Ferrocenecarboxylic acid and microwave-assisted synthesis of ferrocenoyl hydrazones

Article abstract of DOI:10.1007/s11172-017-1768-x

A protocol to access ferrocenecarboxylic acid via carboxylation of ferrocene with carbon dioxide in the presence of aluminum chloride was elaborated. An efficient microwave-assisted synthesis of ferrocenoyl hydrazones by condensation of ferrocene carbohydrazide with carbonyl compounds was developed. Structures of the synthesized compounds were examined by NMR spectroscopy and mass spectrometry. Structures of N′-(4-chlorobenzylidene)ferrocenecarbohydrazide, N′-(4-methoxybenzylidene)ferrocenecarbohydrazide, and N′-(2-hydroxybenzylidene)ferrocenecarbohydrazide were determined by X-ray diffraction analysis. Synthesized compounds were found to have no toxicity against P. aeruginosa, E. coli, S. aureus, B. subtilis, M. rubrum, and C. albicans.

Full text of DOI:10.1007/s11172-017-1768-x

Russian Chemical Bulletin, International Edition, Vol. 66, No.3, pp. 537—544, March, 2017
537
Ferrocenecarboxylic acid and microwaveꢀassisted synthesis of
ferrocenoyl hydrazones
V. N. Kulikov,a,b R. S. Nikulin,a,b D. E. Arkhipov, A. N. Rodionov, E. S. Babusenko,
a
a
b
b
a
L. V. Kovalenko, and Yu. A. Belousov
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
8 ul. Vavilova, 119991 Moscow, Russian Federation.
2
Fax: +7 (499) 135 5085. Eꢀmail: belur@ineos.ac.ru
D. Mendeleev University of Chemical Technology of Russia,
b
9
Miusskaya pl., 125047 Moscow, Russian Federation.
Fax: +7 (495) 609 2964. Eꢀmail: kulikov_v_n@mail.ru
A protocol to access ferrocenecarboxylic acid via carboxylation of ferrocene with carbon
dioxide in the presence of aluminum chloride was elaborated. An efficient microwaveꢀassisted
synthesis of ferrocenoyl hydrazones by condensation of ferrocene carbohydrazide with carbonꢀ
yl compounds was developed. Structures of the synthesized compounds were examined by
NMR spectroscopy and mass spectrometry. Structures of N´ꢀ(4ꢀchlorobenzylidene)ferroceneꢀ
carbohydrazide, N´ꢀ(4ꢀmethoxybenzylidene)ferrocenecarbohydrazide, and N´ꢀ(2ꢀhydroxyꢀ
benzylidene)ferrocenecarbohydrazide were determined by Xꢀray diffraction analysis. Syntheꢀ
sized compounds were found to have no toxicity against P. aeruginosa, E. coli, S. aureus,
B. subtilis, M. rubrum, and C. albicans.
Key words: ferrocene, ferrocenecarboxylic acid, hydrazones, microwaveꢀassisted synthesis,
antimicrobial activity.
Ferrocene derivatives exhibit a wide range of biological
anhydrous benzene in the presence of AlCl at 50 °C has
been described. However, this method gives low converꢀ
3
1
—5
11
activities as a rule combined with low toxicity.
Ferroꢀ
cene derivatives possess amphiphilic and membrane tropic
properties due to lipophilicity of ferrocene, hydrophilicity
of ferrocenium salts and reversibility of the ferrocene/ferroꢀ
sion of ferrocene (<60%) and low yield of ferrocenecarbꢀ
oxylic acid (<50%). Moreover, no information about posꢀ
sibility to scale up the process has been published.
We elaborated a modified protocol for the synthesis of
ferrocenecarboxylic acid under increased pressure of
carbon dioxide maintaining the reaction temperature beꢀ
low 30 °C (Scheme 1).
6
cenuim redox couple. These properties along with the
relative stability of a ferrocene scaffold in the complex bioꢀ
7
logical media introduced ferrocene as a promising buildꢀ
ing block for the design of biologically active substances.
Synthesis of ferrocenyl hydrazones for chemosensory
applications and as antibacterial agents in the transition
Scheme 1
8
—10
metal complexes has attracted considerable attention.
However, the known procedures to access these comꢀ
pounds suffer from such drawbacks as prolonged reaction
times, medium yields, and requirement of chromatographic
product purification.
In the present work, we report a simple protocol for
the synthesis of ferrocenecarboxylic acid and its hydrazide
as well as an efficient synthetic approach towards ferroꢀ
cene carbohydrazones providing a high reaction rate, high
yields and purity of the target products.
Reagents and conditions: 1) CO2 (2—5 bar), AlCl , toluene,
3
+
1
5—30 °C; 2) H , H O.
2
Results and Discussion
It is of note that this reaction can occur even at atmoꢀ
Synthesis of ferrocenylcarboxylic acid by bubbling gasꢀ
eous carbon dioxide through a solution of ferrocene in
spheric pressure. Thus, bubbling CO through the reacꢀ
tion mixture at room temperature for 7 h gives ferrocene
2
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0537—0544, March, 2017.
066ꢀ5285/17/6603ꢀ0537 © 2017 Springer Science+Business Media, Inc.
1

5
38
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kulikov et al.
conversion of 17%. When pressure of carbon dioxide of
0—60 bar was used, the reaction completed within a few
ferrocene carbohydrazides 3 and the corresponding carboꢀ
nyl compounds preꢀwetted with small amount of EtOH
(Scheme 3, Table 1). Liquid aldehydes were preliminary
mixed with EtOH.
5
minutes and accompanied with a strong exothermic effect
causing resinification of the reaction mixture. Therefore,
using dry ice as a source of carbon dioxide, it is strongly
recommended to add it by several portions. At pressure of
carbon dioxide of 2—5 bar and room temperature, carbꢀ
oxylation is completed within 1.5—2 h. A low exothermic
effect observed during the reaction can be easily compenꢀ
sated by cooling with water, which prevents resinification.
It should be emphasized that the developed reaction conꢀ
ditions allow performing the reaction not only in the steel
autoclave or a Parr reaction bottle but also without special
equipment, for instance, in a plastic bottle.
Scheme 3
We studied the solvent effect on the product yield. The
highest yield (70%) was achieved in toluene. In dichloroꢀ
methane or in a toluene—dichloromethane mixture (2 : 1),
the reaction rate increases but the yields of ferrocenecarbꢀ
oxylic acid 2 drop to 55 and 64%, respectively, due to
significant oxidation of ferrocene. The use of the solvent
mixtures is not advisable since the reaction rate is high
enough irrespectively the solvent used and does not limit
the process.
