Diethyl/dimethyl acetylenedicarboxylate

Keywords Phencyl bromides, amines, diethyl/dimethyl acetylenedicarboxylate, [bmim]BF4, room temperature, one-pot multicomponent reaction, functionalized pyrroles... 

A mixture of phenacyl bromide (1 1.05 mmol) and amine (2 1 mmol) in [bmim]BF4 (2 mL) was added diethyl/dimethyl acetylenedicarboxylate (3 1 mmol) drop-wise and stirred at room temperature for 0.5-1 h. After completion of the reaction, as indicated by TLC, the reaction mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic extracts were washed with saturated brine solution, dried over anhydrous sodium sulfate, and concentrated under vacuum the resulting crude product was purified by means of column chromatography (silica gel 60-120 mesh) using 5-10% ethylacetate/n-hexane as eluent to obtain pure product of functionalized pyrroles 4. The residual ionic liquid was reused after drying under vacuum. All the products were characterized by elemental analyses and spectral studies including H-NMR,... 

In contrast, addition of dimethyl acetylenedicarboxylate to cyclopent[6]azepine (6) is slow and furnishes, in 53% yield, a mixture of the dimeric 1 2 adduct 7 (red crystals), the 1 3 adduct 8 (yellow oil), and an unidentified purple oil.2 Surprisingly, cyclopent[6]azcpine fails to react with other common dienophiles such as ethenetetracarbonitrile, diethyl maleate and chlorosulfonyl isocyanate. 

Indole and dimethyl acetylenedicarboxylate yield 2-(indol-3-yl)-2,3-dihydro-l//-l-ben-zazepine (mp 240-242 C) by addition of indole to the initially formed l//-l-benzazepinc,21 whereas 1,3-dimethylindole (10, R = H) fails to react with the diester under a variety of conditions.145 However, in the presence of boron trifluoride-diethyl ether complex at room tem-... 

A convenient alternative to LP-DE is lithium trifluoromethanesulfonimide (LiNTf2) in acetone or diethyl ether (LT-AC, LT-DE). Representative examples are the Diels-Alder reactions of citraconic anhydride with cyclopen-tadiene and of dimethyl acetylenedicarboxylate with isoprene [47] (Scheme 6.26). 

Rzdtc) ] reacts with diethyl azodicarboxylate, azobenzene, or dimethyl acetylenedicarboxylate to give the appropriate hydrazine and disulfide... 

Three reactions of 1 successively with diethyl fumarate, maleic anhydride, and dimethyl acetylenedicarboxylate (DMAD) are highly representative of the variety of experimental conditions used in the GS/MW process [26, 27]. Continuous MW irradiation (CMWI) with an incident power of 120 W for 1 min led to a high increase in temperature (Tmax> 300 °C). Adduct 4 was obtained almost quantitatively (Tab. 7.1, entry 1), whereas only traces of adducts 5 and 6 were detected. When the incident power was reduced (30 W) and sequential MW irradiation (SMWI) was used, adducts 5 and 6 were obtained in good yield (Tab. 7.1, entries 3 and 4). This controlled irradiation enabled the temperature to be limited (Tmax < 200 °C) and avoided the retro-DA reaction. In the reaction between 1 and diethyl fumarate similar SMWI conditions also gave the adduct 4 in high yield (Tab. 7.1, entry 2). 

Ylides forming from the thermolysis of compound 59 (R1, R2 = Me, R3 = Ar, R4 = OMe) reacted also with dimethyl acetylenedicarboxylate (DMAD) or diethyl azodicarboxylate (DEAD) <2003TL5029> in the presence of aldehydes, quinones <2001TL2043>, or ketones <20020L2821, 20000L3501> to give 2,5-dihydrofuran derivatives, for example, 67 (Rs = Me, Et). 

General Procedure for the Formation of Benzene Derivatives (see Eq. 2.48) At 0°C, dimethyl acetylenedicarboxylate (284 mg, 2 mmol) and CuCl (198 mg, 2 mmol) were added to a solution of zirconacyclopentadiene (1 mmol) in THF, prepared in situ according to the known procedure [12]. The reaction mixture was then allowed to warm to room temperature and was stirred for 1 h. After hydrolysis with 3 n HC1, the mixture was extracted with diethyl ether. The combined extracts were washed sequentially with water, aq. NaHC03 solution, brine, and water, and then dried over MgS04. Concentration in vacuo followed by flash-chromatography eluting with a mixture of hexane and diethyl ether (10 %) afforded benzene derivatives. 

Thiatriazoles are generally not characterized by cycloaddition reactions. Neunhoeffer et al. were not able to induce a reaction between 5-phenyl-1,2,3,4-thiatriazole (7) and 1,2-diphenylacetylene or dimethyl acetylenedicarboxylate (36) even at 12 kbar <85LA1732>. Similar negative results are reported with other reagents (see Section 4.19.4.1). However, a reaction between 7V,A-diethyl-l-propynylamine (40) and 5-phenyl-1,2,3,4-thiatriazole (7) took place at 12 kbar and a compound assigned structure (41) on the basis of MS and NMR was isolated in 17% yield. The suggested reaction pathway, initiated by a 1,3-dipolar cycloaddition reaction at N(2) and N(4) is shown in Scheme 5. Formation of an alternative triazabicyclo[2.2.1]heptadiene was left open. 

