The Reactions of Heterocyclic Compounds

The Reactions of Heterocyclic Compounds Calculations similar to those given above may be extended to organic compounds other than hydrocarbons for example, in the series furan, 

Reference to the bond angles and interatomic distances for these molecules shows that as far as the carbon atoms are concerned their values are little different from those of the olefin molecule. It would be expected, therefore, that catalysts which were effective for hydrogenation of the latter would also function with the heterocyclic molecules. This is found to be so, in that nickel catalysts are known to give tetrahydrofuran and pyrrolidine by the hydrogenation of furan and pyrrole at 180° (Padoa, 25). Tetrahydrofuran is also formed by the use of platinum (Starr and Hixon, 26), osmium, or palladium (Shuikin, Nikiforov, and Stolyarova, 27) as the catalyst, and pyrrolidine is similarly produced by palladium or rhodium catalysts (Zelinskii and Yurev, 28). In all these metals there are spacings of the atoms very similar to those in metallic nickel, the hexagonal osmium lattice having a equal to 2.71 A. 

The corresponding change with thiophene does not take place because the catalysts are poisoned by the sulfur. In order to hydrogenate thiophene, therefore, sulfur-resisting catalysts must be sought. These have been found in the sulfides of molybdenum and nickel, described by Moldavskii and Kumari (29) and by Cawley and Hall (30). In both these series of experiments, static systems under pressure were used, so that no sulfur was carried away from the reaction zone and at least part of the catalyst remained in the form in which it was originally added. The structures of M0S2 and NiS are therefore to be considered. 

What has already been said about the disposition of olefins on MoSa can obviously be applied equally to the thiophene molecule, assuming that one double bond is opened by two-point adsorption. This argument, which can explain the known activity of MoSa for this conversion, would also indicate a similar activity for NiS, since this sulfide consists of a hexagonal lattice with alternate layers of nickel and sulfur atoms in which the shortest Ni—Ni distance is 2.65A., and which would, therefore, be suitable for two-point adsorption of thiophene. 

Nickel subsulfide. Plans of the 100-pIane (upper) and of the 111-plane (lower). 

---

Identification of the product(s) resulting from the reaction of heterocyclic compounds with diazomethane has been used in attempts to elucidate their tautomeric composition (for summaries, see references 7 and 41). This work was based on the assumption that if a compound which is capable of existing in both an —NH and an —OH form produced only the =NMe derivative when it w as treated with diazomethane, it existed entirely in the =NH form. On the other hand, formation of the —OMe derivative was interpreted to mean that a finite amount of the compound existed in the —OH form. In some cases the tautomer present in the solid state w as concluded to be different from that present in solution for example, 41 42 gave a higher proportion of the 3,4-dimethoxy derivative when ethereal diaz-... 

The reactions of carbenes, which are apparently unique in displaying electrophilic character in strongly basic solutions, include substitution, addition to multiple bonds, and co-ordination with lone pairs of electrons to form unstable ylides. This last reaction is of obvious relevance to a consideration of the reactions of heterocyclic compounds with carbenes and will be summarized. 

The Reactions of Heterocyclic Compounds with Carbenes C. W. Rees and C. E. Smithen... 

For a review of the reactions of heterocyclic compounds with carbenes, see Rees Smithcn Adv. Heterocycl. Chem. 1964, 3, 57-78. 

Transient products of the reactions of heterocyclic compounds with e q have been observed for adenine, purine, cytosine, methylcytosine and thiobarbituric acid (Gordon, 1964) as well as for pyridine (Cercek and Ebert, 1967). A systematic study of the chemical behaviour of these transients is desired, as some of them may be intermediates of biochemical and radiobiological importance. 

Rees, C.W. and Smithen, C.E. 1964. The reactions of heterocyclic compounds with carbenes. Advances in Heterocyclic Chemistry, 3 57-78. 

Rees, C. W., Smithen, C. E., The Reactions of Heterocyclic Compounds with Carbenes, 3,57. Reid, S. T., The Photochemistry of Heterocycles, 11,1 The Photochemistry of Oxygen- and Sulfur-Containing Heterocycles, 33, 1 Photochemistry of Nitrogert-Containing Heterocycles, 30, 239. 

The authors of this review believe that the rationalization of the reactions of heterocyclic compounds would be considerably assisted by semiquantitative estimates of aromaticity clearly this field is wide open for development. The existing information needs to be collated and extended and new quantitative investigations are required. More work is needed on the interrelationship of the various available methods, existing methods need to be generalized, new general methods discovered, and the general relation of aromaticity to reactivity developed. 

The reactions of heterocyclic compounds composed of fused systems (6 6 6), such as electrophilic and nucleophilic attack at a ring or a substituent and partial reduction, are often highly selective. Unfortunately, there are few unifying features among the reactivities of the three different classes of systems, and a detailed treatment of the reactivity is beyond the scope of this concise chapter. All references to the chemistry of a particular parent compound and derivatives are given in Tables U3. 

---