N- Benzyl group

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Both the 0-benzyl and N-benzyl groups were removed using 10% Pd/C (0.09 mol Pd/mol compound) and concentrated HCl in EtOH under hydrogen for 14 hours (Scheme 4.87).335... 

O-Benzyl and N-benzyl groups were also removed in MeOH using 10% Pd/ C (0.19 mol Pd/mol compound) at 3 atm hydrogen for 24 hours.336... 

Molecular modelling (AMI) indicated that the bridge hetero-atom separations in 137 were as follows N-N = 8A, N-0 = 4.6A, 0-0 = 2.7 A. In addition, the invertomer preference of the N-benzyl groups position them over the aromatic rings thereby ensuring that the lone pairs on the heteroatoms are concentrated within the cavity section of the molecule. 

The ion pairing between the enolate of 5 and the catalyst should make the asymmetric induction sensitive to the electronic effects of substituents on the N-benzyl group. A Hammett plot of log ee/eeQ vs the substituent constant o of the para N-benzyl substituted catalysts (R = CH3O, CH3 H, F, Cl, CF3) gave a reaction constant of p - 0.21 + 0.02 with ee s in the range of 60% to 92% demonstrating that substituents with increasing... 

Very few publications are available on the reactivity of substituents attached to the ring nitrogen and sulfur atoms of thiadiazole. The N-benzyl group in (107) can be removed with AICI3 to give the cyanamide (108) and the antiviral compound (109) on further treatment with base <92MI 410-01 >. 

Heterocycles containing an NH group, such as pyrroles, indoles, imidazoles, triazoles, etc., can be linked to insoluble supports as N-alkyl, N-aryl, or N-acyl derivatives (Table 3.29). The optimal choice depends mainly on the NH acidity of the heterocycle in question. Increasing acidity will facilitate the acidolytic cleavage of N-benzyl groups and the nucleophilic cleavage of /V-acyl groups from these heterocycles. 

Two groups have developed effective immobilized Chinchona alkaloid phase transfer catalysts, with a connection to a polymer support either through the N-benzyl group or an O-benzyl group [13-15]. 

The p-methoxybenzyl group has also been recommended as an N-protecting group. In this use, it is cleaved by trifluoroacetic acid at 65°, conditions to which an N-benzyl group is stable.3... 

Clearly, there is a fine balance between [2 + 2]- and [4 + 2]-cycloaddition in the reaction of TCNE with vinylindoles. The cycloaddition of 1-methyl-3-vinyl compound and TCNE in benzene gives mainly the [4 + 2]-product, although a small amount of the [2 + 2]-adduct also appeared to be formed. In liquid sulfur dioxide this [4 + 2]-adduct completely isomerized to the [2+ 2]-product. It is probable that in the reaction between diene 205 and TCNE the transition state for [4 + 2]-cycloaddition is destabilized by the steric requirements of the bulky N-benzyl group. 

Eprosartan was developed in 1997 using a different lead-optimization from S-8308. The main structural change was not the extension of the N-benzyl group, but in order to mimic the C-terminal end of angiotensin II the 5-acetic acid group was replaced with an a-thienylacrylic acid and a 4-carboxy-substituent was introduced, as in the case of the above optimization (Fig. 5.7). 

The trihaloboranes are particularly efficacious for the deprotection of benzyl ethers, Trifluoroborane in conjunction with ethanethiol270 removes an O-benzyl in the presence of an N-benzyl group without adversely affecting an ethyl ester function.271 Trichloroborane will cleave a primary benzyl ether without causing migration of an adjacent secondary ester function [Scheme 4.146].272 In the exam-... 

Benzphetamine (6), diethylpropion (4), and phendimetrazine (7) are amphetaminelike drugs that have been available for several decades, but that are now considered second-tier agents for weight loss. These drugs produce modest reductions in body weight and are indicated for short-term use only. Benzphetamine contains a bulky N-benzyl group... 

Another route to amine ID used the isomerically-mixed 1,2-cyclopropanedicarboxylic acid 2. directly without recourse to the anhydride D. Thus, ca. one mole of crude acid 2. was treated with benzylamine at 180°C to afford a crystalline sample of impure imide D (72%). Nevertheless, when this impure material was reduced with lithium aluminum hydride, the amine D (68%) was isolated by distillation in a high state of purity. As before, catalytic hydrogenolysis of the N-benzyl group led to a quantitative yield of the bicyclic amine hydrochloride ID. In this... 

Zn, ammonium formate, MeOH or ethylene glycol, rt, 90% yield. O- and N-benzyl groups are also cleaved. "... 

Scheme 19.11 Phenoxybenzamine s (35) irreversible interaction with its targeted biological surface, namely that for treating pheochromacytoma. Note that while this is analogous to the mechanism of the nitrogen mustards displayed in Scheme 19.10, in this case the rate of formation of the aziridinium species has been attenuated by the steric features of the N-benzyl group. This feature, in turn, allows 35 to first associate with its target biological surface (A). Once bound at this intended destination, formation of an aziridinium does occur (B) and this is rapidly followed by a reaction with an endogenous nucleophile located within this immediate locale (C). Ultimately, this biological surface is selectively shut down (D).

The structure of huperzine A was confirmed by total synthesis. There are several reports on total synthesis [27]. The following described was recently accomplished by Kozikowski s group [28,29]. The monoprotected diketone, 1,4-cyclohexanedione monoethylene ketal 5-4 was used as starting material. The pyrrolidine enamine of 5-5 was heated with acrylamide followed by hydrolysis to provide an 85 15 mixture of the lactam 5-6 and 5-7. After protection of the lactam nitrogen by benzylation, dehydrogenation of the latter mixtures afforded pyridone 5-8, then hydrogenolysis of its N-benzyl group, followed by O-methylation with methyl iodide and silver carbonate which yielded methoxypyridine 5-... 

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