Synthesis of functionalised cyclic nitrones via regioselective and unusual [3 + 2] cycloadditions of α-nitrosostyrenes with 1,3-diazabuta-1,3-dienes and imines

Article abstract of DOI:10.1039/a702254i

The α-nitrosostyrenes 2, generated in situ from α-halogeno oximes, undergo regioselective [3 + 2] cycloaddition with 1,3-diazabuta-1,3-dienes 1 and 5 leading to the cyclic nitrones 3 and 6, respectively. Similarly, the cyclic nitrones 12 are also formed i

Full text of DOI:10.1039/a702254i

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Synthesis of functionalised cyclic nitrones via regioselective and
unusual [3 ؉ 2] cycloadditions of á-nitrosostyrenes with 1,3-
diazabuta-1,3-dienes and imines
Arun K. Sharma,a Sujit N. Mazumdara and Mohinder P. Mahajan*,a,b
a Department of Chemistry, North-Eastern Hill University, Shillong-793 003, India
b Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143 005,
India
The á-nitrosostyrenes 2, generated in situ from á-halogeno oximes, undergo regioselective [3 ϩ 2]
cycloaddition with 1,3-diazabuta-1,3-dienes 1 and 5 leading to the cyclic nitrones 3 and 6, respectively.
Similarly, the cyclic nitrones 12 are also formed in reactions of 2 with the trisubstituted amidines 11.
Thermolysis of the nitrones 3 and 12d–f gives imidazole derivatives 13. The nitrones 6, on the other hand,
on thermolysis under similar conditions, give the amidine derivatives 17. Interestingly, the treatment of
both 3 and 6 with NaBH4 in methanol and the reactions of 2 with N-arylbenzamidines also yield the
imidazole derivatives 13.
The nitroso group is known to participate effectively as a 2π
C6H4R-p
Ph
NC6H4R-p
component in Diels–Alder cycloadditions.1 On the other hand
nitrosoalkenes, usually generated in situ by the reactions of
α-halogeno ketoximes with bases,2 have been successfully
trapped as 4π components in Diels–Alder cycloadditions with a
variety of polarised and unpolarised alkenes,2 allenes3 and all-
carbon dienes.4 In almost all these cases, the major isolable
product is an oxazine derivative. Recently, an unusual [3 ϩ 2]
cycloaddition has been observed in the reactions of α-nitroso-
styrenes with a carbon–carbon double bond attached to the
pyrimidinone ring.5
There are numerous reports concerning the cycloadditions of
α-nitrosostyrenes with carbon–carbon double bonds. In con-
trast, the reports concerning the cycloadditions with carbon–
nitrogen double bonds are very rare.6 Mackay et al., while
investigating the reactions of 2,5-dimethylfuran with α-nitroso-
alkenes, isolated, in addition to an oxazine derivative, a second
product, a cyclic nitrone, arising from [3 ϩ 2] cycloaddition of
the second nitrosoalkene molecule with the oxazine derivative.
However, the authors failed to observe the reactions of α-
nitrosoalkenes with various cyclic and acyclic models bearing a
carbon–nitrogen double bond and hence such a cycloaddition
mode could not be generalised. Thus, they concluded that the
preliminary requirement for such reactions are (i) oxazine
oxygen and (ii) an alkene function allylic to this oxygen in a
rigid bicyclic system.
The observed formation of cyclic nitrones resulting from the
[3 ϩ 2] cycloaddition of nitrosoalkene is thought to be of great
synthetic utility since the methods of preparing such nitrones,
which can provide a flexible entry into a range of heterocyclic
targets, are limited to a relatively few routes.7–10 Since so
little was known about the cycloadditions of carbon–nitrogen
double bonds with nitrosoalkenes and because of the reported
structural limitations upon the carbon–nitrogen double bond
systems for carrying out such cycloadditions, we earlier investi-
gated the reactions of 1,3-diazabuta-1,3-dienes and amidines
with α-nitrosostyrenes.11 Here we report further work in this
area in which we have attempted to generalise the observed
cycloaddition pathway.
Ph
N
C6H4R2-p
N
R1
N
+
Ha
+
i
N
R1
N
R3
1/5
O
R3
O–
2
Ha
R2
1 R = H, Me R1 = H, Me
R3 = NMe2
5 R = H, Me R1 = SMe, SEt
R3 = Secondary amine
R
2 = H, Me
3 (R3 = NMe2)/6
3a R = R1 = R2 = H
b R = Me, R1 = R2 = H
c R = Cl, R1 = R2 = H
d R = Br, R1 = R2 = H
e R = R1 = H, R2 = Me
f R = R2 = Me, R1 = H
g R = Cl, R1 = H, R2 = Me
h R = Br, R1 = H, R2 = Me
i R = R1 = Me, R2 = H
j R = R1 = R2 = Me
Ar
Ph
N
N
O
N
Ar
N
R1
4
6
a R = R2= H, R1 = SMe, R3 = Mor
b R = R2 = H, R1 = SMe, R3 = Pip
c R = R2 = H, R1 = SMe, R3 = Pyr
d R = R2 = H, R1 = SMe, R3 = NMe2
e R = Me, R1 = SMe, R2= H, R3 = Mor
f R = Me, R1 = SMe, R2 = H, R3 = Pip
g R = Me, R1 = SMe, R2 = H, R3 = Pyr
h R = Me, R1 = SMe, R2 = H, R3 = NMe2
i R = R2 = H, R1 = SEt, R3 = Mor
j R = R2 = H, R1 = SEt. R3 = Pyr
Mor
=
k R = H, R1 = SMe, R2 = Me, R3
l R = R2 = Me, R1 = SMe, R3 = Mor
m R = R2 = Me, R1 = SMe, R3 = Pip
n R = R2 = Me, R1 = SMe, R3 = Pyr
o R = R2 = Me, R1 = SMe, R3 = NMe2
p R = Cl, R1 = SMe, R2 = H, R3 = Pip
q R = Cl, R1 = SMe, R2 = Me, R3 = NMe2
r R = Cl, R1 = SEt, R2 = H, R3 = Pyr
s R = Cl, R1 = SEt, R2 = H, R3 = NMe2
Scheme 1 Reagents and conditions: i, Na2CO3, CH2Cl2, 34–48 h
(Mor = morpholino, Pyr = pyrrolidinyl, Pip = piperidino)
(78–93%) of the cyclic nitrones 3 (Scheme 1). The products were
characterised as 1,4-diaryl-2-(dimethylaminomethyleneamino/
dimethylaminoethylideneamino)-2-phenyl-1,2-dihydro-5H-
imidazole 3-oxides 3 on the basis of analytical and spectral
data. The detailed spectral features are discussed in the
Experimental section, only the salient features being mentioned
here. Their IR spectra showed strong absorptions around 1590
and 1521 cmϪ1 and ca. 1220 cmϪ1 ascribed to C᎐N and N᎐O of
a nitrone, respectively. The nitrone structure 3, as opposed to
the oxadiazine structure 4, for the products was supported by
the H NMR signals for the methylene and ortho phenyl pro-
The 1,3-diazabuta-1,3-dienes 1 reacted with the nitroso-
styrenes 2, generated in situ from α-halogeno oximes and
sodium carbonate, in methylene chloride, to give good yields
᎐
1
tons of the nitrone ring. The former gave an AB quartet
(unresolved at 90 MHz but resolved at 200 MHz) at δ ca. 4.95
* Correspondence should be sent to address b.
