Synthesis of Dibenzo[ d, f][1,3]Diazepines via Elemental Sulfur-Mediated Cyclocondensation of 2,2′-Biphenyldiamines with 2-Chloroacetic Acid Derivatives

Article abstract of DOI:10.1021/acs.joc.9b02002

The three-component reaction of 2,2′-biphenyldiamines with 2-chloroacetic acid derivatives and elemental sulfur was developed for the practical synthesis of unknown 2-carboxamide-substituted dibenzo[d,f][1,3]diazepines. This protocol is distinguished by efficiency in water and good tolerance to functional groups and can be adapted to a large-scale synthesis. The chemoselective preparation of a variety of 2-S,N,O-substituted dibenzo[d,f][1,3]diazepines was accomplished using the developed method.

Full text of DOI:10.1021/acs.joc.9b02002

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Article
Synthesis of Dibenzo[d,f][1,3]diazepines via Elemental
Sulfur-Mediated Cyclocondensation of 2,2'-
Biphenyldiamines with 2-Chloroacetic Acid Derivatives
Tatyana A. Tikhonova, Konstantin A. Lyssenko, Igor V. Zavarzin, and Yulia Alexeevna Volkova
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02002 • Publication Date (Web): 15 Nov 2019
Downloaded from pubs.acs.org on November 16, 2019
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Synthesis of Dibenzo[d,f][1,3]diazepines via Elemental Sulfur-Mediated Cyclocondensation of 2,2'-
Biphenyldiamines with 2-Chloroacetic Acid Derivatives
†
‡, §
†
†*
Tatyana A. Tikhonova, Konstantin A. Lyssenko, Igor V. Zavarzin, Yulia A. Volkova
†
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991,
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Moscow, Russia, yavolkova@gmail.com
‡
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991, Moscow,
Russia.
§
Plekhanov Russian University of Economics, Stremyanny per. 36, Moscow, 117997, Russia.
R1
R1
N
NH
O
N
N
NH2
NH
S
H2N
NH
NH
NH
S8
R2
R2
O
NH
NH
NH
NH
Cl
S
O
R3
Inexpensive reagents
Up to 86% yield
Ease of scale-up
Functional group tolerant
Operationally simple, versatile
28 examples
ABSTRACT: The three-component reaction of 2,2'-biphenyldiamines with 2-chloroacetic acid derivatives and
elemental sulfur was developed for the practical synthesis of unknown 2-carboxamide-substituted
dibenzo[d,f][1,3]diazepines. This protocol is distinguished by efficiency in water, good tolerance to
functional groups and can be adapted to a large‐scale synthesis. The chemoselective preparation of a variety
of 2-S,N,O-substituted dibenzo[d,f][1,3]diazepines was accomplished using the developed method.
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INTRODUCTION
Benzodiazepines are important structural units found in a variety of biologically active agents, including
1
natural products (e.g., streptocarbazoles A and B ) and major drugs (e.g., anxiolytics, such as cloxazolam,
ketazolam, flumazenil, clobazam, delorazepam, alprazolam, etc., the anesthetic midazolam, the tranquillizer
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ethyl loflazepate). The prevalence of the dibenzo[d,f][1,3]diazepine motif in medicinally relevant
compounds, dyes, catalysts, MOFs,6,7 and organic electronics materials (Figure 1) has inspired the
2
3
4,5
8
development of many novel methods for their preparation.9-12
HO2C
BuO
N
OBu
S
S
NH
NH
N
NH
O
N
O
MeO
S
NH
N
OBu
HO2C
Catalyst
OBu
EHMT2 inhibitor
Semiconductor
[
ref. 2,3]
[ref. 4]
[ref. 8]
MOF linker
[
ref. 7]
Figure 1. Importance of dibenzo[d,f][1,3]diazepines.
10
Thus, iodine-mediated coupling of 2,2′-diaminobiphenyl with aldehydes, cyclocondensation of silylamines
with CO2,13 the reaction of 2,2′-diaminobiphenyl with bis(isothiocyanate), the titanacarborane monoamide-
14
1
5
catalyzed reaction of diamines with carbodiimides, cyclization reactions of 3-methyleneoxindoles with 2-
1
6
cyano-2-(3,4-dihydronaphthalen-1(2H)-ylidene)acetate, and indolin-2-ones with 4-methylthio-2H-pyran-2-
one-3-carbonitriles17,18 have been recently reported. However, there is a limited number of protocols for
assembling 2-carboxy-substituted dibenzo[1,3]diazepine derivatives that hold promise for materials science
and medicinal chemistry. Intramolecular cyclization of α-amido-α-aminonitrones derived from 2,2'-
biphenyldiamine19,20 and condensation of 2,2'-biphenyldiamine with α-hydroxy-andethanimidic acid esters21
were described (Figure 2, lines a,b). Despite the impressive progress made in this area, it is still a great
challenge to synthesize functionalized dibenzo[d,f][1,3]diazepines from readily available and easily varied
starting materials using simple procedures. Known methods suffer from a limited substrate scope, toxic
reagents, a strict anaerobic procedure, and harsh conditions.
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a)
O
Ph
O
N
NHR
O
NH2
N
+
H2N
NHR
NH
[ref. 19,20]
PhHN
R = Ar
b)
NH3 Cl-
+
N
Ar
O
1
1
1
1
1
1
1
1
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NH2
+
Ar
H2N
RO
NH
[ref. 21]
OH
R = Et
This work:
1
R1
R
S8
N
R3
O
NH2
Cl
R3
H2N
H2O, reflux
NH
O
R2
R2
efficiency in water
ease of operation and good scale-up potential
broad substrate scope and high yields.
R1, R2 = Me, Cl, Br
R3 = NH2, NHAr, NHHet,
NHAlk, NHCH2Ph
Figure 2. Synthetic approaches for 2-carboxy-substituted dibenzo[d,f][1,3]diazepines.
On the other hand, cascade organic reactions involving elemental sulfur are valued for their mild conditions,
excellent functional group tolerance, and ability to produce various heterocycles.22-25 A number of reports
published in the past decade demonstrate the utility of elemental sulfur in reactions with amines for the
2
6
27
synthesis of five- and six-membered N-heterocyclic compounds, such as imidazoles, benzo[d]imidazoles,
2
8
and pyrazole. In particular, noteworthy are [Cu]-catalyzed intramolecular cyclization of ynamides with
2
9
30
elemental sulfur and cyclization of 2-(2-isocyanophenyl)ethanols with elemental sulfur giving seven-
membered products. To the best of our knowledge, the elemental sulfur-promoted synthesis of
dibenzo[d,f][1,3]diazepines is currently unknown. Recently, our group has disclosed the Willgerodt-type31
three-component reaction of 2-chloroacetamides with amines and sulfur as a highly efficient approach to
3
2
phosphoryl-substituted thioamides, 2-imidazoline, and 1,4,5,6-tetrahydropyrimidine. Herein, we propose
that using 2,2'-biphenyldiamines in the reaction with 2-chloroacetic acid derivatives and sulfur is efficient
for the construction of 2-carboxy-substituted dibenzo[1,3]diazepine derivatives (Figure 1). Additionally, the
elaborated approach was applied to the preparation of 2,2'-biphenylenethiourea, 2,2'-biphenyleneurea,
sulfanyl-5H-dibenzo[d,f][1,3]diazepine, and 2-aminodibenzo-1,3-diazepine.
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RESULTS AND DISCUSSION
We began our study by examining the cascade reaction using 2,2'-biphenyldiamine (1a) and 2-
o
chloroacetamide 2a as the standard substrates (Table 1). Heating at 60 C with 3 equiv. of elemental sulfur
and Et N for 6 h was used as the initial conditions. The reactions in non-polar solvents, including hexane and
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CHCl , gave product 3a in low yields (7% and 16%, respectively; Table 1, entries 1, 2). The reaction in
3
polar solvents, such as 1,4-dioxane and DMSO, afforded compound 3a in slightly higher yields (21% and
o
o
3
5%, respectively; Table 1, entries 3, 4). Heating in DMF at 60 C and 90 C led to product 3a with the
yields increased to 37% and 58%, respectively (Table 1, entries 5, 6). An increase in the yield of compound
o
3
a is largely driven by an increase in the conversion of biphenyldiamine 1a from 25% at 60 C in hexane
o
(
Table 1, entry 1) to 71% at 90 C in DMF (Table 1, entry 6). In the absence of elemental sulfur, no apparent
o
changes were observed upon keeping this reaction mixture with Et N as the base at 60 C in DMF, with both
3
starting materials remaining intact. Surprisingly, the reaction occurs in a heterogeneous manner in water at
reflux (Table 1, entries 7-15). To our pleasure, the desired product 3a was obtained in 86% yield within 4 h
when the reaction was performed in water at reflux in the presence of 10 equiv. of Et N (Table 1, entry 11).
