Benzylamine reactions

The reaction (which is essentially the direct aminolysis of esters with benzylamine) proceeds readily when R is methyl or ethyl. Esters of higher alcohols should preferably be subjected to a preliminary methano-lysis by treatment with sodium methoxide in methanol ... 

Reflux a mixture of 1 g. of the ester, 3 ml. of benzylamine and 0 1 g. of powdered ammonium chloride for 1 hour in a Pyrex test-tube fltted with a short condenser. Wash the cold reaction mixture with water to remove the excess of benzylamine. If the product does not crystallise, stir it with a httle water containing a drop or two of dilute hydrochloric acid. If crystallisation does not result, some unchanged ester may be present ... 

Chapter IV. a-Chloromethylnaphthalene (IV,23) benzylamine (Gabriel synthesis) (IV,39) i r.N -dialkylanilines (from amines and trialkyl orthophosphates) (IV,42) a-naphthaldehyde (Sommelet reaction) (IV,120) a-phenyl-cinnamic acid (Perkin reaction using triethylamine) (IV,124) p-nitrostyrene (IV,129) p-bromonaphthalene and p naphthoic acid (from 2 naphthylamine-1 -sulphonic acid) (IV,62 and IV,164) diphenic acid (from phenanthrene) (IV,165). 

In the reaction of phenol and bisphenol F with hexa, nmr spectra show the transient appearance of benzoxazine intermediates after 2 h at 103°C, all the benzoxazine decomposed to the diphenyknethylene and benzylamine intermediates (15). 

A variation involves the reaction of benzylamines with glyoxal hemiacetal (168). Cyclization of the intermediate (35) with sulfuric acid produces the same isoquinoline as that obtained from the Schiff base derived from an aromatic aldehyde and aminoacetal. This method has proved especially useful for the synthesis of 1-substituted isoquinolines. 

Nearly all uses and appHcations of benzyl chloride are related to reactions of the active haUde substituent. More than two-thirds of benzyl chloride produced is used in the manufacture of benzyl butyl-phthalate, a plasticizer used extensively in vinyl flooring and other flexible poly(vinyl chloride) uses such as food packaging. Other significant uses are the manufacture of benzyl alcohol [100-51-6] and of benzyl chloride-derived quaternary ammonium compounds, each of which consumes more than 10% of the benzyl chloride produced. Smaller volume uses include the manufacture of benzyl cyanide [140-29-4], benzyl esters such as benzyl acetate [140-11-4], butyrate, cinnamate, and saUcylate, benzylamine [100-46-9], and benzyl dimethyl amine [103-83-8], and -benzylphenol [101-53-1]. In the dye industry benzyl chloride is used as an intermediate in the manufacture of triphenylmethane dyes (qv). First generation derivatives of benzyl chloride are processed further to pharmaceutical, perfume, and flavor products. 

The following reaction sequence provides a regiospecific route to 3,4-disubstituted 5-isoxazolones (328) (73ACS2802). The /3-ketoesters (325) were heated under reflux with benzylamine in benzene in the presence of molecular sieves (3 A) to give the )3 -benzylamino-a,)3-unsaturated esters (326). The latter reacted first with hydroxylamine hydrochloride in... 

A later variation of the general method, which extends the scope to 20-ketones, involves reaction of the ketone with benzylamine to give the imine, followed by conversion to the A-acetyl derivative with acetic anhydride. Although the resulting compound also has a A -double bond, it does not react sufficiently fast with peracid, and a A -double bond can not be preserved. 

Other secondary amines such as pyrrolidine, di- -butylamine, tetrahydro-quinoline, n-benzylamine, and piperidine were also found to be capable of effecting this reduction. Interestingly, morpholine does not reduce enamines as readily (47) and its acid-catalyzed reaction with norbornanone was reported (45) to give only the corresponding enamine (93), although trace amounts of the reduction product were detected when cyclohexanone was treated with morpholine under these conditions (47a). The yield of morpholine reduction product was increased by using higher temperatures. 

