Ag3PW12O40: A novel and recyclable heteropoly acid for the synthesis of 1,5-benzodiazepines under solvent-free conditions

Article abstract of DOI:10.1055/s-2004-816013

o-Phenylenediamines undergo smooth condensation with ketones having hydrogens at a-position on the surface of heteropoly acid (Ag₃PW ₁₂O₄₀) under extremely mild conditions to afford the corresponding 1,5-benzodiazepines in

Full text of DOI:10.1055/s-2004-816013

PAPER
901
Ag3PW12O40: A Novel and Recyclable Heteropoly Acid for the Synthesis of
1,5-Benzodiazepines under Solvent-Free Conditions
N
ovel and
.
Recyclable
S
H
eteropoly
A
c
.
id for 1,5-B
enzodiazepines adav,* B. V. S. Reddy, S. Praveenkumar, K. Nagaiah, N. Lingaiah, P. S. Saiprasad
Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)27160512; E-mail: yadav@iict.ap.nic.in
Received 16 December 2003; revised 4 February 2004
and selectivity so that they can be conveniently used in
continuous flow reactions. Among various heterogeneous
catalysts, heteropoly acids are most attractive, because of
their reusability, flexibility in modifying the acid strength,
Abstract: o-Phenylenediamines undergo smooth condensation
with ketones having hydrogens at a-position on the surface of het-
eropoly acid (Ag3PW12O40) under extremely mild conditions to af-
ford the corresponding 1,5-benzodiazepines in excellent yields with
high selectivity. The catalyst can be recovered by simple filteration ease of handling, environmental compatibility, non-toxic-
ity and experimental simplicity.9 However, there are no
and can be reused in subsequent reactions.
examples of the use of the silver salt of heteropoly acid for
the preparation of 1,5-benzodiazepines. The use of het-
eropoly acid as a recyclable catalyst makes the reaction
process more convenient, economic and environmentally
benign.
Keywords: heteropoly acids, o-phenylenediamines, ketones, ben-
zodiazepines
Benzodiazepines have received great importance because
of their medicinal and therapeutic properties.1 Many func-
tionalized benzodiazepines are widely used as anticonvul-
sant, antianxiety, analgesic, sedative, antidepressive, and
hypnotic agents.2 Benzodiazepines also find commercial
use as dyes for acrylic fibers3 and as anti-inflammatory
agents.4 In addition, 1,5-benzodiazepines are key interme-
diates for the synthesis of various fused ring compounds
such as triazolo-, oxadiazolo-, oxazino-, or furanobenzo-
diazepines.5 Due to their wide range of biological, indus-
trial, and synthetic applications, these compounds have
recently received a great deal of attention. The simplest
and the most straightforward procedure for the synthesis
of 1,5-benzodiazepines involves the acid catalyzed con-
densation of o-phenylenediamines with ketones.6 A vari-
ety of catalysts such as BF3·OEt2, NaBH4, polyphosphoric
acid–SiO2, MgO–POCl3, Yb(OTf)3, Al2O3–P2O5, HOAc–
microwave, SO42––ZrO2, and 1-butyl-3-methylimidazoli-
um bromide ([bmim]Br) have been employed to effect
this transformation.6,7 Since 1,5-benzodiazepines have be-
come increasingly useful and important in the fields of
drugs and pharmaceuticals, the development of clean,
high-yielding and environmentally friendly approaches
are desirable.
In view of the emerging importance of the use of hetero-
geneous solid acids as reusable catalysts in organic syn-
thesis, herein we wish to disclose a mild and efficient
protocol for the synthesis of 1,5-benzodiazepines using a
silver salt of heteropoly acid (Ag3PW12O40)10 as a novel
heterogeneous catalyst (Scheme 1).
Scheme 1
Accordingly, treatment of o-phenylenediamine with ace-
tone in the presence of silver salt of 12-tungustophospho-
ric acid (Ag3PW12O40) at room temperature afforded
2,4,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine in
92% yield (Table 1, entry 3a). Similarly, various ketones
such as acetone, acetophenone, 2-butanone, and isobutyl
methylketone underwent smooth condensation with o-
phenylenediamines in solvent-free conditions11 to give the
corresponding 1,5-benzodiazepines in 80–95% yields
(Table 1, entries 3a–3m). The reactions were clean and
the products were obtained in high yields in short reaction
times. The crude products were purified either by recrys-
tallization from a mixture of Et2O–n-hexane or by silica
gel column chromatography. The reaction of cyclic ke-
tones such as cyclohexanone, cyclopentanone, and cyclo-
heptanone with o-phenylenediamine in the presence of
In recentyears, the use of solid acids as heterogeneous cat-
alysts has received considerable interest in different areas
of organic synthesis.8 Heterogeneous solid acids are ad-
vantageous over conventional homogeneous acid cata-
lysts as they can be easily recovered from the reaction
mixture by simple filtration and can be reused after acti-
vation or without activation, thereby making the process
economically viable. In many cases, heterogeneous cata-
lysts can be recovered with only minor change in activity
SYNTHESIS 2004, No. 6, pp 0901–0904
x
x
.
