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The Photochemical Isomerization Reactions in Furan, Thiophene, and Pyrrole Derivatives Maurizio D’Auria Dipartimento di Chimica, Universitą della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy Received 10 June 1997 Received revised 20 July 1997 Accepted 20 July 1997 Published 30 July 1997 Abstract The photochemical behaviour of furan, thiophene, and pyrrole derivatives appears to be very complex and, apparently, no common description of the reactivity of these heterocycles is possible. On the basis of PM3-RHF-CI semiempirical calculations an unitary description of the behaviour of these molecules can be made. Furan reacts giving the cyclopropenyl derivative because its triplet state can give the biradical intermediate 7a, while the isomerization products can be obtained only by the excited singlet state via the corresponding Dewar furan. Thiophene can give only Dewar thiophene from the excited singlet state, while the triplet state can not give the biradical intermediate 7b. Finally, pyrrole can not give the Dewar pyrrole, thus preventing the formation of isomeric products, and only 2-cyanopyrrole is able to give this intermediate. Introduction Same years ago, in a text on the heterocyclic chemistry, Newcome and Paudler reported that the photochemical isomerization in p excessive heterocycles was restricted to furan and thiophene derivatives, while pyrrole did not give this type of reaction. Furthermore, the mechanisms reported for the reactivity of furans and thiophenes are quite different, giving the impression that the reactivity of these two heterocycles was completely different.1 Gilchrist reported the photochemical isomerization of the thiophene while furan and pyrrole can not be treated in his book. Furthermore, two mechanisms are reported for this isomerization, inducing the reader to consider this field in a confused status.2 Actually, the descriptions of the photochemical isomerization of furan, thiophene, and pyrrole derivatives were reported separately (see below) and no attempt was made to give an unitary explanation of the different behaviour of these molecules. In this paper we want to report a first unitary description of the photochemical isomerization of these p excessive heterocycles by using semiempirical calculations. We do not consider it a definitive explanation but only a first attempt to understand the photochemistry of these heterocycles. The Photoisomerization of Furans, Thiophenes, and Pyrroles The first report on the gas phase photolysis of furan was published in 1967.3 The author reported that the photolysis of furan and mercury vapour at 254 nm gave carbon monoxide and a fraction containing mainly cyclopropene and a very little amount of propyne or allene. Successively, carrying out the reaction at higher pressure, the same author showed that three new products were obtained. The first two compounds were the Diels-Alder adducts obtained by the coupling between furan and cyclopropene while the third was a Diels-Alder adduct obtained by the coupling between furan and cyclopropene-3-carbaldehyde. Nine of the products reported was observed on direct irradiation of furan in solution.4,5 Liquid phase photolysis of furan was in agreement with the formation of cyclopropene-3-carbaldehyde.6 The direct flash photolysis of furan gave, on the contrary, a different behaviour. Mass fragments corresponding to C4H+, C4H2+, C4H3+, and C4H4+ were observed together with the formation of cyclopropene-3-carbaldehyde.7 This behaviour can be explained assuming that Dewar furan is the precursor of the cyclopropene derivative. Dewar furan can be obtained also by the photolysis of furan in argon matrices at 10 K.8 The direct irradiation of the furan gave carbon monoxide, methylacetylene, and allene, while cyclopropene was detected only in traces.9 Similarly, 2-methylfuran, irradiated in the presence of mercury vapour, gave carbon monoxide and a fraction containing 1,3-butadiene and 3-methylcyclopropene (45 :55).3 Successively, it was found that in both sensitised and direct photolysis of 2-methylfuran a more complex mixture of products was obtained where 3-methylfuran was present.10-11 The obtaining of these products can be explained assuming that the triplet 2-methylfuran gave the ring contraction product 1, which was the key intermediate of all the products observed (Scheme 1). The mercury sensitised irradiation of 3-methylfuran gave 2-butyne, 1,2-pentadiene, 1-methylcyclopropene, 1-butyne, and 1,3-butadiene.11 In the direct irradiation, 1-methylcyclopropene