Reactions of fluoroalkyl-containing lithium 1,3-diketonates with diaminoarenes and 2-aminobenzenethiol

Article abstract of DOI:10.1007/s11172-010-0314-x

1,5-Benzo[b]- and 1,5-naphtho[2,3-b]diazepines were synthesized by the reaction of lithium 1,3-diketonates with 1,2-diaminobenzene and 2,3-diaminonaphthalene in an MeOH-AcOH-HCl mixture at 0°C. The reactions of fluoroalkyl-containing lithium 1,3-diketonates with 1,2-diaminobenzene and 1,2-diamino-4,5-difluorobenzene under reflux in acetic acid afford 2-fluoroalkyl-containing benzimidazoles as the major products, whereas the reaction with 2-aminothiophenol gives 2-phenylbenzothiazole. The reactions of lithium diketonate containing the cyclohexane and cyclopentane moieties with 1,2-diaminoarenes and 2-aminobenzenethiol are accompanied by the opening of the carbocycle to form 2-(6-oxo-7,7,7-trifluoroheptyl)benzimidazole and 2-(5-oxo-6,6,6-trifluorohexyl)benzothiazole hydrates, respectively.

Full text of DOI:10.1007/s11172-010-0314-x

Russian Chemical Bulletin, International Edition, Vol. 59, No. 9, pp. 1791—1796, September, 2010
1791
Reactions of fluoroalkylꢀcontaining lithium 1,3ꢀdiketonates
with diaminoarenes and 2ꢀaminobenzenethiol
V. I. Filyakova,a N. S. Boltacheva,a D. V. Sevenard,b and V. N. Charushina
aI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 369 3058. Eꢀmail: vif@ios.uran.ru
bHansa Fine Chemicals GmbH, BITZ,
1 Fahrenheitstr., 28359 Bremen, Germany
1,5ꢀBenzo[b]ꢀ and 1,5ꢀnaphtho[2,3ꢀb]diazepines were synthesized by the reaction of
lithium 1,3ꢀdiketonates with 1,2ꢀdiaminobenzene and 2,3ꢀdiaminonaphthalene in an
MeOH—AcOH—HCl mixture at 0 °C. The reactions of fluoroalkylꢀcontaining lithium 1,3ꢀdiꢀ
ketonates with 1,2ꢀdiaminobenzene and 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene under reflux in acetic
acid afford 2ꢀfluoroalkylꢀcontaining benzimidazoles as the major products, whereas the reacꢀ
tion with 2ꢀaminothiophenol gives 2ꢀphenylbenzothiazole. The reactions of lithium diketonate
containing the cyclohexane and cyclopentane moieties with 1,2ꢀdiaminoarenes and 2ꢀaminoꢀ
benzenethiol are accompanied by the opening of the carbocycle to form 2ꢀ(6ꢀoxoꢀ7,7,7ꢀ
trifluoroheptyl)benzimidazole and 2ꢀ(5ꢀoxoꢀ6,6,6ꢀtrifluorohexyl)benzothiazole hydrates,
respectively.
Key words: fluoroalkylꢀcontaining lithium 1,3ꢀdiketonates, 1,2ꢀdiaminobenzene, 2,3ꢀdiꢀ
aminonaphthalene, 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene, 2ꢀaminobenzenethiol, 1,5ꢀbenzo[b]diꢀ
azepines, 1,5ꢀnaphtho[2,3ꢀb]diazepines, 2ꢀfluoroalkylꢀcontaining benzimidazoles, 2ꢀ(6ꢀoxoꢀ
7,7,7ꢀtrifluoroheptyl)benzimidazole hydrate, 2ꢀ(6,6,6ꢀtrifluoroꢀ5ꢀoxohexyl)benzothiazole
hydrate, 11ꢀhydroxyꢀ4ꢀtrifluoroacetylꢀ11ꢀtrifluoromethylꢀ1,2,3,4,10,11ꢀhexahydroꢀ5Hꢀdiꢀ
benzo[b,e][1,4]diazepine, 1,3ꢀdihydrospiro[benzimidazoleꢀ2,1´ꢀcyclohexane].
