Acetylenedicarboxylic acid, diethyl

Krapcho and Vivelo have described a new formal total synthesis of tropinone (124) and ( )-cocaine (98) (94). Cycloaddition of IV-methylpyrrole (182) and acetylenedicarboxylic acid leads to 183, which is hydrogenated to 184. The diacid mixture 184 is refluxed in MeOH/HCl to yield the diester mixture 185. Addition of this to an excess of metallic sodium in liquid ammonia at — 78°C leads to the N-methylpyrrolidine derivative 186 (cf. 95), whose diethyl analog 147 has earlier been converted to tropinone (124) and (+)-cocaine (98) (78-80) (Scheme 13). 

The same general method has been used by the submitters to prepare diethyl acetylenedicarboxylate. In this case absolute ethanol was used, and the ether extract was dried over anhydrous magnesium sulfate. The yield of diethyl ester from 100 g. of the acid potassium salt of acetylenedicarboxylic acid was 57-59 g. (51-53%) b.p. 96-98°/8 mm. n 1.4397. 

We were not able to obtain any cycloadduct from unactivated 2-azadienes 139 and esters of acetylenedicarboxylic acid. However, we found that 139 did cycloadd to typical electron-poor dienophiles such as esters of azodicarboxylic acid and tetracyanoethylene (Scheme 62). Thus, diethyl and diisopropyl azodicarboxylates underwent a concerted [4 + 2] cycloaddition with 139 to afford in a stereoselective manner triazines 278 in 85-90% yield (86CC1179). The minor reaction-rate variations observed with the solvent polarity excluded zwitterionic intermediates on the other hand, AS was calculated to be 48.1 cal K 1 mol-1 in CC14, a value which is in the range of a concerted [4 + 2] cycloaddition. Azadienes 139 again reacted at room temperature with the cyclic azo derivative 4-phenyl-1,2,4-triazoline-3,5-dione, leading stereoselectively to bicyclic derivatives 279... 

HETEROCYCLES Copper phcnylace-tylide. Dichlorobis(benzonitrile)palladium. N-Dichloromethylene-N,N-dimcthylammo-nium chloride. Diiminosuccinonitrile. Dimethyl acetylenedicarboxylate. Dipotassium cyanodithioimidocarbonate. Ethoxy-carbonyl isothiocyanate. Ethyldiisopropyl-amine. Ethylene oxide. Hydrogen fluoride. Isocyanomethane-phosphoric acid diethyl ester. Lead tetraacetate. Lithium aluminium hydride. Methylhydrazine. Phosphoryl chloride. Polyphosphate ester. Polyphosphoric acid. Potassium amide. Potassium hydroxide. Tolythiomethyl isocyanide. Tosylmethyl isocyanide, Trichlo-romethylisocyanide dichloride. Trimethyl-silyldiazomethane. 

To a suspension of 1.31 g A-acetyl-D,L-alanine (10 mmol) in 10 mL acetic anhydride was added 3.2 mL diethyl acetylenedicarboxylate (20 mmol). The reaction mixture was maintained at 110°C for 2 h, cooled, and then evaporated under reduced pressure. The oily residue was dissolved in hot cyclohexane and left in the refrigerator overnight with crystal seeds. Diethyl 2,5-dimethyl pyrrole-3,4-dicarboxylate was isolated as white needles by filtration, in amount of 274 mg, in a yield of 11.4%. The filtrate was evaporated and chromatographed (dry column vacuum chromatography) using CH2CI2 and then CH2Cl2/EtOH (99 1 to 98 2) to afford 1.58 g 2-(2,5-dimethyl-3,4-diethoxycarbonyl)-pyrrolyl maleic acid diethyl ester as a yellowish oil, in a yield of 39%. 

Nonetheless, furan does react with bromine in methanol to produce the corresponding addition compounds, (E)- and (Z)-2,5-dimethoxy-2,5-dihydrofuran (Equation 8.55) and aromaticity can also be lost through a Diels-Alder reaction of furan and substituted furans with reactive dienophiles such as the diethyl ester of acetylenedicarboxylic acid (Equation 8.56)... 

Dichlorobenzo quinone -4-chloroimide Diethyl acetylenedicarboxylate Dimethyl 2-chloro-4-nitrophenyl thionophosphate Dimethyl 3-chloro-4-nitrophenyl thionophosphate Dimethyl 4-nitrophenyl thionophosphate A,A-Dimethyl-4-nitrosoaniline, Acetic anhydride. Acetic acid t Dimethyl sulfoxide... 

