Lithiation of 1-arylimidazol-2(1H)-ones and 1-aryl-4,5-dihydroimidazol- 2(1H)-ones

Article abstract of DOI:10.1139/v04-137

1-Arylimidazol-2(¹H)-ones are shown to be readily lithiated, using 2 mol equiv. of n-butyllithium, on the benzene ring, ortho to the heterocycle. 1-Aryl-4,5-dihydroimidazol-2(1H)-ones also undergo metalation on the aromatic substitutuent ortho to the heterocycle, but less efficiently. 1-Aryl-3-methylimidazol-2(1H)-ones are lithiated on the heterocyclic ring and then on the benzene ring ortho to the heterocycle. No ortho-directing effect was found for 1-aryl-4,5-dihydro-3-methylimidazol-2(1H)-ones.

Full text of DOI:10.1139/v04-137

1649
Lithiation of 1-arylimidazol-2(1H)-ones and 1-aryl-
4,5-dihydroimidazol-2(1H)-ones
Carme Cantos Llopart, Conchita Ferrer, and John A. Joule
Abstract: 1-Arylimidazol-2(1H)-ones are shown to be readily lithiated, using 2 mol equiv. of n-butyllithium, on the
benzene ring, ortho to the heterocycle. 1-Aryl-4,5-dihydroimidazol-2(1H)-ones also undergo metalation on the aromatic
substitutuent ortho to the heterocycle, but less efficiently. 1-Aryl-3-methylimidazol-2(1H)-ones are lithiated on the
heterocyclic ring and then on the benzene ring ortho to the heterocycle. No ortho-directing effect was found for 1-aryl-
4,5-dihydro-3-methylimidazol-2(1H)-ones.
Key words: ortho-lithation, ureas for directed ortho metalation, 1-arylimidazol-2-ones, 1-arylimidazolidin-2-ones.
Résumé : On a démontré que les 1-arylimidazol-2(1H)-ones, sous l’action de 2 équivalents molaires de n-butyllithium,
subissent facilement une réaction de lithiation sur le noyau benzénique, en position ortho par rapport à l’hétérocycle.
Les 1-aryl-4,5-dihydroimidazol-2(1H)-ones subissent aussi une métallation sur le substituant aromatique ortho par
rapport à l’hétérocycle, mais la réaction est moins efficace. Les 1-aryl-3-méthylimidazol-2(1H)-ones subissent une
réaction de lithiation sur le noyau hétérocyclique avant de procéder à une lithiation sur le noyau benzénique en
ortho de l’hétérocycle. On n’a pas observé d’effet d’orientation vers la position ortho avec les 1-aryl-4,5-dihydro-3-
méthylimidazol-2(1H)-ones.
Mots clés : lithiation en ortho, urées pour des métallations orientées en ortho, 1-arylimidazol-2-ones, 1-
arylimidazolidin-2-ones.
[Traduit par la Rédaction] Llopart et al. 1661
Introduction
found no ortho assistance in the case of the latter; the former
underwent lithiation in the heterocyclic ring and then ortho
to the heterocycle. We are aware of no other attempts to use
imidazolones or 4,5-dihydroimidazolones as ortho-directing
groups in this way.
Aside from our own work (1), there are only two reports
of the use of ureas as ortho-directing substituents, and in
both of these, the urea was acyclic. Quéguiner and co-
workers (9) lithiated N,N-dimethyl-N′-(quinolin-3-yl)urea
with lithium di-isopropylamide leading to the 2-lithio deriva-
tive as the thermodynamic product. Smith et al. (10) used
2.5 equiv. of n-butyllithium or tert-butyllithium at 0 °C to
deprotonate N-aryl-N′,N′-dimethylureas ortho to the urea
unit; in some cases, the use of tert-butyllithium led to lithia-
tion at N-methyl as well as, or instead of, ring lithiation.
Carpenter and Chadwick (11) examined the lithiation
of five-membered aromatic heterocycles carrying a 1,3-
dimethylimidazolidin-2-yl substituent at an α-position
and found a weak ortho-directing effect. Earlier, it had been
shown that in 1,3-dimethyl-2-phenylimidazolidine, efficient
ortho lithiation of the phenyl ring is possible with n-
butyllithium at room temperature (12). Simig and co-workers
(13) demonstrated ortho lithiation in 2-aryl-2-methyl-1,3-
dioxolanes; when a meta-chlorine was present on the ben-
zene ring, lithiation took place at the carbon between the
chlorine and the ketal-directing groups.
We have described (1) our investigations into the use of
the heterocyclic substituent in 1-arylpyrimidin-2(1H)-ones
and in 1-aryl-3,4,5,6-tetrahydropyrimidin-2(1H)-ones to as-
sist lithiation at an ortho position (2, 3). In the former case,
the use of the pyrimidinone as a directing group was foiled
by its strong tendency to undergo addition of the lithiating
reagent. In the case of the six-membered cyclic ureas (1-
aryl-3,4,5,6-tetrahydropyrimidin-2(1H)-ones), we showed that
the substituent has a weak ortho directing effect (1). Our
study was designed to produce intermediates for a route (4),
alternative to those (5–7) previously described, to the biolog-
ically active variolin group (8) of alkaloids. The route will
allow flexibility and easy introduction of diverse analogues
for subsequent biological assessment. We have now exam-
ined the analogous five-membered compounds as a further
element of eventual diversity in this context.
In the work described here, we have demonstrated the for-
mation and exploitation of intermediates that are summa-
rized as 1 and 2, formed from 3 and 4, implying significant
ortho-directing effects in these cyclic ureas, which we be-
lieve have considerable potential in synthesis. We have also
examined the lithiation of N-methyl analogues, 5 and 6, and
Received 6 May 2004. Published on the NRC Research Press
Web site at http://canjchem.nrc.ca on 23 December 2004.
Following the efficient ortho lithiation of 2-phenylimi-
dazoline (14), Chadwick and Ennis (15) examined 2-(2-
heteroaryl)imidazolines and confirmed a strong ortho-
directing effect. With an appropriate choice of lithiating
agent (sec-BuLi–TMEDA at –78 °C) ortho lithiation of 2-(2-
C.C. Llopart, C. Ferrer, and J.A. Joule.1 Chemistry
Department, The University of Manchester, Manchester
M13 9PL, UK.
1Corresponding author (e-mail: john.joule@manchester.ac.uk).
Can. J. Chem. 82: 1649–1661 (2004)
doi: 10.1139/V04-137
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Can. J. Chem. Vol. 82, 2004
Scheme 1.
Scheme 2.
methylphenyl)-4,4-dimethyloxazolidine can be made to
compete with lithiation of the methyl group (16). The ortho-
directing strength of a 1H-tetrazol-5-yl-substitutent was
shown to be more than that of a methoxyl but less than that
of diethylaminocarbonyl and this in turn less than that of a
2-(triphenylmethyl)-2H-tetrazol-5-yl substituent (17).
acetaldehyde dimethyl acetal (18) and the resulting ureas 7
cyclised (19) by treatment with acid producing the
imidazolones 3a–3d. Reaction of each of these with 1 mol
equiv. of n-butyllithium and then iodomethane cleanly gave
their N-methyl derivatives, 5a–5d (Scheme 1).
1-Aryl-4,5-dihydroimidazol-2(1H)-ones 4a–4d were pre-
pared following the method reported (20) for the synthesis
of 4b, namely cyclising N-aryl-1,2-diamines 8, obtained by
reaction of the aromatic amines with 2-bromoethanamine,
using carbonyl diimidazole (CDI). The imidazolidinones 4a–
4d reacted smoothly with 1 mol equiv. of n-butyllithium and
then iodomethane giving their N-methyl derivatives, 6a–6d
(Scheme 2).
Syntheses of 1-arylimidazol-2(1H)-ones (3a–
3d and 5a–5d) and 1-aryl-4,5-dihydro-
imidazol-2(1H)-ones (4a–4d and 6a–6d)
The commercially available phenyl and 2-, 3-, and 4-
methoxyphenyl isocyanates were each reacted with amino-
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Llopart et al.
1651
Table 1. Products and yields from lithations.
Lithiation of 1-arylimidazol-2(1H)-ones 3a–
3d and 5a–5d
n-BuLi
Product
Product
Substrate (mol equiv.)
Electrophile (% yield) (% yield)
Treatment of the N-hydrogen imidazolones 3a–3d with
2.5 mol equiv. of n-butyllithium and then excess iodo-
methane proceeded smoothly and gave rise to N- and ben-
zene-ring-dimethylated products in good yields (Table 1).
Noteworthy are: (i) the absence of products of nucleophilic
addition to the unsaturated five-membered ring (cf. 1-
arylpyrimidin-2(1H)-ones in ref. 1); (ii) the clean nature of
the transformations, even in the substrate 3a with no elec-
tron-withdrawing methoxyl on the benzene ring (→ 5e);
(iii) the regiochemistry of lithiation of the meta-methoxy
substrate 3c — between the methoxyl group and the
imidazolone (→ 5h) — the combined effect of the two
groups producing this result; (iv) the formation from the
ortho-methoxy substrate 3b of a mixture of dimethylated
products (5f and 5g) from lithiation either ortho to the
heterocycle (18%) or ortho to the methoxyl (25%); and
(v) the regiochemistry of lithiation of the para-methoxy sub-
strate 3d in which there was no trace of lithiation ortho to
the methoxyl group — the influence of the imidazolone be-
ing the greater (→ 5i). Where there was ambiguity regarding
the position of the introduced aromatic methyl, nOe experi-
ments were employed. Thus, in 5g the proximity of the
methoxyl methyl and the ring methyl was established, and
for 5i there was no nOe on the methyl (δ 2.23) on irradiation
of the methoxyl methyl (δ 3.83) and conversely, irradation at
2.23 had no effect on the methoxyl but did show an nOe to
the imidazolone signal at δ 6.27. We interpret the trapping
results as involving the double methylation of dilithio spe-
cies 1, the formation of which are favoured by the aromatic
character of the five-membered ring in these.
3a
3b
3c
3d
4a
4b
4c
4d
3a
3b
3c
3d
5a
5b
5d
5a
5b
5c
5d
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
1.2
1.2
1.1
2.5
2.5
2.5
2.5
MeI
MeI
MeI
MeI
MeI
MeI
MeI
MeI
5e (88)
5f (18)
5h (60)
5i (96)
6e (34)
6f (28)
6h (22)
6i (9)
5g (25)
6g (37)
6j (12)
9b (86)
9d (18)
9f (21)
9h (30)
5k (46)
5m (36)a
5o (16)
PhNCO
PhNCO
PhNCO
PhNCO
MeI
MeI
MeI
MeI
MeI
9a (3)
9c (15)
9e (36)
9g (6.5)
5j (12)
5l (12)a
5n (49)
5p (95)
5q (88)
5r (24)
5s (97)
MeI
MeI
1
aEstimate from the H NMR spectrum of the mixture.
ortho-directing group, we treated the N-methyl imidazolones
5a–5d with n-BuLi and quenched with iodomethane. Here,
there was a complete reversal of selectivity and a total pref-
erence for lithiation of the five-membered heterocycle when
using approximately 1 equiv. of the strong base, though not
very efficiently. Both 4- and 5-methylated products were
formed — 5j/5k, 5l/5m, 5n/5o — with the 4-methylated iso-
mers predominating (Table 1). The regiochemistry of the
methylation was established by nOe experiments — for the
3,4-dimethylimidazolones, e.g., 5k, irradation of the N-
methyl signal (δ 3.26) gave an effect with the C-methyl
(δ 2.11), but not the remaining imidazolone ring proton
(δ 6.33).