The condensation of 1,3ꢀdiketones with 1,2ꢀdiaminoꢀ
arenes is most commonly used for the synthesis of
1,5ꢀbenzodiazepine derivatives.1—6 However, the reactions
of fluoroalkylꢀcontaining unsymmetrical 1,3ꢀdiketones
with diaminoarenes generally afford complex mixtures,
from which 3Hꢀ1,5ꢀbenzo[b]ꢀ and 3Hꢀ1,5ꢀnaphtho[2,3ꢀb]ꢀ
diazepines were isolated along with aminovinyl ketones,
2ꢀsubstituted benzimidazoles, and other products.7—9
The use of lithium enolates instead of fluoroalkylꢀconꢀ
taining unsymmetrical 1,3ꢀdiketones (the former comꢀ
pounds are more easily available, more stable during storꢀ
age, and are more convenient for the use in chemical proꢀ
cesses than the corresponding diketones) often results in
an increase in the selectivity of the reactions.10—20 Hence,
we studied the reactions of diketonates 1a—i with diamiꢀ
noarenes and 2ꢀaminobenzenethiol (Scheme 1).
The reaction of equimolar amounts of diketonate 1b
and 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene under reflux in glaꢀ
cial acetic acid (the conventional conditions of heteroꢀ
cyclization of fluoroalkylꢀcontaining lithium 1,3ꢀdiketonꢀ
ates with binucleophiles10—20) during 1 h gave 3Hꢀ1,5ꢀ
benzo[b]diazepine 2b in 67% yield. Under similar conꢀ
ditions, considerable amounts of the starting comꢀ
pounds remain intact in the reactions of diketonates 1a—i
with 1,2ꢀdiaminobenzene, 2,3ꢀdiaminonaphthalene, and
2ꢀaminothiophenol (TLC monitoring of the reactions).
Under reflux for a longer period of time, diketonates 1c
and 1d react with 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene to give
2ꢀfluoroalkylꢀcontaining benzimidazoles (2ꢀRFꢀbenzimidꢀ
azoles) 4a,b (see Scheme 1, Table 1), whereas the reacꢀ
tions of diketonates 1a,e—i with 1,2ꢀdiaminobenzene and
2ꢀaminothiophenol afford complex mixtures of products.
The synthesis of 3Hꢀ1,5ꢀbenzo[b]ꢀ and 3Hꢀ1,5ꢀnaphꢀ
tho[2,3ꢀb]diazepines 2a—f and 3a,b from diketonates 1
was carried out under the conditions, which are generally
used for the synthesis of benzodiazepines from fluoroalkylꢀ
containing 1,3ꢀdiketones (glacial AcOH and concentratꢀ
ed HCl were successively added to a solution of equimolar
amounts of the reagents in methanol at 0 °C)7 (see Scheme 1,
Table 1).
The reactions of lithium diketonates 1a—i with 1,2ꢀdiꢀ
aminoarenes can give two regioisomeric intermediates A
and B, whose condensation can afford 3Hꢀ1,5ꢀbenzo[b]ꢀ
and 3Hꢀ1,5ꢀnaphtho[2,3ꢀb]diazepines 2a—f and 3a,b.
2ꢀRFꢀBenzimidazoles 4a,b may be formed both as a result
of the acid hydrolysis of diazepines 2 and through the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1744—1749, September, 2010.
1066ꢀ5285/10/5909ꢀ1791 © 2010 Springer Science+Business Media, Inc.

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Filyakova et al.
Scheme 1
condensation of the intermediate B accompanied by the
elimination of ketone R1CH2C(O)R2 (see Scheme 1). The
former pathway seems to be more probable because it was
shown14,18 that the formation of the intermediate A is
more favorable, and the transformation of benzoꢀ1,5ꢀdiꢀ
azepines into 2ꢀsubstituted benzimidazoles upon heating
Table 1. Reaction products of lithium 1,3ꢀdiketonates 1 with 1,2ꢀdiaminoarenes
Starting compounds
Lithium diketonate
Reaction
conditionsa
Reaction
product
Yield
(%)
Arene,
X
1
RF
R1
R2
a
b
HCF2
HCF2
H
H
Me
Ph
H
i
i
iii
iii
i
ii
iii
iii
ii
i
2a
3a
2b
4a
2c
3b
55
90
67
58
72
79
92
—
4320
67
64
67
—(CH=CH)2—b
F
F
H
c
d
HCF2
CF3
—(CH2)4—c
Ph
H
—(CH=CH)2—b
F
H
H
H
H
H
4b
d
e
f
g
h
i
CF3
CF3
H(CF2)2
H(CF2)2
C4F9
—(CH2)3—c
—(CH2)4—c
6
H
H
H
Me
Ph
Ph
2d
2e
2f
i
i
a i. MeOH, AcOH, HCl; ii. AcOH, HCl; iii. AcOH, reflux.
b X +X.
c R1 + R2.
d A mixture of adducts.