x
x
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0
0
4
Advanced online publication: 15.03.2004
DOI: 10.1055/s-2004-816013; Art ID: Z17903SS.pdf
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

902
J. S. Yadav et al.
PAPER
Ag3PW12O40 afforded fused ring 1,5-benzodiazepines in
good yields (Table 1, entries 4n, 4o, 4p; Scheme 2).
Table 1 Ag3PW12O40-Catalyzed Synthesis of 1,5-Benzodiazepines
under Solvent-Free Conditions
In all cases, the reactions proceeded efficiently at room
temperature under solvent-free conditions. All of the
Entry Diamine
Ketone
Producta
Reaction Yield
Time (h) (%)
1
products were characterized by H, 13C NMR, IR, and
a
CH3COCH3
3.0
92
mass spectral analysis and also by comparison with au-
thentic samples.6,7 Both cyclic and acyclic ketones
worked well under similar reaction conditions. This meth-
od is effective for the preparation of benzodiazepines
from both electron-rich as well as electron-deficient o-
phenylenediamines. However, in the absence of het-
eropoly acid, the reaction did not proceed at room temper-
ature even after long reaction times (8–12 h). The efficacy
of other solid acids such as K10 clay, SiO2, and H-ZSM-
5 was studied for this reaction. Among these catalysts, sil-
ver salt of 12-tungustophosphoric acid (Ag3PW12O40) was
found to be superior in terms of conversion and reaction
rates. The catalyst was easily separated by simple filtra-
tion and reused after drying with gradual decrease in ac-
tivity. For instance, the reaction of o-phenylenediamine
and acetone afforded 2,3-dihydro-1,5-benzodiazepine in
95%, 89%, 85%, and 80% yields over four cycles. Thus,
this procedure provides an easy access to the preparation
of substituted 1,5-benzodiazepines with a wide range of
substitution patterns.
b
PhCOCH3
5.0
86
c
CH3COCH2CH3
3.5
4.0
85c
82
d
e
f
CH3COCH3
PhCOCH3
2.5
5.5
93
85
g
CH3COCH2CH3
4.0
4.5
83c
80
h
In summary, we describe a mild, convenient and efficient
protocol for the synthesis of 2,3-dihydro-1H-1,5-benzodi-
azepines via the condensation of o-phenylenediamines
with ketones using heteropolyacid as a recyclable hetero-
geneous catalyst. The simple experimental procedure
combined with ease of recovery and reuse of this novel
catalyst makes this procedure quite simple, more conve-
nient and environmentally benign.
i
CH3COCH3
PhCOCH3
3.0
4.5
95
84
j
k
l
CH3COCH3
CH3COCH3
PhCOCH3
3.5
5.0
6.5
92
86
82
Melting points were recorded on Buchi R-535 apparatus and are un-
corrected. IR spectra were recorded on a Perkin-Elmer FT-IR 240-
1
c spectrophotometer using KBr optics. H NMR and 13C spectra
m
were recorded on Gemini-200 spectrometer in CDCl3 using TMS as
internal standard. Mass spectra were recorded on a Finnigan MAT
1020 mass spectrometer operating at 70 eV. All commercially
available reagent grade chemicals were purchased from Aldrich
Chemical Company and used as received without further purifica-
tion unless otherwise stated. All the solvents were distilled, dried
and stored under nitrogen prior to use.
n
o
5.5
6.0
79
85
Synthesis 2,3-dihydro-1,5-benzodiazepines; General Procedure
A mixture of o-phenylenediamine (1 mmol), ketone (2.5 mmol),
and Ag3PW12O40 (0.3 mmoL) was stirred at ambient temperature for
an appropriate time (Table 1). After completion of the reaction, as
indicated by TLC, the reaction mixture was filtered and washed
with EtOAc (2 × 10 mL). The combined organic extracts were con-
centrated in vacuo and the resulting product was directly charged on
small silica gel column and eluted with a mixture of EtOAc–n-hex-
ane (2:8) to afford pure diazepine. The recovered catalyst was
washed with MeOH and activated at 120 °C for 3–4 h prior to re-
use.7,8
p
7.0
72
a All products were characterized by 1H NMR, IR, and mass spectros-
copy.
b Isolated and unoptimized yields
c 5–8% of other regioisomer was observed in 1H NMR spectrum of
crude product.
