Reactions of alkyl 2-benzylidene-2-polyfluoroacylacetates with N,N-dinucleophiles

Article abstract of DOI:10.1023/B:RUCB.0000042284.03940.41

Alkyl 2-benzylidene-2-polyfluoroacylacetates react with urea and thiourea to yield 5-ethoxycarbonyl-4-fluoroalkyl-4-hydroxy-6-phenylhexahydropyrimidin-2- ones and -2-thiones and with guanidine sulfate to form 2-amino-5-ethoxycarbonyl- 4-fluoroalkyl-6-phenyl-1,6-dihydropyrimidines and 3,6-diethoxycarbonyl-2,7- difluoroalkyl-4,5-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]pyrimidines, and they react with phenylhydrazine to afford 4-alkoxycarbonyl-3-fluoroalkyl-3-hydroxy-1, 5-diphenylpyrazolidines. Hydrazine hydrate catalyzes the formation of 3,5-diethoxycarbonyl-2,6-difluoroalkyl-2,6-dihydroxy-4-phenyltetrahydropyrans. When treated with anhydrous hydrazine and o-phenylenediamine, these esters cleave to form the products of condensation of fluoroacyl ester and benzaldehyde with diamines.

Full text of DOI:10.1023/B:RUCB.0000042284.03940.41

Russian Chemical Bulletin, International Edition, Vol. 53, No. 6, pp. 1261—1266, June, 2004
1261
Reactions of alkyl 2ꢀbenzylideneꢀ2ꢀpolyfluoroacylacetates
with N,Nꢀdinucleophiles
M. V. Pryadeina, Ya. V. Burgart, M. I. Kodess, V. I. Saloutin,ꢀ and O. N. Chupakhin
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
2
0 ul. S. Kovalevskoi, 620219 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 5954. Eꢀmail: saloutin@ios.uran.ru
Alkyl 2ꢀbenzylideneꢀ2ꢀpolyfluoroacylacetates react with urea and thiourea to yield
ꢀethoxycarbonylꢀ4ꢀfluoroalkylꢀ4ꢀhydroxyꢀ6ꢀphenylhexahydropyrimidinꢀ2ꢀones and
2ꢀthiones and with guanidine sulfate to form 2ꢀaminoꢀ5ꢀethoxycarbonylꢀ4ꢀfluoroalkylꢀ6ꢀ
phenylꢀ1,6ꢀdihydropyrimidines and 3,6ꢀdiethoxycarbonylꢀ2,7ꢀdifluoroalkylꢀ4,5ꢀdiphenylꢀ
5
ꢀ
4
4
,5ꢀdihydroꢀ1Нꢀpyrido[1,2ꢀа]pyrimidines, and they react with phenylhydrazine to afford
ꢀalkoxycarbonylꢀ3ꢀfluoroalkylꢀ3ꢀhydroxyꢀ1,5ꢀdiphenylpyrazolidines. Hydrazine hydrate cataꢀ
lyzes the formation of 3,5ꢀdiethoxycarbonylꢀ2,6ꢀdifluoroalkylꢀ2,6ꢀdihydroxyꢀ4ꢀphenylꢀ
tetrahydropyrans. When treated with anhydrous hydrazine and oꢀphenylenediamine, these
esters cleave to form the products of condensation of fluoroacyl ester and benzaldehyde with
diamines.
Key words: alkyl 2ꢀbenzylideneꢀ2ꢀpolyfluoroacylacetates, dinucleophiles, urea, thiourea,
guanidine, hydrazine, phenylhydrazine, oꢀphenylenediamine.
Recently synthesized fluoroalkylꢀcontaining 2ꢀbenꢀ
zylideneꢀ3ꢀoxoalkanoates1 are promising reagents for
syntheses of heterocycles, because they contain three
nonequivalent reaction centers: keto group, ester fragꢀ
ment, and C=C bond. Therefore, 2ꢀbenzylideneꢀ3ꢀoxoꢀ
alkanoates can possess reactivity of both 3ꢀoxoalkanoates
and vinyl ketones.
pyrimidine series.3—6 Data on reactions of the fluorinated
analogs with dinucleophiles are lacking.
