The surprising nucleophilic addition of aminochlorocarbenes to diethyl acetylenedicarboxylate and to oxalyl chloride: Quinolines and benzo[1,4]diazepines from N-alkylformanilides and oxalyl chloride in the presence of Huenig's base

Article abstract of DOI:10.1039/b307278a

Vilsmeier reagents derived from N-methylformanilides undergo ready deprotonation with Huenig's base. In xylene, the derived nucleophilic arylaminochlorocarbenes bearing 4-methyl- and 4-methoxy-substituents react with acetylenedicarboxylates to give 2-(2-c

Full text of DOI:10.1039/b307278a

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The surprising nucleophilic addition of aminochlorocarbenes to
diethyl acetylenedicarboxylate and to oxalyl chloride:
quinolines and benzo[1,4]diazepines from N-alkylformanilides
and oxalyl chloride in the presence of Hünig’s base
Ying Cheng,*a Hua Yanga and Otto Meth-Cohn*b
a Department of Chemistry, Beijing Normal University, Beijing 100875, China.
E-mail: yincheng@95777.com; Tel: ϩ86 1062205558
b Chemistry Department, Sunderland University, Sunderland, UK SR1 3SD.
E-mail: otto.meth-cohn@sunderland.ac.uk
Received 27th June 2003, Accepted 1st September 2003
First published as an Advance Article on the web 17th September 2003
Vilsmeier reagents derived from N-methylformanilides undergo ready deprotonation with Hünig’s base. In xylene, the
derived nucleophilic arylaminochlorocarbenes bearing 4-methyl- and 4-methoxy-substituents react with
acetylenedicarboxylates to give 2-(2-chloro-1,2-bis(ethoxycarbonyl)vinyl)-3,4-bis(ethoxycarbonyl)-1-methyl-1,2-
dihydroquinolines while most derivatives react with oxalyl chloride to give substituted 1-methyl-4-
phenylbenzo[f ][1,4]diazepine-2,3-dicarboxylic anhydrides.
anilide 1 and oxalyl chloride 2, was deprotonated with Hünig’s
Introduction
base 3 in dry chloroform or THF at Ϫ10 to 0 ЊC under a nitro-
Carbenes have been extensively studied for more than half a
gen atmosphere, followed by addition of diethyl acetylene-
century. They can be divided into electrophilic, nucleophilic and
ambiphilic types on the basis of their chemical reactivity. The
most important synthetic application of electrophilic carbenes,
such as dichlorocarbene, is undoubtedly the cyclopropanation
of olefins, which has been widely used in synthesis. By contrast,
nucleophilic carbenes (i.e. those in which the divalent carbon is
attached to at least one group 5 or 6 element) only add to
certain electrophilic alkenes. For example, fluorophenoxy-
dicarboxylate 4. After stirring at room temperature for a period
of time, work-up gave solely the known hydrogen chloride
adduct of diethyl acetylenedicarboxylate 5, together with the
usual carbene dimers 6. Isolation of these products indicated
that the ‘dimerisation’ of the carbenes was much faster than its
possible reaction with 4.
In order to inhibit the dimerisation, firstly a non-polar
solvent was used, which would minimise the solubility of the
Vilsmeier reagent, and secondly, a much lower initial reaction
temperature was employed. Thus, the Vilsmeier reagent pre-
pared by reaction of 4-methoxy- or 4-methyl-N-methylform-
anilide 1a,b and oxalyl chloride at 0 ЊC, was cooled to Ϫ78 ЊC.
carbene is more reactive towards electron-deficient alkenes than
to dimethylethenes,1 and cyclopropanes are derived in good
yield from dimethoxycarbene addition to acrylonitrile and to
methyl acrylate.2 Carbonyl groups such as in cycloheptanone,3
certain anhydrides4 and benzoyl chloride,5 also behave as inter-
To the suspension of the Vilsmeier reagent in dry xylene,
ceptors for dialkoxycarbenes.
Hünig’s base
3 was added followed by diethyl acetyl-
An intriguing feature of nucleophilic carbenes is the unpre-
dictable outcome of their annulation reactions with electrophiles.