2,4,4-Trimethyl-2,3-dihydro-1H-1,5-benzodiazepine (3a)
Light yellow solid; mp 136–138 °C.
IR (KBr): 3340, 1650, 1600 cm–1.
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PAPER
Novel and Recyclable Heteropoly Acid for 1,5-Benzodiazepines
903
1H NMR (200 MHz, CDCl3): d = 1.35 (s, 6 H), 2.20 (s, 2 H), 2.35
(s, 3 H), 2.95 (br s, 1 H, NH), 6.65–7.30 (m, 4 H).
2-Methyl-2,4-diphenyl-2,3-dihydro-8-methyl-1H-1,5-benzodi-
azepine (3f)
Yellow solid; mp 91–93 °C.
IR (KBr): = 3315,1657, 1600 cm–1.
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 29.7, 30.4, 45.0,
67.8, 121.6, 122.0, 125.4, 126.7, 137.8, 140.6, 171.8.
EIMS: m/z (% relative intensity) = 188 (100) [M+], 173 (52), 132
(15), 104 (15), 77 (32), 65 (20).
1H NMR (200 MHz, CDCl3): d = 1.80 (s, 3 H), 2.41 (s, 3 H), 2.98
(d, J = 12.7 Hz, 1 H), 3.15 (d, J = 12.7 Hz, 1 H), 3.50 (br s, 1 H, NH),
6.70–7.69 (m, 13 H).
2-Methyl-2,4-diphenyl-2,3-dihydro-1H-1,5-benzodiazepine
(3b)
Yellow crystalline solid; mp 150–152 °C.
IR (KBr): = 3325, 1635, 1598 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.80 (s, 3 H), 2.95 (d, J = 12.8 Hz,
1 H), 3.15 (d, J = 12.8 Hz, 1 H) 3.45 (br s, 1 H, NH), 6.55–7.0 (m,
3 H), 7.15–7.35 (m, 7 H), 7.55–7.65 (m, 4 H).
13C NMR (1H-decoupled, CDCl3): d = 29.7, 42.9, 73.3, 121.2,
121.4, 125.2, 126.1, 126.8, 126.9, 127.8, 128.1, 128.5, 129.5, 137.9,
139.5, 139.9, 147.4, 167.3.
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 20.6, 28.5, 45.8,
51.2, 113.5, 125.5, 126.4, 127.3, 128.1, 128.3, 128.6, 128.8, 129.1,
130.9, 131.2, 134.0, 136.8, 164.8.
EIMS: m/z (%) = 326 (10) [M+], 261 (100), 246 (90), 206 (40), 145
(50), 102 (35), 76 (30).
2-Methyl-2,4-diethyl-8-methyl-2,3-dihydro-1H-1,5-benzodiaz-
epine (3g)
Light yellow solid; mp 116–118 °C.
IR (KBr): 3500, 3220, 1620 cm–1.
EIMS: m/z = 312 (10) [M+], 295 (100), 235 (25), 194 (30), 103 (20),
77 (60), 40 (80).
1H NMR (300 MHz, CDCl3): d = 0.95 (t, J = 7.0 Hz, 3 H), 1.15–1.30
(m, 6 H), 1.50–1.70 (m, 2 H), 2.05–2.10 (d, J = 12.8 Hz, 1 H), 2.15–
2.20 (d, J = 12.8 Hz, 1 H), 2.30 (s, 3 H), 2.50–2.65 (m, 2 H), 2.90
(brs, 1 H, NH), 6.55–7.00 (m, 3 H).
2,4-Diethyl-2-methyl-2,3-dihydro-1H-1,5-benzodiazepine (3c)
Yellow solid; mp 137–139 °C.
IR (KBr): 3329, 1637, 1605 cm–1.
EIMS: m/z (%) = 230 (15) [M+], 201 (20), 172 (40), 132 (100), 90
(50), 56 (25).
