Reductive amination of ferrocenylformylpyrazoles

Article abstract of DOI:10.1007/s11172-010-0093-4

1-Aryl-3-ferrocenyl-4-formylpyrazoles were obtained from appropriate acetylferrocene arylhydrazones by the Vilsmeier-Haack reaction. Direct reductive amination of the resulting aldehydes with primary and secondary amines and amino acid esters in the prese

Full text of DOI:10.1007/s11172-010-0093-4

Russian Chemical Bulletin, International Edition, Vol. 59, No. 2, pp. 405—410, February, 2010
405
Reductive amination of ferrocenylformylpyrazoles
A. N. Rodionov,a A. A. Simenel,a Yu. S. Nekrasov,a V. V. Kachala,b E. Yu. Osipova,a and K. Ya. Zherebkera
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: alexsim@ineos.ac.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
1ꢀArylꢀ3ꢀferrocenylꢀ4ꢀformylpyrazoles were obtained from appropriate acetylferrocene
arylhydrazones by the Vilsmeier—Haack reaction. Direct reductive amination of the resulting
aldehydes with primary and secondary amines and amino acid esters in the presence of
NaBH(OAc)3 was studied.
Key words: acetylferrocene, the Vilsmeier—Haack reaction, pyrazoles, reductive amination,
sodium triacetoxyborohydride.
Scheme 1
Pyrazole derivatives exhibit a wide spectrum of pharꢀ
macological activity.1 Introduction of a ferrocenyl fragꢀ
ment into a heterocyclic molecule often imparts a new
biological activity to it or modifies its inherent activity.
For instance, ferroceneꢀcontaining pyrazoles have antibacꢀ
terial2 and antitumor effects in combination with low toxꢀ
icity3 and are plant growth regulators.4 In addition, optiꢀ
cally active ferrocenylpyrazole derivatives are suitable as
ligands in asymmetric catalysis and can catalyze hydrogeꢀ
nation, silylation, and cyanation of carbonyl compounds.5
In the present work, we studied direct reductive amiꢀ
nation of 1ꢀarylꢀ3ꢀferrocenylpyrazoleꢀ4ꢀcarbaldehydes in
reactions with primary and secondary aliphatic amines.
Ar = Ph (a), βꢀC10H7 (b)
Yield (%): 84 (2a), 65 (2b)
Results and Discussion
Aryl methyl ketones are easily accessible reagents for
the preparation of pyrazolecarbaldehydes. The synthesis
involves condensation of ketones with arylhydrazines folꢀ
lowed by intramolecular cyclization of the resulting
hydrazones under the conditions of the Vilsmeier—Haack
formylation (Scheme 1).
Reactions of acetylferrocene (1) with phenylꢀ and
βꢀnaphthylhydrazines gave the corresponding hydrazones
in high yields, which were used in roomꢀtemperature reꢀ
actions with three equivalents of the Vilsmeier—Haack
complex (DMF—POC13) in DMF. Upon hydrolysis of
the iminium salts with aqueous Na2CO3, the correspondꢀ
ing 1ꢀarylꢀ3ꢀferrocenylpyrazoleꢀ4ꢀcarbaldehydes 2a,b
were isolated in 84 and 65% yields, respectively.
respectively. These reactions are known as reductive amiꢀ
nation of carbonyl compounds or reductive alkylation of
amines and can be effected in direct and stepwise ways. In the
former case, a carbonyl compound and an amine are mixed
with an appropriate reducing agent without isolating an
intermediate imine or iminium salt. In the latter case, the
formation of an intermediate imine is followed by its reꢀ
duction. Secondary amines from pyrazolecarbaldehydes
were obtained in the second way with sodium borohydride
as a reducing agent,6 while direct reductive amination of
arylformylpyrazoles has not been implemented hitherto.
Using sodium borohydride as a reducing agent in diꢀ
rect reductive amination of 1ꢀarylꢀ3ꢀferrocenylpyrazoleꢀ
4ꢀcarbaldehydes in different solvents and at different temꢀ
peratures, we isolated the corresponding alcohols only.
Modification of sodium borohydride with the electronꢀ
withdrawing cyano or acetoxy group enhances the selecꢀ
Aldehydes and ketones react with ammonia and priꢀ
mary and secondary amines in the presence of reducing
agents to give primary, secondary, and tertiary amines,
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 397—402, February, 2010.
