Photochemical dimerization of methyl 2-furyl- and 2-thienylacrylate and related compounds in solution

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1990 Photochemical Dimerization of Methyl 2-Furyl- and 2-Thienylacrylate and Related Compounds in Solution Maurizio Drsquo;Auria,rdquo; Giovanni Piancatelli and Anna Vantaggi Centro CNR per lo Studio della Chimica delle Sostanze Urganiche Naturali, Dipartirnento di Chimica, Universita di Roma lsquo;La Sapienza, * P. le A. Moro, 2,00985 Roma, Italy ~~ ~ Irradiation of methyl 3-(2-furyl)acrylate 1 in the presence of benzophenone led to the formation of a mixture of t-3,t-4-and ~-3~c-4-dimethyl 3,4-di-(2-furyl)cyclobutane-r-I,~-2-dicarboxylates2 and 3 in 2: 1 ratio and 90 overall yield. The reaction is an efficient synthetic method when using the corresponding acid 4, the acrylaldehyde derivative 7a and the corresponding methyl ketone 7b as well.On the other hand the presence of a methyl group on the double bond inhibited the reaction, while the presence of a methyl group on the furan ring also depressed the reactivity of the double bond, giving only a 27 yield of the corresponding dimer. Methyl 3-(2-thieny1)acrylate 13 gave a mixture of two dimers 14 and 15 in an overall yield of 25, while methyl cinnamate showed only euro;2isomerization. During our researches devoted to the study of the photo- chemical reactivity of heterocycles,rsquo; we have tested the photochemical behaviour of heterocyclically substituted acrylic derivatives. The results of this work could give interesting information on the photochemical interaction between aryl- substituted olefins and halogeno-thiophene and -furan deriv- atives2 In this paper we report our results concerning the dimeriz- ation of heterocyclic derivatives of cinnamic acid in acetonitrile solution. Results and Discussion Irradiation of methyl 3-(2-furyl)acrylate 1in acetonitrile in the presence of benzophenone as sensitizer furnished a mixture of two compounds, 2 and 3, in 61 and 27 yield, respectively (Table 1).The lsquo;H NMR spectrum of compound 2 showed a doublet of doublets at SH7.32, a doublet of doublets at SH6.25, and a doublet at 6H 6.12 (furyl protons), a singlet at 8H3.68 (C02Me), and an A2X2 system at gH 3.74 (JAx10 Hz) and at 3.51 (JAx10Hz). The observed J-value was in agreement with a trans relationship between the cyclobutane protons as reported in P-truxinic acid.3 This completely symmetric structure was confirmed by the 13CNMR spectrum where we observed only eight carbon signals (multiplicity from DEPT experiments), at 6c 172.1 (s, COz), 153.0 (s), 142.1 (d), 110.3 (d) and 106.6 (d) (furyl carbons), 52.1 (9, OMe), and 42.92 (d) and 39.57 (d, cyclobutane carbons). Similarly, compound 3 showed lsquo;H NMR signals at 6, 7.14, 6.11 and 5.87 (multiplets) relative to the furyl protons, a singlet at 6, 3.65, and an A2X2system at 4.17 and 3.79 (JAx7 Hz); this J-value is in agreement with a cis relationship between the cyclobutane protons.The I3C NMR spectrum confirmed the symmetric structure: in this case we again observed only eight signals, at 6, 172.4 (s, C02),152.7 (s), 141.8 (d), 110.2 (d) and 107.0 (d) (furyl carbons), 52.0 (9, OMe), 42.9 (d) and 38.3 (d).The symmetric nature of the compounds was confirmed by their mass spectra, which showed a peak at m/z 304 (relative abundance 4) and a parent peak at m/z 152: this behaviour is diagnostic for a head-to-head configuration of the substitu- ent~.