,2
In this work, we studied the reactions of alkyl 2ꢀbenꢀ
zylideneꢀ2ꢀpolyfluoroacylacetates 1 with various N,Nꢀdiꢀ
nucleophiles, such as urea, thiourea, guanidine, hydrꢀ
azine, phenylhydrazine, and oꢀphenylenediamine.
It was found that refluxing of equimolar amounts of
esters 1a,b with urea or thiourea in DMF in the presence
of sodium acetate for 6—8 h afforded substituted 4ꢀhydrꢀ
Nonfluorinated 2ꢀarylideneꢀ3ꢀoxoalkanoates are
known to be used for syntheses of heterocycles of the
Scheme 1
F
F
R
R
= HCF (1a, 3a, 4a), X = O (2a)
= CF3 (1b, 3b), X = S (2b)
2
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1210—1215, June, 2004.
066ꢀ5285/04/5306ꢀ1261 © 2004 Plenum Publishing Corporation
1

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Pryadeina et al.
Table 1. Main physicochemical characteristics of compounds 3a,b, 4а, 6b, and 8a—c
Comꢀ
pound
M.p.
/°C
Yield
(%)
Found
Calculated
Molecular
formula
(
%)
С
H
F
N
3
3
4
6
8
8
8
a
b
a
b
a
b
c
203—205
166—168
172—175
160
45
59
56.85
5.09
5.12
4.45
4.50
4.88
4.74
0.83
0.75
5.14
5.03
4.83
4.85
3.29
3.32
12.90
12.87
18.13
18.19
14.21
14.29
61.39
61.41
14.68
14.98
18.59
18.43
33.19
33.11
14.32
14.23
13.46
13.41
8.01
7.91
7.01
6.97
7.10
7.36
6.75
6.78
5.40
5.42
C14H15F N O
2
2
3
5
6.94
53.67
3.68
C14H14F N O
2
3
3
5
36*
59)
48
60.99
61.01
26.85
C27H25F N O
4 3
4
(
C H F N O
9
3
13
2
2
6.89
59.92
0.00
58.24
8.26
48.81
8.85
97—99
66
52
49
C19H19F N O
3 2
3
6
95—97
C20H20F N O
4 2
3
5
155—157
C21H17F N O
9 2
3
4
*
The yield of the product synthesized by method А, and that by method B is given in parentheses.
oxyhexahydropyrimidinꢀ2ꢀones 2a and 4ꢀhydroxyhexaꢀ
hydropyrimidinꢀ2ꢀthiones 2b (Scheme 1). The same
heterocycles have been synthesized previously by the
threeꢀcomponent Biginelli reaction from 3ꢀoxoalkanoates,
urea or thiourea, and benzaldehyde.
ponent Biginelli condensation of benzoylacetate, aldeꢀ
hyde, and guanidine affords 2ꢀaminodihydropyrimidines
as the main products (yields up to 70%). We succeeded
7
,8
6
to isolate only an insignificant amount of pyrimidine 3b
from the reaction of ester 1b with benzaldehyde and guaniꢀ
dine, because the mixture of products that formed was
difficult to separate.
The reactions of 2ꢀbenzylideneꢀ3ꢀoxoalkanoates 1a,b
with hydrazine hydrate in diethyl ether or ethanol afford
substituted tetrahydropyrans 5a,b instead of expected
pyrazoles (Scheme 2).
Note that the reactions of nonfluorinated 2ꢀarylideneꢀ
3
ꢀoxoalkanoates with urea or thiourea afford tetrahydroꢀ
4
pyrimidinꢀ2ꢀon(thion)es. In the case of the fluorinated
analogs, the formation of hexahydropyrimidines with the
gemꢀaminoalcohol fragment is explained by the presence
of electronꢀwithdrawing fluoroalkyl substituents, which
prevent water molecule elimination.
