One-pot formation of 1,3,4-oxadiazol-2(3 H)-ones and dibenzo[c, e]azepines by concomitant cathodic reduction of diazonium salts and phenanthrenequinones

Article abstract of DOI:10.1021/jo401264w

The one-pot concomitant electrochemical reduction of phenanthrenequinones (1, 2) and arenediazonium salts (3a-f) led to the formation of 1,3,4-oxadiazol-2(3H)-ones (4a-f, 5a) and dibenzo[c,e]azepines (6a-f) when N-methylformamide was used as the solvent. A new pathway, different from those previously described with other aprotic solvents, is proposed. The experimental data support a radical mechanism for the electrochemical process followed by an internal rearrangement to give the products.

Full text of DOI:10.1021/jo401264w

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Note
One-pot Formation of 1,3,4-Oxadiazol-2(3H)-ones
and Dibenzo[c,e]azepines by Concomitant Cathodic
Reduction of Diazonium salts and Phenanthrenequinones
Belen Batanero, Fructuoso Barba, and Avelino Martín
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo401264w • Publication Date (Web): 19 Aug 2013
Downloaded from http://pubs.acs.org on August 21, 2013
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The Journal of Organic Chemistry
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Oneꢀpot Formation of 1,3,4ꢀOxadiazolꢀ2(3H)ꢀones and
Dibenzo[c,e]azepines by Concomitant Cathodic
Reduction of Diazonium salts and
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Phenanthrenequinones
Belen Batanero* and Fructuoso Barba.
Department of Organic Chemistry. University of Alcalá. 28871 Alcalá de Henares (Madrid). Spain
Avelino Martin
Department of Inorganic Chemistry. University of Alcalá. 28871 Alcalá de Henares (Madrid). Spain
belen.batanero@uah.es;Tel. 34 91 885 2517. FAX: 34 91 8854686.
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X
X
1
2
3
4
5
6
7
8
O
X
O
X
+ e-
-0.5V
X
X
+
N
N
Ar
N
+
N
MeNHCOH
N Ar
N
Ar
N
-N2
O
H
O
3
O
Me
X=CH (6)
O
NHMe
X= CH(1), N(2)
X=CH (4), N(5)
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Ar= C6H5 (a), 4-MeO-C6H4 (b), 2-MeS-C6H4 (c), 4-Cl-C6H4 (d), 4-Br-C6H4 (e), 4-MeCO-C6H4 (f)
ABSTRACT
The oneꢀpot concomitant electrochemical reduction of phenanthrenequinones (1, 2) and arenediazonium
salts (3a-f) led to the formation of 1,3,4ꢀoxadiazolꢀ2(3H)ꢀones (4a-f, 5a) and dibenzo[c,e]azepines (6a-
f) when Nꢀmethylformamide is used as solvent. A new pathway, different from those previously
described with another aprotic solvents, is proposed. Experimental data support a radical mechanism for
the electrochemical process, followed by an internal rearrangement to give the products.
KEYWORDS: radical anion, electrode reduction, radical coupling, 1,2ꢀquinones, diazonium salts.
In a previous work1 we found that the concomitant electrochemical reduction of benzene
diazonium tetrafluoroborate and 1,2ꢀquinones, in DMF as solvent, afforded the corresponding
introduction of a N,Nꢀdimethylaminocarbonyl group in the quinone (Scheme 1). This radical pathway
was supported by the isolation of N,Nꢀdimethylbenzamide when the reaction was performed in the
absence of quinone.
+ e-
H-CO-NMe2
-N2
Ph-H + . CO-NMe2
N
.
N
N
Ph
O
Ph
N
O
Scheme 1
OH
O
O
O
O
Me
N
.
+ e-
CO-NMe2
+ H+
.
Me
-0.5V
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The Journal of Organic Chemistry
The simultaneous reduction of 1,2ꢀquinones and diazonium salt has been carried out with
1
2
different solvents such as acetonitrile, 1,2ꢀdichloroethane, dichloromethane, chloroform,
chloroacetonitrile or ethyl acetate with positive results.1,2 Here we report a similar reaction using Nꢀ
methylformamide as solvent, instead of DMF. The obtained results are significantly different, although
the initial process is again a radical reaction, however the subsequent radical coupling is followed by an
unexpected cleavage and rearrangement that evolves to 1,3,4ꢀoxadiazolꢀ2(3H)ꢀones and/or 1Hꢀazepines,
depending on the nature of the electrolyte used.