Comꢀ
pound 4
R
Yield of 4
(%)
97
4
4
4
a
b
c
Ph
4ꢀMeC H4
2ꢀClC H4
4ꢀClC H4
4ꢀMeOC6H4
97
95
96
97
93
97
96
6
6
4d
4e
6
4
4
4
f
g
h
3,4ꢀ(MeO) C H
3ꢀMeO(4ꢀHO)C H3
3ꢀEtO(4ꢀHO)C H3
2
6
3
6
6
Aluminum chloride AlCl was used as a Lewis acid. An
4i
2ꢀHOC H4
99
99
100
96
96
3
6
4
4
4
4
j
k
l
2,4ꢀ(HO) C H
increase in the amount of AlCl from 1.2 to 3.0 equiv.
2
6
3
3
3ꢀO NC H
2
6
4
insignificantly increases the yield of compound 2 without
formation of either ferrocenedicarboxylic acid or products
of carboxylation of toluene. Thus, the elaborated proceꢀ
dure can be regarded as a selective approach to ferroceneꢀ
carboxylic acid.
4ꢀO NC H
2
6
4
m
4ꢀMe NC H
2
6
4
4n
4ꢀpyridyl
2ꢀfuryl
95
94
4
o
Ferrocene carbohydrazide 3 was prepared from ferroꢀ
cenecarboxylic acid via its acid chloride (Scheme 2). Acid 2
was treated with oxalyl chloride under argon. Acid
chloride obtained by concentrating the reaction mixture
in vacuo was used on the next step without further purifiꢀ
cation. Acid chloride was dissolved in dichloromethane
and the resulting solution was added dropwise to a vigorꢀ
ously stirred mixture of hydrazine hydrate and triethylꢀ
amine. This procedure gives hydrazide 3in 91% isolated yield.
4p
94
98
4
q
CH CHMe2
2
4
r
95
Conditions: EtOH, microwave irradiation (750 W, 20—40 s).
Microwave irradiation results in fast homogenization
of the reaction mixture and facilitates the reaction. After
cooling, the target hydrazones precipitate from the reacꢀ
tion mixture. Filtration of the precipitate, washing with
cold ethanol, and drying under vacuum afforded analytiꢀ
cally pure products 4.
Scheme 2
With the aim to estimate the efficiency of microwaveꢀ
assisted synthesis of ferrocenoyl hydrazones 4, we syntheꢀ
sized compounds 4a,p by the conventional method, i.e., by
refluxing the reagents in methanol for 1 h under an inert
atmosphere. Following this procedure, compounds 4a,p
were obtained in 77 and 63% isolated yields, respectively
(cf. yields of 97 and 94% achieved in microwave synthesis).
A decrease in the product yield in the conventional
Reagents and conditions: 1) (COCl) (1.5 equiv.), CH Cl , Ar;
2
2
2
reaction we attributed to a partial decomposition of the
starting hydrazide 3 or target hydrazones 4 upon prolonged
heating. This also leads to the necessity of chromatographic
purification of the target products. Purification of hydrꢀ
2
) N H •H O (2.5 equiv.), Et N, CH Cl .
2
4
2
3
2
2
Ferrocenoyl hydrazones 4a—r were synthesized using
microwave irradiation of a mixture of finely powdered

Microwave synthesis of ferrocenoylhydrazones
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
539
Table 1. Physicochemical properties of hydrazones 4a—r
Comꢀ
pound
M.p./°C
Found
Calculated
Molecular formula
C H FeN O
(
%)
C
H
N
Fe
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a
b
c
d
e
f
200—202*
208—209*
207—209*
196—198
217—219*
165—166
200—202*
192—194
217—218
257—260*
208—210*
230—232*
160—162*
210—212
208—210
244—246
122—124
227—229*
65.05
4.89
4.85
5.25
5.24
4.14
4.12
4.12
4.12
5.03
5.01
5.14
5.14
4.84
4.80
5.17
5.14
4.64
4.63
4.45
4.43
4.01
4.01
3.99
4.01
5.65
5.64
4.56
4.54
4.40
4.38
4.38
4.33
6.53
6.46
4.23
4.20
8.35
8.43
8.07
8.09
7.60
7.64
7.59
7.64
7.70
7.73
7.11
7.14
7.38
7.41
7.12
7.14
8.04
8.05
7.67
7.69
11.15
11.14
11.16
11.14
11.19
11.20
12.61
12.61
8.65
8.70
15.01
15.05
9.03
8.97
5.51
5.56
16.70
16.81
16.10
16.13
15.20
15.23
15.20
15.23
15.30
15.42
14.20
14.24
14.60
14.77
14.20
14.24
16.00
16.04
15.20
15.33
14.80
14.81
14.70
14.81
14.80
14.88
16.70
16.76
17.40
17.34
15.00
15.00
17.90
17.89
11.00
11.08
1
8
16
2
6
5.08
65.90
5.92
58.91
8.97
58.93
8.97
62.95
3.00
61.21
1.24
60.29
0.34
61.20
1.24
62.07
2.09
59.32
9.36
57.32
7.32
57.30
7.32
64.00
4.02
61.25
1.29
59.62
9.65
61.26
1.31
61.46
1.56
52.37
2.41
C H FeN O
1
9
18
2
6
C H ClFeN O
1
8
15
2
5
C H ClFeN O
1
8
15
2
5
C H FeN O
2
1
9
18
2
6
C20H FeN O
20
2
3
3
6
g
h
i
C H FeN O
19 18 2
6
C20H FeN O
20
2
3
2
3
3
3
6
C H FeN O
1
8
16
2
6
j
C H FeN O
18 16 2
5
k
l
C H FeN O
18 15 3
5
C H FeN O
1
8
15
3
5
m
n
o
p
q
r
C H FeN O
20 21 3
6
C H FeN O
1
7
15
3
6
C H FeN O
1
6
14
2
2
5
C H FeN O
1
9
16
4
6
C H FeN O
1
6
20
2
6
C H FeMnN O •MeOH
2
0
15
2
4
5
*
Decomposition.
–
1
–1
azones 4 is complicated by their low solubility in the
solvents used for chromatography and their noticeable adꢀ
sorption on both silica gel and aluminum oxide during
column chromatography. Microwave irradiation minimizꢀ
es the formation of decomposition products and gives prodꢀ
ucts requiring no chromatographic purification.