1066ꢀ5285/10/5902ꢀ0405 © 2010 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Rodionov et al.
Scheme 2
nylhydrazine, NaBH(OAc)3, and amines (Acros Organics) were
used as purchased. Amino acid methyl ester hydrochlorides
were prepared from amino acids and SOCl2 in methanol;8,9
βꢀnaphthylhydrazine hydrochloride was synthesized by diazoꢀ
tization of βꢀnaphthylamine with NaNO2 in conc. HCl followed
by reduction with SnCl2•2H2O in HCl (see Ref. 10).
3ꢀFerrocenylꢀ1ꢀphenylpyrazoleꢀ4ꢀcarbaldehyde (2a) was obꢀ
tained as described earlier.11 Yield 80%, m.p. 118 °C (cf. Ref. 11:
m.p. 118 °C). MS, m/z (Irel (%)): 386 [M]+ (100%). 1H NMR
(CDCl3, 500 MHz), δ: 4.15 (s, 5 H, Fc); 4.42, 5.96 (both s, 2 H
each, Fc); 7.37 (t, 1 H, CH, J = 7.5 Hz); 7.94 (m, 2 H, CH); 7.76
(d, 2 H, CH, J = 8 Hz); 8.44 (s, 1 H, CH); 10.32 (s, 1 H, CHO).
13C NMR (CDCl3, 125 MHz), δ: 69.4, 69.7, 69.8, 75.7, 119.4,
122.6, 127.6, 129.6, 131.4, 138.9, 153.7, 184.5.
3ꢀFerrocenylꢀ1ꢀ(2ꢀnaphthyl)pyrazoleꢀ4ꢀcarbaldehyde (2b)
Sodium methoxide (0.57 g, 10.6 mmol) was added to a solution
of acetylferrocene (2.28 g, 10.00 mmol) and βꢀnaphthylhydrazine
hydrochloride (1.95 g, 10.65 mmol) in ethanol (10 mL). The
reaction mixture was refluxed with stirring for 1 h and cooled to
room temperature. The precipitate that formed was filtered off,
washed with cold ethanol (10 mL), and dried in vacuo over CaCl2
for 1 h. The hydrazone obtained was dissolved in DMF (15 mL),
whereupon POCl3 (2.25 mL, 27.22 mmol) was added under arꢀ
gon. The reaction mixture was stirred at room temperature for
18 h, poured onto ice (30 g) with water (30 mL), and hydrolyzed
with a solution of Na2CO3 (40 g) in water (100 mL). The preꢀ
cipitate of aldehyde 2b that formed was filtered off, washed with
a large amount of water, and dried over Na2SO4. The product
was purified by column chromatography on SiO2 with benzene
tivity of the reducing agent. For instance, sodium triꢀ
acetoxyborohydride is successfully employed in the reducꢀ
tion of carbonyl compounds containing multiple carꢀ
bon—carbon bonds, cyano groups, and nitro groups, as
well as acetals and ketals. Moreover, this reagent selecꢀ
tively reduces aldehydes in the presence of ketones. The
selectivity of this reaction is due to steric and electronꢀ
withdrawing properties of three acetoxy groups stabilizing
the B—H bond.7 We used sodium triacetoxyborohydride
as a reducing agent in reductive amination of 1ꢀarylꢀ3ꢀ
ferrocenylpyrazoleꢀ4ꢀcarbaldehydes. The reactions with
various sterically unhindered primary and secondary (cyꢀ
clic and acyclic) amines afforded the target products in
30—90% yields (Table 1, Scheme 2). Alcohols occasionꢀ
ally formed as byꢀproducts were separated by column chroꢀ
matography. With the sterically hindered diisopropylꢀ
amine, the major reaction product is the corresponding
alcohol (see Scheme 2).