We have previously isolated heterocycles 5a,b from
the reactions of 2ꢀpolyfluoroacylacetates with aldehydes
or 2ꢀbenzylideneꢀ3ꢀoxoalkanoates in ethanol in the presꢀ
Unlike urea and thiourea, guanidine sulfate reacts with
2
ꢀbenzylideneꢀ3ꢀoxoalkanoates 1a,b in boiling DMF in
2
the presence of the base (Na CO ) to yield 2ꢀaminoꢀ
ence of the base. Probably, 2ꢀbenzylideneꢀ3ꢀoxoalkanoꢀ
2
3
dihydropyrimidines 3a,b (Table 1). The formation of
dihydropyrimidines 3 instead of hexahydropyrimidines 2
in the case of guanidine is caused, most likely, by the
higher basicity of the latter (pKa1 = 13.6, pKa2 = 11)
ate 1 decomposes partially, under the reaction condiꢀ
tions, to benzaldehyde and 3ꢀoxoalkanoate. The latter
reacts with ester 1, and hydrazine acts as a base.
Pyrazoles 6a,b were isolated from the products of the
reactions of 2ꢀbenzylideneꢀ3ꢀoxoalkanoates 1a,f with anꢀ
hydrous hydrazine in absolute ethanol (see Scheme 2).
They are formed due to transformations of the products of
cleavage of the starting ester 1, 3ꢀoxoalkanoate, and aldeꢀ
hyde. Attempts to obtain pyrazoles using hydrazine in the
form of its hydrochloride were unsuccessful.
Phenylhydrazine reacts readily with 2ꢀbenzylideneꢀ3ꢀ
oxoalkanoates 1b,c,e in anhydrous diethyl ether to form
pyrazolidine derivatives 8a—c (see Scheme 2) containꢀ
ing, as in the case of hexahydropyrimidines 2 and tetraꢀ
hydropyrans 5, the hydroxyl group in the position adjaꢀ
cent to the fluoroalkyl substituent. This reaction is acꢀ
companied by the partial decomposition of the starting 2ꢀ
benzylideneꢀ3ꢀoxoalkanoate 1, which is indicated
compared to those of urea (pK = 0.31) and thiourea
а
9
(
pK = –0.96).
a
The reaction products of 2ꢀbenzylideneꢀ3ꢀoxoalkanoꢀ
ate 1a containing the difluoromethyl substituent yielded
pyrimidine 3a and pyrimidopyrimidine 4a (see Scheme 1).
The latter was also obtained from 2ꢀaminodihydroꢀ
pyrimidine 3a and ester 1a. It is most likely that bicycle 4b
is also formed in the reaction of ester 1b with the guaniꢀ
dine salt. However, this compound cannot be isolated
because of the formation of a large amount of byꢀproducts.
5
It has previously been shown that similar binuclear
heterocycles are formed from 2ꢀaminodihydropyrimidines
and also by the reactions of 2ꢀarylideneꢀsubstituted
benzoylacetates with guanidine sulfate. The threeꢀcomꢀ

2
ꢀBenzylideneꢀ2ꢀpolyfluoroacylacetates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
1263
Scheme 2
R = Et, RF = HCF2 (1a, 5a, 6a, 9a), CF3 (1b, 5b, 8a),
H(CF ) (1c, 4a, 8b, 9b), H(CF2)4 (1d, 9c), C6F13 (1f, 6b)
2
2
F
R = Me, R = C4F9 (1e, 4b, 8c)
by hydrazone 7 isolated from the reaction mixture
Based on the data obtained, we can conclude that
pyrazolidines 8 are formed due to the primary addition of
the free amino group of phenylhydrazine to the fluoroacyl
fragment of ester 1 followed by ring closure due to
the addition of the second amino group to the С=С
double bond.
(
Scheme 2).
