1-Alkyl- and azeto[1,2-a][1,5]benzodiazepine derivatives in the reaction of o-phenylenediamine with 3-(dimethylamino)propiophenones

Article abstract of DOI:10.1002/(sici)1099-0690(200005)2000:10<1973::aid-ejoc1973>3.0.co;2-m

The reaction of o-phenylenediamine (4) with one, two or three equivalents of p-substituted 3-dimethylaminopropiophenone hydrochlorides 5a-e was studied. 4-Aryl-2,3-dihydro-1H-1,5-benzodiazepine derivatives 6a-e were obtained in good yields, along with the 1:2-adducts 7c-e and the unexpected l:3-adducts rac-8c-e. The type of adduct formed is determined by the molar ratio of the reactants 4 and 5 and by the nature of the substituent in the para position of the propiophenone 5.

Full text of DOI:10.1002/(sici)1099-0690(200005)2000:10<1973::aid-ejoc1973>3.0.co;2-m

FULL PAPER
1-Alkyl- and Azeto[1,2-a][1,5]benzodiazepine Derivatives in the Reaction of
o-Phenylenediamine with 3-(Dimethylamino)propiophenones
Braulio Insuasty,[a] Rodrigo Abonia,[a] Jairo Quiroga,[a] Angela Salcedo,[a] Heinz Kolshorn,[b]
and Herbert Meier*[b]
Keywords: 1,5-Benzodiazepines / Heterocycles / Azeto[1,2-a]-1,5-benzodiazepines / Cyclizations / Cycloadditions
The reaction of o-phenylenediamine (4) with one, two or
the unexpected 1:3-adducts rac-8c−e. The type of adduct
three equivalents of p-substituted 3-dimethylaminopropi- formed is determined by the molar ratio of the reactants 4
ophenone hydrochlorides 5a−e was studied. 4-Aryl-2,3-di-
hydro-1H-1,5-benzodiazepine derivatives 6a−e were ob-
tained in good yields, along with the 1:2-adducts 7c−e and
and 5 and by the nature of the substituent in the para position
of the propiophenone 5.
Introduction
Results and Discussion
A preliminary experiment was carried out by refluxing
diamine 4 with one equivalent of p-nitropropiophenone hy-
drochloride (5e) in dry ethanol. The two products obtained
were separated by column chromatography on silica gel, us-
ing ethyl acetate/hexane (1:2) as eluent, and were character-
ized by NMR spectroscopy. The compound obtained as the
first fraction was the 1:2-adduct 7e, while the second frac-
tion (main product) was the expected compound 6e. The
reaction conditions (time and solvent) were then optimized
to obtain only the products 6a؊b when reacting propio-
phenones 5a؊b with o-phenylenediamine (4). Similar con-
ditions for the propiophenones 5c؊e led to the expected
products 6c؊e, accompanied by small amounts of the com-
pounds 7c؊e.
The reaction of o-phenylenediamines with salts of 3-ami-
nopropiophenones has been previously reported in the liter-
ature.[1,2] Some 1,5-benzodiazepine derivatives thus ob-
tained (e.g. compound 1 in Scheme 1) have been utilized as
neoplasm inhibitors.[2] Recently, our group has also re-
ported the synthesis of diazepine derivatives 2 and 3 in
good yields,[3,4] starting from heterocyclic 1,2-diamines and
3-dimethylaminopropiophenone hydrochlorides 5.
In a further experiment, aiming at the formation of the
1:2-adduct 7e as the main product, more than two equiva-
lents of propiophenone 5e were used, and the reaction mix-
ture was heated for a longer time. However, a mixture of
two components was again obtained. The first fraction sep-
arated by column chromatography was the compound 7e as
the main product, followed by the 1:3-adduct 8e. Several
experiments under various reaction conditions showed that
compounds of type 8 were accessible only for the propio-
phenones 5c؊e and not for 5a,b.
We further established the best reaction conditions to ob-
tain the compounds 6a؊e as major products by refluxing
equimolar amounts of diamine 4 and the propiophenones
2a؊e for ca. 15 min. in an excess of dry ethanol. When a
1:2 ratio of diamine 4 and propiophenone 5c؊e was re-
fluxed for ca. 2 h, compounds of type 7 were obtained as
the main products. Finally, when a 1:3 mixture of diamine
4 and propiophenone 5c؊e was refluxed for 3 to 4 h, com-
pounds 8c؊e were obtained as major products.