Modification of the Erlenmeyer reaction has been developed using imines of the carbonyl compounds, obtained with aniline," benzylamine or n-butylamine. Ivanova has also shown that an A-methylketimine is an effective reagent in the Erlenmeyer azlactone synthesis. Quantitative yield of 19 is generated by treatment of 3 equivalents of 2-phenyl-5(4ff)-oxazolone (2) (freshly prepared in benzene) with 1 equivalent of iV-methyl-diphenylmethanimine (18) in benzene. Products resulting from aminolysis (20), alkali-catalyzed hydrolysis (21), and alcoholysis (22) were also described. 

The Schlittler-Muller variation of the Pomeranz-Fritsch reaction involves reaction of diethoxyethanal 17 with benzylamine 16 to prepare the desired imine 18. Intermediate 18 is subsequently cyclised to substituted isoquinoline 19. The advantage here lies in the fact that the initial condensation can still take place between an aldehyde and an amine. 

Finally, with compounds of type 7, which have one chlorine atom and two ZR substituents, the reactions are, as expected, more frequently acid catalyzed than with compounds of type 6 e.g., the reaction with aniline in acetone is distinctly acid catalyzed. Again, reactions stiU occur, e.g., with benzylamine in tetrahydrofuran, in which autocatalysis is absent, possibly because of a combination of the marked basicity of the reagent and the low solubility of the acidic product. 

Amino-3-alkyl derivatives of474 have been prepared and found to undergo facile nucleophilic 5-substitution with methanolic hydrazine (65°, 4 hr, 75% yield), hydroxide ion (20°, 3 hr, 75% yield), or pro-panolic benzylamine (100°, 5 hr, 80% yield). The first two reactions may proceed by a ring-opening and reclosure sequence. ... 

A -methyl-5//,7//-dibenzo[d,.g][l,5]telluroazocine 65, its thiooxide 67a (X=S, R= Me) (95JA6388). The same type of reaction with benzylamine and sodium selenide gives A-benzyl-5//,7//-dibenzo[d,g][l,5]telluroazocine selenoxide 67b (X = Se, R = CH2Ph). Reaction of the tellurium dibromide 66 with sodium sulfide carried out in the absence of the primary amines affords the eight-member Te,S-containing heterocycle 5//,7//-dibenzo[d,g][l,5]telluroazocine (92CL151). 

The majority of analgesics can be classified as either central or peripheral on the basis of their mode of action. Structural characteristics usually follow the same divisions the former show some relation to the opioids while the latter can be recognized as NSAlD s. The triamino pyridine 17 is an analgesic which does not seem to belong stmcturally to either class. Reaction of substituted pyridine 13 (obtainable from 12 by nitration ) with benzylamine 14 leads to the product from replacement of the methoxyl group (15). The reaction probably proceeds by the addition elimination sequence characteristic of heterocyclic nucleophilic displacements. Reduction of the nitro group with Raney nickel gives triamine 16. Acylation of the product with ethyl chlorofor-mate produces flupirtine (17) [4]. 

Nickel in the presence of ammonia is often used for reduction of nitriles to primary amines. The reaction is done at elevated temperatures and pressures ( 100 C, 1000 psig) unless massive amounts of nickel are used. Cobalt is used similarly but mainly under even more vigorous conditions. Nitriles containing a benzylamine can be reduced over Raney nickel to an amine without hydrogenolysis of the benzyl group (7). A solution of butoxycarbonyl)-3-aminopropyl]-N-<3-cyanopropyl)benzylamine (13.6 g) in 100 ml of ethanol containing 4 g. NaOH was reduced over 3.0 g Raney nickel at 40 psig for 28 h. The yield of A/ -benzyl-Air -(f-butoxycarbonyl)s >ermidine was 95% (7). 

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