Thiophenes, acetyl-, bromination

The difference in p values for equivalent reactions is probably not significant, particularly as there are often differences in reaction conditions and interpretations. Thus the kinetic form of some of the thiophene brominations are in doubt,258 there is a variation in acidic media used for the protodetritiation,260 and a different catalyst, SnCl4, is used for the thiophene acetylations 261,262 cf that for the benzenoid reaction, A1C13. In general, therefore, and in particular for the chlorination reaction,257 there appears to be a constant oi value for thiophene with additivity of substituents effects, but there is certainly room in this area for further experimentation and debate. 

Dimethoxy- and 5,6-methylenedioxybenzo[6]thiophene undergo bromination, Vilsmeier-Haack formylation, and Friedel-Crafts acetylation in the 2-position (see Section VI, A).189 With nitric acid, however, 5,6-methylenedioxybenzo[6]thiophene affords an unidentified mononitro derivative, which is not the 2-nitro compound.548... 

Nitration of 4-(2-thienyl)- (301) and 4-(3-thienyl)-pyrazoles (302) mainly occurs on the thiophene ring, but when acetyl nitrate is used as the nitration agent small quantities of products nitrated on the pyrazole ring are isolated (position of the nitro group uncertain) (80CS( 15)102). Pyrazol-l -ylpyridines (303) undergo electrophilic reactions (bromination, chlorination and nitration) preferentially in the pyrazole ring. Thus, the nitration of (303 R = R = = H) either with a mixture of nitric acid and sulfuric acid at 10-15 °C or with... 

In the reactions of 2,5-disubstituted thiophenes elimination of an a-substituent occurs to a much greater extent than in the benzene series. The Friedel-Crafts acetylation of 5-bromo-2-ethylthiophene in the presence of SnCE gives 2-ethyl-5-acetyIthiophene. Elimination of an a-bromine occurs also in the chloromethylation of 2,5-di-bromothiophene, leading to a mixture of 2-bromo-5-chloromethyIthio-phene and 2,5-dibromo-3-chloromethyIthiophene. Bromine atoms at both the and -position are exchanged for chlorine in the... 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (a) formylation by phosgene and V,iV-dimethylformamide, (b) acetylation by acetic anhydride and tin(IV) chloride, and (c) trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235) are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate for trifluoroacetylation, by the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 5) (2-methylindole ss V-methylindole > indole > pyrrole > furan > thiophene (73CC540)). 

Tetrahydrobenzo[ ]thiophene behaves like thiophene in electrophilic substitution reactions. Thus, it is formylated with a mixture of vV-methylformanilide and phosphorus oxychloride,436 iodinated in the presence of mercuric oxide,193 and brominated by V-bromosuccinimide,193 all in the 2-position in Friedel-Crafts reactions with acetyl chloride,194-436 propionyl chloride,436 succinic... 

Alkoxybenzo[6]thiophenes undergo electrophilic substitution in the 2-position. Thus, 6-ethoxybenzo[6]thiophene affords its 2-bromo, 2-formyl, and 2-acetyl derivatives on bromination, Vilsmeier-Haack formylation, and Friedel-Crafts acetylation, respectively,424 and 6-methoxybenzo[6]thiophene undergoes Friedel-Crafts reaction with /3-carbomethoxypropionyl chloride in the 2-position.618... 

Relative rates of substitution for a number of substituted thiophenes sufficient to test the applicability of po+ relationships are available for seven reactions bromination by molecular bromine, chlorination by molecular chlorine, protodetritiation, proto-dedeuteriation, acetoxymercuration, tin tetrachloride-catalyzed acetylation, and trifluoroacetylation. The relevant data are assembled in Table XXIII. 

Isatin forms a blue condensation-product (indophenine) with thiophene. On reduction with ammonium sulphide, isatide C16H12N2O4 [16] is formed. With zinc powder in acetic-acid solution, isatin yields bydroisatinj by more energetic reducing-agents oxy- and dioxy-indol are formed. Chlorine and bromine react with isatin, forming chlorine and bromine derivatives respectively. Acetic anhydride produces an acetyl isatiu [15],... 

Friedel-Crafts acylation, nitration, sulfonation, and bromination of benzo[ )naphtho[l,2-d]thio-phene take place at the position shown in (369) <84PJCI243>. Nitration as well as Friedel-Crafts acetylation of phenanthro[4,5-Z>c. 

