Efficient synthesis of 4,4′-Bi-1H-imidazol-2-ones from 5-amino-α-imino-1H-imidazole-4-acetonitriles and isocyanates

Article abstract of DOI:10.1021/jo011192z

Reactions of 5-amino-α-imino-1H-imidazole-4-acetonitriles 1 with alkyl and aryl isocyanates led to efficient syntheses of 5′-amino-5-imino-4,4′-bi-1H-imidazol-2-ones 3 formed by intramolecular cyclization of the corresponding 5-amino-α-(N-alkyl/arylcarbamoyl)imino-1H-imidazole-4-acetonitriles 2. The cyclization occurs only slowly in solution but is considerably accelerated by the addition of a catalytic amount of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). The reaction of the N-arylamidine 6b, the synthetic precursor of the imidazole 1b, with benzyl isocyanate also led to the formation of 4,4′-bi-1H-imidazol-2-one 3b in quantitative yield. The imidazole intermediate 2b has been isolated and found to be identical with the compound obtained by reaction of the imidazole 1b and benzyl isocyanate. The N-arylamidine 6c (R = 4-NCC₆H₄) reacted with benzyl isocyanate in a similar way, but the electrophilicity of the amidine carbon atom resulted in rapid hydrolysis of the intermediate 7c leading ultimately to the isolation of the urea 9. The N-alkylamidines 6a and 6d behaved differently in their reaction with benzyl isocyanate, and the major product isolated in these reactions is again the urea 9.

Full text of DOI:10.1021/jo011192z

Efficien t Syn th esis of 4,4′-Bi-1H-im id a zol-2-on es fr om
5-Am in o-r-im in o-1H-im id a zole-4-a ceton itr iles a n d Isocya n a tes
Alice M. Dias, Isabel Cabral, M. Fernanda Proenc¸a,* and Brian L. Booth†
Departamento de Quı´mica, Universidade do Minho, Campus de Gualtar, 4710 Braga, Portugal
fproenca@quimica.uminho.pt
Received December 31, 2001
Reactions of 5-amino-R-imino-1H-imidazole-4-acetonitriles 1 with alkyl and aryl isocyanates led
to efficient syntheses of 5′-amino-5-imino-4,4′-bi-1H-imidazol-2-ones 3 formed by intramolecular
cyclization of the corresponding 5-amino-R-(N-alkyl/arylcarbamoyl)imino-1H-imidazole-4-acetoni-
triles 2. The cyclization occurs only slowly in solution but is considerably accelerated by the addition
of a catalytic amount of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). The reaction of the N-arylamidine
6b, the synthetic precursor of the imidazole 1b, with benzyl isocyanate also led to the formation of
4,4′-bi-1H-imidazol-2-one 3b in quantitative yield. The imidazole intermediate 2b has been isolated
and found to be identical with the compound obtained by reaction of the imidazole 1b and benzyl
isocyanate. The N-arylamidine 6c (R ) 4-NCC6H4) reacted with benzyl isocyanate in a similar
way, but the electrophilicity of the amidine carbon atom resulted in rapid hydrolysis of the
intermediate 7c leading ultimately to the isolation of the urea 9. The N-alkylamidines 6a and 6d
behaved differently in their reaction with benzyl isocyanate, and the major product isolated in
these reactions is again the urea 9.
SCHEME 1
In tr od u ction
Our previous work on the reaction of 5-amino-R-imino-
1H-imidazole-4-acetonitriles 1 with tosyl isocyanate re-
sulted in efficient syntheses of 6-amidino-2-oxopurines.1
Mechanistic studies suggested that this process starts
with reaction of the imino nitrogen of 1 with the isocy-
anate leading to structures 2 that cyclize to give 3
(Scheme 1). Rearrangement of the imidazolones 3 via the
isocyanates 4 finally affords the 2-oxopurines 5. However,
none of the intermediates could be isolated or detected
in solution, and thus, the mechanism could not be
unambiguously established. In the present work, the
imidazoles 1a ,b were reacted with alkyl and aryl isocy-
anates to understand the chemical behavior of less
electrophilic isocyanates. These reactions proved to be
an efficient method for syntheses of hitherto unreported
4,4′-bi-1H-imidazol-2-ones 3. To our knowledge, there is
only one reference in the literature reporting the syn-
thesis of 4,4′-biimidazoles,2 which were prepared by
palladium-catalyzed coupling of 4-iodo-1-triphenylmeth-
ylimidazoles.
Resu lts a n d Discu ssion
All reactions of imidazoles 1 were carried out under a
nitrogen atmosphere, in dry acetonitrile with 2-5 equiv
of the isocyanate. The reaction mixtures were stirred at
23 °C or below (Table 1).
The reactive aryl isocyanates [phenyl and 4-(trifluo-
romethyl)phenyl] gave good yields with both N-aryl- and
N-alkylimidazoles. With the less reactive alkyl isocyan-
ates (R2 ) benzyl, ethyl, n-butyl, and allyl), longer
reaction times were required. Good yields were still
obtained with the more stable N-arylimidazoles, but in
some cases, e.g., reaction between 1a and ethyl isocyan-
* To whom the correspondence should be addressed.
† Current address: Chemistry Department, University of Manches-
ter Institute of Science and Technology, Manchester M60 1QD, U.K.
(1) Booth, B. L.; Cabral, I. M.; Dias, A. M.; Freitas, A. P.; Matos
Beja, A. M.; Proenc¸a M. F.; Ramos Silva, M. J . Chem. Soc., Perkin
Trans. 1 2001, 1241-1251.
(2) Cliff, M. D.; Pyne, S. G. Synthesis 1994, 681.
10.1021/jo011192z CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/27/2002
5546
J . Org. Chem. 2002, 67, 5546-5552

Synthesis of 4,4′-Bi-1H-imidazol-2-ones
TABLE 1
intramolecular cyclization does not necessarily require
the addition of base but it is considerably accelerated by
it. Thus, when compound 2a was refluxed in ethanol for
8 h in the absence of a base, the biimidazol-2-one 3a was
isolated in 88% yield.
The bicyclic structure 3 is characterized by the absence
of a cyano stretching vibration in the IR spectrum. A very
strong band at 1708-1717 cm-1 indicates that the
carbonyl group is now part of the heterocyclic ring. In
the 13C NMR spectrum the carbonyl signal is shifted to
δ 165-167, while the signals for the imidazole ring are
almost unchanged with C-2 at δ 139-140, C-4 at δ 113-
1
114 and C-5 at δ 152-153. In the H NMR spectrum the
imine N-H appears at δ 9.6-10.2. The 1H/13C NMR
signals were assigned on the basis of a correlation study
by HMBC (heteronuclear multiple bond correlation) for
compound 3b.