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Surprisingly, the literature does not describe oneꢀpot procedures to obtain substituted 1,3,4ꢀ
oxadiazolꢀ2(3H)ꢀones. Although a series of them were prepared from aldehydes, ketones, phenyl acetic
acids and 1,2ꢀ or 1,3ꢀdiketones, conditions for the formation of these oxadiazolones from the precursor
Nꢀcarbamoyl chlorides depend on the structure, and differ from spontaneous ring closure to those
requiring bases.3 Also, a novel process for the preparation of 3,5ꢀdisubstituted 3Hꢀ[1,3,4]ꢀoxadiazolꢀ2ꢀ
ones from the reaction of Nꢀtertꢀbutylꢀdiacylhydrazines with potassium tertꢀbutoxide followed by
treatment with phosgene has been reported.4
A more recent synthesis of 3ꢀmethylꢀ5ꢀarylꢀ1,3,4ꢀoxadiazolones has been performed starting
from 1ꢀRꢀ3ꢀarylꢀ5ꢀmethylꢀ6ꢀoxoverdazyl radicals.5 Substituted 1,3,4ꢀoxadiazolꢀ2ꢀones are potent
hormoneꢀsensitive lipase (HSL) inhibitors. HSL plays an important role in the mobilization of free fatty
acids (FFA) from adipocytes. In this sense, the inhibition of HSL may offer a pharmacological approach
to reduce FFA levels in plasma and diminish peripheral insulin resistance in type 2 diabetes.6 1,3,4ꢀ
Oxadiazolꢀ2ꢀones have also been used in therapy as modulators of peroxisome proliferatorꢀactivated
receptor delta,7 and are useful for treating conditions modulated by a peroxisome proliferators activated
receptor such as diabetes mellitus.8
On the other hand, 1Hꢀazepines result from spontaneous valenceꢀbond isomerization of
azanorcaradienes, which are themselves made by reaction of arenes with nitrenes.9 A 1Hꢀazepine ring
has been described to show interesting pharmacological properties as potent and highly selective
inhibitor of human neuronal nitric oxide synthase.10
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As it has been indicated above, the concomitant electrochemical reduction of 1,2ꢀdicarbonyl
compounds (1, 2) and arenediazonium salts (3), in Nꢀmethylformamide as solvent, gives 1,3,4ꢀ
oxadiazolꢀ2(3H)ꢀones (4a-f, 5a) and dibenzo[c,e]azepines (6a-f), following a reaction pathway
completely different from those previously described in another aprotic solvents. Transformation of 1
and 3a to 4a and 6a is indicated in scheme 2.
1
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O
O
+ e-
-0.5V
+
N
N
Ph
N
+
N
MeNHCOH
-N2
N Ph
N
Ph
N
O
H
3a
O
1
O
Me
O
NHMe
4a
6a
Scheme 2
The first electrochemical step provides, once again, the radical anion of 1 and the aryl radical of
3, which abstracts a hydrogen atom from the carbonyl position in the Nꢀmethylformamide. A further
radical coupling produces the alkoxide anion indicated in scheme 3. On the other hand, we have
observed that, in the absence of a dicarbonyl compound, the electrochemical reduction of the arene
diazonium salt in Nꢀmethylformamide produces the corresponding Nꢀmethylbenzamide. This fact
supports the radical nature of this pathway.
H-CO-NHMe
+ e-
-N2
.
.
Ar-H + . CO-NHMe
N
N
N
O
Ar
Ar
Ar
N
3
.
Ar
Ar CONHMe
O
O
O
O
O
O
.
+ e-
CO-NHMe
.
N
Me
H
-0.5V
Scheme 3
1
Once the radical coupling reaction takes place, and due to the absence of steric hindrance
(present when DMF was used as solvent), the remaining alkoxide anion is added to the amide carbonyl
group. A similar intramolecular nucleophilic attack from the alkoxide was already observed when the
reaction was carried out in 1,2ꢀdichloroethane as solvent. In that case, 14% of spiroepoxide was
obtained as a side product together with the expected 1,2ꢀdichloroethylated derivative.1
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The Journal of Organic Chemistry
Then, after the attack of the alkoxide, the following processes should take place simultaneously:
1
2
1) migration of the leaving group to the carbonyl group of the ketone, 2) carbonꢀcarbon bond cleavage
(assisted by the diazonium salt) and 3) ring formation to afford 3,5ꢀdiarylꢀ1,3,4ꢀoxadiazolꢀ2(3H)ꢀone
(4). This plausible reaction pathway is summarized in Scheme 4.