~,~ Similar results were obtained by using the corresponding acid 4: we obtained the cyclobutane derivative 5 together with its isomer 6 (yield SO, Table 1). lsquo;COR (2) R=OMe (5) R=OH (Sa) R = H (8b) R= Me (1) R=OMe (4) R= OH pa) R=H (7b) R= Me (3) R=OMe (6) R= OH (9) R= Me The furyl acrylates 10 and 11, with a methyl group respectively in an a-position to the carboxylic ester and in an a-position on the furan ring, showed different behaviour.While compound 10 did not give any photodimer, its isomer 11 furnished only the photodimer 12, in 22 yield. We did not observe the formation of products of type 3. The presence of substituents on the double bond seems to be incompatible with photodimer formation while, unexpectedly, substitution on the furan ring also depresses the reactivity of the double bond. We then tested the reactivity of both the acrylaldehyde derivative 7a and the methyl ketone 7b. While the furylacrylaldehyde gave only the dimer 8a in 42 yield, the photoreaction of ketone 7b in the presence of benzophenone led to a 1 :1 mixture of dimers 8b and 9 in 70 overall yield (Table 1). Finally, we wanted to verify the effect of a change in the nature of aromatic ring on the reactivity: for this purpose we used the thienyl derivative 13 and methyl cinnamate 16.3000 Table 1. Photochemical dimerization of arylacrylic derivatives. Irradiation Entry Substrate time (h) Product Yield ()a 1 1 7 2 61 3 27 2 4 6 5 55 6 25 3 10 11 4 11 11 12 22 5 7 6 8a 42 6 7 5 8b 38 9 32 7 13 10 14 13 15 12 8 16 5 a All yields refer to isolated, chromatographically pure products. r+o 0 hv0 xPh@. 0 MeCN yof-CO2Et r+Me 0 hv *s Ph@. 0 MeCN (15) hv c xPhpCO, MeCN Compound 16 did not show any reactivity under our irradi- ation conditions, showing only the previously mentioned E-2 isomerization. The thienyl derivative 13 gave a mixture of two cyclobutane derivatives 14 and 15 in 1: 1 ratio but we obtained these compounds with an overall yield of 25.The photochemical dimerization of cinnamic acid has been known for 70 Cinnamic acid 17, irradiated in the solid state, gave the corresponding photodimer depending on the crystal form of the starting material: the metastable p-form is reported to yield p-truxinic acid 18, while the stable a-form gave a-truxillic acid 19.8*9 This type of reaction can also be performed on 3-(2-furyl)- J. CHEM. SOC. PERKIN TRANS. 