Experiments with 3a–3d again using 2.5 mol equiv. of n-
butyllithium, but with phenyl isocyanate as the trapping
electrophile, produced N- and C-disubstituted, biuret-anilide
products 9b–9e and 9h, with exactly comparable regio-
selectivity, but only in moderate yields, and in some cases
accompanied by minor amounts of the mono-N-substituted
biuret (9a, 9f, 9g) (Table 1).
To determine whether an imidazolone that is not capable
of N-deprotonation could act as an ortho-directing group, in
partial analogy to the use of an N,N-dialkylamide as an
Even more intriguingly, when 2.5 mol equiv. of n-
butyllithium were employed for the lithiation of 5a–5d,
dimethylated products were obtained in which one methyl
had been introduced onto the benzene ring ortho to the
imidazolone, presumably with its assistance, and the other at
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1652
Can. J. Chem. Vol. 82, 2004
to the trimethylated 3,4-dimethylimidazolones 5p–5s as
shown.
Lithiation of 1-arylimidazolidin-2(1H)-ones
(4a–4d) and attempted lithiation of 6a–6d
The use of 2.5 mol equiv. of n-butyllithium and then ex-
cess iodomethane gave rise to products 6e–6j dimethylated
on nitrogen and the benzene ring; when the N-hydrogen
imidazolidinones 4a–4d were examined (Table 1), however,
these transformations were not as efficient as those involving
the imidazolones 3a–3d. Noteworthy are: (i) benzene ring
lithiation ortho to the heterocycle (→ 6e), even in the sub-
strate 4a with no electron-withdrawing methoxyl; (ii) the
regiochemistry of lithiation of the meta-methoxy-substrate
4c — between the methoxyl group and the imidazolidinone
(→ 6h); and (iii) the regiochemistry of lithiation of the
ortho-4b and para-methoxy 4d substrates — alternative
lithiations ortho to either methoxyl or imidazolidinone
groups being observed in both cases, giving 6f/6g (ortho to
the heterocycle 28% and ortho to the methoxyl 37%) and
6i/6j (ortho to the heterocycle 9% and ortho to the methoxyl
12%), respectively.
The significantly more facile ortho lithiations observed
with the N-arylimidazolones 3 as opposed to the N-
arylimidazolidinones 4 seem unlikely to reside in their rela-
tive ease of N-deprotonation, even though in the former case,
an aromatic alkoxide anion is generated. Rather, we suggest
that subtle stereochemical factors, that influence the ease
with which ortho assistance can be conveyed, are at play. We
hope to be able to comment further on this aspect in future
publications.
C-4 of the imidazolone, with no C-5-methylation. Products
5p, 5q, and 5s were formed very efficiently, but 5r only in
poor yield (Table 1). Again, nOe experiments involving irra-
diation of the N-methyl signals in the products 5p–5s caused
nOe enhancement of the C-methyl signal in each case, but
had no effect on the imidazole C-5-proton signals.
The results described above in the lithiations of 5a–5d
were unexpected and a full understanding will require fur-
ther experimentation. We offer the following explanation
(Scheme 3) as a speculative rationalization for the observa-
tions. We suggest that initial lithiation of 5a–5d takes place
at C-4 of the imidazolone ring, giving A and that trapping of
this species in the experiments using 1 mol equiv. of n-BuLi
leads to the 3,4-dimethylated products 5k, 5m, and 5n. We
further speculate that A can undergo ring opening to gener-
ate an alkyne, rather as has been reported for lithiated
isoxazoles (21) and oxazoles (22), generating B, which after
conversion to the C-lithiated species C gives rise to the 3,5-
dimethylated products 5j, 5l, and 5o via alkyne C methyl-
ation then ring closure of D. In the experiments where
2.5 mol equiv. of the base were employed, benzene ring C
lithiation of B using the second equivalent of base with
ortho assistance, would give E and thence benzene-ring-
methylated F, final closure of which would lead specifically
Attempted lithiation ortho to the N-methylimidazolidinone
unit in substrates 6a–6d failed.
Experimental
General
See ref. 1.
Typical procedure for synthesis of ureas (7)
N-(2-Methoxyphenyl)-N′-(2,2-dimethoxyethyl)urea (7b)
2-Methoxyphenyl isocyanate (4.77 g, 31.98 mmol) was
added over a period of 5 min to aminoacetaldehyde dimethyl
acetal (3.36 g, 31.98 mmol, 1 equiv.) while cooling in an ice
bath. The reaction was allowed to warm up to rt for 1 h dur-
ing which time a yellow crystalline mass was formed. The
solid was washed with petroleum ether, dissolved in CH2Cl2,
and the solution evaporated. Column SiO2 chromatography
(50% EtOAc in hexane) gave N-(2-methoxyphenyl)-N′-(2,2-
dimethoxyethyl)urea 7b as white crystals (6.98 g, 85%), mp
1
92–94 °C. H NMR (300 MHz, CDCl3) δ: 3.42 (2H, m,
CH2CH), 3.48 (6H, s, 2 × OCH3), 3.88 (3H, s, OCH3), 4.47
(1H, t, J = 5.2, CH2CH), 5.05 (1H, bt, J = 5.5, NH), 6.86–
7.06 (4H, m, Ar-H), 8.05 (1H, m, Ar-NH). 13C NMR
(75 MHz, CDCl3) δ: 41.8, 54.4, 55.5, 103.4, 110.0, 119.5,
121.0, 122.3, 128.5, 142.1, 155.6. m/z (CI): 255 (MH+,
100%), 223 (95), 75 (30). Anal. calcd. for C12H18N2O4 (M):
254.126 65; found (M+): 254.126 9.
© 2004 NRC Canada

Llopart et al.
1653
Scheme 3.
was prepared as above from 3-methoxyphenyl isocyanate
(1 g, 6.7 mmol) and aminoacetaldehyde dimethyl acetal
(0.7 g, 6.7 mmol, 1 equiv.) giving 7c as a white crystalline
solid (1.615 g, 95%) pure enough for its subsequent use. An
analytical sample was recrystallized from EtOAc–hexane,
mp 102 °C. IR νmax (film, cm–1): 1556, 1606, 1653, 2875,
2958. 1H NMR (300 MHz, d6-DMSO) δ: 3.44 (2H, m,
CH2CH), 3.44 (6H, s, 2 × OCH3), 3.72 (3H, s, OCH3), 4.39
(1H, t, J = 5.1, CH2CH), 6.49 (1H, apparent dd, J = 8.2, 2.9,
ArH), 6.84 (1H, apparent dd, J = 8.2, 2.9, ArH), 7.12 (1H,
bs, ArH), 7.14 (1H, bs, NH), 7.15 (1H, t, J = 8.2, ArH), 8.6
(1H, s, NH). 13C NMR (75 MHz, d6-DMSO) (DEPT) δ: 41.0
(d), 53.7 (q), 55.2 (q), 102.9 (d), 103.7 (d), 106.9 (d), 110.3
(d), 129.7 (d), 141.9 (s), 155.4 (s), 160.0 (s). m/z (CI): 255
(MH+, 7%), 208 (25), 191 (100). Anal. calcd. for
C12H18N2O4 (%): C 56.68, H 7.13, N 11.02; found (%): C
57.07, H 7.00, N 10.99. Anal. calcd. for C12H18N2O4 (M):
254.1267; found (M+): 254.1272.
N-(Phenyl)-N′-(2,2-dimethoxyethyl)urea (7a)
N-(Phenyl)-N′-(2,2-dimethoxyethyl)urea (7a) was pre-
pared as above from phenyl isocyanate (5 g, 41.9 mmol) and
aminoacetaldehyde dimethyl acetal (4.5 mL, 41.9 mmol,
1 equiv.) giving 7a as a white crystalline solid (9.53 g,
89%), mp 89–91 °C, lit. value (18) mp 86–89 °C. IR νmax
(film, cm–1): 755, 1070, 1130, 1238, 1311, 1441, 1499,
1
1555, 1597, 1654, 3340. H NMR (300 MHz, CDCl3) δ:
3.41 (6H, s, OCH3), 3.41 (2H, m, CH2CH), 4.43 (1H, t, J =
5.1, CH2CH), 5.82 (1H, t, J = 5.8, NH), 7.03 (1H, m, ArH),
7.28 (4H, m, ArH), 7.58 (1H, s, NH). 13C NMR (75 MHz,
CDCl3) δ: 41.7, 54.5, 103.5, 120.1, 123.1, 128.9, 138.8,
156.3. m/z (CI): 225 (MH+, 74%), 193 (100), 75 (92). Anal.
calcd. for C11H16N2O3 (M): 224.116 1; found (M+):
224.115 9.
N-(3-Methoxyphenyl)-N′-(2,2-dimethoxyethyl)urea (7c)
N-(3-Methoxyphenyl)-N′-(2,2-dimethoxyethyl)urea (7c)
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Can. J. Chem. Vol. 82, 2004
d, J = 2.5, ImH), 6.86 (1H, dd, J = 8.1, 2.5, ArH), 7.17 (1H,
apparent d, J = 8.1, ArH), 7.23 (1H, bs, ArH), 7.38 (1H, t,
J = 8.1, ArH). 13C NMR (75 MHz, CDCl3) δ: 55.4, 108.3,
109.6, 111.0, 111.8, 114.4, 129.9, 138.0, 153.8, 160.2. m/z
N-(4-Methoxyphenyl)-N′-(2,2-dimethoxyethyl)urea (7d)
N-(4-Methoxyphenyl)-N′-(2,2-dimethoxyethyl)urea (7d)
was prepared from 4-methoxyphenyl isocyanate (5 g,
33.5 mmol) and aminoacetaldehyde dimethyl acetal
(3.61 mL, 33.5 mmol, 1 equiv.) giving 7d as a white crys-
talline solid (7.9 g, 92%), mp 112–114 °C. IR νmax (film, cm–1):
1240, 1509, 1551, 1560, 1638, 1654, 3400. 1H NMR
(300 MHz, CDCl3) δ: 3.40 (6H, s, OCH3), 3.40 (2H, d, J =
5.0, CH2CH), 3.78 (3H, s, ArOCH3), 4.41 (1H, t, J = 5.0,
CH2CH), 6.82 (1H, d, J = 6.9, ArH), 7.19 (2H, d, J = 6.9,
ArH), 7.21 (1H, s, NH). 13C NMR (75 MHz, CDCl3) δ: 41.7,
54.4, 55.4, 103.4, 114.3, 123.2, 131.4, 156.2, 156.7. m/z
(CI): 255 (MH+, 100%), 223 (90), 75 (100). Anal. calcd. for
C12H18N2O4 (%): C 56.68, H 7.13, N 11.02; found (%): C
57.07, H 7.00, N 10.99. Anal. calcd. for C12H18N2O4 (M):
254.126 7; found (M+): 254.126 4.
+
(CI): 208 (MNH4 , 30%), 191 (MH+, 100). Anal. calcd. for
C10H10N2O2 (M): 190.074 2; found (M+): 190.073 8.