1H NMR (200 MHz, CDCl3): d = 0.99 (t, J = 6.9 Hz, 3 H), 1.25 (t,
J = 7.0 Hz, 3 H),1.70 (q, J = 6.9 Hz, 2 H), 2.15 (m, 2 H), 2.35 (s, 3
H), 2.69 (q, J = 7.0 Hz, 2 H), 3.25 (br s, 1 H, NH), 6.78–7.35 (m, 4
H).
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 8.7, 10.8, 26.9,
35.5, 35.7, 42.1, 70.5, 121.8, 125.4, 126.2, 127.0, 137.9, 140.8,
175.6.
2-Methyl-2,4-diisobutyl-8-methyl-2,3-dihydro-1H-1,5-benzodi-
azepine (3h)
Pale yellow solid; mp 124–126 °C.
IR (KBr): 3550, 3253, 1670 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.95–1.05 (m, 12 H), 1.30 (s, 3 H),
1.45–1.50 (m, 2 H), 1.70–1.80 (m, 1 H), 2.05–2.25 (m, 3 H), 2.28
(s, 3 H), 2.40–2.45 (m, 2 H), 3.0 (br s, 1 H, NH), 6.55–7.05 (m, 3 H).
EIMS: m/z (%) = 216 (15) [M+], 141(5), 108 (100), 80 (38), 40 (75).
EIMS: m/z (%) = 286 (15) [M+], 271 (10), 229 (100), 228 (50), 187
2-Methyl-2,4-diisobutyl-2,3-dihydro-1H-1,5-benzodiazepine
(12), 146 (25), 41 (10).
(3d)
Light yellow solid; mp 118–120 °C.
IR (KBr): 3320, 1650, 1599 cm–1.
2,2,4-Trimethyl-2,3-dihydro-7,8-dimethyl-1H-1,5-benzodiaz-
epine (3i)
Yellow solid; mp 112–114 °C.
IR (KBr): 3290, 1635, 1597 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.35 (s, 6 H), 2.19 (s, 3 H), 2.20
(s, 3 H) 2.22 (s, 2 H), 2.34 (s, 3 H), 2.80 (br s, NH, 1 H), 6.52 (s, 1
H), 6.39 (s, 1 H).
13C NMR (1H-decoupled, 75 MHz, CDCl3): d = 18.9, 19.1, 29.8,
30.3, 30.4, 45.3, 67.7, 122.8, 127.8, 129.9, 133.6, 135.5, 138.4,
171.3.
1H NMR (300 MHz, CDCl3): d = 0.95–1.05 (m, 12 H), 1.32 (s, 3 H),
1.49–1.52 (m, 2 H), 1.65–1.75 (m, 1 H), 2.05–2.25 (m, 3 H), 2.24
(d, J = 12.7 Hz, 2 H), 6.60–6.65 (m, 1 H), 6.85–6.95 (m, 2 H), 7.05–
7.15 (m, 1 H).
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 22.5, 22.7, 24.2,
24.9, 25.0, 26.3, 28.1, 43.5, 51.7, 51.9, 70.8, 121.4, 121.5, 125.2,
127.2, 137.8, 140.4, 173.9.
EIMS: m/z(%) = 272 (10) [M+], 157 (12), 141 (25), 105 (100), 80
(50), 53 (14).
EIMS: m/z (%) = 216 (20) [M+], 201 (60), 161 (30), 145 (15), 97
(17), 71 (50), 43 (100).
2,2,4-Trimethyl-2,3-dihydro-8-methyl-1H-1,5-benzodiazepine
(3e)
2-Methyl-2,4-diphenyl-2,3-dihydro-7,8-dimethyl-1H-1,5-ben-
zodiazepine (3j)
Solid; mp 127–129 °C.
Solid; mp 115–116 °C.
IR (KBr): 3285, 1635, 1609 cm–1.
IR (KBr): 3325, 1665, 1600 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.30 (s, 6 H), 2.19 (s, 2 H), 2.23
(s, 3 H), 2.80 (s, 3 H), 6.65–6.75 (s, 1 H), 6.70–6.80 (1 H), 7.05–
7.10 (m, 1 H).
13C NMR (1H-decoupled, 75 MHz, CDCl3): d = 20.9, 29.6, 30.4,
30.8, 45.8, 67.0, 122.6, 126.6, 127.0, 131.8, 136.7, 138.1, 174.3.