Scheme 1. 1,5-Diazepine derivatives formed from 4 and heterocyc-
lic o-diamino compounds with 3-dimethylaminopropiophenones
Our interest in the synthesis and chemistry of fused di-
azepine ring systems[5Ϫ8] led us to a more detailed study of
this reaction, and to an analysis of the effect of the molar
ratio of the reactants and the nature of the para substituent
of the propiophenone on the reaction products.
[a]
The structures of compounds 6a؊e, 7c؊e and 8c؊e were
assigned by 1H and 13C NMR spectra and confirmed by IR
and mass spectrometric data (see Experimental Section).
The most characteristic 1H NMR signals for the com-
Department of Chemistry, Universidad del Valle,
A.A. 25360, Cali, Colombia
E-mail: abonia@quimica.univalle.edu.co
[b]
Institute of Organic Chemistry, University of Mainz
Duesbergweg 10Ϫ14, 55099 Mainz, Germany
Eur. J. Org. Chem. 2000, 1973Ϫ1976
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0510Ϫ1973 $ 17.50ϩ.50/0
1973

B. Insuasty, R. Abonia, J. Quiroga, A. Salcedo, H. Kolshorn, H. Meier
FULL PAPER
1
Figure 1. Correlation of the H and 13C NMR signals with certain
positions of the ring skeleton of compound 8d; arrows indicate the
obtained nuclear Overhauser effects
pounds 6a؊e are represented by a broad singlet at δ ϭ
3.55Ϫ3.95 (deuterium exchangeable) corresponding to the
NϪH proton and a typical AAЈBBЈ pattern for the building
block 2-CH2-3-CH2. The spectra of the compounds 7c؊e
show also the pattern for the building block 2-CH2-3-CH2
and additionally two multiplets for the CH2ϪCH2 segment
1
in the side chain. The H NMR spectra of compounds rac-
8c؊e show a complicated spin pattern at δ ϭ 1.67Ϫ3.84
owing to aliphatic protons. However, an extended study in-
cluding DEPT and two-dimensional (COSY, NOESY and
13C,1H shift correlation) measurements for rac-8d con-
firmed the proposed structure. Figure 1 depicts the correla-
Scheme 2. Reaction of o-phenylendiamine 4 with aryl-3-dimethyl-
aminopropiophenones 5
trolled by the reactivity of the propiophenones. According
to Scheme 3, compounds 7c؊e were formed by an N-al-
kylation of the diazepines 6c؊e with a second equivalent of
propiophenone 5c؊e or its well-known[10] synthetic equiva-
1
tion of the 13C and the H NMR signals with the nuclei of
the tricyclic skeleton and the most important nuclear Over-
hauser effects (arrows). Apart from the cis fusion of the
azete and the diazepine ring, the stereogenic center C-2 has
to be considered. The geminal protons on C-1 can be as-
signed by the NOE between the aromatic 9-H (δ ϭ 6.38)
and the lowfield signal of 1-H (δ ϭ 3.67). The latter proton
and 2-H are in a trans position i.e. the (2R,2aR) configura-
tion and its enantiomer (2S,2aS) were formed. Besides the
ABM spin pattern of the protons on the azete ring, the
spectrum contains an ABCD pattern for the protons on the
diazepine ring and an ABCD pattern for the protons of the
side chain attached on N-5. The individual correlation is
again based on NOESY measurements (Figure 1). The 13C
1
NMR spectroscopic data were assigned by a H,13C shift
correlation measurement. The compounds rac-8c and 8e
gave very similar results (see Experimental Section).
In the infrared spectra of the compounds 6a؊e the band
characteristic for the NϪH stretching vibration is present
at 3401Ϫ3391 cmϪ1 together with a band at 1619Ϫ1625
cmϪ1, assignable to the CϭN group.[9] In the compounds
7c؊e, a band assignable to the NϪH stretching is not pre-
sent; apart from the CϭN stretching vibration an absorp-
tion at 1671Ϫ1676 cmϪ1 could be assigned to the CϭO
stretching vibration. Compounds rac-8c؊e did not exhibit
absorptions for NϪH or CϭN groups. However, a strong,
broad band can be observed at 1676Ϫ1683 cmϪ1; it is as-
signed to the two CϭO groups.