1 1990 acrylic acid 4 or with 3-(2-thienyl)acrylic acid 20 to give the corresponding photodimers 5 and 21 if the irradiation is performed in the solid state." It is noteworthy that these reactions need 30 and 20 days of irradiation, respectively, to give the products.Irradiation of the acids 4 and 20 in solution (MeOH) showed only E-Z isomerization of the starting materials.' While the reactivity of cinnamic acid is well defined, the reactivity of the esters is more complex. Irradiation of liquid ethyl cinnamate 22 furnished a mixture of two compounds 23 and 24 in 55 and 25 yield, respectively.'* When the reaction was performed in a mixture of water (82.1), cyclohexane (3.2), butanol(9.8), and sodium dodecyl sulphate (4.9) an 8:2 mixture of trans-diesters 23 and 25 was obtained.I3 On the other hand, irradiation in methanolic solution did not furnish any cyclodimerization product, giving instead only E-2 i~omerization,'~ while irradiation in the presence of BF, furnished a mixture of seven dimers.' Ph"' I We have found that the photodimerization of furan-acrylic derivatives in solution is possible in contrast to the reported data for cinnamic acid derivatives.The observed order of reactivity is furan thiophene benzene, in the reverse order of aromaticity. J. CHEM. SOC. PERKIN TRANS. 1 1990 The reaction is extremely sensitive to steric hindrance on both the double bond and on the furan ring. This behaviour can be explained if complete superposition of two molecules is needed in order to initiate the reaction. Our photochemical reactions furnished dimers with high stereospecificity. In contrast with the complex mixtures obtained with ethyl cinnamate,' we ob-tained only two head-to-head dimers and only the symmetric isomers.The use of acetonitrile can explain the formation of head-to-head dimers: it is known that in enone dimerization excited charge-transfer complexes can be involved. The formation of charge-transfer complexes, favoured in polar solvents, results in a predominance of head-to-head dimers.I6 In contrast, the topochemical justifications used for the reactions in the solid state are useless for justification of the observed stereochemistry in our experiments. The quantum yield of the conversion 7b -8b + 9 was 0.078 f0.002 and was determined by the use of phenylglyoxylic acid as actinometer" at 350 nm. As regards the sensitizer, acetone (ET79-82 kcal mol-') * and acetophenone (ET74.1 kcal mol-')'* were unable to induce the reaction as well as did benzophenone (ET69.2 kcal mol-1).18 It is noteworthy that the dimerization did not work in the absence of benzophenone.The triplet energy of compound 7b was estimated to be 52 kcal mol-' by using (E)-stilbene isomerization." All the above reported data are in agreement with the hypothesis that the described reactions occur through a ben- zophenone-sensitized mechanism. Further investigations are needed to verify if benzophenone has the same role as that shown in coumarin dimerization.20 Experimental M.p.s were obtained with a Mettler FP81 cell equipped with a Mettler FP80 Central Processor 'H and "C NMR spectra were recorded with Varian Gemini 200 MHz and with Varian XL300 spectrometers, with CDC13 as solvent.Mass spectra were obtained with a Kratos MS-80 instrument by direct insertion at a source temperature of 150 "C. IR spectra were obtained on a Perkin-Elmer 457 spectrometer. GLC analyses were performed with Hewlett-Packard 5880A and 5890 instruments (flame- ionization detector). Commercial Merck silica gel was used for column chromatography. Starting Materials.