Experimental
1
H and 13C NMR spectra were recorded on a Bruker
DRXꢀ500 spectrometer (500.13 and 125.76 MHz, respectively)
in CDCl3 and DMSOꢀd6. Mass spectra were measured on
a Finnigan Polaris Q spectrometer (electron ionizing energy 70 eV,
ionization chamber temperature 250 °C). Acetylferrocene, pheꢀ

Reductive amination of ferrocenylformylpyrazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
407
Table 1. 4ꢀHydroxymethylꢀ (3a,b) and 4ꢀaminomethylꢀ1ꢀarylꢀ3ꢀferrocenylpyrazoles (4a,b—15a,b)
Amine
Product Yield
(%)
M.p./°C
Found
Calculated
Molecular
formula
(%)
C
H
N
Diisopropylamine
3a
3b
92a
90a
118—119
136—137
66.98
67.06
70.64
70.60
—
5.04
5.06
4.98
4.94
—
7.80 C20H18FeN2O
7.82
6.85 C24H20FeN2O
6.86
nꢀButylamine
tꢀButylamine
Benzylamine
Dipropylamine
4a
4b
75b
60
147—148
55—56
—
—
72.63
72.57
6.30
6.31
9.10
C28H29FeN3
9.07
—
c
c
c
c
5a
5b
58
55
162—163
171—172
—
—
—
72.59
72.57
72.51
72.49
—
70.73
70.75
73.27
73.32
67.52
67.46
70.43
70.45
—
6.28
6.31
5.60
5.63
—
7.10
7.08
6.73
6.77
5.94
5.90
5.73
5.70
—
9.10
9.07
9.42
9.39
C28H29FeN3
6a
45
102—103
C27H25FeN3
6b
7a
58b
65
131—132d
Oil
—
—
9.47
9.53
8.50
8.55
C26H31FeN3
7b
8a
8b
65
65
67
Oil
C30H33FeN3
Morpholine
169—170d
145—146
9.75 C24H25FeN3O
9.83
8.76 C28H27FeN3O
8.80
Piperidine
9a
9b
10a
10b
44b
33b
81
45—46d
120d
173—174
182—184d
—
—
—
—
—
—
—
c
c
c
c
4ꢀMethylpiperidine
—
—
—
73
73.73
73.62
—
6.43
6.38
—
8.54
8.59
C30H31FeN3
4ꢀBocꢀAminopiperidine
11a
11b
12a
54b
30b
67
141—142
104—105d
140—142
—
—
—
—
—
—
1ꢀMethylpiperazine
68.23
68.19
71.00
71.02
70.15
70.08
72.96
72.89
64.25
64.35
—
6.38
6.41
6.20
6.17
6.08
6.13
5.95
5.90
5.38
5.40
—
12.70
12.72
11.45
11.42
10.21
10.22
9.04
C25H28FeN4
12b
13a
13b
14a
50
45
64
90
147—148d
78—79
91—92
102
C29H30FeN4
C24H25FeN3
C28H27FeN3
Pyrrolidine
9.11
Glycine methyl ester
Proline methyl ester
9.80 C23H23FeN3O2
9.79
14b
15a
36b
80
133—134d
140
—
—
8.90 C26H27FeN3O2
8.95
66.51
66.53
69.40
69.37
5.85
5.80
5.58
5.63
15b
38
122—123
8.11 C30H29FeN3O2
8.09
a An alcohol was isolated.
b Isolated as hydrochloride. No satisfactory elemental analysis data were obtained. The structure was deterꢀ
mined from NMR and mass spectra.
c The highꢀresolution mass spectrum was recorded (see Table 2).
d Decomposes when melting.
as an eluent. The yield was 2.63 g (65%), m.p. 190—192 °C.
Found (%): C, 70.69; H, 4.44; Fe, 13.50. C24H18FeN2O. Calcuꢀ
lated (%): C, 70.90; H, 4.43; Fe, 13.79. MS, m/z (Irel (%)): 406
[M]+ (100%). 1H NMR (CDCl3), δ: 4.23 (s, 5 H, Fc); 4.50, 5.04
(both s, 2 H each, Fc); 7.62 (m, 2 H, Ar); 7.95 (m, 4 H, Ar); 8.28
(s, 1 H, Ar); 8.65 (s, 1 H, Pz); 10.41 (s, 1 H, CHO). 13C NMR
(CDCl3), δ: 69.1, 69.4, 70.0, 76.2, 117.7, 118.6, 123.2, 127.0,
127.7, 128.3, 130.2, 132.1, 132.8, 133.8, 136.8, 142.4, 185.0.

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Rodionov et al.