3
A decrease in the amount of Et N (up to 1 equiv.) and elemental sulfur (up to 10 mol%), as well as the use of
3
DIPEA as the base, proved to be considerably less effective under similar conditions (Table1, entries 7–10,
1
2-15).
Table 1. Optimization of the reaction conditionsa
S8 (x eq)
Cl
NH2
O
base (y eq)
N
HN
O
Cl
H2N
Cl
N
H
solvent, T oC
NH
1a
2a
3a
Reaction
time, h
Conv. of
Yield of
3а, %
entry
Solvent
Base (eq)
S
8
, eq
T, ⁰C
b
b
1a, %
1
2
n-hexane
Et
3
3
N (3)
N (3)
3
3
60
60
6
6
25
38
7
CHCl
3
Et
16
1
,4-
3
Et
3
N (3)
3
60
6
26
21
dioxane
4
5
DMSO
Et
3
3
N (3)
N (3)
3
3
60
60
6
6
52
60
35
DMF
Et
37c
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58c
6
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DMF
Et
Et
Et
Et
Et
3
3
3
3
3
N (3)
N (3)
N (1)
N (5)
N (7)
3
3
90
6
4
4
4
4
4
4
4
4
4
71
82
65
85
91
100
69
15
53
90
H
H
H
H
H
H
H
H
H
2
2
2
2
2
2
2
O
O
O
O
O
O
O
O
O
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
37
28
49
53
86c
56c
8
8
3
9
3
10
3
11
12
13
Et
3
N (10)
3
1
1
1
1
1
1
1
1
1
1
2
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2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
DIPEA (5)
3
Et
3
Et
3
Et
3
N (10)
N (10)
N (10)
0.1
1
14
15
2
2
28
53
6
a)
Reaction conditions: 2,2'-biphenyldiamine (1) (50 mg, 0.27 mmol), 2-chloro-N-(4-
chlorophenyl)acetamide (2a) (110 mg, 0.54 mmol, 2 eq), S (207 mg, 0.81 mmol, 3 eq), base,
8
b)
1
с)
solvent (1 mL). Determined by H NMR with internal standard. Isolated yield.
It was shown that under the optimized conditions, N-(4-chlorophenyl)-2-bromoacetamide (3) and N-
(
4-chlorophenyl)-2-iodoacetamide (4), as well as N-(4-chlorophenyl)-2-chloroacetamide (2a),
smoothly undergo this reaction (Scheme 1). Product 3a was isolated in 89%, 49% and 85% yields,
respectively. The reaction with 2-bromoacetamide 4 was accompanied by formation of a complex
mixture of side products.
Scheme 1. Scope of the reaction
NH2
H2N
S8 (3 eq)
Et3N (10 eq)
N
HN
O
Cl
1a
H2O, reflux, 4 h
NH
from 2a, R = Cl, yield 86%
from 4, R = Br, yield 49%
from 5, R = I, yield 85%
Cl
O
3a
R
N
H
2a, 4, 5
The substrate scope was explored with a variety of 2,2'-biphenyldiamine and 2-chloroacetic acid
derivatives. This method features remarkable generality with respect to chloroacetamides 2 (Table
2
). Compounds bearing both electron-withdrawing groups (4-Cl, 4-Br, 4-I, 4-F, 2-Cl, 2,4-Cl , 2-
2
NO , 4-NO ) and electron-donating groups (2-OMe, 3-OMe, 4-OMe, 3-Me, 4-Me, 2,4-Me ) were
2
2
2
tolerated under the reaction conditions. Products 3a-o were isolated in 61–89% yields.
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Unfunctionalized product 3i was obtained from 2-chloro-N-phenylacetamide (2i) in 78% isolated
yield. Compound 3p derived from 2-chloro-N-(naphthalen-1-yl)acetamide was synthesized in 85%
yield. In addition, 2-chloro-N-(pyridin-3-yl)acetamide 2q was tolerated under these reaction
conditions. The corresponding polyheterocyclic product 3q was synthesized in 40% yield. Under the
optimized conditions, N-heptyl-substituted chloroacetamide 2r, as well as benzyl-substituted 2s,
produced desired products 3r and 3s in 69% and 88% yields, respectively. The reaction can also be
performed with unsubstituted chloroacetamide, namely, 2-chloroacetamide 2t, producing product 3t
in 61% yield.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 2. Scope of the reaction with respect to 2-chloroacetamidesa,b
S8 (3 eq)
Et3N (10 eq)
O
NH2
N
HN
O
R
Cl
Cl
R
H2N
N
H
H2O, reflux, 4 h
NH
1a
2a-t
3a-t
Cl
NO2
N
HN
O
R
N
NH
HN
O
N
HN
O
Cl
N
HN
O
NH
NH
NH
3g, para, 73%
h, ortho, 68%
3
3
3
a, R = Cl, 86%
b, R = Br, 80%
c, R = I, 76%
3d, R = F, 77%
3e, 84%
3f, 81%
3
OMe
Me
N
HN
O
N
HN
O
N
HN
O
N
HN
O
Me
NH
NH
NH
NH
Me
3i, 78%
3j, para, 70%
3o, 76%
3
m, para, 61%
3k, meta, 69%
l, ortho, 71%
3n, meta, 74%
3
N
HN
O
N
HN
N
NHC H
N
NHCH Ph
N
O
7
15
2
N
NH
NH O Cl
NH
O
NH
O
NH NH2
3p, 85%
3q, 40%
3r, 69%
3s, 88%
3t, 61%
a)
Reaction conditions: 2,2'-biphenyldiamine (1) (100 mg, 0.54 mmol, 1 equiv), 2-
chloroacetamide 2 (1.08 mmol, 2 eq), S (414 mg, 1.62 mmol, 3 eq), Et N (0.75 mL, 5.40
O (5 mL). Isolated yield.
8
3
b)
mmol, 10 eq), H
2
This method was shown to be quite general with respect to 2,2'-biphenyldiamines (Table 3). Different
symmetrically and asymmetrically substituted diamines 1b-e, bearing both electron-withdrawing groups
(
5,5'-Cl, 5,5'-Br, 5’-Cl) and electron-donating groups (5,5'-Me , 4,6-Me ), proved to be competent substrates
2 2
and provided the corresponding dibenzo[d,f][1,3]diazepines 3u-x in reasonable-to-good yields. Low yield of
product 3x can be attributed with destabilizing steric interference on dibenzo[d,f][1,3]diazepine cycle from
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
4
4
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5
5
5
5
5
6
methyl-group. As expected, sterically unfavorable substrates, such as 6,6'-dimethyl-[1,1'-biphenyl]-2,2'-
diamine (1f), failed to undergo the reaction under the optimized conditions. Thus, product 3y was not
detected. Attempts to perform the reaction with electron-deficient 5,5'-dinitro-[1,1'-biphenyl]-2,2'-diamine
(1g) failed (compound 3z); the reactions gave complex mixtures of products.
Table 3. Scope of the reaction with respect to 2,2'-biphenyldiaminesa,b
0
1
2
3
4
5
6
7
8
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0
1
2
3
4
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9
0
1
2
3
4
5
6
7
8
9
0
R1
R1
S8 (3 eq)
Et3N (10 eq)
O
HN R3
O
NH2
N
Cl
R3
H2N
N
H
H2O, reflux, 4 -6 h
NH
R2
R2
1b-g
2l,u
3u-z
Cl
Br
N
O
N
O
N
O
NH HN
NH HN
NH HN
Cl
Br
3u, 87%
3v, 71%
3w, 77%
Cl
O2N
N
O
N
O
N
O
NH HN
NH HN
NH HN
O2N
3x, 5%
3y, --%
3z, --%
a)
Reaction conditions: 2,2'-biphenyldiamine 1 (0.54 mmol, 1
equiv), 2-chloroacetamide 2 (1.08 mmol, 2 eq), S (414 mg, 1.62
8
b)
mmol, 3 eq), Et
3 2
N (0.75 mL, 5.40 mmol, 10 eq), H O (5 mL).