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Ar
Ar
N
N
N
N2
O
N
Ar
O
O
O
O
O
O
Me
O
O
N
O
O
O
NHMe
ii
NHMe
4
H
i
NHMe
Scheme 4
It is important to highlight that, although several steps take place in the electrochemical cell, the
products are obtained in a oneꢀpot process.
This pathway proposal is supported by the isolation of 3ꢀmethyl phenanthro[9,10ꢀd]oxazolꢀ
2(3H)ꢀone (< 4% yield) (see scheme 5) formed by the reaction of i with a small amount of water present
in the Nꢀmethylformamide, used as solvent.
+H+
Scheme 5
O
O
O
-H2O
O
N
O
N
O
O
N
Me
Me
Me
i
H
It should be noticed that in the Nꢀmethylformamide molecule, two possibilities of radical
hydrogen abstraction can be considered, being the hydrogen bonded to the carbonyl group faster
abstracted than that bonded to the nitrogen atom, as it had been already suggested by Cadman11 et al.
It is well known that in absence of a diazonium salt, the radical anion of 1 evolves to the starting
substrate by electron transfer to the oxygen in the air. However, once the radical anion is formed and the
potentiostat is switched off, if the diazonium salt is immediately added, some amount of 4 was formed,
probably due to an electronꢀtransfer process between the radical anion of 1 and the diazonium salt, as
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indicated in scheme 6.
1
2
3
O
O
O
O
4
5
6
7
E.T.
N
.
.
N
N
Ar
+
Ar
N
+
Scheme 6
3
1
8
9
O
O
H-CO-NHMe
-N2
Ar-H + . CO-NHMe
N
.
.
.
N
Ar
Ar
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4
Moreover, when the lithium salt is substituted by a tetrabutylammonium salt as electrolyte, 1H
azepine is also obtained together with (or ). The results are indicated in Table 1.
ꢀ
6
4
5
1,2-dicarbonyl compound
ArN2+ (3)
a: C6H5
% 4 (5):(*)
% 6:(*)
% 4 (5):(**)
% 6:(**)
13
1:9,10-Phenanthrenequinone
91
60
3
78
8
b: 4-MeO-C6H4
c: 2-MeS-C6H4
d: 4-Cl-C6H4
e: 4-Br-C6H4
f: 4-MeCO-C6H4
a: C6H5
-
62
92
traces
83
-
traces
71
88
-
-
82
1
88
83
5
-
2
84
2:1,10-Phenanthroline-5,6-dione
(64)
(60)
-
Table 1. Obtained yields (%) of 4 (5) and 6 in the concomitant reduction of 1 (2) and 3.
(*) SSE: N-methylformamide/LiClO4. (**) SSE: N-methylformamide/Bu4NClO4.
The formation of the azepines
in the formation of . However the azepines are formed after the loss of a carbon dioxide molecule from
this intermediate, as shown in scheme 7.
6 can be rationalized through the same intermediate (ii) postulated
4
Scheme 7
N
Ar
N
N
-CO2
N
N
Ar
N
Ar
N
O
H
O
O
O
Me
H
O
6
NHMe
MeN
ii
6
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The Journal of Organic Chemistry
The possible provenance of
DMF, during 24 h, did not afford any amount of
Finally, the hydrolysis of compound was carried out, providing the corresponding Nꢀmethylꢀ
dibenzo[c,e]azepineꢀ5,7ꢀdione, supporting the proposed structure for . Nevertheless the structures of
and were unequivocally determined by the corresponding single crystal Xꢀray diffraction studies on
4a 5a and 6b (see Supporting Information file).
6 by thermal decomposition of 4 was ruled out when a reflux of 4 in
1
2
3
4
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9
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.
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,
Experimental Section
The peak potentials are given in volts (V) (vs. Ag/Ag+(3M)). Mass spectra were determined using
EI, ionizing voltage 70 eV. IR spectra of the compounds were recorded as dispersions in KBr or NaCl
1
films. H and 13C NMR spectra were recorded in CDCl3 on a 300 MHz spectrometer with
tetramethylsilane (TMS) as the internal standard. The chemical shifts are given in ppm. All melting
points are uncorrected.