J. Chem. Soc., Perkin Trans. 1, 1997
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(J 14.4 Hz) downfield from the position, δ ca. 3.50, typical of
oxadiazine.6a Similarly, the ortho protons of the phenyl group
attached to the nitrone ring resonated at δ ca. 8.40 downfield
from the corresponding signals, δ ca. 7.70 of typical oxazines.2b
The signals around δ 140 and 160 in their 13C NMR spectra
were assigned to nitrone carbon and amidino carbon, respect-
ively. Their mass spectra exhibited intense M Ϫ 16 peaks diag-
nostic of nitrones,6a in addition to strong M Ϫ amidino and
imidazole ion peaks. The oxadiazine structure 4 thus was clear-
ly ruled out on the basis of the above spectral information.
Further to our studies on such regioselective [3 ϩ 2] cyclo-
additions, we examined the reactions of α-nitrosostyrenes with
various 1-aryl-4-secondary amino-4-alkylthio-2-phenyl-1,3-
diazabuta-1,3-dienes 5 having two polarising functions at the
4-position. Thus, the reactions of α-nitrosoalkenes with 1,3-
diazabuta-1,3-dienes 5, performed under similar conditions,
were found to follow a similar regioselective [3 ϩ 2] cyclo-
addition pathway to yield the nitrones 6 in almost quantitative
yields (Scheme 1). The reaction products were characterised as
1,4-diaryl-2-phenyl-2-[(methylthio)secondaryaminomethylene-
amino]-1,2-dihydro-5H-imidazole 3-oxides 6 on the basis of
analytical and spectral observations. The 1H NMR spectra (90
MHz, CDCl3) of these nitrones exhibited a two-proton doublet/
multiplet centred around δ 8.40, assigned to two ortho phenyl
protons Ha characteristic of cyclic nitrones. The methylene
protons appeared, in these cases, as a singlet around δ 5.00.
A possible mechanism leading to the formation of nitrones 3
and 6 is illustrated in Scheme 2. The addition of nitrosoalkenes
be explained by the initial formation of a resonance-stabilised
cationic intermediate 10 via nucleophilic displacement of halide
by N-1 of 1,3-diazabuta-1,3-dienes 1 and 5 from α-chloroaceto-
phenone oxime. The intermediates 10 after possible deproton-
ation may then cyclise to yield the nitrones 3 and 6. Analogies to
such a two-step cyclisation of α-chloro oximes are known14
including ones to N-oxides.15 However, in all such cases, a
recognisably strong nucleophile is involved and it is unlikely
that weaker nucleophiles like N-1 of imino nitrogen in the
present case could behave in a similar fashion. This is also in
agreement with the earlier conclusions drawn about the inter-
mediacy of nitrosostyrenes under similar reaction conditions.6a
In view of the above observations, it was felt that all polar-
ised carbon–nitrogen double bonds might perhaps behave in a
similar fashion with addition to α-nitrosoalkenes in a similar
[3 ϩ 2] manner. Hence, in order to generalise the synthetic
versatility of this reaction we have examined the reactions of
the α-nitrosostyrenes 2 with N,N,NЈ-trisubstituted amidines 11.
As expected, these reactions were also found to follow the
unusual and exclusive [3 ϩ 2] cycloaddition mode resulting in
good yields of the nitrones 12 (Scheme 3) which were character-
C6H4R-p
R1
N
C6H4R-p
N
i
+
R3
+
2
N
R3
R1
C6H4R2-p
O–
11
R = H, Me
1 = H, Ph
R3 = NMe2, Pyr, Pip
12
11,12a R = R1 = R2 = H, R3 = NMe2
b R = Me, R1 = R2 = H, R3 = NMe2
c R = R1= H, R2 = Me, R3 = NMe2
d R = H, R1 = Ph, R2 = Me, R3 = Pyr
e R = R2 = H, R1 = Ph, R3 = Pip
R
Ar
Ar
Ph
N
Ph
N
N
–
R1
N
O
O
f R = H, R1 = Ph, R2 = Me, R3 = Pip
+
N
Ar
Ar
N
N
Ar
N
N
R1
Scheme 3 Reagents and conditions: i, Na2CO3, CH2Cl2, 40–52 h
8
9
Ar
O
Ph
Path II
+
R1
ised on the basis of analytical and spectral data. Interestingly,
N
N
1
Ar
Ar
the H NMR (300 MHz) spectrum of 12b indicated that two
N+ Cl–
Ph
Ph
N
N
methylene protons couple with each other as well as with the
methine proton and appeared as a doublet of doublets. The
corresponding coupling constants are also exhibited by the
methine proton signal which couple with both methylene pro-
tons and appear as a doublet of doublets. Further support for
Path I
R1
R1
N
N
Ar
N
+
N
Ar
1/5
N
O–
N
O
H
Ar
N
1
7
Ph
N
this was derived from the H NMR spectrum of 12d in which
10
the two methylene protons appeared as doublets instead of a
doublet of doublets. In contrast to the formation of nitrones in
the above reactions, Nakanishi et al.16 reported the formation
of imidazole derivatives probably via oxadiazines, in the
reactions of α-halogeno oximes with N-phenyl-N-methylbenz-
amidines in the presence of iron carbonyls.
N
Ar
N
O–
R1
3/6
Scheme 2
The structures 3, 6 and 12 for cyclic nitrones were further
confirmed by thermal degradation studies. Thermolysis of
the nitrones 3 in dry benzene in a sealed tube at 140–150 ЊC
for 6–7 h resulted in the isolation of products which were
characterised as 1,4-diaryl-2-phenylimidazoles on the basis
of analytical data and spectral evidences. Compound 13a, for
example, had an analysis consistent with its formation as
C21H16N2 and exhibited a molecular ion peak at m/z 296. Its 1H
NMR spectrum showed both the absence of a formamidino
unit and the presence of two downfield (ca. δ 7.92) ortho phenyl
protons together with a multiplet consisting of other aromatic
protons and an olefinic proton. The products 13 were initially
assigned the corresponding N-oxide structures 1411 because of
expected similar spectral features and the tendency of nitrones
to show the absence of a molecular ion peak and the presence
of intense Mϩ Ϫ 16 peaks in their mass spectra. However,
elemental analysis, which indicated the absence of oxygen in
these compounds, and other spectroscopic features are more
consistent with the revised structure 13.