Isolated yield.
The structures of dibenzo[d,f][1,3]diazepines 3 were confirmed by single crystal X-ray analysis of the
representative compound 3k (Figure 3). CCDC 1942000 contains the supplementary crystallographic data
for compound 5k. The data can be obtained free of charge from The Cambridge Crystallographic Data
Centre.
Figure 3. The general view of X in representation of atoms by thermal ellipsoids (p=50%) for compound 3k.
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2
2
2
2
2
2
2
2
2
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3
3
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3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
As shown in Scheme 2, this method can easily be scaled up without loss in yield regardless of the 2-
chloroacetamide substitution. Thus, the treatment of 2,2'-biphenyldiamine (1a) (1.0 g, 5.4 mmol) with 2-
chloro-N-(2,4-dichlorophenyl)acetamide 2f (2.6 g, 11.0 mmol) and sulfur at reflux in water for 4 h gave
dibenzo[d,f][1,3]diazepine 3f in 76% yield (1.6 g, recrystallization from EtOH) (line a). 2-Chloroacetamide
(2t) (1.9 g, 12.0 mmol) also smoothly reacted with amine 1a (2.0 g, 10.8 mmol) and sulfur on heating in
DMF to form product 3t in 60% yield (1.4 g, recrystallization from EtOH) (line b).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 2. Scale-up experiments
a)
Cl
S8 (3 eq)
Cl
O
Et3N (10 eq)
NH2
N
HN
O
Cl
Cl
H2N
N
H
H2O, reflux, 6 h
NH
Cl
1a
2f
3f, 82%
1.0 g
2.6 g
1.6 g
b)
S8 (3 eq)
O
Et3N (3 eq)
N
NH2
NH2
O
Cl
H2N
NH2
DMF, 60 oC, 6 h
NH
1
2.0 g
a
2t
1.9 g
3t
, 60%
1.4 g
Surprisingly, the reactions of 2,2'-biphenyldiamine (1a) with 2-chloroacetic acid (4a) or ethyl chloroacetate
4b) and elemental sulfur the under optimized conditions were accompanied by the formation of cyclic
(
thiourea 5 (Scheme 3). An X-ray crystal structure analysis of compound 5 unambiguously confirmed the
elucidated structure and the chemoselectivity of the reaction (CCDC 1941997). 5,7-
Dihydrodibenzo[d,f][1,3]diazepine-6-thione (5) was isolated as a single product in 82% and 63% yields,
respectively. The reaction with 4a was carried out on a 0.6 mmol scale; but it can easily be scaled up.
Indeed, compound 5 was prepared in 85% isolated yield (1.9 g) on a 10.8 mmol scale from 2.0 g of amine 1a
and 1.2 mL of 2-chloroacetic acid (2a).
Scheme 3. Synthesis of 5,7-dihydro-dibenzo[d,f][1,3]diazepine-6-thione (5)
S8 (3 eq)
Et3N (10 eq)
O
NH2
NH
NH
Cl
H2N
OR
S
H2O, reflux, 4 h
R = H, yield 85%
R = Et, yield 63%
1a
4a,b
5
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The Journal of Organic Chemistry
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5
6
5,7-Dihydrodibenzo[d,f][1,3]diazepine-6-thione (5) is a valuable compound since it can provide access to
other functionalized dibenzo[d,f][1,3]diazepines. Scheme 4 shows several examples of their conversion to
structurally diverse products. The synthesis of 2,2'-biphenyleneurea (6, CCDC 1941998) was accomplished
by the oxidative desulfurization of thiourea 5 in a water/CH CN mixture in the presence of silver carbonate.
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
The alkylation of compound 5 with 2-bromoacetic acid gave secondary thiol 7 in reasonable yield.
Additionally, we showed that the S group in 4 is a good leaving group. The stepwise treatment of thiourea 5
with methyl iodide and 2-amino-4,6-dimethylpyrimidine afforded cyclic bis(guanidine) 8 in 58% yield. The
foregoing demonstrates that the new method provides a feasible route to structurally interesting and
potentially useful 2-fuctionalized dibenzo[d,f][1,3]diazepines and offers new opportunities for the ligand
development in medicinal chemistry and materials science.
Scheme 4. Chemical transformations of 5,7-dihydrodibenzo[d,f][1,3]diazepine-6-thione (5)
Ag2CO3
NH
NH
O
MeCN/H2O (1:1)
rt, 4 h
6
, 68%
NH
NH
BrCH2CO2H
N
CO2H
S
S
acetone, rt, 18 h
NH
7
, 45%
5
1
. MeI, MeCN
rt, overnight
N
N
N
NH
2. 2-amino-4,6-di-
methylpyrimi-
dine
NH
1
70 oC, 1.5 h
8, 65%
Additional experiments were performed to gain insights into the reaction mechanism (Scheme 5). The
o
treatment of 2,2'-biphenyldiamine (1a) with 2-chloroacetamide 2a at 60 C in DMF furnished product 3a
along with oxoethanethioamide 9. The former was quantitatively converted into dibenzo[d,f][1,3]diazepine
3a at reflux in water in the presence of a base.
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9
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1
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 5. Studies of the heterocyclization pathway
NH2
H2N
S8 (3 eq)
Cl
N
HN
O
Cl
H2N
O
Et3N (3 eq)
H
1a
N
+
NH
N
DMF, 60 oC, 3 h
H
S
Cl
O
9
, 27%
3a, 14%
Cl
N
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H
Et3N (3 eq)
2a
H O, reflux, 2 h
yield 90%
2
Based on the literature precedents22,31 and experimental data, we propose a tentative mechanism for the
sulfur-mediated condensation of 2,2'-biphenyldiamines with 2-chloroacetic acid derivatives (Scheme 6). The
process is initiated by the thiolation of chloride III with polysulfide II derived from 2,2'-biphenyldiamine I
and elemental sulfur. In the presence of amine, the resulting polysulfide IV undergoes S–S bond decoupling
accompanied by proton abstraction giving thioaldehyde V, which is highly reactive in imination to form VI.
The cascade addition of polysulfides II to VI and elimination of polysulfides II’ from VII afford thioamide
VIII. The intramolecular ring closure of VII followed by hydrogen sulfide elimination gives 2-carboxy-
substituted dibenzo[d,f][1,3]diazepine IX. Compounds IX derived from 2-chloroacetic acid or its esters in
situ undergo decarboxylation followed by the addition of hydrogen sulfide and proton migration to form
thiourea X.
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The Journal of Organic Chemistry
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8
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1
1
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1
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1
1
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2
2
2
2
2
2
2
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4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 6. Proposed mechanistic pathway
O
H
R2
Cl
S8
N
Sn S-
S
NH2
III
R1
R1
II, n = 0-6
I
S
H2N
=
-S
R1
O
S
nS-
S
S
N
H
R2
S n
N
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
R1
H
R1
II'
IV
O
O
S
S
R2
S n
N
H
S
R2
R1
N
H
V
R1
R1
O
VII
I
N
R2
H
VI
II
H2N
=
if R2 = CO2H
H2S
O
H
R1
NH
O
NH
N
R2
S
S
-H2S
N
R2
-HCOOH
NH
R1
VIII
IX
X
CONCLUSION
In conclusion, we demonstrated the utility of the three-component cyclocondensation for the easy access to
dibenzo[1,3]diazepines starting from 2,2'-biphenyldiamines, 2-chloroacetic acid derivatives, and elemental
sulfur. A variety of products can be prepared from readily available materials in water. The new strategy
significantly expands the synthetic scope of sulfur-mediated reactions. Due to operational simplicity, these
protocols may be useful in pharmacological research and the design of materials and ligands in metal
complex-catalyzed reactions. Further investigation and extension of results are currently underway.
