Pyridine reaction with benzylic

Benzyl and p-nitrobenzyl esters are usually made by classical methods such as reaction of benzyl alcohol with an acid chloride in the presence of pyridine or with a carboxylic acid in the presence of a carbodiimide (see general esterification methods). We have already shown the conversion of the cesium salt of a carboxylic acid to its benzyl ester by reaction with benzyl bromide [Scheme 6.40] ... 

Zinc Derivatives. Direct zincation of 6-bromoxazolo[4,5-b]pyridmes can be effected using activated zinc (Scheme 69). The zincated species 164 and 165 from oxazolo[4,5- ]pyridin-2(3 0-ones or 2-phenyl- or 2-benzyloxyoxazolo[4,5-b]pyridmes were used in Negishi-type coupling in a one-pot reaction with benzyl bromide for the preparation of 6-benzyl derivatives. ... 

The oxidations of benzyl alcohols and substituted mandelic acids by pyridinium chlorochromate have been described. This oxidant is a complex of Cr03,pyridine and hydrochloric acid, and is known to convert alcohols into carbonyl compounds in high yield. In the reaction with benzyl alcohol the reaction is... 

The striking effect of the catalyst is exemplified by the reaction of pregna-4, 16-diene-3,20-dione (10) with benzyl mercaptan. In the presence of piperidine only conjugate addition occurs to give (11) whereas with pyridine hydrochloride only the 3-benzyl thioenol ether (12) is formed. In the presence of p-toluenesulphonic acid both reactions take place to yield (13). 

Cyclic hydroxamic acids and V-hydroxyimides are sufficiently acidic to be (9-methylated with diazomethane, although caution is necessary because complex secondary reactions may occur. N-Hydroxyisatin (105) reacted with diazomethane in acetone to give the products of ring expansion and further methylation (131, R = H or CH3). The benzalphthalimidine system (132) could not be methylated satisfactorily with diazomethane, but the V-methoxy compound was readil3 obtained by alkylation with methyl iodide and potassium carbonate in acetone. In the pyridine series, 1-benzyl-oxy and l-allyloxy-2-pyridones were formed by thermal isomeriza-tion of the corresponding 2-alkyloxypyridine V-oxides at 100°. 

For example, the Diels-Alder reaction of A-benzyl-3-carboxamido-1,6-dihydro-pyridine (14a) andlV-benzyl-3-cyano-l,6-dihydropyridine (14b) with methyl vinyl ketone yielded isoquinuclidines 15a and 15b, respectively, which can be converted into ibogamine alkaloid (16). 

The results are consistent with the rate-determining step being addition of the aryl radical to the aromatic ring, Eq. (9). Support for this mechanism is derived from the results of three other studies (a) When A -nitrosoacetanilide is decomposed in pyridine, the benzene formed by abstraction of hydrogen from pyridine by phenyl radical accounts for only 1 part in 120 of the reaction leading to phenyl-pyridines. (b) 9,9, 10,lCK-Tetrahydro-10,10 -diphenyl-9,9 -bianthryl is formed in the reaction between phenyl radicals and anthracene, probably by the addition mechanism in Eq. (11). Adducts are also formed in the reactions of benzyl radicals with anthracene- and acridine. ... 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base 20 treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary imini urn salt 23. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

However, Baker and Nathan ° observed that the rates of reaction with pyridine of p-substituted benzyl bromides (see Reaction 10-44) were about opposite that expected from electron release by the field effect. That is, the methyl-substituted compound reacted fastest and the tert-butyl-substituted compounded reacted slowest. 

Another SBU with open metal sites is the tri-p-oxo carboxylate cluster (see Section 4.2.2 and Figure 4.2). The tri-p-oxo Fe " clusters in MIL-100 are able to catalyze Friedel-Crafts benzylation reactions [44]. The tri-p-oxo Cr " clusters of MIL-101 are active for the cyanosilylation of benzaldehyde. This reaction is a popular test reaction in the MOF Hterature as a probe for catalytic activity an example has already been given above for [Cu3(BTC)2] [15]. In fact, the very first demonstration of the catalytic potential of MOFs had aheady been given in 1994 for a two-dimensional Cd bipyridine lattice that catalyzes the cyanosilylation of aldehydes [56]. A continuation of this work in 2004 for reactions with imines showed that the hydrophobic surroundings of the framework enhance the reaction in comparison with homogeneous Cd(pyridine) complexes [57]. The activity of MIL-lOl(Cr) is much higher than that of the Cd lattices, but in subsequent reaction rans the activity decreases [58]. A MOF with two different types of open Mn sites with pores of 7 and 10 A catalyzes the cyanosilylation of aromatic aldehydes and ketones with a remarkable reactant shape selectivity. This MOF also catalyzes the more demanding Mukaiyama-aldol reaction [59]. 

The pyridine-catalysed lead tetraacetate oxidation of benzyl alcohols shows a first-order dependence in Pb(OAc)4, pyridine and benzyl alcohol concentration. An even larger primary hydrogen kinetic isotope effect of 5.26 and a Hammett p value of —1.7 led Baneijee and Shanker187 to propose that benzaldehyde is formed by the two concurrent pathways shown in Schemes 40 and 41. Scheme 40 describes the hydride transfer mechanism consistent with the negative p value. In the slow step of the reaction, labilization of the Pb—O bond resulting from the coordination of pyridine occurs as the Ca—H bond is broken. The loss of Pb(OAc)2 completes the reaction with transfer of +OAc to an anion. 

Lack of selectivity in the reaction of the /3-D-glucoside derivative with one molar equivalent of benzylthiocarbonyl chloride has also been noted 40% of the 2,3-diester and 40% of the starting material were isolated.40 Similarly, unimolar benzoylation of phenyl 4,6-0-benzylidene-/3-D-glucopyranoside gave only 9% of the 3-ester, together with 47% of the 2,3-diester.41 Acylation of benzyl 4,6-0-benzylidene-/8-D-glucopyranoside with acetic anhydride-pyridine-pyridine hydrochloride yielded,42 in contrast to the reaction with the... 

The benzyl ligand of benzylbis(dimethylglyoximato)pyridine cobalt complex has been selectively converted to 3,5-dibenzyl-l,2,4-oxadiazole by a reaction with alkyl nitrite in the presence of light (426). The reaction proceeds by the in situ formation of an oxime and a nitrile oxide (Scheme 1.44). 

The alkylation of the sp3 C-H bonds adjacent to a heteroatom becomes more practical when the chelation assistance exists in the reaction system. The ruthenium-catalyzed alkylation of the sp3, C-H bond occurs in the reaction of benzyl(3-methylpyridin-2-yl)amine with 1-hexene (Equation (30)).35 The coordination of the pyridine nitrogen to the ruthenium complex assists the C-H bond cleavage. The ruthenium-catalyzed alkylation is much improved by use of 2-propanol as a solvent 36 The reaction of 2-(2-pyrrolidyl)pyridine with ethene affords the double alkylation product (Equation (31)). 

Analogous to its reaction with carbonyl compounds (see 6.3.4), benzyltrimethyl-silane undergoes a fluoride-induced nucleophilic substitution reaction on pyridine-1-oxides and quinoline-l-oxide to form 2-benzylpyridines (>70%) and 2-benzyl-quinoline (65%), respectively [57], Allyltrimethylsilane reacts with pyridine-l-oxide to produce 2-propenylpyridine (56%). 

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