to a C᎐C bond has been reported to be a single-step reaction,12
᎐
which is less likely in the case of addition to a more polar C᎐N
᎐
bond of diazabuta-1,3-dienes. Hence, the possibility of path I in
these cases is ruled out. α-Nitrosostyrene is known to react with
morpholine13 preferentially in the transoid form and may also
do so with weakly nucleophilic N-1, which is more nucleophilic
as compared to N-3 of 1,3-diazabuta-1,3-dienes. Hence, these
reactions may follow path II leading to resonance stabilised
zwitterionic intermediate 7 which then leads to the preferential
formation of the nitrones 3 and 6. Even though intermediate
7 may be preferred, still a crossover mechanism between the
intermediates 7 and 8 is possible, which could result in a six-
membered oxadiazine ring structure 9. The crossing over of the
zwitterionic intermediate 7 to 8 perhaps is discouraged due to
steric constraints as evidenced by the total absence of oxadi-
azines 9. Thus, the nitrones are probably the result of the formal
[3 ϩ 2] dipolar addition of free α-nitrostyrene in a 1,3-mode to
a 1,2-carbon–nitrogen double bond of the polarised 1,3-
diazabuta-1,3-dienes. The formation of the nitrones may also
To gain insight into the mechanism of formation of product
3066
J. Chem. Soc., Perkin Trans. 1, 1997

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13, the thermolysis of imidazole N-oxides 12d–f was carried out
under similar conditions. Interestingly, this also resulted in the
formation of the imidazoles 13. The formation of 13 by the
thermolysis of 3 and 12d–f may possibly arise via any of the
two paths illustrated in Scheme 4. Path I assumes the initial
plausible mechanistic pathways involved in this transformation
are shown in Scheme 6. In this mechanism it is assumed that the
i
13
3/6
C6H4R-p
C6H4R-p
C6H4R-p
C6H4R-p
N
13a R = R2 = H
b R = Me, R2 = H
c R = H, R2 = Me
H
N
Ph
N
N
i
Ph
3/ 12d-f
Ph
Ph
H
Ph
N
C6H4R2-p
HN
C6H4R1-p
H2N
N
C6H4R1-p
N
C6H4R1-p
N
NH
13
O–
19
OH
20
OH
Ar
N
Ar
N
21
Path I
Ph
Path I
Path II
C6H4R-p
+
+
N
ii
R
N
N
+ 2
Ar
Ar
O–
3/ 12d-f
O–
H2N
Ph
14
Path II
22
R = H, Me
Ar
Ar
N
R =
Scheme 6 Reagents and conditions: i, NaBH4, MeOH, RT, 20–22 h;
N
N
Ph
R
N
H
Ph
H,
ii, Na2CO3, CH2Cl2, 2–3 h
Deoxygenation
Ar
H
Pip, Pyr,
13
O
O
N
N
Ar
sodium borohydride reduction of the amidino carbon–nitrogen
double bond of the nitrones 3 and 6 leads initially to the
2-amino N-oxide intermediate 19, which, probably being
unstable, is transformed into the intermediate 20. The inter-
medate 20 then cyclises, as shown, to yield another intermediate
21 which ultimately undergoes elimination of H2NOH to yield
the imidazoles 13. The mechanistic paths I and II proposed
earlier (Scheme 4) for the transformation of imidazole N-oxides
into the imidazoles 13 may be ruled out in this case because the
conversion of N-oxide intermediate 14 into bicyclic inter-
mediate 16 (Path I) and interconversion of nitrones to oxazines
(Path II) are less likely at room temperature.
In order to confirm the mechanism proposed above, we have
investigated the reactions of simple N-arylbenzamidines 22
with α-nitrosostyrenes 2. It was thought that the absence of any
N-oxide 19 should confirm its unstable nature and the form-
ation of the imidazoles 13 could confirm the mechanism pro-
posed in Scheme 6. The reaction of 22 with 2 resulted in the
isolation of the expected imidazoles 13. The formation of 13 in
this case could either be explained via the intermediates 19, 20
and 21 (Path I) or via initial displacement of halide from the
α-chloro oxime leading to the intermediate 20 which by the
depicted path II then yields 13 via 21 (Scheme 6).
N
N
15
16
Me
Scheme 4 Reagents and conditions: i, Sealed tube, 140–150 ЊC, C6H6,
6–7 h
elimination of
a dimethylaminomethyleneamino/dimethyl-
aminoethylideneamino/secondary amino moiety to give the N-
oxide 14, which is then transformed into a bicyclic intermediate
16 and finally deoxygenated to yield 13. Path II proposes that
the nitrones 3 and 12d–f, at elevated temperatures, are inter-
convertible with the corresponding oxadiazines 15. Elimination
of a formamidino/acetamidino/secondary amino moiety from
this oxadiazine intermediate 15 leads to the bicyclic intermedi-
ate 16 which then undergoes the customary deoxygenation to
give 13. Pathway II seems to be more plausible because such
nitrone to oxazine17 and oxazine to imidazole16 interconver-
sions are already known in the literature.
However, the thermolysis of the nitrones 6, under similar
conditions, yielded the amidine derivatives 17 (Scheme 5).
C6H4R-p
C6H4R-p
In conclusion, the reactions of various polarised 1,3-diaza-
buta-1,3-dienes and amidines with α-nitrosostyrenes undergo
regioselective and unusual [3 ϩ 2] cycloadditions and offer an
interesting route to a variety of substituted cyclic nitrones. The
thermolysis of most of these cyclic nitrones resulted in the
formation of imidazole derivatives via oxazine intermediates.
Ph
Ph
NH
N
i
6 d,e
N
N
O
N
C6H4R2-p
O
R3
R3
17a R = H, R3 = NMe2
b R = Me, R3 = Mor
18
Scheme 5 Reagents and conditions: i, Sealed tube, 140–150 ЊC, C6H6,
6–7 h
Experimental
Melting points were determined with a Toshniwal melting point
apparatus and are uncorrected. IR spectra were recorded on
a Perkin-Elmer 983 Infrared Spectrophotometer. 1H NMR
spectra were recorded in deuteriochloroform, with a Varian 390
(90 MHz) and Bruker AC-F 300 (300 MHz) Spectrometer
using TMS as internal standard. Chemical shift values are
expressed as δ (ppm) downfield from TMS and J values are in
Hz. Splitting patterns are indicated as: s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet and br = broad. 13C NMR
spectra were also recorded on a Bruker AC-F 300 spectrometer
in deuteriochloroform using TMS as internal standard. Mass
spectra were obtained by electron impact at 70 eV. Column
chromatography was performed on silica gel 60–120 mesh.
Structure 17 was readily established on the basis of analytical
and spectral evidence. Compound 17a, for example, showed a
molecular ion peak at m/z 267 and IR absorptions at 3422br
and 1635 cmϪ1 assigned to NH and CO groups respectively. Its
1H NMR spectrum exhibited the absence of alkylthio and
the presence of dimethylamino protons, in addition to an
exchangeable proton (δ 12.40). The mechanism involved in the
transformation of nitrones 6 to 17 is not well understood.
However, it is assumed that there might be an initial attack of
N-oxide oxygen on the imino carbon leading to an intermediate
18 which on subsequent degradation might yield the products
17.
Interestingly, the treatment of both the nitrones 3 and 6 with
sodium borohydride in methanol at room temperature for 20–
22 h resulted again in the isolation of the imidazoles 13. The
Starting materials
All the 1,3-diazabuta-1,3-dienes 1, 5,18 N-arylformamidines
J. Chem. Soc., Perkin Trans. 1, 1997
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11a–c,19 N-arylbenzamidines 22,20 and the chloro oximes 221 of
acetophenone and p-methylacetophenone were prepared by
reported procedures.