-3-(2-Furyl)acrylic acid 4 was conver- ted into the methyl ester 1 by reaction of the corresponding acyl chloride 21 with MeOH in the presence of pyridine.22 Ethyl 3-(2-furyl)-2-methylacrylate10 was obtained by condensation between furan-Zcarbaldehyde with ethyl pr~pionate.~~ The same procedure was utilized to prepare ethyl 3-(5-methyl-2- fury1)acrylate 11.4-(2-Furyl)but-3-en-2-one7b was obtained through condensation between furan-Zcarbaldehyde and acetone.24 Methyl 3-(2-thienyl)acrylate 13 was prepared from the corresponding acid by reaction with acidic MeOH.25 (E)-Methyl 3-(2-Furyl)ucrylute 1.-B.p. 1 14-1 16 "C/18 mmHg (lit.,26 114-115 "C/16 mmHg); 6" 7.50 (1 H, m), 7.10 (1 H, d, J 16 Hz), 6.59 (1 H, d, J4 Hz), 6.44 (1 H, dd, J1 2, J2 4 Hz), 6.29 (1 H, d, J 16 Hz) and 3.77 (3 H, s); v,,, 1720, 1645, 1560, 1485, 1435, 1390, 1310, 1275, 1260, 1210, 1200, 1168, 1075, 1040,1020,970,930,883,860,818,750,730 and 680 cm-'; m/z 152. (E)-Ethyl 3-(2-Furyl)-2-methylacrylate 10.-B.p. 102-105 "C/5mmHg (lit.,23 103-104 "C/4.5 mmHg); 6H7.50 (1 H, d, J 1.7 Hz), 7.41 (1 H, m), 6.58 (1 H, d, J 3.5 Hz), 6.47 (1 H, dd, J, 1.7,J23.5 Hz), 4.22 (2 H, q, J7 Hz), 2.19 (3 H, s) and 1.31 (3 H, t, * 1cal = 4.184 J.3001 J 7 Hz); v,,, 1695, 1630, 1368, 1150, 1110, 1082, 1012 and 885 cm-'; m/z 180. (E)-Ethyl 3-(5-Methyl-2-furyl)acrylute 11 .-B.p. 146-148 "C/30 mmHg (lit.,27 128-130 "C/16-18 mmHg); ijH7.33 (1 H, d, J 15.7 Hz), 6.47 (1 H, d, J3 Hz), 6.20 (1 H, d, J 15.7 Hz), 6.04 (1 H, dd, J 3, J20.9 Hz), 4.20 (2 H, q, J 7 Hz), 2.31 (3 H, s) and 1.28 (3 H, t, J7 Hz); vmaX1718,1645,1590,1530, 1370,1310, 1260,1193,1162,1025 and 975 cm-'; m/z 180. (E)-4-(2-Furyl)but-3-en-2-one 7b.-B.p. 130-1 35 "C/30 mmHg (lit.,24 114-1 18 "C/10 mmHg); 6H7.48 (1 H, d, J 1.8 Hz), 7.25 (1 H, d, J 15.9 Hz), 6.64 (1 H, d, J3.5 Hz), 6.59 (1 H, d, J 15.9 Hz), 6.46 (1 H, dd, J, 3.5, J21.8 Hz) and 2.30 (3 H, s); vmaX1700, 1675,1620,1480,1390,1360,1320,1305,1285,1250,1205,1170, 1100,1020,970,930,910 and 885cm-'; m/z 136.(E)-Methyl 3-(2- 7"hienyl)acrylute 13.-M.p. 4142 "C (lit.,** 40-42.2"C);6,7.76(1H,d,J 15.7Hz),7.34(1 H,d, J5Hz),7.22 (1 H, d, J 3.7 Hz), 7.02 (1 H, dd, J15,J23.7 Hz), 6.21 (1 H, d, J 15.7 Hz) and 3.75 (3 H, s); vmax 1730, 1635, 1440, 1430, 1365, 1310, 1268,1202, 1168,1045,970,928 and 860 cm-'; m/z 168. Synthesis of Cyclobutane Derivatives. General Procedure.- An alkene 1, 4, 7, 10, 11, 13, or 16 (1 g) was dissolved in acetonitrile (300 ml) in the presence of benzophenone (100 mg). The solution was outgassed with nitrogen for 1 h and was then irradiated in an immersion apparatus with a 500 W high-pressure mercury arc (Helios-Italquartz) surrounded by a Pyrex water-jacket.At the end of the reaction (Table l), removal of the solent under reduced pressure yielded a crude product, which was chromatographed on silica gel. The following compounds were thus prepared. Dimethyl t-3,4-Di-(2-furyl)cyclobutane-r-1 ,c-2-dicurbox~vlute 2.