was obtained in lower yields while both 3-methylcyclopropene and 2-methylfuran appeared.11 2,4-Dimethylfuran, in the sensitised reaction, gave 1,3-dimethylcyclopropene (the main product), isoprene, cis and trans 1,3-pentadiene, 2-pentyne, and 1-methylcyclopropenyl methyl ketone.11 It is noteworthy that the ring contraction showed a high selectivity. Calculation on the excited state of the substrates showed that the direction of the ring contraction can be predicted, on the basis of the mechanism depicted in Scheme 2, if the weakest bond in the excited furan derivative is known.12,13 Nevertheless, we have to note that cyclopropene-3-carbaldehyde can be obtained also by thermal rearrangement from the Dewar furan.14-16 The irradiation of 2,5-dimethylfuran in the presence of mercury vapour gave a complex mixture of products. Carbon monoxide and propene were removed as gaseous products. Then, cis and trans 1,3-pentadiene, isoprene, 1,3-dimethylcyclopropene, 2-pentyne- 2-ethyl-5-methylfuran, hexa-3,4-dien-2-one, 1-methyl-3-acetylcyclopropene, and 4-methylcyclopent-2-enone were obtained.17 On the contrary, in the direct irradiation of 2,5-dimethylfuran, the only isolated product was 2,4-dimethylfuran.10 The direct or sensitised irradiation of furan-2-carbaldehyde gave the same type of products : carbon monoxide, methylacetylene, cyclopropene, and furan. In this case, the most important process in the reaction seems to be the homolytic cleavage of a C-C bond to give the loss of the carbonyl group.9,18,19 All the reactions described above were reported to be effective in vapour phase, while no reaction occurred in solution. Only a few reactions are described in pentane solution. 2,5-Di-t-butylfuran, irradiated in pentane, gave the corresponding cyclopropenyl ketone, 2,4-di-t-butylfuran, and an allene.20,21 The irradiation of the cyclopropenyl ketone gave 2,5-di-t-butylfuran, 2,4-di-t-butylfurane and the allene showing it was an intermediate in the reaction mixture. The irradiation of 2,4-di-t-butylfuran gave the corresponding cyclopropenyl derivative. Finally, 2,3,5-tri-t-butylfuran gave the cyclopropenyl derivative 2 (5%), and the ketone 3 (95%) (Scheme 3). More recently, the same reaction was attempted with 2-trimethylsilylfuran, which gave an allene derivative in 68% yield. Also 2,5-di-trimethylsilylfuran, 2,4-di-trimethylsilylfuran, 5-methyl-2-trimethylsilylfuran gave the same type of products.22 The formation of all the compounds can be explained assuming the presence of a cyclopropyl intermediate that, then, was converted into the allene. Such a cyclopropyl intermediate can be isolated in the reaction of furan-2-carbonitrile in the presence of methanol. In this case, the reaction gave a mixture of three isomeric products containing MeO substituents.23,24 These products clearly were obtained from the cyclopropenyl intermediate through a Michael addition of methanol. The irradiation of furan derivatives in propylamine led to the formation of the corresponding pyrrole. The reaction mechanism can be explained as depicted in Scheme 4.25,26 It is noteworthy, however, that, when the tetrakis(trifluoromethyl)cyclopropene derivative of the proposed imine was synthesised, it could not be converted into the corresponding pyrrole. In this case the observed behaviour can be explained assuming the formation of a Dewar furan intermediate.27 The UV spectrum of the pyrrole in vapour phase showed absorptions at 211.0, 217.0, and 237.5 nm. The absorption at 237.5 nm was identified as relative to a p,p* transition and no decomposition of the starting material was observed.28 Successively, pyrrole vapours were irradiated at 214 nm at room temperature showing that some decomposition products were obtained: so propyne, allene, ethylene, acetylene, and propene were observed in the reaction mixture together with HCN.29 It should be noted that authors identified only decomposition products, while they did not find isomerisation products, as in vapour phase photochemistry of furan. Furthermore, vapour phase photolysis of 2,5- and 2,4-dimethylpyrroles at 214 and 229 nm showed only hydrogen, methane, and ethane, while no product derived from ring opening was observed.30 To confirm these experimental data, Dewar pyrrole, generated by photofragmentation of a suitable substrate, showed to be very unstable in comparison to similar compounds obtained with furans or thiophenes.31 In 1970 Hiraoka reported that 2-cyanopyrrole, irradiated in methanol with a low pressure mercury arc for 20 h, gave a mixture of 3-cyanopyrrole and pyrrole-2-carbaldehyde.32 