■
EXPERIMENTAL SECTION
Experimental Section:
General Information
NMR spectra were acquired at room temperature; the chemical shifts δ were measured in ppm relative to the
1
13
solvent ( Н: CDCl , δ = 7.27 ppm, DMSO-d , δ = 2.50 ppm; C: CDCl , δ = 77.00 ppm, DMSO-d , δ =
3
6
3
6
3
9.50 ppm). Splitting patterns are designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd,
double doublet. The coupling constants (J) are in Hertz. The structures of all compounds were established
1
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using 1D NMR ( H, 13C) spectroscopy. High-resolution mass spectra (HRMS) were obtained using
electrospray ionization (ESI) with Q-TOF detection and electron ionization (EI) techniques. IR spectra were
obtained either as potassium bromide pellets or as liquid films between two potassium bromide pellets with
an infrared spectrometer. Melting points (mp) are uncorrected. Analytical thin layer chromatography (TLC)
was carried out on silica gel plates (silica gel 60 F254 aluminum supported plates); the visualization was
accomplished with an UV lamp (365 nm). Column chromatography was performed on silica gel 60 (230-400
mesh). 2,2'-Biphenyldiamine, sulfur, 2-amino-4,6-dimethylpyrimidine, 2-bromoacetic acid, 2-chloroacetic
acid, ethyl chloroacetate, methyl iodide, and silver carbonate were commercially available and were used
without additional purification. All reactions were carried out using freshly distilled and dry solvents. Parent
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
-chloroacetamides were prepared according to published procedures.33 2-Iodoacetamide34 and 2-
3
5
36
bromoacetamide were synthesized by published procedures. 5,5'-Dimethyl-[1,1'-biphenyl]-2,2'-diamine,
,5'-dichloro-[1,1'-biphenyl]-2,2'-diamine,36 5'-chloro-4,6-dimethyl-[1,1'-biphenyl]-2,2'-diamine,36 5,5'-
dibromo-[1,1'-biphenyl]-2,2'-diamine,37 6,6'-dimethyl-[1,1'-biphenyl]-2,2'-diamine,38 and 5,5'-dinitro-[1,1'-
5
3
9
biphenyl]-2,2'-diamine were prepared according to published procedures.
General procedure for the synthesis of 5H-dibenzo[d,f][1,3]diazepine-6-carboxamides 3.
o
2
-Chloroacetamide 2 (1.08 mmol, 2 equiv) was added portionwise at 100 C (oil bath) during 2 h to the
mixture of 2,2'-biphenyldiamine 1 (0.54 mmol, 1.0 equiv), triethylamine (0.75 mL, 5.40 mmol, 10 equiv),
and sulfur (414 mg, 1.62 mmol, 3 equiv) in water (5 mL). The mixture was stirred for 4 h at reflux until the
complete conversion of 2,2'-biphenyldiamine (TLC monitoring). The resulted mixture was cooled to room
temperature and decanted, precipitate was dissolved in EtOAc (10 mL) and solution was washed with water
(3  10 mL). Organic layer was dried over Na SO , solvent was removed under reduced pressure and
2
4
product was isolated by column chromatography (eluent: petroleum ether - EtOAc, 4:1  3:1).
N-(4-chlorophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3a). Yield 76% (132 mg), yellow
1
solid, mp 132 - 134 °C; R = 0.22 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.59
f
6
(
br.s, 1H), 8.51 (br.s, 1H), 7.87 (d, J = 8.80 Hz, 2H), 7.44 (d, J = 8.80 Hz, 2H), 7.31 (d, J = 7.34 Hz, 2H),
1
3
1
7
.00-7.23 (m, 6H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.7, 153.0, 147.9, 147.4, 137.1, 135.0, 130.2,
6
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The Journal of Organic Chemistry
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8
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
6
129.6, 129.1, 128.6, 127.8, 125.5, 122.5, 118.6, the signal of the one C group was not observed; IR (KBr)
402 (s), 3385 (s), 3181 (s), 1635 (s), 1497 (w), 1483 (s), 1446 (s), 1292 (w), 1138 (w), 862 (w), 754 (s)
3
−
1
+
+
cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 348.0887; Found 348.0898.
2
0
15
3
N-(4-bromophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3b). Yield 80% (157 mg), yellow
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
solid, mp 146 - 148 °C; R = 0.24 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.60
f
6
(br.s, 1H), 8.53 (br.s, 1H), 7.82 (d, J = 8.80 Hz, 2H), 7.59 (d, J = 8.80 Hz, 2H), 7.32-7.34 (m, 3H), 7.22-7.24
1
3
1
(
m, 3H), 7.10 (d, J = 7.33 Hz, 1H), 7.00 (d, J = 7.33 Hz, 1H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.7,
6
153.0, 147.9, 147.3, 137.5, 135.0, 132.0, 130.2, 129.9, 129.6, 129.1, 127.8, 125.5, 122.8, 121.4, 116.7; IR
(KBr) 3326 (s), 3288 (s), 1685 (s), 1655 (s), 1541 (w), 1500 (s), 1439 (s), 1412 (s), 1334 (w), 1116 (w), 831
−
1
+
+
(
w), 747 (s) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 392.0393; Found 392.0382.
2
0
15
3
N-(4-iodophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3c). Yield 76% (167 mg), yellow solid,
1
mp 148 - 150 °C; R = 0.18 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.55 (br.s,
f
6
1
H), 8.50 (br.s, 1H), 7.66 – 7.81 (m, 4H), 7.30 (d, J = 7.34 Hz, 1H), 7.20 – 7.23 (m, 4H), 6.99 - 7.07 (m,
1
3
1
3
H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.7, 152.9, 147.9, 147.3, 137.9, 131.6, 131.2, 130.2, 129.6,
6
129.1, 127.8, 125.8, 125.4, 123.2, 122.0, 121.3, 117.9, 116.4; IR (KBr) 2982 (w), 1734 (s), 1488 (w), 1468
−1
+
(
w), 1249 (w), 1188 (w), 836 (w), 756 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for
+
C H ClN O 440.0254; Found 440.0257.
2
0
15
3
N-(4-fluorophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3d). Yield 77% (127 mg), yellow
1
solid, mp 194 - 196 °C; R = 0.27 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.54
f
6
(br.s, 1H), 8.51 (br.s, 1H), 7.82 – 7.88 (m, 2H), 7.30 – 7.32 (m, 3H), 7.20 - 7.26 (m, 5H), 7.09 (dd, J = 8.07,
1
3
1
7.33 Hz, 1H), 7.00 (d, J = 8.07 Hz, 1H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.6, 159.17, 157.6, 153.2,
6
1
48.0, 147.4, 135.0, 134.6, 130.2, 129.7, 129.1, 127.8, 125.5, 122.8, 121.4, 115.8; IR (KBr) 3320 (w), 1672
−
1
(
s), 1652 (s), 1492 (w), 1483 (w), 1211 (w), 1158 (w), 834 (w), 750 (w) cm ; HRMS (ESI/Q-TOF) m/z:
+
+
[
M+H] Calcd. for C H ClN O 332.1194; Found 332.1195.
20 15
3
N-(2-chlorophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3e). Yield 84% (146 mg), yellow
1
solid, mp 131 - 134 °C; R = 0.25 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.52
f
6
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5
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
6
(br.s, 1H), 8.68 (br.s, 1H), 8.20 (d, J = 8.06 Hz, 1H), 7.60 (d, J = 8.06 Hz, 1H), 7.83 (dd, J = 8.06, 7.33 Hz,
13
1
1
1
1
H), 7.23 - 7.33 (m, 6H), 7.03 - 7.05 (m, 3H); C{ H} NMR (75 MHz, DMSO-d ): δ 158.8, 152.5, 147.3,
6
47.0, 139.5, 134.2, 131.5, 130.4, 130.2, 130.0, 129.8, 129.6, 128.6, 126.6, 124.8, 122.4; IR (KBr) 3323 (w),
−
1
675 (s), 1656 (s), 1491 (w), 1483 (w), 1435 (w), 1283 (w), 771 (w), 749 (w) cm ; HRMS (ESI/Q-TOF)
+
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
m/z: [M+H] Calcd. for C H ClN O 348.0898; Found 348.0898.
