Photocycloadditions to a pyrone analogue

307

J. Photochem. Photobiol. A: Chem., 58 (1991) 307-314

Photocycloadditions Christopher

to a pyrone analogue

J. Samuel+, Haydn

G. Beaton,

Kenneth

Davey and C. James Reader

Deparrment of Chemistry, University of Warwick, Coventry CV4 7AL (VX) (Received

September

11, 1990)

Abstract Irradiation of the dicyanomethylenepyran 1 in methanol gave two dimers, 5 and 6. In the presence of ethyl vinyl ether and acrylonitrile, the major photoproducts were 9 and 12 respectively. Ail these results are explained by initial [2+ 21 cycloaddition to the exocyclic double bond of 1 to give cyclobutane intermediates, which undergo ring opening to highly stabilized

zwitterions,

followed

by further

reactions.

1. Introduction Extensive studies of the photochemistry of 4-pyrones have shown a wide variety of end products depending on the substitution pattern and the solvent, but all the reactions can be accommodated within a mechanistic scheme which involves one of two possible initial steps [l]. Either a bond is formed between the 2 and 6 positions to give an oxabicyclohexenyl zwitterion or the 2,3 double bond participates in a [2 + 21 cycloaddition. Studies of the protonated pyrones, 4-hydroxypyrylium cations, have also shown that formation of the 2,6 bond is the normal process, although in some cases 2,5 bonding occurs [2]. A number of analogues also fit into the same pattern as the pyrones [3], but more recently some exceptions have been reported [4, 51. Spectroscopic and photophysical studies have established the singlet as the reactive state, at least for the arylated pyrones, but have left uncertain its orbital character (i.e. no* or rr#) [6]. A non-spectroscopic approach to this question involved the investigation of the behaviour of a compound in which the exocyclic oxygen atom had been replaced by a dicyanomethylene group, which has similar electron-withdrawing properties, but no accessible nr* excited state 171. With this in mind, and with an interest in extending our studies of pyrone photochemistry, we have examined the photochemistry of the dicyanomethylenepyran 1. Some years ago [4], we gave a preliminary account of its photodimerization and now report full details of that work, together with the results of studies designed to explore the scope and mechanism of the reaction.

2. Experimental 2.1. General

details

methods

Proton nuclear magnetic resonance (rH NMR) spectra Perkin-Elmer R34 at 220 MHz. Chemical shifts are reported ‘Author

to whom correspondence

lOlO-6030/91/$3.50

were recorded on a in parts per million

should be addressed.

0 Elsevier Sequoia/Printed

in The Netherlands

308 downfield from internal tetramethylsilane. IR spectra were recorded on a Perkin-Elmer 58OB. UV spectra were recorded on a Perkin-Elmer 552. Mass spectra (MS) were recorded on a Kratos MSSO. Melting points were uncorrected. Elemental analyses were carried out by Butterworth Laboratories, Teddington, Middlesex. Preparative photolyses were carried out using a 500 W medium pressure mercury lamp in a watercooled Pyrex housing. Preparative thin layer chromatography (PTLC) was carried out on 1 mm layers of silica gel 60 PF254 (ex Merck) (eluting with the solvent and for the number of times indicated). Preparative high performance liquid chromatography (HPLC) used a Waters 6000A pump, a Z-module fitted with an 8Si5 cartridge and a model 440 UV detector. Petrol refers to petroleum ether (boiling point (b.p.), 60-80 “C).