Thus, the advantages of the microwaveꢀassisted synꢀ
thesis are the shortened reaction time, the smaller volꢀ
umes of the solvents used, the increased product yields,
and the simplification of product isolation.
1450—1460 cm (C—C ), 1000—1100 cm (CH ),
Fc Fc
–
1
–1
815—840 cm (CH ), and 480—510 cm (Fe—Cp).
Fc
Electron impact mass spectra of compounds 4a—r
(Table 2) contain the molecular ion peaks and a set of
fragment ion peaks. The main fragmentation reactions of
the molecular ions are the cleavage of the C—C bonds
between cyclopentadiene ring and carbonyl group, the
C—N bond between carbonyl and amide groups, and the
N—N bond between imine and amide nitrogen atoms
(Scheme 4).
IR spectra of compounds 4a—r exhibit absorptions
characteristic of the functional groups present in the
It was found that ferrocenecarboxylic acid hydrazones
do not undergo the cleavage of the bond between metal—
cyclopentadienyl ligand to form the [M – Cp] and
[M – CpFe]+ ions, which is typical for a majority of
–
1
+
structures in the ranges of 3000—3500 cm (CH, NH),
–
1
–1
1
635—1650 cm (C=O), 1600—1620 cm (C—N),

5
40
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kulikov et al.
Table 2. Spectral characteristics of hydrazones 4a—r
Comꢀ
pound
MS
m/z (Irel (%))
1H NMR, δ (J/Hz)
13C NMR, δ
+
+
+
4a
4b
4c
332 [M] (100), 229 [M – NCHR]
4.21 (s, 5 Н, С Н5); 4.45 (s, 2 Н, С Н );
68.5 (С Н ), 69.5 (С Н ), 70.6
5 4 5 5
(С Н ), 74.8 (C H ꢀipso), 126.9
5 4 5 4
(R), 128.8 (R), 129.8 (Rꢀipso),
134.6 (R), 145.9 (C=N), 166.0
5
5
4
+
(
1
18), 213 [M – NHNCHR] (98),
85 [M – CONHNCHR] (78)
4.97 (s, 2Н, С Н ); 7.35—7.51
5
4
+
(m, 3 Н, R); 7.69—7.75 (m, 2 Н, R), 8.45
br.s, 1 Н, N=СН), 11.22 (br.s, 1 Н, NН)
(
(
C=O)
+
346 [M] (100), 229 [M – NCHR]
2.34 (s, 3 Н, СН ), 4.21 (s, 5 Н, С Н ); 4.45
3 5 5
21.0 (СН ), 68.5 (C H ), 69.5 (C H ),
3
5
4
5
5
+
(
1
28), 213 [M – NHNCHR] (95),
85 [M – CONHNCHR] (70)
(s, 2 Н, С Н ); 4.94 (s, 2 Н, С Н ); 7.27 (d,
70.5 (C H ), 74.9 (C H ꢀipso), 126.9
5
4
5
4
5 4 5 4
+
2 Н, R, J = 7.6); 7.61 (d, 2 Н, R,
J = 7.6); 8.39 (s, 1 Н, N=CH);
(R), 129.4 (R), 131.9 (R), 139.5 (R),
146.0 (C=N), 165.9 (C=O)
1
1.10 (s, 1 Н, NН)
+
+
367 [M] (15), 229 [M – NCHR]
4.23 (s, 5 Н, С Н ); 4.48 (s, 2 Н, С Н );
68.5 (C H ), 69.5 (C H ), 70.7
5
5
5
4
5
4
5
5
+
(
1
26), 213 [M – NHNCHR] (100), 4.97 (s, 2 Н, С Н ); 7.39—7.48 (m, 2 Н, R);
85 [M – CONHNCHR] (59)
(C H ), 74.4 (C H ꢀipso), 126.6 (R),
5 4 5 4
5
4
+
7.50—7.56 (m, 1 Н, R); 7.99—8.05 (m, 1 Н,
R); 8.82 (br.s, 1 Н, N=CH); 11.42 (br.s,
127.5 (R), 129.9 (R), 131.1 (R),
131.8 (R), 132.9 (R), 141.5
(C=N), 166.2 (C=O)
1
Н, NН)
+
+
4
d
e
366 [M] (8), 229 [M – NCHR]
4.22 (s, 5 Н, С Н ), 4.50 (s, 2 Н, С Н );
68.6 (С Н ), 69.5 (С Н ), 70.8
5
5
5
4
5
4
5
5
+
(
1
12), 213 [M – NHNCHR] (100), 4.98 (s, 2 Н, С Н ); 7.59—7.72 (m, 2 Н, R);
85 [M – CONHNCHR] (55)
(С Н ), 74.2 (С Н ꢀipso), 120.9 (R),
5
4
5 4 5 4
+
8.42 (s, 1 Н, N=СН); 8.61—8.69 (m, 2 Н, R); 141.8 (R), 143.4 (C=N), 150.2 (R),
1
1.43 (br.s, 1 Н, NН)
166.5 (C=O)
+
+
4
362 [M] (22), 229 [M – NCHR]
3.80 (s, 3 Н, ОMe); 4.20 (s, 5 Н, С Н );
55.3 (OMe), 68.4 (С Н ), 69.4
5
5
5
4
+
(
1
33), 213 [M – NHNCHR] (100), 4.43 (s, 2 Н, С Н ); 4.95 (s, 2 Н, С Н );
85 [M – CONHNCHR] (51)
(С Н ), 70.4 (С Н ), 75.0
5 5 5 4
(С Н ꢀipso), 114.3 (R), 127.1
