Cyclization of Active Methylene Compounds with ω-Chloroalkyl Isocyanates and Isothiocyanates and Related Species

Ahmad Basheer ,  Zvi Rappoport 

Department of Organic Chemistry, The Hebrew University, Jerusalem 91904, Israel

Abstract

Enols and thioenols Y'YC=C(XH)NHR (X=O,S) were previously obtained by condensing CH2YY' with isocyanates or isothiocyanates. These dipolar polyfunctional (NHR, OH, electrophilic C=C) species are potential synthons. In the present work we prepared >25 heterocyclic compounds by reaction of active methylene compounds 1 with organic isocyanates or isothiocyanates carrying a terminal nucleofuge, such as Cl. Compounds 1 gave with 2-chloroethyl isocyanate (or isothiocyanate) 2 (n= 1, X=O, S) the 1,3-oxazolidines and 1,3-thiazolidines 3 (n=1, X=O, S), respectively.

zvi1.jpg

Reaction of 1 with 2 (n= 2, X= O) gave the 1,3-oxazines 3 (n=2, X=O). The analogous asymmetric 1,3-thiazolidine 3 (n= 1, X= S) showed E and Z isomers, the one displaying the lower field NH group being in excess. Replacing the Cl by a CO2Et, e.g. in ethyl 2-isothiocyanatobenzoate 4a and reacting with CH2(CN)CO2Me gave E/Z methyl cyano (1,4-dihydro-2-oxo-1H-3,1-benzothiazin-2-ylidene) acetate 5, while the ethyl 2-isocyanatobenzoate analogue 4b gave with 1 the non-cyclized enols 2-(EtO2C)C6H4NHC(OH)=CYY' 6. Ethoxycarbonyl isothiocyanate 7 and CH2(CN)CO2Me gave the non-cyclized thioenol EtO2CNHC(SH)=C(CN)CO2Me 8. Finally, while 3 was formed from NaCH(CN)CONHMe with 2 (n=1, X=O) in dry THF, reaction of CH2(CN)CONHMe with 2 (n=1, X=O) in the presence of dry Et3N/ dry DMF gave the bicyclic aminopyrimidinedione 9. Possible mechanisms for formation of the products will be discussed.

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  1. Hydrolysis of α-Alkyl-α-(methylthio) Methylene Meldrum's Acides. A Kinetic and Computational Investigation of Steric Effects.

Presentation: oral at 18th Conference on Physical Organic Chemistry, Symposium 1, by Zvi Rappoport
See On-line Journal of 18th Conference on Physical Organic Chemistry

Submitted: 2006-06-01 18:46
Revised:   2009-06-07 00:44
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