The N-aryl- and N-alkylamidines 6a -d were also
treated with benzyl isocyanate in an attempt to generate
imidazoles 2 and/or 3 by intramolecular cyclization of the
acylated amidines (Table 2).
The reaction of the formamidine 6b with benzyl iso-
cyanate in acetonitrile led to a quantitative yield of a
colorless solid identified as the N-(benzylcarbamoyl)-
amidine 7b. When this reaction was carried out at room
temperature, extensive decomposition occurred and the
product 7b was isolated in only 47% yield. Application
of the HMBC technique indicated the presence of the
amino function (δ 8.0) of 7b in the vicinity of the cyano
group (δ 114.7). The amidine C-H (δ 8.46) turned out to
be linked to the carbon atom at δ 146.9 and to be three
bonds separated from the ipso carbon atom of the aryl
group (δ 143.7) and from C-1 of the vinylidene substituent
(δ 86.7). The IR spectrum showed an intense carbonyl
stretching vibration at 1676 cm-1 and absorptions at 2243
cm-1 (weak) and 2195 cm-1 (medium) for two cyano
groups. Stirring a solution of compound 7b in acetonitrile
at room temperature for 18 h afforded the amidine 8b
(60%) as a yellow solid. This product arose by migration
of the benzylcarbamoyl group from the amidine nitrogen
atom to the amino group, possibly via a five-membered
ring intermediate. The IR spectrum of compound 8b
showed a strong carbonyl stretching vibration at 1650
cm-1 and a single band of medium intensity at 2219 cm-1
a
b
Not isolated. From 1a in ethanol in the absence of DBU.
c From 1b in the absence of DBU.
ate, the long reaction time required (7 days at 23 °C)
resulted in extensive degradation of the imidazole 1a
resulting in a poor product yield even when 5 equiv of
the isocyanate was used.
1
for the two cyano groups. The H and 13C NMR spectra
The structures of imidazoles 2 were confirmed spec-
troscopically. In the IR spectra, weak bands at 2200-
2250 cm-1 indicated the presence of the cyano group. A
strong band at 1645-1660 cm-1 was assigned to the
carbonyl stretching vibration. The presence of both
carbonyl and cyano groups was confirmed by 13C NMR
spectroscopy with signals around δ 159-161 and 112-
113. The peak for C-2 at δ 135-138 is characteristic for
could be interpreted assuming the presence of tautomers
8bA and 8bB in a 1.5:1 ratio. The major isomer showed
three N-H signals as broad singlets at δ 10.3 and 8.3
and under the aromatic multiplet at δ 7.2-7.4. The C-H
signal at δ 7.9 turned out to be associated with the carbon
signal at δ 150.9. In the minor isomer, the C-H signal
occurred at δ 8.3 (underneath of one of the N-H peaks
of 8bA). The N-H bands appeared as broad signals at δ
10.5, 8.5 and 7.5. The presence of the two tautomers and
the fact that compound 8b rapidly cyclized in solution to
give the imidazole 2b led to a complex mixture that was
difficult to analyze with NMR techniques. When a
solution of 8b in acetonitrile was stirred at room tem-
perature for 30 min in the presence of a catalytic amount
of DBU compound 3b was formed quantitatively via 2b.
These results suggest that imidazole 1b reacts with
benzyl isocyanate either directly at the imino nitrogen
to give 2b or at the 5-amino substituent followed by acyl
migration affording 2e.
1
the imidazole ring as is the signal for C-2(H) in the H
1
NMR spectrum (δ 7.3-7.5). In the H NMR spectra, the
amino group gave rise to broad singlets at δ 7.6-8.2 while
the singlets for the amide protons were found at δ 7.9-
8.4 if R2 ) alkyl, respectively at δ 10.0-10.4 for R2
aryl.
)
The addition of DBU (0.03-1 equivalent) to the sus-
pension of a imidazole 2 in acetonitrile immediately lead
to the formation of yellow/orange solids isolated in
excellent yields after 15 min at 23 °C. These products
were identified as 4,4′-bi-1H-imidazol-2-ones 3. This
J . Org. Chem, Vol. 67, No. 16, 2002 5547

Dias et al.
TABLE 2
a
b
8b was also isolated (6%). From 8b, with DBU. c From 6c and benzyl isocyanate.
with excess of benzyl isocyanate (Table 3) furnished a
creamy solid product identified as the amidine 10a , in
low yields. The structure of the amidine 10a was con-
firmed by HMBC and COSY techniques. In the IR
spectrum a single band at 2220 cm-1 of medium intensity
was observed for the cyano groups.
When the amidine 6a and benzylisocyanate (1:2.6
molar ratio) in dry acetonitrile were kept at -18 °C for
1 week, compound 11 was isolated in low yield (13%).
This product was formed from 10 by intramolecular
nucleophilic attack of the hydroxyl group on the amidine
carbon atom. The constitution of compound 11 was
secured using HMBC and COSY techniques.
As the NMR spectra were determined in wet DMSO-
d6, compound 11 was slowly hydrolyzed to the urea 9 and
2-(3-benzylureido)ethyl formate. The urea 9 was also
isolated in 29% yield from the reaction mixture where
compound 11 was generated. All reactions involving the
amidine 6a and benzyl isocyanate led to 9 as a major
product.
From the reaction of benzyl isocyanate with the ami-
dine 6d the urea 9 was isolated as the major product
(30%). The acylated amidine 10d could only be isolated
in one of the experiments (3% yield) after dry flash
chromatography. Its structure was confirmed by spec-
troscopic analysis.
F IGURE 1. Tautomeric and configurational equilibrium of
compounds 6 in solution.
The reaction of the amidine 6c with benzyl isocyanate
under conditions used for 6b afforded the urea 9 (59%)
as an off-white solid probably resulting from hydrolysis
of 7c during the workup procedure. The electron-
withdrawing effect of the aryl substituent enhances the
electrophilicity of the amidine carbon atom. When the
reaction of the amidine 6c with 1 equiv of benzyl
1
isocyanate was followed by H NMR, the formation of
compound 7c was almost complete after 2 h at 20 °C. As
the DMSO-d6 was not completely anhydrous, some hy-
drolysis product 9 was observed after 1 day.
Previous work indicated that in solution N-alkylfor-
mamidines 6a and 6d adopt a constitution other than
N2-arylformamidines (Figure 1).3,4 This could be the
reason for the different reactions of these two types of
formamidines with isocyanates. Reactions of 6a and 6d
(3) (a) Booth, B. L.; Dias A. M.; Proenc¸a, M. F. J . Chem. Soc., Perkin
Trans. 1 1992, 2119. (b) Alves, M. J .; Booth B. L.; Proenc¸a, M. F. J .