5 4
(R), 128.5 (R),145.9 (C=N), 160.6
(R), 165.7 (C=O)
5
4
5
4
+
6.91—7.08 (m, 2 H, R); 7.78—7.76 (m,
Н, R); 8.39 (s, 1 Н, N=СН); 11.07
s, 1 Н, NН)
2
(
+
+
4
4
4
f
392 [M] (100), 229 [M – NCHR]
3.81 (m, 3 Н, OMe); 3.83 (m, 3 Н, OMe);
4.21 (s, 5 Н, С Н ); 4.45 (s, 2 Н, С Н );
55.4 (OMe), 55.6 (OMe), 68.5
+
(
1
50), 213 [M – NHNCHR] (98),
85 [M – CONHNCHR] (61)
(С Н ), 69.5 (С Н ), 70.5 (С Н ),
5
5
5
4
5
4
5
5
5
4
+
4.94 (s, 2 Н, С Н ); 6.99—7.07 (m, 1 Н, R);
75.0 (C H ꢀipso), 108.0 (R), 111.5
5 4
(R), 121.8 (R), 127.3 (R), 146.4
(C=N), 149.1 (R), 150.5 (R), 165.8
5
4
7
8
.14—7.22 (m, 1 Н, R); 7.33 (s, 1 Н, R);
.36 (s, 1 Н, N=CH); 11.04 (s, 1 Н, NН)
(
C=O)
+
+
g
h
392 [M] (43), 229 [M – NCHR]
3.82 (s, 3 Н, OMe); 4.20 (s, 5 Н, С Н );
5 5
55.5 (OMe), 68.4 (С Н ), 69.5
5
4
+
(
1
34), 213 [M – NHNCHR] (100), 4,43 (s, 2 Н, С Н ); 4,95 (s, 2 Н, С Н );
85 [M – CONHNCHR] (62)
(С Н ), 70.5 (С Н ), 75.1
5 5 5 4
(С Н ꢀipso), 108.7 (R), 115.4 (R),
5 4
122.1 (R), 126.0 (R), 146.8 (R), 148.1
(C=N), 148.8 (R), 165.8 (C=O)
5
4
5
4
+
6.76—6.93 (m, 1 Н, R); 6.99—7.13 (m,
1
1
Н, R); 7.21—7.47 (m, 1 Н, R); 8.35 (s,
Н, N=CH); 9.52 (s, 1 H, OH); 11.08
(
br.s, 1 Н, NH)
+
+
378 [M] (45), 229 [M – NCHR]
1.36 (t, 3 Н, CH , J = 6.1); 4.08—4.28
14.8 (CH ), 63.9 (OCH ), 68.4
3
3
2
+
(
1
34), 213 [M – NHNCHR] (100), (m, 7 Н, С Н , OCH ); 4.43 (s, 2 Н, С Н );
85 [M – CONHNCHR] (67)
(С Н ), 69.5 (С Н ), 70.4 (С Н ),
5 4 5 5 5 4
5
5
2
5
4
+
4.94 (s, 2 Н, С Н ); 6.80—6.92 (m, 1 Н, R);
75.1 (С Н ꢀipso), 110.0 (R), 115.5
5
4
5 4
7
1
.00—7.10 (m, 1 Н, R); 7.22—7.33 (m,
Н, R); 8.32 (s, 1 Н, N=CH); 9.44
(R), 122.0 (R), 126.0 (R), 146.8 (R),
147.2 (C=N), 149.0 (R), 165.8 (C=O)
(
s, 1 H, OH); 11.06 (br.s, 1 Н, NH)
+
+
4
i
j
348 [M] (18), 282 [M – Cp—H]
4.23 (s, 5 Н, С Н ); 4.48 (s, 2 Н, С Н );
68.5 (С Н ), 69.6 (С Н ), 70.7
(С Н ), 74.1 (С Н ꢀipso), 116.4 (R),
5 4 5 4
118.8 (R), 119.3 (R), 129.4 (R), 131.0
(R), 146.6 (C=N), 157.3 (R), 165.9
(C=O)
5
5
5
4
5
4
5
5
+
(
[
[
[
100), 227 [M – Cp—Fe] (18), 229 4.95 (s, 2 Н, С Н ); 6.84— 7.00 (m, 2 H, R);
M – NCHR] (20), 213
M – NHNCHR] (42), 185
M – CONHNCHR] (53)
5
4
+
7.29 (t, 1 H, R, J = 7.4); 7.52 (d, 1 H, R,
J = 7.4); 8,59 (s, 1 Н, N=CH); 11.34
(s, 1 Н); 11.43 (br.s, 1 Н)
+
+
+
+
4
364 [M] (28), 298 [M – Cp—H]
4.20 (s, 5 Н, С Н ); 4.44 (s, 2 Н, С Н );
68.4 (С Н ), 69.5 (С Н ), 70.6
5
5
5
4
5
4
5
5
+
(
100), 243 [M – Cp—Fe] (12),
29 [M – NCHR] (20),
13 [M – NHNCHR] (45),
85 [M – CONHNCHR] (51)
4.93 (s, 2 Н, С Н ); 6.25—6.47 (m, 2 Н, R);
(С Н ), 74.5 (С Н ꢀipso), 102.7 (R),
5
4
5 4 5 4
+
2
2
1
7.20—7.40 (m, 1 Н, R), 8.47 (s, 1 Н, N=CH), 107.7 (R), 110.7 (R), 131.2 (R), 147.5
9.93 (br.s, 1 H), 11.26 (уш. s, 1 Н),
11.53 (br.s, 1 Н)
+
(C=N), 159.3 (R), 160.5 (R), 165.5
(C=O)
+
(
to be continued)

Microwave synthesis of ferrocenoylhydrazones
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
541
Table 2 (continued)
Comꢀ
pound
MS
m/z (Irel (%))
1H NMR, δ (J/Hz)
13C NMR, δ
+
+
4
k
377 [M] (30), 229 [M – NCHR]
4.23 (s, 5 Н, С Н ); 4.49 (s, 2 Н, С Н );
68.6 (С Н ), 69.5 (С Н ), 70.7
(С Н ), 74.3 (С Н ꢀipso), 120.6 (R),
5 4 5 4
123.8 (R), 130.4 (R), 133.2 (R), 136.5
(R), 143.3 (C=N), 148.2 (R),
166.3 (C=O)
5
5
5
4
5
4
5
5
+
(
7), 213 [M – NHNCHR] (100),
85 [M – CONHNCHR] (54)
4.98 (s, 2 Н, С Н ); 7.72—7.80 (m, 1 H, R);
