Starting from 4‐chlorocoumarin‐3‐carbaldehyde (1) and Wittig phosphoranes 2a‐d the title compounds 6a‐c have been synthesized via a four‐step sequence. The intermediate 4‐alkylamino‐3‐vinylcoumarins 5a‐k have been prepared by the reaction of 4‐chloro‐3‐vinylcoumarins 3a‐d with primary amines 4a‐h. The coumarin derivatives 5 (except 5k) underwent an unusual pyridine ring closure under Vilsmeier conditions to form the benzopyrano[4,3‐b]pyridines 6. When the aminoaldehydes 7 were treated with the Wittig reagent 2b the fused N‐alkyl‐2(1H)‐pyridinones 8 have been obtained as expected.

Abstract:Reaction of 4-hydroxy-6-methyl-2-pyrone (1a) as well as 4-hydroxy-6-methyl-2(1H)-pyridones (1b-d) with arylmethylene malononitriles or arylmethylene methyl cyanoacetates (2a-h) leads to the formation of the very stable 5,6-fused bicyclic 2-amino-4H-pyran derivatives 3a-3af.

Reaction of the methyl benzylideneacetoacetate (Ia) with the ethyl acetoacetate (II) gives nitrendipine (IIIc) as the main product, together with the symmetrical esters (IIIa) and (IIIb).

In the preparation of the anticoagulants warfarin (3a) and its 4'-substituted derivatives (e.g. acenocoumarol, 3b) by Michael addition of 4-hydroxycoumarin (1) to the corresponding 4-aryl-3-buten-2-ones (2). ammon-ialV2), aliphatic or acromatic amine~~.~), ~yridine~.~.~', quinoline3"), alkali phosphate^^'^^'. sodium acetate or citrate3', borax3' and alkali alkoxides6) have been used as catalysts till now.We found out that by accomplishing this reaction in aqueous medium either alkali fluorides (KF, NaF) or quarternary ammonium salts (phase-transfer catalysts) can be applied as highly efficient catalysts ( Table 1). For comparison of the reaction times the addition process was carried out also without any catalyst (entries 1 and 12) and in the presence or triethylamine or trisodium phosphate (entries 10 and 11) being the most recommended catalysts in the literature. Accomplished in pyridiae or in glacial acetic acid in the presence of sodium acetate the reaction gave dark-coloured by-products and the purification of the products was complicated. Diluted sulfuric acid inhibited or stopped this reaction.The following general conclusions can be drawn from the experimental data presented in Table 1.First, for the preparation of warfarin (3a) the phase-transfer catalysts in optimum concentration of 5 mol per cent are more suitable. The yield of 3a is not essentially influenced by the nature of the quartemary salt. The use of these catalysts reduces the reaction time to about 5 % while the use of KF reduces it only to about 50 '% (entry 9). Even more, the catalysed processes give markedly higher yields of 3a.Second, the alkali fluorides in a concentration of 5 mol per cent are more useful for the preparation of acenocoumarol (3b). There is practically no difference in the effects of the salts used in entries 13 and 16. Alkali fluorides reduce the reation time to 33 9% while triethylbenzylammonium chloride (entry 17) shortens it to about 50 %. The simultaneous application of both catalysts (entry 18) does not PH 52 1 enhance the catalytic effect, and the product isolated in these trials is of low quality.High yields are achieved when using the catalysts described abovenearly 80 % for triethylbenzylamrnoniurn chloride in 3a (entry 3) and for NaF in 3b (entry 16). The reaction mixture remains pale-coloured till the end of the process and the corresponding product can be isolated easily in a rather pure state. The Michael addition occurs by refluxing in a heterogeneous mixture, since 4-hydroxycoumarin (1) is soluble in hot water and the unsaturated ketone 2 is a melt. Obviously, fluoride ions act as a week basic catalyst with good solubility in the org. phase lo). However, complementary studies should be undertaken for a reasonable explanation of the catalytic effect of quartemary ammonium salts in the absence of any base (in contrast to the numerous examples in lit. ")). Experimental Part M.p.: Btichi 510 apparatus (Switzerland), uncorrected. -TLC: Al-foils Kieselgel 60 FZ4. Merck (FRG), developed by cyclohexane-chlorofoma...

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