Heterocyclic analogs of pleiadiene. 67. Formylation of perimidones, 2,3-dihydroperimidines, and perimidines

Abstract

Perimidones, 2,3-dihydroperimidines [2, 3] and perimidines [4] are known to be easily acylated at the 6(7)-(para) or 4(9)-(ortho) positions. Carboxylic acids in polyphosphoric acid were used as the acylating agents. For perimidones, acyl chlorides in the presence of anhydrous AICI3 were used [5]. Therefore, we expected that formylation of these compounds might proceed just as easily. The present work tests that hypothesis.We found that 1,3-dialkylperimidones (Ia and Ib) undergo the Vilsmeier reaction (POC13-DMF) at 60-80~ to form the perimidon-6-carboxaldehydes Ha, b in 80-85% yield. It seemed interesting to determine if the monoaldehydes could be further formylated, keeping in mind that perimidones readily undergo diacylation [3]. Heating IIa with an excess of Vilsmeier reagent (60-80~ 5.5 h) led to formation of resin. The only product in about 20% yield was 1,3-dimethylperimidon-4-carboxaldehyde (III), which was somewhat unexpectedly isolated. A similar isomerization was previously observed for 6-acylperimidines with an unsubstituted N-H group [4]. It was proposed that this isomerization is driven by the formation in 9-acyl derivatives of a strong intramolecular hydrogen bond (IHB). Since this is not a factor for aldehyde III, the migration of the formyl group to the more sterically hindered ortho position is apparently due to some other reason. It is noteworthy that aldehyde IIa is completely destroyed by heating with polyphosphoric acid for -30 min, forming a dark green crystalline product. Judging from the PMR spectrum, the product is a complex mixture of oligomers. The tendency to oligomerize in acidic medium probably explains the relatively low yield oflII. Formylation of 1,3-dimethyl-2,3-dihydroperimidine (IV) is more complicated and significantly less regioselective. The reaction goes slowly even at -20-(-30)~ However, it is better conducted at room temperature.

Heterocyclic analogs of pleiadiene 76. Synthesis and tautomeric conversions of mono- and disubstituted perimidines with electron-withdrawing substituents in the naphthalene fragment

“…Compound 13 formed pale-yellow crystals, mp 163-164 o C (benzene with petroleum ether [16], and 10 [6] in the corresponding publications. New spectral data of compounds discussed in the present work are given below.…”

“…A characteristic feature of such compounds is the presence in their 1 H NMR spectra in nonpolar solvents of a low-field signal of the chelated NH proton at 12-13 ppm. For example, in the spectrum of 9-formyl-2-trifluoromethylperimidine (6) in CDCl 3 it is found at 12.34 against 8.23 ppm for the peak of the nonchelated NH proton in the 6(7) isomeric analog [6]. The fixed (N-methylated) 4-CO forms of the same aldehydes and ketones 8-10 have a series of characteristic special features.…”

“…+ unchanged on transferring to DMSO-d 6 . Only on heating to 50 o C was the signal of the ortho protons converted into a broadened doublet and the fine structure of the signals of the other aromatic protons displayed (see Table 1).…”

“…It is interesting that even heating 4(9)-acetylperimidine (5) in DMSO-d 6 to 110 o C does not change the picture of the spectrum significantly. Attention is drawn by the fact that on going from CDCl 3 to DMSO-d 6 the chemical shift of the NH···O signal is changed insignificantly, but the proton in position 2 is split into a doublet in both solvents (J 2H-NH = 3.1 and 3.3 Hz respectively).…”

“…Since 4(9)-isomeric aldehydes, ketones, and sulfones are formed together with 6(7) derivatives on acylation, formylation, and arene sulfonation [5][6][7], it seemed of interest to investigate the possibility of their prototropic conversions, and also the degenerate tautomerism of 4,9-disubstituted analogs. Due to the formation of an extremely stable intramolecular hydrogen bond between the NH proton and the oxygen of the carbonyl group, the 4(9)-formyl-(4, 6) and 4(9)-acetylperimidines (5, 7) in nonpolar solvents, and judging overall, in the solid state exist exclusively in the chelated 9-CO form.…”