The reaction of indolizines with dialkyl acetylenedicarboxylates in the presence of a dehydrogenating catalyst leads to 1,2-dicarbalkoxycycl-[3,2,2]azines.22 23 Methyl phenylpropiolate may be used instead, although attempts to effect reaction between indolizine and certain other dienophiles including diphenylacetylene, diethyl azodicarboxylate, and 1,3-cyclohexadiene were unsuccessful. Hydrolysis of the diesters yielded the corresponding acids. Subsequent decarboxylation proceeded in high yield using copper chromite in quinoline [Eq. (5)]. 

Very little work has been done on fluoro derivatives of thiophenes. 2-Fluorothiophene was obtained in low yield from treatment of 2-iodothiophene with arsenic trifluoride. The action of fluoroboric acid on thiophenediazonium salts was unsuccessful. It may be useful for the preparation of 4-, 5-, 6- or 7-fluorobenzo[6]thiophenes from the appropriate amines. However, these are more conveniently prepared from fluorine-substituted benzenethiols by ring-closure reactions. For example 4,5,6,7-tetrafluorobenzo[6 Jthiophene was obtained by decarboxylation of the corresponding 2,3-dicarboxylic acid (equation 99) prepared by condensation of pentafluorobenzenethiol with diethyl acetylenedicarboxylate (Section 3.15.3.4.1). 2-Fluorothiophene has been prepared from 2-thienyllithium using perchloryl fluoride, and 2-fluorobenzo[ Jthiophene from the 2-lithio derivative in a similar manner (Section 3.14.3.9.1). 

Both diethyl acetylenedicarboxylate and chlorofumarate have found frequent application as the second component, but other unsaturated acid derivatives are acceptable. The initially formed aryloxyalkenoic acids or their esters (471) are readily cyclized with acid or acetyl chloride. 

Treatment of 2-iodothiophene 830 with Z molar equiv of diethyl acetylenedicarboxylate in the presence of Pd catalyst affords tetrasubstituted benzothiophene 834. d y -addition of intermediate 831, generated by oxidative addition of 830 to Pd(0), to the acetylene gives vinylpalladium 832. Cyclization of 832 to 833 and its subsequent reaction with the acetylene affords the final product 834 (Scheme 126) <2003JOC6836>. Intramolecular electro-cyclization of the intermediate 837, produced by the reaction of the propargyl methyl carbonate 835 with 2-thiophene boric acid 836 in the presense of Pd catalyst, affords benzothiophene 838 (Scheme 127) <2004CEJ5338>. 

Reaction of thione 276 (R = H) with diethyl acetylenedicarboxylate in acetic acid or ethanol similarly gives both thiazolidinone (277) and thiazinone (278) as expected (79TL53) (Scheme 67). Condensation of 276 (R = Me, Cl, NO2, CO2H) and 280 with acetylenedicarboxylic esters gives a cyclized product in each case for which respective thiazolidinone structures 279 and 281 were assigned (77M11). This work warrants reinves-... 

Condensations of chloroacetyl chloride (and similar compounds) with substituted ethylenediamines to give 1,4-disubstituted piperazin-2-ones have been described, and a number of 4-alkyl(or aralkyl)- -arylpiperazin-2-ones has been prepared either by catalytic debenzylation or pyrolytic debenzylation (or demethylation) of I,l-dialkyl(or l,l-diaralkyl)-3-oxo-4-arylpiperazinium halides (1609). 3-Ethoxy-carbonylmethylene-6-methylpiperazin-2-one has been synthesized by the reaction of diethyl acetylenedicarboxylate with propylenediamine (1610), and treatment of diethyl fumarate with propylenediamine has been shown to give 3-ethoxycarbonyl-methyl-6-methylpiperazin-2-one, also prepared from the diethyl ester of N- 2 -hydroxyiminopropyl)aspartic acid (84) (1611). 

Diels-Alder dienophiles a-Acetoxyacrylonitrile. Acetylenedicarboxyhc acid. Acrolein (see 1-o-Nitrophenylbutadiene). Allyl alcohol (see Lithium). 1,4-Benzoquinone (see also 1,4-Naphthoquinone, preparation). /rans-l,2-Dibenzoylethylene. Di-(-butyl azodiformate. Dichloroketene. Dicyanoacetylene. Diethyl acetylenedicarboxylate. 1,4-Dihydronaphthalene-... 

In 1967, two reactions that proceeded by the intramolecular cyclization mechanism and led to fluorinated benzo[Z>]thiophenes were carried out. The first is based on the reaction of the lithium salt of pentafluorothiophenol and diethyl acetylenedicarboxylic ether (67JCS(C)1225) (Scheme 148). Here the intermediate species is a carbanion. In the second process, the starting compound is a benzylidene rhodanine derivative, giving benzo[Z>]thiophene carboxylic acid 157 in alkaline media. This reaction occurs via the intermediate S-nucleophile (Scheme 149). 

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