5
4
+
1
8.11—8.17 (m, 1 Н, R); 8.22—8.23 (m,
1
1
H, R); 8.49—8.57 (m, 2 Н, N=СН, R);
1.43 (br.s, 1 Н, NН)
+
+
4
l
377 [M] (73), 229 [M – NCHR]
4.23 (s, 5 Н, С Н ); 4.50 (s, 2 Н, С Н );
68.6 (С Н ), 69.6 (С Н ), 70.8
5
5
5
4
5
4
5
5
+
(
1
10), 213 [M – NHNCHR] (100), 4.99 (s, 2 Н, С Н ); 7.98 (d, 2 Н, R,
85 [M – CONHNCHR] (62)
(С Н ), 74.2 (С Н ꢀipso), 124.1 (R),
5
4
5 4 5 4
+
J = 8.4); 8.31 (d, 2 Н, R, J = 8.4);
.53 (br.s, 1 Н, N=CH); 11.47 (s, 1 Н, NН)
2.96 (s, 6 Н, NMe2); 4.20 (s, 5 Н, С Н );
127.8 (R), 141.1 (R), 143.3 (C=N),
147.6 (R), 158.6 (R), 166.4 (C=O)
8
+
+
4m
375 [M] (47), 229 [M – NCHR]
39.8 (NMe ), 68.3 (С Н ), 69.4
5
5
2
5
4
+
(
1
100), 213 [M – NHNCHR] (46), 4.42 (s, 2 Н, С Н ); 4.94 (s, 2 Н, С Н );
85 [M – CONHNCHR] (44)
(С Н ), 70.3 (С Н ), 75.4
5 5 5 4
5
4
5
4
+
6.64—6.86 (m, 2 H, R); 7.44—7.63 (m,
H, R); 8.30 (s, 1 H, N=СН); 10.91
s, 1 Н, NН)
4.22 (c, 5 Н, С Н ); 4.50 (s, 2 Н, С Н );
(С Н ꢀipso), 111.8 (R), 121.9 (R),
5 4
2
(
128.2 (R), 147.0 (C=N), 151.3 (R),
165.4 (C=O)
+
4
n
o
333 [M] (100),
68.6 (С Н ), 69.5 (С Н ), 70.8
5
5
5
4
5
4
5
5
+
2
2
1
29 [M – NCHHet] (8),
13 [M – NHNCHHet] (93),
85 [M – CONHNCHHet] (52)
4.98 (s, 2 Н, С Н ); 7.59—7.72 (m, 2 Н, R); (С Н ), 74. 2 (С Н ꢀipso), 120.9 (R),
5 4 5 4 5 4
+
8.42 (br.s, 1 Н, N=CH); 8.61—8.69 (m,
2 Н, R); 11.43 (s, 1 Н, NН)
141.8 (R), 143.4 (C=N), 150.2 (R),
166.5 (C=O)
+
+
4
322 [M] (33),
4.21 (s, 5 Н, С Н ); 4.46 (s, 2 Н, С Н );
68.5 (С Н ), 69.5 (С Н ), 70.6
5
5
5
4
5
4
5
5
+
2
2
1
29 [M – NCHHet] (14),
13 [M – NHNCHHet] (100),
85 [M – CONHNCHHet] (71)
4.92 (s, 2 Н, С Н ); 6.62—6.65 (m, 1 H, R); (С Н ), 74.7 (С Н ꢀipso), 112.2 (R),
5 4 5 4 5 4
6.86—6.91 (m, 1 Н, R); 7.81—7.88 (m,
1 Н, R); 8.33 (s, 1 Н, N=СН); 11.10
+
112.8 (R), 135.9 (C=N), 144.9
(R), 149.7 (R), 166.0 (C=O)
+
(
s, 1 Н, NН)
+
+
4
4
4
p
q
r
372 [M] (23), 307 [M – Cp]
4.24 (s, 5 Н, С Н ); 4.50 (s, 2 Н, С Н );
68.7 (С Н ), 69.6 (С Н ), 71.3
5
5
5
4
5
4
5
5
+
(
1
100), 280 [M – Cp—CO] (8),
85 [M – CONHNCHHet] (11)
4.99 (s, 2 Н, С Н ); 7.16—7.30 (m, 2 Н, R); (С Н ), 74.2 (С Н ꢀipso), 111.9 (R),
5 4 5 4 5 4
+
7.46—7.57 (m, 1 Н, R); 7.63—7.71 (m, 1 H, 119.3 (R), 121.9 (R), 123.7 (R), 134.8
R); 8.48 (s, 1 Н, N=СН); 11.49
s, 1 Н, CONН); 12.93 (br.s, 1 Н, NН)
(R), 137.4 (R), 143.7 (C=N), 148.2
(R), 166.3 (C=O)
(
+
+
312 [M] (85), 229 [M – NCHAlk] 0.94 (d, 6 Н, R, J = 6.6); 1.76—1.93
22.3 (R), 26.3 (R), 40.8 (R), 68.3
(С Н ), 69.4 (С Н ), 70.3 (С Н ),
+
(
1
38), 213 [M – NHNCHAlk] (100), (m, 1 Н, R); 2.13 (t, 2 Н, R, J = 6.1);
85 [M – CONHNCHR] (85)
5
4
5
5
5
4
+
4.18 (s, 5 Н, С Н ); 4.41 (s, 2 Н, С Н );
75.1 (С Н ꢀipso), 149.7 (C=N),
5 4
5
5
5
4
4
1
.87 (s, 2 Н, С Н ); 7.69 (s, 1 Н, N=CH);
0.71 (s, 1 Н, NН)
165.4 (C=O)
68.5 (С Н Fc), 69.5 (С Н ), 70.7
5
4
+
374 [M – C3O3] (10),
29 [M – NCHCm] (21),
13 [M – NHNCHCm] (10),
86[M – CONHNCHCm + H]+
4.18 (s, 5 Н, С Н ); 4.24 (s, 5 Н, С Н );
5 5 5 5
5
4
5
5
+
2
2
1
4.45 (s, 2 Н, С Н Fc); 4.92 (s, 2 Н,
(С Н Fc), 74.4 (С Н ꢀipso Fc), 83.8
5 4 5 4
(С Н Cm), 83.9 (С Н Cm), 96.4
5 4 5 4
5
4
+
С Н Fc); 5.14 (s, 2 Н, С Н Cm);
5
4
5
4
5.56 (s, 2 Н, С Н Cm); 8.10 (s, 1 Н, N=СН); (С Н ꢀipso Cm), 140.3 (C=N),
5 4 5 4
(
100)
11.13 (s, 1 Н, NН)
165.9 (C=O)
Scheme 4

5
42
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kulikov et al.
