Tetrahedron Letters, No, 8, pp.l-3,1959.Pergemon PressLtd. Printedin Great Britain.

ORI~ATIO~ IN TRE REACTION OF ~I~I~~~

~-~STITCTED PYRIDINEES

R, A. Abramovitch, A. D, Notation and Giam Choo Sex@ Chemistry Department, University of Seekztohewan, Saskatoon, Sazkstchewan (Reaeived 4 June 1959)

A STKDYof the addition of phenyllithimn to 3-substituted pyridinez m.z undertaken to detemine the orientatfon of the entering phenylgroup,
.

While thiswork was in progrees W&leg et al*' reported that the reaction of 3-phenylpyridine I(R - C H ) with phenyllithium II wag aelective in giving 65 The formation of 2,3_diph~i2,+iiphenylpyridine III(R- C&) exolusively. pyridine IV(R = C H f, which%iley et al, regardaz less probable,
65 ma

not observed.

The

addition of othernucleophilic reagent8 such az aodzmide 2*3 and butyl-

' R. R. Wiley,C. H. Jarboe, P. X. Callzhan and J, T, Nielsen, J. Org. Ch@, 2, 780 (1958), m L E. Plazek,A. Mzrcinikov znd Ch, Stammer, Rocm. Chem,1;& 365 (1935); mm. Abstr,& 1377 (1936). 3 E. Eerdegger and E. Nfklez,Helv. Chim.Aota 2, 5Ofi (1956).

Orientationin the reaction of phenyllithium

lithium4 to j-substituted pyridines indicated the preferentialformatinn of the 2,3-isomer in such reactions.Since our results with phenyllithiumalso show this trend we report some of our observations. With 3-picoline,II gave P-phenyl-3-picoline IV(R - CH3), b.p. 154156'/18 mm, (picrate,m.p. 165-166'),and 6-phenyl-3-picoline III(R = CH3), b.p. 162-164'/20mm, (picrate,m.p, 181-183'),the relative yields of IV and III being in the ratio of 8:l respectively,The structure of the main

product was proved by permanganate oxidation to 2-phenylpyridine-3-carboqlic acid IV(R = COOH), m.p. 168-169' (1it.5 m.p, 168-169')which was converted 6 via the acid chloride into 4-aeafluorenone, m.p. 139.5-141.5',by AlC13 in light petroleum.When the acid chloride was treated with AlC13 in benzene 3-benzoyl-2-phenylpyidine IV(R - C6H5CO), b.p. 155-160/15mm, picrate, was obtained.The structure of 2-phenyl-3-picoline was m.p. 137.5-138.5', confirmed by direct comparisonwith a specimen obtained unambiguouslyby Ishiguro et a1,,5 the IR spectra of the products and their picrates being identical and a mixed melting point of the picrates being undepressed.The NMR spectrum of the product was also consistentwith its formulationas 2-phenyl-3-picoline. The structureof III(R = CH3) was similarly proved by oxidation to 2-phenylpyridine-5-carboxylic acid, m.p. 232-233' (1ite7 m.p. 233'). A dimethyldipyridyl, characterized as the dipicrate,m.p. 2O4206' (decomp.),was isolated as a byproduct of the reaction and shown to

4 N. J. Leonard and B. L. Ryder, J. Org. Chem, ig, 596 (1953). 5 T. Ishiguro, Y. Morita and K. Ikushima, Yalcugaku Zasshi 12, 220 (1958); Chem. Abstr, 22, 118468 (1958). 6 Z. Skraup and A. Cobenzl,Monatsh, 4, 436 (1883), report m.p. 140-141' for 4-azafluorenone. 7 N. Nienburg, Chem. Ber, 51, 874 (1934).

Orientationin the reaction of phenyllithium

be different from j,j'-dimethyland 5,5'-dimethyl-2,2'-dipyridyl by a comparison of the picrates. The structure of this byproduct was not investigated further at this stage. 1 In view of the results of Wiley et al, the possible steric effect of the 5-substituent upon the orientationof the entering phenyl groups was investigatedin the reaction of II with nicotine. The product was shown to be a 1:l mixture of 2-phenyl- IV(R - 4-C H NCR ) and 6-phenylnicotine 47 3 III(R = -a-C B NCH ) by vapour phase chromatography. The two isomers were 47 3 separated by preparativevapour phase chromatography giving 2_phenylnicotine, b.p. 145/0.7 mm, picrate, b.p. 165/0.6mm, m.p. 211-213' and 6_phenylnicotine,

picrate, m.p, 170-171O.The structuresof the isomers were assigned on the basis of their infrared spectra (characteristic bands at 1610-1570 cm-') and by oxidation of the second fraction to 2-phenylpyridine-5-carboqylic acid. Addition of II and of other nucleophilicreagents seems to occur preferentiallyat the P-positionbut the j-substituent, if sufficiently bulky, may exert a steric effect resulting in appreciable addition at the 6-positionalso, The exclusive formation of 2,5_diphenylpyridine' might be attributed to steric inhibitionof coplanarityin the transitionstate in the formation of the 2,j-isomer, Acknowledgements - The authors wish to thank Dr. Ishiguro for samples of P-phenyl-j-picoline and its picrate, and Varian Associates for the NMR spectrum of 2-phenyl-3-picoline and its interpretation. This work was supported by a National Research Council of Canada grant.