Reactions of lithium 1,3ꢀdiketonates
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
1793
in an acidic medium is well known.2 The formation of
2ꢀ(fluoroalkyl)benzimidazoles 4a,b in the reactions of
diketonates 1c,d with 1,2ꢀdiaminoarenes is not quite usual
because it is known that unsymmetrical polyfluoroalkylꢀ
containing 1,3ꢀdiketones react with 1,2ꢀdiaminobenzene
to form benzimidazoles 5 containing the unfluorinated
substituent in position 2. The formation of 2ꢀRFꢀbenzꢀ
imidazoles 4 was observed only when the starting diketone
contained two RF groups (R2 is fluoroalkyl)7 or the cycloꢀ
hexanone moiety (R1 + R2 = —(CH2)4—).9
The reaction of diketonate 1f containing the cyclohexꢀ
anone moiety with 1,2ꢀdiaminobenzene is accompanied
by the ring opening and the formation of 2ꢀ(6ꢀoxoꢀ7,7,7ꢀ
trifluoroheptyl)benzimidazole hydrate 6 (see Scheme 1,
Table 1).20 The opening of the cyclohexanone ring was
observed in the reactions of 2ꢀ(polyfluoroacyl)cycloꢀ
hexanones with 1,2ꢀdiaminoarenes under the same condiꢀ
tions, as well as after the treatment of 1ꢀ[Nꢀ(2ꢀaminoꢀ
phenyl)amino]ꢀ2ꢀtrifluoroacetylcyclohexene with a mixꢀ
ture of AcOH and HCl, which afforded 2ꢀ(6ꢀoxoꢀ
7,7,8,8,9,9,10,10,11,11,12,12,12ꢀtridecafluorododecyl)ꢀ
benzimidazole and 2ꢀ(6,6ꢀdioxyꢀ7,7,7ꢀtrifluoroheptyl)ꢀ
benzimidazole, respectively.8,9
cycle (δF = 83.09) correspond to the hemiaminal strucꢀ
ture. The position of the NH signal of the enamino ketone
moiety (δH = 13.3) in the 1H NMR spectrum (acetoneꢀd6)
indicates that it is involved in an intramolecular hydroꢀ
gen bond and corresponds to the Uꢀshaped structure
of this moiety of the molecule. The mass spectrum
has a peak of the molecular ion, whose fragmentaꢀ
tion corresponds to structure 8. Benzimidazole 9 is apparꢀ
ently formed as a result of the acid hydrolysis of diꢀ
azepine 8 and the elimination of two trifluoroacetic acid
molecules.
It should be noted that the reactions of "linear" (i.e.,
those containing no cycloalkyl substituents) fluorinated
1,3,5ꢀtriketones with 1,2ꢀdiaminobenzene give exclusiveꢀ
ly 1,5ꢀbenzodiazepines.21
The reactions of lithium diketonates 1b,d,e with
2ꢀaminothiophenol can afford four isomeric products
(C, D, E, and F), whose transformations can give
1,5ꢀbenzo[b]thiazepines 10 and 11 or benzothiazoles 12
and 13. However, the reactions of diketonates 1b,d with
2ꢀaminothiophenol gave the only product, viz., 2ꢀphenylꢀ
11ꢀHydroxyꢀ4ꢀtrifluoroacetylꢀ11ꢀtrifluoromethylꢀ
1,2,3,4,10,11ꢀhexahydroꢀ5Hꢀdibenzo[b,e][1,4]diazepine
(8) and 1,3ꢀdihydrospiro[benzimidazoleꢀ2,1´ꢀcyclohexꢀ
ane] (9) were isolated in 10% and 24% yields, respectively,
as the reaction products of enolate of the trifluoroacyl
derivative of diketonate 1f (triketonate 7) with 1,2ꢀdiꢀ
aminobenzene (Scheme 2).