Theoretical calculations on the pyrrole are in agreement with the experimental results. In fact, they showed that the decomposition reactions to give acetylene were more likely that the photoisomerisation. Furthermore, they showed that strong electron donor or acceptor substituents can modify this behaviour.33 1-Methyl-2-cyanopyrrole also gave this reaction.34 In this case the author isolated the product of the isomerisation, the product of the shift in C-2 of the N-methyl group, and a third product that be assumed to be derived from the addition of methanol to the Dewar pyrrole. The reaction depends on the temperature used : in fact, no reaction occurred when the reaction was performed at -68°C. This datum is in agreement with the presence of a thermal activated step.35 More recently, the nature of this third product was re-evaluated and the structure 4 was proposed.35 This structure was confirmed also by performing the reaction in the presence of furan. In this case, 4+2 photoadducts were isolated. All these data seem to be in agreement with a mechanism depicted in Scheme 5, where the thermal activated step is the 1,2-sigmatropic shift between 5 and 6. Similar results were obtained using methyl substituted 2-cyanopyrroles.36 Recently, the 1,3-sigmatropic shift on 2-cyanopyrrole was studied by using the SINDO1 semiempirical method.37 This study showed that the reaction occurred via a p,p* transition and that some biradical intermediates are probably involved in the reaction. The irradiation of the thiophene in gas phase yields ethylene, allene, methylacetylene, carbon disulphide, and vinylacetylene. No Dewar thiophene or cyclopropene derivatives were isolated.38 The irradiation in liquid phase gave the Dewar thiophene which can be trapped as a Diels-Alder adduct with furan.39 The Dewar thiophene and cyclopropene-3-thiocarbaldehyde can be obtained by irradiation in argon matrices at 10 K.8 Finally, the Dewar thiophene can be obtained by irradiation of tetrakis(trifuoromethyl)thiophene.40-44 The most interesting reaction in this field has been discovered by Wynberg in 1965. The irradiation of 2-substituted thiophenes gave the corresponding 3-substituted derivatives.45 In the first experiments, only arylthiophenes were used as substrates.45-50 The dithienyls gave this reaction efficiently while 2-(2-pyridyl)thiophene and 2-(2-furyl)thiophene did not give this reaction in a reasonable yield.51,52 The alkylthiophenes reacted also but they showed a lower reactivity.53 Carbonyl and olefinic substituents inhibit the rearrangement.54-62 Several studies have been accomplished on the mechanism of this photoisomerisation showing that the reaction takes place from the singlet excited state of the molecule,63 that the interchange between C2 and C3 occurs without the concomitant interchange between C4 and C5, and that the bonds between ring carbons and the substituents are not broken.64 Three mechanisms have been proposed (Scheme 6) and Wynberg preferred the third. More recently several studies showed that the mechanism two is the most probable.65,66 Furthermore, in the photoisomerisation reaction of cyanothiophene derivatives, a Dewar thiophene was isolated and it showed to be an intermediate in the isomerisation reactions.67,68 As reported for the furan derivatives, also thiophenes, when irradiated in the presence of an amine gave the corresponding pyrroles.25,26 The authors proposed the formation of a cyclopropenyl intermediate, but, successively, a Dewar thiophene derivative, treated with aniline, gave the corresponding pyrrole showing that, probably, it is the true intermediate in this reaction.27 Results and Discussion As reported above, we are in front of very different behaviours depending on the nature of the heterocycle. Briefly, the photochemistry of the furan is characterised by the presence of cyclopropenyl derivatives in the sensitised reactions, while, upon direct irradiation, also isomeric furans were observed. When thiophene is used as starting material, only isomeric thiophenes were observed in an excited singlet state process, probably involving the formation of a Dewar thiophene, while no cyclopropenyl derivative was observed. Finally, the irradiation of the pyrrole gave only decomposition products. Only, 2-cyanopyrroles give isomeric pyrrole derivatives upon irradiation. We started calculations on these molecules in order to consider the possibility to find a unitary interpretation of the above described behaviour. The results are summarised in Table 1. We performed our calculations by using PM3-RHF-CI semiempirical