The formation of two regioisomeric pyrazolidines 8А
and 8В is theoretically possible through the reactions of
2
ꢀbenzylideneꢀ3ꢀoxoalkanoates 1 with phenylhydrazine.
The structures of pyrazolidines 8а—с are characterꢀ
ized by three chiral centers. Therefore, four possible diaꢀ
stereomers (and, in addition, four their enantiomeric
forms) can be proposed for these compounds. However,
1
19
analysis of the H and F NMR spectra shows that only
one diastereoisomer is present in each case. The high
The structures of pyrazolidines 8 were established by
conformational energy of the phenyl group (∆G
=
Ph
1
1
13
1
13
–1
H 2D NOESY, 2D Hꢀ C HSQC, and 2D Hꢀ C
HMBC NMR spectra using compound 8a as an example.
The 2D NOESY NMR spectrum of 8a contains cross
peaks between the Н(5) proton and orthoꢀprotons of the
Nꢀphenyl group and between the orthoꢀprotons of two
phenyl substituents, which can take place in structure 8А.
This structure is favored by the presence of cross peaks of
the H(5) proton with the Сipso atom of the Nꢀphenyl
substituent and the proton of the amino group with the
carbon atom bound to the trifluoromethyl group in the
12.1 kJ mol ) makes it possible to fix preferentially the
1
0
conformation in which this group is equatorial. In addiꢀ
tion, the experimentally found value of the spinꢀspin couꢀ
pling constant (9.4—10.0 Hz) corresponding to the axialꢀ
axial interaction of protons at the С(4) and С(5) carbon
atoms indicates the equatorial arrangement of the pheꢀ
1
1
nyl and alkoxycarbonyl groups. The conformational
1
0
–1
energies for the CF (∆GСF3 8.8 kJ mol ) and OH
3
(∆GOH 2.2 kJ mol–1) groups in substituted cyclohexanones
suggest the preferential equatorial arrangement of the
trifluoromethyl residue. Moreover, according to Xꢀray
1
13
2
D Hꢀ C HMBC NMR spectrum.

1264
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
Pryadeina et al.
diffraction data, this arrangement of the trifluoromethyl
and hydroxyl substituents is observed for ethyl 2ꢀoxoꢀ4ꢀ
phenylꢀ6ꢀtrifluoromethylꢀ1,2,3,4ꢀtetrahydropyrimidineꢀ
2ꢀBenzylideneꢀ3ꢀoxoalkanoates 1 in the reactions with
oꢀphenylenediamine also undergo retroꢀdecomposition
similarly to transformations with anhydrous hydrazines.
Regardless of the reaction conditions (refluxing in anꢀ
hydrous benzene, diethyl ether, and ethanol), esters 1a,c,е
yield benzodiazepines 9a—c and benzimidazole 10, which
5
ꢀcarboxylate12 and 2,6ꢀdihydroxyꢀ3,5ꢀdimethoxycarboꢀ
nylꢀ4ꢀphenylꢀ2,6ꢀdi(1,1,2,2ꢀtetrafluoroethyl)tetrahydroꢀ
pyran.2