This is seen in their reactions with acetylenedicarboxylates,6,7 di-
substituted maleic anhydrides,4,8 dibenzoylethylene9 and iso-
cyanates10,11 making nucleophilic carbenes useful intermediates
for the construction of polyfunctionalised heterocycles.
enedicarboxylate 4. The mixture was then allowed to reach
room temperature over a 3–4 h period. A red crystalline prod-
uct was isolated in both cases, the structures of which were
finally put beyond doubt as quinoline derivatives 7 by X-ray
crystallographic studies (Scheme 1 and Fig. 1).15
In our earlier work, we found Vilsmeier reagents are surpris-
ingly acidic, undergoing ready deprotonation with Hünig’s
base. This process yields arylaminochlorocarbenes (weakly
nucleophilic carbenes). However, in all cases, these carbenes
reacted rapidly with the parent Vilsmeier reagent to give a
dimer, which was capable of isolation or of further conversion
into a series of heterocyclic compounds.12,13,14
We have now discovered how to inhibit this dimerisation.
This has allowed us to study the reactivity of arylamino-
chlorocarbenes, in particular their intermolecular reactions
with electrophiles. The results proved most unexpected and
surprising and we herein describe the formation of quinolines
and benzodiazepines by interaction of these carbenes with
acetylenedicarboxylates or oxalyl chloride.
Scheme 1
Results and discussion
The interaction of arylaminochlorocarbenes with diethyl
acetylenedicarboxylate was first studied. Initially, the Vilsmeier
reagent, derived from 4-methoxy- or 4-methyl-N-methylform-
The products derived from the interaction of one aryl-
aminochlorocarbene and two acetylenedicarboxylate moieties
are formed in 33% and 17% yield respectively.16 A mechanism
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 6 0 5 – 3 6 1 0
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Fig. 1 ORTEP drawing of compound 7a.
Scheme 3
Fig. 2 ORTEP drawing of compound 13c.
acetylenedicarboxylate was proved by repeating the reaction in
its absence, the same products 13c,d being formed in similar
yield (41 and 26% respectively).
Other substituted formanilides, 1e–h, reacted similarly to give
the products 13e–h (Scheme 3) in 22–60% yield.
The mechanism for the formation of the benzo[1,4]-
diazepinedicarboxylic anhydrides 13 is not trivial to explain
being formed solely from the formanilide 1 and oxalyl chloride.
The formation of 13 appears to involve addition of the carbene
9 to oxalyl chloride to form an iminium salt 14 and thence 15.
The proton of the methyl group adjacent to the iminium func-
tion appears to be sufficiently acidic to be deprotonated by the
base18 allowing the new iminium ion 17 to cyclise to a diazepine
18. The resulting enamine 19 can then undergo electrophilic
addition of oxalyl chloride at the less hindered carbon atom of
the double bond. The bis-acid chloride 21 might undergo
decarbonylation in the warm-up process or during the removal
of xylene to form the anhydrides 13 with traces of water or
upon work-up (Scheme 4).
Scheme 2
for their formation is depicted in Scheme 2, and involves the bis-
addition of the carbene to the acetylene.
In order to study the effect of the substituents on the nucleo-
philicity of the carbenes, we examined the reactions between
arylaminochlorocarbenes derived from 4-fluoro- and 4-chloro-
N-methylformanilides 1c,d, and diethyl acetylenedicarboxylate
under the same conditions. Although red crystalline products
were again isolated, they proved to be totally different to the
above quinolines. These products, 13, showed two weak infra-
red absorptions at around 1800 cmϪ1 and one strong peak at
about 1750 cmϪ1, indicative of an anhydride. The NMR and
MS spectra showed that the products were derived from
two formanilide moieties, but incorporated no acetylene-
dicarboxylate unit. Finally, the structure of one of the products
was shown to be a derivative of 1-methyl-4-phenylbenzo[1,4]-
diazepine 13c (X = F) by X-ray crystallography (Scheme 3 and
Fig. 2).17
In order to prove that the key cyclisation step (17
18) does
indeed utilise the N-methyl group of the N-methylformanilide
we treated several examples of the corresponding N-benzyl-
formanilide 22 with oxalyl chloride in the presence of Hünig’s
base. Gratifyingly, benzo[1,4]diazepines 23 bearing an aryl
group at the 5-carbon atom were isolated in 18–32% yield
(Scheme 5). In the proton NMR of 23, a one proton singlet
appeared at about 5.5 ppm, and the equivalent methylene pro-
tons of the azepines 13 had disappeared. Meanwhile, two doub-
let peaks with a large coupling constant (∼15 Hz) appeared at
∼4.7 ppm, indicative of the two non-equivalent protons of the
N-benzyl methylene. This data was further supported by X-ray
crystallography (Fig. 3).19
It would seem that the compounds 13c,d were derived from
the intermolecular reaction of arylaminochlorocarbenes and
oxalyl chloride, the two carbonyl groups of the anhydride being
derived from the oxalyl chloride. The non-involvement of the
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 6 0 5 – 3 6 1 0
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Table 1 Reaction conditions for and chemical yields of compounds 13
and 23
Reactants
Yield (%)
1
22
Reaction temp./ЊC
Reaction time/h
13
23
1a
1b
1c
1d
1e
1f
Ϫ78 to rt
Ϫ78 to rt
Ϫ78 to 50
Ϫ78 to 50
Ϫ78 to 50
Ϫ78 to rt
Ϫ78 to 50
Ϫ78 to 50
Ϫ78 to rt
Ϫ78 to rt
Ϫ78 to 50
Ϫ78 to rt
7
4
9
7
7
9
7
7
26
30
46
28
22
60
35
26
1g
1h
22a
22b
22c
22f
18
18
7
32
18
29
23
18
Scheme 4
Fig. 3 ORTEP drawing of compound 23a.