1-(4-Methoxyphenyl)imidazol-2(1H)-one (3d)
1-(4-Methoxyphenyl)imidazol-2(1H)-one (3d) was prepared
as above from N-(4-methoxyphenyl)-N′-(2,2-dimethoxy-
ethyl)urea 7d (7 g, 27.5 mmol) in aq. 2.5 mol L–1 HCl
(60 mL) giving 3d as a white crystalline solid (4.69 g, 89%),
mp 158 °C. IR νmax (film, cm–1): 1234, 1247, 1512, 1667. 1H
NMR (300 MHz, CDCl3) δ: 3.86 (s, 3H, OCH3), 6.42 (1H,
apparent t, J = 2.5, ImH), 6.49 (1H, apparent t, J = 2.5,
ImH), 7.00 (2H, d, J = 6.9, ArH), 7.48 (2H, d, J = 6.9, ArH),
11.1 (1H, s, NH). 13C NMR (75 MHz, CDCl3) δ: 55.5,
109.2, 111.5, 114.4, 124.3, 129.9, 157.9. m/z (CI): 208
Typical procedure for the synthesis of imidazolones (3)
+
(MNH4 , 2%), 191 (MH+,100). Anal. calcd. for C10H10N2O2
(%): C 63.15, H 5.30, N 14.73; found (%): C 63.20, H 5.38,
N 14.79. Anal. calcd. for C10H10N2O2 (M): 190.074 2; found
(M+): 190.073 9.
1-(2-Methoxyphenyl)imidazol-2(1H)-one (3b)
N-(2-Methoxyphenyl)-N′-(2,2-dimethoxyethyl)urea (7b)
(1.12 g, 4.4 mmol) was dissolved in aq. 2 mol L–1 HCl
(10 mL). The solution was stirred at rt for 20 h. The result-
ing clear solution was made basic with aq. 2 mol L–1 NaOH,
extracted with CH2Cl2, then the extract was dried over
MgSO4 and evaporated, yielding 1-(2-methoxyphenyl)imi-
dazol-2(1H)-one 3b as a white crystalline solid (0.92 g,
82%), mp 160–162 °C. IR νmax (film, cm–1): 764, 1024,
1244, 1283, 1431, 1465, 1510, 1684, 2934. 1H NMR
(300 MHz, CDCl3) δ: 3.88 (s, 3H, OCH3), 6.39 (1H, appar-
ent t, J = 2.6, ImH), 6.44 (1H, apparent t, J = 2.6, ImH),
7.07 (2H, m, ArH), 7.37 (1H, m, ArH), 7.49 (1H, dd, J =
7.6, 1.6, ArH). 13C NMR (75 MHz, CDCl3) δ: 55.7, 108.5,
112.2, 113.5, 120.8, 125.0, 128.2, 129.0, 154.2, 154.4. m/z
(CI): 191 (MH+, 100%). Anal. calcd. for C10H10N2O2 (%): C
63.15, H 5.30, N 14.73; found (%): C 63.23, H 5.40, N
14.55. Anal. calcd. for C10H10N2O2 (M): 190.074 2; found
(M+): 190.074 5.
Typical procedure for synthesis of 1-aryl-3-
methylimidazolones (5)
1-(2-Methoxyphenyl)-3-methylimidazol-2(1H)-one (5b)
A solution of 1-(2-methoxyphenyl)imidazol-2(1H)-one 3b
(0.26 g, 1.37 mmol) in anhyd. THF at –78 °C was treated
with n-BuLi (1.6 mol L–1, 0.89 mL, 1.1 equiv.) over 30 min
under N2. The solution was warmed up to 0 °C for 2 h and
then cooled to –78 °C for the addition of iodomethane
(0.09 mL, 1.43 mmol, 1.1 equiv.). The reaction mixture was
allowed to warm up to rt and after 20 h the reaction was
quenched with satd. aq. NH4Cl and evaporated to remove the
THF. The organic residue was dissolved in CH2Cl2, the solu-
tion washed with brine, dried and evaporated to give 1-(2-
methoxyphenyl)-3-methylimidazol-2(1H)-one 5b as a clear
yellow oil (0.25 g, 94%). IR νmax (film, cm–1): 1045, 1224,
1
1-Phenylimidazol-2(1H)-one (3a)
1270, 1405, 1461, 1497, 1605, 1687. H NMR (300 MHz,
CDCl3) δ: 3.35 (3H, s, NCH3), 3.87 (3H, s, OCH3), 6.31
(1H, d, J = 2.9, ImH), 6.47 (1H, d, J = 2.9, ImH), 7.04 (2H,
apparent t, J = 8.0, ArH), 7.34 (1H, m, ArH), 7.47 (1H, dd,
J = 8.0, 1.6, ArH). 13C NMR (75 MHz, CDCl3) δ: 30.5, 55.7,
107.2, 110.1, 111.3, 112.1, 112.2, 120.8, 127.9, 128.6,
1-Phenylimidazol-2(1H)-one (3a) was prepared as above
from N-(phenyl)-N′-(2,2-dimethoxyethyl)urea 7a (7 g,
31.2 mmol) in aq. 2.5 mol L–1 HCl (60 mL) giving 3a as a
white crystalline solid (3.27 g, 65%), mp 127 °C, lit. value
(19) mp 123–126 °C. IR νmax (film, cm–1): 756, 1424, 1503,
1598, 1667, 3061, 3156. 1H NMR (300 MHz, CDCl3) δ: 6.45
(1H, apparent t, J = 2.5, ImH), 6.57 (1H, apparent t, J = 2.5,
ImH), 7.31 (1H, m, ArH), 7.48 (2H, m, ArH), 7.61 (2H, m,
ArH), 11.1 (1H, bs, NH). 13C NMR (75 MHz, CDCl3) δ:
109.6, 111.0, 122.3, 126.1, 129.2, 136.9, 153.8. m/z (CI):
+
154.0. m/z (CI): 222 (MNH4 , 22%), 205 (MH+, 100).
C11H12N2O2 (M): 204.089 9; found (M+): 204.090 0.
3-Methyl-1-phenylimidazol-2(1H)-one (5a)
3-Methyl-1-phenylimidazol-2(1H)-one (5a) was prepared
as above from 1-phenylimidazol-2(1H)-one 3a (0.5 g,
3.12 mmol) and n-BuLi (1.6 mol L–1, 2.15 mL, 1.1 equiv.)
then iodomethane (0.29 mL, 4.7 mmol, 1.5 equiv.) giving 5a
as a white solid (0.52 g, 96%). An analytical sample was
prepared by column SiO2 chromatography (50% EtOAc in
hexane), mp 119–121 °C, lit. value (23) mp 119 °C. IR νmax
(film, cm–1): 766, 1266, 1344, 1402, 1452, 1459, 1507,
1600, 1672, 3060, 3135. 1H NMR (300 MHz, CDCl3) δ: 3.35
(3H, s, NCH3), 6.35 (1H, d, J = 3.0, ImH), 6.59 (1H, d, J =
3.0, ImH), 7.26 (1H, m, ArH), 7.44 (2H, apparent t, J = 8.0
ArH), 7.63 (2H, m, ArH). 13C NMR (75 MHz, CDCl3) δ:
+
178 (MNH4 , 100%), 161 (MH+, 99). Anal. calcd. for
C9H8N2O: (M): 160.063 7; found (M+): 160.063 8.
1-(3-Methoxyphenyl)imidazol-2(1H)-one (3c)
1-(3-Methoxyphenyl)imidazol-2(1H)-one (3c) was prepared
as above from N-(3-methoxyphenyl)-N′-(2,2-dimethoxy-
ethyl)urea 7c (1.2 g, 4.7 mmol) in aq. 2.5 mol L–1 HCl
(20 mL) giving 3c as a white crystalline solid (0.87 g, 97%),
pure enough for its subsequent use, mp 136 °C. IR νmax
(film, cm–1): 1230, 1497, 1687. 1H NMR (300 MHz, CDCl3)
δ: 3.88 (s, 3H, OCH3), 6.50 (1H, d, J = 2.5, ImH), 6.62 (1H,
© 2004 NRC Canada

Llopart et al.
1655
30.4, 109.1, 112.6, 111.06, 121.5, 125.6, 129.1, 137.3,
d6-DMSO) δ: 2.85 (2H, t, J = 6.3, CH2), 3.16 (2H, m, CH2),
5.07 (2H, bs, NH2), 5.75 (1H, bs, NH), 6.57 (3H, m, ArH),
7.10 (2H, m, ArH). 13C NMR (75 MHz, d6-DMSO) δ: 39.7,
44.3, 112.8, 116.6, 129.7, 149.4. m/z (CI): 137 (MH+,
100%).
+
155.4. m/z (CI): 192 (MNH4 , 32%), 175 (MH+, 100).
1-(3-Methoxyphenyl)-3-methylimidazol-2(1H)-one (5c)
1-(3-Methoxyphenyl)-3-methylimidazol-2(1H)-one (5c) was
prepared as above from 1-(3-methoxyphenyl)imidazol-
2(1H)-one 3c (0.8 g, 4.2 mmol) and n-BuLi (1.6 mol L–1,
2.9 mL, 1.1 equiv.) then iodomethane (0.29 mL, 4.6 mmol,
N-(3-Methoxyphenyl)-1,2-diaminoethane (8c)
N-(3-Methoxyphenyl)-1,2-diaminoethane (8c) was pre-
pared as above from m-anisidine (20 g, 0.16 mmol) and 2-
bromoethylamine hydrobromide (16.6 g, 0.8 mol, 0.5 equiv.)
giving 8c (9.78 g, 73%) as a brown semi-solid, lit. value (24)
1
1.1 equiv.) giving 5c as a clear yellow oil (0.73 g, 86%). H
NMR (300MHz, CDCl3) δ: 3.35 (3H, s, NCH3), 3.87 (3H, s,
OCH3), 6.35 (1H, d, J = 3.0, ImHa), 6.59 (1H, d, J = 3.0,
ImHb), 6.81 (1H, dd, J = 8.1, 3.0, ArH), 7.15 (1H, dd, J =
8.1, 3.0, ArH), 7.29 (1H, s, ArH), 7.34 (1H, t, J = 8.1, ArH).
13C NMR (75 MHz, CDCl3) δ: 30.4, 55.3, 107.2, 109.1,
111.6, 111.7, 112.6, 113.3, 129.7, 138.5, 160.2. m/z (CI):
1
mp 45 to 46 °C. H NMR (300 MHz, CDCl3) δ: 1.42 (2H,
bs, NH2), 2.98 (2H, m, CH2), 3.17 (2H, m, CH2), 3.80
(3H, s, OCH3), 6.20–6.35 (3H, m, ArH), 7.12 (1H, t, J = 8.1,
ArH). 13C NMR (75 MHz, CDCl3) δ: 41.1, 46.4, 54.9, 98.8,
102.4, 106.0, 129.8. m/z (CI): 167 (MH+, 100%), 136 (20).
+
222 (MNH4 , 22%), 205 (MH+, 100). Anal. calcd. for
C11H12N2O2 (M): 204.089 9; found (M+): 204.090 5.
