For examples of Ru-catalyzed hydrogenation of N-(3.4-dihydro-2-naphthalenyl)-acetamide see (a) Renaud. J.L., Dupau, P., Hay. A.-E.. Guingouain. M., Dixneuf P.H. and Brtmeau. C. (2003) Ruthenium-catalysed enantioselective hydrogenation of trisubstituted enamides derived from 2-tetralone and 3-chromanone Influence of substitution on the amide ai m and the aromatic ring. Adv. Synth. Catal.. 345. 230-238. 

Some reactions of 2,3,4-trisubstituted isoxazolium salts (exemplified by 70) leading to ring transformations, are summarized in Scheme 14.180 Other active methylene compounds such as ethyl acetoacetate and cyano-acetamide give analogous results to those with diethyl malonate products of base-induced ring opening by ethoxide are also obtained. When the reaction with phenylhydrazine is carried out in the presence of sodium hydroxide in ethanol the product is 71, presumably formed via the im-inoketene 72. 

TOSMIC can be converted into an A-tosylmethylimidic ester or thioester (10) which will react with an aldimine to form a 1,2,5-trisubstituted imidazole (Scheme 4.2.3). These esters (10) can be made from A-tosylmethylacetamidc (from the Mannich condensation of p-toluenesulfonic acid, formaldehyde and acetamide [10]), which is smoothly converted by P4S10 in DME into the thioamide which forms the 5-methylated imidate when treated with methyl fluorosulfonate in dichloromethane. Yields of the Al-tosylmethylimidic thioesters are good (65-93%) they are fairly stable crystalline solids which are best stored under nitrogen at —20°C. In reaction with an aldimine in the presence of sodium hydride or potassium t-butoxide (in DME -DMSO or... 

Katritzky et al. [387] have presented a synthesis of 3,4,6-trisubstituted pyrid-2-ones starting with solid support-bound acetophenone, which was deprotonated with NaOCHs to give the corresponding enolate. The latter was condensed with various benzaldehydes to give the resin-bound chalcones [388], which then can react with benzotriazolyl acetamides [389] to give 3,4,6-trisubstituted pyrid-2-ones (Scheme 104). 

Some multicomponent syntheses of trisubstituted oxazoles were described. a-Isocyano-a-alkyl(aryl)acetamides, as 131 <05S161>, was demonstrated to be a useful starting material for a three-component reaction involving isoquinoline 129 <05SL532>. A four-component synthesis was also published starting from an aldehyde, a silylamide, an acyl chloride and a terminal acetylene derivative. The overall process is a modification of a four-component synthesis of a propargylic amide 134 which can be eventually isolated <05T 11317>. 

A microwave assisted solid-phase synthesis of trisubstituted 2-(2,6-purin-9-yl)acetamides has been described <05TL2873>. New trisubstituted purin-8-ones 71 have been synthesized starting from cheap and readily available 5-bromouracil 70 <05S2227>. 

CHCHg group, and a trisubstituted double bond. An NMR examination of 0-acetylserratinidine (60) showed that it had the same structural unit as that found in ring D of 56 and it seemed probable that 0-acetylserratinidine differed from 56 in having an acetamide group at C-5 instead of a carbonyl, and this proved to be the case. Thus 56 was converted into an oxime, thence into an amine by reduction over RaNi, and finally into an acetamide by reaction with acetic anhydride. 

This type of reaction has some preparative value, especially for the preparation of trisubstituted acetamides and the amines derivable from them by Hofmann... 

Scheme 16.29. Polymer-supported synthesis of trisubstituted purin-9-yl acetamides.

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