General Electrochemical Procedure.
The electroactive diazonium tetrafluoroborates were prepared according to conventional
methods.12 The electrolyses were carried out under argon atmosphere and potentiostatic conditions.
Cyclic voltammetry of
1
shows, under aprotic conditions1, two reversible reduction peaks with values:
Epc1= ꢀ0.5V and Epc2= ꢀ1.0V. A concentric cell with two compartments, separated by a porous (D4) glass
frit diaphragm, and equipped with a magnetic stirrer was used. The temperature was maintained constant
at 5 ºC with a cryostat. A mercury pool was used as the cathode (12 cm2) and a platinum plate as the
anode (2 x 2 x 0.1 cm). A reference Ag/Ag+(3M) electrode was used. The solventꢀsupporting electrolyte
system (SSE) was anhydrous Nꢀmethylformamide containing 0.1M lithium perchlorate or
tetrabutylammonium perchlorate.
A solution of 9,10ꢀphenanthrenequinone (1) or 1,10ꢀphenanthrolineꢀ5,6ꢀdione (2) (1.0 mmol in
60ml of SSE) was electrolyzed at the constant potential of ꢀ0.5V, vs. Ag/Ag+(3M). The diazonium salts
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(3) (2 mmol) were added, as solid portions, to the cathodic compartment during the electrolysis (5h).
1
2
3
4
5
6
7
8
9
Initial current of 100 mA was decreased during the reduction (except when a new diazonium salt portion
was added). The complete disappearance of the radical anion red coloration in the cathode solutions
(once the diazonium salt was completely added) indicated the end of the electrolysis. When the final
current was close to 3mA, a charge consumption of 3F/mol was achieved.
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Once the reduction was finished, the solvent in the cathodic solution was removed under reduced
pressure. The residue was extracted with ether/water and the organic phase dried over Na2SO4 and
concentrated by evaporation. The resulting products were purified by silica gel 60 (35ꢀ70 mesh) in a
(30x3cm) column, using mixtures CH2Cl2/EtOH as eluents. Spectroscopic description of the obtained
compounds is given below. Yields are given as isolated product in (*) SSE: Nꢀmethylformamide/LiClO4
or (**) SSE: Nꢀmethylformamide/Bu4NClO4.
3-Methyl phenanthro[9,10-d]oxazol-2(3H)-one: Mp 208ꢀ210 ºC.[Lit.13 210ꢀ211ºC]. MS m/z (relative
intensity) EI: 250 (M++1, 21), 249 (M+, 100), 234(7), 220(40), 206(18), 192(34), 177(12), 165(56),
151(15).
N-Methyl-5H-dibenzo[c,e]azepine-5,7(6H)-dione: Mp 161ꢀ163 ºC.[Lit.14 165ꢀ167 ºC]. IR (KBr) ν/cmꢀ
1 = 3058, 2924, 1596, 1504, 1445, 1281, 1224, 1029, 752, 725. MS m/z (relative intensity) EI: 237 (M+,
19), 209 (100), 192(24), 181(30), 165(31), 152(28) 126(4), 76(12).
5-[2-(2´-(methylcarbamoyl)phenyl)phenyl]-3-phenyl-1,3,4-oxadiazol-2(3H)-one
(4a): (337 mg,
91%)*. Mp 129ꢀ132 ºC. IR (KBr) ν/cmꢀ1 = 3370, 3062, 2924, 1782, 1649, 1597, 1501, 1373, 1145, 753.
1H NMR (300 MHz; CDCl3) δ (ppm): 2.78 (d, 3H, J=5.0 Hz), 5.9 (bs, 1H), 7.1ꢀ7.6 (m, 11H), 7.8ꢀ7.9
13
(m, 2H). C NMR (75.4 MHz, CDCl3) δ: 26.6, 117.8, 122.0, 126.1, 127.5, 128.1, 128.3, 128.4, 129.7,
130.0, 130.1, 131.2, 131.6, 132.0, 138.3, 140.2, 165.5, 169.7. MS m/z (relative intensity) EI: 371(M+,
18), 314(24), 313(100), 269 (15), 204(21), 194(35), 167(16), 151(14), 91(8), 77(5). Anal. Calc. for C22
H17 N3 O3: C, 71.16; H, 4.58; N, 11.32. Found: C, 70.86; H, 4.80; N, 11.07.