N-(4-Methoxyphenyl)-1,2-diaminoethane (8d)
N-(4-Methoxyphenyl)-1,2-diaminoethane (8d) was prepared
as above from p-anisidine (5 g, 40 mmol) and 2-bromoethyl-
amine hydrobromide (4.15 g, 20 mmol, 0.5 equiv.) giving 8d
(1.35 g, 40%) as a brown solid, mp 60–62 °C, lit. value (25)
mp 64 °C. IR νmax (film, cm–1): 823, 1034, 1236, 1512,
1668, 2932. 1H NMR (300 MHz, CD3OD) δ: 2.78 (2H, t, J =
6.1, CH2), 3.07 (2H, t, J = 6.1, CH2), 3.26 (1H, bs, NH),
4.83 (1H, bs, NH2), 6.60 (2H, d, J = 9.0, ArH), 6.81 (2H, d,
J = 9.0, ArH). 13C NMR (75 MHz, CDCl3) δ: 41.6, 47.8,
56.1, 114.6, 115.2, 126.0, 142.9. m/z (CI): 167 (M+, 100%),
136 (20), 124 (65).
1-(4-Methoxyphenyl)-3-methylimidazol-2(1H)-one (5d)
1-(4-Methoxyphenyl)-3-methylimidazol-2(1H)-one (5d) was
prepared as above from 1-(4-methoxyphenyl)imidazol-2(1H)-
one 3d (0.5 g, 2.6 mmol) and n-BuLi (1.6 mol L–1, 1.8 mL,
1.1 equiv.) then iodomethane (0.24 mL, 3.9 mmol, 1.5 equiv.)
giving 5d as a white solid (0.516 g, 96%), mp 116–118 °C,
lit. value (23) mp 114 °C. IR νmax (film, cm–1): 1248, 1458,
1514, 1678, 2360. 1H NMR (300 MHz, CDCl3) δ: 3.32
(3H, s, NCH3), 3.83 (3H, s, OCH3), 6.31 (1H, d, J = 2.9,
ImH), 6.50 (1H, d, J = 2.9, ImH), 6.95 (2H, d, J = 6.9,
ArH), 7.48 (2H, d, J = 6.9, ArH). 13C NMR (75 MHz,
CDCl3) δ: 30.4, 55.4, 109.7, 111.8, 112.2, 114.2, 123.4,
+
130.5, 157.5. m/z (CI): 222 (MNH4 , 22%), 205 (MH+, 100).
Typical procedure for the synthesis of N-
arylimidazolidinones (4)
Anal. calcd. for C11H12N2O2 (M): 204.089 9; found (M+):
204.089 7.
4,5-Dihydro-1-(2-methoxyphenyl)imidazol-2(1H)-one (4b)
To a solution of N-(2-methoxyphenyl)-1,2-diaminoethane
8b (9.97 g, 0.06 mol) in anhyd. THF (50 mL), 1,1-
carbonyldiimidazole (18.44 g, 0.145 mol, 2.4 equiv.) was
added under N2. The solution was refluxed for 21 h and then
evaporated to dryness to remove the THF. The yellow resi-
due was taken up with EtOAc, the solution washed with
brine, dried over MgSO4 and evaporated. Column SiO2 chro-
matography (25% of EtOAc in hexane) yielded 4,5-dihydro-
1-(2-methoxyphenyl)imidazol-2(1H)-one 4b as a white crys-
talline solid (2.77 g, 25%), mp 150–152 °C, lit. value (26)
Typical procedure for the synthesis of aryldiamines (8)
N-(2-Methoxyphenyl)-1,2-diaminoethane (8b)
A mixture of freshly distilled o-anisidine (19.7 g,
160 mmol) and 2-bromoethylamine hydrobromide (19.7 g,
160 mmol, 1 equiv.) in dry toluene (40 mL) was heated at
reflux temperature for 18 h, and then cooled. A solution of
50% aq. NaOH and CH2Cl2 were added and the layers sepa-
rated. The aqueous layer was saturated with NaCl and ex-
tracted with CH2Cl2. The combined organic layers were
dried over MgSO4, filtered and evaporated to dryness. Dry
flash column SiO2 chromatography (40%–100% of CH2Cl2
in hexane) yielded N-(2-methoxyphenyl)-1,2-diaminoethane
1
mp 151–153 °C. H NMR (300 MHz, CDCl3) δ: 3.60 (2H, t,
J = 8.2, ImH), 3.85 (2H, t, J = 8.2, ImH), 3.90 (3H, s,
OCH3), 5.18 (1H, bs, NH), 6.99 (2H, m, ArH), 7.26 (1H, m,
ArH), 7.39 (1H, dd, J = 7.7, 1.6, ArH). 13C NMR (75 MHz,
CDCl3) δ: 38.7, 47.3, 55.5, 111.9, 120.9, 127.7, 127.8, 128.6,
155.2, 162.0. m/z (CI): 193 (MH+, 100%). Anal. calcd. for
C10H12N2O2 (M): 192.089 9; found (M+): 192.090 0.
1
8b (9.99 g, 75%) as a light brown low oil. H NMR (24)
(300 MHz, CDCl3) δ: 1.98 (2H, bs, NH2), 3.02 (2H, t, J =
5.6, CH2), 3.24 (2H, t, J = 5.6, CH2), 3.5 (1H, bs, NH), 3.9
(3H, s, ArOCH3), 6.70 (2H, m, ArH), 6.80 (1H, m, ArH),
6.90 (1H, m, Ar). 13C NMR (75 MHz, CDCl3) δ: 41.3, 46.5,
55.4, 109.7, 110.2, 116.5, 121.4, 138.0, 146.8. m/z (CI): 167
(MH+, 100%). Anal. calcd. for C8H11N2O (M – Me):
151.082 1; found: 151.063 7.
4,5-Dihydro-1-phenylimidazol-2(1H)-one (4a)
4,5-Dihydro-1-phenylimidazol-2(1H)-one (4a) was pre-
pared as above from N-phenyl-1,2-diaminoethane 8a (1.5 g,
11 mmol) and 1,1-carbonyldiimidazole (7.2 g, 47 mmol,
4.3 equiv.) giving 4a as a white crystalline solid (1.35 g,
76%), mp 159 °C, lit. value (27) mp 162 to 163 °C. IR νmax
N-Phenyl-1,2-diaminoethane (8a)
N-Phenyl-1,2-diaminoethane (8a) was prepared as above
from aniline (5 g, 53 mmol) and 2-bromoethylamine hydro-
bromide (5.5 g, 26 mmol, 0.5 equiv.) giving 8a (1.5 g, 42%)
as a clear oil (23). IR νmax (film, cm–1): 749, 1320, 1506,
1
(film, cm–1): 748, 1150, 1484, 1680, 2906, 3424. H NMR
(300 MHz, CDCl3) δ: 3.41 (2H, t, J = 7.9, ImH), 3.85 (2H,
apparent t, J = 7.9, ImH), 6.94 (1H, bs, NH), 7.06 (1H, ap-
parent t, J = 8.6, ArH), 7.35 (2H, apparent t, J = 8.6, ArH),
1
1602, 2862, 2937, 3024, 3048, 3343. H NMR (300 MHz,
© 2004 NRC Canada

1656
Can. J. Chem. Vol. 82, 2004
7.56 (2H, apparent d, J = 8.6, ArH). 13C NMR (75 MHz,
CDCl3) δ: 42.0, 49.9, 122.4, 126.9, 134.0.
0.68 mL, 1.1 equiv.) then iodomethane (0.06 mL, 1.1 mmol,
1.1 equiv.) giving 6a as a white crystalline solid (126 mg,
71%). An analytical sample was prepared by column SiO2
chromatography (50% of EtOAc in hexane), mp 99 °C, lit.
value (29) mp 110 to 111 °C. IR νmax (film, cm–1): 742, 899,
1275, 1387, 1404, 1439, 1476, 1504, 1598, 1702, 2826,
2887, 2917, 2952. 1H NMR (300 MHz, CDCl3) δ: 2.93
(3H, s, NCH3), 3.48 (2H, t, J = 8.3, ImH), 3.80 (2H, t, J =
8.3, ImH), 7.05 (1H, dt, J = 7.3, 1.0, ArH), 7.32 (1H, m,
ArH), 7.60 (1H, m, ArH). 13C NMR (75 MHz, CDCl3) δ:
31.4, 42.5, 44.3, 117.4, 122.4, 129.0, 140.9, 158.4. m/z (CI):
177 (MH+, 100%), 105 (2).
4,5-Dihydro-1-(3-methoxyphenyl)imidazol-2(1H)-one (4c)
4,5-Dihydro-1-(3-methoxyphenyl)imidazol-2(1H)-one (4c)
was prepared as above from N-(3-methoxyphenyl)-1,2-
diaminoethane 8c (6 g, 0.036 mol) and 1,1-carbonyldi-
imidazole (25 g, 0.18 mol, 5.2 equiv.) giving 4c as a white
crystalline solid (4.35 g, 63%), mp 123 °C, lit. (20). IR νmax
(film, cm–1): 662, 1259, 1411, 1482, 1601, 1705, 2923,
1
3257. H NMR (300 MHz, CDCl3) δ: 3.60 (2H, apparent t,
J = 7.8, ImH), 3.80 (s, 3H, OCH3), 3.98 (2H, apparent t, J =
7.8, ImH), 6.67 (1H, dd, J = 8.2, 2.5, ArH), 7.09 (1H, dd,
J = 8.2, 2.06, ArH), 7.26–7.32 (2H, m, ArH). 13C NMR
(75 MHz, CDCl3) δ: 41.3, 42.2, 55.3, 118.4, 129.5, 129.8,
4,5-Dihydro-1-(3-methoxyphenyl)-3-methylimidazol-2(1H)-
one (6c)
+
138.4, 148.5, 151.09, 160.1. m/z (CI): 210 (MNH4 , 25%),
4,5-Dihydro-1-(3-methoxyphenyl)-3-methylimidazol-2(1H)-
one (6c) was prepared as above from 4,5-dihydro-1-(3-
methoxyphenyl)imidazol-2(1H)-one 4c (200 mg, 1.04 mmol,
1 equiv.) and n-BuLi (1.6 mol L–1, 0.875 mL) then
iodomethane (0.60 mL, 1.04 mmol, 1 equiv.) giving 6c
(200 mg, 93%) as white solid, mp 95 °C, lit. value (29) mp
97–99 °C. IR νmax (film, cm–1): 1221, 1452, 1500, 1601,
193 (100). Anal. calcd. for C10H12N2O2 (M): 192.089 9;
found (M+): 192.089 4.
4,5-Dihydro-1-(4-methoxyphenyl)imidazol-2(1H)-one (4d)
4,5-Dihydro-1-(4-methoxyphenyl)imidazol-2(1H)-one (4d)
was prepared as above from N-(4-methoxyphenyl)-1,2-di-
aminoethane 8d (1 g, 6 mmol) and 1,1′-carbonyldiimidazole
(3.9 g, 52 mmol, 3.9 equiv.) giving 4d as a white crystalline
solid (0.45 g, 44%), mp 205–207 °C, lit. value (28) mp
211 °C. IR νmax (film, cm–1): 830, 1034, 1251, 1519, 1679,
1
1703. H NMR (300 MHz, CDCl3) δ: 2.93 (3H, s, NCH3),
3.50 (2H, apparent t, J = 7.9, ImH), 3.83 (2H, m, ImH), 3.85
(3H, s, OCH3), 6.63 (1H, dd, J = 8.2, 2.2, ArH), 7.04 (1H,
dd, J = 8.2, 2.2, ArH), 7.25 (1H, t, J = 8.2, ArH), 7.41
(1H, m, ArH). 13C NMR (75 MHz, CDCl3) δ: 31.1, 42.3,
43.9, 55.2, 103.1, 108.1, 109.1, 109.7, 129.3, 141.9, 159.9.
m/z (CI): 207 (M+, 100). Anal. calcd. for. C10H12N2O2 (M):
206.105 5; found (M+): 206.105 5.
