Substitution reactions hydrogenolysis

Surprisingly, the bulkiness of the 4-substituent on the phenol ring did not have a significant influence on the cis/trans ratio of the formed alkylcyclohexylamines at the same reaction conditions, whereas a bulky substituent in 2-position made the reduction of the intermediate cyclohexanone more difficult. After one hour of reaction time, 2-tert. butylcyclohexanone was the only product formed. Prolonged reaction led to the slow formation of 2-alkylcyclo-hexanols. In the case of the methoxy-substituted phenol, hydrogenolysis of the ether group took place. 

Sulfur-containing pyrimidines are frequent intermediates in substitution reactions. Several methods exist for exchange of the thiol group with hydrogen, either by hydrogenolysis, especially by the use of Raney Nickel, or by oxidative desulfurization which involves a sulfinic acid intermediate. Oxidation may also lead to a sulfonic acid. The 2- and 4-/6-thiones are considerably more stable to air oxidation than 5-thiol derivatives. Disulfides are conveniently formed by oxidation with bromine. Oxidation with chlorine at low temperature can be used to prepare sulfonyl chlorides. These reactions have been summarized [Pg.187]

Cyclopropane and Cyclopropene Adds.— The undesirable physiological properties of cyclopropene acids such as malvalic acid (20 R = H) and sterculic acid (21 R = H) and their presence, albeit in small amount, in cottonseed oil has aroused interest in these compounds. The content of cyclopropene acids is reduced by heating with palladium catalysts, though not with nickel or platinum catalysts. Palladium treatment cleaves the cyclopropene ring and produces methyl- and methylene-substituted acids. Hydrogenolysis of cyclopropane acids is reported to give methyl-substituted fatty acids which can be identified by their g.l.c. behaviour on capillary columns. The chemical reactions of cyclopropene acids (malvalic and sterculic) shown in Scheme 5 have been reported. ... 

The monoimines of the substituted -diketones formed can usually be isolated but sometimes they undergo further reactions. Thus, 5-substituted 3-chloroisoxazoles yield / -ketonitriles, and hydrogenation of 5-acylaminoisoxazoles (174) is a general method of synthesizing 4-hydroxypyrimidines (175). 2 3,214 One should note the increased stability of the isoxazole ring in styrylisoxazoles toward reduction. No hydrogenolysis of the 0—N... 

Hydrogenolysis of methylenediisoxazoles have been useful in preparing substituted resorcinols and aminophenols (7). The isoxazole annelation reaction (71,89,90,91,103) is well suited to the synthesis of steroids and other complex molecules. 

Palladium-catalyzed aminations of aryl halides is now a well-documented process [86-88], Heo et al. showed that amino-substituted 2-pyridones 54 and 55 can be prepared in a two-step procedure via a microwave-assisted Buchwald-Hartwig amination reaction of 5- or 6-bromo-2-benzyloxypyri-dines 50 and 51 followed by a hydrogenolysis of the benzyl ether 52 and 53, as outlined in Fig. 9 [89]. The actual microwave-assisted Buchwald-Hartwig coupling was not performed directly at the 2-pyridone scaffold, but instead at the intermediate pyridine. Initially, the reaction was performed at 150 °C for 10 min with Pd2(dba)3 as the palladium source, which provided both the desired amino-pyridines (65% yield) as well as the debrominated pyridine. After improving the conditions, the best temperature and time to use proved... 

Cyclopropanes can be cleaved by catalytic hydrogenolysis. Among the catalysts used have been Ni, Pd, and Pt. The reaction can often be run under mild condi-tions." ° Certain cyclopropane rings, especially cyclopropyl ketones and aryl-substituted cyclopropanes," can be reductively cleaved by an alkali metal (generally Na or Li) in liquid anunonia." Similar reduction has been accomplished photo-chemically in the presence of LiC104." ... 

As seen in the retro-synthetic Scheme 5.3, intermediate 15 is useful for both routes. The choice of benzyl protection group was made based on the robust stability of benzyl phenol ethers toward most reactions and several possible avenues to remove it, although it was reported from Medicinal Chemistry that benzyl group removal via hydrogenolysis posed challenges in this compound. The choice of iodide substitution was born out of the known high reactivity of iodides in the Ullmann-type coupling reaction with alcohols and the robust stability of aryl iodides in many other common reactions. 

Hydrogenolysis of Cyclic Nitronates Since hydrogenolysis of substituted cyclic nitronates afford polyfunctional derivatives, this reaction is of interest for the development of a methodology of organic synthesis. However, this process has been poorly studied. 

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