-Very dense oil (Found: C, 63.5; H, 5.2. C16H1606 requires C,63.15;H,5.30);6,7.32(1H,dd,J,2,J2 lHz),6.25(1H,dd,Jl3,J22Hz),6.l2(1H,d,J3Hz),3.74(1H,m,JlOHz),3.68(3 H, s) and 3.51 (1 H, m, J 10 Hz); 172.06 (s), 153.02 (s), 142.13 (d), 110.27 (d), 106.58 (d), 52.08 (q), 42.92 (d) and 39.56 (d); v,,, 1735, 1600, 1440, 1380, 1150, 1010,950 and 885 cm-'; m/z 304.Dimethyl c-3,c-4- Di-( 2-furyl)cyclobutane-r- 1 ,c-2-dicarboxyl- ate 3.-Very dense oil (Found C, 62.8; H, 5.2); 6, 7.14 (1 H, m), 6.11 (1 H, m), 5.87 (1 H, m),4.17 (1 H, m, J7 Hz), 3.79 (1 H, m, J 7 Hz) and 3.65 (3 H, s); 6c 172.38 (s), 152.66 (s), 141.80 (d), 110.21 (d), 106.97 (d), 52.01 (q), 42.92 (d) and 38.31 (d); vmax 1740,1600,1505,1440,1360,1320,1285,1205,1170,1150,1075, 1015,910 and 885 cm-'; m/z 304. t-3,t-4-Di-(2-furyl)cyclobutane-r-l,c-2-dicarboxylic Acid 5.-M.p. 177-178 "C (lit.," 179-179 "C) (Found: C, 61.0; H, 4.2. Calc. for Cl4HI2O6: C, 60.87; H, 4.38); tiH 7.35 (1 H, m), 6.38 (1 H, m), 6.17 (1 H, m), 3.82 (1 H, m, J 10 Hz) and 3.58 (1 H, m, J 10 Hz); m/z 276. ~-3,~-4-Di-(2-furyl)cyclobutane-r-1 ,~-2-dicarboxylic Acid 6.-Syrup (Found: C, 60.6; H, 4.3); tiH7.48 (1 H, m), 7.20 (1 H, m), 5.94 (1 H, m), 4.24 (1 H, m, J7 Hz) and 3.93 (1 H, m, J7 Hz); mjz 276.Diethyl t-3, t-4-Bis-(5-methyl-2- fury1)cyclobutune-r- 1~-2-di-carboxylate 12.-Very dense oil (Found: C, 66.7; H, 6.9. C20H2406requires C, 66.75; H, 6.71); tiH5.99 (1 H, d, J 3 Hz), 5.83 (1 H, dd, J, 3, J21 Hz),4.16 (2 H, q, J7 Hz), 3.66 (1 H, m, J 10 Hz), 3.41 (1 H, m, J 10 Hz), 2.24 (3 H, s) and 1.23 (3 H, t, J 7 Hz); v,,, 1730, 1620, 1570, 1450, 1370, 1320, 1300, 1155, 1 100,1020, 910 and 860 cm-'; m/z 360. t-3,t-4- Di-(2- fury1)cyclobutane-r- 1 ,~-2-dicarbaldehyde 8.-Very dense oil (Found: C, 69.0; H, 4.8. C14H1204 requires C, 68.85; H, 4.95); 8H 9.80 (1 H, s), 7.35 (1 H, d, J 1.8 Hz), 6.29 (1 H, dd, J13.2, J21.8 Hz), 6.14 (1 H, d, J 3.2 Hz), 3.80 (1 H, m, J9.6 Hz) and 3.67 (1 H, m, J 9.6 Hz); v,,, 2720, 1725, 1605, 1383, 1150,1010 and 885 cm-'; m/z 244.r-1 ,c-2- Diacetyl-t-3,t-4-di-( 2-furyl)cyclobutane 8b.-Very dense oil (Found: C, 70.4; H, 6.1. C16H1604requires C, 70.59; H, 5.92); 8H 7.33 (1 H, dd, J1 1.8, JZ 0.8 Hz), 6.27 (1 H, dd, J1 3.3, J21.8 Hz), 6.13 (1 H, dd, J13.3, J20.8 Hz), 3.58 (2 H, s) and 2.07 (3 H, s); vmaX1700,1600,1355,1145,1010 and 880 cm-'; m/z 272. r-1,c-2-Diacetyl-c-3,c-4-di-(2-furyl)cyclobutane 9.-Very dense oil (Found: C, 70.3; H, 6.1); 7.21 (1 H, d, J 1.8 Hz), 6.19(1H,dd,J1 3.2,J2 1.8Hz),5.91(1H,d,J3.2Hz),4.03(1H, m, J 7 Hz), 3.89 (1 H, m, J 7 Hz) and 2.15 (3 H, s); v,,, 1710, 1600,1365,1150,101 5 and 885 cm-'; m/z 272.Dimethyl t-3,t-4-Di-(2-thienyl)cyclobutane-r-l,c-2-dicarbo-xylate 14.-Very dense oil (Found: C, 57.2; H, 4.9. C16H1604S2requires C, 57.12; H, 4.79); 8" 7.19 (1 H, dd, J, 3.9, J22.5 Hz), 6.96 (2 H, m), 3.82 (1 H, m, J9.6 Hz), 3.72 (3 H, s) and 3.44 (1 H, m, J 9.6 Hz); vmaX1730, 1625, 1435, 1170, 1030, 920,880 and 845 cm-'; m/z 336. J. CHEM.SOC. PERKIN TRANS. I 1990 5 S. Caccamese, P. Maravigna, G. Montaudo and M. Przybylski, f. Polym. Sci., Polym. Chem. Ed., 1975, 13,2061. 