5-[2-(2´-(methylcarbamoyl)phenyl)phenyl]-3-(4-methoxyphenyl)-1,3,4-oxadiazol-2(3H)-one
(4b):
(240 mg, 60%)*. Mp 62ꢀ64 ºC. IR (KBr) ν/cmꢀ1 = 3401, 3058, 2929, 1771, 1653, 1513, 1380, 1251,
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1
1029, 833, 757. H NMR (300 MHz; CDCl3) δ (ppm): 2.64 (d, 3H, J=5.0 Hz), 3.81(s, 3H), 5.8(bs, 1H),
1
2
3
13
6.87(d, 2H, J=9.4 Hz), 7.18ꢀ7.22(m, 1H), 7.4ꢀ7.5(m, 3H), 7.57(t, 2H, J=8.0 Hz), 7.65ꢀ8.0(m, 4H). C
4
5
6
7
8
NMR (75.4 MHz, CDCl3) δ: 26.6, 55.5, 114.4, 119.7, 127.6, 127.7, 127.9, 128.1, 128.2, 128.3, 128.6,
129.2, 129.8, 129.9, 130.2, 131.2, 131.5, 150.4, 153.2, 157.7, 169.6. MS m/z (relative intensity) EI: 402
(M++1, 20), 401(M+, 76), 343(49), 222(100), 204(41), 195(25), 178(18), 151(22), 121(47), 106(12).
Anal. Calc. for C23 H19 N3 O4: C, 68.83; H, 4.74; N, 10.47. Found: C, 68.57; H, 4.55; N, 10.72.
5-[2-(2´-(methylcarbamoyl)phenyl)phenyl]-3-[2-(methylthio)phenyl]-1,3,4-oxadiazol-2(3H)-one
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(
4c): (383 mg, 92%)*. Mp 92ꢀ94 ºC. IR (KBr) ν/cmꢀ1 = 3421, 3051, 2921, 1786, 1652, 1534, 1479, 1337,
1
974, 751. H NMR (300 MHz; CDCl3) δ (ppm): 2.3(s, 3H), 2.55(d, 3H, J=5.0 Hz), 6.0(bs, 1H), 7.12(t,
13
2H, J=7.6 Hz), 7.19(t, 2H, J=8.9 Hz), 7.28ꢀ7.36(m, 4H), 7.40ꢀ7.51(m, 3H), 7.80(d, 1H, J=7.6 Hz). C
NMR (75.4 MHz, CDCl3) δ: 15.9, 26.6, 122.3, 125.7, 127.2, 127.7, 127.9, 128.1, 128.8, 129.7, 129.8,
130.1, 131.4, 131.5, 132.2, 136.8, 137.0, 137.7, 140.4, 151.8, 154.0, 170.0. MS m/z (relative intensity)
EI: 418(M++1, 4), 417(M+, 14), 360(26), 359(100), 268(7), 238(16), 206(28), 194(31), 181(52),
166(23), 152(25), 136(72), 122(21), 78(9). Anal. Calc. for C23 H19 N3 O3 S: C, 66.19; H, 4.56; N, 10.07;
S, 7.67. Found: C, 65.87; H, 4.31; N, 9.80; S, 7.95.
5-[2-(2´-(methylcarbamoyl)phenyl)phenyl]-3-(4-chlorophenyl)-1,3,4-oxadiazol-2(3H)-one
(4d):
(356 mg, 88%)*. Mp 59ꢀ61 ºC. IR (KBr) ν/cmꢀ1 = 3411, 3058, 2921, 1785, 1647, 1534, 1495, 1377,
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1095, 974, 934, 830, 736. H NMR (300 MHz; CDCl3) δ (ppm): 2.56(d, 3H, J=4.7 Hz), 5.62(bs, 1H),
7.10ꢀ7.16(m, 1H), 7.17ꢀ7.43(m, 7H), 7.48(t, 2H, J= 6.8Hz), 7.54ꢀ7.63(m, 1H), 7.83(d, 1H, J=6.8 Hz).
13C NMR (75.4 MHz, CDCl3) δ: 26.5, 118.9, 121.7, 127.5, 128.0, 128.2, 128.3, 129.1, 129.8, 129.9,
131.1, 131.3, 131.6, 134.3, 136.0, 138.1, 140.2, 150.0, 153.3, 169.2. MS m/z (relative intensity) EI:
407(M++2, 6), 405(M+, 18), 349(35), 347(100), 303(8), 268(9), 222(27), 204(36), 194(51), 167(28), 151
(21), 125(16), 90(18), 63(9). Anal. Calc. for C22 H16 Cl N3 O3: C, 65.10; H, 3.95; N, 10.36. Found: C,
64.88; H, 4.11; N, 10.56.