1
3476, 3583. H NMR (300 MHz, CDCl3) δ: 3.90 (3H, s,
OCH3), 3.97 (2H, t, J = 7.9, ImH), 4.17 (2H, t, J = 7.9,
ImH), 7.01 (2H, d, J = 7.8, ArH), 7.41 (2H, d, J = 7.8, ArH).
13C NMR (75 MHz, CDCl3) δ: 37.9, 46.2, 55.8, 114.3,
+
120.3, 141.6, 142.2, 158.7. m/z (CI): 210 (MNH4 , 10%),
193 (MH+, 100).
4,5-Dihydro-1-(4-methoxyphenyl)-3-methylimidazol-2(1H)-
one (6d)
Typical procedure for the synthesis of 1-aryl-3-
methylimidazolidinones (6)
4,5-Dihydro-1-(4-methoxyphenyl)-3-methylimidazol-2(1H)-
one (6d) was prepared as above from 4,5-dihydro-1-(4-
methoxyphenyl)imidazol-2(1H)-one 4d (0.25 g, 1.3 mmol)
and n-BuLi (1.6 mol L–1, 0.89 mL, 1.1 equiv.) then
iodomethane (0.085 mL, 1.43 mmol, 1.1 equiv.) giving 6d
(180 mg, 68%) as a solid, mp 56 to 57 °C. IR νmax
(film, cm–1): 828, 1038, 1252, 1686, 2948. 1H NMR
(300 MHz, CDCl3) δ: 2.83 (3H, s, NCH3), 3.39 (2H, appar-
ent t, J = 7.6, ImH), 3.71 (2H, apparent t, J = 7.6, ImH),
3.73 (3H, s, OCH3), 6.82 (2H, d, J = 8.9, ArH), 7.39 (2H, d,
J = 8.9, ArH). 13C NMR (75 MHz, CDCl3) δ: 31.6, 43.1,
44.6, 55.8, 114.4, 119.5, 134.4, 146.2, 155.6. m/z (CI): 207
(MH+, 100). Anal. calcd. for. C10H12N2O2 (M): 206.105 5;
found (M+): 206.105 8.
4,5-Dihydro-1-(2-methoxyphenyl)-3-methylimidazol-2(1H)-
one (6b)
A solution of 4,5-dihydro-1-(2-methoxyphenyl)imidazol-
2(1H)-one 4b (0.250 g, 1.3 mmol) in anhyd. THF was
treated with n-BuLi (1.6 mol L–1, 0.9 mL, 1.1 equiv.) at
–78 °C over 30 min under N2. The solution was warmed
then maintained at 0 °C for 2 h and cooled down to –78 °C
again for the addition of iodomethane (0.09 mL, 1.43 mmol,
1.1 equiv.). The reaction mixture was warmed up to rt and
after 20 h quenched with satd. aq. NH4Cl and evaporated to
remove the THF. The colourless residue was dissolved with
CH2Cl2, the solution washed with brine, dried over MgSO4
and evaporated to yield 4,5-dihydro-1-(2-methoxyphenyl)-3-
methylimidazol-2(1H)-one 6b (0.26 g, 95%) as a dark yel-
Typical procedure for reaction of imidazolones (3a–3d)
and imidazolidinones (4a–4d) with 2.5 equiv. of n-BuLi
then trapping with MeI
1
low oil. H NMR (300 MHz, CDCl3) δ: 2.92 (3H, s, NCH3),
3.48 (2H, t, J = 7.7, ImH), 3.78 (2H, t, J = 7.7, ImH), 3.88
(3H, s, OCH3), 6.92 (2H, m, ArH), 7.25 (1H, m, ArH), 7.38
(1H, dd, J = 7.8, 1.6, ArH). 13C NMR (75 MHz, CDCl3) δ:
31.5, 44.6, 45.4, 55.5, 111.8, 120.8, 127.4, 128.4, 129.3,
155.1, 160.0. m/z (CI): 207 (MH+, 100%). Anal. calcd. for
C11H14N2O2 (M): 206.105 5; found (M+): 206.105 5.
1-(2-Methoxy-3-methylphenyl)-3-methylimidazol-2(1H)-
one (5g) and 1-(2-methoxy-6-methylphenyl)-3-
methylimidazol-2(1H)-one (5f)
A solution of 1-(2-methoxyphenyl)imidazol-2(1H)-one 3b
(0.26 g, 1.3 mmol) in anhyd. THF was treated with n-BuLi
(1.6 mol L–1, 2 mL, 2.5 equiv.) at –78 °C over 30 min under
N2. The solution was warmed up to then maintained at 0 °C
for 2 h and cooled down to –78 °C again for the addition of
iodomethane (0.2 mL, 3.25 mmol, 2.5 equiv.). The reaction
4,5-Dihydro-3-methyl-1-phenylimidazol-2(1H)-one (6a)
4,5-Dihydro-3-methyl-1-phenylimidazol-2(1H)-one (6a)
was prepared as above from 4,5-dihydro-1-phenylimidazol-
2(1H)-one 4a (0.162 mg, 1 mmol), n-BuLi (1.6 mol L–1,
© 2004 NRC Canada

Llopart et al.
1657
mixture was allowed to warm up to rt and after 20 h
quenched with satd. aq. NH4Cl, and evaporated to remove
the THF. The organic residue was taken up with CH2Cl2, the
solution washed with brine, dried and evaporated. Column
SiO2 chromatography (50% of EtOAc in petroleum ether)
yielded firstly 1-(2-methoxy-3-methylphenyl)-3-methylimi-
dazol-2(1H)-one 5g (70 mg, 25%), secondly 1-(2-methoxy-
6-methylphenyl)-3-methylimidazol-2(1H)-one 5f (50 mg,
analytical sample was prepared by column SiO2 chromatog-
raphy (50% of EtOAc in hexane). IR νmax (film, cm–1
:
)
1242, 1458, 1508, 1677. 1H NMR (300 MHz, CDCl3) δ: 2.23
(3H, s, ArCH3), 3.35 (3H, s, NCH3), 3.83 (3H, s, OCH3),
6.27 (1H, d, J = 2.9, ImH), 6.32 (1H, d, J = 2.9, ImH), 6.79
(1H, dd, J = 8.5, 2.9, ArH), 6.83 (1H, d, J = 2.9, ArH), 7.15
(1H, d, J = 8.5, ArH). 13C NMR (75 MHz, CDCl3) δ: 18.2,
30.6, 55.4, 111.9, 116.0, 128.5, 128.8, 130.7, 137.0, 159.2,
1
+
18%) as yellow oils. Spectroscopic data for 5g: H NMR
152.7, 166.7. m/z (CI): 236 (MNH4 , 13%), 219 (MH+, 100).
(300 MHz, CDCl3) δ: 2.25 (3H, s, ArCH3), 3.27 (3H, s,
NCH3), 3.57 (3H, s,OCH3), 6.24 (2H, d, J = 3.0, ImH), 6.45
(1H, d, J = 3.0, ImH), 7.07 (1H, d, J = 8.2, ArH), 7.15 (1H,
d, J = 8.2, ArH), 7.35 (1H, t, J = 8.2, ArH). 13C NMR
(75 MHz, CDCl3) δ: 15.9, 30.5, 55.7, 111.4, 111.8, 111.9,
124.0, 125.4, 128.7, 129.6, 130.2, 156.0. m/z (CI): 219
(MH+, 100%). Anal. calcd. for. C12H14N2O2 (M): 218.105 5;
Anal. calcd. for. C12H14N2O2 (M): 218.105 5; found (M+):
218.105 4.
4,5-Dihydro-1-(2-methylphenyl)-3-methylimidazol-2(1H)-
one (6e)
4,5-Dihydro-1-(2-methylphenyl)-3-methylimidazol-2(1H)-
one (6e) was prepared from 4,5-dihydro-1-phenylimidazol-
2(1H)-one 4a (0.162 mg, 1 mmol) giving 4,5-dihydro-1-(2-
methylphenyl)-3-methylimidazol-2(1H)-one 6e (64 mg,
34%) as a yellow oil. IR νmax (film, cm–1): 756, 1265, 1400,
1
found (M+): 218.105 6. Spectroscopic data for 5g: H NMR
(300 MHz, CDCl3) δ: 2.22 (3H, s, ArCH3), 3.37 (3H, s,
NCH3), 3.82 (3H, s, OCH3), 6.23 (2H, d, J = 2.9, ImH), 6.32
(1H, d, J = 2.9, ImH), 6.84 (1H, d, J = 7.9, ArH), 6.91 (1H,
d, J = 7.9, ArH), 7.27 (1H, t, J = 7.9, ArH). 13C NMR
(75 MHz, CDCl3) δ: 18.2. 31.2, 55.8, 109.2, 111.8, 111.9,
113.3, 122.4, 125.9, 129.1, 138.0, 155.9. m/z (CI): 233
1
1431, 1494, 1701, 2871, 2933. H NMR (300 MHz, CDCl3)
δ: 2.30 (3H, s, ArCH3), 2.91 (3H, s, NCH3), 3.49 (2H, t, J =
7.9, ImH), 3.81 (2H, t, J = 7.9, ImH), 7.21 (4H, m, ArH).
13C NMR (75 MHz, CDCl3) δ: 18.3, 31.9, 42.6, 45.7, 117.5,
126.9, 127.4, 129.0, 131.4, 136.5, 158.4. m/z (CI): 208
(MH+, 50%), 191 (MH+, 100), 177 (20). Anal. calcd. for.
C11H14N2O (M): 190.110 6; found (M+): 190.110 8.
+
(MNH4 , 10%), 219 (MH+, 100), 205 (20). Anal. calcd. for.
C12H14N2O2 (M): 218.105 5; found (M+): 218.105 4.
1-(2-Methylphenyl)-3-methylimidazol-2(1H)-one (5e)
1-(2-Methylphenyl)-3-methylimidazol-2(1H)-one (5e) was
prepared as above from 1-phenylimidazol-2(1H)-one 3a
(0.18 g, 1.12 mmol) giving 1-(2-methylphenyl)-3-methyl-
imidazol-2(1H)-one 5e as a yellow oil (189 mg, 88%). An
analytical sample was prepared by column SiO2 chromatog-
raphy (50% EtOAc in hexane). IR νmax (film, cm–1): 1460,
4,5-Dihydro-1-(2-methoxy-3-methylphenyl)-3-methyl-
imidazol-2(1H)-one (6g) and 4,5-dihydro-1-(2-methoxy-6-
methylphenyl)-3-methylimidazol-2(1H)-one (6f)
4,5-Dihydro-1-(2-methoxy-3-methylphenyl)-3-methylimida-
zol-2(1H)-one (6g) and 4,5-dihydro-1-(2-methoxy-6-methyl-
phenyl)-3-methylimidazol-2(1H)-one (6f) were prepared as
above from 4,5-dihydro-1-(2-methoxy)phenylimidazol-
2(1H)-one 4b (0.4 g, 2.1 mmol) giving from the column
firstly 6g (0.168 g, 37%), then 6f (0.130 g, 28%) as yellow
1
1499, 1686. H NMR (300 MHz, CDCl3) δ: 2.27 (3H, s,
ArCH3), 3.35 (3H, s, NCH3), 6.31 (1H, d, J = 2.9, ImH),
6.34 (1H, d, J = 2.9, ImH), 7.27 (4H, m, ArH). 13C NMR
(75 MHz, CDCl3) δ: 17.9, 30.6, 115.6, 112.11, 126.6, 127.4,
1
oils. Spectroscopic data for 6g: H NMR (300 MHz, CDCl3)
+
128.2, 131.0, 135.5, 137.0, 156.7. m/z (CI): 236 (MNH4 ,
δ: 2.29 (3H, s, ArCH3), 2.90 (3H, s, NCH3), 3.47 (2H, t, J =
7.3, ImH), 3.73 (3H, s, OCH3), 3.77 (2H, t, J = 7.3, ImH),
7.04 (2H, m, ArH), 7.23 (1H, m, ArH). 13C NMR (75 MHz,
CDCl3) δ: 15.8, 31.4, 44.5, 45.5, 59.9, 123.9, 124.0, 125.6,
128.8, 131.9, 154.0, 159.9. m/z (CI): 221 (M+,100%). Anal.
calcd. for. C12H16N2O2 (M): 206.121 2; found (M+):
76%), 489 (MH+, 100). Anal. calcd. for. C11H12N2O (M):
188.094 5; found (M+): 188.094 8.