Table 2. Spectroscopic data for compounds 3a—15a
Proꢀ
duct
MS
(EI, 70 eV),
m/z (Irel (%))
1H NMR
(solvent, δ, J/Hz)
13C NMR
(solvent, δ)
3a
4a
358 [M]+ (100)
CDCl3: 2.02 (br.s, 1 H, OH); 4.14 (s, 5 H, Fc); 4.36, 4.89 (both s,
2 H each, Fc); 4.85 (s, 2 H, CH2); 7.29 (t, 1 H, Ar, J = 7.0); 7.47
(m, 2 H, Ar); 7.73 (d, 2 H, Ar, J = 8.0); 7.89 (s, 1 H, Pz)
CDCl3: 56.1, 67.4, 68.8, 69.4,
77.6, 118.7, 120.5, 126.0, 127.0,
129.4, 140.0, 150.1
413 [M]+ (100)
CDCl3: 0.99 (t, 3 H, CH3, J = 7.5); 1.44 (m, 2 H, CH2); 1.63 (m,
2 H, CH2); 2.29 (br.s, 1 H, NH); 2.82 (t, 2 H, CH2, J = 7.0);
3.98 (s, 2 H, CH2); 4.15 (s, 5 H, Fc); 4.35, 4.84 (both s, 2 H each,
Fc); 7.27 (t, 1 H, Ar, J = 7.0); 7.46 (m, 2 H, Ar); 7.75 (d, 2 H, Ar,
J = 8.0); 7.95 (s, 1 H, Pz)
CDCl3: 14.0, 20.5, 32.1, 44.2,
49.5, 67.3, 68.6, 69.4, 78.3,
118.5, 119.5, 125.7, 126.6,
129.3, 140.1, 149.7
5a
Found:
DMSOꢀd6: 1.39 (s, 9 H, CH3); 3.45 (br.s, 1 H, NH); 4.05 (s, 2 H,
CH2); 4.11 (s, 5 H, Fc); 4.31, 4.75 (both s, 2 H each, Fc); 7.26 (t,
1 H, Ar, J = 7.0); 7.47 (m, 2 H, Ar); 7.78 (d, 2 H, Ar, J = 8.0);
8.72 (s, 1 H, Pz)
DMSOꢀd6: 26.7, 35.8, 39.5, 67.2,
68.1, 68.8, 77.5, 95.5, 117.6,
125.4, 128.8, 129.1, 139.4, 149.1
413.1498 [M]+
C24H27FeN3
Calculated:
M = 413.1554
6a
447 [M]+ (100)
441 [M]+ (80)
427 [M]+ (100)
425 [M]+ (100)
CDCl3: 3.85 (s, 2 H, CH2); 3.98 (s, 2 H, CH2); 4.04 (s, 5 H, Fc);
4.28, 4.52 (both s, 2 H each, Fc); 7.24—7.45 (m, 8 H, Ar); 7.72—7.74 69.3, 77.2, 113.1, 118.7, 126.2,
(m, 2 H, Ar); 8.30 (s, 1 H, Pz)
CDCl3: 40.8, 50.7, 67.6, 68.7,
128.6, 128.8, 129.0, 129.3, 129.7,
133.0, 139.7, 150.1
7a
CDCl3: 0.94 (m, 6 H, CH3); 1.18 (m, 4 H, CH2); 2.55 (m, 4 H,
CH2); 3.72 (s, 2 H, CH2); 4.21 (s, 5 H, Fc); 4.37, 4.94 (both s,
2 H each, Fc); 7.22 (t, 1 H, Ar, J = 8.0); 7.41 (m, 2 H, Ar); 7.71 (d,
2 H, Ar, J = 8.0); 8.09 (s, 1 H, Pz)
CDCl3: 12.0, 20.0, 49.5, 56.1,
67.3, 68.6, 68.9, 77.6, 118.7,
126.2, 128.6, 129.7, 137.0,
139.7, 150.5
8a
CDCl3: 2.64 (m, 4 H, CH2); 3.68 (s, 2 H, CH2); 3.82 (m, 4 H,
CH2); 4.16 (s, 5 H, Fc); 4.35, 4.97 (both s, 2 H each, Fc); 7.28 (t,
1 H, Ar, J = 6.5); 7.47 (m, 2 H, Ar); 7.76 (d, 2 H, Ar, J = 7.0);
7.91 (s, 1 H, Pz)
CDCl3: 52.9, 53.4, 66.7, 67.7,
68.5, 69.2, 78.1, 118.3, 125.7,
127.8, 129.2, 139.9, 150.7
9a
CDCl3: 1.51 (m, 2 H, CH2); 1.68 (m, 4 H, 2 CH2); 2.56 (m, 4 H,