C, 75.35; H, 6.58; N, 14.06); νmax/cmϪ1 (KBr) 1593, 1519 and
1223; δH(90 MHz) 2.38 (s, 3H, CH3), 2.80–3.00 [br d, 6H,
N(CH3)2], 4.93–5.00 (unresolved ABq, 2H, CH2), 6.63–6.76 (m,
2H, ArH), 7.03–7.40 (m, 8H, ArH), 7.50 (s, 1H, N᎐CH), 7.63–
᎐
General procedure for the preparation of N-aryl-2-secondary
amino benzamidines 11d–f
7.80 (m, 2H, ArH) and 8.26–8.35 (d, J 8.0, 2H, ArH); m/z 398
(Mϩ).
A solution of imidoyl chloride (10 mmol) and secondary amine
(22 mmol) in THF (30 ml) was stirred at room temperature
(RT) for 3 h. The reaction mixture was then filtered and the
residue washed with THF (10 ml). The combined filtrates were
concentrated in vacuo and the residue thus obtained was diluted
with CH2Cl2 (30 ml), washed with water (3 × 100 ml), dried
(Na2SO4) and evaporated under reduced pressure. The residue
was purified by column chromatography on silica gel.
1,4-Bis(p-tolyl)-2-(dimethylaminomethyleneamino)-2-phenyl-
1,2-dihydro-5H-imidazole-3-oxide 3f. Yield 90%; mp 135 ЊC
(Found: C, 76.12; H, 6.78; N, 13.47. C26H28N4O requires C,
75.70; H, 6.84, N, 13.58); νmax/cmϪ1 (KBr) 1589, 1523 and 1226;
δH(90 MHz) 2.16 (s, 3H, CH3), 2.36 (s, 3H, CH3), 2.80–2.98 [br
d, 6H, N(CH3)2], 4.90–4.94 (unresolved ABq, 2H, CH2), 6.63–
7.00 (m, 2H, ArH), 7.20–7.33 (m, 8H, ArH), 7.50 (s, 1H,
N᎐CH), 7.62–7.76 (m, 2H, ArH) and 8.20–8.33 (d, J 8.0, 2H,
᎐
ArH); m/z 412 (Mϩ).
Reactions of 1,3-diazabuta-1,3-dienes 1 and 5 with á-nitroso-
styrenes 2
1-(p-Chlorophenyl)-2-(dimethylaminomethyleneamino)-2-
phenyl-4-(p-tolyl)-1,2-dihydro-5H-imidazole 3-oxide 3g. Yield
76%; mp 193 ЊC (Found: C, 69.67; H, 5.78; N, 12.84. C25H25-
N4OCl requires C, 69.42; H, 5.83; N, 12.96); νmax/cmϪ1 (KBr)
1583, 1520 and 1219; δH(90 MHz) 2.38 (s, 3H, CH3), 2.83–2.93
[br d, 6H, N(CH3)2], 4.90–4.93 (unresolved ABq, 2H, CH2),
6.63–6.74 (m, 2H, ArH), 7.14–7.36 (m, 7H, ArH), 7.50 (s, 1H,
General procedure for nitrones 3 and 6. A solution of the 1,3-
diazabuta-1,3-diene 1/5 (4.0 mmol) and the α-chloro oxime (4.2
mmol) in dry CH2Cl2 (40 ml) was stirred at RT in the presence
of anhydrous sodium carbonate (6 mmol) for 34–48 h. The
deposited salt and excess of sodium carbonate were filtered off
and washed with small portions (2 × 10 ml) of CH2Cl2. The
combined filtrates were washed with water, dried (Na2SO4) and
concentrated under reduced pressure. Trituration of the residue
with ether gave the crude product which was recrystallised from
benzene–hexane (2:1).
2-(Dimethylaminomethyleneamino)-1,2,4-triphenyl-1,2-di-
hydro-5H-imidazole 3-oxide 3a. Yield 80%; mp 131–132 ЊC
(Found: C, 75.52; H, 6.31; N, 14.60. C24H24N4O requires C,
74.96; H, 6.30; N, 14.58); νmax/cmϪ1 (KBr) 1591, 1525 and
1225; δH(90 MHz) 2.81–2.93 [br d, 6H, N(CH3)2], 4.93–4.97
(unresolved ABq, 2H, CH2), 6.72–6.80 (m, 2H, ArH), 7.01–
N᎐CH), 7.60–7.73 (m, 2H, ArH) and 8.23–8.35 (d, J 8.0, 2H,
᎐
ArH); m/z 432 (Mϩ).
1-(p-Bromophenyl)-2-(dimethylaminomethyleneamino)-2-
phenyl-4-(p-tolyl)-1,2-dihydro-5H-imidazole 3-oxide 3h. Yield
90%; mp 198 ЊC (Found: C, 63.29; H, 5.27; N, 11.71. C25H25-
N4OBr requires C, 63.01; H, 5.29; N, 11.76); νmax/cmϪ1 (KBr)
1585, 1521 and 1223; δH(200 MHz) 2.42 (s, 3H, CH3), 2.87 (s,
3H, NCH3), 3.40 (s, 3H, CH3), 4.94 (ABq, J 14.4, 2H, CH2),
6.72 (AAЈBBЈ, J 9.1, 2H, ArH), 7.20–7.40 (m, 7H, ArH), 7.54
(s, 1H, N᎐CH), 7.65–7.73 (m, 2H, ArH) and 8.30 and 8.34
᎐
(d, J 8.3, 2H, ArH); δC(75.5 MHz) 21.5 (CH3), 34.3 (NCH3),
40.3 (NCH3), 50.4 (C-5), 103.8 (C-2), 110.2 (C-10), 115.6
(C-8, 8Ј), 139.5, 141.1, 141.5 (C-2, 4, 7), 124.4, 126.8, 128.1,
128.8, 129.2, 131.3, 131.9 (ArH) and 154.7 (C-12); m/z 476
(Mϩ).
2,4-Diphenyl-1-(p-tolyl)-2-(1-dimethylaminoethylideneamino)-
1,2-dihydro-5H-imidazole 3-oxide 3i. Yield 86%; mp 140–141 ЊC
(Found: C, 75.81; H, 6.81; N, 13.51. C26H28N4O requires C,
75.70; H, 6.84; N, 13.58); νmax/cmϪ1 (KBr) 1580, 1521 and 1217;
δH(90 MHz) 1.82 (s, 3H, CH3), 2.23 (s, 3H, CH3), 3.17 [s, 6H,
N(CH3)2], 5.08 (s, 2H, CH2), 6.72 (d, J 8.2, 2H, ArH), 7.00 (d,
J 8.2, 2H, ArH), 7.25–7.56 (m, 6H, ArH), 7.72–7.87 (m, 2H,
ArH) and 8.40–8.56 (m, 2H, ArH); m/z 412 (Mϩ) and 396
(Mϩ Ϫ 16).