Heterocycl. Chem. 1994, 31, 345.
(4) Alves, M. J .; Booth, B. L.; Kh Al-Duaij, O.; Eastwood, P.; Nezhat,
L.; Proenc¸a M. F.; Ramos, A. S. J . Chem. Res., Synop. 1993, 402; J .
Chem. Res., Miniprint 1993, 2701.
Con clu sion s
It has been demonstrated that 4,4′-bi-1H-imidazol-2-
ones 3 are formed in excellent yields from reactions of
1-alkyl- or 1-arylimidazoles 1 with either alkyl or aryl
5548 J . Org. Chem., Vol. 67, No. 16, 2002

Synthesis of 4,4′-Bi-1H-imidazol-2-ones
mmol); dec above 167 °C; 1H NMR (DMSO-d6, 300 MHz) δ 8.33
(t, 1H, J ) 6.0 Hz), 7.75 (brs, 2H), 7.34 (s, 1H), 7.27-7.33 (m,
5H), 5.05 (brs, 1H), 4.35 (d, 2H, J ) 6.0 Hz), 3.93 (t, 2H, J )
5.0 Hz), 3.61-3.65 (m, 2H); 13C NMR (DMSO-d6, 75 MHz) δ
160.7, 149.0, 139.6, 136.4, 136.1, 128.4, 127.4, 126.9, 119.5,
112.3, 58.9, 45.6, 43.5; IR (Nujol mull) 2240 (w, CN), 1630 (s,
CdO); MS (FAB) m/z (rel int) 313 (M + 1, 30); HRMS (FAB)
m/z calcd for C15H16N6O2 313.1413, found 313.1414.
TABLE 3
5-Am in o-R-(N-ben zylca r ba m oyl)im in o-1H-im id a zole-1-
(4′-m eth oxyp h en yl)-4-a ceton itr ile (2b): 71% yield (1.47
mmol); mp 223-225 °C; 1H NMR (DMSO-d6, 300 MHz) δ 8.51
(t, 1H, J ) 6.0 Hz), 7.68 (brs, 2H), 7.49 (s, 1H), 7.43 (d, 2H, J
) 9.0 Hz), 7.27-7,33 (m, 5H), 7.13 (d, 2H, J ) 9.0 Hz), 4.35
(d, 2H, J ) 6.0 Hz), 3.82 (s, 3H); 13C NMR (DMSO-d6, 75 MHz)
δ 160.6, 159.6, 148.5, 139.5, 136.5, 135.6, 128.3, 127.4, 127.0,
126.8, 125.9, 119.0, 115.1, 112.3, 55.6, 43.4; IR (Nujol mull)
2223 (w, CN), 1653 (s, CdO); MS (FAB) m/z (rel int) 375 (M +
1, 100); HRMS (FAB) m/z calcd for C20H18N6O2 375.1569, found
375.1553.
5-Am in o-R-(N-eth ylcar bam oyl)im in o-1-(2′-eth ylcar bam -
oyloxyeth yl)-1H-im id a zole-4-a ceton itr ile (2c): 6% yield
(0.16 mmol); mp 209-210 °C dec; 1H NMR (DMSO-d6, 300
MHz)) δ 7.88 (t, 1H, J ) 5.0 Hz), 7.73 (brs, 2H), 7.29 (s, 1H),
7.21 (t, 1H, J ) 5.0 Hz), 4.16 (t, 2H, J ) 5.0 Hz), 4.11 (t, 2H,
J ) 5.0 Hz), 3.11 (qui, 2H, J ) 7.0 Hz), 2.95 (qui, 2H, J ) 7.0
Hz), 1.08 (t, 3H, J ) 7.0 Hz), 0.97 (t, 3H, J ) 7.0 Hz); 13C
NMR (DMSO-d6, 75 MHz) δ 160.3, 155.5, 148.3, 136.0, 135.7,
118.9, 112.3, 58.6, 45.6, 35.1, 34.5, 15.0, 14.9; IR (Nujol mull)
2200 (w, CN), 1736 (s, CdO), 1633 (s, CdO). Anal. Calcd for
C
13H19N7O3‚H2O: C, 46.02; H, 5.61; N, 28.91. Found: C, 45.67;
H, 5.88; N, 29.11.
5-Am in o-R-(N-eth ylca r ba m oyl)im in o)-1H-im id a zole-1-
(4′-m eth oxyp h en yl)-4-a ceton itr ile (2d ): 76% yield (1.57
mmol); mp 209-210 °C; 1H NMR (DMSO-d6, 300 MHz) δ 7.99
(t, 1H, J ) 5.0 Hz), 7.56 (brs, 2H), 7.47 (s, 1H), 7.46 (d, 2H, J
) 9.0 Hz), 7.13 (d, 2H, J ) 9.0 Hz), 3.82 (s, 3H), 3.17 (q, 2H,
J ) 7.0 Hz), 1.08 (t, 3H, J ) 7.0 Hz); 13C NMR (DMSO-d6, 75
MHz) δ 160.2, 159.6, 148.2, 136.3, 135.3, 127.2, 125.9, 118.6,
115.1, 112.3, 55.6, 34.5, 14.8; IR (Nujol mull) 2200 (w, CN),
1652 (s, CdO); MS (EI) m/z (rel int) 312 (M+, 18). Anal. Calcd
for C15H16N6O2: C, 57.69; H, 5.13; N, 26.92. Found: C, 57.69;
H, 5.40; N, 26.73.
5-Am in o-R-(N-bu tylca r ba m oyl)im in o-1H-im id a zole-1-
(4′-m eth oxyp h en yl)-4-a ceton itr ile (2e): 81% yield (1.44
mmol); mp 205-206 °C; 1H NMR (DMSO-d6, 300 MHz) δ 7.98
(t, 1H, J ) 5.0 Hz), 7.56 (brs, 2H), 7.47 (s, 1H), 7.43 (d, 2H, J
) 9.0 Hz), 7.14 (d, 2H, J ) 9.0 Hz), 3.82 (s, 3H), 3.12 (q, 2H,
J ) 7.0 Hz), 1.45 (qui, 2H, J ) 7.0 Hz), 1.28 (sex, 2H, J ) 7.0
Hz), 0.88 (t, 3H, J ) 7.0 Hz); 13C NMR (DMSO-d6, 75 MHz) δ
160.4, 159.6, 148.1, 136.3, 135.3, 127.2, 125.9, 118.6, 115.1,
112.3, 55.6, 39.4, 31.4, 19.7, 13.7; IR (Nujol mull) 2227 (w, CN),
1645 (s, CdO); MS (FAB) m/z (rel int) 341 (M + 1, 93). Calcd
for C17H20N6O2: C, 60.00; H, 5.88; N, 24.71. Found: C, 60.03;
H, 5.94; N, 24.64.
isocyanates. Synthesis of compounds 3 can also be
achieved from isocyanates and N-arylamidines with
electron-donating groups (6b, R ) 4-CH3OC6H4). N-Aryl-
and N-alkylamidines adopt different constitutions in
solution. As a consequence, N-alkylamidines 6 incorpo-
rate two isocyanate molecules to give diacyl products 10,
which are easily hydrolyzed leading to the formation of
urea 9. A similar behavior was registered for N-aryla-
midines with electron-withdrawing groups (6c, R )
4-NCC6H4).
