Dimethyl acetylenedicarboxylate, reaction with aldehyde

Paal-Knorr synthesis, 4, 118, 329 Pariser-Parr-Pople approach, 4, 157 PE spectroscopy, 4, 24, 188-189 photoaddition reactions with aliphatic aldehydes and ketones, 4, 232 photochemical reactions, 4, 67, 201-205 with aliphatic carbonyl compounds, 4, 268 with dimethyl acetylenedicarboxylate, 4, 268 Piloty synthesis, 4, 345 Piloty-Robinson synthesis, 4, 110-111 polymers, 273-274, 295, 301, 302 applications, 4, 376 polymethylation, 4, 224 N-protected, 4, 238 palladation, 4, 83 protonation, 4, 46, 47, 206 pyridazine synthesis from, 3, 52 pyridine complexes NMR, 4, 165... 

Thiazolotriazines 636 (R = CO,Me) were prepared [84JCS(P1)2707] by cycloaddition of dimethyl acetylenedicarboxylate with triazine derivative 632. Derivatives of thiazolo[3,2-b][l,2,4]triazin-3,7-diones 637 have been formed (74JPR163) on reaction with aromatic aldehydes and diazonium salts to give 636 (R = Ar) and 638, respectively. Regioselective catalyzed... 

Triazole-fused pyridopyrimidines can be prepared by reaction of aldehydes with the substituted pyridopyrimidine 309 (Equation 106). The pyrazole-fused derivative 311 can be prepared by the reaction of the sulfonimine 310 with dimethyl acetylenedicarboxylate (DMAD) (Equation 107) <1998H(47)871>. 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

Aldehyde azines 87 react with two equivalents of dimethyl acetylenedicarboxylate in a 1,3-dipolar reaction to give iV-allyl pyrazoles 88 in good yields (Scheme 48) <2002CJC1293>. 1,3-Dipolar cycloaddition of polymer-supported -silylnitrosoamides 89 with dimethyl acetylenedicarboxylate gives pyrazole derivatives 90 without the necessity for a separate cleavage operation (Scheme 49) <2000TL691>. 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

Saidi and co-workers [141] have reported a three-component reaction of different thiosemicarbazides with dimethyl or diethyl acetylenedicarboxylate and an aldehyde under solvent-free conditions applying a domestic microwave oven. Thiazolines 102 were obtained in good to excellent yields. Interestingly, the presence of electron-donating groups on the aromatic aldehyde resulted in faster reactions and higher product yields (Scheme 79). 

Reaction with enamines and related substances. Brannock el al. found that the enamines derived from acyclic aldehydes and ketones react with dimethyl acetylene-dicarboxylate to give products derived by rearrangement of cyclobutenes initially formed by 1,2-cycloaddition. Thus, N,N-dimethylisobutcnylamine (1) reacts with dimethyl acetylenedicarboxylate in refluxing ether to give dimethyl 2-dimethylamino-methylenc-3-isopropylidencsuceinate (2) in 49 % yield. 

Similarly, reaction of a thiazolium salt with aldehydes and dimethyl acetylenedicarboxylate provided 3-amino tetrasubstituted furans in moderate to good yields. The substitution pattern differs from the reactions illustrated above <05JOC8919 05OL1343>. 

The thiazolium-mediated three-component reaction of thiazolium salts 201, aryl aldehydes and dimethyl acetylenedicarboxylate provides a facile synthesis of 2-amino-2-arylfurans 202 <05OL1343>. The reaction pathway may involve the sequential nucleophilic addition of thiazol-2-ylidene 203 with the aldehyde and DMAD to form the spirocyclic intermediate 204 through the simultaneous formation of two C-C bonds and a C-O bond Selective ring opening of the spirocyclic intermediate 204 followed by hydrolysis leads to 3-aminofuran 202 via 205. 

Zwitterionic salts with Meldrum s acid as the anionic structural element are easily accessible by reacting a CH-acidic A-aUcyl pyridinium salt 434 with 2-alkylidene Meldrum s acid derivatives (Scheme 13.90) [175]. The 2-alkyhdeneMeldrum s acids are generated in situ from Meldrum s acid 112 and an aldehyde 435 under basic conditions. Other heterocycles have been reported to undergo the same reaction [176]. In a 4CR, the pyridinium salts can be formed in situ [177]. The generation of zwitterionic salts from Meldrum s acid, several heterocycles and dimethyl acetylenedicarboxylate has been reported [178]. 

A variety of aldehydes and amines were used. Aromatic aldehydes with both electron-withdrawing and electron-donating substituents (like Cl, Br, NO2, OMe, Me grou ps) at different positions of the aromatic ring resulted in good-to-excellent yields. The yield was also very high with aliphatic aldehydes and heteroaromatic aldehyde like pyridine-2-carboxaldehyde. With aliphatic aldehydes, the reaction was completed even at room temperature (25-28 °C) with stirring. Use of aniline, substituted anilines, heteroaromatic amine, and ahphatic amines increased the diversity of the products. No product was, however, obtained with two different aromatic amines. Dimethyl acetylenedicarboxylate and diethyl acetylenedicarboxylate were used as but-2-ynedioate part and both of them are equally efficient for this reactiom... 

One recent example of applying this process was reported by Johnson et al. for the preparation of furan derivatives (Scheme 16.12) [19]. This reaction involved the rhodium(II)-catalyzed intermolecular generation of carbonyl ylides A or B from diazosulfone (18) and aldehydes 19 or 21, respectively. The 1,3-dipolar cycloaddition of the resulting carbonyl ylides with an intramolecular tethered alkyne moiety or dimethyl acetylenedicarboxylate (DMAD, an intermolecular process), followed by elimination of phenylsulfinic acid, could access furan derivatives. 

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