2 CH2); 3.62 (s, 2 H, CH2); 4.14 (s, 5 H, Fc); 4.32, 4.94 (both s,
2 H each, Fc); 7.26 (t, 1 H, Ar, J = 7.5); 7.45 (m, 2 H, Ar); 7.75
(d, 2 H, Ar, J = 8.0); 7.90 (s, 1 H, Pz)
CDCl3: 24.9, 26.4, 53.8, 55.0,
68.3, 69.2, 69.8, 78.9, 118.9,
126.1, 128.2, 129.8, 140.6, 151.2
10a
Found:
CDCl3: 0.96 (d, 3 H, CH3, J = 6.5); 1.35 (m, 2 H, 2 CH2(ax));
1.44 (m, 1 H, CH); 1.67 (d, 2 H, 2 CH2(eq), J = 12.0); 2.05 (t,
2 H, 2 CH2(ax), J = 11.0); 3.05 (d, 2 H, 2 CH2(eq), J = 11.5);
3.62 (s, 2 H, CH2); 4.13 (s, 5 H, Fc); 4.32, 4.93 (both s, 2 H each,
Fc); 7.24 (t, 1 H, Ar, J = 7.5); 7.45 (m, 2 H, Ar); 7.73 (d, 2 H,
Ar, J = 7.5); 7.87 (s, 1 H, Pz)
CDCl3: 22.3, 31.4, 34.8, 53.5,
54.5, 68.3, 69.0, 69.7, 78.9,
118.9, 119.1, 126.1, 128.1,
129.8, 140.5, 151.1
439.1688 [M]+
C26H29FeN3
Calculated:
M = 439.1711
11a
540 [M]+ (70)
DMSOꢀd6: 1.47 (s, 9 H, 3 CH3); 1.50 (m, 2 H, CH2); 1.97 (d,
1 H, CH2, J = 11.5); 2.18 (t, 1 H, CH2, J = 11.0); 2.97—2.99
(m, 1 H, CH2); 3.54 (m, 1 H, CH); 3.59 (s, 2 H, CH2); 4.11 (s,
DMSOꢀd6: 28.4, 32.7, 47.9, 48.4,
52.3, 52.7, 67.8, 68.5, 69.2, 78.3,
118.4, 125.7, 127.6, 129.1, 129.3,
5 H, Fc); 4.31, 4.94 (both s, 2 H each, Fc); 7.25 (t, 1 H, Ar, J = 7.0); 140.1, 150.1, 155.2
7.45 (m, 2 H, Ar); 7.73 (d, 2 H, Ar, J = 8.0); 7.81 (s, 1 H, Pz)
12a
13а
14a
440 [M]+ (100)
411 [M]+ (100)
429 [M]+ (100)
CDCl3: 2.36 (s, 3 H, CH3); 2.58—2.69 (m, 8 H); 3.63 (s, 2 H,
CH2); 4.11 (s, 5 H, Fc); 4.30, 4.93 (both s, 2 H each, Fc); 7.24 (t,
1 H, Ar, J = 7.2); 7.44 (m, 2 H, Ar); 7.71 (d, 2 H, Ar, J = 7.5);
7.82 (s, 1 H, Pz)
CDCl3: 45.7, 52.5, 52.7, 55.0,
67.7, 68.6, 69.2, 78.2, 117.3,
118.4, 125.7, 127.7, 129.3,
140.0, 150.8
CDCl3: 1.92 (m, 4 H, 2 CH2); 2.76 (m, 4 H, 2 CH2); 3.88 (s, 2 H,
CH2); 4.18 (s, 5 H, Fc); 4.37, 4.92 (both s, 2 H each, Fc); 7.30 (t,
1 H, Ar, J = 7.1); 7.50 (m, 2 H, Ar); 7.78 (d, 2 H, Ar, J = 7.8);
8.03 (s, 1 H, Pz)
CDCl3: 23.6, 50.1, 54.2, 67.8,
68.6, 69.4, 78.6, 118.5, 125.8,
127.4, 129.4, 129.7, 140.1, 150.1
CDCl3: 3.64 (s, 2 H, CH2); 3.77 (s, 3 H, CH3); 4.13 (s, 2 H,
CH2); 4.17 (s, 5 H, Fc); 4.33, 4.82 (both s, 2 H each, Fc); 7.28
(t, 1 H, Ar, J = 7.5); 7.45 (m, 2 H, Ar); 7.75 (d, 2 H, Ar, J = 8.0);
8.12 (s, 1 H, CH)
CDCl3: 42.9, 48.9, 52.1, 67.6,
68.8, 69.4, 77.9, 116.9, 118.6,
125.9, 127.6, 129.3, 139.9,
150.1, 171.4
(to be continued)