As shown in Scheme 2, the 1:2- and 1:3 adducts were
obtained only when the p-substituent in 5 is an electron-
withdrawing group, such as nitro or halogen, while for Ar ϭ
C6H5 or C6H4ϪOCH3 only diazepines of type 6 were ob-
tained. This finding suggests that the reaction course is con- Scheme 3. Stepwise formation of 6, 7, 8 and proposed intermediate
1974 Eur. J. Org. Chem. 2000, 1973Ϫ1976

1-Alkyl- and Azeto[1,2-a][1,5]benzodiazepine Derivatives
FULL PAPER
228 (52), 119 (51). Ϫ C15H13ClN2 (256.7): calcd. C 70.21, H 5.07,
N 10.91; found C 70.14, H 5.12, N 10.86.
lent arylvinylketone, generated in situ from the correspond-
ing propiophenone. On the other hand, formation of the
compounds rac-8 could occur by the attack of a third mole-
cule of propiophenone 5 at the imino nitrogen of 7 (via the
alkyliminium intermediate shown in Scheme 3), and sub-
sequent cyclization to form the fused azete ring.
4-(4-Bromophenyl)-2,3-dihydro-1H-1,5-benzodiazepine (6d): Orange
crystals, yield 600 mg, 72%, m.p. 140 °C. Ϫ 1H NMR (CDCl3): δ ϭ
3.00 (t, J ϭ 5.7 Hz, 2 H, 3-H), 3.80 (br. s, 1 H, NH), 3.81 (t, J ϭ
5.7 Hz, 2 H, 2-H), 6.71 (d, 1 H), 6.93 (m, 1 H), 7.02 (m, 1 H), 7.34
(d, 1 H), 7.54 (br. d, 2 H), 7.84 (br. d, 2 H, aromat. H). Ϫ 13C
NMR (CDCl3): δ ϭ 32.1 (C-3), 54.1 (C-2), 119.8, 120.8, 124.6,
127.2, 128.8, 130.8, 131.7, 137.8, 138.7, 140.4 (aromat. C), 166.2
(CϭN). Ϫ MS (70 eV): m/z (%) ϭ 300/302 (100) [Mϩ, Br pattern]
299 (68), 272 (30), 119 (65). Ϫ C15H13BrN2 (301.2): calcd. C 59.84,
H 4.32, N 9.30; found C 59.81, H 4.44, N 9.21.
The structure and generation of the azeto[1,2-a][1,5]ben-
zodiazepines are unprecedented; a somewhat related reac-
´
tion was observed by Cortes et. al. when β-lactams were
unexpectedly obtained in the reaction of some benzodiazep-
ines with methoxyacetyl chloride.[11]
As further support for the assertions in Scheme 3, the
adducts 7c؊e and 8c؊e were alternatively obtained by the
reaction of 6c؊e with one or two equivalents of the propio-
phenones 5c؊e.
2,3-Dihydro-4-(4-nitrophenyl)-1H-1,5-benzodiazepine (6e): Red crys-
tals, yield 445 mg, 60%, m.p. 129 °C. Ϫ 1H NMR (CDCl3): δ ϭ
3.10 (t, J ϭ 5.7 Hz, 2 H, 3-H), 3.77 (t, J ϭ 5.7 Hz, 2 H, 2-H), 3.95
(br. s, 1 H, NH), 6.72 (d, 1 H), 6.93 (m, 1 H), 7.05 (m, 1 H), 7.40
(d, 1 H), 8.10 (d, 2 H), 8.24 (d, 2 H). Ϫ 13C NMR (CDCl3): δ ϭ
33.3 (C-3), 49.8 (C-2), 119.1, 120.3, 123.5, 127.6, 127.8, 132.2,
135.9, 141.1, 145.7, 148.4 (aromat. C), 163.7 (CϭN). Ϫ MS
(70 eV): m/z (%) ϭ 267 (100) [Mϩ], 266 (89), 239 (24), 119 (55). Ϫ
C15H13N3O2 (267.3): calcd. C 67.44, H 4.87, N 15.72; found C
67.38, H 4.84, N 15.66.