Table 3. Main crystallographic parameters of ferrocenoyl hydrazones 4d,e,i
Parameter
4d
4e
4i
Molecular formula
C H ClFeN O
C H FeN O
C H FeN O
2
1
8
15
2
19 18
2
2
18 16
2
Molecular weight
366.62
362.20
348.18
Crystal system
Space group
Z
a/Å
b/Å
Monoclinic
C2/c
Tetragonal
Monoclinic
I4 /a
P2 /c
1
1
8
16
20.3940(18)
20.3940(18)
16.1314(16)
90.00
90.00
90.00
6709.3(14)
1.434
8
10.8381(10)
25.365(2)
12.0322(11)
90.00
115.197(2)
90.00
2993.0(5)
1.545
18.6516(6)
10.4699(4)
16.8929(6)
90.00
112.1510(10)
90.00
c/Å
α/deg
β/deg
γ/deg
V/Å3
dcalc/g cm
3055.37(19)
1.594
–
3
–
1
μ/cm
F(000)
θmax/deg
11.67
1504
60.34
9.12
3008
60.14
10.19
1440
62.24
2
Number of measured reflections
Number of independent reflections (Rint
Number of reflections with I > 2σ(I)
Number of refined parameters
R1
20041
4510 (0.0320)
3792
27983
4853 (0.1049)
3145
39112
9483 (0.1625)
5575
)
212
222
415
0.0667
0.1584
1.004
0.0290
0.0768
1.037
0.0497
0.1028
1.014
wR2
GOOF
Residual electron density
–
3
/
e Å (ρmax/ρmin)
0.454/–0.336
0.371/–0.430
0.737/–1.074
the ferrocene derivatives. The only exception is comꢀ
pound 4p since in this case the radical cation arisen
from the Cpꢀelimination is stabilized by complexꢀ
ation of the iron atom to the benzimidazole nitrogen
atom.aaa
Structures of compounds 4d,e,i were examined by Xꢀray
diffraction analysis (Fig. 1). The crystallographic paraꢀ
meters of the studied compounds are summarized in Table 3.
It is of note that compound 4i crystallizes in two isoforms.
In ferrocenoyl hydrazones 4d,e,i, the cyclopentadienyl
rings of the Cp fragment are nearly coplanar (the dihedral
angles between the Cp rings do not exceed 4.5°) (Table 4).
The ferrocene cyclopentadienyl rings are orientated very
close to the eclipsed configuration. The iron atom is slightly
closer to the substituted cyclopentadienyl ring.
1H NMR spectra of hydrazones 4a—r were recorded in
DMSOꢀd . The ferrocene protons resonate mainly in the
6
ranges of δ 4.00—4.20 and δ 4.20—4.50 for unsubstituted
and substituted Cp rings, respectively. The imine proton
signal appears in the δ 8.10—8.90 range, the amide proton
13
signals are observed in the δ 11.10—11.50 range. In C NMR
spectra, the ferrocene carbon atoms resonate in the range
of δ 68.5—73.5, the C=N carbon atoms are observed in
the δ 145.5—150.0 range, and the carbon C=O atoms are
found in the δ 165.0—167.0 range (see Table 2).
Antimicrobial activity. Antibacterial and antifungal
activities of ferrocenecaboxylic acid hydrazide 3 and its
hydrazones 4a—r (in concentrations of 400 mmol L–
1
)
were tested against Pseudomonas aeruginosa, Escherichia
coli, Staphylococcus aureus, Bacillus subtilis, Mycobacteriꢀ
Table 4. Main crystallographic parameters of the ferrocenyl fragment of hydrazones 4d,e,i
Parameter
4d
4e
4i*
Angle between planes Cp and CpR/deg
Ring conformation
d(Fe—Cp)/Å
2.08(6)
Eclipsed
1.652(1)
1.91(11)
Staggered
1.656(1)
4.48(16) [0.85(17)]
Eclipsed
1.651(2)
d(Fe—CpR)/Å
d(Fe—C)/Å
1.647(1)
2.040(1)—2.056(1)
1.648(1)
2.034(2)—2.061(3)
1.645(2) [1.650(2)]
2.029(3)—2.061(3),
2
.034(4)—2.064(4)
*
The data different for the second isoform are given in the square brackets.

Microwave synthesis of ferrocenoylhydrazones
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
543
С(1)
H(1)
N(2)
O(1)
С(5)
with the conventional method. This protocol can be of
interest for the synthesis of new ferroceneꢀcontaining
ligands, intermediates, and biologically active substances.
С(12)
С(13)
С(18)
С(16)
С(2)
С(17)
Сl(1)
N(1)
С(11)
Fe(1)
С(6)
С(4)
С(7)
Experimental
С(3)
С(14)
С(10)
С(9)
С(15)
Commercially available aldehydes (REAKHIM, Acros, and
SigmaꢀAldrich), hydrazine hydrate (REAKHIM), ferrocene,
anhydrous aluminum chloride (Acros Organics), gaseous carbon
dioxide (NII KM), and dry ice (Refrigerating plant No. 7,
Moscow) were used as purchased. All solvents were purified by
С(8)
4d
С(5)
С(1)
С(4)
С(3)
1
3
O(1)
the known procedures.
C(19)
For microwave irradiation, a household oven Samsung
Fe(1) С(11)
С(10)
С(17)
С(18)
С(13)
1
N(2)
CE2638NR (working frequency of 2.45 GHz) was used. H and
13
C NMR spectra were run on Bruker DRXꢀ300 and Bruker
С(2)
С(9)
С(6)
С(16) O(2)
С(15)
С(14)
DRXꢀ400 instruments at working frequencies of 300 MHz (comꢀ
N(1)
С(12)
H(1)
1
pounds 2, 3, and 4a—c,f,l) and 400 MHz (4d,e,g—k,m—r) ( H)
С(7)
13
or 100 MHz ( C) at 30 °C. Chemical shifts are given in the δ
С(8)
4e
scale relative to the residual solvent signal (DMSOꢀd ). Elecꢀ
6
tron impact mass spectrometry was performed with a Finnigan
Polaris Q instrument, the ion source temperature of 250 °C,
energy of ionizing electrons of 70 eV. IR spectra were recorded
with a URꢀ20 spectrophotometer in the KBr pellets. Melting
points were measured in sealed capillary tubes. The reaction
courses were monitored by TLC on the precoated Silufol UVꢀ254
plates. For column chromatography, Celite 545 (Biochem,
С(5)
С(4)
С(1)
С(2)
O(2)
С(15)
С(3)
С(14)
O(1)
С(16)
H(2)
N(2)
Fe(1)
N(1)
H(1)
40 mesh), neutral aluminum oxide (Brockmann Grade II, Reanal),
С(11)
С(13)
С(9)
С(8)
С(10) С(6)
С(17)
and Kieselgel 60 F254 (Merck) were used. Antimicrobial activiꢀ
ties of the synthesized compounds were determined by arag disc
С(12)
С(18)
С(7)
1
2
4
i
diffusion method.