6 H. Stobbe, Ber. Dtsch. Chem. Ges., Pt. B, 1919,52,666. 7 H. Stobbe and A. Bremer, J. Prakt. Chem., 1929,123, 1. 8 M. D. Cohen, G. M. J. Schmidt and F. I. Sonntag, f. Chem. Soc., 1964, 2000, G. M. J. Schmidt, J. Chem. SOC., 1964, p.2014; J. Bregman, K. Osaki, G. M. J. Schmidt and F. I. Sonntag, J. Chem. SOC.,1964, p. 2021; G. M. J. Schmidt, Pure Appl. Chem., 1971,27,647. 9 F. Nakanishi, H. Nakanishi, M. Tsuchiya and M. Hasegawa, Bull. Chem. SOC. Jpn., 1976,49,3096. 10 M. Lahav and G. M. J. Schmidt, J. Chem. SOC. B, 1967,239. 11 M. Norval, T. J. Simpson, E. Bardshiri and S. E. M. Howie, Phorochem. Photobiol., 1989,49,633. 12 P. L. Egerton, E. M.Hyde, J. Trigg, A. Payne, P. Beynon, I,.. 'I Mijovic and A. Reiser, J. Am. Chem. SOC., 1981, 103,3859. 13 H. Amarouche, C. de Bourayne, M. Riviere, and A. Lattes, C. R. Acad. Sci., 1984,298, 121. 14 H. C. Curme, C. C. Natale and D. J. Kelley, J. Phys. Chem., 1967,71, 767. 15 F. D. Lewis and J. D. Oxman, J. Am. Chem.SOC., 1984,106,466. 16 P. J. Wagner and D. J. Bucheck, J. Am. Chem. SOC., 1969,91,5090. 17 A. Defoin, R. Defoin-Straatman, K. Hildebrand, E. Bittersmann, D. Kreft and H. J. Kuhn, J. Photochem., 1986,33,237; H. J. Kuhn and A. Defoin, EPA Newslert., 1986, 26, 27; S. E. Braslavsky and H. J. Kuhn, EPA Newslett., 1987,29,49. 18 A. Albini, Synthesis, 1981,249. 19 G. S. Hammond, J. Saltiel, A. A. Lamola, N. J. Turro, J. S. Bradshaw, D. 0.Cowan, R. C. Counsell, V. Vogt and C. Dalton, J.Am. Chem. SOC.,1964,86, 3197; A. A. Lamola and G. S. Hammond, J. Chem. Phys., 1965, 43, 2129; W.G. Herkstroeter and G. S. Hammond, f. Am. Chem. SOC.,1966,88,4769. 20 G. S. Hammond, C. A. Stout and A. A. Lamola, J. Am. Chem. Soc., 1964,86,3103. Dimethyl xylate 15.-Very dense oil (Found: C, 57.0; H, 4.9); 6H7.06 (1 H, dd, J1 5.1, J2 1.2 Hz), 6.82 (1 H, dd, J1 5.1, J2 3.5 Hz), 6.70 (1 H, dd, J13.5, J21.2 Hz), 4.50 (1 H, m, J6 Hz), 3.78 (1 H, m, J6 Hz) and 3.71 (3 H, s); v,,, 1730,1610,1440,1375,1320and 1165 cm-'; m/z 336.References 1 M. DAuria, Guzz. Chim. Ital., 1989, 119,419. 2 M. DAuria, A. De Mico and F. DOnofrio, Heterocycles, 1989, 29, 1331. 3 D. A. Ben-Efraim and B. S. Green, Tetrahedron, 1974,30,2357. 4 S. Caccamese, G. Montaudo and M. Przybylski, Org. Muss Spectrum., 1974,9, 11 14. 21 T. Sasaki, Biochem. Z., 1910,25,272.~-3,~-4-Di-(2-thieny~cyclobutane-r-l,c-2-dicarbo-1947,69,460.22 P. D. Bartlett and S. D. Ross, J. Am. Chem. SOC., 23 I. Kasiwagi, Bull. Chem. Soc. Jpn., 1927,2, 310. 24 G. J. Leuck and L. Cejka, Org. Synth., 1932, Coll. Vol. 1, p. 278. 25 R.C. Larock, D. R. Leach and S. M. Bjorge, J. Org. Chem., 1986,51, 522 1. 26 A. P. Dunlop and F. N. Peters, The Furans, Reinhold, New York, 1953. 27 D. Pirillo, G. Rescia, G. Traverso and A. de Paoli, N Farm., Ed. Sci., 1980,35,324. 28 R. F. Heck, J. Am. Chem. SOC., 1968,90,5518. Paper 9/04640B Received 30th October 1989 Accepted 3rd June 1990