Thiophenes, acetyl

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. 

Scheme 12 Use of Sc(III) or Sn(II) inflates as effective catalysts Iot thiophene acetylation [32]...

Thiophenes, acetyl-, 239, 241 dinitro- reactions of, 350 2-halogono-, reactivity of, 351 halogeno-nitro-, 293, 347, 348 mercuration of, 239 nitro-, polarograi c reduction of, 239, 241... 

Acetylthiophene Is prepared by the acetylation of thiophene with acetic anhydride In the presence of orthophosphoric acid ... 

Chapter V. Quinaldine (V,2) 2-methyl-, 2 5-dimethyl- and 2-acetyl-thiophene (V,8-V,10) 2 5-dimethyl and 2 4-dimethyl-dicarbethoxy-p3nrole (V,12-V,13) 2-amino- and 2 4 dimethyl-thiazole (V,15-V,16) 3 5-dimethyl-pyrazole (V,17) 4-ethylp3rridine (from pyridine) (V,19) n-amyl-pyridines from picolines) (V,28) picolinic, nicotinic and isonicotinic acid (V,21-V,22) (ethyl nicotinate and p-cyanop3n idine (V,23-V,24) uramil (V,25) 4-methyl-(coumarin (V,28) 2-hyi-oxylepidine (V,29). 

Sulfonated styrene—divinylbensene cross-linked polymers have been appHed in many of the previously mentioned reactions and also in the acylation of thiophene with acetic anhydride and acetyl chloride (209). Resins of this type (Dowex 50, Amherljte IR-112, and Permutit Q) are particularly effective catalysts in the alkylation of phenols with olefins (such as propylene, isobutylene, diisobutylene), alkyl haUdes, and alcohols (210) (see Ion exchange). Superacids. 

Manufacture of 2-acetylthiophenes involves direct reaction of thiophene or alkylthiophene with acetic anhydride or acetyl chloride. Preferred systems use acetic anhydride and have involved iodine or orthophosphoric acid as catalysts. The former catalyst leads to simpler workup, but has the disadvantage of leading to a higher level of 3-isomer in the product. Processes claiming very low levels of 3-isomer operate with catalysts that are proprietary, though levels of less than 0.5% are not easily attained. 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared in a variety of substitution reactions. Table 2 shows the rates of substitution compared to thiophene for formylation by phosgene and iV,AT-dimethylfor-mamide, acetylation by acetic anhydride and tin(IV) chloride, and trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235). 

Thiophene is much more easily nitrated than benzene and it is therefore possible to use mild nitrating agents such as acetyl or benzoyl nitrate. Like pyrrole and furan the principal nitration product is the 2-derivative. The a selectivity decreases with increasing vigour of the reagent and up to 15% of the 3-isomer has been obtained. 

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

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... 

Thiophene, 3-acetamido-5-methyl-JV-di(2-hydroxyethyl)aniline-4,2 -azo-5 -acetyl-3 -nitro-... 

Benzo[6]thiophene, 2-acetyl-3-hydroxy-synthesis, 4, 892 Benzo[6]thiophene, 2-acyl-synthesis, 4, 918 Benzo[6]thiophene, 3-acyl-synthesis, 4, 918- 19 Benzo[6]thiophene, acylamino-synthesis, 4, 815 Benzo[6]thiophene, alkenyl-synthesis, 4, 917 Benzo[6]thiophene, 2-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 3-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 4-alkoxy-synthesis, 4, 930 Benzo[6]thiophene, 2-alkyl-synthesis, 4, 877-878 Benzo[6]thiophene, 2-alkylthio-synthesis, 4, 931 Benzo[6]thiophene, 2-amino-diazotization, 4, 810 reactivity, 4, 797 stability, 4, 810 synthesis, 4, 869, 924-925 tautomerism, 4, 38 Benzo[6]thiophene, 3-amino-cycloaddition reactions, 4, 68 synthesis, 4, 109, 881, 925 Benzo[6]thiophene, 4-amino-synthesis, 4, 925 Benzo[6]thiophene, 5-amino-synthesis, 4, 925 Benzo[6]thiophene, 7-amino-synthesis, 4, 925 Benzo[6]thiophene, 3-t-amyl-synthesis, 4, 915 Benzo[6]thiophene, 2-aryl-synthesis, 4, 881... 