Scheme 2
i. MeOH, 0→20 °C. 1) AcOH; 2)HClconc
The structure of compound 8 was confirmed by 1H and
19F NMR spectroscopy and mass spectrometry. The sigꢀ
nals for the protons of the groups 11ꢀOH and 10ꢀNH
(δH = 5.76 and 6.21, respectively, both are exchanged with
CD3COOD) and the chemical shifts of the fluorine nuclei
of the trifluoromethyl group in position 11 of the heteroꢀ

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Filyakova et al.
benzothiazole 13 (R2 = Ph), whereas the reaction of diꢀ
ketonate 1e containing the cyclopentanone moiety with
2ꢀaminothiophenol was accompanied by the ring opening
to form 2ꢀ(5ꢀoxoꢀ6,6,6ꢀtrifluorohexyl)benzothiazole
hydrate (14).
Experimental
Fluoroalkylꢀcontaining lithium 1,3ꢀdiketonates 1 were synꢀ
thesized according to a procedure described previously.10 The
names and characteristics of diketonates 1 were reported in the
study.19 Triketonate 7 was described in the study.22
The possible pathway of the formation of compounds
6 and 14 is presented in Scheme 3.
The course of the reactions was monitored by TLC (Silufol
UVꢀ254, CHCl3 as the eluent). The visualization of the spots
was performed with the use of aqueous KMnO4 solutions.
The results of the condensation of fluoroalkylꢀconꢀ
taining lithium diketonates 1 with 1,2ꢀdiaminoarenes and
2ꢀaminothiophenol are determined not only by the strucꢀ
tures of the reagents and the reaction conditions but also
by the tendency of the reaction products to undergo furꢀ
ther transformations. It should be noted that 3Hꢀ1,5ꢀ
benzo[b]ꢀ and 3Hꢀ1,5ꢀnaphtho[2,3ꢀb]diazepines 2 were
synthesized only by the reactions of diketonates 1a,b,d,g—i
containing R1 = H with 1,2ꢀdiaminoarenes. In other casꢀ
es, the fragmentation of the carbon skeleton of the diꢀ
carbonyl or cycloalkanone moiety occurs to form 2ꢀsubꢀ
stituted benzimidazoles 4 and 6 and benzothiazoles 13
and 14, respectively. The formation of the condensation
products at one of the carbonyl groups (aminovinyl keꢀ
tones), which were isolated in the reaction of 2ꢀpolyfluoroꢀ
acylcyclohexanones with 1,2ꢀdiaminobenzene,9 was not
observed. Nevertheless, diketonates 1 act as synthetic
equivalents of fluoroalkylꢀcontaining diketones in the reꢀ
actions under consideration.
The H, 19F, and 13C NMR spectra were recorded on Tesla
1
BSꢀ567A (80 MHz for 1H and 75 MHz for 19F), Bruker AC 200
(200 MHz for H and 188 MHz for 19F), and Bruker DRXꢀ400
1
(400 MHz for H, 376 MHz for 19F, and 100 MHz for 13C)
1
spectrometers with the use of Me4Si (1H and 13C) and C6F6
(19F) as the internal standards. The IR spectra were recorded on
a Spectrum I Fourierꢀtransform infrared spectrometer (Perkin
Elmer) in Nujol mulls. The mass spectrum (EI, 70 eV) was obꢀ
tained on a Finnigan MATꢀ95 spectrometer.
Reaction of diketonates 1 with diaminoarenes in glacial acetic
acid. A mixture of equimolar amounts of diketonate 1 and diꢀ
aminoarene in glacial AcOH (10 mL) was refluxed until the
starting compounds were consumed (TLC monitoring). The reꢀ
action mixture was poured into water, and the precipitate that
formed was filtered off, treated with sodium hydrocarbonate,
dried, and recrystallized from MeOH or a mixture of chloroform
and hexane (1 : 10).
The reactions of diketonates 1a,e—i with 1,2ꢀdiaminobenꢀ
zene, 2,3ꢀdiaminonaphthalene, and 2ꢀaminothiophenol gave
complex mixtures of products.
Therefore, in spite of the fact that the condensation of
lithium diketonates 1 with 1,2ꢀdiaminoarenes can follow
different pathways, this reaction can be considered as
a convenient method for the formation of fluoroalkylꢀconꢀ
taining 3Hꢀ1,5ꢀbenzo[b]ꢀ and 3Hꢀ1,5ꢀnaphtho[2,3ꢀb]ꢀ
diazepines unsubstituted in position 3. The reactions of
fluoroalkylꢀcontaining lithium diketonates containing
cycloalkanone moieties (R1 + R2 = —(CH2)n—) with 1,2ꢀdiꢀ
aminobenzene and 2ꢀaminothiophenol result in the openꢀ
ing of the carbocycle to form benzimidazole and benꢀ
zothiazole derivatives 6 and 14.
