Furan 2-ethyl-5-thiophen

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

A template synthesis using Group I metal ions has recently been developed (114) for producing crown ether compounds from substituted benzenes, furans, and thiophenes, e.g., the reactions of l,2-bis(bromo-ethyl)benzene with disodium or dipotassium glycolates produced... 

Presumably for similar reasons, cathodic reduction of diethyl terephthalate and diethyl furan- and thiophene-2,5-dicarboxylate [51-53] in a buffered ethanolic solution of pH 4.2 affords the aldehyde ester under controlled potential electrolysis (CPE) conditions (in the interval between —1.50 and —1.65 V). Diethyloxalate [77] is reduced at a mercury cathode in acidic medium to give the ethyl hemiacetal of ethyl glyoxylate (38-50% yield). In contrast, diethyl and monoethyl phthalate gave phthalide under similar conditions [21,78]. 

Reactives of Side-Chains of Monocyclic Thiophens. - The rate constants for the esterification of some 3-, 4-, and 5-substituted thiophen-2-carboxylic acids and of some 2- and 4-substituted thiophen-3-carboxylic acids with diazodiphenylmethane in methanol solution have been measured, and linear correlations gave information about the transmission of substituent effects. The rates of alkaline hydrolysis of ethyl thiophen-2-carboxylate in ethanol-water and DMSO-water media have been measured and compared with those of other heterocyclic esters. The kinetics of iodination of 2-acetylthiophen in methanol-water, using different carboxylate buffers, have been studied.Basicity constants have been measured for j3-(2-thienyl)-acrylamides and compared with those of the corresponding benzene and furan derivatives. The acidity constants of ( )-a-phenyl-j3-(2-thienyl)-acrylic acids and analogous furan-, selenophen-, and pyridine-substituted compounds have been measured, and have been rationalized by an equation involving separate contributions of polar, conjugative, and steric effects of the heterocycles. ... 

Similar results were obtained with TpRu(Me)(CO)(NCMe) and furan yielding, catalytically, 2-ethyl furan [Eq. (3)] and thiophene yielding 2-ethyl thiophene. 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

Among the less widely exploited interconversion processes are those involving thermal reactions with ethyl azidoformate, which convert furan into A-ethoxycarbonyl-A -pyrrolin-2-one, and thiophenes into A-ethoxycarbonylpyrroles (Scheme 96a) (64TL2185). The boron trifluoride catalyzed reaction of l,3-diphenylbenzo[c]furan with A-sulfinylaniline results in the replacement of the oxygen by an iV-phenyl group (Scheme 96b) 63JOC2464). 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria pK values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The pK values were determined and the ester hydrolyses studied for all three substitution orientations in the thiophene series. For the 4-R-2-Y and 5-R-2-Y series, the p-values do not appear significantly different and the data could probably be combined into a single series unfortunately, however, no limits of accuracy are reported for the p-values, and some of the raw data are not readily available so recalculation is not easily possible. For the 5-R-3-Y series the p-values deviate considerably from the other values however, whereas they are higher for the pK values, they are lower for the ester hydrolyses, and it is possible that the differences are neither systematic nor significant. 

Ferrocene, like thiophene, furan, and other so-called superaromatic systems, reacts readily with mercuric acetate to form mercurated derivatives. Nes-meyanov and coworkers first reported that ferrocene could be mercurated under relatively mild conditions in either ethyl ether-alcohol or benzene-alcohol solution (63). The acetoxymercuriferrocenes formed in this manner are usually treated with an alcoholic solution of an alkali metal halide. The resulting products, chloro-mercuriferrocene (XXVII) and l,l -di(chloromercuri)ferrocene (XXVIII), can be conveniently separated by extraction with n-butyl alcohol. 

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

In the previous sections, the reactions of nucleophilic alkyl and acyl radicals with electron-deficient aromatics via SOMO-LUMO interaction have been described. At this point, we introduce the reactions of electrophilic alkyl radicals and electron-rich aromatics via SOMO-HOMO interaction, though the study is quite limited. Treatment of ethyl iodoacetate with triethylborane in the presence of electron-rich aromatics (36) such as pyrrole, thiophene, furan, etc. produces the corresponding ethyl arylacetates (37) [50-54]. 

Reaction of 2-[bis(methylthio)methylene]cyclohexanone 124 with lithium hexamethyldisilazide (LHMDS) and ethyl bromoacetate generates intermediate 125, which gives thiophene 126 and furan derivatives 127 (Scheme 30) <1997JOC1599>. 

Japanese workers were the first to use the reactive properties of nitrile compounds to synthesize thiazolo[3,2-a]pyridin-3(2//)-ones (77S839). Ethyl a-cyanocinnamate (88, R = Ph, R = CO Et) reacts with ethyl mer-captoacetate in the presence of triethylamine to give 5-amino-2-benzyli-dene-6,8-bis (ethoxycarbonyl )-7-phenyl-7//-thiazolo [3,2-n]pyridin-3(2//)-one (89, R = R- = Ph, R = R = C02Et), which is also obtained from the reaction of 5-benzylidene-2-ethoxycarbonylmethyl-2-thiazolin-4-one (90a) with ehtyl a-cyanocinnamate (77S839). Reaction of 90a,b with ben-zylidenemalononitrile (88, R- = Ph, R" = CN) and of 90c with ethyl a-cyanocinnamate furnish the respective bicyclic compounds 89 [83ZN(B)781] (Scheme 21). Similar results were also obtained from 88 (R = furan-2-yl-or thiophen-2-yl) (86M105). 

An alternate route for the annelation of a pyrrole ring employs the base-catalyzed condensation of furan-, thiophene-, and selenophene-carbox-ald ydes with ethyl azidoacetate the bicyclic products are indole Isoster-es. The Isomeric (3,2-b)pyrroles can be similarly prepared from the corresponding 2-carboxaldehydes. 

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