5-Am in o-1-(2′-h yd r oxyeth yl)-R-(N-p h en ylca r ba m oyl)-
im in o-1H-im id a zole-4-a ceton itr ile (2f): 66% yield (1.84
mmol); mp 187-191 °C; 1H NMR (DMSO-d6, 300 MHz) δ 9.98
(s, 1H), 8.05 (brs, 2H), 7.63 (d, 2H, J ) 8.0 Hz), 7.40 (s, 1H),
7.31 (t, 2H, J ) 8.0 Hz), 7.01 (t, 1H, J ) 8.0 Hz), 5.10 (brs,
1H), 3.97 (t, 2H, J ) 5.0 Hz), 3.66 (brs, 2H); 13C NMR (DMSO-
d6, 75 MHz) δ 158.5, 150.0, 139.7, 137.4, 135.9, 128.9, 122.6,
120.7, 118.3, 112.7, 58.8, 45.6; IR (Nujol mull) 2222 (w, CN),
1660 (s, CdO); MS (FAB) m/z (rel int) 299 (M + 1, 100); HRMS
(FAB) m/z calcd for C14H14N6O2 299.1256, found 299.1254.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of 5-Am in o-
R-(N-a lk yl/a r ylca r ba m oyl)im in o-1H-im id a zole-4-a ceton i-
tr iles (2). A suspension of 1 in dry MeCN was stirred at 0 °C
under an N2 atmosphere. After 10 min, the isocyanate (1.5-
5.0 equiv) was added. The mixture was stirred under the
conditions described in Table 1. The reaction was followed by
TLC. When the starting material was consumed, the yellow/
orange product was isolated by filtration and washed with
MeCN and cold Et2O.
5-Am in o-R-[N-(4′-t r iflu or om et h ylp h en yl)ca r b a m oyl]-
im in o-1-(2′-h ydr oxyeth yl)-1H-im idazole-4-aceton itr ile (2h ):
100% yield (3.90 mmol); mp 243-246 °C; 1H NMR (DMSO-d6,
300 MHz) δ 10.27 (s, 1H), 8.19 (brs, 2H), 7.83 (d, 2H, J ) 9.0
Hz), 7.66 (d, 2H, J ) 9.0 Hz), 7.44 (s, 1H), 5.10 (brs, 1H), 3.95-
4.00 (m, 2H), 3.67 (brs, 2H); 13C NMR (DMSO-d6, 75 MHz) δ
5-Am in o-R-(N-b en zylca r b a m oyl)im in o-1-(2′-h yd r oxy-
eth yl)-1H-im id a zole-4-a ceton itr ile (2a ): 93% yield (2.66
J . Org. Chem, Vol. 67, No. 16, 2002 5549

Dias et al.
158.8, 150.7, 143.4, 138.1, 136.1, 126.3 (q, J ) 3.6 Hz), 124.5
(q, J ) 270.0 Hz), 122.4, (q, J ) 32.0 Hz), 121.5, 118.1, 112.6,
58.8, 45.7; IR (Nujol mull) 2254 (w, CN), 1647 (s, CdO); MS
(FAB) m/z (rel int) 367 (M + 1, 93); HRMS (FAB) m/z calcd
for C15H13N6O2F3 367.1130, found 367.1116.
5′-Am in o-1-eth yl-5-im in o-1′-(4-m eth oxyp h en yl)-4,4′-bi-
1H-im id a zol-2-on es (3d ): 81% yield (0.26 mmol); mp 239-
1
242 °C; H NMR (DMSO-d6, 300 MHz) δ 9.60 (brs, 1H), 7.83
(s, 1H), 7.47 (d, 2H, J ) 9.0 Hz), 7.40 (brs, 2H), 7.17 (d, 2H
J ) 9.0 Hz), 3.83 (s, 3H), 3.60 (brs, 2H), 1.13 (brs, 3H); 13C
NMR (DMSO-d6, 75 MHz) δ 166.1, 160.4, 159.4, 157.3, 151.9,
139.4, 127.3, 125.5, 115.2, 113.2, 55.7, 33.7, 13.1; IR (Nujol
mull) 1708 (s, CdO), 1651 (s); MS (EI, 70 eV) m/z (rel int) 312
(M+, 29). Anal. Calcd for C15H16N6O2: C, 57.69; H, 5.13; N,
26.92. Found: C, 57.99; H, 5.33; N, 26.83.
5-Am in o-R-[N-(4′-t r iflu or om et h ylp h en yl)ca r b a m oyl]-
im in o-1H -im id a zole 1-(4′-m e t h oxyp h e n yl)-4-a ce t on i-
1
tr ile (2i): 100% yield (2.57 mmol); mp 270-274 °C; H NMR
(DMSO-d6, 300 MHz) δ 10.43 (s, 1H), 8.20 (brs, 2H), 7.83 (d,
2H, J ) 9.0 Hz), 7.67 (d, 2H, J ) 9.0 Hz), 7.47 (d, 2H, J ) 9.0
Hz), 7.44 (s, 1H), 7.16 (d, 2H, J ) 9.0 Hz), 3.82 (s, 3H); 13C
NMR (DMSO-d6, 75 MHz) δ 159.8, 158.6, 150.1, 143.3, 137.2,
136.6, 127.4, 126.1 (q, J ) 3.7 Hz), 125.6, 124.5 (q, J ) 270.0
Hz), 122.3 (q, J ) 32.0 Hz), 120.8, 118.3, 115.2, 112.5, 55.6;
IR (Nujol mull) 2234 (w, CN), 1667 (s, CdO); MS (EI, 70 eV)
m/z (rel int) 428 (M+, 40). Anal. Calcd for C20H15N6O2F3: C,
56.06; H, 3.74; N, 19.62. Found: C, 56.08; H, 3.70; N, 19.44.
