Acylation-reduction, alkylation

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

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... 

Thiazolidine-2,4-dione, 2-dialkylamino-bisimide synthesis, 5, 129 Thiazolidine-2,4-diones IR spectroscopy, 6, 242 tautomerism, 6, 270 Thiazolidine-2,5-diones synthesis, 5, 138 Thiazolidine-4,5-diones synthesis, 5, 129 6, 316-317 Thiazolidine-2,4-dithiones tautomerism, 6, 270 Thiazolidines "C NMR, 6, 243 conformation, 6, 242, 247 dihydrothiazines from, 2, 93 hydrolysis, 6, 273 IR spectra, 6, 242 ring fission, 5, 80 synthesis, 5, 118 6, 316-321 Thiazolidines, imino-tautomerism, 6, 273 Thiazolidines, methyl-conformation, 6, 242 Thiazolidine-2-thione, 3-acyl-reduction, 1, 469 Thiazolidine-2-thione, 4-alkyl-synthesis, 6, 318... 

Incorporation of extensive branching in the side chain similarly does not decrease pharmacologic activity. Reductive alkylation of aminoalcohol, 42, with isobutyraldehyde affords the amine, 43. Acylation of the amine with benzoyl chloride probably goes initially to the amide (44). The acid catalysis used in the reaction leads to an N to 0 acyl migration to afford iso-bucaine (45). ... 

In an analogous sequence, reductive alkylation of aminoalcohol, 46, with cyclohexanone affords the secondary amine (47). Acylation with benzoyl chloride affords hexylcaine (48) in a reaction that may again involve acyl migration. 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Besides acylation and alkylation reactions, typical carbonyl reactions, such as reduction and substitution, are known. Thus, the oxo group in position 3 of 8 is attacked by sodium cyanide, resulting in the cyanohydrin in 55% yield. Subsequent dehydration with p-toluene-sulfonic acid and acetylation in position 5 gives 1-benzothiepin 12.90... 

Recent progress of basic and application studies in chitin chemistry was reviewed by Kurita (2001) with emphasis on the controlled modification reactions for the preparation of chitin derivatives. The reactions discussed include hydrolysis of main chain, deacetylation, acylation, M-phthaloylation, tosylation, alkylation, Schiff base formation, reductive alkylation, 0-carboxymethylation, N-carboxyalkylation, silylation, and graft copolymerization. For conducting modification reactions in a facile and controlled manner, some soluble chitin derivatives are convenient. Among soluble precursors, N-phthaloyl chitosan is particularly useful and made possible a series of regioselective and quantitative substitutions that was otherwise difficult. One of the important achievements based on this organosoluble precursor is the synthesis of nonnatural branched polysaccharides that have sugar branches at a specific site of the linear chitin or chitosan backbone [89]. 

Quinoxaline gave l,4-diethyl-l,2,3,4-tetrahydroquinoxaline by indirect reductive alkylation (AcOH, KBHai, <15°C, 1 h, then reflux, 6h 87% presumably by nuclear reduction, A-acylation, and further reduction of the acetyl groups ). ... 

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