Ferrocenecarboxylic acid (2). A 2 L autoclave (a plastic bottle)
Fig. 1. Xꢀray crystal structures of N´ꢀ(4ꢀchlorobenzylidene)ferroꢀ
cenecarbohydrazide (4d), N´ꢀ(4ꢀmethoxybenzylidene)ferroceneꢀ
carbohydrazide (4e), and N´ꢀ(2ꢀhydroxybenzylidene)ferroꢀ
cenecarbohydrazide (4i).
was charged with ferrocene (50.0 g, 0.269 mol), AlCl (43.0 g,
3
0
.326 mol), and toluene (150 mL). The autoclave was flushed
with CO , charged with dry ice (8.0 g), and tightly closed. The
2
reaction vessel was cooled with cold water with continuous shakꢀ
ing for 15 min and then kept at room temperature for 1 h. The
autoclave was opened, charged with additional portion of dry ice
um rubrum, and Candida albicans by the arag disc diffusion
method.12 Streptomycin (bacterial strains), amphotericin
B (C. albicans), and isoniazid (M. rubrum) were used as
the positive controls.
The synthesized compounds do not inhibit the growth
of the test strains, while positive controls show well deꢀ
fined zones of inhibition. Thus, the studied compounds
are of low toxicity against both prokaryotic bacterial strains
and eukaryotic C. Albicans, which is characteristic of the
ferrocene derivatives. Moreover, some compounds (3 and
(
6.0 g), tightly closed, cooled with cold water for 5 min at conꢀ
tinuous shaking, and then kept at room temperature for 1 h. The
reaction mixture was poured into a 1 L beaker, and the reaction
vessel was washed with toluene (2×150 mL). The resulting soluꢀ
tion was treated with crashed ice (300 g) and the mixture was
stirred for 20 min. An organic phase containing suspended
ferrocenecarboxylic acid 2 was separated. Compound 2 was
extracted from the organic solution with a 10% aqueous NaOH
solution (4×150 mL). The combined aqueous layers were filꢀ
tered through a Celite pad (d = 4.5 cm, h = 5.0 cm) and acidified
with concentrated hydrochloric acid to pH ≈ 3. The precipitate
was collected by filtration, washed with distilled water, dried in
air and then in a vacuum desiccator over CaCl2 to constant
weight. Yield 43.21 g (70%), yellow powder. M.p. 215—217 °C.
4
n,q) were consumed by the test strains (decolorization of
the filterꢀpaper discs impregnated with the compounds to
be tested) without formation of brown inorganic iron comꢀ
pounds, which is typical for the ferrocene derivatives. This
fact indicates that these compounds are easily penetrate
through the cell membranes and potentially can be inꢀ
volved in the cell metabolism.
In summary, the elaborated protocol for microwaveꢀ
assisted synthesis of ferrocenoyl hydrazones via condenꢀ
sation of ferrocenecarboxylic acid with carbonyl comꢀ
pounds is less timeꢀconsuming, solvent saving, gives high
yields of the target products with high purity as compared
+
+
MS (EI, 70 eV), m/z (Irel (%)): 230 [M] (100), 165 [M – Cp]
+
1
(
4
12), 138 [CpFeOH] (82). H NMR, δ: 4.21 (s, 5 H, C H );
5 5
.44 (s, 2 H, C H ); 4.70 (s, 2 H, C H ); 12.15 (s, 1 H, COOH).
5 4 5 4
Ferrocenecarboxylic acid hydrazide 3. The reaction was carꢀ
ried out under argon. A 250 mL threeꢀneck flask was successiveꢀ
ly charged with ferrocenecarboxylic acid 2 (10.0 g, 43.5 mmol),
anhydrous CH Cl2 (100 mL), and oxalyl chloride (5.6 mL,
2
6
5.2 mmol). The reaction mixture was stirred for 3 h and conꢀ
centrated in vacuo at 40 °C. The residue was dissolved in CH Cl
2
2
(50 mL) and the resulting solution was added dropwise to a stirred

5
44
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kulikov et al.
solution of hydrazine hydrate (5 mL, 102.9 mmol) and triethylꢀ
amine (14.3 mL, 102.9 mmol) in CH Cl (100 mL). After 1 h
(4d); CCDC 1495493 (4e); CCDC 1495492 (4i)) and are
available free of charge at deposit@ccdc.cam.ac.uk; http://
www.ccdc.cam.ac.uk.
2
2
stirring, the mixture was diluted with CH Cl2 (150 mL) and
2
washed with water (3×100 mL) and brine (100 mL). The organic
layer was dried with Na SO , filtered through a Celite pad
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos 14ꢀ03ꢀ31469
and 16ꢀ03ꢀ00881).
2
4
(
(
d = 2.0 cm, h = 1.5 cm), and concentrated in vacuo to give 10.0 g
94%) of compound 3, orange powder. Crystallization of the
i
crude product from Pr OH gave 7.75 g (73%) of pure 3, dark
orange crystals. M.p. 168—170 °C (from Pr OH). MS (EI,
7
1
i
References
+
+
0 eV), m/z (Irel (%)): 244 [M] (95), 213 [M – NHNH ] (100),
2
+
1
78 [M – Cp – H] (60). H NMR, δ: 4.17 (s, 5 H, C H ); 4.38
5
5
(
s, 2 H, C H ); 4.80 (s, 2 H, C H ); 9.22 (br.s, 1 H, CONH).
1. L. V. Snegur, V. N. Babin, A. A. Simenel, Yu. S. Nekrasov,
L. A. Ostrovskaya, N. S. Sergeeva, Russ. Chem. Bull., 2010,
59, 2167.
2. L. V. Snegur, A. A. Simenel, A. N. Rodionov, V. I. Boev,
Russ. Chem. Bull., 2014, 63, 26.
3. V. N. Babin, Yu. A. Belousov, V. I. Borisov, V. V. Gumenyuk,
Yu. S. Nekrasov, L. A. Ostrovskaya, I. K. Sviridova, N. S.
Sergeeva, A. A. Simenel, L. V. Snegur, Russ. Chem. Bull.,
2014, 63, 2405.
5
4
5
4
Synthesis of ferrocenoyl hydrazones 4a—r (general procedure).
Finely powdered hydrazide 3 (1.0 g, 4.1 mmol) and the correꢀ
sponding carbonyl compound (4.1 mmol) was thoroughly mixed in
a 20 mL vial. Solid aldehydes were finely powdered prior to use.