Table 2. Main spectral characteristics of compounds 3a,b, 4а, 6b, and 8a—c
Comꢀ
pound
IR, ν/cm–1
NMR (DMSOꢀd ) δ, J/Hz
6
1H
1.14 (t, 3 H, OCН CН , J = 7.1); 4.03 (q, 2 H,
19F
3
3
4
6
a
b
a
b
3470, 3380, 3320, 1600; 1580
39.16 (d, НCF , J = 55.3)
2
3
2
(
1
(
NH, NH ); 3020 (C—H stret.);
OCН Me, J = 7.1); 5.34 (s, 1 H, CH); 6.37 (br.s,
2
2
660 (CO Et); 1600, 1580, 1500
2 H, NH ); 7.31 (m, 5 H, Ph); 7.42 (t, 1 H, HCF ,
2
2
2
C=C, C=N); 1220—1140 (C—F)
3420, 3350, 3320, 1590, 1550
NH, NH ); 3110 (C—H stret.);
J = 55.3); 7.96 (br.s, 1 H, NН)
1.13 (t, 3 H, OCН CН , J = 7.1); 4.03 (q, 2 H,
OCН Me, J = 7.1); 5.44 (s, 1 H, CH); 5.99
(br.s, 2 H, NH ); 7.09 (br.s, 1 H, NH);
98.92 (s, CF3)
2
3
(
1
(
2
2
650 (CO Et); 1590, 1575, 1500
2
2
C=C, C=N); 1230—1130 (C—F)
3370, 1620, 1550 (NH); 3010
C—H stret.); 1700 (CO Et); 1620, 2 OCН Me, J = 7.1); 5.38 (s, 2 H, 2 CH); 7.32
550, 1500 (C=C, C=N);
220—1020 (C—F)
7.25—7.36 (m, 5 H, Ph)
1.05 (t, 6 H, 2 OCН CН , J = 7.1); 3.98 (q, 4 H,
41.92 (d, НCF , J = 54.3)
2
3
2
(
1
1
2
2
(t, 2 H, 2 HCF , J = 54.3); 7.35 (m, 10 H, 2 Ph);
2
11.13 (br.s, 1 H, NH)
,
3229, 1536 (NH); 2596, 2200
OH); 1140—1242 (C—F)
5.66 (s, 1 H, CH); 11.26 and 12.96 (both с,
1 H each, NH and OH)
35.75 (m, 2 F, CF );
39.05 (m, 2 F, CF );
2
(
2
4
4
8
0.66 (m, 4 F, (CF ) );
2
2
5.78 (m, 2 F, CF );
2
1.03 (s, 3 F, CF3)
8
a
3340, 3267, 1597 (NH, OH); 3015
C—H stret.); 1694 (CO Et);
1.13 (t, 3 H, OCН CН , J = 7.1); 3.24 (dd, 1 H,
CH(4), J = 9.4, J = 1.7); 4.11, 4.03 (two dq,
81.60 (s, CF )*
2
3
3
(
2
1
175—1237 (C—F)
both 1 H, OCН Me, J = 10.8, J = 7.1); 5.11
2
(
d, 1 H, CH(5), J = 9.4); 6.71 (tt, 1 H, (N)CHp,
J = 7.3, J = 1.1); 6.85 (dd, 2 H, (N)CH , J = 8.8,
o
J = 1.1); 6.96 (s, 1 H, NH); 7.01 (d, 1 H, OH,
J = 1.7); 7.11(dd, 2 H, (N)CH , J = 8.8, J= 7.3);
m
7
2
.31 (tt, 1 H, CH , J = 7.3, J = 1.3); 7.39 (dd,
p
H, CH , J= 8.2, J = 7.3); 7.54 (dd, 2 H, CH ,
m
o
J = 8.2, J = 1.3)
8
b
3360, 3275 (NH, OH); 3020
C—H stret.); 1680 (CO Et);
1.23 (t, 3 H, OCН CН , J = 7.1); 3.45 (d, 1 H,
CH(4), J = 10.0); 4.24, 4.27 (both dq, 1 H each,
—
2
3
(
2
1
1
585, 1480 (C=C, C=N);
200—1090 (C—F)
OCН Me, J = 10.8, J = 7.1); 4.84 (d, 1 H, CH(5),
J = 10.0); 4.88 (dt, 1 H, OH, J = J = 1.4);
2
5
.68 (d, 1 H, NH, J = 1.7); 6.29 (dddd, 1 H,
HCF , J = 53.8, J = 52.0, J = 11.6, J = 2.0);
2
6
2
.84 (tt, 1 H, (N)H , J = 7.3, J = 1.1); 6.98 (dd,
p
H, (N)H , J = 8.8, J = 1.1); 7.16 (dd, 2 H,
o
(
N)H , J = 8.8, J = 7.3); 7.4 (m, 5 H, Ph(5))*
m
8
c
3400, 3320 (NH, OH); 3020
C—H stret.); 1710 (CO Me);
3.50 (d, 1 H, CH(4), J = 9.8); 3.79 (s, 3 H, OMe);