7.43 (m, 9H, ArH), 7.48 (s, 1H, N᎐CH), 7.60–7.74 (m, 2H,
᎐
ArH) and 8.30–8.43 (d, J 8.0, 2H, ArH); δC(75.5 MHz) 49.2,
51.0 [N(CH3)2], 66.8 (C-5), 100.9 (C-2), 113.1 (C-8/8Ј), 118.2
(C-10), 140.5, 141.2, 141.5 (C-7/8/9), 133.2 (C-6), 126.8,
127.9, 128.2, 128.7, 128.8, 130.5 and 160.7 (C-12); m/z 384
(Mϩ).
2-(Dimethylaminomethyleneamino)-2,4-diphenyl-1-(p-tolyl)-
1,2-dihydro-5H-imidazole 3-oxide 3b. Yield 86%; mp 151 ЊC
(Found: C, 75.50; H, 6.57; N, 14.00. C25H26N4O requires C,
75.35; H, 6.58; N, 14.07); νmax/cmϪ1 (KBr) 1597, 1520 and 1221;
δH(90 MHz) 2.42 (s, 3H, CH3), 2.86–2.97 [br d, 6H, N(CH3)2],
4.85–4.93 (unresolved ABq, 2H, CH2), 6.66–6.80 (m, 2H, ArH),
7.03–7.36 (m, 8H, ArH), 7.51 (s, 1H, N᎐CH), 7.56–7.88 (m, 2H,
᎐
ArH) and 8.23–8.33 (d, J 8.0, 2H, ArH); δC(75.5 MHz) 20.2
(CH3), 34.4 and 40.3 [N(CH3)2], 50.5 (C-5), 104.2 (C-2), 113.8
(C-7), 127.0, 127.4 (C-8/10), 131.7 (C-9), 139.9, 140.1 (C-4/6),
126.7, 128.0, 128.2, 128.5, 128.7, 129.2, 130.4 and 154.8 (C-12);
m/z 398 (Mϩ).
1-(p-Chlorophenyl)-2-(dimethylaminomethyleneamino)-2,4-
diphenyl-1,2-dihydro-5H-imidazole 3-oxide 3c. Yield 76%; mp
188–189 ЊC (Found: C, 69.10; H, 5.53; N, 13.42. C24H23N4OCl
requires C, 68.87; H, 5.54; N, 13.38); νmax/cmϪ1 (KBr) 1589,
1521 and 1223; δH(90 MHz) 2.85–2.92 [br d, 6H, N(CH3)2],
4.92–4.95 (unresolved ABq, 2H, CH2), 6.66–6.76 (m, 2H, ArH),
1,4-Bis(p-tolyl)-2-phenyl-2-(1-dimethylaminoethylidene-
amino)-1,2-dihydro-5H-imidazole 3-oxide 3j. Yield 89%; mp
141–143 ЊC (Found: C, 75.94; H, 7.12; N, 13.19. C27H30N4O
requires C, 76.03; H, 7.09; N, 13.13); νmax/cmϪ1 (KBr) 1596,
1521 and 1221; δH(90 MHz) 1.75 (s, 3H, CH3), 2.17 (s, 3H,
CH3), 2.36 (s, 3H, CH3), 3.05 [s, 6H, N(CH3)2], 4.88 (s, 2H,
CH2), 6.62 (d, J 8.4, 2H, ArH), 6.90 (d, J 8.4, 2H, ArH), 7.11–
7.28 (m, 5H, ArH), 7.56–7.71 (m, 2H, ArH) and 8.20 (d, J 8.0,
2H, ArH); δC(75.5 MHz) 13.5 (CH3), 20.1 (CH3), 21.5 (CH3),
38.4 [N(CH3)2], 50.6 (CH2), 101.8 (C-2), 113.2, 124.7, 126.5,
126.6, 127.7, 127.8, 128.2, 129.1, 129.2, 131.3, 140.0, 140.7
(C-4), 142.7, 161.8 (C-dimethylaminoethylideneamino); m/z
426 (Mϩ), 410 (Mϩ Ϫ 16).
7.03–7.36 (m, 8H, ArH), 7.54 (s, 1H, N᎐CH), 7.57–7.70 (m, 2H,
᎐
ArH) and 8.33–8.43 (d, J 8.0, 2H, ArH); m/z 418 (Mϩ).
1-(p-Bromophenyl)-2-(dimethylaminomethyleneamino)-2,4-
diphenyl-1,2-dihydro-5H-imidazole 3-oxide 3d. Yield 78%; mp
193–194 ЊC (Found: C, 62.01; H, 4.91; N, 12.14. C24H23N4OBr
requires C, 62.32; H, 5.02; N, 12.12); νmax/cmϪ1 (KBr) 1586,
1521 and 1225; δH(90 MHz) 2.85–3.00 [br d, 6H, N(CH3)2],
4.92–4.95 (unresolved ABq, 2H, CH2), 6.63–6.73 (m, 2H, ArH),
2-[Methylthio(morpholino)methyleneamino]-1,2,4-triphenyl-
1,2-dihydro-5H-imidazole 3-oxide 6a. Yield 72%; mp 161.5–
162.5 ЊC (Found: C, 68.59; H, 5.96; N, 11.87. C27H28N4O2S
requires C, 68.62; H, 5.97; N, 11.85); νmax/cmϪ1 (KBr) 1599,
1547 and 1229; δH(90 MHz) 2.06 (s, 3H, CH3), 3.73 (br s, 8H,
morpholino), 5.03 (s, 2H, CH2), 6.78 (d, J 8.5, 2H, ArH), 7.18
(d, J 8.5, 2H, ArH), 7.33–7.56 (m, 7H, ArH), 7.73–7.90 (m, 2H,
ArH) and 8.40–8.56 (m, 2H, ArH); m/z 472 (Mϩ).
7.20–7.56 (m, 9H, ArH and N᎐CH), 7.58–7.70 (m, 2H, ArH)
᎐
and 8.30–8.43 (d, J 8.0, 2H, ArH); m/z 463 (Mϩ).
2-(Dimethylaminomethyleneamino)-1,2-diphenyl-4-(p-tolyl)-
1,2-dihydro-5H-imidazole 3-oxide 3e. Yield 85%; mp 149–
150 ЊC (Found: C, 75.10; H, 6.56; N, 14.10. C25H26N4O requires
2-[Methylthio(piperidino)methyleneamino]-1,2,4-triphenyl-
1,2-dihydro-5H-imidazole 3-oxide 6b. Yield 88%; mp 145–
146.5 ЊC (Found: C, 71.40; H, 6.43; N, 11.97. C28H30N4OS
3068
J. Chem. Soc., Perkin Trans. 1, 1997

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requires C, 71.46; H, 6.42; N, 11.90); νmax/cmϪ1 (KBr) 1599,
1553 and 1222; δH(90 MHz) 1.56–1.75 (br s, 6H, CH2CH2CH2),
2.06 (s, 3H, SCH3), 3.60–3.76 (br s, 4H, CH2NCH2), 5.06 (s, 2H,
CH2), 6.78 (d, 2H, ArH), 7.20 (d, 2H, ArH), 7.40–7.60 (m, 7H,
ArH), 7.83–7.95 (m, 2H, ArH) and 8.35–8.60 (m, 2H, ArH);
m/z 470 (Mϩ).