20 15 3
N-(2,4-dichlorophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3f). Yield 81% (155 mg), yellow
1
solid, mp 111 − 112 °C; R = 0.25 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.55
f
6
(br.s, 1H), 8.52 (br.s, 1H), 7.61 (d, J = 8.06 Hz, 2H), 7.42 (dd, J = 8.06, 7.89 Hz, 1H), 7.32 - 7.34 (m, 3H),
13
1
6
1
,98 - 7.28 (m, 5H); C{ H} NMR (75 MHz, DMSO-d ): δ 160.2, 152.0, 148.0, 147.5, 135.1, 134.2, 133.1,
6
30.2, 130.1, 129.9, 129.6, 129.6, 129.2, 129.0, 127.9, 125.5, 121.4; IR (KBr) 2982 (w), 1734 (s), 1488 (w),
−
1
+
1468 (w), 1249 (w), 1188 (w), 836 (w), 756 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for
+
C H ClN O 382.0508; Found 382.0502.
2
0
15
3
N-(4-nitrophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3g). Yield 73% (131 mg), yellow solid,
1
mp 254 - 256 °C; R = 0.28 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.07 (br.s,
f
6
1H), 8.79 (br.s, 1H), 8.24 – 8.32 (m, 2H), 8.08 – 8.16 (m, 2H), 7.89 – 7.98 (m, 1H), 7.31 (d, J = 7.61 Hz,
13
1
1
1
H), 7.02 – 7.29 (m, 4H), 6.55 – 6.63 (m, 2H); C{ H} NMR (75 MHz, DMSO-d ): δ 160.3, 156.2, 152.7,
6
47.6, 147.0, 144.3, 143.5, 141.4, 136.1, 130.3, 129.4, 128.5, 126.8, 125.9, 125.2, 121.9, 120.7, 112.8; IR
(KBr) 3326 (s), 3288 (s), 1685 (s), 1655 (s), 1541 (w), 1500 (s), 1439 (s), 1412 (s), 1334 (w), 1116 (w), 831
−1
+
+
(
w), 747 (s) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 359.1139; Found 359.1144.
20 15 3
N-(2-nitrophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3h). Yield 68% (122 mg), yellow solid,
4
0
1
mp 235 - 236 °C (mp 233-235 °C ); R = 0.27 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz,
lit
f
DMSO-d ): δ 10.06 (br.s, 1H), 8.54 (d, J = 7.40 Hz, 1H), 8.24 (d, J = 8.41 Hz, 1H), 7.95 (d, J = 8.66 Hz,
6
2
1
H), 7.84 (dd, J = 8.66, 7.89 Hz, 1H), 7.36 – 7.43 (m, 4H), 6.89 – 7.35 (m, 3H), 6.61 (dd, J = 8.41, 6.82 Hz,
1
3
1
H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.5, 152.1, 147.1, 147.1, 138.5, 138.3, 136.2, 133.2, 133.1,
6
130.4, 129.6, 126.4, 124.9, 122.2, the signal of the one C group was not observed; IR (KBr) 3345 (s), 3306
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(s), 2962 (s), 1665 (s), 1650 (s), 1529 (w), 1514 (s), 1433 (s), 1248 (w), 1035 (w), 829 (w), 748 (s) cm ;
+
+
HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 359.1139; Found 359.1138.
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N-phenyl-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3i). Yield 78% (122 mg), yellow solid, mp 121 -
1
1
23 °C; R = 0.20 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.46 (br.s, 1H), 8.53
f
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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7
8
9
0
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8
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0
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(br.s, 1H), 7.83 (d, J = 7.32 Hz, 2H), 7.40 (dd, J = 8.16, 7.32 Hz, 2H), 7.32-7.34 (m, 3H), 7.22-7.26 (m, 3H),
13
1
7
.17 (dd, J = 8.07, 7.33 Hz, 1H), 7.09 (dd, J = 8.07, 7.33 Hz, 1H), 7.00 (d, J = 8.07 Hz, 1H); C{ H} NMR
(
75 MHz, DMSO-d ): δ 159.0, 152.7, 147.5, 146.9, 137.6, 134.5, 129.8, 129.7, 129.2, 129.1, 128.8, 128.6,
6
128.5, 127.3, 125.0, 124.4, 120.9, 123.6; IR (KBr) 3323 (w), 1675 (s), 1654 (s), 1491 (w), 1481 (w), 1435
−1
+
+
(
w), 1283 (w), 760 (w), 750 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O
20 15 3
3
14.1288; Found 314.1289.
N-(4-methoxyphenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3j). Yield 70% (120 mg), yellow
1
solid, mp 154 - 155 °C; R = 0.31 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.36
f
6
(
br.s, 1H), 8.47 (br.s, 1H), 7.73 (d, J = 8.89 Hz, 2H), 7.31 (d, J = 7.33 Hz, 2H), 7.15 - 7.27 (m, 3H), 7.03 -
1
3
1
7
.15 (m, 2H), 6.89 - 6.97 (m, 3H), 3.76 (s, 3H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.1, 156.5, 153.4,
6
147.9, 147.5, 134.9, 131.2, 130.3, 130.1, 129.9, 129.6, 129.6, 129.1, 127.7, 125.4, 122.3, 121.3, 114.4, 55.7;
IR (KBr) 3345 (s), 3306 (s), 2962 (s), 1665 (s), 1650 (s), 1529 (w), 1514 (s), 1433 (s), 1248 (w), 1035 (w),
−
1
+
+
8
29 (w), 748 (s) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 344.1394; Found
20 15 3
344.1394.
N-(3-methoxyphenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3k). Yield 69% (119 mg), yellow
1
solid, mp 165 - 167 °C; R = 0.25 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.42
f
6
(br.s, 1H), 8.52 (br.s, 1H), 7.52 (s, 1H), 7.44 (d, J = 8.07 Hz, 1H), 7.29-7.32 (m, 4H), 7.19-7.27 (m, 3H),
13
1
7
.08 (dd, J = 8.17, 7.33 Hz, 1H), 6.99 (dd, J = 8.07 Hz, 1H), 6.75 (d, J = 7.33 Hz, 1H), 3.78 (s, 3H); C{ H}
NMR (75 MHz, DMSO-d ): δ 160.0, 159.5, 153.1, 148.0, 147.4, 139.3, 135.0, 130.3, 130.2, 130.1, 130.0,
6
1
29.8, 129.6, 129.1, 127.8, 125.5, 121.4, 113.0, 110.6, 106.4, 55.6; IR (KBr) 3323 (w), 1675 (s), 1654 (s),
−
1
+
1491 (w), 1481 (w), 1435 (w), 1283 (w), 760 (w), 750 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd.
+
for C H ClN O 344.1394; Found 344.1397.
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N-(2-methoxyphenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3l). Yield 71% (123 mg), yellow
1
solid, mp 174 - 176 °C; R = 0.25 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.31
f
6
(br.s, 1H), 8.63 (br.s, 1H), 8.24 (d, J = 8.06 Hz, 1H), 7.30-7.31 (m, 3H), 7.15-7.27 (m, 5H), 7.08-7.11 (m,
1
3
1
1
H), 7.00-7.05 (m, 2H), 3.95 (s, 3H); C{ H} NMR (75 MHz, DMSO-d ): δ 158.2, 152.9, 149.2, 147.5,
6
0
1
2
3
4
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6
7
8
9
0
1
2
3
4
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8
9
0
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8
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0
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147.0, 135.0, 130.4, 130.3, 129.7, 129.6, 129.4, 128.0, 126.6, 125.3, 121.5, 121.1, 119.4, 111.6, 56.6; IR
(KBr) 3345 (s), 3306 (s), 2962 (s), 1665 (s), 1650 (s), 1529 (w), 1514 (s), 1433 (s), 1248 (w), 1035 (w), 829
−
1
+
+
(
w), 748 (s) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 344.1394; Found 344.1397.
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0
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N-(p-tolyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3m). Yield 61% (100 mg), yellow solid, mp
1
1
66-167 °C; R = 0.23 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.36 (br.s, 1H),
f
6
8
.48 (br.s, 1H), 7.70 (d, J = 8.06 Hz, 2H), 7.30-7.32 (m, 3H), 7.19-7.24 (m, 5H), 7.04 - 7.11 (m, 1H), 6.97
1
3
1
(d, J = 6.70 Hz, 1H), 2.29 (s, 3H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.4, 153.2, 147.9, 147.4, 138.5,
6
1
38.0, 134.9, 130.3, 130.1, 129.9, 129.7, 129.6, 129.1, 127.8, 125.6, 125.5, 121.3, 121.3, 117.8, 21.6; IR
(
(
KBr) 3328 (s), 3285 (s), 1685 (s), 1665 (s), 1541 (w), 1505 (s), 1439 (s), 1412 (s), 1338 (w), 1116 (w), 836
−
1
+
+
w), 751 (s) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 328.1444; Found 328.1445.