2ꢀDifluoromethylꢀ5,6ꢀdifluorobenzimidazole (4a). Benzimidꢀ
azole 4a was synthesized from diketonate 1c (0.77 g, 4.2 mmol)
and 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene (0.61 g, 4.2 mmol) in
a yield of 0.5 g (58%). Colorless crystals, t.decomp. 161—162 °C.
1
IR, ν/cm–1: 1580, 1560 (C=N); 3019—3114 (NH). H NMR
(CDCl3), δ: 7.12 (t, 1 H, HCF2, 2JH,F = 53.5 Hz); 7.58 and 7.68
(both br.s, 1 H each, Ar); 12.50 (br.s, 1 H, NH). Found (%):
C, 47.32; H, 1.81; F, 37.33; N, 13.79. C8H4N2F4. Calculated (%):
C, 47.07; H, 1.98; F, 37.23; N, 13.72.
5,6ꢀDifluoroꢀ2ꢀtrifluoromethylbenzimidazole (4b). Benzimidꢀ
azole 4b was synthesized from diketonate 1d (1.6 g, 6.9 mmol)
and 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene (1.0 g, 6.9 mmol) in a yield
Scheme 3
X = NH, n = 2 (6); X = S, n = 1 (14)

Reactions of lithium 1,3ꢀdiketonates
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
1795
of 1.4 g (92%). Colorless crystals, m.p. 145—146 °C. IR, ν/cm–1
:
the dilithium salt of triketone 7 (1.70 g, 5.6 mmol) and 1,2ꢀdiꢀ
1
1580, 1560 (C=N); 3000—3300 (NH). H NMR (CDCl3), δ:
7.64 and 7.75 (both br.s, 1 H each, Ar); 12.96 (br.s, 1 H, NH).
19F NMR (CDCl3), δ: 99.60 (s, CF3). Found (%): C, 43.32;
H, 1.41; F, 42.33; N, 12.79. C8H3N2F5. Calculated (%): C, 43.26;
H, 1.36; F, 42.77; N, 12.61.
aminobenzene (0.61 g, 5.6 mmol) in methanol (10 mL). The
reaction mixture was stirred at this temperature for 5 min. Then
concentrated HCl (5 mL) was added dropwise. The reaction
mixture was stirred at room temperature for 16 h. The resulting
system (a yellow precipitate in an orange solution) was poured
into ice water (100 mL), and the reaction mixture was brought to
pH = 10 with a 30% NaOH solution. The precipitate that formed
was filtered off, washed on the filter with water (5 mL), dried,
and recrystallized from a heptane—toluene system (3 : 2). Comꢀ
pound 8 was obtained in a yield of 200 mg (10 %). Yellow crysꢀ
2ꢀDifluoromethylꢀ7,8ꢀdifluoroꢀ4ꢀphenylꢀ3Hꢀ1,5ꢀbenzodiꢀ
azepine (2b). Benzodiazepine 2b was synthesized from diketonꢀ
ate 1b (0.6 g, 2.9 mmol) and 1,2ꢀdiaminoꢀ4,5ꢀdifluorobenzene
(0.42 g, 2.9 mmol) in a yield of 0.6 g (67%). Colorless crystals,
1
m.p. 123—124 °C. IR, ν/cm–1: 1580, 1560 (C=N). H NMR
2
1
(CDCl3), δ: 3.47 (br.s, 2 H, CH2); 6.15 (t, 1 H, HCF2, JH,F
=
tals, m.p. 210—212 °C. H NMR (acetoneꢀd6), δ: 1.43 and 1.83
= 55.0 Hz); 7.29—7.51 (m, 7 H, Ar). Found (%): C, 62.89;
H, 3.39; F, 24.78; N, 9.17. C16H10N2F4. Calculated (%): C, 62.75;
H, 3.29; F, 24.81; N, 9.14.
(both m, 1 H each, CH2); 2.00—2.18 (m, 2 H, CH2); 2.35—2.51
(m, 2 H, CH2); 3.22 (t, 1 H, *CH, 3JH,H = 6.4 Hz); 5.76 and 6.21
(both s, 1 H each, OH, 10ꢀNH); 7.23 (m, 4 H, Ar); 13.3 (br.s, 1 H,
5ꢀNH). The signals at δ 5.76, 6.21, and 13.3 disappeared after
the addition of CD3COOD. 19F NMR (acetoneꢀd6), δ: 83.09
(s, 3 F, 11ꢀCF3); 90.14 (s, 3 F, COCF3). MS (EI, 70 eV), m/z
(Irel (%)): 380 [M]+ (100); 362 [M – H2O]+ (84); 311 [M – CF3]+
(80); 293 [M – CF3 – H2O]+ (98); 283 [M – COCF3]+ (22); 265
[M – COCF3 – H2O]+ (24). Found (%): C, 50.75; H, 3.84.