described above. However, the more weakly nucleophilic carb-
enes derived from halogen substituted formanilides needed to
be warmed to 40–50 ЊC to ensure complete reaction. Because of
the sensitivity of the reactions to the conditions employed we
found that while products were always formed, yields proved
somewhat erratic. The best results are listed in Table 1.
It would appear that only the more nucleophilic carbenes
derived from the 4-methyl- and the 4-methoxy-substituted
formanilides, are sufficiently nucleophilic to react with acetyl-
enedicarboxylate, while all react with the more electrophilic
oxalyl chloride.
As well as diethyl acetylenedicarboxylate and oxalyl chloride,
other electrophiles were examined. These included N-phenyl-
maleimide, diethyl maleate, phenyl isocyanate and phenyl
isothiocyanate. All of these reagents proved ineffective. The
N-phenylmaleimide, diethyl maleate, and phenyl isothiocyanate
were recovered and the phenyl isocyanate was converted to
diphenylurea during work-up.
In summary, we have discovered the unique nucleophilicity
of arylaminochlorocarbenes which afford a simple method to
novel benzo[1,4]diazepine derivatives by the interaction of
substituted formanilides and oxalyl chloride with base and
to quinolines with the same reagents plus diethyl acetylene-
dicarboxylate.
Scheme 5
Xylene proved to be the optimally effective solvent, poor or
no yields being obtained using chloroform, dichloromethane,
THF or toluene. Varying the molar ratio of formanilide to
oxalyl chloride showed that the best yields were derived from
the ratio of 1 : 1.5. Larger excesses of oxalyl chloride did not
improve the yield of azepine, but led to dark reaction mixtures.
It seemed that the reactions were very sensitive to acidic condi-
tions, moisture, temperature, and particularly the physical
status of the Vilsmeier reagent in xylene. Finely suspended
Vilsmeier reagent (as generally obtained with xylene as solvent)
resulted in smooth deprotonation and normally good yields of
products. On the other hand, if the Vilsmeier reagent dissolved
or aggregated to form a large mass of solid in the solvent, the
yields of azepine were generally poor.
Experimental
General
1
Melting points are uncorrected. H NMR and 13C NMR were
obtained on a Bruker Avance 500; chemical shifts are given in
ppm and coupling constants in Hz. IR spectra were recorded
using an AVATAR 360 FT-IR spectrometer. Mass spectra
were recorded on a Trace MS instrument (EI-MS) or Bruker
The reactions between 4-methoxy- or 4-methyl-N-methyl-
formanilide, oxalyl chloride and Hünig’s base gave the diaze-
pine 13a and 13b respectively under the optimised conditions
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 6 0 5 – 3 6 1 0
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APEX-2 (HRMS) and elemental analyses were performed on a
GMBH Vario EL instrument.
All glassware was oven dried (120 ЊC) over a 10 h period.
Xylene was distilled from sodium benzophenone ketyl. Light
petroleum refers to the fraction bp 60–90 ЊC.
CDCl3) 7.08 (1H, d, J 8.9), 6.90 (2H, d, J 8.9), 6.85 (1H, dd,
J 8.9, 2.9), 6.82 (2H, d, J 8.9), 6.41 (1H, d, J 2.9), 4.66 (2H, s),
3.79 (3H, s), 3.71 (3H, s), 3.65 (3H, s); δC (125 MHz, CDCl3)
161.9, 160.5, 156.8, 155.1, 142.6, 138.3, 131.6, 129.2, 123.7,
123.4, 122.5, 115.6, 114.7, 113.9, 57.6, 55.5, 55.4, 40.9; HRMS
(EI): 366.1207, C20H18N2O5 requires 366.1216.