5′-Am in o-1-bu tyl-5-im in o-1′-(4-m eth oxyp h en yl)-4,4′-bi-
1H-im id a zol-2-on e (3e): 85% yield (1.03 mmol); mp 211-213
°C; 1H NMR (DMSO-d6, 300 MHz) δ 9.76 (brs, 1H), 7.76 (s,
1H), 7.65 (brs, 2H), 7.47 (d, 2H, J ) 9.0 Hz), 7.14 (d, 2H, J )
9.0 Hz), 3.82 (s, 3H), 3.53 (t, 2H, J ) 7.0 Hz), 1.56 (qui, 2H, J
) 7.0 Hz), 1.26 (sex, 2H, J ) 7.0 Hz), 0.88 (t, 3H, J ) 7.0 Hz);
13C NMR (DMSO-d6, 75 MHz) δ 166.7, 159.8, 159.7, 157.5,
151.5, 138.6, 127.2, 125.6, 115.1, 113.7, 55.6, 38.0, 29.5, 19.4,
13.6; IR (Nujol mull) 1708 (s, CdO), 1652 (s). Anal. Calcd for
C17H20N6O2: C, 60.00; H, 5.88; N, 24.70. Found: C, 60.14; H,
6.00; N, 24.67.
R-(N-Allylcar bam oyl)im in o-5-am in o-1-(2′-h ydr oxyeth yl)-
1H-im id a zole-4-a ceton itr ile (2j): 24% yield (0.61 mmol); mp
148-150 °C; 1H NMR (DMSO-d6, 300 MHz) δ 8.01 (t, 1H, J )
6.0 Hz), 7.74 (brs, 2H), 7.32 (s, 1H), 5.87 (ddt, 1H, J ) 17.4,
10.2, 5.1 Hz), 5.18 (dd, 1H, J ) 17.4, 1.8 Hz), 5.09 (dd, 1H, J
) 10.2, 1.8 Hz), 5.05 (brs, 1H) 3.93 (t, 2H, J ) 5.0 Hz), 3.77 (t,
2H, J ) 6.0 Hz), 3.63 (brs, 2H); 13C NMR (DMSO-d6, 75 MHz)
δ 160.5, 148.9, 136.3, 135.5, 132.9, 119.8, 115.4, 112.4, 58.8,
45.5, 42.2; IR (Nujol mull) 2219 (w, CN), 1640 (s, CdO); MS
(FAB) m/z (rel int) 263 (M+1, 100); HRMS (FAB) m/z calcd
for C11H14N6O2 263.1256, found 263.1262. Anal. Calcd for
5′-Am in o-1′-(2-h yd r oxyeth yl)-5-im in o-1-p h en yl-4,4′-bi-
1H-im id a zol-2-on e (3f): 90% yield (0.27 mmol); mp 180-181
1
°C; H NMR (DMSO-d6, 300 MHz) δ 10.06 (s, 1H), 7.95 (brs,
2H), 7.61 (s, 1H), 7.46 (m, 4H), 7.32 (m, 1H), 5.10 (brs, 1H),
3.99 (t, 2H, J ) 5.0 Hz), 3.65 (t, 2H, J ) 5.0 Hz); 13C NMR
(DMSO-d6, 75 MHz) δ 165.6, 159.7, 156.5, 152.3, 140.1, 134.0,
128.5, 126.6, 113.9, 58.8, 45.8; IR (Nujol mull) 1708 (s, CdO),
1644 (s); MS (FAB) m/z (rel int) 299 (M + 1, 100). Anal. Calcd
for C14H14N6O2: C, 56.34; H, 4.70; N, 28.19. Found: C, 56.55;
H, 4.88; N, 27.97.
C
11H14N6O2‚0.25 H2O: C, 49.53; H, 5.44; N, 31.52. Found: C,
49.38; H, 5.28; N, 31.33.
R-(N-Allylca r b a m oyl)im in o-5-a m in o-1H -im id a zole-1-
(4′-m eth oxyp h en yl)-4-a ceton itr ile (2k ): 61% yield (1.11
mmol); mp 202-204 °C; 1H NMR (DMSO-d6, 300 MHz) δ 8.17
(t, 1H, J ) 6.0 Hz), 7.63 (brs, 2H), 7.48 (s, 1H), 7.44 (d, 2H, J
) 9.0 Hz), 7.14 (d, 2H, J ) 9.0 Hz), 5.87 (ddt, 1H, J ) 17.1,
10.5, 5.4 Hz), 5.19 (dd, 1H, J ) 17.1, 1.8 Hz), 5.10 (dd, 1H, J
) 10.5, 1.8 Hz), 3.83 (s, 3H), 3.78 (t, 2H, J ) 6.0 Hz); 13C NMR
(DMSO-d6, 75 MHz) δ 160.3, 159.6, 148.4, 136.4, 135.4, 132.8,
127.2, 125.9, 118.8, 115.4, 115.3, 112.3, 55.6, 42.1; IR (Nujol
mull) 2234 (w, CN), 1660 (s, CdO); MS (FAB) m/z (rel int) 325
(M + 1, 100). Anal. Calcd for C16H16N6O2: C, 59.26; H, 4.94;
N, 25.93. Found: C, 59.46; H, 5.07; N, 25.75.
5′-Am in o-5-im in o-1′-(4-m eth oxyp h en yl)-1-p h en yl-4,4′-
bi-1H-im id a zol-2-on e (3g): 95% yield (1.97 mmol); mp 219-
1
221 °C; H NMR (DMSO-d6, 300 MHz) δ 10.08 (s, 1H), 7.90
(brs, 2H), 7.82 (s, 1H), 7.47 (m, 4H), 7.43 (d, 2H, J ) 9.0 Hz),
7.32 (m, 1H), 7.13 (d, 2H, J ) 9.0 Hz), 3.82 (s, 3H); the sample
was not soluble enough in DMSO-d6 for 13C NMR; IR (Nujol
mull) 1717 (s, CdO), 1655 (s); MS (FAB) m/z (rel int) 361 (M
+ 1, 9). Anal. Calcd for C19H16N6O2: C, 63.33; H, 4.44; N, 23.33.
Found: C, 63.49; H, 4.61; N, 23.34.