1-(3-Methoxy-2-methylphenyl)-3-methylimidazol-2(1H)-
one (5h)
1
1-(3-Methoxy-2-methylphenyl)-3-methylimidazol-2(1H)-
one (5h) was prepared as above from 1-(3-methoxy-
phenyl)imidazol-2(1H)-one 3c (0.5 g, 2.6 mmol, 1 equiv.)
giving 5h as a yellow oil (317 mg, 60%). IR νmax (film, cm–1):
1260, 1435, 1476, 1694. 1H NMR (300 MHz, CDCl3) δ: 2.11
(3H, s, ArCH3), 3.34 (3H, s, NCH3), 3.86 (3H, s, OCH3),
6.31 (1H, d, J = 3.0, ImH), 6.33 (1H, d, J = 3.0, ImH), 6.87
(2H, d, J = 8.1, ArH), 7.22 (1H, t, J = 8.1, ArH). 13C NMR
(75 MHz, CDCl3) δ: 11.0, 30.5, 55.7, 109.0, 110.0, 111.7,
112.9, 119.5, 126.5, 126.6, 136.6, 158.4. m/z (CI): 219
(MH+, 100%), 102 (30). Anal. calcd. for. C12H14N2O2 (MH):
219.113 3; found (MH+): 219.113 7.
220.121 4. Spectroscopic data for 6f: H NMR (300 MHz,
CDCl3) δ: 2.17 (3H, s, ArCH3), 2.73 (3H, s, NCH3), 3.42
(2H, m, ImH), 3.62 (2H, m, ImH), 3.76 (3H, s, OCH3) 6.85
(1H, apparent d, J = 8.0, ArH), 6.90 (1H, apparent d, J =
8.0, ArH), 7.20 (1H, apparent t, J = 8.0, Ar). 13C NMR
(75 MHz, CDCl3) δ: 17.6, 31.6, 44.6, 45.8, 55.7, 109.2,
122.5, 128.1, 129.0, 139.2, 156.7, 160.1. m/z (CI): 221
(MH+, 100%), 207 (70). Anal. calcd. for. C12H16N2O2 (M):
206.121 2; found (M+): 220.121 4.
4,5-Dihydro-1-(3-methoxy-2-methylphenyl)-3-methyl-
imidazolidin-2-one (6h)
4,5-Dihydro-1-(3-methoxy-2-methylphenyl)-3-methylimi-
dazolidin-2-one (6h) was prepared as above from 4,5-
dihydro-1-(3-methoxyphenyl)imidazol-2(1H)-one 4c (0.1 g,
5.2 mmol) giving 6h (0.08 g, 22%) as a yellow oil. H NMR
(300 MHz, CDCl3) δ: 2.16 (3H, s, ArCH3), 2.92 (3H, s,
NCH3), 3.51 (2H, t, J = 7.9, ImH), 3.68 (2H, t, J = 7.9,
1-(4-Methoxy-2-methylphenyl)-3-methylimidazol-2(1H)-
one (5i)
1-(4-Methoxy-2-methylphenyl)-3-methylimidazol-2(1H)-
one (5i) was prepared from 1-(4-methoxyphenyl)imidazol-
2(1H)-one 3d (0.2 g, 1.05 mmol) giving 5i (0.22 g, 96%); an
1
© 2004 NRC Canada

1658
Can. J. Chem. Vol. 82, 2004
+
ImH), 3.87 (3H, s, OCH3), 6.80 (1H, d, J = 7.9, ArH), 6.85
(1H, d, J = 7.9, ArH), 7.19 (1H, t, J = 7.9, ArH). 13C NMR
(75 MHz, CDCl3): 10.9, 31.5, 42.3, 42.5, 55.2, 103.1, 108.8,
118.7, 125.2, 129.3, 141.9, 159.9. m/z (CI): 221 (M+, 100%),
207 (87). Anal. calcd. for. C12H16N2O2 (M): 220.121 2;
found (M+): 220.121 0.
297 (MNH4 , 20%), 280 (MH+, 100). Anal. calcd. for.
C16H13N3O2 (M): 279.100 8; found (M+): 279.100 5. Spec-
troscopic data for 9b: IR νmax (film, cm–1): 754, 1234, 1320,
1411, 1443, 1495, 1553, 1601, 1678, 1730. 1H NMR
(300 MHz, CDCl3) δ: 6.59 (1H, d, J = 3.2, ImH,), 7.12
(2H, m, ArH), 7.22 (1H, d, J = 3.2, ImH), 7.35 (5H, m,
ArH), 7.58 (6H, m, ArH), 7.79 (1H, d, J = 7.3, ArH), 8.49
(1H, bs, NH), 10.65 (1H, bs, NH). 13C NMR (75 MHz,
CDCl3) δ: 109.1, 113.9, 119.9, 120.1, 124.5, 124.7, 127.7,
128.3, 129.0, 129.3, 129.4, 131.5, 132.0, 135.0, 136.7,
4,5-Dihydro-1-(4-methoxy-2-methylphenyl)-3-methyl-
imidazol-2(1H)-one (6i) and 4,5-dihydro-1-(4-methoxy-3-
methylphenyl)-3-methylimidazol-2(1H)-one (6j)
+
137.6, 146.7, 151.4, 164.7. m/z (CI): 416 (MNH4 , 5%), 399
4,5-Dihydro-1-(4-methoxy-2-methylphenyl)-3-methylimida-
zol-2(1H)-one (6i) and 4,5-dihydro-1-(4-methoxy-3-methyl-
phenyl)-3-methylimidazol-2(1H)-one (6j) were prepared
from 4,5-dihydro-1-(4-methoxyphenyl)imidazol-2(1H)-one
4d (30 mg, 0.16 mmol) giving firstly from the column 6i
(3 mg, 9%) as a foamy yellow solid, and secondly, 6j (4 mg,
12%) as a yellow oil. Spectroscopic data for 6i: IR νmax
(film, cm–1): 1030, 1106, 1244, 1400, 1433, 1505, 1700,
(MH+, 8), 297 (20), 280 (100). Anal. calcd. for. C23H18N4O3
(M): 398.137 9; found (M+): 398.137 5.
3-(Phenylaminocarbonyl)-1-[6-methoxy-2-(phenylaminocar-
bonyl)phenyl]imidazol-2(1H)-one (9c) and 3-(phenylamino-
carbonyl)-1-[2-methoxy-3-(phenylaminocarbonyl)phenyl]-
imidazol-2(1H)-one (9d)
1
3-(Phenylaminocarbonyl)-1-[6-methoxy-2-(phenylaminocar-
bonyl)phenyl]imidazol-2(1H)-one (9c) and 3-(phenylamino-
carbonyl)-1-[2-methoxy-3-(phenylaminocarbonyl)phenyl]imidazol-
2(1H)-one (9d) were made from a solution of 1-(2-
methoxyphenyl)imidazol-2(1H)-one 3b (0.23 g, 1.2 mmol)
with n-BuLi (1.6 mol L–1, 1.95 mL, 2.5 equiv.), then phenyl
isocyanate (0.34 mL, 3.12 mmol, 2.5 equiv.) was added giv-
ing firstly from chromatography 9c (80 mg, 15%, slightly
contaminated by a phenyl isocyanate derivative), and sec-
ondly, 9d (97 mg, 18%) as low mp yellow solids. Spectro-
scopic data for 9c: IR νmax (film, cm–1): 754, 1055, 1233,
2923. H NMR (300 MHz, CDCl3) δ: 2.22 (3H, s, ArCH3),
2.90 (3H, s, NCH3), 3.45 (2H, apparent t, J = 7.9, ImH),
3.75 (2H, apparent t, J = 7.9, ImH), 3.80 (3H, s, OMe), 6.80
(1H, d, J = 7.7, ArH), 7.25 (1H, s, ArH), 7.57 (1H, m, ArH).
+
m/z (CI): 238 (MNH4 , 20%), 221 (MH+, 100). Anal. calcd.
for C12H16N2O2 (M): 220.121 2; found (M+): 220.121 6.
Spectroscopic data for 6j: IR νmax (film, cm–1): 1046, 1097,
1
1241, 1401, 1433, 1505, 1698, 3424. H NMR (300 MHz,
CDCl3) δ: 2.30 (3H, s, ArCH3), 2.80 (3H, s, NCH3), 3.48
(2H, t, J = 7.9, ImH), 3.65 (2H, t, J = 7.9, ImH), 3.82 (3H, s,
OMe), 6.76 (1H, m, ArH), 6.80 (1H, m, ArH), 7.12 (1H, d,
J = 7.8, ArH). 13C NMR (75 MHz, CDCl3) δ: 18.4, 31.9,
46.8, 46.0, 55.7, 112.4, 116.4, 128.5, 131.7, 138.1, 146.8,
1
1409, 1440, 1492, 1550, 1599, 1680, 1707, 1728. H NMR
(300 MHz, CDCl3) δ: 3.85 (3H, s, OCH3), 6.42 (1H, d, J =
3.2, ImH), 7.01–7.81 (14H, m, ArH + ImH), 8.54 (1H, s,
NH), 10.63 (1H, s, NH). 13C NMR (75 MHz, CDCl3) δ:
56.4, 102.9, 108.7, 113.9, 115.4, 120.0, 120.4, 120.7, 124.8,
124.9, 126.6, 128.6, 129.0, 129.3, 131.4, 138.0, 156.0,
+
158.7. m/z (CI): 238 (MNH4 , 20%), 221 (MH+, 100). Anal.
calcd. for. C12H16N2O2 (M): 220.121 2; found (M+):
220.121 1.
+
163.3, 164.8. m/z (CI): 446 (MNH4 , 25%), 429 (MH+, 40),
Typical procedure for lithiation of imidazolones (3a–3d)
with 2.5 equiv. n-BuLi and then reaction with phenyl
isocyanate
These experiments followed exactly the method described
previously for trapping with iodomethane, but used phenyl
isocyanate as the electrophile.
