Debenzylation, of benzyl ethers

Other examples of debenzylation of benzyl ethers on the frequently used Pd/C catalysts are summarized in Table 4.2. 

Figure 5 depicts the hydrogen uptake curves of debenzylation of benzyl ether on 3Pd/CPSl at 30,40 and 50°C. Assuming zero order reaction, the rate constants at 30, 40 and 50°C are 4.7 X 10 9.2 X 10 and 1.58 X lO moles/min./g catalyst respectively. Product analyses show that there is no selectivity change under these reaction tenyeratures, and hydrogenation of the benzene ring was not observed. 

Figure 5 Hydrogen uptake curves for debenzylation of benzyl ether on 3%Pd/CPSl at different temperatures. Other reaction conditions 1.1 bar hydrogen pressure, 2000 rpm, 20 g benzyl ether diluted to 100 ml with THF, 0.333 g 3%Pd/CPSl catalyst.

Benzyl esters of carboxylic acids are frequently used in organic synthesis for the protection of carboxyl groups. The C-O bond in benzyl esters can be cleaved more easily than the corresponding benzyl ether bond. The hydrogenolysis of an ester leads to carboxylic acid and toluene. Examples of debenzylation of benzyl esters of carboxylic acids on Pd/C catalysts are summarized in Table 4.4. 

Similar utilization for cleavage of benzyl alcohols, ethers and esters has made this method the preferred one where regioselectivity is required, but for allylic cleavage double bond isomerization becomes a problem. A number of benzylic ethers and alcohols (equation 13), and benzhydric ethers and acetals (equation 14) have been cleaved in relatively high yield using cyclohexene in the presence of AlCb. Mild conditions of cleavage are frequently required for debenzylation of carbohydrates and a number of protected carbohydrates have been cleaved with formic acid as donor (equation 15). ... 

Debenzylation. MgBr2 effects a selective cleavage of benzyl ethers of o-hydroxy phenones. 

The use of DDQ in dichloromethane/water for the cleavage of primary allyl and benzyl ethers has been reported, and anhydrous ferric chloride in dichloromethane debenzylated sugar benzyl ethers, without affecting acetals, benzoates, phthalimides and glycosidic linkages. 4-Methoxy- and 3,4-dimethoxy-benzyl ethers have been deprotected with catalyic DDQ and ferric chloride. The combination of Ti(0 Pr)4 and BuMgCl has been used to cleave allyl ethers to the corresponding alcohols. 

Preceding hydrogenolysis of benzyl ethers s. 11, 66 with simultaneous N-debenzylation s. 12, 51 1,3-Diols from 3-keto-l,2-en-l-ols... 

Debenzylation of benzylamines and benzyl ethers is carried out with ammonium formate[l 13,l 14]. Hydrosilanes are also used for debenzylation[l I5. ... 

Figure 3 Debenzylation of a pharmaceutical intermediate containing benzyl ether and aromatic chlorine.

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. 

Hydroxythiadiazole and neat trimethyl orthoacetate showed a 20 80 ratio of N- versus O-alkylation products by H NMR <2002EJ01763>. The acidic hydroxyl group of thiadiazole 130 can be selectively protected as the benzyl ether 113 (Equation 22) <2004TL5441>. Nonhydrogenative debenzylation of the bisbenzyl thiadiazole 116 was achieved with boron tribromide to afford the bis-l,2,5-thiadiazole 131 (Equation 23) <2004TL5441>. 

With the nitrogen atom well protected as the cyclic carbamate 105, all attempts to open the 1,6-anhydro ring under acidic conditions failed owing to the lability of the two allylic benzyl ethers present in the molecule. However, it was possible to debenzylate 105 with lithium in ammonia to form the new cyclic carbamate 108 and acetylation then gave 109. 

Most of the early syntheses of psilocin and psilocybin employ the O-benzyl ether as a protecting group. This provides more stability to the chemical intermediates, but also requires the additional step of reductive debenzylation. The flow chart of this process is conversion of 4-hydroxyindole to 4-benzyloxyindole via the sodium salt, with benzyl chloride the conversion of this with oxalyl chloride to 4-benzyloxyindole-3-glyoxylchloride the conversion of this to 4-benzyloxy-3-(N,N-dimethyl-glyoxamide with anhydrous dimethylamine the conversion of this to... 

Cyclization of the bis-epoxides 123 (mixtures of diastereomers) with benzylamine afforded the azepanes 124 in a preferential 1-endo-tet methodology (Equation 17) <1995JOC5958> however, with the corresponding 3,4-benzyl ethers of the bis-epoxides rather than the // / -acetonide protecting group, no cyclization to six-membered ting species was observed. The azepanes 124 were then converted in two steps to the amino sugar hydrochloride salts 126 via the N-debenzylated intermediates 125 (Scheme 16). 

Hydroxy-8,9-methylenedioxyphenanthridine, [10]. The method developed by Kessar et al. [11] for phenanthridines and related compounds was applied to the synthesis [10] of 3-hydroxy-8,9-methylenedioxyphenanthridine (22) (Scheme 5). Thus, the benzylidene aniline 23, prepared from 6-chloropiperonal and 3-benzyloxyaniline, was reduced to the secondary amine 24. Treatment of 24 with excess lithium diisopropylamide furnished, on work-up, the benzyl ethers 25 (22%) and 26 (6%) respectively. Catalytic debenzylation of the former generated 22. 

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