5′-Am in o-1′-(2-h yd r oxyeth yl)-1-(4-tr iflu or om eth ylp h e-
n yl)-5-im in o-4,4′-bi-1H-im id a zol-2-on e (3h ): 76% yield (2.13
mmol); mp 247-250 °C; 1H NMR (DMSO-d6, 300 MHz) δ 10.21
(s, 1H), 8.00 (brs, 2H), 7.82 (s, 4H), 7.64 (s, 1H), 5.10 (brs, 1H),
4.00 (t, 2H J ) 5.0 Hz), 3.65 (t, 2H, J ) 5.0 Hz); 13C NMR
(DMSO-d6, 75 MHz) δ 165.0, 159.1, 156.2, 152.9, 140.4, 137.8,
126.27, 126.30 (q, J ) 32.0 Hz), 125.5 (q, J ) 3.7 Hz), 124.2
(q, J ) 272.0 Hz), 114.2, 58.8, 45.9; IR (Nujol mull) 1709 (s,
CdO), 1650 (s). Anal. Calcd for C15H13N6O2F3‚0.5H2O: C,
48.00; H, 3.73; N, 22.40. Found: C, 47.81; H, 3.66; N, 22.18.
Gen er a l P r oced u r e for th e P r ep a r a tion of 5′-Am in o-
5-im in o-4,4′-bi-1H-im id a zol-2-on es (3). At 23 °C, a suspen-
sion of the imidazole 2 in MeCN was stirred. Addition of DBU
(0.03-1.0 molar equiv) caused an immediate color change, and
a yellow solid gradually precipitated. Stirring was continued
according to the conditions given in Table 1. Filtration and
washing of the residue with MeCN/Et2O afforded the pure
products.
5′-Am in o-1-(4-t r iflu or om et h ylp h en yl)-5-im in o-1′-(4-
m eth oxyp h en yl)-4,4′-bi-1H-im id a zol-2-on e (3i): 83% yield
(0.19 mmol); mp 292-294 °C; H NMR (DMSO-d6, 300 MHz)
δ 10.23 (s, 1H), 7.90 (brs, 2H), 7.86 (s, 1H), 7.84 (s, 4H), 7.50
(d, 2H, J ) 9.0 Hz), 7.16 (d, 2H, J ) 9.0 Hz), 3.83 (s, 3H); the
sample was not soluble enough in DMSO-d6 for 13C NMR; IR
(Nujol mull) 1714 (s, CdO), 1652 (s); MS (EI, 70 eV) m/z (rel
int) 428 (M+, 5). Anal. Calcd for C20H15N6O2F3: C, 56.06; H,
3.74; N, 19.62. Found: C, 56.10; H, 3.73; N, 19.59.
5′-Am in o-1-ben zyl-1′-(2-h yd r oxyeth yl)-5-im in o-4,4′-bi-
1H-im id a zol-2-on e (3a ): 60% yield (0.06 mmol); dec 182-201
°C; 1H NMR (DMSO-d6, 300 MHz) δ 9.77 (s, 1H), 7.57 (s, 1H),
6.60-7.40 (brs, 2H), 7.20-7.30 (m, 5H), 4.70 (s, 2H), 3.97 (t,
2H, J ) 5.0 Hz), 3.64 (t, 2H, J ) 5.0 Hz); 13C NMR (DMSO-d6,
75 MHz) δ 166.8, 159.7, 156.8, 152.4, 139.8, 137.7, 128.4, 127.2,
127.0, 113.9, 58.8, 45.8, 41.6; IR (Nujol mull) 1708 (s, CdO),
1650 (s); MS (EI, 70 eV) m/z (rel int) 312 (M+, 16). Anal. Calcd
for C15H16N6O2: C, 57.66; H, 5.13; N, 26.38. Found: C, 57.73;
H, 5.34; N, 26.91.
1
1-Allyl-5′-a m in o-1′-(2-h yd r oxyeth yl)-5-im in o-4,4′-bi-1H-
im id a zol-2-on es (3j): 27% yield (0.04 mmol); mp 187-190 °C;
1H NMR (DMSO-d6, 300 MHz) δ 9.65 (s, 1H), 7.54 (s, 1H),
7.20-6.80 (brs, 2H), 5.82 (ddt, 1H, J ) 17.5, 10.5, 5.0 Hz), 5.06
(dd, 1H, J ) 10.5, 1.5 Hz), 5.00 (dd, 1H, J ) 17.5, 1.5 Hz),
3.93 (t, 2H, J ) 5.0 Hz), 3.77 (t, 2H, J ) 6.0 Hz), 3.62 (t, 2H,
J ) 5.0 Hz); 13C NMR (DMSO-d6, 75 MHz) δ 166.6, 159.4,
157.0, 152.2, 139.7, 132.9, 115.4, 113.7, 58.9, 45.8, 40.3; IR
(Nujol mull) 1711 (s, CdO), 1638 (s).
5′-Am in o-1-b en zyl-5-im in o-1′-(4-m et h oxyp h en yl)-4,4′-
bi-1H-im id a zol-2-on e (3b): 88% yield (0.83 mmol); mp 236-
237 °C; 1H NMR (DMSO-d6, 300 MHz) δ 9.80 (brs, 1H), 7.60-
7.80 (brs, 2H), 7.80 (s,1H) 7.47 (d, 2H, J ) 9.0 Hz), 7.20-7.30
(m, 5H), 7.14 (d, 2H, J ) 9.0 Hz), 4.73 (s, 2H), 3.82 (s, 3H); 13
C
NMR (DMSO-d6, 75 MHz) δ 166.6, 159.8, 159.5, 157.4, 151.9,
139.0, 137.6, 128.4, 127.3, 127.2, 127.1, 125.6, 115.2, 113.5,
55.7, 41.7; IR (Nujol mull) 1714 (s, CdO), 1651 (s); MS (EI, 70
eV) m/z (rel int) 374 (M+, 25). Anal. Calcd for C20H18N6O2: C,
64.17; H, 4.81; N, 22.46. Found: C, 64.07; H, 5.01; N, 22.13.
1-Allyl-5′-a m in o-5-im in o-1′-(4-m eth oxyp h en yl)-4,4′-bi-
1H-im id a zol-2-on e (3k ): 92% yield (0.43 mmol); mp 235-238
5550 J . Org. Chem., Vol. 67, No. 16, 2002

Synthesis of 4,4′-Bi-1H-imidazol-2-ones
°C; 1H NMR (DMSO-d6, 300 MHz) δ 9.78 (s, 1H), 7.77 (s, 1H),
7.70 (brs, 2H), 7.47 (d, 2H, J ) 9.0 Hz), 7.14 (d, 2H, J ) 9.0
Hz), 5.85 (ddt, 1H, J ) 17.1, 10.8, 5.1 Hz), 5.08 (dd, 1H, J )
10.8, 1.2 Hz), 5.03 (dd, 1H, J ) 17.1, 1.2 Hz), 4.14 (d, 2H, J )
5.1 Hz), 3.83 (s, 3H); 13C NMR (DMSO-d6, 75 MHz) δ 166.3,
159.8, 159.2, 157.4, 151.7, 138.8, 132.8, 127.2, 125.6, 115.8,
115.2, 113.3, 55.6, 40.4; IR (Nujol mull) 1711 (s, CdO), 1651
(s). Anal. Calcd for C16H16N6O2: C, 59.26; H, 4.94; N, 25.93.