20 15
3
N-(m-tolyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3n). Yield 74% (121 mg), yellow solid, mp
1
1
8
85 - 157 °C; R = 0.22 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.35 (br.s, 1H),
f
6
.48 (br.s, 1H), 7.63 (d, J = 8.06 Hz, 2H), 7.26 - 7.33 (m, 3H), 7.18 - 7.26 (m, 4H), 7.07 (dd, J = 8.17, 7.33
1
3
1
Hz, 1H), 6.97 (d, J = 8.06 Hz, 2H), 2.32 (s, 3H); C{ H} NMR (75 MHz, DMSO-d ): δ 160.0, 153.1, 147.9,
6
1
1
47.4, 138.5, 138.0, 135.0, 130.3, 130.1, 129.9, 129.7, 129.6, 129.1, 127.8, 125.6, 125.5, 121.4, 121.3,
17.8, 21.6; IR (KBr) 3320 (w), 1672 (s), 1652 (s), 1492 (w), 1483 (w), 1211 (w), 1158 (w), 834 (w), 750
−
1
+
+
(w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 328.1444; Found 328.1450.
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0
15
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N-(2,4-dimethylphenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3o). Yield 76% (130 mg), yellow
1
solid, mp 130 − 132 °C; R = 0.20 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.12
f
6
(br.s, 1H), 8.44 (br.s, 1H), 7.27-7.32 (m, 3H), 7.16-7.24 (m, 3H), 7.13 (m, 3H), 7.06 (dd, J = 8.31, 7.33 Hz,
1
3
1
1H), 6.95 (d, J = 8.31 Hz, 1H), 2.18 (s, 6H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.8, 152.9, 148.0,
6
1
47.7, 135.7, 135.0, 134.9, 130.3, 130.1, 130.0, 129.8, 129.6, 129.1, 128.2, 127.7, 127.4, 125.4, 121.3, 18.6,
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the signal of the one C group was not observed; IR (KBr) 2982 (w), 1734 (s), 1488 (w), 1468 (w), 1249 (w),
−1
+
+
1
188 (w), 836 (w), 756 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 342.1600;
20 15 3
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N-(naphthalen-1-yl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3p). Yield 85% (155 mg), yellow
1
0
1
2
3
4
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7
8
9
0
1
2
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7
8
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solid, mp 173 - 176 °C; R = 0.31 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.78
f
6
(br.s, 1H), 8.58 (br.s, 1H), 7.95 - 8.01 (m, 2H), 7.88 (d, J = 8.06 Hz, 1H), 7.83 (d, J = 7.33 Hz, 1H), 7.56-
1
3
1
7
.66 (m, 3H), 7.34-7.37 (m, 3H), 7.03-7.26 (m, 5H); C{ H} NMR (75 MHz, DMSO-d ): δ 160.2, 153.1,
6
147.8, 147.6, 134.2, 133.0, 130.3, 129.6, 129.3, 128.8, 128.2, 127.9, 126.9, 126.8, 126.6, 126.1, 125.7,
22.7, 121.9, 121.5; IR (KBr) 3323 (w), 1675 (s), 1654 (s), 1491 (w), 1481 (w), 1435 (w), 1283 (w), 769
1
−
1
+
+
(
w), 750 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 364.1444; Found 364.1444.
20 15 3
N-(2-chloropyridin-3-yl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3q). Yield 40% (70 mg), yellow
1
solid, mp 275 - 276 °C; R = 0.34 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 10.07
f
6
(br.s, 1H), 8.52 (d, J = 8.06 Hz, 1H), 8.27 (d, J = 5.13 Hz, 1H), 7.54 (dd, J = 8.06, 5.13 Hz, 1H), 7.25 - 7.34
1
3
1
(
m, 3H), 7.13 - 7.20 (m, 4H), 7.05 (d, J = 8.06 Hz, 2H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.4, 152.1,
6
147.2, 145.7, 142.2, 131.6, 131.1, 130.8, 130.4, 129.6, 128.6, 124.6, 124.4, 117.4, 115.6; IR (KBr) 3323 (w),
−1
1
675 (s), 1654 (s), 1491 (w), 1481 (w), 1435 (w), 1283 (w), 760 (w), 750 (w) cm ; HRMS (ESI/Q-TOF)
+
+
m/z: [M+H] Calcd. for C H ClN O 349.0851; Found 349.0850.
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N-heptyl-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3r). Yield 69% (116 mg), yellow solid, mp 165 -
1
1
67 °C; R = 0.30 (petroleum ether - EtOAc, 3:1). H NMR (300 MHz, DMSO-d ): δ 8.70 (t, J = 6.1 Hz,
f
6
1
H), 8.29 (br.s, 1H), 7.27-7.30 (m, 2H), 7.23 – 7.12 (m, 2H), 7.05 (dd, J = 3.29, 7.86 Hz, 2H), 6.91 (d, J =
7.86 Hz, 2H), 3.10-3.26 (m, 2H), 1.38-1.60 (m, 2H), 1.25 (d, J = 3.07 Hz, 8H), 0.84 (t, J = 6.68 Hz, 3H);
13
1
C{ H} NMR (75 MHz, DMSO-d ): δ 160.9, 153.2, 147.9, 147.6, 134.9, 130.3, 130.0, 129.7, 129.5, 129.3,
6
1
1
29.0, 127.5, 125.3, 121.1, 39.1, 31.6, 29.3, 28.8, 26.8, 22.5, 14.4; IR (KBr) 2965 (w), 1701 (s), 1456 (w),
−
1
+
423 (w), 1247 (w), 1180 (w), 889 (w), 742 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for
+
C H ClN O 336.2070; Found 336.2070.
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1
1
1
43 °C; R = 0.25 (petroleum ether – EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 9.29 (t, J = 6.59 Hz,
f
6
H), 8.38 (br.s, 1H), 7.14 – 7.33 (m, 10H), 7.02 – 7.08 (m, 2H), 6.93 (d, J = 8.06 Hz, 1H), 4.43 (d, J = 6.59
1
3
1
Hz, 2H); C{ H} NMR (75 MHz, DMSO-d ): δ 161.4, 153.2, 148.1, 147.8, 139.4, 135.0, 130.3, 129.6,
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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7
8
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0
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8
9
0
1
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8
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0
128.8, 127.9, 127.4, 125.4, 121.2; IR (KBr) 2982 (w), 1734 (s), 1488 (w), 1468 (w), 1249 (w), 1188 (w), 836
−1
+
+
(
w), 756 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 328.1444; Found 328.1442.
20 15 3
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H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3t). Yield 61% (73 mg), yellow solid, mp 195 - 197 °C; Rf
1
= 0.38 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz, DMSO-d ): δ 8.26 (br.s, 1H), 8.07 (br.s, 1H),
6
13
1
7
.79 (br.s, 1H), 7.14-7.30 (m, 5H), 7.00-7.07 (m, 2H), 6.91 (d, J = 7.97 Hz, 1H); C{ H} NMR (75 MHz,
DMSO-d ): δ 163.2, 153.3, 147.9, 147.6, 134.8, 130.2, 130.1, 129.8, 129.6, 129.4, 129.1, 127.6, 125.3,
6
121.0; IR (KBr) 3323 (w), 1675 (s), 1654 (s), 1491 (w), 1481 (w), 1435 (w), 1283 (w), 760 (w), 750 (w)
−1
+
+
cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 238.1444; Found 238.1444.
2
0
15
3
2
,10-Dimethyl-N-phenyl-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3u). Yield 87% (160 mg),
1
yellow solid, mp 128 - 129 °C; R = 0.24 (petroleum ether – EtOAc, 5:1). H NMR (300 MHz, CDCl ): δ
f
3
9.85 (br.s, 1H), 7.96 (d, J = 8.05 Hz, 1H), 7.75 (br.s, 1H), 7.26 – 7.35 (m, 3H), 7.15 – 7.24 (m, 2H), 7.07 –
13
1
7
1
.10 (m, 4H), 6.68 (d, J = 7.75 Hz, 1H), 2.37 (s, 3H), 2.35 (s, 3H); C{ H} NMR (75 MHz, CDCl ): δ
3
58.2, 152.0, 146.8, 146.6, 134.9, 134.8, 132.6, 131.2, 130.2, 130.1, 129.9, 129.4, 129.3, 128.7, 128.1,
127.5, 127.4, 125.2, 120.9, 120.0, 20.9, 17.5; IR (KBr) 3288 (w), 2975 (s), 1682 (w), 1648 (w), 1489 (w),
−1
+
+
1
3
286 (w), 1153 (w), 812 (w), 755 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O
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42.1601; Found 342.1596.