EIMS: m/z (%) = 202 (40) [M+], 187 (100), 146 (70), 77(15), 41
(20).
1H NMR (CDCl3): d = 1.70 (s, 3 H), 2.25 (s, 6 H), 2.90 (d, J = 12.8
Hz, 1 H), 3.10 (d, J = 12.8 Hz, 1 H), 3.45 (br s, 1 H, NH), 6.60 (s, 1
H), 7.15 (s, 1 H), 7.30–7.18 (m, 6 H), 7.50–7.60 (m, 4 H).
13C NMR (1H-decoupled, CDCl3): d = 18.6, 19.3 29.7, 43,2, 73.0,
122.3, 125.4, 126.8, 126.9, 127.8, 128.2, 129.3, 129.4, 129.6, 134.8,
135.7, 137.6, 139.7, 147.8, 166.8.
EIMS: m/z (%) = 340 (20) [M+], 195 (100), 103 (75), 77 (55), 65
(15).
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J. S. Yadav et al.
PAPER
2,2,4-Trimethyl-2,3-dihydro-8-chloro-1H-1,5-benzodiazepine
EIMS: m/z (%) = 268 (25) [M+].
(3k)
Pale yellow solid; mp 90–92 °C.
IR (KBr): 3283, 1649, 1597 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.27 (s, 6 H), 2.23 (s, 2 H), 2.26
(s, 3 H), 5.58–6.60 (s, 1 H), 6.86–6.90 (s, 1 H), 6.98–7.05 (s, 1 H).
13C NMR (1H-decoupled, 75 MHz, CDCl3): d = 29.2, 29.8, 30.0,
44.9, 67.0, 120.4, 120.8, 125.9, 127.8, 129.8, 139.1, 172.5.
EIMS: m/z (%) = 222 (10) [M+], 207 (24), 167 (38), 142 (100), 114
(20), 80 (25), 41 (30).
10-Spirocycloheptan-6,7,8,9,10,10a,11,12-octahydroben-
zo[b]cyclohepta[e][1,4]diazepine (4p)
Pale yellow solid; mp 135–136 °C.
IR (KBr): 3320, 3275, 1630, 1600 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.90–1.95 (m, 20 H), 2.25–2.95
(m, 3 H), 3.60 (br s, NH, 1 H), 6.60–7.38 (m, 4 H).
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 22.5, 23.2, 26.5,
28.4, 28.9, 29.5, 29.7, 30.1, 38.2, 38.5, 40.9, 54.3, 72.5, 121.3,
121.6, 125.5, 127.6, 137.5, 139.8, 179.1.
2,2,4-Tri-methyl-2,3-dihydro-8-nitro-1H-1,5-benzodiazepine
EIMS: m/z (%) = 296 (15) [M+].
(3l)
Pale yellow solid; mp 113–114 °C.
IR (KBr): 3280, 1645, 1640 cm–1.
Acknowledgment
BVS, SPK thank CSIR, New Delhi, for the award of fellowships.
1H NMR (300 MHz, CDCl3): d = 1.90 (s, 6 H), 2.95 (s, 3 H), 3.20
(s, 2 H), 4.0 (s, 1 H, NH), 7.15–7.20 (s, 1 H), 8.0–8.15 (m, 1 H),
8.75–8.80 (m, 1 H).
13C NMR (1H-decoupled, 75 MHz, CDCl3): d = 29.9, 30.0, 30.2,
45.6, 60.8, 118.3, 121.2, 126.2, 132.4, 137.9, 145.2, 170.7. EIMS:
m/z (%) = 233 (30) [M+], 218 (100), 177 (48), 172 (48), 131 (30),
90 (40), 63 (45).
References and Notes
(1) (a) Schutz, H. Benzodiazepines; Springer: Heidelberg,
1982. (b) Landquist, J. K. In Comprehensive Heterocyclic
Chemistry, Vol. 1; Katritzky A. R., Rees C. W., Pergamon:
Oxford, 1984, 166–170.
(2) Randall, L. O.; Kappel, B. Benzodiazepines; Garattini, S.;
Mussini, E.; Randall, L. O., Eds.; Raven Press: New York,
1973, 27.
(3) Haris, R. C.; Straley, J. M. U. S. Patent, 1537757, 1968;
Chem. Abstr. 1970, 73, 100054w.
2-Methyl-2,4-diphenyl-2,3-dihydro-8-nitro-1H-1,5-benzodiaz-
epine (3m)
Yellow color solid; mp 136–138 °C.