5-[2-(2´-(methylcarbamoyl)phenyl)phenyl]-3-(4-bromophenyl)-1,3,4-oxadiazol-2(3H)-one
(4e):
(368 mg, 82%)*. Mp 60ꢀ62 ºC. IR (KBr) ν/cmꢀ1 = 3414, 3060, 2962, 1784, 1653, 1540, 1492, 1262,
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1096, 1035, 803. H NMR (300 MHz; CDCl3) δ (ppm): 2.57(d, 3H, J=5.0 Hz), 5.62(bs, 1H), 7.10ꢀ
7.18(m, 1H), 7.30ꢀ7.42(m, 7H), 7.42ꢀ7.56(m, 2H), 7.56ꢀ7.64(m, 1H), 7.83(dd, 1H, J1=7.6 Hz, J2=1.5
Hz). 13C NMR (75.4 MHz, CDCl3) δ: 26.6, 119.2, 119.3, 121.8, 127.6, 128.1, 128.3, 128.4, 129.9,
130.0, 131.2, 131.7, 132.2, 134.9, 136.1, 138.2, 140.3, 149.9, 153.5, 169.3. MS m/z (relative intensity)
EI: 451(M++2, 19), 449(M+, 18), 394(22), 393 (90), 392(22), 391(90), 350(9), 348(9), 296(12), 268(26),
239(12), 222(66), 204(72), 194(100), 167(50), 151(51), 90(49), 63(36). Anal. Calc. for C22 H16 Br N3
O3: C, 58.67; H, 3.56; N, 9.33. Found: C, 58.72; H, 3.81; N, 9.07.
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5-[2-(2´-(methylcarbamoyl)phenyl)phenyl]-3-(4-acetylphenyl)-1,3,4-oxadiazol-2(3H)-one (4f):
(342 mg, 83%)*. Mp 61ꢀ63 ºC. IR (KBr) ν/cmꢀ1 = 3419, 2923, 1786, 1643, 1602, 1377, 1266, 933, 841,
770. 1H NMR (300 MHz; CDCl3) δ (ppm): 2.61 (s, 3H), 2.67 (d, 3H, J=4.9 Hz), 5.7(bs, 1H), 7.44(d, 1H,
J=7.4 Hz), 7.48ꢀ7.68(m, 7H), 7.68ꢀ7.74(m, 1H), 7.94ꢀ8.0(m, 3H). 13C NMR (75.4 MHz, CDCl3) δ: 26.5,
26.6, 117.2, 121.7, 127.6, 128.1, 128.2, 128.3, 129.6, 129.9, 130.0, 131.1, 131.8, 133.2, 136.0, 138.2,
139.5, 148.8, 149.8, 171.8, 196.7. MS m/z (relative intensity) EI: 414 (M++1, 4), 413(M+, 13), 356(24),
355(100), 312(4), 297(17), 269(9), 222(11), 204(18), 194(33), 166(17), 151(12). Anal. Calc. for C24 H19
N3 O4: C, 69.73; H, 4.60; N, 10.17. Found: C, 70.07; H, 4.91; N, 9.89.
5-[2-(3-(methylcarbamoyl)-pyridin-2-yl-)pyridin-3-yl-]-3-phenyl-1,3,4-oxadiazol-2(3H)-one
(5a):
(238 mg, 64%)*. Mp 161ꢀ162 ºC. IR (KBr) ν/cmꢀ1 = 3415, 3056, 2925, 1773, 1663, 1578, 1378, 1043,
735. 1H NMR (300 MHz; CDCl3) δ (ppm): 2.72 (d, 3H, J=5.0 Hz), 6.4 (bs, 1H), 7.15 (t, 1H, J=8.0 Hz),
7.3 (t, 2H, J=8.0 Hz), 7.4ꢀ7.54 (m, 4H), 8.06 (dd, 1H, J1=7.9 Hz, J2=1.6 Hz), 8.28 (dd, 1H, J1=8.2 Hz,
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J2=1.6 Hz), 8.64 (dd, 1H, J1=4.6 Hz, J2=1.6 Hz), 8.72 (dd, 1H, J1=4.6 Hz, J2=1.6 Hz). C NMR (75.4
MHz, CDCl3) δ: 26.7, 117.9, 119.6, 123.3, 123.5, 126.1, 129.0, 136.0, 136.3, 136.6, 150.3, 150.6, 151.8,
155.0, 156.4, 167.4. MS m/z (relative intensity) CI: 414(M++41, 6), 402(M++29, 19), 374(M++1, 40),
343 (100), 329(21), 269(11), 207(14). Anal. Calc. for C20 H15 N5 O3: C, 64.34; H, 4.02; N, 18.77.