C16H14F6N2O2. Calculated (%): C, 50.53; H, 3.71.
The filtrate was extracted with CHCl3 (2×10 mL). The comꢀ
bined extracts were dried with MgSO4 and concentrated. The
oily residue rapidly crystallized. The residue was purified by reꢀ
crystallization from heptane. (1,3ꢀDihydrospiro[benzimidazoleꢀ
2,1´ꢀcyclohexane]) (9) was obtained in a yield of 250 mg (24%).
Yellowish crystals, m.p. 139—140 °C. The 1H NMR spectroꢀ
scopic data and m.p. are consistent with the data published in
the literature.24
Reaction of diketonates 1 with 1,2ꢀdiaminobenzene and 2,3ꢀdiꢀ
aminonaphthalene in a mixture of glacial acetic acid and hydroꢀ
chloric acid. 1,2ꢀDiaminoarene (0.01 mol) was added to a soluꢀ
tion of diketonate 1 (0.01 mol) in methanol (10 mL). The reacꢀ
tion mixture was cooled to 0 °C. Then glacial AcOH (0.02 mol)
and concentrated HCl (0.02 mol) were added. The reaction mixꢀ
ture was kept for 16 h. The precipitate that formed was filtered
off, washed with sodium hydrocarbonate, dried, and recrystalꢀ
lized from hexane or methanol.
2ꢀDifluoromethylꢀ4ꢀmethylꢀ3Hꢀ1,5ꢀbenzodiazepine (2a).
Benzodiazepine 2a was synthesized from diketonate 1a (1.0 g,
7 mmol) and 1,2ꢀdiaminobenzene (0.76 g, 7 mmol) in a yield of
0.8 g (55%). Colorless crystals, m.p. 76—78 °C. IR, ν/cm–1: 1630,
1585 (C=N). 1H NMR (CDCl3), δ: 2.38 (s, 3 H, Me); 2.97 (br.s,
2
2 H, CH2); 6.18 (t, 1 H, HCF2, JH,F = 55.2 Hz); 7.23—7.43
(m, 4 H, Ar). Found (%): C, 63.73; H, 4.85; F, 18.78; N, 13.48.
C11H10N2F2. Calculated (%): C, 63.45; H, 4.84; F, 18.25;
N, 13.45.
4ꢀMethylꢀ2ꢀ(1,1,2,2ꢀtetrafluoroethyl)ꢀ3Hꢀ1,5ꢀbenzodiꢀ
azepine (2d). Benzodiazepine 2d was synthesized from diketonꢀ
ate 1g (1.0 g, 5.2 mmol) and 1,2ꢀdiaminobenzene (0.56 g,
5.2 mmol) in a yield of 0.9 g (67%). Colorless crystals, m.p.
109—110 °C (cf. lit. data7).
4ꢀPhenylꢀ2ꢀ(1,1,2,2ꢀtetrafluoroethyl)ꢀ3Hꢀ1,5ꢀbenzodiꢀ
azepine (2e). The reaction of diketonate 1h (1.0 g, 3.9 mmol)
with 1,2ꢀdiaminobenzene (0.43 g, 3.9 mmol) gave benzodiꢀ
azepine 2e in a yield of 0.8 g (64%). Colorless crystals, m.p.
87 °C (cf. lit. data7).
2ꢀDifluoromethylꢀ4ꢀphenylꢀ3Hꢀ1,5ꢀnaphtho[2,3ꢀb]diazepine
(3a). The reaction of diketonate 1b (0.5 g, 2.5 mmol) with 2,3ꢀ
diaminonaphthalene (0.4 g, 2.5 mmol) gave compound 3a in
a yield of 0.7 g (90%). Colorless crystals, m.p. 122—123 °C. IR,
1
ν/cm–1: 1640, 1625 (C=N). H NMR (CDCl3), δ: 4.79 (br.s,
2
2 H, CH2); 6.60 (t, 1 H, HCF2, JH,F = 53.5 Hz); 7.31—7.73
(m, 11 H, Ar). Found (%): C, 75.15; H, 4.38; F, 11.80; N, 8.69.