Irradiation of 4-dicyanomethylene-2,6-dimethyi-4H-pyran in methanol A solution of 4-dicyanomethylene-2,6-dimethyl-4H-pyran (0.20 g) in methanol (60 cm”) was degassed by bubbling nitrogen and irradiated for 60 h. The solution was concentrated under reduced pressure, and the residue was subjected to PTLC (ether X 2) to give three bands. Band 1 gave an orange solid (45 mg, 23%) which was purified by recrystallization (melting point (m.p.), 217-217.5 “C; from methanol). Found: C, 70.35%; H, 5.09%; N, 15.77%. t&H1aN402 requires C, 70.37%; H, 5.06%; N, 15.63%. IR (CHC13): 2220 (s), 1670 (s), 1582 (s) cm-‘. UV (MeOH): 449 nm (13800). UV (cyclohexane): 424 nm. ‘H NMR (CDCI,): 2.09 (3H, s), 2.18 (3H, s), 2.27 (3H, s), 2.53 (3H, s), 4.09 (3H, s), 5.55 (lH, s), 6.01 (lH, s), 6.59 (lH, s). MS m/z (%): 358 (M+, loo), 357 (23), 172 (11). M+ 358.1410 (calculated, 358.1429). Band 2 gave starting material (56 mg, 28%). Band 3 gave a dark solid which was resubjected to PTLC (ethyl acetate x4) to give one major band. This gave an orange solid (21 mg, 11%) which was recrystallized (m.p.>330 “C; from methanol-chloroform). IR (mull): 2215 (s), 1668 (s), 1648 (s), 1611 (s) cm-‘. UV (MeOH): 443, 352 nm. ‘H NMR (CDCl,): 2.16 (3H, s), 2.27 (3H, s), 2.31 (3H, s), 2.47 (3H, s), 5.79 (lH, s), 5.99 (2H, br s). ‘H NMR (CD+SOCD3): 2.17 (3H, s), 2.21 (3H, s), 2.26 (6H, s), 3.30 (lH, s), 6.07 (lH, s), 6.10 (lH, s), 6.45 (lH, s). MS m/z (%): 344 (M+, loo), 172 (39). MC 344.1265 (calculated, 344.1273). 2.2.

2.3. Irradiation of 4-dicyanomethylene-2,6-dimethyl-4-H-pyran in the presence of ethyl vinyl ether 4-Dicyanomethylene-2,6-dimethyl-4H-pyran (0.51 g) and ethyl vinyl ether (25 cm”) in methanol (250 cm3) were irradiated for 240 h. The solution was concentrated under reduced pressure, and the residue was subjected to filtration chromatography on silica gel, eluting with ether, followed by PTLC (CH,Cl,x3) to give three bands. Band 1 gave a yellow solid (150 mg) which was shown by NMR to contain reactant and a product. This was further fractionated by preparative HPLC eluting with hexane-ethyl acetate (50:50) to give reactant and 4-(3,3-dicyanoprop-2-enylidene)-2,6-dimethyl-4Hpyran as salmon pink needles (m.p., 185-186 “C; from methanol). Found: C, 72.42%; H, 4.90%; N, 14.08%. &H,,,N20 requires C, 72.71%; H, 5.09%; N, 14.13%. IR (CHC13): 2210 (s), 1670 (s), 1590 (m) cm - ‘. UV (MeOH): 466 nm (45 650), 438 nm (54 195), 262 nm (5970). ‘H NMR (CDC13): 2.20 (3H, s), 2.23 (3H, s), 5.86 (lH, d, J 13 Hz), 6.06 (lH, s), 6.40 (lH, s), 7.67 (lH, d, J 13 Hz). MS m/z (%): 199 (ll), 198 (M’, 100) 155 (20), 147 (32). M’ 198.0795 (calculated, 198.0793). Band 2 from PTLC was dimer 5 (79 mg, 16%).

