Chloromethyl selenophenes

Thiophene and selenophene can be chloromethylated by treatment with formaldehyde and hydrochloric acid. Depending on the conditions, 2-chloromethyl or 2,5-bis(chloromethyl) derivatives are obtained. The chloromethylation of benzo[6]thiophene gives the 3-chloromethyl derivative and that of benzo[6]furan the 2-chloromethyl compound (71AHC(13)235). 

Selenophene, bis(TV-chlorothioimino)-molecular structure, 4, 939 Selenophene, 2-bromo-mercuration, 4, 946 Selenophene, 3-bromo-lithiation, 4, 949 synthesis, 4, 955 Selenophene, 3-bromo-2-lithio-synthesis, 4, 955 Selenophene, bromonitro-debromination, 4, 78 synthesis, 4, 955 Selenophene, 2-chloromethyl-solvolysis, 4, 952 Selenophene, 3-cyano-synthesis, 4, 955 Selenophene, deutero-deuterium exchange, 4, 949 Selenophene, 2,5-diacyl-3,4-dihydroxy-synthesis, 4, 964... 

Selenophene has been converted into both 2-chloromethyl (62JGU253) and 2-dimethyl-aminomethyl (59JGU3606) derivatives under standard conditions, and 2,5-diphenyltel-lurophene, where the more reactive a-positions are blocked, has been shown to yield a 3,4-bis(chloromethyl) derivative (76ZN(B)367>. 

The synthesis failed in the case of 2-chloromethyl-3-formylbenzofuran. The reduction product (307) was isolated in high yield instead of the desired selenophene (308 Scheme 104) (78JHC589). 

Selenophene is very similar in chemical behavior to thiophene4 90 therefore, it is not surprising that also here a 2-alkyl group directs the substitution preferentially to C-5. This has been observed in acetylation,265 chloromethylation,266 aminomethylation,267 and formylation268 of 2-methylselenophene. 

Selenophene undergoes various electrophilic substitutions nitration, sulfonation, halogenation, mercuration, chloromethylation, aminomethylation, acylaminomethylation, acylation, formylation, and hydrogen exchange. 

Chloromethylation of selenophene, like other electrophilic substitutions, occurs at the a position, and 2-chloromethylselenophene is formed together with small amounts of the 2,5-bischloromethyl derivative. Selenophene and its homologs have been chloromethyl-ated by diverse reagents formalin and hydrogen chloride, a mixture of mono- and bischloromethyl ether, or formaldehyde bischloro-methylacetal. A mixture of mono- and bischloromethyl ether is the most convenient reagent. 

Catalysts (ZnCl2, SnCl2, H3P04, or P0C13) sharply decrease the reaction yield. Methyl selenophenes are chloromethylated under milder conditions than the unsubstituted compound, and 3-methyl-selenophene is chloromethylated easier than the 2-methyl compound.60... 

Acyl selenophenes are chloromethylated at the free a. position (as in sulfonation and halogenation). A second chloromethyl group can be introduced ortho to the first and meta to the acyl group.61 5-Methyl-2-acetylselenophene is chloromethylated in the 4-position.61 When reduced by stannous chloride in hydrochloric acid, 5-chloro-methyl-2-acetylselenophene simply undergoes reduction of the chloromethyl group, and 2-methyl-5-acetylselenophene is formed61 (Scheme 2). 

Chloromethyl-2,5-dimethyl derivatives of furan, thiophene, and selenophene are solvolyzed faster than their 2-chloromethyl derivatives. For both the 2-chloromethyl and the 3-chloromethyl-3,5-dimethyl series the solvolysis rate increases in the order thiophene < selenophene < furan. 

The chlorine atom of chloromethyl derivatives of selenophene is very reactive and easily displaced in substitution reactions. Thus, 2-chloromethylselenophene and its homologs readily exchange the chlorine for dialkylamino, alkoxy, and acetoxy groups, and the chloromethyl can be converted into an aldehyde group, providing a synthesis for 2,5-dimethylselenophene-3-aldehyde (7) which cannot be obtained by direct formylation.102... 

Selenophene chloromethyl derivatives readily form di(/3-hydroxy-ethyl)aminomethylselenophenes (8) which, with thionyl chloride, give the corresponding di(/3-chloroethyl)aminomethylselenophenes (9).103 Chloromethylselenophenes condense with trisubstituted ethylene-diamines to yield tetrasubstituted diamines containing the selenophene nucleus.104 The reaction of 2-chloromethylselenophene with sodium derivatives of malonic and acetoacetic ester yields the acid (10) and ketone (11), respectively, whereas with alkyl magnesium halides 2-(alkylmethyl)selenophenes are formed.105... 

Bis[methoxymethyl]-2,S-diphcnylte1lurophene 430 mg (1 mmol) of 3,4-bis[chloromethyl]-2,5-diphenyl-tellurophene are added to a solution of sodium methoxide prepared from 40 ml of absolute methanol and 200 mg (8.7 mmol) of sodium and the mixture is heated under reflux for 10 h. The mixture is then allowed to cool to 20°, poured into water, and extracted several times with diethyl ether. The combined extracts are dried with anhydrous sodium sulfate, filtered, and the filtrate is evaporated. The residue is chromatographed on silica gel with benzene as the mobile phase to give the product as a light yellow oil yield 350 mg (83%). l,3-Diphenyl-4//,6//-selenophene[3,4-c]tellurophene A solution of disodium selenide, prepared from 1.58 g (20 mmol) of selenium and 0.92 g (40 mmol) of sodium in liquid ammonia, in absolute methanol is saturated with nitrogen. 1.28 g (3 mmol) of 3,4-bis[chloromethyl]-2,5-diphenyltellurophene are added and the mixture is refluxed under nitrogen for 15 h. The mixture is then filtered, the filter cake is dissolved in chloroform in the presence of activated charcoal, filtered, and the product is recrystallized from chloroform/methanol yield 0.79 g (60%) m.p. 220°... 

Selenophene-2,5-dicarboxylic acid, cis-tetrahydro-synthesis, 4, 962 Selenophenes, 4, 935-971 acetylation, 4, 948 alkylation, 4, 948 annelation, 4, 969 applications, 4, 971 aromaticity, 4, 30 bromination, 4, 947 chloromercuration, 4, 83 chloromethylation, 4, 54 cycloaddition reactions, 4, 67, 950 deprotonation, 4, 59 /3-diketones applications, 4, 971 a-directing effect, 4, 44 2,5-disubstituted synthesis, 4, 964, 965 electrophilic substitution, 4, 43, 946 formylation, 4, 946, 948 with fused six-membered heterocyclic rings, 4, 973-1036... 

The reactivity of selenophen has been compared with that of thiophen and the relative reactivities in five different electrophilic substitutions have been determined by kinetic or competitive procedures. Selenophen was found to be 1.5—47.5 times more reactive than thiophen. Selenophen has been chloromethylated to 2,5-dichloromethylselenophen, which has been used for the syntheses of other 2,5-substituted derivatives such as the diacetic acid. ... 

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