Tibor Eszenyi

A novel synthesis of 4-halo-2H-chromenes

Abstract substituted 4-halo-2H-chromenes were synthesized from the corresponding 4-chromanones and phosphorus trihalides.

ON THE FORMATION OF 3,4-DICHLORO-2,2-DIMETHYL-2H-CHROMENES FROM 2,2-DIMETHYL-4-CHROMANONES

The reaction of 7-methoxy-2,2-dimethyl-4-chromanone and PCIS is reinvestigated. The product distributions for the reactions of several acetoxy derivatives of 2,2-dimethyl~4chromanones and PCI5 have been studied to confirm an extended pathway. In the course of our research project different 3,4-dichloro-2,2-dimethyl-2/-/-chromenes (4) were needed for the syntheses of target compounds with insecticidal activity (1). We attempted the preparation of 4a (R, R = H, R = MeO) according to the literature procedure (2) (4h reflux in CCU using a 1:1 1a and PCIS molar ratio). We obtained 14% 2a and 54% 4a (3) after TLC mesh chromatography (4). This result was unexpected because it was reported (2) that under these conditions 98% 4a had been prepared and no conditions had been found which led to the formation of the corresponding 4-chloro-2H-chromene (2a) without further chlorination. We repeated the experiment using 1:1.5 1a and PCIS molar ratio: 7% 2a and 60% 4a were obtained after chromatography. Applying 1:3 1a and PCI5 molar ratio the reaction mixture did not contain 2a. According to Camps and co-workers (5) we repeated the preparation of 4a using 1:2 1a and PCIs molar ratio (4h iri CCU at room temperature). We got practically the expected result but a small amount of 2a was detected by TLC from the reaction mixture (compared to an authentic sample (6)). These results suggest that, as well the formation of 4-chloro-2H-chromenes (2) and their further chlorination at C-3 as the formation of 3-chloro-2,2-dimethyl-4-chromanones (3) are involved in the pathway of this reaction (5). Scheme

Synthesis of new bischromenes: Chemical probes for precocene receptors

Synthesis of new bischromenes (5-10) possessing potential insect antijuvenile hormone activity using the reaction of α,ω-dibromoalkanes with hydroxy-2,2-dimethyl-4-chromanones (la-e) is described. The structures of new intermediate bis-4-chromanones (2-4) as well as the target bis-2/-/-chromenes (5-10) were determined by H-NMR and MS methods. INTRODUCTION Precocene 1 and 2 are naturally occuring chromonoids (1) possessing insect antijuvenile hormone activity (2). A considerable effort has been made to elucidate the mode of action of these compounds and details of the chemical structure essential for this unique bioactivity (3) in order to produce synthetic precocenes of more pronounced activity. For these purposes hundreds of analogs of natural precocenes have been synthesized (4) and as a result of these extensive chemical and biological investigations the mechanism by which precocenes exert their action is now partly understood (5). It is well established that the precocenes are selectively activated by specific enzymes in the insect corpus allatum, and that these biotransformation products then alkylate important cellural components causing death and destruction of the allatal cells (6). During the structureactivity relationship studies relatively few attention has been focused on geometrical requirements of whole precocene molecule, that must also be of importance for optimal bioactivity (7). To learn the extent to which the geometrical requirements needed for elevated insect antijuvenile hormone activity and gain some information about precocene receptor(s) we decided to synthesize a series of new bis-2H-chromenes (5-10) thereby changing considerably the environment of C-7 position, as well as the shape and size of the whole precocene molecule, particularly in the case of the synthesis of these bis-2H-chromenes linked by spacers of different length. 5 4

NOVEL SYNTHETIC APPROACH TO ALKYLENE-DIOXY- PRECOCENES

A b e t r a c t j A n o v e l s y n t h e t i c r o u t e to a l k y l e n e d l o x y p r e c o c e n e s l_fi h a v i n g p o t e n t i a l p r e c o c e n e a n t a g o n i s t a c t i v i t y u s i n g t h e r e a c t i o n of α , ωd i b r o m o a l k a n e s w i t h 6 , 7 or 7 , 8 d i h y d r o x y 2 , 2 d i m e t h y l 4 c h r o m a n o n e s 4. 5 is d e s c r i b e d . T h e s t r u c t u r e s of i n t e r m e d i a t e 4 c h r o m a n o n e s 6 9 as we l l es t h e f i n a l r e g i o i s o m e r p r o d u c t s j_5 w e r e d e t e r m i n e d by 1 H N M R a n d MS m e t h o d s