4.87 (d, 1 H, CH(5), J = 9.8); 4.91 (dt, 1 H, OH,
J = J = 1.4); 5.34 (d, 1 H, NH, J = 1.7); 6.85 (tt,
35.96 (AB system, 2 F,
(
γꢀCF , ∆АВ= 0.67, JАВ
=
2
2
1
600, 1500 (C=C, C=N);
230—1120 (C—F)
294.0); 40.84 (AB system,
1
1 H, (N)H , J = 7.3, J = 1.2); 6.99 (dd, 2 H,
2 F, βꢀCF , ∆ = 1.53,
p
2
АВ
(
N)H , J = 8.8, J = 1.2); 7.17 (dd, 2 H, (N)H ,
JАВ = 301.0); 42.27 (t.m,
O
m
J = 8.8, J = 7.3); 7.4 (m, 5 H, Ph(5))*
2 F, αꢀCF , J = 15.0);
2
8
1.03 (tt, 3 F, CF3,
J = 10.2, J = 2.4)*
*
In CDCl3.

2
ꢀBenzylideneꢀ2ꢀpolyfluoroacylacetates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
1265
are the products of the reaction of oꢀphenylenediamine
with 3ꢀoxoalkanoate and benzaldehyde, respectively
5ꢀEthoxycarbonylꢀ4ꢀfluoroalkylꢀ4ꢀhydroxyꢀ6ꢀphenylhexaꢀ
hydropyrimidinꢀ2ꢀon(thion)es (2a,b) (general procedure). A mixꢀ
ture of 2ꢀbenzylideneꢀ3ꢀoxoalkanoate 1a,b (0.01 mol), urea
(
2
Scheme 2). The formation of benzodiazepine from
ꢀbenzylideneꢀ3ꢀoxoalkanoate 1 is likely thermodynamiꢀ
(
thiourea) (0.01 mol), and sodium acetate (0.16 g, 0.003 mol) in
DMF (10 mL) was heated for 6—8 h at 70 °C. Then the reaction
mixture was poured into water, and the precipitate that formed
was filtered off and recrystallized from ethanol. Compounds 2а
cally unfavorable.
Thus, 2ꢀbenzylideneꢀ2ꢀpolyfluoroacylacetates in the
reactions with dinucleophiles (urea, thiourea, guanidine,
phenylhydrazine) behave as typical vinyl ketones adding
dinucleophiles to the carbon—carbon double bond and
keto group. The reaction of guanidine manifests an addiꢀ
tional possibility of formation of the binuclear heteroꢀ
cycle, viz., pyrimidopyrimidine. However, it is difficult to
use 2ꢀbenzylideneꢀ3ꢀoxoalkanoates because of their easy
cleavage to 3ꢀoxoalkanoate and benzaldehyde. This proꢀ
cess becomes the main reaction in the case of the reacꢀ
tions with oꢀphenylenediamine and hydrazine.
(
1.91 g, 64%) and 2b (1.81 g, 52%) were obtained, whose physicoꢀ
chemical characteristics correspond to published data.8
2ꢀAminoꢀ5ꢀethoxycarbonylꢀ4ꢀfluoroalkylꢀ6ꢀphenylꢀ1,6ꢀdiꢀ
hydropyrimidines (3а,b). A mixture of 2ꢀbenzylideneꢀ3ꢀoxoꢀ
alkanoate 1а,b (0.01 mol), guanidine sulfate (1.89 g, 0.01 mol),
and sodium bicarbonate (1.10 g, 0.013 mol) in DMF (10 mL)
was heated for 8—10 h at 70 °C. Then the reaction mixture was
poured into water, and the precipitate that formed was filtered
off, washed with hot chloroform, and recrystallized from ethaꢀ
nol. Compounds 3а (1.33 g) and 3b (1.84 g) were obtained (see
Tables 1 and 2).
