N benzyl

The barriers to rotation about the N-C bond have been determined b dynamic nuclear magnetic resonance for A -isopropyl (80. 81). propanoic acid (74). A -ethyl (82). N-benzyl. and A -neopentyl substituents (82). Selected values of these barriers are given in Tables VII-6 and VII-7. 

Cm.OROCARBONSANDCm.OROHYDROCARBONS - BENZYL Cm ORIDE, BENZAL Cm ORIDE AND BENZOTRICm ORIDE] (Vol 6) N-Benzyl-2-cyano-l,2-dihydroquinoline [13721-17-0]... 

Adenine, 9-y3-D-arabinofuranosyl-occurrence, 5, 602 as pharmaceutical, 1, 160 Adenine, N -benzoyl-glycosylation, 5, 536 Adenine, 1-benzyl-benzylation, 5, 530 Adenine, 3-benzyl-benzylation, 5, 530 N NMR, 5, 515 synthesis, 5, 594 Adenine, 6-benzyl- N NMR, 5, 515 Adenine, 7-benzyl-benzylation, 5, 530 Adenine, N -benzyl-methylation, 5, 530 occurrence, 5, 602... 

Imidazo[4,5-6]pyridine, 5-acetamido-7-chloro-3-jS-D-ribofuranosyl-N-benzylation, 5, 619... 

Pyridinium salts, l-aryl-4-methoxy-2,6-dimethyl-synthesis, 3, 762 Pyridinium salts, N-aryloxy-rearrangements, 2, 354 Pyridinium salts, 1-benzyl-covalent amination, 2, 239 Pyridinium salts, N-benzyl-reactions... 

Pyrimidin-4-amine, N-benzyl-2-chloro-dehalogenation, 3, 91 Pyrimidin-4-amine, 2-benzyIthio-6-chloro-reactions... 

Thieno[2,3-d ]pyrimidin-4(3 H) -one, 3-methyl-synthesis, 4, 1017 Thieno[2,3-d ]pyrimidin-4-ones synthesis, 4, 1017, 1018, 1022 Thieno[2,3-6]pyrrole, 5-aryl-synthesis, 6, 1009 Thieno[2,3-6]pyrrole, N-benzyl- H NMR, 4, 1042 UV spectra, 4, 1044 Thieno[2,3-c]pyrrole, N-ethyl-UV spectra, 4, 1044 Thieno[3,2-6]pyrrole, 5-aryl-synthesis, 6, 1009 Thieno[3,2-6]pyrrole, N-benzyl- H NMR, 4, 1041, 1042 lithiation, 4, 1051 UV spectra, 4, 1044 Thieno[3,2-6]pyrrole, 2,3-dihydro-desulfurization, 6, 984 oxidation, 6, 981... 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Crystd from aqueous EtOH. For N-benzyl chloride see entry in Chapter 6. 

The synthesis of 1 was accomplished by stirring N-benzyldiethanolamine in the presence of NaH/DMF and tetraethylene glycol ditosylate at 25 °C for 48 h. After chromatography, N-benzyl-7 was isolated in 25% yield as a yellow oil. Debenzylation (Hj/Pd)... 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

On the basis of this successful application of 23d, this catalyst was applied in a series of reactions (Scheme 6.22). For all eight reactions of nitrones 1 and alkenes 19 in which 23d was applied as the catalyst, diastereoselectivities >90% de were observed, and most remarkably >90% ee is obtained for all reactions involving a nitrone with an aromatic substituent whereas reactions with N-benzyl and N-alkyl nitrones led to lower enantioselectivities [65]. 

A solution was made of N-benzyl-L-tyrosine (5.7 g, 20 mmols) and N-methylmorphollne (2,04 g, 20 mmols) In 60 ml of THF, at -15°C, and to it was added ethyl chloroformate (2,08 g, 20 mmols), After 12 minutes, p-aminobenzoic acid (2.74 g, 20 mmols) dissolved in 25 ml of THF and 0.38 g of p-toluenesulfonic acid (2 mmols) were added, and the temperature allowed to rise to 5°C. After 2 hours and forty minutes, the mixture was poured into 1 liter of 0,1 N cold HCI, stirred one-half hour, filtered and dried, to give 8,7 g, MP 192°-223°C. The product was recrystallized from 90 ml methanol and 40 ml water, to give 6 g (74%) of product, N-benzoyl-L-tyrosyl-p-amlnobenzoic acid, MP 240°-242°C. 

The benzene was distilled from the extract and the residue of d-N-methyl-N-benzyl-)3-phenyl-isopropylamine was distilled at reduced pressure. The thus obtained free base, distilling at 127°C at a pressure of 0.2 mm of mercury and having an np of 1.5515, was dissolved in ethyl acetate and a molar equivalent of ethanolic hydrogen chloride was added thereto. Anhydrous ether was added to the mixture and d-N-methyl-N-benzyl-)3-phenylisopropyl-amine hydrochloride precipitated from the reaction mixture as an oil which was crystallized from ethyl acetate to give crystals melting at 129° to 130°C. 