IR (KBr): 3300, 1651 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.80 (s, 3 H), 3.05–3.15 (d, J =
12.6 Hz, 1 H), 3.35 (d, J = 12.6 Hz, 1 H), 4.40 (br s, 1 H, NH), 6.80–
7.95 (m, 13 H).
EIMS: m/z (%) = 357 (20) [M+], 345 (10), 282 (20), 241 (100), 194
(10), 130 (25), 119 (30), 78 (10), 57 (50).
(4) De Baun, J. R.; Pallos, F. M.; Baker, D. R. U. S. Patent,
3978227, 1976; Chem. Abstr. 1977, 86, 5498d.
(5) (a) Aversa, M. C.; Ferlazzo, A.; Gionnetto, P.; Kohnke, F. H.
Synthesis 1986, 230. (b) Chimirri, A.; Grasso, S.; Ottana, R.;
Romeo, G.; Zappala, M. J. Heterocycl. Chem. 1990, 27,
371. (c) Essaber, M.; Baouid, A.; Hasnaoui, A.; Benharref,
A.; Lavergne, J. P. Synth. Commun. 1998, 28, 4097. (d) El-
Sayed, A. M.; Abdel-Ghany, H.; El-Saghier, A. M. M. Synth.
Commun. 1999, 29, 3561.
(6) (a) Herbert, J. A. L.; Suschitzky, H. J. Chem. Soc., Perkin
Trans 1 1974, 2657. (b) Kaupp, G.; Pogodda, U.;
Schmeyers, J. Chem. Ber. 1994, 127, 2249. (c)Balakrishna,
M. S.; Kaboudin, B. Tetrahedron Lett. 2001, 42, 1127.
(d) Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.
Tetrahedron Lett. 2001, 42, 3193.
(7) (a) Morales, H. R.; Bulbarela, A.; Contreras, R. Heterocycles
1986, 24, 135. (b) Pozarentzi, M.; Stephanatou, J. S.;
Tsoleridis, C. A. Tetrahedron Lett. 2002, 43, 1755.
(c) Reddy, B. M.; Sreekanth, P. M. Tetrahedron Lett. 2003,
44, 4447. (d) Jarikote, D. V.; Siddiqui, S. A.; Rajagopal, R.;
Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. Tetrahedron Lett.
2003, 44, 1835.
10-Spirocyclopentan-1,2,3,9,10,10a-hexahydrobenzo [b]-cyclo-
penta[e][1,4] diazepine (4n)
Yellow solid; mp 137–138 °C.
IR (KBr): 3338, 1659, 1600 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.30–1.90 (m, 12 H), 2.30–2.60
(m, 3 H), 4.50 (br s, NH, 1 H), 6.70–7.39 (m, 4 H).
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 23.4, 24.1, 24.3,
28.7, 33.4, 38.5, 39.2, 54.4, 67.3, 118.6, 119.3, 126.9, 132.1, 139.2,
143.4, 178.0.
EIMS: m/z (%) = 240 (30) [M+].
10-Spirocyclohexan-2,3,4,10,11,11a-hexahydro-1H-diben-
zo[b,e][1,4]diazepine (4o)
Pale yellow solid; mp 136–137 °C.
(8) Clark, J. H. Acc. Chem. Res. 2002, 35, 791.
(9) (a) Okuhara, T.; Mizuno, N.; Misono, M. Applied Catalysis
A: General 2001, 222, 63. (b) Kozhevnikov, I. V. Chem.
Rev. 1998, 98, 171.
(10) Preparation of catalyst: Haber, J.; Pamin, K.; Matachowski,
L.; Napruszewska, B.; Poltowicz, J. J. Catal. 2002, 207, 296.
(11) Solvent-free reactions: Tanaka, K.; Toda, F. Chem. Rev.
2000, 100, 1025.
IR (KBr): 3290, 1640, 1600 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.23–1.85 (m, 16 H), 2.30–2.70
(m, 3 H), 4.45 (br s, 1 H, NH), 6.65–7.35 (m, 4 H).
13C NMR (1H-decoupled, 50 MHz, CDCl3): d = 21.6, 21.7, 23.2,
24.5, 25.3, 33.2, 34.4, 39.3, 40.5, 52.4, 63.1, 121.3, 121.5, 126.3,
129.6, 138.1, 142.6, 178.9.
Synthesis 2004, No. 6, 901–904 © Thieme Stuttgart · New York