Low-valent titanium induced cyclization of dimeric dianions of anils with triphosgene: A safe and efficient method for the syntheses of substituted imidazolidine 2-ones

Article abstract of DOI:10.1081/SCC-120006022

Induced by low-valent titanium reagent, substituted imidazolidine 2-ones were synthesized from imines and triphosgene in moderate to good yields.

Full text of DOI:10.1081/SCC-120006022

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
LOW-VALENT TITANIUM INDUCED CYCLIZATION OF
DIMERIC DIANIONS OF ANILS WITH TRIPHOSGENE:
A SAFE AND EFFICIENT METHOD FOR THE
SYNTHESES OF SUBSTITUTED IMIDAZOLIDINE 2-
ONES
Zhifang Li & Yongmin Zhang
To cite this article: Zhifang Li & Yongmin Zhang (2002) LOW-VALENT TITANIUM INDUCED
CYCLIZATION OF DIMERIC DIANIONS OF ANILS WITH TRIPHOSGENE: A SAFE AND EFFICIENT
METHOD FOR THE SYNTHESES OF SUBSTITUTED IMIDAZOLIDINE 2-ONES, Synthetic
Communications, 32:17, 2613-2618, DOI: 10.1081/SCC-120006022
To link to this article: http://dx.doi.org/10.1081/SCC-120006022
Published online: 20 Aug 2006.
Submit your article to this journal
Article views: 30
View related articles
Citing articles: 9 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [Gazi University]
Date: 08 April 2016, At: 07:39

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONS
Vol. 32, No. 17, pp. 2613–2618, 2002
LOW-VALENT TITANIUM INDUCED
CYCLIZATION OF DIMERIC DIANIONS
OF ANILS WITH TRIPHOSGENE: A SAFE
AND EFFICIENT METHOD FOR THE
SYNTHESES OF SUBSTITUTED
IMIDAZOLIDINE 2-ONES
Zhifang Li1 and Yongmin Zhang1,2,
*
1Department of Chemistry, Zhejiang University
(Campus Xixi), Hangzhou 310028, P.R. China
2State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, P.R. China
ABSTRACT
Induced by low-valent titanium reagent, substituted imidazo-
lidine 2-ones were synthesized from imines and triphosgene in
moderate to good yields.
Key Words: Low-valent titanium; Imidazolidine 2-ones; Tri-
phosgene
Since its introduction by McMurry[1] and two other groups[2] in the
1970’s, low-valent titanium has been extensively investigated as a versatile
reagent in organic synthesis, especially with it’s exceptional ability to
promote reductive coupling of many functional groups.[3–5] Alexakis and
*Corresponding author. Fax: 86-571-8807077; E-mail: yminzhang@mail.hz.zj.cn
2613
DOI: 10.1081/SCC-120006022
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2614
LI AND ZHANG
Scheme 1.
co-workers[6] reported the synthesis of symmetrical vicinal dl-diamines from
the corresponding imines using low-valnet titanium species generated using
TiCl4 and Hg-Mg system. Recently Chen and co-workers[7] described the
reaction of imines and trimethyl orthoformate induced by TiCl4/Zn powder
system to give imidazolidines in moderate yields. In connection with our
interest in investigating new reduction coupling reactions induced by
low-valent titanium, now we describe the cross-coupling reaction of
imines with triphosgene to give substituted imidazolidine 2-ones (Scheme 1).
Triphosgene, as a safe, and stable substitute for phosgene, has been
used in various chloroformylation, chlorination, carbonylation and dehy-
dration reactions.[8] However, to date the chemical utility of triphosgene[9]
remains relatively unexploited, as it has only been reported in the preparation
of N-carboxy-a-amino acid anhydrides,[10] synthesis of b, g and ꢀ-lactams,[11]
and chlorination of benzylic or allylic alcohols.[12] Herein we reported the
preparation of imidazolidine 2-one derivatives (2) by treatment of triphos-
gene with the dianions of anil, which were generated by the induction of
low-valent titanium.
We observed that both N-phenylbenzalimine and N-alkylamine could
react with triphosgene smoothly suing low-valent titanium species obtained
from TiCl4/Sm THF system, and the imidazolidine 2-ones (2) were afforded
in moderated to good yields. The results and scope of this reaction are
summarized in Table 1.
Although the detailed mechanism of this reaction is not clear at this
stage, it is probable that the reaction starts by an electron transfer from low-
valent titanium, thus the radical anion (A) is formed, then (A) dimerizes into
dianion (B), which reacts with triphosgene to give imidazolidine 2-ones
(Scheme 2).
In conclusion, the present studies described a safe and efficient method
for the syntheses of substituted imidazolidine 2-ones, some of which have
been reported to be biologically active.[15] This method has a distinct
advantage over the conventional method, which involved condensing 1,2-
ethylenediamines and diethylcarbonates,[13] since the preparation of
diamines alone needed several steps.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SUBSTITUTED IMIDAZOLIDINE 2-ONES
2615
Table 1. Conversion of Imines to Imidazolidine 2-Ones Using TiCl4/Sm System
Entry
Ar1
C6H5
C6H5
4-CH3C6H4
4-CH3C6H4
2-CH3C6H4
C6H5
4-CH3OC6H4
C6H5
4-ClC6H4
6H5
C6H5
R
Compound
Yield (%)a
Meso/dlb,c
1
2
3
4
5
6
7
8
9
C6H5
4-CH3C6H4
C6H5
4-CH3C6H4
C6H5
4-ClC6H4
4-CH3OC6H4
C3H7
C3H7
C7H15
2a
2b
2c
2d
2e
2f
2g
2h
2i
85
87
82
79
95/5
95/5
90/10
95/5
96/4
72
/10 8090
85
65
87
74
83
84
96/4
95/5
95/5
70/30
95/5
95/5
10C
11
12
2j
2k
2l
-ðCH2Þ -
-ðCH2Þ66-
4-CH3C6H4
aIsolated yields based on the starting imines utilized; bPure dl isomer was obtained by
c
recrystallization; Ratio of meso and dl isomer was determined by H NMR.
1
Scheme 2.
EXPERIMENTAL
Tetrahydrofuran (THF) was distilled from sodium-benzophenone
immediately prior to use. All reactions were conducted under a nitrogen
atmosphere. Melting points were uncorrected. Infrared spectra were recorded
on a Bruker Vecter-22 spectrometer in KBr or film with absorption in cmꢀ1
.
1H NMR spectra were determined in a Bruker AC-400 spectrometer as
CDCl3 solutions. J values are in Hertz. Chemical shifts are expressed