310 (100). Anal. calcd. for. C24H20N4O4 (M): 428.148 4;
found (M+): 428.149 3. Spectroscopic data for 9d: IR νmax
(film, cm–1): 753, 1441, 1598, 1710, 3329. 1H NMR
(300 MHz, CDCl3) δ: 3.75 (3H, s, OCH3), 6.24 (1H, bs,
ImH), 6.30 (1H, bs, ImH), 7.03 (3H, m, ArH), 7.21 (4H, ap-
parent t, J = 8.0, ArH), 7.29 (2H, apparent d, J = 7.7, ArH),
7.43 (2H, t, J = 8.0, ArH), 7.60 (2H, d, J = 7.7, ArH), 9.60
(1H, s, NH), 9.97 (1H, s, NH). 13C NMR (75 MHz, CDCl3)
δ: 56.3, 109.4, 113.6, 115.0, 115.5, 120.2, 120.6, 121.1,
122.5, 124.5, 128.1, 129.1, 130.9, 131.9, 138.5, 138.7,
1-Phenyl-3-(phenylaminocarbonyl)imidazol-2(1H)-one
(9a) and 3-(phenylaminocarbonyl)-1-[(2-phenylamino-
carbonyl)phenyl]imidazol-2(1H)-one (9b)
+
1-Phenyl-3-(phenylaminocarbonyl)imidazol-2(1H)-one
(9a) and 3-(phenylaminocarbonyl)-1-[(2-phenylaminocar-
bonyl)phenyl]imidazol-2(1H)-one (9b) were made from
1-phenylimidazol-2(1H)-one 3a (0.2 g, 1.25 mmol) with n-
BuLi (1.6 mol L–1, 1.95 mL, 2.5 equiv.), then phenyl
isocyanate (0.34 mL, 3.12 mmol, 2.5 equiv.) was added giv-
ing from chromatography firstly 9a as a yellow solid
(12 mg, 3%), mp 122 °C, lit. value (18) mp 123 °C, and sec-
ondly, 9b as a white solid (300 mg, 86%), mp 150 °C. Spec-
troscopic data for 9a: IR νmax (film, cm–1): 755, 1077, 1236,
1259, 1412, 1502, 1555, 1598, 1690, 1730. 1H NMR
(300 MHz, CDCl3) δ: 6.81 (1H, d, J = 3.2, ImH), 7.20
(1H, m, ArH), 7.28 (1H, d, J = 3.2, ImH), 7.40 (4H, m,
ArH), 7.59 (5H, m, ArH), 10.91 (1H, bs, NH). 13C NMR
(75 MHz, CDCl3) δ: 108.6, 111.7, 120.0, 122.4, 124.4,
127.1, 129.0, 129.4, 136.9, 147.3, 150.3, 162.7. m/z (CI):
142.2, 154.8, 156.0, 165.3. m/z (CI): 446 (MNH4 , 2%), 429
(MH+, 4), 327 (8), 310 (100), 217 (5), 102 (5). Anal. calcd.
for. C24H20N4O4 (M): 428.148 4; found (M+): 428.149 2.
1-[(3-Methoxy-2-phenylaminocarbonyl)phenyl]-3-phenyl-
aminocarbonylimidazol-2(1H)-one (9e) and 1-(3-methoxy-
phenyl)-3-(phenylaminocarbonyl)imidazol-2(1H)-one (9f)
1-[(3-Methoxy-2-phenylaminocarbonyl)phenyl]-3-phenyl-
aminocarbonylimidazol-2(1H)-one (9e) and 1-(3-methoxy-
phenyl)-3-(phenylaminocarbonyl)imidazol-2(1H)-one
(9f)
were made from 1-(3-methoxyphenyl)imidazol-2(1H)-one 3c
(0.27 g, 1.42 mmol) with n-BuLi (1.6 mol L–1, 2.2 mL, 2.5
equiv.) then phenyl isocyanate (0.39 mL, 3.5 mmol,
2.5 equiv.) giving from chromatography firstly 9e as a white
solid (160 mg, 36%), mp 101 °C, and secondly, 9f as a white
solid (95 mg, 21%), mp 180 °C. Spectroscopic data for 9e:
© 2004 NRC Canada

Llopart et al.
1659
IR νmax (film, cm–1): 735, 1233, 1410, 1440, 1474, 1554,
1601, 1679, 1729. 1H NMR (300 MHz, CDCl3) δ: 3.91
(3H, s, OCH3), 6.60 (1H, d, J = 3.3, ImH), 7.03 (2H, t, J =
7.8, ArH), 7.12 (1H, d, J = 3.3, ImH), 7.14 (2H, m, ArH),
7.33 (4H, m, ArH), 7.52 (3H, m, ArH), 7.58 (2H, apparent
d, J = 8.4, ArH), 8.41 (1H, s, NH), 10.73 (1H, s, NH). 13C
NMR (75 MHz, CDCl3) δ: 56.3, 108.5, 111.9, 113.9, 119.6,
119.9, 120.1, 124.4, 124.6, 128.9, 129.0, 131.4, 133.0,
133.4, 136.8, 137.6, 146.9, 151.3, 157.2, 162.4. m/z (CI):
429 (MH+, 3%), 310 (12), 217 (100), 119 (10). Anal. calcd.
for. C24H20N4O4 (M): 428.148 4; found (M+): 428.148 5.
Spectroscopic data for 9f: IR νmax (film, cm–1): 758, 1263,
1441, 1474, 1597, 1680. 1H NMR (300 MHz, CDCl3) δ: 3.94
(3H, s, OCH3), 6.47 (1H, d, J = 3.0, ImH), 6.58 (1H, d, J =
3.0, ImH), 7.07 (1H, m, ArH), 7.13 (1H, m, ArH), 7.21 (2H,
d, J = 8.1, ArH), 7.32 (2H, m, ArH), 7.55 (3H, apparent t,
J = 8.1, ArH). 13C NMR (75 MHz, CDCl3) δ: 55.3, 108.9,
111.0, 113.6, 119.5, 119.9, 124.0, 124.1, 125.0, 128.3,
130.6, 132.1, 138.2, 156.0, 157.2. m/z (CI): 310 (MH+,
35%), 217 (100). Anal. calcd. for. C17H15N3O3 (M):
309.1113; found (M+): 309.110 9.
n-BuLi (1.6 mol L–1, 0.79 mL, 1.1 equiv.) at –78 °C over
30 min under N2. The solution was warmed up to then main-
tained at 0 °C for 2 h and cooled down to –78 °C again for
the addition of iodomethane (0.1 mL, 1.72 mmol, 1.5 equiv.).
The reaction mixture was allowed to warm up to rt and after
20 h quenched with satd. aq. NH4Cl, and evaporated to re-
move the THF. The white organic residue was taken up with
CH2Cl2, the solution washed with brine, dried over MgSO4
and evaporated. Column SiO2 chromatography (50%–70%–
100% of EtOAc in hexane) yielded firstly 1-(2-
methylphenyl)-3,5-dimethylimidazol-2(1H)-one 5j (28 mg,
12%) as a low mp solid, and secondly, 1-(2-methylphenyl)-
3,4-methylimidazol-2(1H)-one 5k (96 mg, 46%) as a solid
mp 130 °C. Spectroscopic data for 5j: IR νmax (film, cm–1):
1
1401, 1500, 1638, 1655, 1676, 1685. H NMR (300 MHz,
CDCl3) δ: 1.84 (3H, s, ImCH3), 3.19 (3H, s, NCH3), 5.94
(1H, bs, ImH), 7.21 (2H, m, ArH), 7.28 (1H, apparent d, J =
7.2, ArH), 7.37 (1H, apparent t, J = 7.2, ArH). 13C NMR
(75 MHz, CDCl3) δ: 10.9, 30.1, 108.5, 118.5, 127.3, 127.5,
+
129.0, 134.7, 152.7. m/z (CI): 206 (MNH4 , 15%), 189
(MH+, 100). Anal. calcd. for. C11H12N2O (M): 188.095 0;
found (M+): 188.094 9. Spectroscopic data for 5k: IR νmax
(film, cm–1): 760, 1400, 1430, 1455, 1503, 1595, 1639,
1-(4-Methoxyphenyl)-3-(phenylaminocarbonyl)imidazol-
2(1H)-one (9g) and 1-[(4-methoxy-2-phenylaminocar-
bonyl)phenyl]-3-phenylaminocarbonylimidazol-2(1H)-one
(9h)
1
1680, 1717. H NMR (300 MHz, CDCl3) δ: 2.11 (3H, s,
ImCH3), 3.26 (3H, s, NCH3), 6.33 (1H, bs, ImH), 7.21
(1H, m, ArH), 7.41 (1H, apparent t, J = 7.5, ArH), 7.37 (1H,
apparent t, J = 7.5, ArH). 13C NMR (75 MHz, CDCl3) δ:
10.2, 27.1, 104.9, 120.2, 121.1, 125.1, 125.6, 128.9, 137.3,
1-(4-Methoxyphenyl)-3-(phenylaminocarbonyl)imidazol-
2(1H)-one (9g) and 1-[(4-methoxy-2-phenylaminocar-
bonyl)phenyl]-3-phenylaminocarbonylimidazol-2(1H)-one
(9h) were made from 1-(4-methoxyphenyl)imidazol-2(1H)-
one 3d (0.24 g, 1.25 mmol) with n-BuLi (1.6 mol L–1,
1.95 mL, 2.5 equiv.), then phenyl isocyanate (0.34 mL,
3.12 mmol, 2.5 equiv) was added giving from chromatogra-
phy firstly 9g as a white foam (20 mg, 6.5%), and secondly,
9h as a white solid (0.091 g, 30%), mp 167–169 °C. Spec-
+
153.3. m/z (CI): 206 (MNH4 , 20%), 189 (MH+, 100), 175
(42). Anal. calcd. for. C11H12N2O (M): 188.095 0; found
(M+): 188.094 8.
