Synthesis and bioactivity of some new 2-substituted-3,4-dihydro-1-(9H- carbazol-4-yloxy)methyl-3-[2-(2-methoxyphenoxy)ethyl]-1,3,2 λ5-oxazaphosphole 2-oxides, sulfides and selenides

K Srinivasulu,M Anil Kumar,C Naga Raju,C Suresh Reddy

doi:10.3998/ark.5550190.0008.e10

Abstract

Novel 2-substituted-3,4-dihydro-1-(9H-carbazol-4-yloxy)methyl-3-(2-(2-methoxyphenoxy) ethyl)-1,3,2λ 5 -oxazaphosphole 2-oxides (3a-e) were synthesized by condensation of 1-(9H- carbazol-4-yloxy)-3-(2-(2-methoxy phenoxy)ethylamino)propan-2-ol (1) (carvedilol) with dichlorides of aryl phosphorodichloridates / N,N-bis(2-chloroethyl)phosphoramidic dichloride (2a-e) in the presence of triethylamine at 40 to 45 °C. The other title compounds (6a-c, and 6d-f) were prepared in two steps. In the first step, dichlorophenylphosphine/ethyl phosphorodichloridite was reacted with 1 in the presence of Et3N to give the corresponding P(III) intermediates (5a,b) in N2 atmosphere. In the second step, 5a,b were treated with H2O2, S or Se to convert them to the corresponding P(V) state (6a-c, 6d-f). Compounds 3a-e, 6a-f were screened for antifungal and antibacterial activity. Most of these compounds exhibited moderate activity.

Highlights

Organophosphorus compounds are ubiquitous in nature and find applications in the field of agriculture, medicine and industry.[1,2]
Synthesis of new multi-ring phosphorus heterocycles for applications in medicine and industry has attracted the attention of researchers in recent years
Carvedilol is a non-selective beta blocker indicated for the treatment of mild to moderate congestive heart failure (CHF)

Summary

Introduction

Organophosphorus compounds are ubiquitous in nature and find applications in the field of agriculture, medicine and industry.[1,2] Some organophosphorus compounds are important pesticides,[3] bactericides,[4,5] and antibiotics.[4]. The novel phosphorus heterocyclic compounds (3a-e), (Scheme 1) were prepared in a one-pot synthetic route, starting from carvedilol (1) with various phenyl phosphoro- dichloridates[7,8] (2) in equimolar quantities in the presence of triethylamine in dry tetrahydrofuran and toluene (1:3) at 40-45 °C. The synthesis of a few of the other title compounds such as oxide, sulfide and selenide derivatives (6a-f) was accomplished through a two-step route involving (1) with dichlorophenylphosphine and ethyl dichlorophosphite (4a,b) in the presence of triethylamine in dry tetrahydrofuran and toluene under N2 to form the corresponding trivalent phosphorus intermediates (5a,b).

Results

Conclusion