Experimental Section
General: All melting points were taken with a Büchi melting point
apparatus and are uncorrected. Ϫ IR: ATI-Mattson spectrophoto-
meter. NMR: Varian-VXR-300S, Bruker ARX 400, CDCl3 as solv-
ent. Ϫ MS: Jeol SX-100 (70 eV). Ϫ Microanalyses: LECO CHNS-
900 elemental analyzer.
General Procedure for the Preparation of the 1-(2-Aroylethyl)-2,3-
dihydro-1H-1,5-benzodiazepines (7c؊e): A solution of 4 (300 mg,
2.77 mmol) and the corresponding ketone (5.55 mmol) 5c؊e in
25 mL of dry ethanol was heated for 2 h to reflux and the reaction
was monitored by TLC. The solid formed during the heating was
filtered off and recrystallized from ethanol. A second crop of crys-
tals was collected after cooling the reaction mixture and purified
as mentioned previously.
General Procedure for the Preparation of the 2,3-Dihydro-1H-1,5-
benzodiazepines (6a؊e): A solution of 4 (300 mg, 2.77 mmol) and
the corresponding ketone 5a؊e (2.77 mmol) in 50 mL of dry eth-
anol was heated for 15 min to reflux and the reaction was mon-
itored by TLC. After the solvent was removed, the residue was
purified by column chromatography on silica gel (3 ϫ 80 cm) with
chloroform as eluent.
1-[2-(4-Chlorobenzoyl)ethyl]-2,3-dihydro-1H-1,5-benzodiazepine
1
(7c): Yellow crystals, yield 750 mg, 64%, m.p. 136 °C. Ϫ H NMR
2,3-Dihydro-4-phenyl-1H-1,5-benzodiazepine (6a): Yellow crystals,
yield 370 mg, 60%, m.p. 129 °C. Ϫ1H NMR (CDCl3): δ ϭ 2.92 (t,
J ϭ 5.7 Hz, 2 H, 3-H), 3.55 (br. s, 1 H, NH), 3.74 (t, J ϭ 5.7 Hz,
2 H, 2-H), 6.67 (d, 1 H), 6.90Ϫ6.99 (m, 2 H), 7.25 (d, 1 H), 7.36
(m, 3 H), 7.91 (br. t, 2 H, aromat. H). Ϫ 13C NMR (CDCl3): δ ϭ
30.6 (C-3), 49.3 (C-2), 116.8, 118.5, 123.5, 126.7, 126.8, 128.4,
129.5, 132.5, 136.2, 140.5 (aromat. C), 166.5 (CϭN). Ϫ MS
(70 eV): m/z (%) ϭ 222 (100) [Mϩ], 221 (88), 194 (43), 119 (47). Ϫ
C15H14N2 (222.3): calcd. C 81.09, H 6.30, N 12.60; found C 81.14,
H 6.38, N 12.50.
(CDCl3): δ ϭ 2.81 (t, J ϭ 6.3 Hz, 2 H, 3-H), 3.00 (t, J ϭ 5.6 Hz,
2 H, 11-H), 3.52 (t, J ϭ 6.3 Hz, 2 H, 2-H), 3.75 (t, J ϭ 5.7 Hz, 2
H, 10-H), 6.90Ϫ7.41 (m, 4 H), 7.52Ϫ8.10 (m, 8 H, aromat. H). Ϫ
13C NMR (CDCl3): δ ϭ 29.9 (C-3), 37.5 (C-11), 47.0 (C-2), 63.4
(C-10), 119.4, 123.1, 124.9, 125.6 127.0, 128.7, 129.0, 129.8, 131.1,
133.1, 135.1, 137.9, 140.3, 144.8 (aromat. C), 169.5 (CϭN), 199.3
(CϭO). Ϫ MS (70 eV): m/z (%) ϭ 426/424/422 (75), [Mϩ, Cl2 pat-
tern], 421 (25), 256 (100), 255 (78), 166 (55), 119 (48). Ϫ
C24H20Cl2N2O (423.3): calcd. C 68.12, H 4.73, N 6.62; found C
68.18, H 4.84, N 6.66.
