THE CHEMICALNATURE OF THIOPHENE AND ITS DERIVATIVES
. HOWARD D. HARTOUGH Socony-Vacuum Laboratories, Research and Development Division, Paulsboro, New Jersey
INTRODUCTION
Table 1 consists of a collection of miscellaneous data Although Victor Meyer specifically chose the generic obtained from private work and the literature, that inname thiophene to designate the similarity in chemical dicate that thiophene is substituted primarily a t the and physical nature of thiophene and benzene, it is 2-position. I t will be noted that alkylation and nitraconsidered today to have been an unwise choice be- tion are the only two reactions studied that have given cause of the multiplicity of the chemical nature of thio- significant amounts of 3-substituted products. The only real anomaly in the substitution of thiophene. The recent theory of "super-aromaticity" attributed to the five-membered heterocyclics, coupled phene is the alkylation reaction. The isolation of with the traditional chemical comparison of benzene and nearly equimolar amounts of 2- and 3-alkylthiophenes thiophene, has definitely hindered thiophene research. is difficultto explain on the basis of typical nucleophilic If one could apply inorganic chemical terms to the substitution. Furthermore, if one considers the polythiophenes, they might best he classed as "amphoteric" merization of thiophene with an acidic catalyst, such as in that they possess definite properties of one major orthophosphoric acid, in which a 2,4-di-(2-thieny1)thioclass (the aromatics), yet they show properties which lane is produced from thiophene ( 1 2), it becomes evident are attributable to their ability to function as another that the usual substitution of a resonating aromatic class of compounds (the olefins). Organic chemists, ring is not involved. This polymerization of thiophene, who in the future will be the greatest contributors to which in one sense is an alkylation of thiophene with thiophene chemistry, will proceed on the theory that thiophene, involves the addition of a proton to the thiothe chemistries of thiophene and benzene are to be phene at the 2-position in the following manner (12). compared only as a zoologist would compare the tortoise and the boa constrictor; basically they are of the same class but of widely separated species. FACTORS AFTECTING SUBSTITUTION IN THE THIOPHENE NUCLEUS (1) (11) (111) (IV) It must be recognized that whereas all positions in the Thus, the resonance type (11) adds thiophene a t the unsubstituted benzene nucleus are equivalent, the replacement of the -CH=CH-moiety by the hetero- 3-position and subsequently in the 5-position to produce atom, sulfur, introduces a factor into the thiophene 2,4di-(2-thieny1)thiolane. nucleus that goes far toward controlling subsequent substitution. Thus substituents on the thiophene nucleus produce orientations only in competition vith or in conjunction with the strong directive influences already present. Prior to 1933, it was believed that electron-witlidrawing groups (e.g, -COOH, -KO,, etc.) which direct entering groups toward the meta-position in benzene, also always direct to this position in the thiophene series. Rinkes (1)disproved this theory with an excellent orientation study and showed that the heterosulfur still was a more powerful directing agent than typical electronwithdrawing groups. Again it was not until the alkylation study of Applehy, et al. (2), that invariability of typical nucleophilic substitution of the 2-position of thiophene was seriously questioned. Since alkylation (V) is an anomalous reaction which yields higher propor2,4-di-(2thienyl)thiolnne tions of 3-substutition than is expected, it will be discussed in some detail below. The resonance form (111) adds thiophene a t the 2500
SEPTEMBER, 1950
position and subsequently in the Cposition to give (V). (IV) is an inactive hybrid that would not enter the reaction. Alkylation is considered in this manner to be the addition of either of the resonance forms (11) or (111) to an olefin with subsequent rearrangement of the olefinic moiety and expulsion of a proton (13). Thus an alkylation product that appears to he the result of a typical nucleophilic reaction is arrived at and explained on the basis of a copolymerization-rearrangement reaction which produces both the 2- and 3-substitution with almost equal ease. Alkylation a t the 2-position may also occur by addition of the proton to the o l e h with subsequent attack of the thiophene by this carhonium ion. DIRECTIVE INFLUENCES OF TYPICAL ORTHO-PARADIRECTING GROUPS
SO1
TABLE 1 Isomer Formation in Monosubstitution Reactions
--
Entering group &position. %position 7 -
'I'ype reaction
Reference -
Acylation 100% None detected! (3) Aminomethylation 100% None detected" (4) Transmetalation 100% None detected" (5,G) Chlorination 99.7% 0.3% (7) Major Trace Sulfonstion (8) Nitration" 97% 3% (69) Alkylation 60% 40% (L .. . . 10-18) .. " Amounts of less than 1 per cent would not have been deteitted by the methods used. By V. Meyer's method described in Reference 9.
the 5-position, nevertheless there is a tendency for an electron pair to be displaced toward this latter position. This fact is born out. by certain chemical reactions (see Table 2).
Only for the chlorination of 2-chlorothiophene has the ratio of isomeric products been determined (7). At TABLE 2 50°, this reaction gives 99 per cent of 2,5dichlorothiophene and 1 per cent of 2,3-dichlorothiophene. The Isomer Formation During Monosubstitution Reactions i n the 3-Methylthiophene Nucleus combined tendencies of the chlorine atom and the - nuclear sulfur atom to direct the second chlorine atom to Entering group the 5-position naturally predominate, hut the residual Type reaclion %Position 5-Position Refewnee tendency of the chlorine atom to orient ortho (in this case, the 3-position) has not been entirely overcome. Hartough and Kosak (IS)did not note isomer formation in the acylation of 2-methylt,hiophene. No isomer formation was noted in the metalation of Z-methylthio~ h e n ewith sodium (1L). However. the Dresence of i per cent or less of'