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2616
LI AND ZHANG
in ppm downfiled from internal tetramethylsilane. Mass spectra were
recorded on a HP 5989B MS spectrometer. Microanalysis was carried out
on a EA 1110instrument.
General Procedure for the Synthesis of Imidazolidine 2-Ones
A dry 50mL flask was charged with Sm powder (2 mmol), TiCl 4
(0.22 mL, 2 mmol) and THF (20 mL). The mixture was refluxed for 2 h
under nitrogen, then cooled to room temperature. When black slurry was
formed, a solution of imine (2 mmol) and of triphosgene (1 mmol) in THF
(1 mL) was added to the reaction mixture, after stirred for about 3 h at room
temperature, then refluxed for 2 h. The black reaction mixture was quenched
with saturated K2CO3 solution (2 N, 5 mL) and extracted with ester
(3 Â10mL). The combined organic extract was washed with brine (10mL),
then dried over with anhydrous MgSO4 and concentrated. The residue was
chromatographed on a silica gel column and the imidazolidine 2-one
derivative was isolated using 20% ethyl acetate in hexane as eluent.
Compound 2a: m.p.: 178–179ꢁC (lit[14] 170–171ꢁC). ꢁmax(KBr)/cmꢀ1
1695. ꢀH(CDCl3): 7.05–7.46 (20H, m), 5.64 (2H, s).
:
Compound 2b: m.p.: 223–224ꢁC (lit[14] 224–225ꢁC). ꢁmax(KBr)/cmꢀ1
1720. ꢀH(CDCl3): 7.10–7.20 (18H, m), 5.66 (2H, s), 2.27 (6H, s).
:
Compound 2c: m.p.: 135–136ꢁC (lit[14] 135). ꢁmax(KBr)/cmꢀ1: 1695.
ꢀH(CDCl3): 7.58–7.70(18H, m), 5.50(2H, s), 2.22 (6H, s).
Compound 2d: m.p.: 171–173ꢁC (lit[14] 172–173ꢁC). ꢁmax(KBr)/cmꢀ1
1700. ꢀH(CDCl3): 7.18–7.25 (16H, m), 5.56 (2H, s), 2.26 (12H, m).
:
Compound 2e: m.p.: 189–191ꢁC (lit[14] 190ꢁC). ꢁmax(KBr)/cmꢀ1: 1700.
ꢀH(CDCl3): 7.05–7.15 (18H, m), 5.76 (2H, s), 2.25 (6H, s).
Compound 2f: m.p.: 186–188ꢁC (lit[14] 188ꢁC). ꢁmax(KBr)/cmꢀ1: 1700.
ꢀH(CDCl3): 7.05–7.20 (18H, m), 5.55 (2H, s).
Compound 2g: m.p.: 236–238ꢁC. ꢁmax(KBr)/cmꢀ1: 1728. ꢀH(CDCl3):
6.47–7.39 (16H, m), 6.20(2H, s), 3.62 (12H, m). m/z(%): 510(M þ, 2.09).
Anal. C31H30N2O5. Calcd: C, 72.94; H, 5.88; N, 5.49. Found: C, 72.90; H,
5.86; N, 5.47%.
Compound 2h: m.p.: 156–158ꢁC. ꢁmax(KBr)/cmꢀ1: 1713. ꢀH(CDCl3):
6.75–7.19 (10H, m), 6.22 (2H, s), 3.08–3.45 (4H, m), 0.57–1.56 (10H, m).
m/z(%): 322 (Mþ, 4.68). Anal. C21H26N2O. Calcd: C, 78.26; H, 8.07; N,
8.69. Found: C, 78.24; H, 8.06; N, 8.67%.
Compound 2i: m.p.: 162–164ꢁC. ꢁmax(KBr)/cmꢀ1: 1720. ꢀH(CDCl3):
7.18–7.53 (8H, m), 6.24 (2H, s), 3.10–3.48 (4H, m), 0.57–1.55 (10H, m).
m/z(%): 390(M þ, 3.37). Anal. C21H24Cl2N2O. Calcd: C, 64.62; H, 6.15;
