Synlett 2019; 30(07): 857-859
DOI: 10.1055/s-0037-1611760
letter
© Georg Thieme Verlag Stuttgart · New York

One-Pot Regioselective Synthesis of 2,5,6,7-Tetrahydroimidazo [1,2-a]imidazol-3-ones Starting from (Vinylimino)phosphoranes

Fen Tan
a   Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients, Hubei University of Education, Wuhan 430205, P. R. of China   Email: huashengxi2@163.com
,
Zheng-Zheng Meng
a   Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients, Hubei University of Education, Wuhan 430205, P. R. of China   Email: huashengxi2@163.com
,
Xiao-Qin Xiong
a   Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients, Hubei University of Education, Wuhan 430205, P. R. of China   Email: huashengxi2@163.com
,
Guo-Ping Zeng*
a   Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients, Hubei University of Education, Wuhan 430205, P. R. of China   Email: huashengxi2@163.com
,
b   Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, Central China Normal University, Wuhan 430079, P. R. of China   Email: mwding@mail.ccnu.edu.cn
› Author Affiliations
We gratefully acknowledge financial support of this work by the National Natural Science Foundation of China (Nos. 21572075 and 21602052), the 111 Project B17019, the Natural Science Foundation of Hubei province (No. 2014CFB567), and Research Startup Funding of Hubei University of Education Grant.
Further Information

Publication History

Received: 27 January 2019

Accepted after revision: 20 February 2019

Publication Date:
26 March 2019 (online)


Abstract

A new, one-pot, regioselective preparation of 2,5,6,7-tetrahydroimidazo[1,2-a]imidazol-3-ones by a sequential aza-Wittig/nucleophilic addition/cyclization reaction was developed. The aza-Wittig reactions of ethyl (2Z)-3-aryl-2-[(triphenylphosphoranylidene)amino] acrylates with aryl isocyanates produced carbodiimide intermediates that were then treated sequentially with 2-aminoethanol and tosyl chloride/triethylamine to give the corresponding (2Z)-2-[(substituted)benzylidene]-2,5,6,7-tetrahydro-3H-imidazo[1,2-a]imidazol-3-ones in good overall yields and with high regioselectivity.

Supporting Information

 
  • References and Notes

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  • 22 (2Z)-2-Benzylidene-7-(4-tolyl)-2,5,6,7-tetrahydro-3H-imidazo[1,2-a]imidazol-3-one (6ab); Typical Procedure (Vinylimino)phosphorane 1a (2.26 g, 5 mmol) was treated with 4-tolyl isocyanate (2b; 0.67 g, 5 mmol) in CH2Cl2 (15 mL) at r.t. for 4 h to give carbodiimide 3ab (monitored by TLC), which was used directly in the next step. Ph3P=O was extracted from the mixture with 1:2 Et2O–PE (20 mL), and carbodiimide 3ab was treated with 2-aminoethanol (4; 0.60 mL, 5 mmol) in CH2Cl2 (15 mL) with stirring for 4 h. The mixture was then concentrated and the residue was dissolved in MeCN (25 mL). Et3N (2.8 mL, 20 mmol) was added, followed after 30 min by TosCl (1.05 g, 5.5 mmol). The mixture was then stirred at r.t. for about 6 h until 5ab was completely consumed (TLC). The reaction was quenched with sat. aq NH4Cl, and the mixture was extracted with CH2Cl2. The extracts were dried (Na2SO4) and the crude mixture was purified directly by flash column chromatography [silica gel PE–CH2Cl2 (4:1 to 2:1)] to give a light-yellow solid; yield: 1.24 g (82%); mp 196­–198 °C.IR: 2954, 2924, 2854, 1730, 1659, 1603, 1591, 1565, 1519, 1492, 1459, 1376, 1305 cm–1. 1H NMR (600 MHz, CDCl3): δ = 8.09 (d, J = 7.6 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.31 (t, J = 7.3 Hz, 1 H), 7.27–7.23 (m, 2 H), 6.76 (s, 1 H), 4.40–4.31 (m, 2 H), 4.00–3.90 (m, 2 H), 2.36 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 166.3, 158.7, 145.2, 135.9, 135.0, 133.2, 130.9, 129.8, 128.5, 128.4, 119.0, 117.1, 50.7, 36.7, 20.8. HRMS (ESI): m/z [M + H]+ calcd for C19H18N3O: 304.1450; found: 304.1444.