309

2.4. Irradiation

of 4-dicyanomefhylene-2,6-dimefhyl-4H-pyran

in the presence of

acrylonitriie

4-Dicyanomethylene-2,6-dimethyl-4H-pyran (0.10 g) and freshly distilled acrylonitrile (7 cm3) in methanol (63 cm3) were irradiated for 42 h. The solution was to PTLC concentrated under reduced pressure, and the residue was subjected (CH2C12 x 3) to give three bands. Band 1 (15 mg, 18%) gave 4-cyanomethylene-2,6dimethyl-4H-pyran (m-p., 94.5-95.5 “C (from petrol); 94 “C [8]). IR (CHCQ: 2185 (s), 1675 (s), 1610 (m) cm-l. UV (EtOH): 308 nm (13800), 228 nm (3400). H ‘ NMR (CDC13): 2.05 (3H, s), 2.09 (3H, s), 4.20 (lH, s), 5.78 (lH, s), 6.20 (lH, s). MS ml z (%): 147 (M+, loo), 146 (7). M+ 147.0685 (calculated, 147.0684). Band 2 was reactant. Band 3 was dimer 5. 2.5. Knoevenagel condensation of acetylacetone and malononim’le Acetylacetone (10.0 g, 0.10 mol), malononitrile (6.6 g, 0.10 mol) and triethylamine (0.5 g) in methanol (100 cm3) were allowed to stand for 21 h. The precipitate (crop 1) was filtered and washed with methanol. The filtrate was concentrated under reduced pressure to afford crop 2. Both crops were l,Zdihydro-4,6-dimethyl-Zoxo-3-pyridinecarbonitrile (12.1 g, 81.8%) whose spectroscopic properties were in good agreement with published data [9]. The mother liquors were subjected to chromatography on silica gel, eluting with dichloromethane. TLC analysis of the early fractions showed another product running ahead of the pyridone. Fractions containing this were combined and subjected to PTLC (petrol-ether, 2:l) to give one significant band containing 2methoxy-4,6-dimethyl-3-pyridinecarbonitrile (0.16 g, 1%; m-p., 95-96 “C (from petrol)), which was spectroscopically and chromatographically identical to authentic material (see below). [IO] 2.6. Methylation of I,2-dihydro-4,6-dimefhyl-2-oxo-3-pyridinecarbonitriIe 1,2-Dihydro-4,6-dimethyl-2-oxo-3-pyridinecarbonitrile (2.17 g, 14.7 mmol) and iodomethane (1.25 cm3, 20 mmol) in dimethylformamide (50 cm’) were stirred under nitrogen during portionwise addition of sodium hydride (50% in oil; 1.00 g, approximately 20 mmol). Stirring was continued for 22 h, the mixture was poured into iced water, and extracted with dichloromethane, which was washed with water, dried over magnesium sulphate and concentrated under reduced pressure. The residue was subjected to column chromatography over silica gel (400X20 mm). Elution with dichloromethane gave fraction 1. Elution with 2% methanol in dichloromethane gave fraction 2. Fraction 1 gave 2-methoxy-4,6-dimethyl-3-pyridinecarbonitrile (0.21 g, 9%; m.p., 95.5-96 “C (from petrol)). Found: C, 66.76%; H, 6.25%; N, 17.30%. CsHloNzO requires C, 66.65%; H, 6.22%; N, 17.27%. IR (CHC13): 2220 (s), 1598 (s), 1565 (s) cm-l. W (MeOH): 290, 232 nm. H ‘ NMR (CDCl,): 2.47 (6H, s), 4.03 (3H, s), 6.69 (lH, s). MS m/z (%): 162 (M’, 98), 161 (loo), 133 (56), 132 (91), 131 (40). Fraction 2 gave ~,2-dihydro-1,4,6-trimethyl-2-oxo-3-pyridinecarbonitrile (2.08 g, 87%; m-p., 203-204 “C (from MeOH); 202-205 “C [ll]). Found: C, 66.55%; H, 6.21%; N, 17.34%. CgHlONzO requires C, 66.65%; H, 6.22%; N, 17.27%. IR (mull): 2210 (s), 1649 (s), 1586 (s) cm-‘. UV (MeOH) 329, 234, 216 nm. H ‘ NMR (CD(&): 2.39 (3H, s), 2.40 (3H, s), 3.56 (3H, s), 6.08 (lH, s). MS m/z (%): 162 (M+, loo), 133 (99). 3. Results Irradiation of 1 in methanol followed by PTLC led to two brange products. The analytical and spectroscopic data of the major product did not permit a structural

310

assignment, but single-crystal X-ray analysis showed that the structure was 5 (Fig. 1). With this structure secure, the spectroscopic data were sufficient to show that the minor product was the related pyridone 6. Irradiation of 1 in methanol containing 10% ethyl vinyl ether gave, in addition to the orange dimers, a yellow product which was isolated by preparative HPLC, and shown by the analytical and spectroscopic data to be the alkylidenepyran 9. Irradiation of 1 in methanol containing 10% acrylonitrile gave, in addition to the orange dimers, a colourless product which was isolated by PTLC and was shown by its melting point and spectroscopic data to be the known cyanomethylenepyran 12 [S]. We also explored the addition of other olefins, with the followingresults: cyclohexene, only orange dimers; ethyl acrylate, traces of a product showing NMR signals similar to those of 12; 2-methoxypropene, traces of a yellow product possibly analogous to 9. Neither of these was formed in sufficient quantities for proper characterization. Analogy with pyrones [l] suggested irradiation in the presence of furan, but this gave

CN

(4)

Nc*om +Ncx.j$L (5) Scheme 1.