N, 7.18. Found: C, 64.61; H, 6.13; N, 7.16%.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SUBSTITUTED IMIDAZOLIDINE 2-ONES
2617
Compound 2j: m.p.: 106–108ꢁC. ꢁmax(KBr)/cmꢀ1: 1715. ꢀH(CDCl3):
6.79–8.04 (10H, m), 6.30 (2H, s), 3.50–3.68 (4H, m), 0.80–1.35 (26H, m).
m/z(%): 434 (Mþ, 1.99). Anal. C29H42N2O. Calcd: C, 80.18; H, 9.67; N,
6.45. Found: C, 80.16; H, 9.63; N, 6.45%.
Compound 2k: m.p.: 164–166ꢁC. ꢁmax(KBr)/cmꢀ1: 1720. ꢀH(CDCl3):
7.22–7.60 (10H, m), 6.26 (2H, s), 3.44 (2H, m), 0.51–1.85 (20H, m).
m/z(%): 402 (Mþ, 2.09). Anal. C27H34N2O. Calcd: C, 80.59; H, 8.45; N,
6.96. Found: C, 80.57; H, 8.43; N, 6.94%.
Compound 2l: m.p.: 174–176ꢁC. ꢁmax(KBr)/cmꢀ1: 1720. ꢀH(CDCl3):
6.75–7.12 (8H, m), 6.26 (2H, s), 3.38 (2H, m), 2.19 (6H, s), 0.99–1.83
(20H, m). m/z(%): 430(M þ, 2.09). Anal. C29H38N2O. Calcd: C, 80.93; H,
8.84; N, 6.51. Found: C, 80.90; H, 8.82; N, 6.49%.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China
(Project No. 20072033) and the NSF of Zhejiang province for financial
support.
REFERENCES
1. McMurry, J.E.; Fleming, M.P. J. Am. Chem. Soc. 1974, 96, 4708.
2. (a) Tyrlik, S.; Wolochwicz, I. Bull. Soc. Chim. Fr. 1973, 2147;
(b) Mukayama, T.; Sato, T.; Hanna, J. Chem. Lett. 1973, 1041.
3. (a) MuMurry, J.E. Chem. Rev. 1989, 89, 1513; (b) Furstner, A.;
Bogadannovic, B. Angew. Chem. Int. Ed. Engl. 1996, 35, 2442.
4. Chen, W.-X.; Zhang, J.-H.; Hu, M.-Y.; Wang, X.-C. Synthesis 1990, 701.
5. Li, J.; Shi, D.-Q.; Chen, W.-X. Heterocycles 1997, 45, 2381.
6. Mangeney, P.; Tejero, T.; Alexakis, A.; Grosjean, F.; Normant, J.
Synthesis 1998, 255.
7. Li, J.; Shi, D.-Q.; Chen, W.-X. Tetrahedron Lett. 1999, 40, 1961.
8. Eckert, H.; Forster, B. Angew. Chem. Int. Ed. Engl. 1987, 26, 894.
9. Ghosh, A.K.; Duong, T.T.; Mckee, S.P. Tetrahedron Lett. 1991,
32, 4251.
10. (a) Wilder, R.; Mobashery, S. J. Org. Chem. 1992, 57, 2755;
(b) Daly, W.H.; Poche, D. Tetrahedron Lett. 1988, 29, 5859.
11. Gill, G.B.; Pattenden, G.; Reynolds, S.J.D. Tetrahedron Lett. 1989,
30, 3229.
12. Goren, Z.; Heeg, M.J.; Mobashery, S. J. Org. Chem. 1991, 56, 7186.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
2618
LI AND ZHANG
13. Hofmann, Klaus. Imidazole and Its Derivatives: Part I; Interscience:
New York, 1953; 226.
14. Prasad, G.; Singh, G.; Mehrotra, K.N. Indian J. Chem. Sect. B 1980,
19B, 653.
15. Butler, D.C.D.; Inman, G.; Alper, H. J. Org. Chem. 2000, 65, 5887,
and References Cited Herein.
Received in the Netherlands August 1, 2001