Benzyl derivatives

Enantioselective enolate alkylation can be done using chiral auxiliaries. (See Section 2.6 of Part A to review the role of chiral auxiliaries in control of reaction stereochemistry.) The most frequently used are the A-acyloxazolidinones.89 The 4-isopropyl and 4-benzyl derivatives, which can be obtained from valine and phenylalanine, respectively, and the c -4-methyl-5-phenyl derivatives are readily available. Another useful auxiliary is the 4-phenyl derivative.90... 

Thermolysis in benzyl alcohol of 4-diazopyrazole 22b gave the corresponding 4-benzyl derivative [60CI(L)659]. The reaction goes through the... 

Benzyl-2,4,6-triphenyl-4//-thiopyran (2451) reacts with perchloric acid with loss of the 4-benzyl group to afford perchlorate 404.236 A similar elimination of the substituents was found for 4-benzyl derivatives 253.3<8 The reported conversion of 4,4-dichloro-4//-thiopyran (336b) to perchlorate 408, involving the loss of a 4-chlorine,325 is not an oxidation process. Similar transformations are also reported.349... 

Hemolytic benzylation of pyridazine yielded only the 4-benzyl derivative in acid solution, and similarly benzoylation gave mainly the 4-benzoyl and... 

Alkyl-3,5-diamino-2/f-l,2,6-thiadiazine 1,1-dioxides (130) with benzyl bromides in the presence of sodium hydroxide or sodium carbonate undergo regioselective benzylation to give the 4-benzyl derivatives (131) in 43-63% yield (Equation (10)) <91AF264>. In contrast, 5-amino-2-benzyl-4H-... 

Benzyl-derived quaternary ammonium compounds are used widely as cationic surface-active agents and as germicides, fungicides, and sanitizers. Benzyl alcohol is used in a wide spectmm of appHcations including pharmaceuticals and perfumes, as a solvent, and as a textile dye assistant. 

Porcine liver esterase (PLE) gives excellent enantioselectivity with both dimethyl 3-methylglutarate [19013-37-7] (lb) and malonate (2b) diester. It is apparent from Table 1 that the enzyme s selectivity strongly depends on the size of the alkyl group in the 2-position. The hydrolysis of ethyl derivative (2c) gives the S-enantiomer with 75% ee whereas the hydrolysis of heptyl derivative (2d) results in the R-monoester with 90% ee. Chymotrypsin [9004-07-3] (CT) does not discriminate glutarates that have small substituents in the 3-position well. However, when hydroxyl is replaced by the much bulkier benzyl derivative (Ic), enantioselectivity improves significantly. 

The methylation of N-methyl derivatives of maleic hydrazide gives in general O-alkylated products. The opposite results are obtained with benzyl halides as alkylating agents. In this case the O-benzyl derivative (71) is formed, which is then further benzylated to the lV,0-dibenzyl derivative (72). When ethyl chloroacetate is used, the direction of alkylation is dependent on pH. At pH above 8, O-alkylation occurs at pH below 8, N-alkylation takes place exclusively in neutral and acidic solutions only IV-alkylated products are formed. 

NBS, CH3CN, H2O, 62-90% yield.The POM group has been selectively removed in the presence of an ethoxy ethyl ether, TBDMS ether, benzyl ether, p-methoxybenzyl ether, an acetate, and an allyl ether. Because the hydrolysis of a pentenyl 2-acetoxyglycoside was so much slower than a pentenyl 2-benzyloxyglycoside, the 2-benzyl derivative could be cleaved selectively in the presence of the 2-acetoxy derivative. The POM group is stable to 75% AcOH, but is cleaved by 5% HCl. 

S-Benzyl and substituted S-benzyl derivatives, readily cleaved with sodium/ammonia, are the most frequently used thioethers. n-Alkyl thioethers are difficult to cleave and have not been used as protective groups. Alkoxymethyl or alkylthio-... 

A number of 5-sulfenylthiocarbonates have been prepared to protect thiols. A benzyl derivative, R =CH2Ph, is stable to trifluoroacetic acid (25°, 1 h) and provides satisfactory protection during peptide syntheses a r-butyl derivative, R = r-Bu, is too labile in base to provide protection. A methyl derivative, R =CH3, has... 