Isomer distributions have been determined for several electrophilic substitutions of thiophen, such as bromination by Bra and Br+, chlorination by tin tetrachloride, or iodine-catalysed acetylation by acetic anhydride, trifluoroacetylation, and Vilsmeyer formylation. The a. ratios vary from 100 to over 1000, according to the selectivity of the electrophilic agent. The results obtained, together with other data from the literature, permit a test of the applicability of linear free-energy treatments to electrophilic substitution at the a- and j8-positions of thiophen. Plots of log (Xf and log jSf against p for nine reactions were linear, and from the slopes values of = — 0.79 and 0)3+ = — 0.52 were obtained. Serious deviations were observed for mercuration and protodemercuration, while nitration and protodeboronation were not taken into account, as deviation could be expected for various reasons. The linearity was taken as evidence... 

Electrophilic Substitution.—The isomer distributions and the rates relative to those of the parent heterocyclic compounds for acetylation, benzoylation, chlorination, and bromination of benzo[Z>]thiophen and benzo[6]furan have been determined. It was found that although the orientation of substitution in the two bicyclic systems is different, the effect caused by annelation on the reactivity of the a- and jS-positions is substantially the same in the two rings the reactivity of the a-position is always decreased by a similar factor, and the reactivity of the j8-position is increased (with some exceptions) in both systems. The different orientation observed in the... 

Acetyl- and 3-formylbenzo[6]thiophen have been nitrated under conditions similar to those used for the acid. Although treatment of the 3-acetyl derivative with concentrated nitric acid in acetic acid containing 10% of sulphuric acid led to furoxan formation, reaction with potassium nitrate in concentrated sulphuric acid at 0 °C, or with a cold mixture of fuming nitric acid and acetic anhydride, gave rise to substitution at all four available positions in the benzene ring. Similar results were obtained with the 3-formyl derivative. In addition, with the last-mentioned method, appreciable amounts of deacetylation and deformylation, leading to the 3-nitro-derivative, were observed. Attempted bromination of both 3-acetyl- and 3-formyl-benzo[6]thiophen by means of bromine in acetic acid failed. ... 

Various Physical Properties.—Radical cations of 2,5-dialkylthiothiophens have been obtained and their e.s.r. spectra interpreted in terms of unequally populated rotational isomers. The mass spectra of some simple thiophens and some azines derived from 2-acetyl- and 2-formyl-thiophens have been obtained. Molecular ion isomerizations occurring in 3-phenylthiophen and two brominated derivatives have been followed in both slow and fast reactions using C-labelling. Affinities, standard heats, and standard entropies of dyeing of some thiophen-containing azo dyes have been... 

The reactions of bromine, acetyl chloride, and butyl-lithium with the zinc chelate (148) have been studied, " as has the action of methyl iodide on some chelates derived from (149). " Chelates derived from 2,5-dimercapto-thiophens such as (150) have been prepared. Interaction of dipotassium... 

Electrophilic Substitution.— The great interest in electrophilic substitution of benzo[b]thiophen derivatives is continuing. The t-butylation of benzo[b]thiophen has been reinvestigated. Isomers and other products obtained in the nitration of 3-t-butyl-2-benzo[b]thiophencarboxylic acid, and in the bromination, nitration, Vilsmeier formylation, and Friedel-Crafts acetylation of 4-methoxybenzo[b]thiophen and its 3-methyl derivative have been carefully determined. Similarly, electrophilic substitution of... 

Electrophilic Substitution. The rate constants and activation parameters for the formylation of selenophen by the DMF-phosgene complex in chloroform have been determined and compared with those of the other five-membered heterocycles. Acylation of 2-benzylselenophen occurs exclusively in the a-position of the selenophen ring. Formylation and acetylation of 2-(2-thienyl)selenophen went predominantly (80 and 75%, respectively) in the a-position of the selenophen ring and 20% in the a-position of the thiophen ring. 2,5-Dimethylselenophen-3-carboxylic acid could be iodinated at position 4 with iodine-iodic acid. Bromination of 2-formylselenophen in AlCh yielded the 4-isomer. Bromination of 2-methylselenophen with N-bromosuccinimide in acetic acid gave 3,5-di-bromo-2-methylselenophen. 

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