Debenzylation hydrogen

In this study, three types of solvents, alcohol, ketones and alkane were used to study the effects of solvent polarity on hydrogenolysis activity. As shown in Table 4 the debenzylation (hydrogenation) reaction is favored by the use of high polarity (high dielectric constants, e) solvents. Under the same reaction conditions, methanol (with the highest dielectric constant) is the best solvent among the three alcohol solvents for N-phenylbenzylamine (NPBA) conversion. Table 4 also shows that under the same reaction conditions, using non-polar solvent cyclohexane (dielectric constant e is 2.02 at ambient temperature), results in low NPBA conversion, 27.1%. 

Catalytic debenzylation of 10-(dibenzylamino)-6-(4-rerr-butylphenyl)-3,4-dihydro-2//-pyrimido[2,l-n]isoquinoline 421 (R = PhCH2) over a 5% Pd/C catalyst under hydrogen at atmospheric pressure in acidified EtOH at ambient temperature afforded the 10-amino derivative 421 (R = H) (98JMC1050). 

Choice of catalyst and solvent allowed considerable flexibility in hydrogenation of 8. With calcium carbonate in ethanol-pyridine, the sole product was the trans isomer 9, but with barium sulfate in pure pyridine the reaction came to a virtual halt after absorption of 2 equiv of hydrogen and traws-2-[6-cyanohex-2(Z)-enyl]-3-(methoxycarbonyl)cyclopentanone (7) was obtained in 90% yield together with 10% of the dihydro compound. When palladium-on-carbon was used in ethyl acetate, a 1 1 mixture of cis and trans 9 was obtained on exhaustive hydrogenation (S6). It is noteworthy that in preparation of 7 debenzylation took precedence over double-bond saturation. 

Oxidative coupling of o-nitrotoluene gives 4,4 -dinitrodibenzyl which is reduced with hydrogen to the diamine. The diamine is pyrolyzed to give dihydrobenzazepine. This is reacted with N-(3-chloropropvl)-N-methylbenzamine to give N-benzyldesipramine. This is debenzylated by reductive cleavage and then reacted with HCI. 

The resulting solution was filtered through animal charcoal and, after addition of 2 liters of methanol, it was debenzylated by hydrogenation at 60°C over palladinized charcoal as a catalyst. After removal of the catalyst by filtration, the filtrate was concentrated by evaporation, whereupon the hydrochloride of 1-p-methoxyphenyl-2-((3-3, 5 -dihydroxyphenyl-(3-oxo)-ethylamino-propane (MP 244°C) crystaiiized out. For the purpose of demethyiation. 

A mixture of 215 parts of 1 -benzyl-4-piperidinopiperidine-4-carboxamide, 1,200 parts of isopropyl alcohol, 1,000 parts of distilled water and 1 57 parts of hydrogen chloride is debenzyl-ated under atmospheric pressure and at a temperature of about 40°C in the presence of 40 parts of a 10% palladium-on-charcoal catalyst. After the calculated amount of hydrogen is taken up, hydrogenation is stopped. The mixture is filtered and the filtrate is evaporated. 

Hydrogenation of 2-butoxy-3//-azepine (3) with palladium on charcoal and hydrogen affords 2-butoxy-4,5,6,7-tetrahydro-3f/-azepine (4),79 whereas reduction of the 2-benzyloxy derivative, under the same conditions, is accompanied by debenzylation and formation of hexahydroazepin-2-one (77% mp 67-69 C).79,241... 

Fluorodehydroxylation of 5-benzyl-5//-dibenz[f>,/]azepin-10(lli/)-one (47) with hydrogen fluoride and sulfur tetrafluoride followed by catalytic debenzylation of the product 48 provides access to 10-fluoro-5//-dibenz[ft,/]azepine (49).134... 

The synthesis is straightforward because for the preparation of the tetrapyrranc a bipyrrole can also be used as a central unit to which a benzyl 5-(acetoxymethyl)pyrrole-2-carboxylate can be attached as the terminal pyrrole rings. Debenzylation by catalytic hydrogenation then gives the desired tetrapyrrane building block 68. 

In order to select a suitable catalyst, a variety of Pd/C catalysts were screened. Table 2 shows that the dechlorinated by-product was minimized to the level less than 1% as the catalyst metal loading increased from 3% to 10%. The catalytic activity for the debenzylation reaction was examined and compared based on the rate of hydrogen uptake (Figures 1 and 2). 

Figure 3 Product distribution as a function of time for debenzylation of SM(S) on Delink io%Pd/CPS4. Parr Reactor, 25 °C, 45 psig hydrogen.

Since both hydrogen in the solution and the product A are weakly adsorbed species, equilibrium constants ka and k, are very small, which leads to KACA 1 and kh CH 1. Thus, the rate expression for the debenzylation can be simplified as a conventional Langmuir-Hinshelwood model. 

During the synthesis of tellimagrandin, debenzylation was accomplished over 10% Pd/C in dry THE The mixture was purged six times with hydrogen and stirred at room temperature under 1 atm of hydrogen for 48 hours and finally purged with argon.67... 

In some cases the hydrogenation of the double bond in an unsaturated benzyl ether is necessary without debenzylation. To hydrogenate the carbon-carbon double bond 5% Pd/C in AcOEt was used for 1.5 hours (Scheme 4.40).136 The benzyl ether-protecting group was removed over Pd(OH)2 in AcOEt for 1 hour. 

An N-benzyl-N-methyl carbonate in EtOH was hydrogenated on 10% Pd/C under 60 psi hydrogen for 20 hours. NMR analysis indicated that no deuterium scrambling had occurred during debenzylation (Scheme 4.81).328... 

N-debenzylation was achieved with Pd black in AcOH-H20 (4 1) at 50 psi hydrogen for 2-3 days. Removing of O-benzyl, N-benzyl, and N-Boc protecting groups was also achieved under these circumstances (Scheme 4.89).337... 

During the enantiospecihc total synthesis of ajmalin-related alkaloids, (-)-suaveoline and (-)-raumacline, N-debenzylation of the hydrochloride salt of the alkaloids was performed with 10% Pd/C (0.12 mol Pd/mol compound) in absolute EtOH at room temperature and 1 atm of hydrogen for 1 or 2 hours. When this catalytic debenzylation was performed, however, using 10% Pd/C (0.28 mol Pd/mol compound) in MeOH for 5 hours, N-methyl derivatives were produced in good yield (Scheme 4.91).339,340... 

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