Found: C, 59.39; H, 5.06; N, 25.73.
Rea ction of (Z)-N-(2-Am in o-1,2-d icya n ovin yl)-N′-(4′-
cya n op h en yl)for m a m id in e 6c w ith Ben zyl Isocya n a te.
A suspension of formamidine 6c (0.22 g, 0.93 mmol) in MeCN
(6 mL) was kept stirring at 0 °C, under N2, before the addition
of benzyl isocyanate (0.18 g, 0.17 mL, 1.35 mmol). The mixture
was stirred at -4 °C for 3 days and then at -18 °C for 18 h.
The solid was filtered and washed with MeCN, MeCO2Et and
Et2O. Dry flash chromatography on the mother liquor led to
the isolation of the same product. The various crops were
combined and identified as urea 9 (0.13 g, 0.55 mmol, 59%);
dec above 173 °C (lit.5 dec above 173 °C); IR (Nujol mull) 2249
(w, CN), 2205 (s, CN) 1644 (s, CdO).
Rea ction of (Z)-N-(2-Am in o-1,2-d icya n ovin yl)-N′-(4′-
m eth oxyp h en yl)for m a m id in e 6b w ith Ben zyl Isocya n -
a te. Meth od A. A suspension of 6b (0.50 g, 2.07 mmol) in
MeCN (5 mL) was stirred at 0 °C, under N2. Benzyl isocyanate
(0.59 g, 0.55 mL, 4.45 mmol) was added, and the mixture was
stirred at 0 °C for 5 min and then allowed to reach room
temperature. The green solution turned brown and then black,
and after 5 min a white solid started to develop. The mixture
was stirred at room temperature for a further 1 h, when the
solid was filtered and washed with MeCN and Et2O. The
product was identified as formamidine 7b (0.36 g, 0.96 mmol,
47%): mp 130-133 °C; 1H NMR (DMSO-d6, 300 MHz) δ 8.46
(s, 1H), 8.31 (t, 1H, J ) 6.0 Hz), 8.00 (brs, 2H), 7.20-7.40 (m,
5H), 7.01 (d, 2H, J ) 9.0 Hz), 6.88 (d, 2H, J ) 9.0 Hz), 4.36 (d,
2H, J ) 6.0 Hz), 3.73 (s, 3H); 13C NMR (DMSO-d6, 75 MHz) δ
157.3, 153.4, 146.9, 143.7, 140.4, 133.5, 129.2, 129.1, 127.9,
127.8, 118.4, 115.2, 114.7, 86.7, 56.3, 44.4; IR (Nujol mull) 2195
(m, CN), 1676 (s, CdO); MS (EI, 70 eV) m/z (rel int) 374 (M+,
20). Anal. Calcd for C20H18N6O2: C, 64.17; H, 4.81; N, 22.46.
Found: C, 64.50; H, 5.03; N, 22.29. The mother liquor was
stirred at 23 °C for another 18 h leading to a yellow solid that
was filtered, washed with MeCN and Et2O and identified as
formamidine 8b (0.04 g, 0.12 mmol, 6%): mp 211-213 °C; 1H
NMR (DMSO-d6, 300 MHz) for 8bA δ 10.50 (brs, 1H), 8.50
(m, 1H), 8.30 (brs, 1H), 7.23-7.37 (m, 5H), 7.22 (d, 2H, J )
8.0 Hz), 7.20-7.40 (brs, 1H), 6.93 (d, 2H, J ) 8.0 Hz), 4.31
(brs, 2H), 3.72 (s, 3H); for 8bB δ 10.30 (brs, 1H), 8.30 (m, 1H),
7.90 (brs, 1H), 7.71 (d, 2H, J ) 8.0 Hz), 7.50 (brs, 1H), 7.23-
7.37 (m, 5H), 6.92 (d, 2H, J ) 8.0 Hz), 4.31 (brs, 2H), 3.72 (s,
3H); 13C NMR (DMSO-d6, 75 MHz) δ 157.3 (8bA), 156.8 (8bB),
153.4, 150.9 (8bB), 149.0 (8bA), 140.6, 136.0 (8bA), 132.6
(8bB), 129.5, 129.4, 128.4, 128.1, 122.5 (8bB), 120.1 (8bA),
118.0, 115.8 (8bA), 115.7, 115.2 (8bB), 109.0, 56.3, 44.0; IR
(Nujol mull) 2217 (m, CN), 1650 (s, CdO); MS (EI, 70 eV) m/z
(rel int) 374 (M+, 20). Anal. Calcd for C20H18N6O2: C, 64.17;
H, 4.81; N, 22.46. Found: C, 64.45; H, 5.00; N, 22.14.
Rep r esen ta tive P r oced u r e for th e Rea ction of (Z)-N-
(2-Am in o-1,2-d icya n ovin yl)-N′-(2′-h yd r oxyet h yl)for m a -
m id in e 6a w ith Ben zyl Isocya n a te. Meth od A. A suspen-
sion of formamidine 6a (0.42 g, 2.35 mmol) in MeCN (5 mL)
was stirred at 0 °C under N2, and after 5 min, benzyl
isocyanate (0.73 g, 0.68 mL, 5.48 mmol) was added. The
mixture was stirred at 4 °C for 5 h and was then allowed to
stand at -18 °C for 18 h. The off-white solid was filtered and
washed with MeCN and Et2O. The product was identified as
formamidine 10a (0.18 g, 0.40 mmol, 17%): mp 164-165 °C;
1H NMR (DMSO-d6, 300 MHz) δ 8.76 (s, 1H), 8.53 (brs, 1H),
8.31 (t, 1H, J ) 6.0 Hz), 7.71 (t, 1H, J ) 5.7 Hz), 7.20-7.40
(m, 10H), 5.15 (t, 1H, J ) 4.8 Hz), 4.38 (d, 2H, J ) 5.4 Hz),
4.31 (d, 2H, J ) 5.7 Hz), 4.04 (t, 2H, J ) 5.0 Hz), 3.58 (dt, 2H,
J ) 5.1 Hz, J ) 4.5 Hz); 13C NMR (DMSO-d6, 75 MHz) δ 154.6,
152.2, 151.8, 139.0, 138.9, 128.5, 128.3, 127.6, 127.2, 127.0,
126.9, 114.4, 113.8, 113.1, 112.7, 58.5, 45.2, 43.9, 43.1; IR
(Nujol mull) 2220 (m, CN), 1681 (s, CdO), 1649 (s, CdO). Anal.