Reductive amination of ferrocenylformylpyrazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
409
Table 2 (continued)
Proꢀ
duct
MS
(EI, 70 eV),
m/z (Irel (%))
1H NMR
(solvent, δ, J/Hz)
13C NMR
(solvent, δ)
15a
469 [M]+ (100)
CDCl3: 1.92—2.09 (m, 3 H); 2.21—2.32 (m, 1 H); 2.54—2.63 (m,
1 H); 3.22—3.27 (m, 1 H); 3.38—3.43 (m, 1 H); 3.75 (s, 3 H, CH3);
3.81 (d, 1 H, CH2, J = 13.5); 4.08 (d, 1 H, CH2, J = 13.5); 4.17
CDCl3: 21.9, 28.3, 47.0, 47.1,
52.8, 64.0, 66.7, 68.5, 69.2,
111.2, 118.4, 126.0, 129.0,
(s, 5 H, Fc); 4.36 (s, 2 H, Fc); 4.95, 4.98 (both s, 1 H each, Fc); 7.28 130.2, 139.0, 150.2, 167.0
(t, 1 H, Ar, J = 7.5); 7.48—7.53 (m, 2 H, Ar); 7.76 (d, 2 H, Ar,
J = 7.8); 7.92 (s, 1 H, Pz)
Table 3. Spectroscopic data for compounds 3b—15b
Proꢀ
duct
MS
(EI, 70 eV),
m/z (Irel (%))
1H NMR
(solvent, δ, J/Hz)
13C NMR
(solvent, δ)
3b
4b
408 [M]+ (100) CDCl3: 4.18 (s, 5 H, Fc); 4.38, 4.93 (both s, 2 H both, Fc); 4.89 CDCl3: 56.2, 67.4, 68.9, 69.4, 77.7, 115.6,
(s, 2 H, CH2); 7.45—7.58 (m, 2 H, Ar); 7.87—7.97 (m, 4 H, Ar); 118.2, 121.2, 125.7, 126.9, 127.3, 127.8,
8.05(s, 1 H, Ar); 8.12 (s, 1 H, Pz)
127.9, 129.4, 131.7, 133.7, 137.4, 150.6
463 [M]+ (100) CDCl3: 0.86 (m, 3 H, CH3); 1.32 (m, 2 H, CH2); 1.63 (m, 2 H, CDCl3: 13.9, 20.6, 32.1, 44.1, 49.5, 67.3,
CH2); 2.89 (m, 2 H, CH2); 3.48 (s, 2 H, CH2); 4.24 (s, 5 H, Fc); 68.5, 69.3, 78.3, 96.4, 117.9, 118.4,
4.42, 4.83 (both s, 2 H both, Fc); 7.50—7.59 (m, 2 H, Ar);
7.87—7.99 (m, 5 H, Ar); 8.15 (s, 1 H, Pz)
120.0, 125.7, 126.6, 127.2, 127.6, 128.1,
131.4, 133.8, 139.3, 149.2
5b
6b
7b
8b
9b
463 [M]+ (100) CDCl3: 1.36 (s, 9 H, CH3); 2.49 (br.s, 1 H, NH); 4.09
CDCl3: 26.6, 35.9, 39.5, 67.3, 68.1, 68.6,
(s, 2 H, CH2); 4.22 (s, 5 H, Fc); 4.39, 4.87 (both s, 2 H both, Fc); 77.5, 95.5, 117.6, 118.2, 120.7, 125.5,
7.49—7.60 (m, 2 H, Ar); 7.89—7.97 (m, 4 H, Ar); 8.17
(s, 1 H, Ar); 8.39 (s, 1 H, Pz)
126.5, 127.3, 127.8, 128.1, 131.4,
133.7, 139.3, 149.2
497 [M]+ (100) CDCl3: 1.92 (br.s, 1 H, NH); 4.01 (s, 2 H, CH2); 4.03
CDCl3: 43.6, 53.9, 67.3, 68.7, 69.4, 78.1,
(s, 2 H, CH2); 4.10 (s, 5 H, Fc); 4.35, 4.86 (both s, 2 H both, Fc); 115.3, 118.2, 119.9, 125.5, 126.9, 127.0,
7.27—7.56 (m, 7 H, Ar) 7.87—7.95 (m, 4 H, Ar);
8.05 (s, 1 H, CH, Ar); 8.15 (s, 1 H, Pz)
127.2, 127.8, 128.2, 128.4, 128.6, 129.4,
131.5, 133.7, 137.5, 140.2, 150.1
