Thiophenes methylation

Keywords thiophene, methyl-thiophene, benzothiophene, H202, Ti-Beta, mechanism, XANES. 

Thiophene, 2,4-dimethyl-Thiophene, methyl-Thiophene, 2-methyl-... 

In the presence of an acetylene, thiophene is produced. The addition occurs across the C-S bond of the thiirene, producing 2,3-substituted thiophenes. Photolysis of 4-methyl or 5-methyl thiadiazole yields only one thiophene, methylated in the 5-position, indicating a preferential addition on the unsubstituted side of the thiirene ring ... 

Part 1 contains mass spectromctric El data for confirmation of results. Part 2 deals with the updated cleanup methods, including SPE with various types of sorbents. Part 3 describes some single residue methods (SRMs), The pertinent methods for OP.s and CMs arc method 261-378-370 for methomyl, carbendazim, and thiophenate-methyl method 378 for car-bendazim method 658-344 for cabosulfan and carbofuran method 522 for fonofus method 405 for glyphosate and method 441 for oxamyl. Part 4 deals with MRMs, and a pertinent method for OPs and CMs is method S8, an updated version of method S19. Method S25 is for methyl CMs. Thin-layer diromaiographic methods using the automated multiple development technique are described in part 6. 

A purely thermal homopolymerization to high molar masses has only been proved for styrene and some of its derivatives, as well as for 2-vinyl pyridine, 2-vinyl furan, 2-vinyl thiophene, methyl methacrylate, and acenaphthylene. In contrast, vinyl mesitylene, 9-vinyl anthracene, and methyl acrylate do not polymerize spontaneously. Some of fhe thermal polymerizations proceed by a free radical mechanism others, however, do not. 

Acetomethylthienone (2-MethyU5-ace U thiophene, methyl methylthienyl ketone)... 

Example 10 Polythiophene-Carboxylic Acid - Synthesis of Water-Soluble 2,5-Poly(thiophene-3-propionic Acid) and Poly(3-thiophene Methyl Acetate) (P3TMA)... 

The presence of thiophene and its derivatives in crude oils was detected in 1899, but until 1953, the date at which the methyl-thiophenes were identified in kerosene from Agha Jari, Iran crude oil, it was believed that they came from the degradation of sulfides during refining operations. Finally, their presence was no longer doubted after the identification of benzothiophenes and their derivatives (Table 8.9), and lately of naphthenobenzothiophenes in heavy cuts. 

Commercial toluene contains methyl thiophenes (thiotolenes), b.p. 112-113°, which cannot be removed by distillation. It may be purified by... 

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). 

A primary isotope effect /ch/ d of 6.4 (extrapolated for 35 C) is observed for the metalation and the methylation of 171b when the C-5 position is deuterated. This value is in excellent agreement with the primary isotope effect of 6.6 reported for the metalation of thiophene (392) and it confirms that the rate-determining step is the abstraction by the base of the acidic proton. 

Pharmaceuticals and Agrochemicals. Thioglycohc acid and its esters are useful as a raw material to obtain biologically active molecules. In cephalosporine syntheses, (4-pyridyl)thioacetic acid [10351 -19-8] (65) and trifluoromethane (ethyl) thioglycolate [75-92-9] (66) are used as intermediates. Methyl-3-ainino-2-thiophene carboxylate can be used as intermediate for herbicidal sulfonylureas (67) and various thiophenic stmctures (68). 

Veterinary Products. Principal users of thiophene are the anthelmintics Pyrantel [15686-83-6] and Morantel [20574-50-9] (Pfizer) (59), based on 2-thiophenecarboxaldehyde and 3-methyl-2-thiophenecarboxaldehyde [5834-16-2], respectively. Tioconazole, one of a range of fungicidal products incorporating thiophene, has also found veterinary appHcations. 

Agrochemical Products. The principal thiophene derivative in herbicidal protection, one of a range of sulfonylurea herbicides, is Harmony [79277-27-3] (Du Pont) (60), based on the intermediate methyl 3-aminothiophene-2-carboxylate (9). The product is characterized by a rapid biodegradabHity in the soil. Many other thiophene derivatives have been shown to have agrochemical activity, but few of these have been developed to the commercial level. 

Mercapto derivatives of furan, thiophene, selenophene (77ACS(B)198) and pyrrole (72AJC985) all exist predominantly in the thiol form. 2-Mercaptobenzothiophene is also a thiol (70JCS(C)243i) whereas 2-mercaptoindole is mainly indoline-2-thione (89) (69CPB550). The finely balanced nature of this system is indicated by the fact that a 3-aryl, but not a 3-alkyl, substituent will stabilize the 2-thiol form, whereas for 3-aryl-fV-methyl derivatives the 2-thione tautomer is preferred (71CC836). 

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

A quantitative study has been made on the effect of a methyl group in the 2-position of five-membered heteroaromatic compounds on the reactivity of position 5 in the formylation and trifluoroacetylation reaction. The order of sensitivity to the activating effect of the substituent is furan > tellurophene >selenophene = thiophene (77AHC(2l)ll9). 

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