Some reactions of 1‐lithio‐2‐<i>n</i>‐butyl‐1,2‐dihydropyridine. VI. Synthesis of β‐substituted pyridines

Knaus, Edward E.; Ondrus, T. A.; Giam, C. S.

doi:10.1002/jhet.5570130420

Cited by 18 publications

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“…The isolation of 5c, which results from reaction of 5a with deuterium oxide, represents the first example of proton abstraction from C-4 in any of our studies involving pyridines and organolithium reagents (2,3,7,8). Abstraction of the C-4 rather than the C-2 proton of 4 may be explained in view of the known ortho-directing influence of a sulfur atom since dibenzothiophene is easily metalated by n-butyllithium to give 12 (10,ll).…”

Section: R Ementioning

confidence: 80%

“…The utility of 2-lithio-1,3-dithianes (9) as organolithium reagents (5) is dependent on this stabilizing effect and at least one report (6) suggests the possibility of n: bonding between the sulfur and the bridgehead carbanions of 10. Although 2,5-dihydropyridines have been postulated as intermediates in the synthesis of 2,5-disubstituted pyridines their instability does not permit isolation (3,7,8). The stable 2,5-dihydropyridine 11 was recently obtained from reaction of N-lithio-2-methyl-l,2-dihydropyridine with phenyl disulfide (9).…”

Section: R Ementioning

confidence: 99%

See 1 more Smart Citation

Some reactions of 10-methyl-10H-pyrido[3,2-b][1,4]benzothiazine-n-butyllithium adduct with electrophiles

Pasutto¹,

Knaus²

1978

Can. J. Chem.

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FRANK M. PASUTTO and EDWARD E. KNAUS. Can. J. Cheni. 56,2365Cheni. 56, (1978. Reaction of 10-methyl-IOH-pyrido[3,2-b][l,4]benzothiazine (4) with tz-butyllithium affords a mixture of the C-4 proton abstraction product 50 and 2-tz-butyl-4a-lithio-lO-methyl-2,4a-dihydropyridyl[3,2-b][l,4]benzothiazine 6a which results froni nucleophilic addition at the C-2 position. Treatment of 5a and 6a with deuterium oxide gave the deuterated products 5c and 6c in a ratio of 1 :4.4 whereas reaction with diethyl chlorophosphate afforded a mixture of the 4-substituted product 5d, 4a-ethyl derivative 6e, oxidation product 7 as well as the Nsubstituted-l,2-dihydropyridyl derivative 13. The stability of the 4a-lithio-2,4a-dihydropyridyl adduct 6a is attributed to the ability of sulfur to stabilize an adjacent carbanion. The mechanism for the formation of 6e is described. P: R Li I R EThe reaction of N-lithio-l,2-dihydropyridines 2, obtained from reaction of organolithium reagents and pyridines (2), with suitable electrophiles (E) is a versatile procedure for the synthesis of N-substituted-1,2-dihydropyridines 3 (3,4). It was therefore of interest to use these procedures to determine what effect elaboration of the pyridyl ring of pyridobenzothiazines had on pharmacological activity. We now Reaction of 10-methyl-10H-pyrido[3,2-b][1,4]-benzothiazine (4) with n-butyllithium afforded a mixture of 5a and 6a which on quenching with water gave rise to a mixture of 56 and 6b in a ratio of 1:4.4.' All efforts to obtain pure 6b were unsuccessful. Thinlayer chromatography on silica gel or fractional crystallization of a mixture of 5b and 6b resulted in aro~natization of 6b t o 7. Reduction of the imine double bond of 6b using sodium cyanoborohydride, sodium borohydride, and lithium aluminium hylspectral determinations were made using a mixture of 56 and 6b which were present in a ratio of 1 :4.4, respectively as determined from the integrals of the H-2 absorption of 56 at 8.08 6 and the H-3, H-4 absorptions of 66 a t 5.6-6.35 6. The mixture of 5c and 6c was similarly found to be in the ratio of 1 :4.4.Can. J. Chem. Downloaded from www.nrcresearchpress.com by 34.212.246.108 on 05/11/18For personal use only.

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Section: R Ementioning

confidence: 80%