491 [M]+ (84) CDCl3: 0.95 (m, 6 H, 2 CH3); 1.16 (m, 4 H, 2 CH2);
2.57 (m, 4 H, 2 CH2); 3.77 (s, 2 H, CH2); 4.17 (s, 5 H, Fc);
4.35, 4.92 (both s, 2 H both, Fc); 7.48—7.53 (m, 2 H, Ar);
7.87—8.08 (m, 5 H, Ar); 8.14 (s, 1 H, Pz)
477 [M]+ (100) CDCl3: 2.66 (m, 4 H, CH2); 3.70 (s, 2 H, CH2); 3.83 (m, 4 H,
CH2); 4.18 (s, 5 H, Fc); 4.38, 5.05 (both s, 2 H both, Fc);
7.48—7.59 (m, 2 H, Ar); 7.89—8.01 (m, 5 H, Ar);
8.16 (s, 1 H, Pz)
CDCl3: 12.1, 20.0, 49.6, 56.1, 67.4, 68.6,
68.9, 77.6, 115.2, 115.5, 118.2, 120.8,
125.5, 126.9, 127.3, 127.8, 128.4, 131.5,
133.6, 137.3, 150.6
CDCl3: 52.9, 53.4, 66.8, 67.7, 68.5, 69.2,
78.1, 115.3, 118.2, 125.5, 126.9, 127.8,
127.8, 128.1, 129.3, 129.5, 131.6, 133.7,
137.3, 150.1
475 [M]+ (100) CDCl3: 1.53 (m, 2 H, CH2); 1.71 (m, 4 H, 4 CH); 2.61 (m, 4 H, CDCl3: 22.7, 24.3, 29.4, 53.3, 54.5, 67.9,
4 CH); 3.68 (s, 2 H, CH2); 4.16 (s, 5 H, Fc); 4.34
(s, 2 H, Fc); 4.95 (s, 2 H, Fc); 7.47—7.55 (m, 2 H, Ar); 7.86
(d, 1 H, Ar, J = 8); 7.90 (d, 1 H, Ar, J = 8); 7.92—7.97
(m, 2 H, Ar); 8.08 (s, 1 H, Ar); 8.14 (s, 1 H, Pz)
68.7, 69.4, 78.3, 115.3, 118.2, 125.5,
126.8, 127.8, 127.9, 128.2, 129.4, 130.0,
131.5, 133.7, 137.5, 151.0
10b 489 [M]+ (100) CDCl3: 0.99 (d, 3 H, CH3, J = 6.5); 1.38 (m, 2 H, CH2(ax));
CDCl3: 21.9, 31.0, 34.5, 53.2, 54.2, 67.9,
68.6, 69.3, 78.5, 115.2, 118.3, 125.5,
126.8, 127.3, 127.8, 127.9, 129.3, 129.5,
1.47 (m, 1 H, CH); 1.70 (d, 1 H, CH2(eq); J = 12.5); 2.09
(t, 1 H, CH2(ax); J = 11); 3.10 (d, 2 H, CH2(eq); J = 11); 3.66
(s, 2 H, CH2); 4.17 (s, 5 H, Fc); 4.35, 4.99 (both s, 2 H both, Fc); 131.6, 133.8, 137.7, 151.0
7.47—7.57 (m, 2 H, Ar); 7.87—7.99 (m, 4 H, Ar); 8.00
(s, 1 H, Ar); 8.14 (s, 1 H, Pz)
11b 590 [M]+ (35) CDCl3: 1.46 (s, 9 H, 3 CH3); 1.53 (m, 2 H, CH2); 1.99 (d, H,
CDCl3: 28.5, 29.7, 32.5, 47.8, 52.4, 52.6,
CH2, J = 11.5); 2.23 (m, 1 H, CH2); 3.04—3.05 (m, 1 H, CH2); 67.8, 68.7, 69.3, 78.2, 115.3, 118.2, 125.5,
3.56—3.58 (m, 1 H, CH); 3.66 (s, 2 H, CH2); 4.14 (s, 5 H,
Fc); 4.34, 4.95 (both s, 2 H both, Fc); 7.47—7.53 (m, 1 H, Ar);
7.85 (d, 1 H, Ar, J = 8); 7.89 (d, 1 H, Ar, J = 8); 7.91—7.96
(m, 2 H, Ar); 8.00 (s, 1 H, Ar); 8.12 (s, 1 H, Pz)
126.9, 127.8, 127.9, 128.1, 129.4, 129.5,
131.5, 133.7, 137.4, 151.0, 155.2
(to be continued)

410
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Rodionov et al.