3
,6ꢀDiethoxycarbonylꢀ2,7ꢀdi(difluoromethyl)ꢀ4,5ꢀdiphenylꢀ
4,5ꢀdihydroꢀ1Нꢀpyrimido[1,2ꢀа]pyrimidine (4а). А. Compound
a was isolated from the filtrate after purification of product 3а.
Experimental
4
IR spectra were recorded on a Specord 75IR spectrometer in
The filtrate was concentrated, and the residue was washed with
–
1
an interval of 400—4000 cm in Nujol. NMR spectra were
Et O. Compound 4а was obtained (1.91 g) (see Tables 1 and 2).
2
1
obtained on Tesla BSꢀ587A ( Н, 80 MHz, relatively to SiMe ;
B. A mixture of ester 1a (2.72 g, 0.01 mol), pyrimidine 3a
(2.95 g, 0.01 mol), and sodium bicarbonate (1.10 g, 0.003 mol)
in DMF (10 mL) was heated for 8—10 h at 70 °C. Then the
reaction mixture was poured into water, and the precipitate that
4,
1
9
F, 75.3 MHz, relatively to С F ) and Bruker DRXꢀ400
6
6
(1
Н, 400 MHz; С, 100 MHz relatively to SiMe4; F, 376 MHz,
13
19
relatively to С F ) spectrometers. Elemental analysis was carꢀ
6
6
ried out on an Carlo Erba CHNSꢀO EA 1108 analyzer.
Physicochemical constants and elemental analysis data are
presented in Tables 1 and 2. The data of the 1 С NMR spectrum
for compound 8а are given in Table 3.
formed was filtered off and washed with Et O. Compound 4а
(3.13 g) was obtained (see Tables 1 and 2).
2
3
3,5ꢀDiethoxycarbonylꢀ2,6ꢀdi(fluoroalkyl)ꢀ2,6ꢀdihydroxyꢀ4ꢀ
phenyltetrahydropyrans (5а,b). A mixture of 2ꢀbenzylideneꢀ3ꢀ
oxoalkanoate 1a,b (0.01 mol) and hydrazine hydrate (0.50 g,
0.01 mol) in EtOH (10 mL) was refluxed for 6—8 ч. Then the
solvent was evaporated, and the residue was recrystallized from
hexane. Compounds 5а (1.97 g, 45%) and 5b (1.80 g, 38%) were
obtained, and their physicochemical characteristics correspond
The starting alkyl 2ꢀbenzylideneꢀ2ꢀpolyfluoroacylacetates
1
а—f were synthesized according to previously described proceꢀ
1,2
dures.
1
to published data.
3
ꢀFluoroalkylꢀ5ꢀhydroxypyrazoles (6a,b). A mixture of
ꢀbenzylideneꢀ3ꢀoxoalkanoate 1a,f (0.01 mol) and hydrazine
0.32 g, 0.01 mol) was refluxed in anhydrous EtOH for 2 h. Then
2
(
the solvent was evaporated, and the residue was recrystallized
from hexane. Compound 6a (0.48 g, 36%), whose physicochemiꢀ
1
3
cal characteristics correspond to published data, and comꢀ
pound 6b (1.93 g, 48%) were obtained (see Tables 1 and 2).