Calcd for C23H23N7O3: C, 62.02; H, 5.17; N, 22.02. Found: C,
61.78; H, 5.44; N, 21.87. The mother liquor was concentrated
in the rotary evaporator, and the solid isolated was identified
as the urea 9 (0.03 g, 0.12 mmol, 5%).
Note: Several reactions were carried out where the ratio of
amidine 6a :benzylisocyanate was varied from 1:1.3 to 1:2.6,
and the reaction conditions (temperature and reaction time)
were also varied according to Table 3.
Meth od B. A suspension of amidine 6a (0.35 g, 1.95 mmol)
in MeCN (4 mL) was stirred at -4 °C under N2 before the
addition of benzyl isocyanate (0.69 g, 0.64 mL, 5.18 mmol) and
stirring the mixture at -4 °C for 1 h. The dark solution was
than allowed to stand at -18 °C for 8 days. Acetic acid (0.01
g, 0.01 mL, 0.17 mmol) was added to the reaction medium,
and the suspension was filtered and washed with Et2O. The
product was identified as 2-[2-(3-benzylureido)-1,2-dicyanovi-
nylamino]-oxazolidine-3-carboxylic acid benzylamide 11 (0.11
g, 0.25 mmol, 13%): mp 132-133 °C; 1H NMR (DMSO-d6, 300
MHz) δ 8.04 (s, 1H), 7.70 (d, 1H, J ) 6.9 Hz), 7.20-7.30 (m,
10H), 7.00 (t, 1H, J ) 6.0 Hz), 6.17 (d, 1H, J ) 6.6 Hz), 4.24
(d, 2 × 2H, J ) 5.1 Hz), 3.54 (m, 1H), 3.44 (m, 1H); 13C NMR
(DMSO-d6, 75 MHz) δ 154.9, 153.8, 140.3, 139.7, 128.3, 128.2,
127.2, 127.1, 126.8, 126.6, 119.4, 115.7, 113.2, 98.2, 92.3, 64.6,
44.3, 43.1; IR (Nujol mull) 2225 (m, CN), 1706 (s, CdO), 1640
(s, CdO). Anal. Calcd for C23H23N7O3‚0.5H2O: C, 60.79; H,
5.29; N, 21.59. Found: C, 61.05; H, 5.11; N, 22.02. The solid
isolated from the mother liquor after concentration on the
rotary evaporator was identified as the urea 9 (0.13 g, 0.56
mmol, 29%).
Meth od B. A suspension of formamidine 6b (0.55 g, 2.28
mmol) in MeCN (5 mL) was stirred at -15 °C (Cardice/
ethyleneglycol bath), under N2, and after 5 min, benzyl
isocyanate (0.40 g, 0.37 mL, 3.00 mmol) was added. The
reaction mixture was stirred at -15 °C for 2 h, when TLC
indicated that the starting material was still present. The
reaction mixture was allowed to stand at -18 °C for a further
2 days. MeCN (3 mL) was than added to the thick suspension,
which was filtered and washed with MeCN and Et2O. The
white solid was identified as formamidine 7b (0.85 g, 2.27
mmol, 100%).
P r ep a r a tion of (Z)-N-(2-Ben zylu r eid o-1,2-d icya n ovi-
n yl)-N′-(4′-m eth oxyp h en yl)for m a m id in e (8b). A solution
of formamidine 7b (0.20 g, 0.53 mmol) in MeCN (10 mL) was
stirred at 23 °C under N2. After 18 h, the yellow solid was
filtered and washed with MeCN and Et2O. The product was
identified as the title compound (0.12 g, 0.32 mmol, 60%).
Rea ction of (Z)-N-(2-Am in o-1,2-d icya n ovin yl)-N′-(2′-
m eth oxyeth yl)for m a m id in e 6d w ith Ben zyl Isocya n a te.
A suspension of formamidine 6d (0.35 g, 1.82 mmol) in MeCN
(4 mL) was stirred at 0 °C under N2. Benzyl isocyanate (0.73
g, 0.68 mL, 5.50 mmol) was added, and the mixture was stirred
at 0 °C for 2 h, followed by 4 days at -18 °C. After this time,
extensive darkening of the reaction mixture had occurred. Dry
flash chromatography on the reaction mixture using Et2O as
Cycliza t ion of (Z)-N-(2-Ben zylu r eid o-1,2-d icya n ovi-
n yl)-N′-(4′-m eth oxyp h en yl)for m a m id in e (8b). A solution
of formamidine 8b (0.02 g, 0.05 mmol) in MeCN (1 mL) was
stirred at 23 °C. DBU (0.04 g, 0.03 mmol) was added, and the
mixture was stirred for 30 min. The orange solid was filtered
and washed with MeCN and Et2O. The product was identified
as imidazole 3b (0.02 g, 0.05 mmol, 100%).
(5) Booth, B. L.; Dias, A. M.; Proenc¸a M. F.; Zaki, M. J . Org. Chem.
2001, 66, 8436.
J . Org. Chem, Vol. 67, No. 16, 2002 5551

Dias et al.
eluant led to the isolation of compound 10d (0.03 g, 0.06 mmol,
3%): mp 151-152 °C; H NMR (DMSO-d6, 300 MHz) δ 8.73
Ack n ow led gm en t. The authors gratefully acknowl-
edge the financial support by the University of Minho
and Fundac¸a˜o para a Cieˆncia e Tecnologia (project
PRAXIS/C/QUI/10101/1998).
1
(s, 1H), 8.55 (brs, 1H), 8.32 (t, 1H, J ) 6.0 Hz), 7.70 (t, 1H, J
) 5.5 Hz), 7.20-7.40 (m, 10H), 4.37 (d, 2H, J ) 5.4 Hz), 4.31
(d, 2H, J ) 5.4 Hz), 4.12 (t, 2H, J ) 5.4 Hz), 3.48 (t, 2H, J )
5.5 Hz), 3.20 (s, 3H); 13C NMR (DMSO-d6, 75 MHz) δ 154.2,
152.0, 151.7, 139.0, 138.9, 128.5, 128.3, 128.2, 127.2, 127.1,
127.0, 114.3, 113.7, 113.0, 112.8, 69.2, 58.2, 43.8, 43.0; IR
(Nujol mull) 2217 (m, CN), 1683 (s, CdO), 1656 (s, CdO). Anal.
Calcd for C24H25N7O3: C, 62.75; H, 5.45; N, 21.35. Found: C,
63.10; H, 5.53; N, 21.11. The urea 9 (0.12 g, 0.48 mmol, 26%)
was also obtained upon elution with CH2Cl2 and MeCO2Et.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O011192Z
5552 J . Org. Chem., Vol. 67, No. 16, 2002