Benzylpyridines oxidation

Because allyltrimethylsilane 82 or benzyltrimethylsilane 83 can be regarded as combinations of the hard trimethylsilyl cation and the soff allyl or benzyl anions, pyridine N-oxide 860 reacts with excess 82 or 83 in the presence of catalytic amounts of tetrabutylammonium fluoride di- or trihydrate in THF to give 2-allyl-or 2-benzylpyridines 948 and 950 [60]. The general reaction of silicon reagents such as 82 and 83 or of trimethylsilyl cyanide 18 with fluoride to generate allyl or... 

Reaction of pyridine N-oxide 860 with excess allyltrimethylsilane 82 affords, via 947, 2-propenylpyridine 948 in 53% yield as the only reaction product which can be isolated. Ehmination of trimethylsilanol 4 from 947 is apparently followed by fluoride-catalyzed isomerization of 2-allylpyridine into 2-propenylpyridine 948. 3-Methylpyridine-N-oxide 867 a is converted into 2-propenyl-3-methylpyridine in 69% yield. Likewise, fluoride-catalyzed addition of excess benzyltrimethylsilane 83 to 860 furnishes, via 949, 2-benzylpyridine 950 in 70% yield. The generated leaving group trimethylsilanol 4 reacts with excess allyltrimethylsilane 82 or benzyltrimethylsilane 83 in the presence of fluoride to give hexamethyldisiloxane (HMDSO) 7 and propylene or toluene, respectively [60] (Scheme 7.16). 

Interestingly, the Fischer indole synthesis does not easily proceed from acetaldehyde to afford indole. Usually, indole-2-carboxylic acid is prepared from phenylhydrazine with a pyruvate ester followed by hydrolysis. Traditional methods for decarboxylation of indole-2-carboxylic acid to form indole are not environmentally benign. They include pyrolysis or heating with copper-bronze powder, copper(I) chloride, copper chromite, copper acetate or copper(II) oxide, in for example, heat-transfer oils, glycerol, quinoline or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. 

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%). 

Hands and Katritzky (58JCSI754) compared the nitration of the phenyl and benzylpyridines and their /V-oxides. The results are shown in Table VIII. The tentative conclusion was that 2-phenylpyridine and its N-oxide nitrated as the free base, but that benzylpyridines may be nitrated as conjugate acids. However, later work has shown that, in fact, both compounds react as their conjugate acids [68JCS(B)862]. Further work has shown that the same result occurs with 4-phenyl and 4-benzylpyridines [71 JCS(B)712]. 

Hydrogenation of 2- and 4-phenyl- or -benzylpyridines usually occurs preferentially in the pyridine ring.18,27,29 In trifluoroacetic acid over platinum oxide, however, 4-phenyl- and 4-(3-phenylpropyl)pyridines gave the products hydrogenated in the benzene ring in 87 and 96% yields, respectively. The hydrogenation of 2-phenylpyridine... 

Oxidation in solution (KMn04, Cr03, etc.) gives carboxylic acid, e.g., 3-picoline nicotinic acid, or ketone, e.g., 2-benzylpyridine 2-benzoylpyridine 645. 

An interesting hydroxylation takes place, probably by an intramolecular transfer of oxygen, on irradiation of the 2-benzylpyridine N-oxide ct)mplex with boron trifluoride (equation 145) [994]. 

Flash vacuum pyrolysis at 800°C of a 2-benzylpyridine-l-oxide gives rise to a benzo [g]quinoline as the major product provided that a methyl group is present at either the 3- or the 2 -position. In the absence of such a substitutent, a pyrido[1,2-a]indole results (A. Ohsawa. T. Kawaguchi and H. Igeta, J. org. Chem., 1982, 47,... 

Flash vacuum pyrolysis of 2-benzylpyridine N-oxide (52) yields 63% of pyrido["1 > 2-a] indole (53) and 11% of 2-benzyl-... 

In an analogous reaction, 2-benzylpyridine was prepared from reaction of pyridine N-oxide and benzyltrimethylsilane in the presence of tetrabutylammonium fluoride. Substituent effects on... 

Oxidative functionalization of the benzyl position can also lead to carbonyl compounds, e.g. the dehydrogenation of picolines in the gaseous phase to the corresponding aldehydes, or the oxidation of 2-benzylpyridine to 2-benzoylpyridine. 

Kappe et al. reported a direct aerobic oxidation of 2-benzylpyridines in a gas-liquid continuous-flow regime [34]. A standard two-feed approach was used. Pressurized air was mixed with the substrate liquid phase in a simple T-shaped mixing device (Figure 23.4). The liquid phase was pumped by the use of an HPLC pump. Pressurized air was monitored by a mass flow controller. The two-phase reaction mixture was pumped through a stainless steel coil (0.8 mm inner diameter, 120 m length) and heated with a standard GC oven. Due to... 

Figure 23.4 Schematic diagram of the gas-liquid continuous-flow reactor for the direct aerobic oxidation of 2-benzylpyridines.

Benzylic Oxidation. During the preparation of 4-ethyl or 4-benzylpyridines via aromatization of dihydropyridine derivatives... 

Tonox 22 Tonox R 202-978-6 Diphenylmethane 202-979-1 2-Benzylpyridine 202-980-7 Dicyclohexylamine 202-981-2 Diphenyl oxide Marvanol Carrier ODP 202-982-8... 

III the benzylpyridines and their oxides the influence of the heterocyclic ring is much diminished. Little difference is found between the two series. It is not known whether free bases, conjugate acids or both are involved. The heterocyclic ring is even less influential in 2,2 -phenylethylpyridine264 and the change m o p ratio with nitrating medium is very small. 

Benzylpyridines can usefully be oxidized to benzoylpyridines by permanganate 132fiF, 280—Itt, 282—3 ... 

Under the conditions of the Kuhn-Roth oxidation, the picolines give only small amoimts of acetic acid presumably the methyl groups are oxidized more rapidly than the ring279. Chromic acid has been used to oxidize a benzylpyridine to a benzoylpyridine si. ... 

Oxidations of alkylpyridines to alcohols are rare. Oparina obtained the diol by oxidizing 3,5-di-isopropylpyridine with permanganate, and 2-benzylpyridine gave the alcohol with mercuric acetate , ... 

In an analogous reaction, 2-benzylpyridine was prepared from reaction of pyridine N-oxide and benzyltrimethylsilane in the presence of tetrabutylammonium fluoride. 9 Substituent effects on the base-catalysed rearrangement of N-(aryloxy)pyridinium salts have been studied. A 3-methyl group directs rearrangement to the 6-position whereas an electron-withdrawing group directs rearrangement mainly to the 2-position. With a suitable choice of substituent it is therefore possible to form tricyclic products as illustrated in Scheme 11. 

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