1-(2-Methoxyphenyl)-3,5-dimethylimidazol-2(1H)-one (5l)
and 1-(2-methoxyphenyl)-3,4-dimethylimidazol-2(1H)-one
(5m)
1-(2-Methoxyphenyl)-3,5-dimethylimidazol-2(1H)-one
(5l) and 1-(2-methoxyphenyl)-3,4-dimethylimidazol-2(1H)-
one (5m) were prepared from 1-(2-methoxyphenyl)-3-
methylimidazol-2(1H)-one 5b (0.25 g, 1.2 mmol) with
n-BuLi (1.6 mol L–1, 1.3 mL, 1.5 equiv.), then iodomethane
(0.15 mL, 2.4 mmol, 2 equiv.) was added giving from chro-
1
troscopic data for 9g: H NMR (300 MHz, CDCl3) δ: 3.77
(3H, s, OCH3), 6.52 (1H, d, J = 3.2, ImH), 6.92 (2H, m,
ArH), 7.06 (1H, m, ArH), 7.13 (1H, d, J = 3.2, ImH), 7.28
(2H, m, ArH), 7.35 (2H, m, ArH), 7.49 (2H, m, ArH), 10.61
(1H, bs, NH). 13C NMR (75 MHz, CDCl3) δ: 55.9, 108.6,
112.6, 114.9, 120.3, 120.9, 124.6, 124.7, 129.3, 130.7,
137.3, 156.0, 158.9. m/z (CI): 310 (MH+, 100%), 191 (70),
94 (25). Anal. calcd. for. C17H15N3O3 (M): 309.113 3; found
(M+): 309.113 1. Spectroscopic data for 9h: 1H NMR
(300 MHz, CDCl3) δ: 3.92 (3H, s, OCH3), 6.54 (1H, d, J =
3.2, ImH), 7.14 (2H, m, ArH), 7.17 (1H, d, J = 3.2, ImH),
7.31 (4H, m, ArH), 7.39 (3H, apt, J = 7.4, ArH), 7.56
(4H, m, ArH), 8.61 (1H, bs, NH), 10.70 (1H, bs, NH). 13C
NMR (75 MHz, CDCl3) δ: 55.8, 108.7, 110.0, 114.0, 114.4,
117.3, 119.8, 120.1, 124.5, 124.6, 124.7, 129.0, 129.4,
136.5, 137.4, 137.9, 146.7, 152.0, 160.1, 164.5. m/z (CI):
429 (MH+, 5%), 310 (100), 217 (14), 119 (14). Anal. calcd.
for. C24H20N4O4 (M): 428.148 4; found (M+): 428.149 6.
matography
a mixture (129 mg) (Anal. calcd. for
C12H14N2O2 (M): 218.105 5; found (M+): 218.204 9) of 5l
1
(12%, estimated by H NMR) and its isomer 5m (36%, esti-
mated by 1H NMR) as yellow oils. Spectroscopic data for 5l:
1H NMR (300 MHz, CDCl3) δ: 2.20 (3H, s, ImCH3), 3.30
(3H, s, NCH3), 3.81 (3H, s, OCH3), 5.95 (1H, bs, ImH),
+
6.86–7.50 (4H, m, ArH). m/z (CI): 233 (MNH4 , 51%), 219
(MH+, 100). Spectroscopic data for 5m: 1H NMR
(300 MHz, CDCl3) δ: 2.12 (3H, bs, ImCH3), 3.28 (3H, s,
NCH3), 3.87 (3H, s, OCH3), 6.21 (1H, s, ImH), 7.01–7.50
+
(4H, m, ArH). m/z (CI): 233 (MNH4 , 51%), 219 (MH+,
100).
1-(4-Methoxyphenyl)-3,4-dimethylimidazol-2(1H)-one (5n)
and 1-(4-methoxyphenyl)-3,5-dimethylimidazol-2(1H)-one
(5o)
1-(4-Methoxyphenyl)-3,4-dimethylimidazol-2(1H)-one
5n and 1-(4-methoxyphenyl)-3,5-dimethylimidazol-2(1H)-
one 5o were prepared from 1-(4-methoxyphenyl)-3-methyl-
imidazol-2(1H)-one 5d (0.2 g, 0.98 mmol) with n-BuLi
(1.6 mol L–1, 0.67 mL, 1.1 equiv.), then iodomethane
Typical procedure for the reaction of 1-aryl-3-
methylimidazolones (5a–5d) with 1 equiv. of n-BuLi
and trapping with iodomethane
1-Phenyl-3,5-dimethylimidazol-2(1H)-one (5j) 1-phenyl-
3,4-dimethylimidazol-2(1H)-one (5k)
A solution of 3-methyl-1-phenyl-imidazol-2(1H)-one 5a
(0.2 g, 1.15 mmol, 1 equiv.) in anhyd. THF was treated with
© 2004 NRC Canada

1660
Can. J. Chem. Vol. 82, 2004
(0.09 mL, 1.47 mmol, 1.5 equiv.) was added giving from
chromatography firstly 5n as yellow oil (104 mg, 49%), and
secondly, 5o as a yellow solid, mp 118–120 °C (33 mg,
16%). Spectroscopic data for 5n: IR νmax (film, cm–1): 1251,
1-(3-Methoxy-2-methylphenyl)-3,4-dimethylimidazol-
2(1H)-one (5r)
1-(3-Methoxy-2-methylphenyl)-3,4-dimethylimidazol-
2(1H)-one 5r was prepared from 1-(3-methoxyphenyl)-3-
methylimidazol-2(1H)-one 5c (0.17 g, 0.83 mmol) with n-
BuLi (1.6 mol L–1, 1.3 mL, 2.5 equiv.), then iodomethane
(0.09 mL, 1.5 mmol, 1.9 equiv.) was added giving 5r as a
clear oil (0.43 mg, 24%). IR νmax (film, cm–1): 1140, 1261,
1
1516, 1678. H NMR (300 MHz, CDCl3) δ: 2.12 (3H, s,
ImCH3), 3.27 (3H, s, NCH3), 3.83 (3H, s, OCH3), 6.26 (1H,
bs, ImH), 6.94 (2H, d, J = 9.1, ArH), 7.48 (2H, d, J = 9.1,
ArH). 13C NMR (75 MHz, CDCl3) δ: 10.1, 30.4, 55.4, 105.5,
109.7, 112.2, 114.2, 123.0, 130.7, 157.1. m/z (CI): 236
1
1402, 1433, 1475, 1589, 1638, 1686. H NMR (300 MHz,
+
(MNH4 , 10%), 219 (MH+, 100), 205 (90). Anal. calcd. for
CDCl3) δ: 2.11 (3H, s, ArCH3), 2.12 (3H, bs, ImCH3), 3.28
(3H, s, NCH3), 3.86 (3H, s, OCH3), 6.04 (1H, bs, ImH), 6.86
(2H, d, J = 8.1, ArH), 7.20 (1H, t, J = 8.1, ArH). 13C NMR
(75 MHz, CDCl3) δ: 10.3, 11.1, 27.3, 55.6, 107.6, 109.5,
119.35, 119.5, 124.6, 126.4, 136.7, 152.5, 158.4. m/z (CI):
C12H14N2O2 (M): 218.105 5; found (M+): 218.105 6. Spec-
troscopic data for 5o: IR νmax (film, cm–1): 1248, 1402,
1
1461, 1514, 1638, 1684, 2361. H NMR (300 MHz, CDCl3)
δ: 1.91 (3H, s, ImCH3), 3.30 (3H, s, NCH3), 3.85 (3H, s,
OCH3), 6.02 (1H, bs, ImH), 6.98 (2H, d, J = 8.9, ArH), 7.22
(2H, d, J = 8.9, ArH). 13C NMR (75 MHz, CDCl3) δ: 10.8,
30.1, 55.0, 108.1, 114.4, 118.9, 127.9, 128.7, 153.3, 158.9.
+
250 (MNH4 , 7%), 233 (MH+, 100), 219 (25). Anal. calcd.
for C13H16N2O2 (M): 232.121 2; found (M+): 232.121 0.
+
m/z (CI): 236 (MNH4 ,10%), 219 (MH+, 100). Anal. calcd.
1-(4-Methoxy-2-methylphenyl)-3,4-dimethylimidazol-
2(1H)-one (5s)
for C12H14N2O2 (M): 218.105 5; found (M+): 218.105 2.
1-(4-Methoxy-2-methylphenyl)-3,4-dimethylimidazol-
2(1H)-one 5s was prepared from 1-(4-methoxyphenyl)-3-
methylimidazol-2(1H)-one 5d (0.1 g, 0.49 mmol, 1 equiv.)
with n-BuLi (1.6 mol L–1, 0.76 mL, 2.5 equiv.), then
iodomethane (0.076 mL, 1.22 mmol, 2.5 equiv.) was added
giving 5s as a yellow oil (0.107 g, 97%). IR νmax (film, cm–1):
1044, 1096, 1161, 1252, 1401, 1432, 1463, 1508, 1686,
Typical procedure for dilithiation of (5a–5d) with
2.5 equiv. n-BuLi and trapping with iodomethane
1-(2-Methylphenyl)-3,4-dimethylimidazol-2(1H)-one (5p)
A solution of 3-methyl-1-phenylimidazol-2(1H)-one 5a
(0.1 g, 0.57 mmol) in anhyd. THF was treated with n-BuLi
(1.6 mol L–1, 0.89 mL, 2.5 equiv.) at –78 °C over 30 min un-
der N2. The solution was warmed up to then maintained at
0 °C for 2 h and cooled down to –78 °C again for the addi-
tion of iodomethane (0.09 mL, 1.43 mmol, 2.5 equiv.). The
reaction mixture was allowed to warm up to rt and after 20 h
quenched with satd. aq. NH4Cl, and evaporated to remove
the THF. The organic residue was taken up with CH2Cl2, the
solution washed with brine, dried over MgSO4, and evapo-
rated to give the title compound 5p as a yellow oil (109 mg,
95%). IR νmax (film, cm–1): 716, 757, 1401, 1432, 1463,
1497, 1689, 1718, 2922. 1H NMR (300 MHz, CDCl3) δ: 2.15
(3H, s, ImCH3), 2.30 (3H, s, ArCH3), 3.30 (3H, s, NCH3),
6.07(1H, s, ImH), 7.25 (4H, m, ArH). 13C NMR (75 MHz,
CDCl3) δ: 10.6, 18.4, 27.7, 107.8, 119.8, 126.8, 127.7,
1
2932. H NMR (300 MHz, CDCl3) δ: 2.11 (3H, s, ArCH3),
2.18 (3H, s, ArCH3), 3.28 (3H, s, NCH3), 3.81 (3H, s,
OCH3), 6.01 (1H, s, ImH), 6.80 (2H, m, ArH), 7.12 (1H, d,
J = 8.6, ArH). 13C NMR (75 MHz, CDCl3) δ: 10.6, 18.5,
27.7, 55.7, 108.0, 112.0, 116.2, 119.4, 128.7, 129.1, 137.2,
+
142.2, 159.2. m/z (CI): 250 (MNH4 , 26%), 233 (MH+, 100),
146.2, 164.5. m/z (CI): 163 (MH+, 100%). Anal. calcd. for
C13H16N2O2 (M): 232.121 2; found (M+): 232.121 7.
References
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+
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1-(2-Methoxy-6-methylphenyl)-3,4-dimethylimidazol-
2(1H)-one (5q)
1-(2-Methoxy-6-methylphenyl)-3,4-dimethylimidazol-
2(1H)-one 5q was prepared from 1-(2-methoxyphenyl)-3-
methylimidazol-2(1H)-one 5b (0.1 g, 0.49 mmol) with
n-
BuLi (1.6 mol L–1, 0.76 mL, 2.5 equiv.), then iodomethane
(0.08 mL, 1.22 mmol, 2.5 equiv.) was added giving 5q as a
yellow oil (0.1 g, 88%). IR νmax (film, cm–1): 776, 1080,
1
1271, 1399, 1433, 1464, 1475, 1495, 1687, 2928. H NMR
(300 MHz, CDCl3) δ: 2.11 (3H, s, ImCH3), 2.17 (3H, s,
ArCH3), 3.29 (3H, s, NCH3), 3.78 (3H, s, OCH3), 5.97
(1H, s, ImH), 6.80 (1H, d, J = 8.0, ArH), 6.87 (1H, d, J =
8.0, ArH), 7.23 (1H, t, J = 8.0, ArH). 13C NMR (75 MHz,
(CD3)2CO) δ: 9.7, 17.5, 30.0, 55.5, 107.8, 109.6, 112.5,
119.2, 120.7, 122.3, 128.9, 134.4, 156.4. m/z (CI): 250
+
(MNH4 18, 4%), 232 (MH+, 100), 219 (30). Anal. calcd. for
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C13H16N2O2 (M): 232.121 2; found (M+): 232.121 5.
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© 2004 NRC Canada