Benzyl carbamates substituted with one or more halogens are much more stable to acidic hydrolysis than are the unsubstituted benzyl carbamates.For example, the 2,4-dichlorobenzyl carbamate is 80 times more stable to acid than is the simple benzyl derivative. Halobenzyl carbamates can also be cleaved by hydrogenolysis with Pd-C. The following halobeni yl carbamates have been found to be useful when increased acid stability is required. 

Phosphinamides are stable to catalytic hydrogenation, used to cleave benzyl-derived protective groups, and to hydrazine. The rate of hydrolysis of phosphin-... 

Cl3SiH, Et3N, CH2CI2,4-48 h, 25-80°, 80-95% yield. Primary, secondary, tertiary, allylic, propargylic, or benzylic derivatives are cleaved by this method. 

Phosphinamides are stable to catalytic hydrogenation, used to cleave benzyl-derived protective groups, and to hydrazine. The rate of hydrolysis of phosphinamides is a function of the steric and electronic factors around the phosphorus. This derivative has largely been used for the protection of amino acids and occurs few, if any, times in the general synthetic literature. 

According to IR-spectroscopic studies, 3-aminoindazole 48 (R = H) and its A -benzyl derivative exist exclusively in the amino forms 48 [76AHC(S1), p. 424],... 

Infrared and NMR spectra show that for the A-benzyl derivative the mercapto tautomer 173a (R = CHaPh) is preferred in chloroform solution, while in the solid this compound exists as the thione 173b [76AHC(S1), p. 395]. 

Drozd and co-workers described cyclization of A-benzyl derivative 285, which takes place without any signs of possible rearrangement providing besides 1,4-dibenzylpiperazine (286) also very low yields of dihydrobenzoxazine derivative 287 (Eq. 27) (77ZOR396). 

Aryl-5-oxo-l,2,3,5-tetrahydropyrido[l,2,3-ife]quinoxaline-6-carboxa-mides were prepared from 1-benzyl derivatives by catalytic hydrogenation over 10% Pd/C (01MIP12). 

Thus, the 2-methyl derivative of the imidazopyrazinone (above) dissolved in DMSO spontaneously emits blue light (A.max 450 nm) in the presence of air (Goto, 1968), like the 2-benzyl derivative (Amax 475 nm), the 2-methyl-6(p-hydroxyphenyl) derivative (MCLA 7max 468 nm), and coelenterazine (Amax 465 nm) under similar conditions (Fig. 5.3). The comparison of the luminescence spectra of these compounds shows that the 6-position substituent has little influence on the luminescence spectrum of coelenterazine derivatives, despite the apparent conjugation between the 6-phenyl ring and the imidazopyrazinone ring in the structures of MCLA and coelenterazine. 

Stable HHTs such as the A -benzyl derivative 22, when reacted with neat diethyl phosphite under fairly forcing conditions, gave the desired a-aminomethylphosphonate... 

Total synthesis of (+)-validamycins A and B starting from a common synthetic intermediate was elaborated by the following sequence. Tetra-(9-benzyl-(-l-)-valienamine (370), derived from 211, and the di-O-benzyl derivative (371) of the epoxide were coupled in 2-propanol to produce the protected dicarba compound (374), the structure of which was confirmed by conversion into (-1-)-validoxylamine B nonaacetate. Concurrently, compound 372 was glycosylated and the product oxidized with a peroxy acid, to afford a mixture of products from which the desired epoxide (373) was obtained in 70% yield. Coupling of 370 with 373 in 2-propanol at 120° afforded two carba-trisaccharides, and the major product (47%) was depro-tected and characterized as the dodecaacetate of validamycin B. The pro-... 

Benzyl derivatives of (1 6)-a-D-glucan, (l->6)-a-D-mannan, and (l-> 6)-a-D-galactan have been studied in 1,4-dioxane. These derivatives have complex and interesting c.d. spectra due to the ww transition of the chromophore with resolved vibrational structure. However, a conformational interpretation of these interesting spectra is not possible at this time. 

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