(6)

311

predominantly the same two orange dimers, together with numerous minor products barely visible by TLC analysis. In the hope that suspected intermediates might be stable in a less polar solvent, the reactions were repeated in carbon tetrachloride solution. Examination of the NMR spectra of the crude products showed that 12, but not 9, was formed. In no case were any signals observed that could be attributed to an intermediate. Our mechanistic speculation suggested an analogy with the Knoevenagel condensation of acetylacetone and malononitrile, which is known to give the pyridone 14 [X2]. However, careful chromatography of the mother liquors from this reaction gave about I% of the methoxypyridine 15, in addition to the pyridone.

4. Discussion In our preliminary communication of the dimerization, we proposed a mechanism in which an initial cycloaddition, involving the exocyclic double bond of one molecule and the endocyclic double bond of the other, is followed by a deep seated rearrangement to give the products 5 and 6 (Scheme 1). Heterolysis of the cyclobutane 2 leads to a highly stabilized zwitterion 3, which is reminiscent of the work of Huisgen [13] on the cycloaddition of tetracyanoethylene to enol ethers. This zwitterion then breaks down, as shown, to an intermediate 4. The later stages of the mechanism are similar to the Knoevenagel condensation of acetylacetone and malononitrile, in which an intermediate 13, analogous to 4, is postulated as the precursor to the pyridone 14 (Scheme 2) [12]. However, in our system the major product was the methoxypyridine, whereas for the model the pyridone was the only reported product. This prompted the reinvestigation described above, which showed that pyridone and methoxypyridine are formed in both cases; only the ratio differs. The mechanism of Scheme 1 implies that the reaction involves one molecule of 1 in its ground state and one in its excited state, but it is not possible to say which state uses which double bond to react. We attempted to establish this by studying the [2 + 21 addition of other olefins to 1. In both the successful cases, those of ethyl vinyl ether and acrylonitrile, the pyran ring remained intact, but the exocyclic portion of the molecule was changed. In fact, reasonable mechanisms for both these reactions

Et&

CN

0

MeOH

+

/ -4 & CN

(13)

NH

’

+

=;

0

CN

(15) Scheme 2.

OMe

312

(1)

(7)

03)

(9)

Scheme 3.

CN

(1) Scheme 4. NO) N(Z)

NW)

4 N(3) O(2)

65 '218) Fig. 1. X-ray structure of 5. involve initial [2 + 2] cycloaddition of the olefin to the exocyclic double bond followed by the further changes shown in Schemes 3 and 4. (Our failure to isolate methylenemalononitrile, the by-product implied by Scheme 4, is not surprising in view of its facile polymerization in the presence of alcohols [14].)

313

(16)

(17) Fig.2. Structures of compounds 16 and 17. These two reactions diverge at the stage of the zwitterion, in that 11 undergoes C-C bond cleavage, whereas 8 expels ethoxide. The latter might be expected to undergo C-C cleavage as an alternative reaction, but neither l,l-dicyano-2-ethoxyethylene nor the 4-methylenepyran could be found. It seems that if there is a leaving group available, as in the case of 8 and 3, it is expelled, whereas if there is no leaving group, C-C cleavage occurs. The work of Huisgen [13] referred to above suggested that if cyclobutanes such as 7 or 10 were intermediates undergoing heterolysis, they might be stabilized by less polar solvents; however, even in carbon tetrachloride, there was no evidence for their presence. In the addition reactions of ethyl vinyl ether and acrylonitrile, it is clearly the pyran which is excited, and it is its exocyclic bond which participates. It thus seems probable that, in the dimerization reaction, it is the excited molecule which uses its exocyclic bond and the ground state which uses its endocyclic double bond to react. It is noteworthy that the reactions of electron-rich and electron-poor olefins were similar in that the initial cycloaddition took place at the exocyclic bond of the methylenepyran; however, they differed in the regiochemistry as shown in Schemes 3 and 4. We attempted to rationalize this by frontier molecular orbital (FMO) theory, using orbitals calculated at various levels, from the Huckel level, using heteroatom parameters, through the w-technique and a pelectron SCF method, to the MNDO level. At all levels of theory, addition to the exocyclic double bond of the excited state was predicted. However, in every case, the predicted regiochemistry was opposite to the direction of addition required to explain the products. This should not be too surprising because, although FM0 theory may give the preferred orientation of an exciplex or a biradical, if there is reversal from either of these intermediates, the product distribution may not reflect the populations of the intermediates (see the recent detailed reinvestigation of [2+23 cycloadditions to cyclohexenones [El). The reactions reported here were not clean enough for quantitative study, but the lengthy irradiation times suggest low quantum yields, and thus the likelihood of such reversal. Irradiation in the presence of furan was carried out in the hope of trapping a zwitterion 16 analogous to 17 (Fig. 2) trapped in the pyrone case [l]; however, this was unsuccessful_