General procedure for the preparation of quinolines 7a,b
1,7-Dimethyl-4-(4-methylphenyl)benzo[ f ][1,4]diazepine-2,3-
dicarboxylic anhydride 13b. 0.50 g, 30%, as red crystals, mp
155–156 ЊC (Found: C 71.5, H 5.3, N 8.5. C20H18N2O3 requires
C 71.8, H 5.4, N 8.4%); IR (KBr) (νmax/cmϪ1): 1833, 1815 and
Under a nitrogen atmosphere, 4-substituted N-methylform-
anilides 1a,b (10 mmol) and oxalyl chloride (11 mmol) were
mixed at 0 ЊC to form a sticky solid, which was then cooled to
Ϫ78 ЊC. To this solid Vilsmeier reagent, xylene (5 ml) followed
by a solution of Hünig’s base (12 mmol) in xylene (10 ml) was
added with stirring to form a suspension. After a ½ h, diethyl
acetylenedicarboxylate 4 in xylene (5 ml) was added and the
temperature increased from Ϫ78 ЊC to room temperature dur-
ing 3 h. The reaction mixture was stirred at room temperature
for 2 h and then at 50 ЊC for another 2 h. The reaction mixture
was chromatographed directly. The xylene was removed by
washing the column with light petroleum. Compound 5 and
dimers 6 were eluted with a mixture of light petroleum and
ethyl acetate (10 : 1). Finally, the red products 7a,b were isolated
by eluting with light petroleum : ethyl acetate (4 : 1).
1749 (O᎐COC᎐O), 1635 (C᎐C); δ (500 MHz, CDCl3) 7.09–
᎐
᎐
᎐
H
7.13 (3H, m), 7.02 (1H, d, J 8.1), 6.86 (2H, d, J 7.5), 6.70 (1H,
s), 4.71 (2H, s), 3.67 (3H, s), 2.32 (3H, s), 2.71 (3H, s); δC (125
MHz, CDCl3) 162.3, 160.7, 147.6, 142.9, 134.4, 133.7, 130.8,
130.6, 130.4, 129.5, 123.6, 122.2, 121.4, 57.4, 41.2, 21.2, 20.9;
m/z (EI) 334 (90, Mϩ).
7-Fluoro-4-(4-fluorophenyl)-1-methylbenzo[ f ][1,4]diazepine-
2,3-dicarboxylic anhydride 13c. 0.79 g, 46%, as red crystals, mp
208–209 ЊC; IR (KBr) (νmax/cmϪ1): 1838, 1812 and 1748
(O᎐COC᎐O), 1637 (C᎐C); δ (500 MHz, CDCl3) 7.12–7.13
᎐
᎐
᎐
H
(1H, m), 6.99–7.06 (3H, m), 6.94 (2H, t, J 4.2), 6.60 (1H, d,
J 7.5), 4.69 (2H, s), 3.68 (3H, s); δC (125 MHz, CDCl3) 161.9,
161.3, 160.5, 159.3 (d), 157.4, 146.0, 141.4, 132.5 (d), 130.0,
124.2 (d), 123.4 (d), 117.1, 116.9 (d), 116.7, 116.6, 57.4, 41.4;
HRMS (EI): 342.0813, C18H12O3F2N2 requires 342.0810.
Diethyl 2-(2-chloro-1,2-bis(ethoxycarbonyl)vinyl)-6-methoxy–
1-methyl-1,2-dihydroquinoline-3,4-dicarboxylate 7a. 0.86 g,
33%, as red crystals, mp 108–109 ЊC; IR (KBr) (νmax/cmϪ1): 1742
(C᎐O), 1733 (C᎐O), 1722 (C᎐O), 1698 (C᎐O); δ (500 MHz,
᎐
᎐
᎐
᎐
H
CDCl3) 6.85 (1H, dd, J 8.9, 2.7), 6.52 (1H, d, J, 2.7), 6.50 (1H,
d, J 9.0), 6.33 (1H, s), 4.37–4.42 (4H, m), 4.20 (2H, q, J 7.1),
3.75 (2H, q, J 6.8), 3.70 (3H, s), 3.04 (3H, s), 1.36–1.42 (6H, m),
1.25 (3H, t, J 7.1), 1.10 (3H, t, J 7.2); δC (125 MHz, CDCl3)
167.4, 165.5, 163.8, 162.4, 152.2, 141.6, 140.6, 139.7, 122.3,
119.8, 118.2, 117.6, 113.4, 112.1, 63.2, 62.7, 62.0, 61.7, 57.4,
56.2; HRMS (FAB): 524.1694, C25H30ClNO9 requires 524.1682.