Table 1
Entry
Product
Yield (%)
Mp (ЊC)
1
2
3
4
5
6
7
8
9
6c
6d
6e
6f
6j
79
75
82
82
83
88
93
78
88
84
143–144.5
149–150
147.5–148.5
149–150
154–155
154–155
2,4-Diphenyl-1-(p-tolyl)-2-[methylthio(pyrrolidino)methylene-
amino]-1,2-dihydro-5H-imidazole 3-oxide 6g. Yield 91%; mp
145–146.5 ЊC (Found: C, 71.55; H, 6.48; N, 11.82. C28H30N4OS
requires C, 71.46; H, 6.42; N, 11.90); νmax/cmϪ1 (KBr) 1597,
1549 and 1229; δH(90 MHz) 1.96–2.00 (m, 4H, 2 × CH2), 2.06
(s, 3H, SCH3), 2.20 (s, 3H, CH3), 3.70–3.76 (m, 4H, CH2NCH2),
5.03 (s, 2H, CH2), 6.71 (d, J 8.8, 2H, ArH), 7.01 (d, J 8.8, 2H,
ArH), 7.30–7.50 (m, 6H, ArH), 7.80–7.90 (m, 2H, ArH) and
8.43–8.53 (m, 2H, ArH); m/z 470 (Mϩ).
2-[Dimethylamino(methylthio)methyleneamino]-2,4-diphenyl-
1-(p-tolyl)-1,2-dihydro-5H-imidazole 3-oxide 6h. Yield 78%; mp
140–141.5 ЊC (Found: C, 70.20; H, 6.33; N, 12.67. C26H28N4OS
requires C, 70.24; H, 6.35; N, 12.60); νmax/cmϪ1 (KBr) 1594,
1548 and 1222; δH(90 MHz) 2.00 (s, 3H, SCH3), 2.20 (s, 3H,
CH3), 3.20 [s, 6H, N(CH3)2], 5.00 (s, 2H, CH2), 6.65 (d, J 8.5,
2H, ArH), 6.98 (d, J 8.5, 2H, ArH), 7.30–7.53 (m, 6H, ArH),
7.80–7.93 (m, 2H, ArH) and 8.40–8.53 (m, 2H, ArH); m/z 444
(Mϩ).
2-[Ethylthio(morpholino)methyleneamino]-1,2,4-triphenyl-1,2-
dihydro-5H-imidazole 3-oxide 6i. Yield 69%; mp 154–155 ЊC
(Found: C, 69.18; H, 6.15; N, 11.60. C28H30N4O2S requires C,
69.11; H, 6.21; N, 11.51); νmax/cmϪ1 (KBr) 1597, 1551 and 1226;
δH(90 MHz) 0.88 (t, J 8.0, 3H, CH3), 2.53 (q, J 8.0, 2H, SCH2),
3.70 (br s, 8H, morpholino), 5.00 (s, 2H, CH2), 6.68 (d, J 8.6,
2H, ArH), 7.15 (d, J 8.6, 2H, ArH), 7.26–7.50 (m, 7H, ArH),
7.73–7.50 (m, 2H, ArH) and 8.36–8.46 (m, 2H, ArH); m/z 486
(Mϩ).
1,2-Diphenyl-4-(p-tolyl)-2-[methylthio(morpholino)methylene-
amino]-1,2-dihydro-5H-imidazole 3-oxide 6k. Yield 75%; mp
149–150 ЊC (Found: C, 69.23; H, 6.16; N, 11.43. C28H30N4O2S
requires C, 69.11; H, 6.21; N, 11.51); νmax/cmϪ1 (KBr) 1598,
1548 and 1228; δH(90 MHz) 2.10 (s, 3H, SCH3), 2.43 (s, 3H,
CH3), 3.75 (br s, 8H, morpholino), 5.00 (s, 2H, CH2), 6.71 (d,
J 8.8, 2H, ArH), 7.10–7.46 (m, 6H, ArH), 7.73–7.86 (m, 2H,
ArH) and 8.30–8.40 (d, J 8.4, 2H, ArH); m/z 486 (Mϩ).
1,4-Bis(p-tolyl)-2-[methylthio(piperidino)methyleneamino]-
1,2-dihydro-5H-imidazole 3-oxide 6m. Yield 81%; mp 147–
149 ЊC (Found: C, 72.36; H, 6.84; N, 11.20. C30H34N4OS
requires C, 72.25; H, 6.87; N, 11.23); νmax/cmϪ1 (KBr) 1593,
1548 and 1229; δH(90 MHz) 1.64 (br s, 6H, CH2CH2CH2), 2.06
(s, 3H, SCH3), 2.20 (s, 3H, CH3), 2.40 (s, 3H, CH3), 3.63 (br s,
4H, CH2NCH2), 4.95 (s, 2H, CH2), 6.72 (d, J 8.6, 2H, ArH),
7.00 (d, J 8.6, 2H, ArH), 7.23–7.43 (m, 5H, ArH), 7.76–7.96
(m, 2H, ArH) and 8.30–8.40 (d, J 8.5, 2H, ArH); m/z 498
(Mϩ).
1-(p-Chlorophenyl)-2-[dimethylamino(methylthio)methylene-
amino]-1,2-dihydro-5H-imidazole 3-oxide 6q. Yield 83%; mp
169–170 ЊC (Found: C, 65.31; H, 5.61; N, 11.65. C26H27N4OSCl
requires C, 65.25; H, 5.68; N, 11.70); νmax/cmϪ1 (KBr) 1598,
1552 and 1226; δH(300 MHz) 2.00 (s, 3H, SCH3), 2.38 (s, 3H,
CH3), 3.18 [s, 6H, N(CH3)2], 4.94 (s, 2H, CH2), 6.62 (d, J 9.0,
2H, ArH), 7.06 (d, J 9.0, 2H, ArH), 7.24–7.32 (m, 5H, ArH),
7.74–7.78 (m, 2H, ArH) and 8.26 (d, J 8.3, 2H, ArH); δC(75.5
MHz) 16.2 (SCH3), 21.7 (CH3), 40.0 [N(CH3)2], 51.4 (CH2),
101.0 (C-2), 114.0, 122.6, 124.8, 126.8, 127.9, 128.2, 128.7,
128.9, 129.3, 133.0, 140.4, 141.0, 141.6 and 159.0 (C-4); m/z 478
(Mϩ).
1-(p-Chlorophenyl)-2,4-diphenyl-2-[ethylthio(pyrrolidino)-
methyleneamino]-1,2-dihydro-5H-imidazole 3-oxide 6r. Yield
89%; mp 163.5–164 ЊC (Found: C, 66.53; H, 5.77; N, 11.15.