2,3-Dihydro-4-(4-methoxyphenyl)-1H-1,5-benzodiazepine (6b): Yel-
low crystals, yield 315 mg, 45%, m.p. 155 °C. Ϫ 1H NMR (CDCl3):
δ ϭ 2.97 (t, J ϭ 5.7 Hz, 2 H, 3-H), 3.60 (br. s, 1 H, NH), 3.83 (t,
J ϭ 5.7 Hz, 2 H, 2-H), 3.84 (s, 3 H, OCH3), 6.71 (d, 1 H),
6.90Ϫ7.00 (m, 4 H), 7.32 (br. d, 1 H), 7.94 (d, 2 H, aromat. H). Ϫ
13C NMR (CDCl3): δ ϭ 28.6 (C-3), 50.3 (C-2), 52.9 (OCH3), 111.2,
117.1, 118.2, 123.4, 126.0, 126.9. 129.4, 135.8, 137.2, 158.9 (aromat.
C), 165.0 (CϭN). Ϫ MS (70 eV): m/z (%) ϭ 252 (100) [Mϩ], 251
(27), 224 (48), 119 (35). Ϫ C16H16N2O (252.3): calcd. C 76.21, H
6.35, N 11.10; found C 76.14 H 6.44, N 11.06.
1-[2-(4-Brombenzoyl)ethyl]-2,3-dihydro-1H-1,5-benzodiazepine (7d):
Yellow crystals, yield 880 mg, 62%, m.p. 149 °C. Ϫ 1H NMR
(CDCl3): δ ϭ 2.82 (t, J ϭ 6.4 Hz, 2 H, 3-H), 3.10 (t, J ϭ 5.7 Hz,
2 H, 11-H), 3.56 (t, J ϭ 6.3 Hz, 2 H, 2-H), 3.73 (t, J ϭ 5.7 Hz, 2
H, 10-H), 6.85Ϫ7.38 (m, 4 H), 7.40Ϫ7.85 (m, 8 H, aromat. H). Ϫ
13C NMR (CDCl3): δ ϭ 30.7 (C-3), 737.0 (C-11), 47.3 (C-2), 63.5
(C-10), 119.3, 123.0, 125.1, 125.9, 126.6, 128.5, 128.8, 129.5, 131.8,
132.0, 135.6, 137.4, 139.2, 144.5 (aromat. C), 169.1 (CϭN), 198.5
(CϭO). Ϫ MS (70 eV): m/z (%) ϭ 514/512/510 (63), [Mϩ, Br2 pat-
tern], 509 (33), 300 (100), 299 (82), 210 (59), 119 (53). Ϫ
C24H20Br2N2O (512.2): calcd. C 56.29, H 3.91, N 5.47; found C
56.18, H 3.84, N 5.53.
4-(4-Chlorophenyl)-2,3-dihydro-1H-1,5-benzodiazepine (6c): Orange
crystals, yield 480 mg, 68%, m.p. 130 °C. Ϫ 1H NMR (CDCl3): δ ϭ
2.96 (t, J ϭ 5.7 Hz, 2 H, 3-H), 3.65 (br. s, 1 H, NH), 3.77 (t, J ϭ
5.7 Hz, 2 H, 2-H), 6.67 (br. d, 1 H), 6.88 (m, 1 H), 6.95 (m, 1 H),
2,3-Dihydro-1-[2-(4-nitrobenzoyl)ethyl]-1H-1,5-benzodiazepine (7e):
Red crystals, yield 840 mg, 68%, m.p. 213 °C. Ϫ 1H NMR (CDCl3):
7.28 (d, 1 H), 7.33 (d, 2 H), 7.85 (d, 2 H, aromat. H). Ϫ 13C NMR δ ϭ 2.89 (t, J ϭ 6.6 Hz, 2 H, 3-H), 3.16 (t, J ϭ 5.9 Hz, 2 H, 11-
(CDCl3): δ ϭ 31.9 (C-3), 52.1 (C-2), 119.5, 120.7, 126.7, 128.2, H), 3.60 (t, J ϭ 6.6 Hz, 2 H, 2-H), 3.78 (t, J ϭ 5.9 Hz, 2 H, 10-H),
128.6, 130.2, 130.4, 136.1, 137.5, 140.2 (aromat. C), 163.0 (CϭN).