7-Chloro-4-(4-chlorophenyl)-1-methylbenzo[ f ][1,4]diazepine-
2,3-dicarboxylic anhydride 13d. 0.53 g, 28%, as red crystals, mp
179–180 ЊC (Found: C 57.1, H 2.8, N 6.9. C18H12Cl2N2O3
requires C 57.6, H 3.2, N 7.5%); IR (KBr) (νmax/cmϪ1): 1840,
1818 and 1763 (O᎐COC᎐O), 1637 (C᎐C); δ (500 MHz, CDCl )
᎐
᎐
᎐
H
3
7.32 (1H, dd, J 8.7, 2.4), 7.27 (2H, d, J 9.6), 7.08 (1H, d, J 8.7),
6.90 (2H, d, J 8.7), 6.88 (1H, d, J 2.4), 4.71 (2H, s), 3.69 (3H, s);
δC (125 MHz, CDCl3) 161.7, 160.2, 148.4, 143.6, 132.2, 130.7,
130.4, 130.1, 130.0, 129.3, 123.2, 123.1, 122.7, 56.8, 41.5;
HRMS (EI): 374.0229, C18H12Cl2N2O3 requires 374.0225.
Diethyl
2-(2-chloro-1,2-bis(ethoxycarbonyl)vinyl)-1,6-di-
methyl-1,2-dihydroquinoline-3,4-dicarboxylate 7b. 0.43 g,
17%, as red crystals, mp 105–106 ЊC (Found: C 58.9, H 5.4, N
2.65. C25H30ClNO8 requires C 59.1, H 5.95, N 2.8%); IR (KBr)
(νmax/cmϪ1): 1744 (C᎐O), 1722 (C᎐O), 1696 (C᎐O); δ (500
7-Bromo-4-(4-bromophenyl)-1-methylbenzo[ f ][1,4]diazepine-
2,3-dicarboxylic anhydride 13e. 0.51 g, 22%, as red crystals, mp
143–146 ЊC (Found: C 47.0, H 2.4, N 5.7. C18H12Br2N2O3
requires C 46.6, H 2.6, N 6.0%); IR (KBr) (νmax/cmϪ1): 1838,
᎐
᎐
᎐
H
MHz, CDCl3) 6.96 (1H, d, J 8.2), 6.65 (1H, s), 6.39 (1H, d,
J 8.3), 6.28 (1H, s), 4.27–4.36 (4H, m), 4.13 (2H, q, J 7.1), 3.66
(2H, q, J 7.1), 2.98 (3H, s), 2.10 (3H, s), 1.27–1.36 (6H, m), 1.17
(3H, t, J 7.1), 1.01 (3H, t, J 7.1); HRMS (EI): 507.1665,
C25H30ClNO8 requires 507.1660
1817 and 1752 (O᎐COC᎐O), 1637 (C᎐C); δ (500 MHz, CDCl )
᎐
᎐
᎐
H
3
7.46 (1H, d, J 8.5), 7.41 (2H, d, J 8.4), 7.03 (1H, s), 7.02 (1H, d,
J 8.8), 6.84 (2H, d, J 8.4), 4.71 (2H, s), 3.69 (3H, s); δC (125
MHz, CDCl3) 161.6, 160.1, 148.9, 144.1, 133.0, 132.8, 132.5,
130.0, 123.5 (two carbons), 122.7, 118.0, 116.9, 56.6, 41.4; m/z
(EI) 462 (30, Mϩ)/464 (32)/466 (25)/468 (10), 155 (100, BrC6H4).
General procedure for the preparation of benzo[1,4]diazepines 13
and 23
Under a nitrogen atmosphere, substituted N-methylformanilide
1a–h or N-benzylformanilide 22a–c,f (10 mmol) and oxalyl
chloride (15 mmol) were mixed at 0 ЊC to form a sticky solid. To
this solid Vilsmeier reagent, xylene (5 ml) was added with stir-
ring to form a suspension, which was then cooled to Ϫ78 ЊC. A
solution of Hünig’s base (15 mmol) in xylene (10 ml) was added
dropwise to the Vilsmeier reagent over 30 min. The temperature
was then increased from Ϫ78 ЊC to room temperature during
3 h. The reaction mixture was stirred at room temperature or at
50 ЊC for a period of time (see Table 1). After removal of the
xylene under vacuum, the reaction mixture was chromato-
graphed on silica gel. The red products 13 and 23 were isolated
by eluting with light petroleum : ethyl acetate (4 : 1) and further
purified by crystallisation from ethyl acetate and light
petroleum.