C28H29N4OSCl requires C, 66.64; H, 5.79; N, 11.11); νmax/cmϪ1
(KBr) 1597, 1551 and 1225; δH(90 MHz) 0.85 (t, J 8.0, 3H,
CH3), 1.83–2.00 (m, 4H, CH2CH2), 2.65 (q, J 8.0, 2H, SCH2),
3.63–3.90 (m, 4H, CH2NCH2), 5.00 (s, 2H, CH2), 7.70 (d, J 8.8,
6l
6n
6o
6p
6s
158–159
158.5–159
161.5–162.5
143.5–145
10
2H, ArH), 7.11 (d, J 8.8, 2H, ArH), 7.30–7.50 (m, 6H, ArH),
7.75–7.85 (m, 2H, ArH) and 8.36–8.50 (m, 2H, ArH); m/z 504
(Mϩ).
The structures of other derivatives of 6 were supported by
their microanalysis and spectroscopic data and are listed in
Table 1 together with their yields and melting points.
Reactions of the amidines 11 with á-nitrosostyrenes 2
General procedure for the nitrones 12. A solution of com-
pound 11 (4 mmol) and α-chloroacetophenone oxime (4.2
mmol) in dry CH2Cl2 (40 ml) was stirred at RT in the presence
of sodium carbonate (6 mmol) for 40–52 h. Following an iden-
tical work-up with that described for the nitrones 6, the crude
product obtained was purified by column chromatography on
silica gel [eluent: EtOAc–hexane (1:3)].
2-Dimethylamino-1,4-diphenyl-1,2-dihydro-5H-imidazole 3-
oxide 12a. Yield 69%; mp 164.5–165.5 ЊC (Found: C, 72.64; H,
6.77; N, 14.89. C17H19N3O requires C, 72.57; H, 6.80; N, 14.93);
νmax/cmϪ1 (KBr) 1610, 1591 and 1220; δH(90 MHz) 2.67 [s, 6H,
N(CH3)2], 4.52 (dd, J 14.0 and 2.0, 1H, CH2), 4.83 (dd, J 14.0
and 4.5, 1H, CH2), 5.76–5.88 (m, 1H, H-2), 6.81 (d, J 8.0, 2H,
ArH), 7.20–7.60 (m, 6H, ArH) and 8.28–8.50 (m, 2H, ArH);
m/z 281 (Mϩ) and 264 (Mϩ Ϫ 17).
2-Dimethylamino-1-(p-tolyl)-4-phenyl-1,2-dihydro-5H-imid-
azole 3-oxide 12b. Yield 76%; mp 170–171 ЊC (Found: C, 73.09;
H, 7.21; N, 14.27. C18H21N3O requires C, 73.19; H, 7.16; N,
14.22); νmax/cmϪ1 (KBr) 1595, 1579 and 1223; δH(300 MHz) 2.28
(s, 3H, CH3), 2.66 [s, 6H, N(CH3)2], 4.50 (dd, J 14.5 and 2.1, 1H,
CH2), 4.79 (dd, J 14.5 and 4.5, 1H, CH2), 5.81 (dd, J 4.5 and
2.1, 1H, methine H-2), 6.75 (d, J 8.5, 2H, ArH), 7.12 (d, J 8.5,
2H, ArH), 7.45–7.52 (m, 3H, ArH) and 8.32–8.35 (m, 2H,
ArH); δC(75.5 MHz) 20.4 (CH3), 37.1 (CH2), 50.8 [N(CH3)2],
101.9 (C-2), 112.7, 126.5, 126.7, 128.1, 128.6, 128.7, 129.2,
129.8, 130.7, 133.8 and 141.7 (C-4); m/z 295 (Mϩ) and 278
(Mϩ Ϫ 17).
2-Dimethylamino-4-(p-tolyl)-1-phenyl-1,2-dihydro-5H-imid-
azole 3-oxide 12c. Yield 63%; mp 177–178 ЊC (Found: C, 73.05;
H, 7.13; N, 14.29. C18H21N3O requires C, 73.19; H, 7.16; N,
14.22); νmax/cmϪ1 (KBr) 1596, 1574 and 1224; δH(90 MHz) 2.41
(s, 3H, CH3), 2.68 [s, 6H, N(CH3)2], 4.52 (dd, J 14.0 and 2.0, 1H,
CH2), 4.83 (dd, J 14.0 and 4.5, 1H, CH2), 5.75–5.83 (m, 1H, H-
2), 6.80–7.02 (m, 3H, ArH), 7.27–7.50 (m, 4H, ArH) and 8.33
(d, J 8.2, 2H, ArH); m/z 285 (Mϩ) and 268 (Mϩ Ϫ 17).
1,2-Diphenyl-4-(p-tolyl)-2-pyrrolidin-1-yl-1,2-dihydro-5H-
imidazole 3-oxide 12d. Yield 81%; mp 164–165 ЊC (Found: C,
78.69; H, 6.81; N, 10.49. C26H27N3O requires C, 78.56; H, 6.85;
N, 10.57); νmax/cmϪ1 (KBr) 1597, 1583 and 1223; δH(300 MHz)
1.88–1.92 (m, 4H, CH2CH2), 2.42 (s, 3H, CH3), 3.00–3.08 (m,
2H, NCH2), 3.44–3.49 (m, 2H, CH2N), 4.41 (d, J 14.1, 1H,
CH2), 4.59 (d, J 14.1, 1H, CH2), 6.82–6.87 (m, 1H, ArH), 7.16–
7.27 (m, 7H, ArH), 7.32 (d, J 8.1, 2H, ArH), 7.45–7.50 (m, 2H,
ArH) and 8.33 (d, J 8.3, 2H, ArH); δC(75.5 MHz) 21.7 (CH3),
25.5 (CH2CH2), 47.7 (CH2NCH2), 48.4 (CH2), 107.3 (C-2),
115.7, 119.7, 124.4, 126.7, 127.3, 128.1, 128.7, 128.9, 129.5,
133.8, 135.6, 141.1 and 142.9 (C-4); m/z 397 (Mϩ) and 381
(Mϩ Ϫ 16).
J. Chem. Soc., Perkin Trans. 1, 1997
3069

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2-Piperidino-1,2,4-triphenyl-1,2-dihydro-5H-imidazole
oxide 12e. Yield 75%; mp 148–149 ЊC (Found: C, 78.44; H, 6.90;
N, 10.62. C26H27N3O requires C, 78.56; H, 6.84; N, 10.57); νmax
3-
column chromatography on silica gel (eluent: EtOAc–hexane,
1:6).
/
3-(N,N-Dimethylcarbamoyl)-1-phenylbenzamidine 17a. Yield
73%; mp 125.5–126.5 ЊC (Found: C, 71.78; H, 6.45; N, 15.67.
C16H17N3O requires C, 71.89; H, 6.41; N, 15.72); νmax/cmϪ1
(KBr) 3422br, 1635 and 1602; δH(90 MHz) 3.05 (s, 3H, NCH3),
3.32 (s, 3H, NCH3), 6.80–7.77 (m, 10H, ArH) and 12.40 (br s,
exchangeable with D2O, 1H, NH); δC(75.5 MHz) 35.2 (NCH3),
37.3 (CH3N), 123.2, 124.3, 128.0, 128.6, 129.2, 130.2, 135.2,
139.1, 163.0 (C᎐N) and 164.7 (C᎐O); m/z 267 (Mϩ, 14%), 223
cmϪ1 (KBr) 1652, 1599 and 1219; δH(90 MHz) 1.65 (br s, 6H,
CH2CH2CH2), 2.83–3.18 (m, 2H, NCH2), 3.27–3.57 (m, 2H,
CH2N), 4.63 (br s, 2H, CH2), 7.20–7.73 (m, 13H, ArH) and
8.45–8.65 (m, 2H, ArH); m/z 397 (Mϩ) and 381 (Mϩ Ϫ 16).