First, dimethylamino-2-phenoxyethane was made by reacting chloro-2-phenoxyethane with dimethylamine. Benzyl chloride (10 grams) was then added to a solution of 1-dimethylamino-2-phenoxyethane (12.3 grams) in acetone (35 ml). The mixture warmed spontaneously and N-benzyl-N,N-dimethyl-N-2-phenoxyethylammonium chloride slowly crystallized. After 24 hours, this solid was filtered off, washed with fresh acetone and dried immediately in vacuo, MP 135°-136°C. 

Hydroxy-3-naphthoic acid (1.BB grams) was dissolved in hot aqueous sodium hydroxide (0.5N 20 ml) and the resulting solution was slowly added to a solution of N-benzyl-N,N-dimethyl-N-2-phenoxyethylammonium chloride (2.9 grams) in water (5 ml). A gum separated at first but it solidified on scratching. After the addition was complete, the mixture was allowed to stand at room temperature for 2 hours and then filtered. The residue was washed with water and dried in vacuo to give N-benzyl-N,N-dimethyl-N-2-phenoxyethylammonium 2-hydroxy-3-naphthoate, MP 170°-171°C. 

To a stirred solution of 5.7 g (0.02 m) of 4-benzyloxy-2-ureidoacetophenone in 100 ml of chloroform is added 3.2 g (0.02 m) of bromine. The mixture is stirred at room temperature for about 45 minutes and the solution is concentrated in vacuo at 25°-30°C. The amorphous residue (hydrobromide selt of 4-benzyloxy-a-bromo-3-ureidoacetophenone) is dissolved in 80 ml of acetonitrile and 98 g (0.06 m) of N-benzyl-N-t-butylamine is added. The mixture is stirred and refluxed for 1.5 hours, then it is cooled toOt in an ice bath. Crystalline N-benzyl-N-t-butylamine hydrobromide is filtered. The filtrate is acidified with ethereal hydrogen chloride. The semicrystalline product is filtered after diluting the mixture with a large excess of ether. Trituration of the product with 60 ml of cold ethanol gives 4-banzyloxy-Of-( N-benzyl-N-t-butylamino)-3-ureidoacetophenone hydrochloride, MP 200°-221°C (decomposition). 

Chemical Name 2,6-Oimethyl-4-(3-nitrophenyl)-3-methoxycarbonyl-1 /4-dihydropyridine-5-carboxylic acld-2(N-benzyl-N-methylamino)ethyl ester hydrochloride... 

Acetoacetic acid N-benzyl-N-methyiaminoethyl ester -Aminocrotonic acid methyl ester m-Nitrobenzaldehyde... 

A mixture of 4.98 g of acetoacetic acid N-benzyl-N-methylaminoethyl ester, 2.3 g of aminocrotonic acid methyl ester, and 3 g of m-nitrobenzaldehyde was stirred for 6 hours at 100°C in an oil bath. The reaction mixture was subjected to a silica gel column chromatography (diameter 4 cm and height 25 cm) and then eluted with a 20 1 mixture of chloroform and acetone. The effluent containing the subject product was concentrated and checked by thin layer chromatography. The powdery product thus obtained was dissolved in acetone and after adjusting the solution with an ethanol solution saturated with hydrogen chloride to pH 1 -2, the solution was concentrated to provide 2 g of 2,6-dimethyl-4-(3 -nitrophenyl)-1,4-dihydropyridlne-3,5-dicarboxylic acid 3-methylester-5- -(N-benzyl-N-methylamino)ethyl ester hydrochloride. The product thus obtained was then crystallized from an acetone mixture, melting point 136°Cto 140°C (decomposed). 

Step 4 A solution of 20 grams of the above amino alcohol is dissolved in 50 ml of dry chloroform and treated with dry hydrogen chloride until acid. Then a solution of 9 grams of thionyi chloride in 50 ml of dry chloroform is added and the reaction mixture is heated on a water bath at 50°-60°C for 2 hours. Most of the chloroform is removed by distillation under reduced pressure. Addition of ether to the residue causes the product to crystallize. After recrystallization from a mixture of alcohol and ether, the N-(phenoxyisopropyl)-N-benzyl-0-chloroethylamine hydrochloride melts at 137.5°-140°C. 

The mixture is heated until the temperature reaches 140°C, the ether distilling out, then finally heated under reduced pressure (150 mm Hg) for A hour. The mass is taken up with dilute hydrochloric acid and ether, neutralized at pH 7, and a-benzylaminopyridine separates. After making alkaline, using excess of potash, it is extracted with benzene, dried and distilled. The product thereby obtained, dimethylamino-ethyl-N-benzyl-N-a-aminopyr-idine, boils at 135° to 190°C/1.7 mm, according to U.S. Patent 2,502,151. 

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