I977Coupling Reactions of 1 -Alkylpyridinium Salts. Part I . With Phosphiteand Phosphinite Ions tBy John G. Carey and John R. Case, I.C.I. Mond Division, P.O. Box 8, The Heath, Runcorn, Cheshire WA74QDDimerisation of 1 -methylpyridinium ion by coupling at the 4-position can be brought about by treatment with di-phenylphosphinite, diphenylthiophosphinite, and diethyl or diphenyl phosphite anions in a range of solvents.Evidence is presented for the intermediate formation of 1.1 rsquo;-dimethyl-4.4rsquo;-(1 H.1 rsquo; H ) -bipyridylidene via addition ofthe phosphorus nucleophile a t the 4-position of the pyridinium ring.EXAMPLES of reactions of heterocyclic systems withnucleophiles are legion. Cyanide ion is notably versatile,affording with N-substituted pyridinium ions a varietyof products depending on the nature of the N-substituent,ring substitution, and conditions such as solvent andtemperature.Representative examples include additionto 3-carbamoyl-N-alkylpyridinium ions to form 1,2-, 1,4-,or 1,6-dihydropyridines, formation of 2- or 4-cyano-pyridine from N-alkoxy- and N-amido-pyridinium salts,and the induced dimerization of N-alkyl- and N-aryl-pyridinium salts to the corresponding 4,4rsquo;-bipyridyl-idenes (2).l These reactions are of theoretical andpractical interest zriz. the oxidation of (2) to (3) to givethe herbicidal l,lrsquo;-dimethyl-4,4rsquo;-bipyridyldiium (para-The structural features of the cyanide ion whichfacilitate these reactions are not unique. They are alsofound in the anions of phosphite diesters (RO),POH andquat) 1 *Me( 1 IH X a Me( 4 l( 2 )( 3 IX I ( EtO), P(O1, (PhOI,P(OI, Ph,P(O), or Ph,P( Slphosphinous acids R2POH and their sulphur analogue^.^For example Redmore has obtained 2-pyridylphos-phonic acid derivatives from diethyl phosphite ion andN-methoxypyridinium salts.The present paper des-cribes the dimerization of N-methylpyridinium ion,(1) (2), brought about by diphenyl phosphite anionin dimethylformamide, liquid ammonia, ethanol, ort In this paper, the phosphorus nucleophiles are named in theform -O*PR,, although they react in the form 0:P-R,.$ Oxidation of the dihydrobipyridyl (2) + (3) by sulphurdioxide is quantitative; oxidation by air, halogens, or oxidisingacids is unreliable, as reported previously.sR. E.Lyle, lsquo; Pyridine and its Derivatives,rsquo; SupplementPart 1, Wiley, New York, pp. 137-182 and references therein.U. Eisner and J. Kuthan, Chem. Rev., 1972, 72, 1.water, so providing a further parallel between thisnucleophile and cyanide.Heating 1-methylpyridinium chloride (1) and sodiumdiphenyl phosphite in dimethylformamide gave 1,lrsquo;-dimethyl-4,4rsquo;-bipyridylidene (2), which on oxidationwith aqueous sulphur dioxide afforded a 53 yield ofl,lrsquo;-dimethyl-4,4rsquo;-bipyridyldiium (3). $Evidence for the intermediacy of the dihydrobipyridyl(2) was obtained by U.V. spectroscopic analysis; absorp-tion peaks at 374 and 400 nm were observed, increasingin intensity with time. Evidence was also obtained tosupport the transient intermediacy of 1-methyl-l,4-dihydropyridine adducts (4) : addition of sodiumdiphenyl phosphite to N-methylpyridinium ion indimethyl formamide at ambient temperature showedinitially a single, but weak U.V.band in the region 300-325 nm before the appearance of bands at 378 and 400 nmcorresponding to the dimer (2).The addition however of diethyl phosphite ion to 1-methylpyridinium ion gave much stronger absorptionpeaks; an initial absorption at 360 nm was rapidlyreplaced by one at 330 nm. The final and lower wave-length absorption may be assigned, on the basis of n.m.r.data and recorded U.V. spectra of analogues, to the 1,4-dihydropyridine adduct ; the transient absorption at360 nm belongs to the extended enamine system of the1,2-dihydropyridine isomer.The lH n.m.r.spectrum of the product of addition ofl-methylpyridinium ion to sodium diethyl phosphite inhexadeuteriodimethyl sulphoxide showed a down fieldshift from 8 3.6 to 4.09 of the CH20 quintet J (7, P) =J(7,8) = 7 Hz for the phosphonate ion, showing thataddition had occurred.Thatat highest field, 6 3.49, showed a large J(3,P) couplingof 15 Hz. The single proton signal, 8 4.49, was partiallyobscured