method. We have calculated the relative energy of the first excited singlet state, the energy of the first excited triplet state, the relative energy of the Dewar heterocycles in their singlet state, and finally, the relative energy of the biradical 7 deriving from the fission of the bond between the heteroatom and C-1. The intermediate 7 is supposed in the isomerisation process leading to the formation of the cyclopropenyl derivatives. We have to note that in literature we could not find data on the singlet and triplet state energy of furan, pyrrole, and thiophene. On the basis of these data we can examine the photochemical behaviour of each heterocycle. Considering the furan, the data collected in Table 1 and Fig. 1 fit the experimental results. In the case of the sensitised reaction, when the excited triplet state is populated, only the formation of the intermediate 7a is allowed. The intermediate 7a can evolve to the corresponding cyclopropenyl derivative or to the decomposition products. In a previously reported mechanism9 the decomposition products resulted from the excited cyclopropenyl derivative. In our hypothesis the formation of both the decomposition products and the cyclopropenyl derivatives can be considered as competitive reactions. Figure 1 - Relative energies of the excited states of furan and of some reactive intermediates
Heterocycles | Biradical intermediate | Electronic state | Relative energy [kcal mol-1]
Furan |  | S1 | 129
Furan |  | T1 | 74
Dewar Furan |  | S0 | 78
| 7a | T1 | 73
Thiophene |  | S1 | 71
Thiophene |  | T1 | 62
Dewar Thiophene |  | S0 | 65
| 7b | T1 | 69
Pyrrole |  | S1 | 96
Pyrrole |  | T1 | 66
Dewar pyrrole |  | S0 | 73
| 7c | T1 | 63
2-Cyanopyrrole |  | S1 | 99
2-Cyanopyrrole |  | T1 | 75
Dewar 2-Cyanopyrrole |  | S0 | 71
Table 1 - Relative energy of both some heterocyclic derivative and reactive intermediates. Figure 2 - Relative energies of the excited states of thiophene and of some reactive intermediates In the case of the direct irradiation, the singlet excited state is populated and, then, the formation of the Dewar furan is energetically possible (Fig. 1). This result is in agreement with both the evidences about the formation of the Dewar furan in the direct irradiation and with the formation of isomeric furans. The direct irradiation of thiophene derivatives gives the isomeric product only. The cyclopropenyl derivatives were not observed. Also in this case our calculation results fit the experimental data (Table 1, Fig. 2). In fact, the singlet excited state can evolve giving the Dewar thiophene (and, then, isomeric thiophenes) or the corresponding excited triplet state. This triplet state can not be converted into the biradical 7b because this intermediate shows a higher energy than the triplet state, thus preventing the formation of the cyclopropenyl derivatives. Figure 3 - Relative energies of the excited states of pyrrole and of some reactive intermediates When pyrrole is irradiated only decomposition products were obtained Our data can fit this statement (Table 1, Fig. 3). In fact, the direct irradiation populates the excited singlet state which can be converted into the Dewar pyrrole or into the corresponding triplet state. Clearly, the intersystem crossing to the triplet state allows to reach the lowest energy state. The excited triplet state can give a biradical intermediate 7c, and this intermediate can give or the decomposition products only, or the cyclopropenyl derivative that thermally evolves to give the decomposition products as reported in Ref. 27. On the contrary, when the irradiation is performed on 2-cyanopyrrole, the isomeric products are observed. In fact, in this case, the corresponding Dewar pyrrole shows a lower energy than in the previous case, allowing the formation of the isomeric products (Table 1, Fig. 4). In conclusion, we can see that the complex reactivity observed in the photochemical behaviour of furan, thiophene, and pyrrole derivatives can be easily explained in terms of the relative energies of the corresponding reactive intermediate. We think that our approach represents only the first attempt to rationalise the photochemistry of these compounds and that work must be done in order to improve the method and its confidence. Nevertheless, our first results allow us to discuss the photochemistry of p excessive heterocycles in satisfactory manner. Figure 4 - Relative energies of the excited states of 2-cyanopyrrole and of some reactive intermediates References Newcome, G. R.; Paudler, W. W. 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