H NMR, 4, 1042 ionization potentials, 4, 1046 synthesis, 4, 1066 UV spectra, 4, 1044 Selenolo[2,3 -cjthiophenes H NMR, 4, 1042 synthesis, 4, 1067 UV spectra, 4, 1044 Selenolo[3,2-6]thiophenes dipole moments, 4, 1049 H NMR, 4, 1042 ionization potentials, 4, 1046 synthesis, 4, 1066 UV spectra, 4, 1044 Selenolo[3,4-6]thiophenes synthesis, 4, 1067 Selenolo[3,4-c]thiophenes addition reactions, 4, 1062 synthesis, 4, 1076 Selenomethionine applications, 4, 970 Selenophene, 3-acetamido-reactions, 4, 953 Selenophene, 2-acetyl-mercuration, 4, 946 nitration, 4, 947 Selenophene, 2-alkyl-reactions, 4, 45 synthesis, 4, 135, 967 Selenophene, 3-alkyl-synthesis, 4, 135, 967 Selenophene, 3-aryl-synthesis, 4, 963 Selenophene, 2-benzyl-reactivity, 4, 946 Selenophene, 2-benzyl-5-ethyl-reduction, 4, 950... 

Thieno[3,2-h]thiinium perchlorates synthesis, 4, 1028 Thieno[3,2-c]thiinium perchlorates synthesis, 4, 1028 Thienothiinium salts, 4, 1027 synthesis, 4, 1028 UV spectra, 4, 1029 Thienothiins synthesis, 6, 1011 Thieno[2,3-h]thiophene, 2-acetyl-nitration, 4, 1054 Thieno[2,3-h]thiophene, 2-amino-synthesis, 4, 1070... 

Substituted thiophenes, such as 2-iodo-, 2-bromo-, 2 chloromethyl-, and 2-acetyl-thiophene have been obtained by reacting crude, coal-tar benzene with the appropriate reagents. ... 

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 a-selectivity is illustrated by the fact that 2-alkyl-, > 2-methoxy-, > and 2-alkyIthio-thiophenes and alkyl thenyl sul-fides ° are metalated exclusively in the 5-position. In electrophilic aromatic substitution, as previously mentioned, an appreciable amount of 3-substitution is obtained with some of these groups. After acetalization ketones can also be metalated. Thus from the diethyl ketal of 2-acetylthiophene, 2-acetyl-5-thiophenealdehyde was obtained after metalation with n-butyllithium followed by the reaction of the metalorganic compound with A,A -dimethylformamide. ... 

Two different sets of experimental conditions have been used. Buu-Hoi et al. and Hansen have employed the method introduced by Papa et using Raney nickel alloy directly for the desulfurization in an alkaline medium. Under these conditions most functional groups are removed and this method is most convenient for the preparation of aliphatic acids. The other method uses Raney nickel catalysts of different reactivity in various solvents such as aqueous ammonia, alcohol, ether, or acetone. The solvent and activity of the catalyst can have an appreciable influence on yields and types of compounds formed, but have not yet been investigated in detail. In acetic anhydride, for instance, desulfurization of thiophenes does not occur and these reaction conditions have been employed for reductive acetylation of nitrothiophenes. Even under the mildest conditions, all double bonds are hydrogenated and all halogens removed. Nitro and oxime groups are reduced to amines. 

Fatty acids are prepared by acylating thiophene with acid chlorides and reducing the ketones (218) to alkylthiophenes according to Wolff-Kishner or Clemmensen. The latter are then acetylated and oxidized by hypochlorite to 5-alkyl-2-thiophenecarboxylic acids, > ... 

Many stilbenelike thiophene compounds have been prepared for a study of estrogenic activity, especially by Buu-Hoi et al. Thiophene derivatives of nonhydroxylated stilbene types showed no significant activitywhereas weak estrogenic activity was found in 5-acetyl-, 5-propionyl-, and 5-benzoyl-2-(-stilbenyl)thiophene. 1-Bromo-l,2-diphenyl-2-(5-bromo-2-thienyl)ethylene (258) was found to inhibit body growth and to produce extensive testicular atropy in male rats. A thiophene analog of estrogenic isoflavones (259)... 

Carbonyl stretching frequency in 2-acetyl-5-R-thiophenes CCI4 0.0075 0.001 0.002 0.951 6 k... 

In a 500-cc. round-bottomed, three-necked flask provided with a thermometer, dropping funnel, a liquid-sealed stirrer, and calcium chloride tube are placed 16.8 g. (0.2 mole) of thiophene (Org. Syn. 12, 72), 15.6 g. (0.2 mole) of acetyl chloride, and 200 cc. of dry benzene. The solution is cooled to o°, and 52 g. (23 cc., 0.2 mole) of freshly distilled stannic chloride is added dropwise, with efficient stirring, during the course of about forty minutes. The reaction mixture assumes a purple color when the first drops of stannic chloride are added, and soon a purple solid precipitates. 

Acctothicnone has been prepared by treating thiophene with acetyl chloride in the presence of aluminum chloride1 or stannic chloride,2 and by treating 2-chloromercurithiophene with acetyl chloride.3 The present method is essentially that of Stadnikoff and Goldfarb.2 Stannic chloride is superior to aluminum chloride as a catalyst for this reaction as the latter induces polymerization of the thiophene. 

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