1-Methyl-4-phenylbenzo[ f ][1,4]diazepine-2,3-dicarboxylic
anhydride 13f. 0.92 g, 60%, as red crystals, mp 162–163 ЊC
(Found: C 70.4, H 4.2, N 9.0. C18H14N2O3 requires C 70.6, H
4.6, N 9.1%); IR (KBr) (νmax/cmϪ1): 1838, 1805 and 1753
(O᎐COC᎐O), 1637 (C᎐C); δ (500 MHz, CDCl3) 7.32–7.34
᎐
᎐
᎐
H
(1H, m), 7.29 (2H, t, J 8.5), 7.15 (1H, d, J 8.2), 7.10 (1H, t,
J 7.4), 6.97 (2H, d, J 7.7), 6.90 (2H, m), 4.79 (2H, s), 3.72 (3H,
s); δC (125 MHz, CDCl3) 161.7, 160.2, 149.7, 144.9, 130.6,
129.9, 129.7, 129.6, 129.4, 124.3, 123.8, 122.8, 121.6, 121.2,
56.8, 40.9; m/z (EI) 306 (100, Mϩ).
8-Fluoro-4-(3-fluorophenyl)-1-methylbenzo[ f ][1,4]diazepine-
2,3-dicarboxylic anhydride 13g. 0.60 g, 35%, as red crystals,
mp 186–188 ЊC (Found: C 63.2, H 3.1, N 8.0. C18H12F2N2O3
requires C 63.2, H 3.5, N 8.2%); IR (KBr) (νmax/cmϪ1): 1834,
7-Methoxy-4-(4-methoxyphenyl)-1-methylbenzo[ f ][1,4]-
diazepine-2,3-dicarboxylic anhydride 13a. 0.48 g, 26%, as red
crystals, mp 160–161 ЊC (Found: C 65.7, H 4.5, N 7.5. C20H18-
N2O5 requires C 65.6, H 4.95, N 7.65%); IR (KBr) (νmax/cmϪ1):
1817 and 1754 (O᎐COC᎐O), 1635(C᎐C); δ (500 MHz, CDCl )
᎐ ᎐ ᎐
H 3
7.23–7.25 (1H, m), 6.87–6.91 (2H, m), 6.78–6.82 (1H, m), 6.68–
6.73 (2H, m), 6.64–6.65 (1H, m), 4.74 (2H, s), 3.71 (3H, s);
δC (125 MHz, CDCl3) 164.3/164.2 (d), 162.4/162.3 (d), 161.2,
159.8, 150.7, 146.3, 131.3/131.2 (d), 130.6/130.6 (d), 129.9,
1832, 1803 and 1740 (O᎐COC᎐O), 1629 (C᎐C); δ (500 MHz,
᎐
᎐
᎐
H
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 6 0 5 – 3 6 1 0
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129.5, 122.1/122.0 (d), 116.9, 111.3/111.1(d), 110.9/110.7 (d),
109.1/108.9 (d), 108.5/108.2 (d), 56.0, 40.8; m/z (EI) 342 (35,
Mϩ)/343 (12), 95 (100, FC6H4).
J 15.3); δC (125 MHz, CDCl3) 160.8, 160.7, 147.9, 146.2, 139.8,
137.1, 132.5, 132.0, 129.9, 129.5, 129.3, 128.4, 128.1, 127.5,
127.4, 127.1, 126.0, 125.1 124.1, 123.1, 122.9, 122.4, 73.7, 56.3;
m/z (EI) 458 (85, Mϩ)/459 (35), 220 (65, 5-phenylbenzo-
diazepine), 91 (100, PhCH2).
Single crystals of compounds 7a, 13c and 23a suitable for
X-ray diffraction were selected directly from the analytical
samples.
8-Chloro-4-(3-chlorophenyl)-1-methylbenzo[ f ][1,4]diazepine-
2,3-dicarboxylic anhydride 13h. 0.49 g, 26%, as red crystals,
mp 192–193 ЊC (Found: C 58.0, H 2.7, N 7.3. C18H12Cl2N2O3
requires C 57.6, H 3.2, N 7.5%); IR (KBr) (νmax/cmϪ1): 1841,
1821 and 1750 (O᎐COC᎐O), 1643 (C᎐C); δ (500 MHz, CDCl )
᎐
᎐
᎐
H
3
7.27 (1H, t, J 8.0), 7.22 (1H, t, J 8.0), 7.03–7.10 (1H, s), 7.02
(4H, m), 6.92 (1H, d, J 7.9), 5.08 (2H, s), 3.70 (3H, s); δC (125
MHz, CDCl3) 161.2, 159.6, 151.5, 145.5, 134.8, 134.2, 130.1,
129.9, 129.4, 128.6, 125.3, 124.8, 123.2, 122.3, 120.3, 120.2,
51.6, 41.3; HRMS (EI): 374.0232, C18H12Cl2N2O3 requires
374.0225.