2,10-Dichloro-N-phenyl-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3v). Yield 71% (140 mg), yellow
1
solid, mp 108 - 110 °C; R = 0.31 (petroleum ether – EtOAc, 5:1). H NMR (300 MHz, CDCl ): δ 9.65 (br.s,
f
3
1
5
H), 7.75 (br.s, 1H), 7.65 (d, J = 7.78 Hz, 2H), 7.33 – 7.45 (m, 5H), 7.27 – 7.31 (m, 1H), 7.20 (dd, J = 7.42,
1
3
1
.28 Hz, 1H), 6.94 (d, J = 8.29 Hz, 1H), 6.54 (d, J = 8.41 Hz, 1H); C{ H} NMR (75 MHz, CDCl ): δ
3
157.9, 151.7, 145.6, 145.5, 136.6, 135.3, 132.6, 132.5, 132.2, 131.0, 130.4, 129.2, 125.1, 121.6, 121.1,
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119.7, 118.0; IR (KBr) 2991 (w), 1686 (s), 1487 (w), 1433 (w), 1283 (w), 1195 (w), 1105 (w), 780 (w) cm ;
+
+
HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 382.0508; Found 382.0505.
2
0
15
3
2
,10-Dibromo-N-(2,3-dimethylphenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3w). Yield 77%
1
(
208 mg), yellow solid, mp 110 - 113 °C; R = 0.35 (petroleum ether – EtOAc, 5:1). H NMR (300 MHz,
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
0
DMSO-d ): δ 10.17 (br.s, 1H), 8.77 (br.s, 1H), 7.50 (m, 3H), 7.38 – 7.41 (m, 2H), 7.04 – 7.15 (m, 3H), 6.96
6
13
1
(
d, J = 8.50 Hz, 1H), 2.28 (s, 3H), 2.13 (s, 3H); C{ H} NMR (75 MHz, DMSO-d ): δ 159.1, 153.5, 147.1,
6
1
46.8, 137.5, 135.6, 132.7, 132.4, 131.6, 130.8, 130.7, 129.7, 127.8, 125.9, 123.6, 122.5, 120.4, 117.6, 20.6,
−
1
14.2; IR (KBr) 2983 (w), 1739 (s), 1481 (w), 1464 (w), 1251 (w), 1192 (w), 831 (w), 754 (w) cm ; HRMS
+
+
(
ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 499.9792; Found 499.9781.
20 15 3
2
-Chloro-9,11-dimethyl-N-phenyl-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3x). Yield 5% (10
1
mg), yellow solid, mp 115 - 117 °C; R = 0.32 (petroleum ether – EtOAc, 5:1). H NMR (300 MHz, CDCl ):
f
3
δ 9.69 (br.s, 1H), 7.67 (d, J = 7.92 Hz, 2H), 7.40 (dd, J = 7.92, 5.41 Hz, 2H), 7.14 – 7.27 (m, 4H), 7.04 (br.s,
1
3
1
1
1
H), 6.90 (br.s, 1H), 6.56 (br.s, 1H), 2.34 (s, 3H), 2.29 (s, 3H); C{ H} NMR (75 MHz, CDCl ): δ 158.2,
3
53.7, 146.5, 138.8, 137.6, 136.8, 133.7, 132.1, 130.9, 129.7, 129.2, 127.7, 124.9, 119.8, 119.7, 116.2, 21.4,
+
+
20.6; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 376.1211; Found 376.1210.
2
0
15
3
Synthesis of 5H-dibenzo[d,f][1,3]diazepine-6(7H)-thione (5). 2-Chloroacetic acid (4a) (32 μL, 0.54 mmol,
o
2
.0 equiv) was added portionwise during 2 h at 100 C (oil bath) to the mixture of 2,2'-biphenyldiamine 1
(50 mg, 0.27 mmol, 1.0 equiv), triethylamine (0.38 mL, 2.71 mmol, 10 equiv), and sulfur (207 mg, 0.81
mmol, 3.0 equiv) in water (2.5 mL). The mixture was stirred for 4 h at reflux until the complete conversion
of 2,2'-biphenyldiamine (TLC monitoring). The resulted mixture was cooled to room temperature and
decanted, precipitate was dissolved in EtOAc (10 mL) and solution was washed with water (3  10 mL).
Organic layer was dried over Na SO , solvent was removed under reduced pressure. Residue was purified by
2
4
column chromatography (eluent: petroleum ether - EtOAc, 4:1  3:1) to get 56 mg (yield 82%) of colorless
4
1
1
solid, mp 245 - 246 °C (mp 242 - 243 °C ); R = 0.30 (petroleum ether - EtOAc, 5:1). H NMR (300 MHz,
lit
f
DMSO-d ): δ 10.08 (br.s, 1H), 7.95 (br.s, 1H), 7.41 (d, J = 7.70 Hz, 2H), 7.30 (dd, J = 8.90, 7.70 Hz, 2H),
6
1
3
1
7
.20 (dd, J = 8.90, 7.70 Hz, 2H), 7.11 (d, J = 7.70 Hz, 2H); C{ H} NMR (75 MHz, DMSO-d ): δ 194.2,
6
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141.4, 141.4, 130.5, 129.6, 129.2, 126.0, 121.9, 121.9; IR (KBr) 2895 (w), 1754 (s), 1456 (w), 1441 (w),
−1
+
+
1
2
252 (w), 1186 (w), 858 (w), 750 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O
20 15 3
27.1484; Found 227.1454.
Synthesis of 5H-dibenzo[d,f][1,3]diazepin-6(7H)-one (6). Silver carbonate (122 mg, 0.44 mmol, 1.0 equiv)
at r.t. was added to a solution of the 5H-dibenzo[d,f][1,3]diazepine-6(7H)-thione (5) (100 mg, 0.44 mmol,
0
1
2
3
4
5
6
7
8
9
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4
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7
8
9
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9
0
1
.0 equiv) in water/CH CN mixture (1:1, 5 mL). The mixture was stirred for 4 h at r.t. until the complete
3
conversion of thione (TLC monitoring). The resulted mixture was filtered through Celite, and solvent was
removed under reduced pressure. Residue was purified by column chromatography (eluent: petroleum ether
42
-
(
EtOAc, 4:1  3:1) to get 63 mg (yield 68%) of colorless solid, mp 312 - 313 °C (mp 310 °C ); R = 0.28
lit
f
1
petroleum ether – EtOAc, 3:1). H NMR (300 MHz, DMSO-d ): δ 8.79 (br.s, 2H), 7.45 (d, J = 7.75 Hz,
6
1
3
1
2H), 7.30 (dd, J = 8.82, 7.75 Hz, 2H), 7.16 (dd, J = 8.82, 7.75 Hz, 2H), 7.09 (d, J = 7.75 Hz, 2H); C{ H}
NMR (75 MHz, DMSO-d ): δ 164.9, 140.6, 129.8, 129.4, 129.0, 124.5, 121.3; IR (KBr) 2805 (w), 1756 (s),
6
−
1
+
1
481 (w), 1474 (w), 1285 (w), 1175 (w), 854 (w), 741 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd.
+
for C H ClN O 211.0866; Found 211.0863.
2
0
15
3
Synthesis of 2-((5H-dibenzo[d,f][1,3]diazepin-6-yl)thio)acetic acid (7). Bromoacetic acid (20 μL, 0.26
mmol, 1.2 equiv) at r.t. was added to a solution of the 5H-dibenzo[d,f][1,3]diazepine-6(7H)-thione (5) (50
mg, 0.22 mmol, 1.0 equiv) in dry acetone (2 mL). The mixture was stirred for 18 h at r.t. until the complete
conversion of thione (TLC monitoring). The resulted mixture was concentrated under reduced pressure.