Isoquinoline, phenyl isocyanate, and dimethyl acetylenedicarboxylate in diethyl ether for 13 h afforded dimethyl l-phenyl-2-oxo-l,2-dihydro-llb//-pyrimido[2,l-a]isoquinoline-3,4-dicarboxylate (64) in 46% yield (67CB1094). 

Ethoxybenzo[c ]f uran (433) is proposed as an intermediate in the thermal decomposition of the phthalide orthoesters (432) with dimethyl acetylenedicarboxylate to give the naphthalene derivatives (434) and with diethyl fumarate to give the adducts (435) (Scheme 113) (78TL4237). 

Functionalization of Ni(MeCOCHCOMe)2 occurs in reactions with isocyanates, diethyl azodi-carboxylate and dimethyl acetylenedicarboxylate, which proceed by formal insertion of the methine C—H unit into the substrate multiple bonds to form respectively amides and ester-substituted hydrazines and alkenes. Similar additions of acetylacetone to these electrophiles is catalyzed by nickel acetylacetonate.217,218... 

Diethyl 4,5,6,7-tetrafluorobenzo[6]thiophene-2,3-dicarboxylate is formed when diethyl acetylenedicarboxylate reacts with lithium pentafluorothiophenoxide [Eq. (I)].109 Similarly, reaction of dimethyl acetylenedicarboxylate with the methyl thiosalicylates (35) affords... 

The conversion of (—)-apomorphine into (+)-apomorphine has been achieved.56 The O-dealkylation of 10,11-dimethoxyaporphine, using sodium thioethoxide in dimethylformamide, has been reported.57 The reactions of the enamine dehydro-nuciferine with dimethyl acetylenedicarboxylate, methyl propiolate, methyl acrylate, and diethyl azodicarboxylate have been investigated, and have resulted in the preparation of a novel series of 7-substituted aporphines.58... 

Methylbenzophenone gives, on photochemical bromination (refluxing CCI4), 2-bromomethylbenzophenone in 80% yield. When the bromination was conducted at room temperature and the crude product treated in refluxing CHCI3 with iV-phenylmaleimide, dimethyl maleate, diethyl fu-marate, methyl vinyl ketone, dimethyl acetylenedicarboxylate, and 1,4-naphthoquinone adducts 92 (mp 227-228°C, 75%), 93 (mp 120-121°C, 65%), 94 (mp 129-130°C, 51%), 95 (mp 81-82 C, 23% an unidentified product was also isolated), 96 (mp 149-150°C, 62%) and 97 (mp 315-316°C, 19%) were obtained. l-Phenylbenzo[c]furan is assumed to be an intermediate in these reactions. Whereas the formation of 92-96 can be simply... 

Dimethylanisole A,A-Dimethylacetamide A,A-Dimethylaniline A,A-Dimethylacetoacetamide (See DMA, dimethylacetamide) dimethyl acetylenedicarboxylate A,A-Dimethylacetamide diethyl acetal 2-Dimethylaminoethyl methacrylate Dimethylaminopropylamine... 

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. 

In a similar reaction, l,2-dichloro-3,3-dimethylcyclopropene underwent addition to dimethyl acetylenedicarboxylate in 18 hours at 20 °C in diethyl ether to give the cyclopropene product (47%), apparently derived by rearrangement of an initial adduct. ... 

Similarly, the addition of diethyl phosphite to dimethyl acetylenedicarboxylate in tolnene at 120°C prodnces tetraethyl l,2-Z z.y(methoxycarbonyl)-l,2-ethylenediphosphonate in 80% yield. ... 

The conjugate Michael addition of phosphonate-stabilized anions with dimethyl acetylenedicarboxylate has been described. For example, when the sodium salt of dimethyl l-(methoxycarbo-nyljmethylphosphonate is treated with dimethyl acetylenedicarboxylate, an (fij/CZ) mixture of two isomeric P.y-unsaturated phosphonates is isolated in modest yield (37%). ° Addition of enolates derived from diethyl 2-oxocycloalkylphosphonates to dimethyl acetylenedicarboxylate in aprotic conditions results in [n + 2] ring-expanded products in reasonable yields (Scheme 8.50). The reaction proceeds via a tandem Michael-aldol-fragmentation mechanism to give the ring enlarged products. 

Additions to compounds with activated double or triple bonds are known. Compound 406 (R = Me) gives 427 with acrylonitrile(405 does not react ), and 401 reacts with diethyl azodicarboxylate and maleic anhydride to give 428 and 429, respectively. The 2,6-dimethyl derivative of 396 undergoes addition to dimethyl acetylenedicarboxyl-ate at C-5 (position a. Scheme 18), but tetracyanoethylene gives both C-5 and C-7 (a and b) products, the latter predominating. Reid had earlier reported that 396 reacts with bulky electrophiles to give mixtures of products and disubstituted derivatives. 

Thermal cycloaddition reactions of benzo[c]cinnoline with butadiene and isoprene are reported to give only small yields of adducts in various solvents. Reactions of 1 and its 3,8-dimethyl derivative with dimethyl acetylenedicarboxylate at room temperature give the 1 2 adducts 56 and 57 via a stepwise process involving dipolar intermediates (see also Sections IV,A and 2.132 corresponding reactions of the diethyl ester in... 

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