Debenzylation hydrogen bromide

Purine 9-oxides on the other hand are best made from imidazole precursors. Thus 9-hydroxy-8-methylxanthine (368) and hypoxanthine (369) have been most conveniently obtained by cyclization of 5-amino-l-benzyloxy-2-methylimidazole-4-carboxamide (370) with carbonate or formate esters, respectively, and debenzylation of the intermediate benzyloxy derivatives with hydrogen bromide in acetic acid (Scheme 156) (72JOC1867). 

Hydrogen bromide Ring closure of acetals with preferential O-debenzylation Quinolizinium ring... 

Similarly Klotzer [24-26] has used the same two ethers of hydroxyurea for the preparation of iV-alkoxy and A-hydroxy derivatives of uracil, barbituric acid, cytosine, thymine, and 5-fluorouracil by condensation reactions catalyzed with sodium ethoxide. Thus, for example, the reaction of N-benzyloxyurea with ethyl cyanacetate gave l-benzyloxy-6-aminouracil which was debenzylated by heating it with hydrogen bromide in acetic acid [24]. In syntheses of 1- and 3-hydroxycytosine [24] and of l-hydroxy-5-fluorouracil the O-benzyl protective group was removed by hydrogenolysis in presence of palladium [25, 26]. 

Also obtained by debenzylation of 4-(benzyloxy)-3,5-dimethoxyacetophenone by means of a cold saturated solution of hydrogen bromide in acetic acid (52%) [3097]. 

Loperamide Loperamide, l-(4-chlorophenyl)-4-hydroxy-iV,iV-dimethyl-a,a-diphenyl-l-piperidinebutyramide (3.1.55), proposed here as an analgesic, is synthesized by the alkylation of 4-(4-chlorophenyl)-4-hydroxypiperidine (3.1.50) using iV,A-dimethyl(3,3-diphenyltetrahydro-2-furylidene)ammonium bromide (3.1.54) in the presence of a base. The 4-(4-chlorophenyl)-4-hydroxypiperidine (3.1.50) is synthesized by reacting l-benzylpiperidine-4-one (3.1.48) with 4-chlorophenylmagnesiumbromide, followed by debenzylation of the product (3.1.49) by hydrogenation using a palladium on carbon catalyst. 

In addition, stereoselective synthesis of solenopsin A has been reported by four research groups. An approach utilizing the stereoselective reductive de-cyanation (596) starts with aminonitrile 229, prepared from 2-picoline. It was selectively hydrogenated in the presence of Pd-C, followed by alkylation with undecyl bromide, affording 231. Reductive decyanation of 231 with NaBH4 in MeOH led to predominant (8 2) formation of the trans isomer (232) which was then debenzylated to ( )-solenopsin A (Id). The cis product (Ic) was in turn prepared by treatment of 231 with sodium in liquid ammonia followed by de-benzylation (Scheme 10). 

The third synthetic route reported by Husson and co-workers 140) is as follows Amino nitrile 472 obtained from the ketal (471) was converted to the 2,6-dialkylpiperidine (473) by catalytic hydrogenation followed by alkylation with lithium diisopropylamide and pentyl bromide. Refluxing a solution of 473 in methanol containing hydrochloric acid led to the formation of 9-benzyladaline (475) in 90% yield. Debenzylation of 475 gave d/-adaline (107) in nearly quantitative yield (Scheme 59) 140). 

The chiral phase-transfer catalysis of le was further applied to the facile synthesis of L-Dopa ester and its analogue, which usually have been prepared by either asymmetric hydrogenation of eneamides or enzymatic processes, and tested as potential drugs for the treatment of Parkinson s disease. Phase-transfer-catalyzed alkylation of 2 with the requisite benzyl bromide 35a in toluene-50% KOH aqueous solution proceeded smoothly at 0 °C under the influence of (R,R)-le to furnish fully protected L-Dopa tert-butyl ester this was subsequently hydrolyzed to afford the corresponding amino ester 36a in 81% yield with 98% ee. Debenzylation of 36a under... 

After debenzylation (Pd-C, cyclohexene) of the hypercores (e.g., 25) by transfer hydrogenation, they were treated with aryl branched, benzyl ether dendrons (Scheme 5.6) that were prepared by similar iterative transformations,1271 i.e., benzylic bromination and phenolic O-alkylation (See Section 5.4.2). Thus, hexaphenol core 27 was reacted with six equivalents of the benzylic bromide building block 28 to give the benzyloxy terminated dendrimer 29. Key features of these dendrimers include cores with flexible alkyl spacers and a three-directional, quaternary carbon branching center. 

Baneijee et al.66 have developed an alternative synthesis of the compound (129) whose utility in synthesis of Mansonone F (120) has been reported by Suh and collaborators.65 This is described in Scheme 13. Tetralone (127) was reduced with sodium borohydride to alcohol which on alkylation with benzyl chloride produced benzyl derivative (132). Its conversion to (133) was attempted by treatment with boron tribromide in dichloromethane. C ompound (133) (characterized b y m ass s pectroscopy) was obtained in poor yield. The major product was the diol (134), whose structure was confirmed by spectral data. It indicates that the demethylation was accompanied by debenzylation. Treatment of diol (134) with triethyl orthoformate and aluminium chloride afforded aldehyde (135) which was subjected to catalytic hydrogenation to produce compound (136). It was transformed to ketone (137) by oxidation and then made to react with methylmagnesium bromide in ether. The resulting tertiary alcohol on heating with p-toluenesulfonic acid in toluene for 24 hr produced the naphthalene (129) in 78% yield. 

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