7.00Ϫ7.30 (m, 4 H), 7.88 (d, 2 H), 8.10 (d, 2 H), 8.18 (d, 2 H), 8.29
Ϫ MS (70 eV): m/z (%) ϭ 256/258 (100) [Mϩ, Cl pattern], 255 (62), (d, 2 H, aromat. H). Ϫ 13C NMR (CDCl3): δ ϭ 29.9 (C-3), 37.4
Eur. J. Org. Chem. 2000, 1973Ϫ1976
1975

B. Insuasty, R. Abonia, J. Quiroga, A. Salcedo, H. Kolshorn, H. Meier
(C-11), 47.1 (C-2), 63.4 (C-10), 119.2, 123.1, 123.8, 126.6, 127.2, 482 (47), 272 (68), 183 (100). Ϫ C33H27Br3N2O2 (723.3): calcd. C
FULL PAPER
127.7, 128.9, 138.8, 141.1, 144.0, 148.9, 150.3 (aromat. C), 167.9
(CϭN), 197.8 (CϭO). Ϫ MS (70 eV): m/z (%) ϭ 444 (60), [Mϩ],
443 (22), 267 (100), 266 (91), 150 (48), 119 (53). Ϫ C24H20N4O5
(444.4): calcd. C 64.89, H 4.50, N 12.61; found C 64.81, H 4.64,
N 12.53.
54.82, H 3.73, N 3.87; found C 54.75, H 3.76, N 3.92.
(±)-1,2,2a,3,4,5-Hexahydro-2-(4-nitrobenzoyl)-5-[2-(4-nitrobenzoyl)-
ethyl]-2a-(4-nitrophenyl)azeto[1,2-a][1,5]benzodiazepine
(rac-8e):
Pale yellow crystals, yield 1.10 g, 64%, m.p. 192 °C. Ϫ 1H NMR
(CDCl3): δ ϭ 1.69Ϫ1.73 (m, 1 H, 3-H), 1.92Ϫ1.96 (m, 1 H, 3-H),
2.09Ϫ2.13 (m, 1 H, 4-H), 2.50Ϫ2.57 (m, 1 H, 4-H), 2.58Ϫ2.65 (m,
1 H, 12-H), 2.86Ϫ2.92 (m, 1 H, 1-H), 2.96Ϫ2.99 (m, 1 H, 12-H),
3.25Ϫ3.32 (m, 1 H, 11-H), 3.39Ϫ3.44 (m, 1 H, 11-H), 3.67Ϫ3.76
(m, 1 H, 2-H), 3.80Ϫ3.84 (m, 1 H, 1-H), 6.37 (d, 1 H, 6-H), 6.47
(d, 1 H, 9-H), 6.56Ϫ6.66 (m, 2 H, 7-H, 8-H), 7.92 (d, 2 H), 7.98
(d, 2 H), 8.15 (d, 2 H), 8.23 (d, 2 H), 8.34 (d, 4 H, aromat. H). Ϫ
13C NMR (CDCl3): δ ϭ 24.4 (C-3), 24.6 (C-4), 37.4 (C-12), 38.3
(C-11), 40.7 (C-2), 42.1 (C-1), 87.2 (C-2a), 104.7, 104.9 (C-6, C-9),
118.6, 118.9 (C-7, C-8), 123.6, 123.7, 123.9, 128.3, 129.2, 129.4,
129.6, 139.0, 140.0, 140.1, 146.7, 147.2, 149.6, 149.9 (aromat. C),
197.4, 200.5 (CO). Ϫ MS (70 eV): m/z (%) ϭ 621 (23), [Mϩ], 593
(16), 444 (42), 416 (28), 239 (100), 150 (38). Ϫ C33H27N5O8 (621.6):
calcd. C 63.80, H 4.35, N 11.27; found C 63.73, H 4.42, N 11.19.
General Procedure for the Preparation of the (±)-Azeto[1,2-a][1,5]-
benzodiazepines (rac-8c؊e): A solution of 4 (300 mg, 2.77 mmol)
and the corresponding ketone 5c؊e (8.35 mmol) in 50 mL of dry
ethanol was heated for 4 h to reflux and the reaction was monitored
by TLC. The products crystallized on cooling and were purified by
column chromatography on silica gel (3 ϫ 80 cm) with chloroform
as eluent.
