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Synlett 2023; 34(04): 353-358
DOI: 10.1055/s-0042-1751410
letter

Synthesis of N–C Fused Bicyclic 1,3,5-Triazinane-2,4-dione Derivatives from Saturated Ring-Fused Urazoles

Subhaskar R. Panga 
a   Syngenta Biosciences Private Limited, Santa Monica Works, Corlim, Goa, 403110, India
c   Department of Chemistry, Mangalore University, Mangalagangothri, 576119, India
,
Roger G. Hall
b   Syngenta Crop Protection AG, Schaffhauserstrasse, 4332 Stein, Switzerland
,
Ashok Shyadligeri
a   Syngenta Biosciences Private Limited, Santa Monica Works, Corlim, Goa, 403110, India
,
Shrikant A. Shete
a   Syngenta Biosciences Private Limited, Santa Monica Works, Corlim, Goa, 403110, India
,
Bhanu N. Manjunath∗
a   Syngenta Biosciences Private Limited, Santa Monica Works, Corlim, Goa, 403110, India
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Abstract

A synthesis of novel bicyclic 1,3,5-triazinane-2,4-diones has been accomplished through base-promoted fragmentation followed by cyclization. Various saturated ring-fused bicyclic urazoles were prepared by two complementary methods: by the reaction of N,N′-bis(2-chloroethyl)urazoles with various nucleophiles or by using 4-substituted urazoles and dibromoalkanes. Treatment of these symmetrical urazole derivatives with LDA at –78 °C to 25 °C resulted in fragmentation of the N–N bond to form an imine that underwent intramolecular cyclization, resulting in moderate yields of nonsymmetric heterocycle derivatives with an asymmetric (racemic) center and various ring sizes. The utility of these transformations was extended to syntheses of a tricyclic system and bicyclic systems containing additional heteroatoms.

Key words

triazinanediones - bridgehead-nitrogen heterocycles - N–N bond fragmentation - atom economy - urazoles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751410.
  • Supporting Information


Publication History

Received: 11 November 2022

Accepted after revision: 28 December 2022

Article published online:
24 January 2023

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  • 13 N–C Fused Perhydrotriazine-2,4-dione Derivatives 19a–g; General Procedure A 0.5 M solution of LDA (freshly prepared from butyllithium and diisopropylamine) in toluene (1.5 mmol, 1.5 equiv) was added to a 0.4 M solution of the appropriate fused urazole derivative 18a–g (1.0 mmol, 1.0 equiv) in toluene at –78 °C. The mixture was slowly brought to 25 °C and stirred for 5 h. When the reaction was complete, the mixture was cooled to 0 °C and sat. aq NH4Cl was added. The resulting mixture was diluted with H2O (10 mL) and EtOAc (50 mL), and the organic layer was separated and washed successively with H2O and brine, dried (Na2SO4), and concentrated. The resulting crude product was triturated with EtOAc.
  • 14 3-(4-Chlorophenyl)hexahydro-2H-pyrido[1,2-a][1,3,5]triazine-2,4(3H)-dione (19a) White solid; yield: 72 mg (52%); mp 215–218 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 8.36 (s, 1 H), 7.41–7.48 (m, J = 8.6 Hz, 2 H), 7.19–7.24 (m, J = 8.6 Hz, 2 H), 4.61 (br d, J = 6.7 Hz, 1 H), 4.00–4.12 (m, 1 H), 2.66–2.77 (m, 1 H), 1.85–1.94 (m, 1 H), 1.79 (br s, 1 H), 1.64 (br d, J = 12.1 Hz, 1 H), 1.42–1.53 (m, 2 H), 1.13–1.41 (m, 1 H). 13C NMR (101 MHz, DMSO-d 6): δ = 152.9, 151.6, 135.6, 132.4, 132.1, 128.7, 63.9, 43.6, 32.8, 24.1, 22.4. HRMS (ESI): m/z calcd for [C13H14ClN3O2]+: 279.0774; found: 279.0777.