Found: C, 63.98; H, 4.23; N, 18.91.
N-Methyl-dibenzo[c,e]azepine-5-one-7-(ylidene-2-phenylhydrazine) (6a):
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(43 mg, 13%)**. Mp 74ꢀ75 ºC. IR (KBr) ν/cmꢀ1 = 3276, 2923, 1642, 1602, 1445, 1372, 1252, 1120, 752,
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736, 696. H NMR (300 MHz; CDCl3) δ (ppm): 2.0(bs, 1H), 3.24(s, 3H), 6.82(t, 1H, J=7.3 Hz), 7.0(d,
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1H, J=7.6 Hz), 7.16(d, 1H, J=7.6 Hz), 7.3ꢀ7.55(m, 5H), 7.57(d, 1H, J=7.6 Hz), 7.67(t, 1H, J=7.9 Hz),
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7.86(d, 1H, J=7.6 Hz), 7.97(d, 1H, J=7.9 Hz), 8.14(d, 1H, J=7.9 Hz). C NMR (75.4 MHz, CDCl3) δ:
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31.8, 113.6, 121.2, 128.0, 128.1, 128.3, 128.5, 129.3, 129.4, 129.8, 130.7, 131.5, 132.2, 132.9, 135.8,
137.1, 137.3, 143.7, 169.0. MS m/z (relative intensity) EI: 328(M++1, 22), 327(M+, 89), 269(17),
222(100), 204(54), 195(28), 178(17), 165(35), 151(15), 91(3), 77(5). Anal. Calc. for C21 H17 N3 O: C,
77.06; H, 5.20; N, 12.84. Found: C, 77.21; H, 5.01; N, 12.66.
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N-Methyl-dibenzo[c,e]azepine-5-one-7-(ylidene-2-(4-methoxyphenyl)hydrazine) (6b):
(220 mg, 62%)**.Mp 213ꢀ215 ºC. IR (KBr) ν/cmꢀ1 = 3264, 3058, 2926, 1643, 1514, 1444, 1366, 1236,
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1035, 826, 740. H NMR (300 MHz; CDCl3) δ (ppm): 3.27(s, 3H), 3.73(s, 3H), 6.8(d, 2H, J=9.1 Hz),
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7.0(d, 2H, J=9.1 Hz), 7.4ꢀ7.55(m, 6H), 7.6(d, 1H, J=7.0 Hz), 7.9(d, 1H, J=7.9 Hz). C NMR (75.4
MHz, CDCl3) δ: 31.6, 55.7, 114.5, 114.6, 125.9, 127.9, 128.0, 128.2, 128.4, 129.3, 129.6, 129.9, 130.6,
130.8, 131.2, 131.4, 137.0, 137.7, 154.3, 168.9. MS m/z (relative intensity) EI: 358(M++1, 19), 357(M+,
72), 300(3), 222 (100), 204 (44), 195(25), 178(19), 165(32), 151(22), 122(41), 92(13), 77(8), 65(5).
Anal. Calc. for C22 H19 N3 O2: C, 73.95; H, 5.32; N, 11.76. Found: C, 74.22; H, 5.60; N, 11.49.
N-Methyl-dibenzo[c,e]azepine-5-one-7-(ylidene-2-(4-chlorophenyl)hydrazine) (6d):
(255 mg, 71%)**. Mp 226ꢀ228 ºC. IR (KBr) ν/cmꢀ1 = 3276, 3058, 2923, 1637, 1616, 1506, 1492, 1370,
1250, 1087, 824, 737. 1H NMR (300 MHz; CDCl3) δ (ppm): 3.22(s, 3H), 6.94(d, 2H, J=8.9 Hz), 7.12 (d,
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2H, J=8.9 Hz), 7.3ꢀ7.55(m, 7H), 7.58 (d, 1H, J=7.8 Hz), 7.82(d, 1H, J=7.8Hz). C NMR (75.4 MHz,
CDCl3) δ: 31.9, 114.0, 114.3, 128.0, 128.3, 128.6, 129.2, 129.4, 129.9, 130.7, 131.6, 132.7, 136.2,
136.7, 137.0, 137.2, 142.4, 169.2.. MS m/z (relative intensity) EI: 363(M++2, 21), 361(M+, 60), 304(12),
269(7), 222 (100), 204(58), 195(31), 178(18), 167(31), 165(36), 151(23), 125(10), 111(12), 90(10),
75(8). Anal. Calc. for C21 H16 Cl N3 O: C, 69.71; H, 4.43; N, 11.62. Found: C, 69.50; H, 4.61; N, 11.53.
