Benzyl hydrate

Benzylie alcohol—Benzoic alcohol—Benzyl hydrate-CiH sfCHsOH) —108—does not exist in nature, and is of interest chiefly as corresponding to two important compounds, benzoic acid and benzoic aldehyde (oil of bitter almonds). It is obtained by the action of potassium hydroxid upon oil of bitter almonds, or by slowly adding sodium amalgam to a boUing solution of benzoic acid. 

Af-benzyl or Af-propyl-N-nitrosohydrazines 28a,b at 50 C fw 6 days or nitrosated to ethyl 2-(hydroxyimino)-3-oxobutanoate 29 which was flien heated wifli benzyl-hydrate 30a OT n-propylhydrazine 30b in ethanol (87JOU1773) (Scheme 8). 

Benzylatnine. Warm an alcoholic suspension of 118-5 g. of finely-powdered benzyl phthalimide with 25 g. of 100 per cent, hydrazine hydrate (CAUTION corrosive liquid) a white, gelatinous precipitate is produced rapidly. Decompose the latter (when its formation appears complete) by heating with excess of hydrochloric acid on a steam bath. Collect the phthalyl hydrazide which separates by suction filtration, and wash it with a little water. Concentrate the filtrate by distillation to remove alcohol, cool, filter from the small amount of precipitated phthalyl hydrazide, render alkaline with excess of sodium hydroxide solution, and extract the liberated benzylamine with ether. Dry the ethereal solution with potassium hydroxide pellets, remove the solvent (compare Fig. //, 13, 4) on a water bath and finally distil the residue. Collect the benzylamine at 185-187° the 3ueld is 50 g. 

In the next step the hydrated benzylic carbonium ions (3 and 4) react with free ortho and para positions on phenols to form methylene-linked bisphenols, 2,2 (5), 2,4 (6), and 4,4 (7). 

THfluoropynivic acid hydrate reacts with //-benzylurea to give 3-benzyl-5-hydroxy-5-ttifluoromethyl-2,4 imidazoledione [107] (equation 93). 

Benzopyran-3-one, l,4-dihydro-6,7-dimethoxy-], 55, 45 Isocyamde, benzyl-, 55, 98 Isocyanide, butyl-, 55, 98 ISOCYANIDE, tert-butyl- [Isocyamde, 1,1-dimethylethyl-], 55, 96 Isocyamde, cyclohexyl-, 55, 98 Isocyamde, dodecanyl-, 55, 98 Isocyamde, ethyl, 55,98 Isocyamde, methyl, 55, 98 Isocyamde, phenyl-, 55, 98 (-)-2,3 4,6-Di-0-isopropylidene-2-keto-L-gulomc acid, hydrate [L-jcy/o-2-Hex-ulosomc acid, bis-<9-( 1 -mcthylcthyl-ldene)-], 55,80, 81 ISOXAZOl F, 3-(4-chlorophenv1)-5-(4-methoxyphenyl)-, 55, 39 Isoxazole,5 -(4-chloropheny l)-3-(4-me th-oxyphenyl)-, 55,42... 

Thus removal of water from classical rather inactive fluoride reagents such as tetrabutylammonium fluoride di- or trihydrate by silylation, e.g. in THF, is a prerequisite to the generation of such reactive benzyl, allyl, or trimethylsilyl anions. The complete or partial dehydration of tetrabutylammonium fluoride di- or trihydrate is especially simple in silylation-amination, silylation-cyanation, or analogous reactions in the presence of HMDS 2 or trimethylsilyl cyanide 18, which effect the simultaneous dehydration and activation of the employed hydrated fluoride reagent (cf, also, discussion of the dehydration of such fluoride salts in Section 13.1). For discussion and preparative applications of these and other anhydrous fluoride reagents, for example tetrabutylammonium triphenyldifluorosilicate or Zn(Bp4)2, see Section 12.4. Finally, the volatile trimethylsilyl fluoride 71 (b.p. 17 °C) will react with nucleophiles such as aqueous alkali to give trimethylsilanol 4, HMDSO 7, and alkali fluoride or with alkaline methanol to afford methoxytri-methylsilane 13 a and alkali fluoride. 

It was previously observed that with a catalytic amount of FeCls, benzylic alcohols were rapidly converted to dimeric ethers by eliminating water (Scheme 14). In the presence of an alkyne this ether is polarized by FeCls and generates an incipient benzylic carbocation. The nucleophilic attack of the alkyne moiety onto the resulting benzyl carbocation generated a stable alkenyl cation, which suffer the nucleophilic attack of water (generated in the process and/or from the hydrated... 

The oxidation by strains of Pseudomonas putida of the methyl group in arenes containing a hydroxyl group in the para position is, however, carried out by a different mechanism. The initial step is dehydrogenation to a quinone methide followed by hydration (hydroxylation) to the benzyl alcohol (Hopper 1976) (Figure 3.7). The reaction with 4-ethylphenol is partially stereospecific (Mclntire et al. 1984), and the enzymes that catalyze the first two steps are flavocytochromes (Mclntire et al. 1985). The role of formal hydroxylation in the degradation of azaarenes is discussed in the section on oxidoreductases (hydroxylases). 

Steric hindrances may also be the reason why quaternary salts of 8-alkylnarcotoline (130) were transformed during Hofmann degradation to analogous keto acids (131) (111,112) and not to the enol lactones (Scheme 24). In some cases (5,87) the keto acids and their esters have been synthesized from the corresponding enol lactones by hydration (Section III,A,2). Nornarceine (107) was prepared from JV-benzyl-(—)-a-narcotinium bromide (139, X = Br) by Hofmann degradation followed by N-debenzylation and ester hydrolysis (109). 

Figure 18 Relationship between permeability coefficients for various model drugs in a series of hydrated benzyl ester membranes of various degrees of esterification (100%, 75%, 50%) and reciprocal hydration. (Reprinted with permission from Ref. 58.)... 

Benzyl-9-phenyl-3,4-dihydro-27/,677-pyrimido[6,l-A [l,3]thiazine-6,8-(7//)-dione was prepared from 3-benzyl-6-chloro-l-(3-chloropropyl)-5-phenylpyrimidine-2,4-(17/,3//)-dione and NaSH hydrate in DMF in 27% yield <1995W035296>. 

The use of hydrazine hydrate in anhydrous methanol with 5% palladium on charcoal under an inert atmosphere gave excellent results for the reduction of l-benzyl-4-nitroimidazole (72 R1 = CH2Ph, R2 = H) with compound (71 R1 = CH2Ph, R2 = H) being isolated as its hydrochloride salt (96%) (74JMC1168). 

The commercially available form of Aspartame is hemihydrate Form II, which transforms into hemihydrate Form I when milled, and a 2.5-hydrate species is also known [57,58]. XRPD has been used to study the desolvation and ultimate decomposition of the various hydrates. When heated to 150°C, both hemihydrate forms dehydrate into the same anhydrous phase, which then cyclizes into 3-(carboxymethyl)-6-benzyl-2, 5-dioxopiperazine if heated to 200°C. The 2.5-hydrate was shown to dehydrate into hemihydrate Form II when heated to 70°C, and this product was then shown to undergo the same decomposition sequence as directly crystallized hemihydrate Form II. 

Boyd, D.R., McMordie, R.A S., Sharma, N.D., Dalton, H., Williams, P. and Jenkins, R.O., Stereospecific benzylic hydroxylation of bicyclic alkenes by Pseudomonas putida isolation of (+)-/ -l-hydroxy-l,2-dihydronaphthalene, an arene hydrate of naphthalene from metabolism of... 

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