by the CH,O resonance. The lowest fieldsignal, 6 5.93, showed couplings of 8 Hz J(2,3) and4 Hz J(2,4), or J(2,P)I. The highest field signal isconsistent with H(3) and H(5), and the lowest fieldsignal with H(2) and H(6), deshielded by the nitrogen.The coupling constants of H(2) and H(6) with H(3) andL. J. Winters, A.L. Borror, and N. G. Smith, TetrahedronLetters, 1967, 2313; J . Beacham and J . Carey, ICI Limited,S. Afr. Pat. 7,100,256 (Chem. Abs., 1972, 76, 126,797~).R. Gomper, Angew. Chem. Internat. Edn., 1964, 3, 560.D. Redmore, J . Org. Chem., 1970, 35, 4114.R. H. Reuss and L. J . Winters, J . Org. Chem., 1973, 38,7 J . G. Carey, J . F. Cairns, and J . E. Colchester, Chem. Comm.,There were three ring CH resonances (2 : 1 : 2).3993.1969, 12802430 J.C.S. Perkin IH(5) (8 Hz), together with the chemical shifts, are inagreement with the 1,4-dihydropyridine structure.The formation of analogous kinetically (1,2-additionjand thermodynamically (1 ,kaddition) determined pro-ducts has been reported for the addition of cyanide ion0 4 09 1 25to pyridinium salts, but only when activated by electro-negative substituents.1 We have found that in thecyanide-ion-catalysed dimerization of N-methylpyri-dinium itself, only the 1,4-adduct (Amx.305 nm) wasdetectable along with the dimer (2) (Amax. 378 and 400nm). The formation of 1,4-addition products supportsthe outlined benzoin condensation type of mechanism(I) ---t (3). In neither the reaction with the phos-phorous-containing nucleophiles nor the reaction withcyanide ion were any 2,4lsquo;- or 2,2rsquo;-diquaternary bipyridy-lium salts detected. This is in contrast to the exclusiveformation of diethyl 2-pyridylphosphonate with diethylphosphite and 2- and 4-cyanopyridines with cyanideion and N-methoxypyridinium. This selectivity couldbe due to steric factors and the unfavourable proximityof the nitrogen lone pair to the carbanion centre in theproposed intermediates.The yields of dimerization of l-methylpyridinium ionto dihydrobipyridyl (2) were highest with the diaryl-phosphinite, diarylthiophosphinite, and diaryl phosphitein dimethylformamide, giving respectively, after 4 h at70-75 ldquo;C, 53, 25, and 410/, yields of 1,lrsquo;-dimethyl-4,4rsquo;-bipyridyldiium after oxidation. Under similar conditionssodium diethyl phosphite gave only 7 yield.Inethanol as solvent diphenylphosphinite ion led to a33 yield of bipyridyldiium ion whereas dimerization wasnot detected with diethyl or diphenyl phosphite (thelatter being solvolysable to the diethyl analogue). Inaqueous alkali, diphenylphosphine oxide and l-methyl-pyridinium chloride gave a low yield of dime1 (4), duein part to its low solubility in water.The poorer yieldsobtained with diethyl phosphite ion, despite itsapparently greater nucleophilicity towards N-methyl-pyridinium ion as compared to diphenyl phosphite anddiphenylphosphinite, point towards significant differ-ences in the acidity of the 4-proton in the respective1,4-dihydropyridine adducts (4) and in the delocalizationenergy of the derived carbanions.It may be that some of the phosphorus-containingnucleophiles which can participate in this reaction wouldbe capable of catalysing other reactions known to be@ J . S. Walia, J . S. Mohinder, M. S. Cattha, and M. Satyanara-lo D. Johnstone and D. M. Smith, J.C.S. Perkin I , 1976, 399.H.D. Becker, J. Org. Chem., 1970, 30, 6.yanah, Tetrahedron Letters, 1969, 3, 195.induced by cyanide ion, such as the dimerization ofaromatic aldehydes and Schiff srsquo; bases.*-1deg;EXPERIMENTALAll reactions were conducted in the absence of air. U.v.-visible spectra were measured for samples obtained directlyfrom each reaction and transferred under nitrogen to avariable path-length cell (R1K BTF9). All reactions wereso examined (unless otherwise stated) and the spectra wereshown to develop absorptions a t Amx. 378 and 400 nm.Path lengths were generally less than 0.1 mm; henceextinction coefficients are too uncertain to be quoted.Analysis for paraquat ion was carried out by the polaro-graphic method l1 or by spectrophotometric determinationof the paraquat radical ion obtained upon reduction byalkaline dithionite.l2Reactions of N-Methylpyridinium Ion.