N-Methyl-dibenzo[c,e]azepine-5-one-7-(ylidene-2-(4-bromophenyl)hydrazine) (6e):
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(357 mg, 88%)**. Mp 232ꢀ234ºC. IR (KBr) ν/cmꢀ1 = 3280, 3058, 2931, 1636, 1593, 1497, 1487, 1368,
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1250, 1140, 1121, 1069, 819, 762, 737. H NMR (300 MHz; CDCl3) δ (ppm): 3.14(s, 3H), 6.81(d, 2H,
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J=8.9 Hz), 7.1 (d, 2H, J=8.9 Hz), 7.2ꢀ7.5(m, 7H), 7.62 (d, 1H, J=7.6 Hz), 7.84(s, 1H). C NMR (75.4
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MHz, CDCl3) δ: 32.0, 112.9, 115.0, 127.9, 128.0, 128.3, 128.5, 129.4, 129.8, 130.7, 131.5, 131.9, 132.6,
135.8, 136.8, 137.0, 137.2, 142.9, 168.7. MS m/z (relative intensity) EI: 407(M++2, 17), 405(M+, 17),
350(4), 348(4), 269(6), 222 (100), 204(52), 195(28), 178(19), 165(35), 151(21), 91(6), 76(4), 63(8).
Anal. Calc. for C21 H16 Br N3 O: C, 62.07; H, 3.94; N, 10.34. Found: C, 62.21; H, 4.13; N, 10.24.
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N-Methyl-dibenzo[c,e]azepine-5-one-7-(ylidene-2-(4-acetylphenyl)hydrazine) (6f):
(310 mg, 84%)**. Mp 138ꢀ140 ºC. IR (KBr) ν/cmꢀ1 = 3256, 3059, 2928, 1654, 1598, 1522, 1444, 1359,
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1261, 1108, 835, 740. H NMR (300 MHz; CDCl3) δ (ppm): 2.5(s, 3H), 3.3(s, 3H), 7.1(d, 2H, J=8.5
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Hz), 7.27ꢀ7.67(m, 7H), 7.85(d, 3H, J=8.9 Hz), 8.0(s, 1H). C NMR (75.4 MHz, CDCl3) δ: 26.3, 32.2,
112.7, 127.9, 128.0, 128.4, 128.6, 129.4, 130.0, 130.3, 130.4, 130.7, 131.6, 132.6, 136.5, 136.9, 137.1,
137.6, 147.5, 168.7, 196.5. MS m/z (relative intensity) EI: 370(M++1, 23), 369(M+, 98), 312(7),
297(16), 269(7), 222 (100), 204 (71), 195(39), 178(21), 165(42), 151(22), 91(8), 77(6). Anal. Calc. for
C23 H19 N3 O2: C, 74.80; H, 5.15; N, 11.38. Found: C, 74.65; H, 5.33; N, 11.46.
ACKNOWLEDGMENT This work was supported by the Spanish Ministry of Science and Education
through B. Batanero I3 program and by Factoría de Cristalización (CONSOLIDERꢀINGENIO 2010).
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Supporting Information. IR, MS and NMR (1H and C) spectra of 4, 5 and
6 are included. Ortep
drawing of compounds 4a
,
5a and 6b, as well as Crystallographic information files (CIF) for 4a
,
5a and
6b are provided. This material is available free of charge via the Internet at http://pubs.acs.org/.
REFERENCES
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Batanero, B.; Saez, R.; Barba, F. Electrochim. Acta 2009, 54, 4872ꢀ4879.
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Batanero, B.; Barba, F.; Ranz, F.; Barba, I.; Elinson, M.N. Tetrahedron 2012, 68, 5979ꢀ5983.
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