Residue was purified by column chromatography (eluent: petroleum ether - EtOAc, 3:1  1:1) to get 28 mg
1
(yield 45%) of colorless solid, mp 110−112 °C; R = 0.20 (petroleum ether - EtOAc, 3:1). H NMR (300
f
MHz, DMSO-d ): δ 8.78 (br.s, 1H), 7.46 (dd, J = 1.20, 7.70 Hz, 1H), 7.36 (dd, J = 1.20, 7.62 Hz, 1H), 7.33-
6
7
2
.32 (m, 2H), 7.16 (dd, J = 1.20, 7.62 Hz, 2H), 7.09 (d, J = 7.90 Hz, 1H), 6.91 (d, J = 7.90 Hz, 1H), 2.54 (s,
1
3
1
H); C{ H} NMR (75 MHz, DMSO-d ): δ 170.9, 164.9, 140.5, 129.8, 129.4, 129.0, 124.5, 121.3, 59.9; IR
6
−
1
(KBr) 2301 (w), 1732 (s), 1502 (w), 1498 (w), 1221 (w), 1175 (w), 841 (w), 751 (w) cm ; HRMS (ESI/Q-
+
+
TOF) m/z: [M+H] Calcd. for C H ClN O 285.0692; Found 285.0699.
2
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Synthesis of N-(4,6-dimethylpyrimidin-2-yl)-5H-dibenzo[d,f][1,3]diazepin-6-amine (8). Methyl iodide
16 μL, 0.24 mmol, 1.1 equiv) at r.t. was added to a solution of the 5H-dibenzo[d,f][1,3]diazepine-6(7H)-
(
thione (5) (53 mg, 0.22 mmol, 1.0 equiv) in dry THF (0.5 mL). The mixture was stirred at r.t. overnight until
the complete conversion of thione (TLC monitoring). The mixture was concentrated under reduced pressure.
Next, 2-amino-4,6-dimethylpyrimidine (51 mg, 0.44 mmol, 2.0 equiv) was added and mixture was heated at
0
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3
4
5
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8
9
0
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4
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7
8
9
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70˚С for 1.5 h. The resulted mixture was cooled and dissolved in EtOAc (10 mL). Organic fraction was
washed with 2% water solution of HCl (3 × 10 mL), dried over Na SO and concentrated under reduced
2
4
pressure. The residue was purified by column chromatography (eluent: petroleum ether - EtOAc, 4:1) to get
1
4
2 mg (yield 65%) of yellow solid, mp 130 − 132 °C; R = 0.20 (petroleum ether - EtOAc, 5:1). H NMR
f
(
300 MHz, DMSO-d ): δ 10.06 (br.s, 2H), 7.42 (d, J = 7.84 Hz, 2H), 7,30 (dd, J = 7.58, 1.48 Hz, 2H), 7.21
6
1
3
1
(dd, J = 7.58, 1.48 Hz, 2H), 7.10 (d, J = 7.84 Hz, 2H), 5.76 (br.s, 1H), 2.50 (s, 6H); C{ H} NMR (75 MHz,
DMSO-d ): δ 194.2, 141.4, 139.4, 130.5, 130.4, 130.1, 129.6, 129.2, 127.9, 126.0, 124.5, 123.5, 122.0, 23.7;
6
−
1
IR (KBr) 2895 (w), 1754 (s), 1456 (w), 1441 (w), 1252 (w), 1186 (w), 858 (w), 750 (w) cm ; HRMS
+
+
(
ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O 316.1557; Found 316.1550.
20 15 3
Synthesis of 2-((2'-amino-[1,1'-biphenyl]-2-yl)amino)-N-(4-chlorophenyl)-2-thioxoacetamide (9). The
mixture of 2,2'-biphenyldiamine 1 (110 mg, 0.59 mmol, 1.2 equiv), and sulfur (376 mg, 1.47 mmol, 3 equiv),
triethylamine (0.21 mL, 1.47 mmol, 3.0 equiv) in DMF (5 mL) was vigorously stirred at r.t. for 15 min. Next
2-chloro-N-(4-chlorophenyl)acetamide (2a) (100 mg, 0.49 mmol, 1.0 equiv) was added and reaction was
stored at 60 ˚С (oil bath) for 3 h until the complete conversion of 2,2'-biphenyldiamine (TLC monitoring).
The resulted mixture was cooled to room temperature, diluted with water (15 mL) and extracted with EtOAc
(3 × 15 mL). Combined organic fractions were washed with water (5 × 15 mL), dried over Na SO .and and
2
4
concentrated under reduced pressure. The residue was purified by column chromatography (eluent:
petroleum ether - EtOAc, 4:1  3:1) to get 33 mg (yield 27%) of yellow solid, mp 130 − 132 °C; R = 0.30
f
1
(petroleum ether - EtOAc, 3:1). H NMR (300 MHz, CDCl ): δ 11.79 (br.s, 1H), 10.28 (br.s, 1H), 8.65 (d, J
3
=
8.03 Hz, 1H), 7.60 (d, J = 8.83 Hz, 2H), 7.57 – 7.49 (m, 1H), 7.46 (d, J = 3,97 Hz, 2H), 7.33 (d, J = 8.83
Hz, 2H), 7.26 (dd, J = 7.56, 1.43 Hz, 1H), 7.16 (dd, J = 7.56, 1.43 Hz, 1H), 6.93 (m, 2H), 3.70 (s, 2H);
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C{ H} NMR (75 MHz, CDCl ): δ 183.2, 156.2, 143.0, 135.8, 135.3, 133.3, 131.4, 130.9, 130.4, 129.9,
3
1
1
3
29.2, 128.3, 128.1, 123.6, 123.4, 121.0, 119.8, 116.5; IR (KBr) 2802 (w), 1756 (s), 1474 (w), 1410 (w),
−
1
+
+
299 (w), 1174 (w), 820 (w), 774 (w) cm ; HRMS (ESI/Q-TOF) m/z: [M+H] Calcd. for C H ClN O
2
0
15
3
82.0775; Found 382.0772.
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Scale-up synthesis of N-(2,4-dichlorophenyl)-5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3f). 2-
chloro-N-(2,4-dichlorophenyl)acetamide (2f) (2.6 g, 10.9 mmol, 2.0 equiv) was added at r.t. to the solution
of 2,2'-biphenyldiamine 1 (1.0 g, 5.4 mmol, 1.0 equiv), triethylamine (7.5 mL, 54.0 mmol, 10.0 equiv), and
sulfur (4.2 g, 16.4 mmol, 3.0 equiv) in DMF (10 mL). The mixture was stirred at 60 ˚С (oil bath) for 6 h
until the complete conversion of 2,2'-biphenyldiamine (TLC monitoring). The resulted mixture was cooled
to room temperature and diluted with water (60 mL). Precipitate formed was filtrated, washed with water (5
× 30 mL) and dried. The product was isolated by recrystallization from ethanol to get 1.6 g (yield 76%) of
product.
Scale-up synthesis of 5H-dibenzo[d,f][1,3]diazepine-6-carboxamide (3t). 2-Chloroacetamide (2t) (12.9
mmol, 2.6 g, 1.2 equiv) was added at r.t. to the solution of 2,2'-biphenyldiamine 1 (2.0 g, 10.8 mmol, 1.0
equiv), triethylamine (4.5 mL, 32.6 mmol, 3.0 equiv), and sulfur (8.4 g, 32.6 mmol, 3.0 equiv) in DMF (10
mL). The mixture was stirred at 60 ˚С for 6 h until the complete conversion of 2,2'-biphenyldiamine (TLC
monitoring). The resulted mixture was cooled to room temperature and diluted with water (60 mL).
Precipitate formed was filtrated, washed with water (5 × 30 mL) and dried. The product was isolated by
recrystallization from ethanol to get 1.4 g (yield 60%) of product.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: Сopies of
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H and C spectra for compounds 3, 5-9 and and X-ray crystallographic analysis (PDF).
X-ray crystallographic data of 3k (CIF)
X-ray crystallographic data of 5 (CIF).
X-ray crystallographic data of 6 (CIF).
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AUTHOR INFORMATION
Corresponding Author
E-mail: yavolkova@gmail.com
ORCID
*
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Tatyana A. Tikhonova 0000-0003-2472-6124
Igor V. Zavarzin 0000-0002-8194-5756
Yulia A. Volkova 0000-0001-8554-838X
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval to the final
version of the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the RFBR grant 18-33-20087.
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