-(a) With sodiumdiethyl phosphite an dimethylformamide. To a solution ofsodium diethyl phosphite from diethyl hydrogen phosphite(4.14 g, 0.03 mol) and sodium hydride (1.44 g) in drydimethylformamide (40 ml) was added N-methylpyridiniumchloride (1.26 g, 0.01 mol). The mixture was stirred andheated for 4 h a t 75 ldquo;C, then cooled and oxidised by additionof aqueous sulphur dioxide (3 g in 100 ml). The resultingsolution was shown by polarographic and spectrophoto-metric analysis to contain l,lrsquo;-dimethyl-4,4rsquo;-bipyridyldiium(62.8 mg, 69).(b) With sodium diphenyl phosphite in dimethy2formamide.To a solution of sodium diphenyl phosphite from diphenylphosphite (7.26 g) and sodium hydride (0.72 g) in dimethyl-formamide (40 ml) was added N-methylpyridinium chloride(1.09 g).The solution when heated to 90 ldquo;C turned frompale orange to dark green-brown. After 4 h the mixturewas cooled and oxidised by aqueous sulphur dioxide asbefore to give a 447; yield of l,lrsquo;-dimethyl-4,4rsquo;-bipyridyldi-ium (3) (0.35 g).(c) With sodium diphenylphosphinite. (i) I n dimethylformamide. Diphenylphosphine oxide-acetone complex(10.4 g) was heated a t 150 ldquo;C and 0.1 mmHg to removeacetone. To the cooled residue of diphenylphosphineoxide were added dimethylformamide (60 ml) and sodium(0.9 g). To the so formed solution of sodium diphenyl-phosphinite was added N-methylpyridinium chloride (1.2 g ) .After 4 h a t 75 ldquo;C the dark red-brown solution was cooledand oxidised with aqueous sulphur dioxide as before.Analysis of the solution indicated the presence of 1,lrsquo;-dimethyl-4,Prsquo;-bipyridyldiium (0.645 g, 53).Further confirmation of the presence of paraquat ion wasobtained by addition of ammonium 4,4rsquo;-diaminostilbene-2,Zrsquo;-disulphonate to the solution to afford the insolubleparaquat diaminostilbenedisulphonate (Found : C, 57.0 ;H, 4.95; N , 10.65; S, 11.9.Calc. for Cl,H14N,,C,4H14-N,O,S,: C, 56.7; H, 5.15; N, 10.8; S, 11.65).To a solution of sodium ethoxide (0.02mol) and diphenylphosphine oxide (0.02 mol) in ethanol(30 ml) was added N-methylpyridinium chloride ( 1.22 g) .After 3 h at reflux the mixture was cooled and oxidised.The solution was shown by analysis to contain paraquat ion(0.3 g, 33).A similar yield was obtained using thediphenylphosphine oxide-acetone complex directly.R. M. Elofson and R. E. Edsberg, Canad. J. Chem., 1957,85, 646.l2 S. H. Yuen, J . F. Bagness, and D. Myles, Analyst, 1967, 92,375.(ii) In ethanol1977(iii) I n liquid ammonia. Diphenylphosphine oxide(0.5 g) , N-methylpyridinium chloride (2.64 g), and liquidammonia (10 ml), were sealed together in a Carius tube a t- 75 ldquo;C under nitrogen and allowed to warm to room temper-ature. After 72 h the tube was opened and the ammoniaevaporated. The red-brown semicrystalline residue gavean ion in the mass spectrum at m/e 186 (M+, C,,H,,N,) andU.V. peaks (in dimethylformamide) a t 374 and 400 nm,consistent with the presence of the dihydrobipyridyl (3).On oxidation as before there was obtained a solution contain-ing l,lrsquo;-dimethy1-4,4rsquo;-bipyridyldiium (0.48 g, 25) and N-methylpyridinium (0.13 g, 17.8) (by polarography).To a slurry of diphenylphosphine oxide(0.01 mol) and lithium hydroxide (0.8 g) in water (15 ml)was added aqueous N-methylpyridinium chloride (1.35 g in10 ml). After 3 h a t 90 ldquo;C, work-up as before afforded an(iv) In water.aqueous solution containing a low yield of paraquat ion(0.03 g, 3.5).(d) With diphenylphosphine sulphide. Sulphur (0.62 g)was added to a solution of diphenylphosphine (3.6 gm) inbenzene (10 ml) to form a solution of diphenylphosphinesulphide. l3 To this were added dimethylformamide (30 ml)and sodium hydride (0.925 g of 50 dispersion in oil) andthe mixture was stirred and heated to 70 ldquo;C (15 min.) Asolution of N-methylpyridinium chloride (1.08 g) indimethylformamide (10 ml) was then added. After 3 hthe mixture was cooled and oxidised as before. Analysisconfirmed the presence of l,lrsquo;-dimethyl-4,4rsquo;-bipyridyldiium(0.177 g, 23).7/581 Received, 4th April, 19771l3 G. Peters, J . A m e v . Chem. SOC., 1960, 82, 4751
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