Benzyl derivatives hydrogenation

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

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. 

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). 

Treatment of ethyl 2,7-di-/ert-butylthiepin-4-carboxylate (24) with 3-chloroperoxybenzoic acid at — 78 °C results in the benzene derivative 25 only, and no sulfur-oxidized products 80 however, the stable 2,7-di-ter/-butylthiepin (26) can be oxidized with 0-benzyl 00-hydrogen monoper-oxycarbonate at — 78 °C to give the corresponding S-oxide 27, which was monitored by HNMR spectroscopy at — 40°C. At —15 C, sulfoxide 27 was converted, via extrusion of sulfur monoxide, with a half-life of 5.5 hours to the benzene derivative 28.87 The oxidation reaction of 26 with excess of the monoperoxycarbonate did not proceed to the S,S-dioxide, even though the parent thiepin 1,1-dioxide is known to be stable at room temperature.15... 

Several benzyl derivatives exhibit potentially hazardous properties arising from the activation by the adjacent phenyl group, either of the substituent or of a hydrogen atom. Halides, in particular, are prone to autocatalytic Friedel Crafts polymerisation if the aromatic nucleus is not deactivated by electron withdrawing substituents. 

For the A-methyl compounds 107 and 108 the syn anti inversion is faster AF = 14 kcal mole ) the NMR spectrum of each compound at 22° consists of three time-averaged signals for the vinylic, bridgehead, and A-methyl hydrogen atoms, each of which broadens and splits into two as the temperature is lowered. The major component of the mixture was tentatively suggested to be the anti invertomer for each of 107 and 108. Similar results were described for the N-benzyl derivatives 102 and 123. ... 

Hydrogenation over rhodium (5% on alumina) in acetic acid at room temperature and 3-4 atm of hydrogen was successfully used for reduction of benzene rings in compounds containing functions which would be hydrogen-olyzed over platinum or palladium catalyst [390], Palladium at low temperature usually does not reduce benzene rings and is therefore suited for hydro-genolysis of benzyl derivatives (pp. 150, 151). 

The method is not adaptable for phosphonodiamides having acidic hydrogens such as the a-allyl or a-benzyl derivatives. Due to the relatively harsh conditions of the substitution reaction (140 °C), elimination is the dominating process in these cases. This drawback can be circumvented by using another approach, in which the chloromethyl derivative of 1 is transformed via the azido compound 6 into the iminomethyldithiolane 7 (70- 75% yield)92. 

For sodium cyanoborohydride — hydrogen chloride reagent the direction of the reductive opening of the dioxolane acetals obeys the same rule, it depends on the stereochemistry at the asymetric, benzylidene acetal carbon [168, 169]. Methyl exo-2,3 4,6-di-0-benzylidene-a-D-mannopyranoside is cleaved in oxolane solution to give 50 % of the 3,6-di-O-benzyl derivative, which is also the major product in the reaction of methyl 3-0-benzyl-4,6-0-benzylidene-a-D-mannopyranoside. The 2-O-benzyl isomer (20) was cleaved nonselectively, indicating again the effect of the bulk of the C-3 substituent [169]. A compatibility of this reagent, as well as of borane — tri-... 

O-Deacetylation of J58 and successive O-benzylation gave the tri-O-benzyl derivative (159), [a]p +36.7° (chloroform). When 159 was hydrolyzed with aqueous acetic acid and subsequently hydrogenated with sodium borohydride, the compound (160), [a] + 4.4° (chloroform), was obtained. Periodic acid oxidation of 160 and reduction with sodium borohydride afforded 4,6-di-0-acetyl-l,2,3-tri-0-benzyl-pseudo-(3-L-allopyr-anose (161), [a] —40.2° (chloroform), after acetylation. Catalytic hydrogenolysis of 161 and successive acetylation gave pseudo-P-L-allopyranose pentaacetate (162), m.p. 135-136 °C, [a] f +3.7° (chloroform) [36]. (Scheme 25). 

Japanese chemists (96) have reported the chemical conversion of kobusine into the chloramine (95). The latter was treated with sodium methoxide in methanol to afford compound 96 in which the bridged C-14-C-20 bond was cleaved. Reduction of kobusine with sodium in n-propanol, followed by acetylation afforded compound 88. Treatment of 88 with excess phenyl chloroformate in refluxing o-dichlorobenzene gave the carbamate 89. The latter was hydrogenated over Pd-C in methanol to obtain compound 90 in 94% yield. Further hydrogenation of 90 in the presence of platinum in acidic solution gave 91. Acidic hydrolysis of 91 afforded compound 92. The carbamate 92 was converted to the benzyl derivative 93 by treating with... 

Hydrogenation of 38b under mild conditions yields the dimeric yttrium hydrides 44b (Eq. 17). The benzyl derivatives 39b can also be used as starting materials, but the rate of hydrogenolysis is considerably slower due to the presence of coordinated THF. The dimeric hydrides are extremely sensitive towards oxygen and moisture but thermally quite stable [27, 55, 65, 66]. 

The preparation of N-benzyl derivatives by replacement of the acidic hydrogen atom of the benzimidazole ring has been described by Moore and Link20 and by Huebner, Lohmar, Dimler, Moore, and Link.22 Pertinent data on these and other miscellaneous derivatives will be found in Table I of this review. 

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