1,2-Diphenyl-4-(p-tolyl)-2-piperidino-1,2-dihydro-5H-imid-
azole 3-oxide 12f. Yield 81%; mp 165–166 ЊC (Found: C, 78.69;
H, 7.07; N, 10.30. C27H29N3O requires C, 78.80; H, 7.10; N,
10.21); νmax/cmϪ1 (KBr) 1596, 1580 and 1226; δH(90 MHz) 1.64
(br s, 6H, CH2CH2CH2), 2.42 (s, 3H, CH3), 2.81–3.13 (m, 2H,
NCH2), 3.27–3.53 (m, 2H, CH2N), 4.55 (s, 2H, CH2), 7.13–7.50
(m, 12H, ArH) and 8.33 (d, J 8.0, 2H, ArH); m/z 411 (Mϩ) and
395 (Mϩ Ϫ 16).
᎐
᎐
(100%), 180 (22%) and 77 (21%).
N-[p-Tolylamino(phenyl)methylene]morpholine-4-carbox-
amide 17b. Yield 66%; mp 141–142.5 ЊC (Found: C, 70.69; H,
6.47; N, 12.91. C19H21N3O2 requires C, 70.56; H, 6.54; N, 12.99);
νmax/cmϪ1 (KBr) 3437br, 1625 and 1590; δH(90 MHz) 2.30 (s,
3H, CH3), 3.70 (br s, 8H, morpholino), 6.83 (d, J 8.7, 2H, ArH),
7.08 (d, J 8.7, 2H, ArH), 7.23–7.67 (m, 5H, ArH) and 12.43 (br
s, exchangeable with D2O, 1H, NH); m/z 323 (Mϩ).
1,4-Diaryl-2-phenylimidazoles 13
(i) Thermolysis of the nitrones 3/12d–f. A solution of the
nitrone 3/12d–f (1.0 mmol) in dry benzene (8 ml) was heated in
a sealed tube at 140–150 ЊC for 6–7 h. After solvent removal in
vacuo the residue was purified by chromatography on silica gel
(eluent: EtOAc–hexane, 1:9) to yield 69–74% of the corre-
sponding imidazoles 13.
(ii) Treatment of the nitrones 3/6 with NaBH4. To a solution
of the nitrone 3/6 (2.50 mmol) in methanol (50 ml) was added
NaBH4 (0.1 g, 2.70 mmol) and the reaction mixture was stirred
at RT for 20–22 h. After solvent removal in vacuo, the residue
was diluted with CH2Cl2 (35 ml) and the solution washed with
water (4 × 50 ml), dried (Na2SO4) and evaporated under
reduced pressure. The residue was purified by chromatography
on silica gel (eluent: EtOAc–hexane, 1:9) to afford the products
13 (53–66%).
(iii) Reactions of N-arylbenzamidine 22 with á-nitrosostyrenes
2. A solution of the N-arylbenzamidine 22 (4.0 mmol) and
α-chloroacetophenone oxime (4.2 mmol) in dry CH2Cl2 (20 ml)
was stirred at RT in the presence of sodium carbonate for 2–3 h.
Work-up identical with that employed for the nitrones 6 gave
the crude product which was further purified by chrom-
atography on silica gel (eluent: EtOAc–hexane, 1:9) to yield the
corresponding products 13 (85–93%).
1,2,4-Triphenylimidazole 13a. Mp 92–94 ЊC (Found: C, 85.19;
H, 5.41; N, 9.41. C21H16N2 requires C, 85.12; H, 5.44; N, 9.45);
νmax/cmϪ1 (KBr) 1591 and 1205; δH(90 MHz) 7.20–7.61 (m,
14H; 13H, ArH and 1H, olefinic) and 7.92–8.11 (m, 2H, ArH);
δC(75.5 MHz) 118.4 (C-5), 124.9, 125.7, 126.9, 128.1, 128.3,
128.5, 128.7, 129.9, 130.2, 133.8, 138.4, 141.6 and 146.9 (C-2);
m/z 296 (Mϩ, 100%), 193 (63%), 165 (25%), 116 (3%), 103 (8%),
89 (32%) and 77 (28%).
2,4-Diphenyl-1-(p-tolyl)imidazole 13b. Mp 147–148 ЊC
(Found: C, 85.05; H, 5.86; N, 9.07. C22H18N2 requires C, 85.13;
H, 5.84; N, 9.02); νmax/cmϪ1 (KBr) 1602 and 1205; δH(300 MHz)
2.35 (s, 3H, CH3), 7.09 (d, J 8.4, 2H, ArH), 7.15 (d, J 8.4, 2H,
ArH), 7.20–7.26 (m, 4H, ArH), 7.35–7.40 (m, 3H, 2H, ArH and
1H, olefinic), 7.44–7.48 (m, 2H, ArH) and 7.86–7.90 (m, 2H,
ArH); δC(75.5 MHz) 21.0 (CH3), 118.5 (C-5), 124.9, 125.4,
126.8, 128.0, 128.2, 128.4, 128.6, 129.9, 130.3, 133.8, 135.8,
138.0, 141.4 and 146.8 (C-2); m/z 310 (Mϩ, 89%), 207 (100%),
165 (13%), 116 (10%), 103 (13%), 77 (33%) and 65 (13%).
1,2-Diphenyl-4-(p-tolyl)imidazole 13c. Mp 113.5–114.5 ЊC
(Found: C, 85.17; H, 5.85; N, 9.07. C22H18N2 requires C,
85.13; H, 5.84; N, 9.02; νmax/cmϪ1 (KBr) 1600 and 1204; δH(90
MHz) 2.38 (s, 3H, CH3), 7.18–7.57 (m, 13H; 12H, ArH and 1H,
olefinic) and 7.83 (d, J 8.0, 2H, ArH); δC(75.5 MHz) 21.2 (CH3),
118.0 (C-5), 124.9, 125.7, 128.0, 128.1, 128.3, 128.7, 129.2,
129.3, 130.3, 131.0, 136.5, 138.5, 141.7 and 146.7; m/z 310 (Mϩ).
Acknowledgements
The authors thank the RSIC, NEHU, Shillong, for spectral
analyses. A. K. S. also thanks the CSIR, New Delhi for a Senior
Research Fellowship.
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Thermolysis of the nitrones 6
General procedure for 17. A solution of 6 (1.0 mmol) in
benzene (8 ml) was heated in a sealed tube at 140–150 ЊC for 6–
7 h. After solvent removal in vacuo the residue was purified by
Paper 7/02254I
Received 2nd April 1997
Accepted 24th June 1997
3070
J. Chem. Soc., Perkin Trans. 1, 1997