4
ꢀAlkoxycarbonylꢀ3ꢀfluoroalkylꢀ3ꢀhydroxyꢀ1,5ꢀdiphenylꢀ
pyrazolidines (8a—с). A mixture of 2ꢀbenzylideneꢀ3ꢀoxoalkaꢀ
noate 1b,c,e (0.01 mol) and phenylhydrazine (1.08 g, 0.01 mol)
Table 3. 13С NMR spectrum (δ, J13C—19F/Hz) of 4ꢀethoxyꢀ
carbonylꢀ3ꢀhydroxyꢀ1,5ꢀdiphenylꢀ3ꢀtrifluoromethylpyrazolꢀ
in anhydrous Et O (10 mL) was kept at ~20 °C for a week. Then
2
idine (8a) in DMSOꢀd6
the solvent was evaporated, and the residue was washed with hot
hexane. Compounds 8а (4.01 g), 8b (2.14 g), and 8с (2.55 g)
were obtained (see Tables 1—3). After the filtrate was concenꢀ
trated, benzaldehyde phenylhydrazone (7) was obtained in 15%
Atom
С(1)
δ (JC,F/Hz)
89.88
Atom
δ (JC,F/Hz)
С(9)
128.95
127.81
152.20
113.38
128.26
118.40
122.27
(q,....
(
0.29 g), 22% (0.43 g), and 29% (0.56 g) yields, respectively, and
(
q, J = 31.0)
62.50
С(10)
С(11)
С(12)
С(13)
С(14)
С(15)
its physicochemical characteristics correspond to those presented
С(2)
С(3)
С(4)
С(5)
С(6)
С(7)
С(8)
1
4
in the literature.
69.07
166.15
60.86
13.79
141.96
126.21
Reaction of 2ꢀbenzylideneꢀ3ꢀoxoalkanoates 1 with oꢀpheꢀ
nylenediamine. A mixture of 2ꢀbenzylideneꢀ3ꢀoxoalkanoate
1
а,c,d (0.01 g) and oꢀphenylenediamine (1.08 g, 0.01 mol) in
anhydrous Et O (benzene or EtOH) (20 mL) was refluxed for
2
4
—6 h. The solvent was evaporated, and the residue was recrysꢀ
J = 286.0)
tallized from ethanol. 4ꢀFluoroalkylꢀ1Hꢀ1,5ꢀbenzodiazepinꢀ2ꢀ

1
266
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 6, June, 2004
Pryadeina et al.
ones 9a—c were obtained in 59% (1.24 g) (9a), 50% (1.30 g) (9b)
and 58% (2.08 g) (9c) yields, and their physicochemical characꢀ
teristics correspond to published data.1 The filtrate was conꢀ
centrated, and the residue was recrystallized from hexane.
7. V. I. Saloutin, Ya. V. Burgart, O. G. Kuzueva, C. O. Kappe,
and O. N. Chupakhin, J. Fluor. Chem., 2000, 103, 17.
8. O. G. Kuzueva, Ya. V. Burgart, M. V. Pryadeina, S. O.
Kappe, and V. I. Saloutin, Zh. Org. Khim., 2001, 37, 915
[Russ. J. Org. Chem., 2001, 37 (Engl. Transl.)].
5
2
ꢀPhenylbenzimidazole (10) was obtained in 19% (0.34 g), 22%
(
0.40 g), and 20% (0.36 g) yields, respectively, and its physicoꢀ
9. A. Albert and E. P. Serjeant, Ionization Constants of Acids
and Bases, Methuen, London, 1962.
1
6
chemical characteristics correspond to published data.
1
0. V. M. Potapov, Stereokhimiya [Stereochemistry], Khimiya,
Moscow, 1988, p. 211 (in Russian).
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos. 03ꢀ03ꢀ33118
and 03ꢀ03ꢀ06472).
11. B. I. Ionin, B. A. Ershov, and A. I. Kol´tsov,
YaMRꢀspektroskopiya v organicheskoi khimii [NMR spectroꢀ
scopy in Organic Chemistry], Khimiya, Leningrad, 1983, p. 154
(
in Russian).
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1
2. C. O. Kappe, S. F. Falsone, W. M. F. Fabian, and F. Belay,
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2
3
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IV Int. Electronic Conf. on Synthetic Org. Chem. (ECSOCꢀ4),
Received December 29, 2003;
in revised form March 22, 2004
2
000, [A0050].