Crystal structure determination of compound 7a
¯
C25H30ClNO9, M = 523.95, triclinic, space group P1, a =
8.312(12), b = 8.487(13), c = 19.91(3) Å, α = 78.19(3)Њ, β =
81.52(3)Њ, γ = 88.99(3)Њ, V = 1360(4) Å3, T = 293(2) K, Z = 2, Dx
= 1.280 Mg mϪ3, µ = 0.191 mmϪ1, 4331 reflections measured,
3760 unique (Rint = 0.1060) which were used in all calculations.
The final R indices [I > 2σ(I )] R1 = 0.0803, wR2 = 0.1756; R
indices R1 = 0.1848, wR2 = 0.2216 (all data).
1-Benzyl-7-methoxy-4-(4-methoxyphenyl)-5-phenylbenzo[ f ]-
[1,4]diazepine-2,3-dicarboxylic anhydride 23a. 0.57 g, 32%, as
red crystals, mp 169–170 ЊC (Found: C 73.9, H 4.95, N 5.3.
Crystal structure determination of compound 13c
C32H26N2O5 requires C 74.1, H 5.05, N 5.4%); IR (KBr) (νmax
/
cmϪ1): 1824 and 1752 (O᎐COC᎐O), 1642 (C᎐C); δH (500 MHz,
C18H12F2N2O3, M = 342.30, monoclinic, space group P2(1)/c,
a = 15.752(6), b = 11.767(4), c = 8.688(3) Å, α = 90Њ, β =
103.607(7)Њ, γ = 90Њ, V = 1565.2(9) Å3, T = 293(2) K, Z = 4,
Dx = 1.453 Mg mϪ3, µ = 0.116 mmϪ1, 6550 reflections measured,
2883 unique (Rint = 0.1421) which were used in all calculations.
The final R indices [I > 2σ(I )] R1 = 0.0569, wR2 = 0.1063;
R indices R1 = 0.2534, wR2 = 0.1883 (all data).
᎐
᎐
᎐
CDCl3) 7.45–7.46 (3H, m), 7.33–7.34 (2H, m), 7.13–7.19 (3H,
m), 7.05 (2H, d, J 8.9), 6.94 (1H, d, J 8.9), 6.87 (2H, d, J 8.9),
6.80 (1H, dd, J 8.9, 2.9), 6.70 (2H, d, J 7.2), 6.61 (1H, d, J 2.9),
5.52 (1H, s), 4.67 (1H, d, J 15.1), 4.61 (1H, d, J 15.1), 3.82 (3H,
s), 3.76 (3H, s); δC (125 MHz, CDCl3) 161.2, 161.0, 157.3, 155.5,
140.3, 129.5, 139.4, 137.3, 133.9, 129.2, 128.3, 128.0, 127.8,
127.6, 127.1, 126.0, 124.9, 124.4, 123.4, 117.7, 114.8, 113.5,
74.0, 56.5, 55.5 (two carbon); m/z (EI) 518 (67, Mϩ)/519 (24),
250 (100, 7-methoxy-5-phenylbenzodiazepine).
Crystal structure determination of compound 23a
¯
C32H26N2O5, M = 518.55, triclinic, space group P1, a =
12.0481(11), b = 14.5004 (17), c = 16.407(2) Å, α = 81.45(3),
β = 83.18(5), γ = 67.320(17)Њ, V = 2609.3(5) Å3, T = 293(2) K,
Z = 4, Dx = 1.320 Mg mϪ3, µ = 0.090 mmϪ1, 17892 reflections
measured, 11548 unique (Rint = 0.0682) which were used in all
calculations. The final R indices [I > 2σ(I )] R1 = 0.0481, wR2 =
0.0726; R indices R1 = 0.2119, wR2 = 0.0918 (all data).
1-Benzyl-7-methyl-4-(4-methylphenyl)-5-phenylbenzo[ f ]-
[1,4]diazepine-2,3-dicarboxylic anhydride 23b. 0.44 g, 18%, as
red crystals, mp 210–212 ЊC (Found: C 79.0, H 5.2, N 5.6.
