1,4-diformyl compounds

Diformylated compounds tend to aldol-condense (Scheme 6.86). This can be avoided by running the reaction in an excess of alcohol, which traps the aldehydes as acetals [35]. 

Deuterated troponoids, e.g., 32 and 33 [Scheme 9 80BSF(1)327], result from condensations involving mono- or dideuterated diformyl compounds (D enters positions 4 and 8 in 32) and/or perdeuterated acetone (D enters... 

The synthesis was performed according to Scheme 9.3. 1,2-Bis (2-methyl-1-ben-zothiophen-3-yl)perfluorocyclopentene (9a) was formylated with dichloromethyl methyl ether to give diformyl compound 14, which treated with 2,3-bis(hydroxy-amino)-2,3-dimethylbutane sulfate followed by sodium periodate. Compound 10a was obtained and purified by column chromatography and gel permeation chromatography (GPC). Recrystallization from hexane-CH2Cl2 gave dark-blue plate crystals of 10a. 

The synthesis was performed according to Scheme 9.9. Compound 20a was synthesized from 1,2-bis(3,4-dimethyl-2-thienyl)hexafluorocyclopentene (21). After iodination, the transformation to diboronic acid followed by Suzuki coupling with 4-formyl-4 -iodobiphenyl gave diformyl compound 23a. The conventional treatment was employed for formyl compounds 23a to convert nitronyl nitroxide radical 20a. 

Dipyrazolyl steroids (242 X = NH)and(244 X = NH) have been obtained by the reaction of the 2,6- and 4,6-diformyl compounds (241) and (243) with hydrazine whilst similar condensation with the unsaturated keto-aldehyde derived from (221) gives the pyridazine (245). 

Ammonia bubbled through a soln. of 350 mg. of the startg. diformyl compound in methanol for 5 min. 230 mg. pyridine derivative. 

Nitromethane added at 15 to a soln. of 1.1 g. of the startg. diformyl compound in anhydrous methanol followed by the addition with gentle stirring during 5 min. of a soln. of Na-meth-oxide cooled to 10, the cooling bath removed, and the mixture stirred 4 hrs. 1 g. nitrobenzene derivative. 

The diformyl compound is readily available by treatment of the enamine with Vilsmeier reagent. F. e. s. R. Sciaky, U. Pallini, and A. Consonni, G. 96, 1284 (1966). 

Mannschreck and Kolle examined various systems in which the dipolar structure 28 was stabilized by delocalization of the negative charge to the other end of enamines. The highest barrier to rotation in their work in 1967 (71) was obtained with 2,3-diformyl-6-dimethylaminofulvene (30). The H NMR spectrum of the compound did not change up to 185°C, and the barrier to rotation was estimated to be >25 kcal/mol. Another candidate that provided stable retainers was 4-(dimethylaminomethylene)-l,2-diphenyldiazolidine-3,5-dione (31). 

Several diformyl derivatives of five-mem bered heterocycles were studied with regard to their conformational properties. Although one formyl group may be considered to behave as a substituent with respect to the other perturbing its conformational equilibrium, in 2,5- and in 2,4-derivatives the groups behave quite independently. In principle, for these compounds four conformations are possible, represented by 15 for 2,5-diformyl derivatives. In... 

A large number of 1,4-dihydropyridines were prepared from 3,5-diformyl-4-ethynyl-4//-pyran (85d). Thus compounds 568a,b and 569a-c were isolated after the reaction of 85d with primary amines,62,442 ammonium acetate,440 urea, and thiourea.440 As shown in Scheme 34, some aromatic amines react with both 3,5-aldehydic groups to afford 1,4-dihydropyridine Schifif bases 570.62,442... 

The title compounds were synthesized from quinazoline precursors as exemplified by the dehydrative cyclization of the diformyl derivatives (456), obtained from 2-methyl-3-phenylquinazoline (455), with phosphoric acid to give the 6-formylquino[2,1 -b]quinazolin-12-one 457 (73IJC532). 

It was natural to turn to 5-(2-formylfuryl) methyl ether (the methyl ether of 5-hydroxymethyl-2-furaldehyde) as a possible cause of these results. This compound has an absorption peak at 284 mp. It was found82 that this compound is difficult to purify, and treatment with adsorbents leaves a bright-yellow solution. A similar color is found with 2,5-diformyl-furan, in solutions of which, color develops spontaneously on exposure to light. The dye may be closely related to the ether-dimer of 5-(hydroxy-methyl)-2-furaldehyde, perhaps with one ring open. It may be significant that development of the intense, yellow color is not observed in solutions of 5-(hydroxymethyl)-2-furaldehyde, for its acyclic form is presumably the intermediate that decomposes to levulinic and formic acids. 

Scheme 3a gives a representation of the main synthetic procedure for these compounds. It started with the condensation of diformyl-substituted dithiedylethene and benzaldehyde with dipyrrolemethane, followed by oxidation with p-chloranil. The dithienylethene-bridged diporphyrin was given in 19% yield. The other products were synthesized by analogous approaches. 

The only synthesis to be reported in this section has no preparative interest and involves the reaction of malonaldehyde with 2 -deoxyadenosine on a small scale. Such a reaction was monitored by high-performance liquid chromatography (HPLC) and led to 9-(/3-D-ribofuranosyl)-6-(5,7-diformyl-2/7-3,6-dihydro-2,6-methano-l,3-oxazocin-3-yl)purine, which, on the other hand, was a known compound <2005MI637>. 

Tetraoxa[22]porphyrin-(2.2.2.2) bisperchlorate 4.158 has also been prepared via the McMurry-type condensation of 2,5-diformyl furan 4.159. Here, the intermediate product of the cyclocondensation was determined to be the dihydro compound 4.160. It was isolated in 0.8% yield," and was determined to possess a cis-trans-cis-trans orientation of the single and double mew-like bonds (Scheme 4.4.3). The unsaturated bonds present in 4.160 posed no significant barrier to aromatiza-tion, however. Indeed, 4.160 underwent smooth oxidation to the 22 jr-electron macrocycle 4.158 upon treatment with DDQ, while maintaining the cis-trans-cis-trans conformation found in the dihydro species 4.160. 

The hydrazino group in 89 is more nucleophilic than the 5-amino group, therefore, formylhydrazino derivative 90 is usually formed at the first stage. This compound, depending on conditions and on the type of cyclizing agent, can be converted then to triazolo[4,3-c]pyrimidine 91 [pathway a in Eq. (27)], l,2-dihydropyrimido[5,4-e]-fls-triazine (92) (pathway b), or diformyl derivative (93) (pathway c). Compound 93 is the precursor of 9-acylaminopurine (94). There is also much evidence of the formation of 9-acylaminopurines via dihydroazines (92) (pathway d). 

Reduction of quinoxaline with lithium aluminum hydride in ether yields 43% of 1,2,3,4-tetrahydroquinoxaline (81), also obtained in 20% yield by reduction with sodium in refluxing alcohol. Both sodium borohydride in acetic acid, and hydrogen and platinum, have been used to reduce 6-substituted quinoxalines to the 1,2,3,4-tetrahydro compounds. Quinoxaline and its 2-methyl derivative undergo reductive formylation when treated with formic acid in formamide 1,4-diformyl-... 

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