(±)-2-(4-Chlorobenzoyl)-5-[2-(4-chlorobenzoyl)ethyl]-2a-(4-chloro-
phenyl)-1,2,2a,3,4,5-hexahydroazeto[1,2-a][1,5]benzodiazepine (rac-
8c): Pale yellow crystals, yield 910 mg, 56%, m.p. 210 °C. Ϫ 1H
NMR (CDCl3): δ ϭ 1.71Ϫ1.79 (m, 1 H, 3-H), 1.97Ϫ2.01 (m, 1 H,
3-H), 2.09Ϫ2.15 (m, 1 H, 4-H), 2.55Ϫ2.58 (m, 1 H, 4-H),
2.61Ϫ2.69 (m, 1 H, 12-H), 2.92Ϫ2.96 (m, 1 H, 1-H), 2.98Ϫ3.03 (m,
1 H, 12-H), 3.29Ϫ3.37 (m, 1 H, 11-H), 3.42Ϫ3.49 (m, 1 H, 11-H),
3.60Ϫ3.66 (m, 1 H, 2-H), 3.69Ϫ3.72 (m, 1 H, 1-H), 6.35 (d, 1 H,
6-H), 6.42 (d, 1 H, 9-H), 6.68Ϫ6.75 (m, 2 H, 7-H, 8-H), 7.34 (d, 2
H), 7.37 (d, 2 H), 7.46 (d, 2 H), 7.61 (d, 2 H), 7.68 (d, 2 H), 7.86
(d, 2 H, aromat. H). Ϫ 13C NMR (CDCl3): δ ϭ 24.5 (C-3), 25.2
(C-4), 37.4 (C-12), 38.4 (C-11), 40.9 (C-2), 43.3 (C-1), 87.5 (C-2a),
104.3, 104.4 (C-6, C-9), 118.6, 119.2 (C-7, C-8), 128.8, 128.9, 129.0,
129.2, 129.4, 129.5, 129.7, 134.1, 134.7, 138.0, 139.0, 139.2, 139.7,
139.9 (aromat. C), 197.4, 199.6 (CO). Ϫ MS (70 eV): m/z (%) ϭ
594/592/590/588 (25), [Mϩ, Cl3 pattern], 560 (17), 422 (100), 394
(15), 228 (29), 139 (62). Ϫ C33H27Cl3N2O2 (589.9): calcd. C 67.21,
H 4.58, N 4.75; found C 67.18, H 4.46, N 4.83.
Acknowledgments
We are grateful to COLCIENCIAS and the Universidad del Valle
for financial support and to Dr. Daniela Oniciu (Alchem Laborat-
ories Corp., Alachua, USA) for her valuable suggestions. We also
thank the DAAD which granted R. A. a study visit to the Institute
of Organic Chemistry at the University of Mainz, Germany.
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3-H), 2.06Ϫ2.12 (m, 1 H, 4-H), 2.51Ϫ2.55 (m, 1 H, 4-H),
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1 H, 12-H), 3.27Ϫ3.33 (m, 1 H, 11-H), 3.39Ϫ3.45 (m, 1 H, 11-H),
3.56Ϫ3.60 (m, 1 H, 2-H), 3.65Ϫ3.73 (m, 1 H, 1-H), 6.32 (d, 1 H,
6-H), 6.39 (d, 1 H, 9-H), 6.66Ϫ6.72 (m, 2 H, 7-H, 8-H), 7.46 (d, 2
H), 7.53 (br.s, 4 H), 7.61 (d, 2 H), 7.62 (d, 2 H), 7.77 (d, 2 H,
aromat. H). Ϫ 13C NMR (CDCl3): δ ϭ 24.4 (C-3), 25.2 (C-4), 37.4
(C-12), 38.4 (C-11), 40.9 (C-2), 43.3 (C-1), 87.6 (C-2a), 104.3 (C-
6), 104.4 (C-9), 118.6, 119.2 (C-7, C-8), 123.0, 128.5, 128.6, 134.5,
135.1, 138.5, 138.9, 139.2 (aromat. Cq), 129.5, 129.6, 130.0, 131.7,
131.9, 132.2 (aromat. CH), 197.6, 199.9 (CO). Ϫ MS (70 eV): m/z
(%) ϭ 726/724/722/720 (18), [Mϩ, Br3 pattern], 692 (10), 510 (63),
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Received December 23, 1999
[O99690]
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