C32H26N2O3 requires C 79.0, H 5.4, N 5.8%); IR (KBr) (νmax
/
cmϪ1): 1827, 1751 (O᎐COC᎐O), 1639 (C᎐C); δ (500 MHz,
᎐
᎐
᎐
H
CDCl3) 7.43–7.45 (3H, m), 7.29–7.31 (2H, m), 7.10–7.18 (6H,
m), 7.01 (2H, d, J 8.3), 6.96 (1H, d, J 8.3), 6.80 (1H, s), 6.63
(2H, d, J 7.3), 5.65 (1H, s), 4.85 (1H, d, J 15.3), 4.70 (1H, d,
J 15.3), 2.36 (3H, s), 2.27 (3H, s); δC (125 MHz, CDCl3) 161.0,
160.8, 145.2, 143.8, 140.0, 137.3, 134.8, 133.7, 132.5, 132.2,
130.2, 130.1, 129.2, 128.3, 128.0, 127.5, 127.2, 127.0 126.0,
123.0, 122.3, 73.7, 56.3, 20.9, 20.6; m/z (EI) 486 (100, Mϩ)/487
(25), 234 (85, 7-methyl-5-phenylbenzodiazepine), 91 (100,
PhCH2).
Acknowledgements
This work was supported by the National Natural Science
Foundation of China and the Excellent Young Teachers
Program of MOE, P. R. C.
References
1 R. A. Moss, G. Kmiecik-Lawrynowicz and K. Krogh-Jespersen,
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1-Benzyl-7-fluoro-4-(4-fluorophenyl)-5-phenylbenzo[ f ][1,4]-
diazepine-2,3-dicarboxylic anhydride 23c. 0.72 g, 29%, as orange
crystals, mp 193–194 ЊC (Found: C 72.7, H 3.8, N 5.5.
C30H20F2N2O3 requires C 72.7, H 4.1, N 5.7%); IR (KBr) (νmax
/
cmϪ1): 1845, 1822 and 1752 (O᎐COC᎐O), 1642 (C᎐C); δ (500
᎐
᎐
᎐
H
MHz, CDCl3) 7.47–7.48 (3H, m), 7.30–7.31 (2H, m), 7.20 (1H,
t, J 7.2), 7.14 (2H, t, J 7.6), 7.06–7.08 (4H, m), 7.02 (1H, d,
J 6.2), 6.81 (1H, d, J 7.8), 6.66 (2H, d, J 7.4), 5.56 (1H, s), 4.74
(1H, d, J 15.1), 4.64 (1H, d, J 15.1); δC (125 MHz, CDCl3)
162.8, 162.2, 162.0, 160.0, 160.9, 160.6, 158.6, 144.8, 143.6,
140.1, 138.1, 135.8, 130.9, 129.9, 129.8, 129.2, 128.8, 127.2,
126.93/126.87 (d), 126.03/125.96 (d), 124.5, 123.1/122.9 (d),
119.9/119.1 (d), 118.1/117.9 (d), 117.8/117.6 (d), 74.8, 58.0; m/z
(EI) 494 (55, Mϩ)/495 (20), 238 (52, 7-fluoro-5-phenylbenzo-
diazepine), 91 (100, PhCH2).
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15 CCDC reference number 195707. See http://www.rsc.org/suppdata/
ob/b3/b307278a/ for crystallographic data in .cif or other electronic
format.
1-Benzyl-4,5-diphenylbenzo[ f ][1,4]diazepine-2,3-dicarboxylic
anhydride 23f. 0.53 g, 23%, as red crystals, mp 211–213 ЊC
(Found: C 78.6, H 4.5, N 6.0. C30H22N2O3 requires C 78.6,
H 4.8, N 6.1%); IR (KBr) (νmax/cmϪ1): 1844, 1822 and 1751
(O᎐COC᎐O), 1641 (C᎐C); δ (500 MHz, CDCl3) 7.45–7.46
᎐
᎐
᎐
H
(3H, m), 7.35–7.37 (2H, m), 7.31–7.34 (3H, m), 7.16–7.20 (2H,
m), 7.11–7.14 (5H, m), 7.07–7.08 (1H, m), 7.02–7.05 (1H, m),
6.63 (2H, d, J 7.4), 5.77 (1H, s), 4.94 (1H, d, J 15.3), 4.76 (1H, d,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 6 0 5 – 3 6 1 0
3609

View Online
16 Part of this work appeared as a preliminary communication:
Y. Cheng, H. Yang and O. Meth-Cohn, Chem. Commun., 2003, 90.
17 CCDC reference number 195706. See http://www.rsc.org/suppdata/
ob/b3/b307278a/ for crystallographic data in .cif or other electronic
format.
18 X. Cattoën, S. Solé, C. Pradel, H. Gornitzka, K. Miqueu,
D. Bourissou and G. Bertrand, J. Org. Chem., 2003, 68, 911.
19 CCDC reference number 203554. See http://www.rsc.org/suppdata/
ob/b3/b307278a/ for crystallographic data in .cif or other electronic
format.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 6 0 5 – 3 6 1 0
3610