Then ethanol (3 mL) was added. The suspension was subjected
to microwave irradiation for 20—40 s at a power of 750 W. The
mixture was cooled to 5 °C, the precipitate formed was collected
by filtration, washed with cold ethanol (2×5 mL), and dried in
a vacuum desiccator over CaCl . This protocol was applied for the
4. A. N. Nesmeyanov, L. G. Bogomolova, I. G. Andrianova,
V. D. Vil´chevskaya, N. S. Kochetkova, Pharm. Chem. J.,
1972, 6, 269.
5. Bioorganometallics: Biomolecules, Labelling, Medicine, Ed. G.
Jaouen, WILEYꢀVCH Verlag GmbH & Co. KGaA, Weinꢀ
heim, 2006, 444 pp.
2
synthesis of the following compounds: N´ꢀbenzylideneferroceneꢀ
carbohydrazide (4a), N´ꢀ(4ꢀmethylbenzylidene)ferrocenecarboꢀ
hydrazide (4b), N´ꢀ(2ꢀchlorobenzylidene)ferrocenecarbohydrꢀ
azide (4c), N´ꢀ(4ꢀchlorobenzylidene)ferrocenecarbohydrazide
(
4d), N´ꢀ(4ꢀmethoxybenzylidene)ferrocenecarbohydrazide (4e),
N´ꢀ(3,4ꢀdimethoxybenzylidene)ferrocenecarbohydrazide (4f),
N´ꢀ(4ꢀhydroxyꢀ3ꢀmethoxybenzylidene)ferrocenecarbohydrazide
6. V. N. Kulikov, O. M. Nikitin, Yu. A. Borisov, A. S. Makarov,
A. N. Rodionov, R. S. Nikulin, L. V. Kovalenko, Yu. A.
Belousov, Russ. Chem. Bull., 2014, 63, 2255.
(
4g), N´ꢀ(3ꢀethoxyꢀ4ꢀhydroxybenzylidene)ferrocenecarbohydrꢀ
azide (4h), N´ꢀ(2ꢀhydroxybenzylidene)ferrocenecarbohydrazide
7. E. G. Perevalova, M. D. Reshetova, K. I. Grandberg, Zheleꢀ
zoorganicheskie soedineniya. Ferrotsen [Organoiron Comꢀ
pounds Ferrocene], Nauka, Moscow, 1983, 544 pp. (in Russian).
8. D. Wu, W. Huang, Z. Lin, Ch. Duan, Ch. He, Sh. Wu,
D. Wang, Inorg. Chem., 2008, 47, 7190.
(
(
4i), N´ꢀ(2,4ꢀdihydroxybenzylidene)ferrocenecarbohydrazide
4j), N´ꢀ(3ꢀnitrobenzylidene)ferrocenecarbohydrazide (4k),
N´ꢀ(4ꢀnitrobenzylidene)ferrocenecarbohydrazide (4l), N´ꢀ(4ꢀ
dimethylamino)benzylidene)ferrocenecarbohydrazide (4m),
(
N´ꢀ(pyridinꢀ4ꢀylmethylene)ferrocenecarbohydrazide (4n),
N´ꢀ(furanꢀ2ꢀylmethylene)ferrocenecarbohydrazide (4o), N´ꢀ[(1Hꢀ
benzo[d]imidazolꢀ2ꢀyl)methylene)ferrocenecarbohydrazide (4p),
N´ꢀ(3ꢀmethylbutylidene)ferrocenecarbohydrazide (4q), N´ꢀ(cyꢀ
mantrenylmethylene)ferrocenecarbohydrazide (4r).
Xꢀray diffraction analyses of compounds 4d,e,i were performed
with a Bruker APEX II diffractometer equipped with a CCD
detector. Single crystals suitable for Xꢀray diffraction studies were
obtained by slow evaporation of the saturated solutions of comꢀ
9. E. A. Raspopova, A. N. Morozov, L. D. Popov, I. N.
Shcherbakov, S. I. Levchenkov, V. A. Kogan, Russ. J. Gen.
Chem., 2012, 82, 131.
10. E. A. Raspopova, L. D. Popov, A. N. Morozov, I. N.
Shcherbakov, V. A. Kogan, S. I. Levchenkov, Russ. J. Gen.
Chem., 2008, 78, 1351.
11. T. Ito, N. Sugahara, Y. Kindaichi, Y. Takami, Nippon Kagaꢀ
ku Kaishi [J. Chem. Soc. Jpn.], 1976, 353 (in Japanese).
12. N. A. Semina, S. V. Sidorenko, S. P. Rezvan, S. A. Grudiniꢀ
na, L. S. Strachunskii, O. U. Stetsyuk, R. S. Kozlov, M. V.
Eidel´shtein, E. A. Ved´mina, E. A. Stolyarova, I. V. Vlasova,
Z. S. Sereda, Klin. mikrobiologiya i antimikrobnaya khimioꢀ
terapiya [Clinical Microbiology and Antimicrobial Chemoteraꢀ
phy], 2004, No. 6, 306 (in Russian).
13. L. F. Titze, Th. Eicher, Reaktionen und Synthesen im orgaꢀ
nischꢀchemischen Praktikum und Forschungslaboratorium,
2. Aufl., Georg Thieme Verlag, Stuttgart—New York, 1991,
672 S.
pounds 4d,e,i in CHCl —MeOH (1 : 1).
3
Structures were solved by a direct method and refined by
full matrix least squares in anisotropic approximation for nonꢀ
hydrogen atoms. Positions of the hydrogen atoms of the alkyl
and aryl moieties were calculated geometrically and refined
with the isotropic thermal parameters of U (H) = 1.2U (C),
eq
eq
1
.5Ueq(CMe) for the carbon atoms directly bonded to the
H atoms. The H atoms of the hydroxy and amide groups were
located by a difference Fourier synthesis and their thermal paraꢀ
meters were refined as above (U (H) = 1.2U (N), 1.5U (O)).
14. G. M. Sheldrick, Acta Crystallogr., Sect. C: Struct. Chem.,
2015, 71, 3.
eq
eq
eq
All computations were performed with a SHELXTLꢀ97 V.5.10
software.14
All atomic coordinates, temperature parameters, bond lengths,
and bond angles for the studied compounds were deposited with
a Cambridge Crystallographic Data Center (CCDC 1495491
Received June 14, 2016;
in revised form October 26, 2016