5. Conclusions Although it was the potential analogy with pyrones which prompted this work, the dicyanomethylenepyran is different in that it yields no products of rearrangement

314

or trapping attributable to 2,6 bonding and no products are formed in which the excited pyran uses the 2,3 bond in cycloaddition. We have thus discovered a group of reactions for a pyrone analogue in which the availability of another reaction channel has completely diverted the photochemistry from that typical of pyrones.

References 1 J. A. Barltrop, A. C. Day and C. J. Samuel, J. Am. Chem. SOL, 201 (1979) 7521, and references cited therein. 2 J. W. Pavlik, A. P. Spada and T. E. Snead, J. Org. Chem., 50 (1985) 3046. J. W. Pavlik, A. D. Patten, D. R. Bolin, K. C. Bradford and E. L. Clennan, J. 0% Chem., 49 (1984) 4523. J. A. Barltrop, J. C. Barrett, R. W. Carder, A. C. Day, J. R. Harding, W. E. Long and C. J. Samuel, J. Am. Chem. Sot., 101 (1979) 7510. J. W. Pavlik and R. M. Dunn, Tetrahedron Lett., (1978) 5071. 3 N. Ishibe, S. Yataka, J. Masui and N. Ihda, J. Org. Chem., 43 (1978) 2144. N. Ishibe and M. Tamura, J. Org. Chem., 41 (1976) 2279. 4 N. W. Alcock and C. J. Samuel, J. Chem. Sot., Chem. Commun., (1982) 603. 5 T. Nishio, J. Chem. Sot., Perkin Trans. 1, (1987) 1225. 6 K. Bhattacharyya, D. Ramaiah, P. K. Das and M. V. George, J. Phys. Chem., 90 (1986) 5984. N. Ishibe and S. Yutaka, J. Org. Chem., 43 (1978) 2138. N. Ishibe, H. Sugimoto and J. B. Gallivan, J. Chem. Sot., Faraday Trans. 2, 71 (1975) 1812. N. Ishibe, M. Sunami and M. Odani, J. Am. Chem. Sot., 95 (1973) 463. 7 H. E. Zimmerman and D. R. Diehl, J. Am. Chem. Sot., 101 (1979) 1841. 8 I. Eelsky, H. Dodiuk and Y. Shvo, J. Org. Chem., 39 (1974) 989. 9 A. AIberola, C. Andres, A. Gonzalez Ortega, R. Pedrosa and M. Vicente, J. Hererocycl. Chem., 24 (1987) 709. T. Kappe, H. P. Stelzel and E. Ziegler, Monatsh. Chem., I24 (1983) 953. 10 N. F. Tsoi and M. E. Konshin, Kniti, (1983) 3802; Chem. Abstr., 102 (1985) 45743k. 11 W. 0. Johnson, M. C. Seidel and H. L. Warner (Rohm and Haas Co., U.S.A.), U.S. Patent #,038,065 (July 26, 1977); Chem. Abstr., 87 (1977) 152034~. 12 U. Basu, J. Indian Chem. Sot., 7 (1930) 815. J. W. Ducker and M. J. Gunter, Aust. J. Chem., 28 (1975) 581. K. Hartke, W. F. Richter and T. Kampchen, Chem. Ber., 122 (1989) 669. P. Victory, J. Sempere, J. I. Bore11 and A. Crespo, J. Chem. Sot., PerJcin Trans. I, (1989) 2269. 13 R. Huisgen, Act. Chem. Rex, 10 (1977) 199. 14 A. E. Ardis, S. J. Averill, H. Gilbert, F. F. Miller, R. F. Schmidt, F. D. Stewart and H. L. Trumbull, J. Am. Chem. Sot., 72 (1950) 1305. 15 D. I. Schuster, G. E. Heibel, P. B. Brown, N. J. Turro and C. V. Kumar, J. Am. Chem. Sot., 110 (1988) 8261. D. I. Schuster, P. B. Brown, L. J. Capponi, C. A. Rhodes, J. C. Scaino, P. C. Tucker and D. Weir, J. Am. Chem. Sot., IO9 (1987) 2533.