C20H14N2F2. Calculated (%): C, 75.01; H, 4.40; F, 11.86;
N, 8.74.
4ꢀPhenylꢀ3ꢀtrifluoromethylꢀ3Hꢀ1,5ꢀnaphtho[2,3ꢀb]diazepine
(3b). The reaction of diketonate 1d (1.0 g, 4.5 mmol) with 2,3ꢀdiꢀ
aminonaphthalene (0.71 g, 4.5 mmol) gave compound 3b in
a yield of 1.02 g (79%). Colorless crystals, m.p. 154 °C. IR, ν/cm–1
:
4ꢀPhenylꢀ2ꢀtrifluoromethylꢀ3Hꢀ1,5ꢀbenzodiazepine (2c). The
reaction of diketonate 1d (1.0 g, 4.5 mmol) with 1,2ꢀdiaminobenꢀ
zene (0.48 g, 4.5 mmol) gave benzodiazepine 2c in a yield of
1666, 1599 (C=N). 1H NMR (CDCl3), δ: 3.56 (br.s, 2 H, CH2);
7.53—8.13 (m, 11 H, Ar). Found (%): C, 70.84; H, 3.80; F, 17.03;
N, 8.28. C20H13N2F3. Calculated (%): C, 71.01; H, 3.87;
F, 16.85; N, 8.28.
1
0.89 g (72%). Colorless crystals, m.p. 83—84 °C. The H NMR
spectroscopic data and m.p. are consistent with those published
Reaction of lithium 4,4ꢀdifluoroꢀ1ꢀphenylbutaneꢀ1,3ꢀdionate
(1b) with 2ꢀaminothiophenol. 2ꢀAminothiophenol (0.61 g,
4.9 mmol) was added to a solution of diketonate 1b (1 g,
4.9 mmol) in methanol. The reaction mixture was cooled to
0 °C. Then glacial AcOH (0.42 g, 7 mmol) and concentrated
HCl (0.26 g, 7 mmol) were added. The reaction mixture was
kept for 16 h. The precipitate that formed was filtered off, treatꢀ
ed with sodium hydrocarbonate, dried, and recrystallized from
hexane. 2ꢀPhenylbenzothiazole (13) was obtained in a yield of
0.9 g (87%), m.p. 113 °C (cf. lit. data25). IR, ν/cm–1: 1589 (C=N).
1H NMR, δ: 7.37—8.10 (m, Ar).
in the study.23 IR, ν/cm–1: 1611, 1590 (C=N).
2ꢀNonafluorobutylꢀ4ꢀphenylꢀ3Hꢀ1,5ꢀbenzodiazepine (2f).
The reaction of diketonate 1i (0.9 g, 2.4 mmol) with 1,2ꢀdiaminoꢀ
benzene (0.26 g, 2.4 mmol) gave benzodiazepine 2f in a yield of
0.7 g (67%). Colorless crystals, m.p. 78—79 °C. IR, ν/cm–1: 1620,
1590 (C=N). 1H NMR (CDCl3), δ: 3.49 (br.s, 2 H, CH2);
7.35—8.11 (m, 9 H, Ar). Found (%): C, 52.27; H, 2.42; F, 38.96;
N, 6.24. C19H11N2F9. Calculated (%): C, 52.07; H, 2.53;
F, 39.01; N, 6.39.
11ꢀHydroxyꢀ4ꢀtrifluoroacetylꢀ11ꢀtrifluoromethylꢀ
1,2,3,4,10,11ꢀhexahydroꢀ5Hꢀdibenzo[b,e][1,4]diazepine (8) and
1,3ꢀdihydrospiro[benzimidazoleꢀ2,1´ꢀcyclohexane] (9). Glacial
AcOH (1 mL) was added with stirring to a cold (0 °C) solution of
Reaction of lithium 4,4,4ꢀtrifluoroꢀ1ꢀphenylbutaneꢀ1,3ꢀdionꢀ
ate (1d) with 2ꢀaminothiophenol. The similar reaction of diketonꢀ
ate 1d (1 g, 4.5 mmol) with 2ꢀaminothiophenol (0.56 g, 4.5 mmol)

1796
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
Filyakova et al.
afforded 2ꢀphenylbenzothiazole (13) in a yield of 0.9 g (95%),
m.p. 111 °C. The IR spectrum is identical to the IR spectrum of
the compound prepared in the previous experiment.
11. V. I. Filyakova, O. A. Kuznetsova, E. N. Ulomskii, T. V.
Rybalova, Yu. V. Gatilov, M. I. Kodess, V. L. Rusinov, K. I.
Pashkevich, Izv. Akad. Nauk, Ser. Khim., 2002, 313 [Russ.
Chem. Bull., Int. Ed., 2002, 51, 332].
12. O. A. Kuznetsova, V. I. Filyakova, K. I. Pashkevich, E. N.
Ulomskii, P. V. Plekhanov, G. L. Rusinov, M. I. Kodess,
V. L. Rusinov, Izv. Akad. Nauk, Ser. Khim., 2003, 1127 [Russ.
Chem. Bull., Int. Ed., 2003, 52, 1190].
13. N. S. Karpenko, V. I. Filyakova, E. G. Matochkina, M. I.
Kodes, K. I. Pashkevich, Izv. Akad. Nauk, Ser. Khim., 2003,
1149 [Russ. Chem. Bull., Int. Ed., 2003, 52, 1215].
14. N. S. Boltacheva, V. I. Filyakova, V. N. Charushin, Zh. Org.
Khim., 2005, 41, 1483 [Russ. J. Org. Chem. (Engl. Transl.),
2005, 41, 1452].
Reaction of lithium 2ꢀtrifluoroacetylcyclopentanoate (1e) with
2ꢀaminothiophenol. The similar reaction of diketonate 1e (0.9 g,
5 mmol) with 2ꢀaminothiophenol (0.63 g, 5 mmol) afforded
2ꢀ(5,5ꢀdihydroxyꢀ6,6,6ꢀtrifluorohexyl)benzothiazole in a yield
of 1.46 g (96%) (14). M.p. 104—105 °C. Found (%): C, 51.98;
H, 4.64; N, 4.20; F, 18.63; S, 10.03. C13H14N F3O2S. Calculatꢀ
ed (%):C, 51.14; H, 4.62; N, 4.58; F, 18.67; S, 10.50. IR, ν/cm–1
:
3363.60 (OH). 1H NMR (DMSOꢀd6), δ: 1.52—1.59, 1.67—1.71,
and 1.80—1.86 (all m, 2 H each, three CH2 groups); 3.12 (t, 2 H,
CH2, J = 7.5 Hz); 6.64 (s, 2 H, OH); 7.36—7.38, 7.46—7.49,
7.82—7.86, and 7.96—7.98 (all m, 1 H each, Ar). 19F NMR, δ:
82.48 (s, CF3).
15. N. S. Boltachova, O. V. Fedorova, I. G. Ovchinnikova, O.
N. Kazheva, A. N. Chekhlov, O. A. Dyachenko, G. L. Rusꢀ
inov, V. I. Filyakova, V. N. Charushin, J. Fluor. Chem., 2007,
128, 762.
This study was financially supported by the Council on
Grants of the President of the Russian Federation (Proꢀ
gram for State Support of Leading Scientific Schools of
the Russian Federation, Grant NShꢀ65261.2010.3).
16. V. I. Filyakova, O. A. Kuznetsova, N. S. Karpenko, P. A.
Slepukhin, V. N. Charushin, in Karbonil´nye soedineniya v
sinteze geterotsiklov [Carbonyl Compounds in Heterocyclic Synꢀ
thesis], Nauchnaya kniga, Saratov, 2004, p. 288 (in Russian).
17. O. A. Kuznetsova, Ph. D. (Chem.) Thesis, I. Ya. Postovsky
Institute of Organic Synthesis, Ural Branch of the Russian
Academy of Sciences, Ekaterinburg, 2002 (in Russian).
18. N. S. Karpenko, Ph. D. (Chem.) Thesis, I. Ya. Postovsky
Institute of Organic Synthesis, Ural Branch of the Russian
Academy of Sciences, Ekaterinburg, 2004 (in Russian).
19. N. S. Boltacheva, V. I. Filyakova, E. F. Khmara, O. V.
Koryakova, V. N. Charushin, Ros. Khim. Zh. (Zh. Vsesoyuz.
Khim. Obshch. im. D. I. Mendeleeva), 2009, 53, No. 1, 54
[Mendeleev Chem. J., 2009, 53, No. 1].
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Received November 6, 2009;
in revised form June 21, 2010