Table 3 (continued)
Proꢀ
duct
MS
(EI, 70 eV),
m/z (Irel (%))
1H NMR
(solvent, δ, J/Hz)
13C NMR
(solvent, δ)
12b 490 [M]+ (100) CDCl3: 2.40 (s, 3 H, CH3); 2.64—2.72 (m, 8 H); 3.70 (s, 2 H,
CH2); 4.14 (s, 5 H, Fc); 4.34, 4.98 (both s, 2 H both, Fc);
7.47—7.55 (m, 2 H, Ar); 7.85—7.98 (m, 5 H, Ar);
8.12 (s, 1 H, Pz)
CDCl3: 45.7, 52.6, 52.6, 55.0, 67.8, 68.6,
69.3, 78.2, 115.3, 117.5, 118.2, 125.5,
126.9, 127.8, 127.8, 128.0, 129.4, 131.5,
133.7, 137.5, 151.1
13b 461 [M]+ (100) CDCl3: 1.97 (m, 4 H, CH2); 2.98 (m, 4 H, CH2); 3.88
CDCl3: 23.4, 49.1, 53.2, 68.0, 68.7, 69.5,
115.7, 118.2, 125.7, 126.9, 127.8, 127.9,
(s, 2 H, CH2); 4.09 (s, 5 H, Fc); 4.36, 4.77 (both s,
2 H both, Fc); 7.46—7.56 (m, 2 H, Ar); 7.86—8.00 (m, 5 H, Ar); 128.0, 129.4, 131.8, 133.7, 149.8
8.17 (s, 1 H, Pz)
14b 479 [M]+ (100) CDCl3: 3.63 (s, 2 H, CH2); 3.77 (s, 3 H, CH3); 4.06 (s, 2 H,
CDCl3: 43.5, 49.8, 52.0, 67.4, 68.8, 69.4,
77.9, 115.4, 118.2, 118.6, 125.6, 126.9,
127.3, 127.8, 127.9, 129.4, 131.6, 133.7,
137.4, 150.2, 172.5
CH2); 4.15 (s, 5 H, Fc); 4.36, 4.87 (both s, 2 H both, Fc);
7.47—7.53 (t, 2 H, Ar); 7.85—7.93 (m, 4 H, Ar); 8.11 (s, 1 H,
Ar); 8.13 (s, 1 H, Pz)
15b 519 [M]+ (92) CDCl3: 1.88—2.17 (m, 3 H); 2.54—2.62 (m, 1 H); 3.16—2.27
CDCl3: 29.4, 43.5, 49.8, 52.0, 67.3, 67.4,
(m, 1 H); 3.38—3.42 (m, 1 H); 3.71 (s, 3 H, CH3); 3.81 (d, 1 H, 67.6, 68.8, 68.9, 115.4, 118.2, 118.6,
CH2, J = 13.5); 4.08 (d, 1 H, CH2, J = 13.5); 4.14 (s, 5 H, Fc); 125.6, 125.6, 126.9, 127.3, 127.8, 127.9,
4.34, 4.94 (both m, 2 H both, Fc); 7.45—7.55 (m, 2 H, Ar);
7.85—7.94 (m, 4 H, Ar); 8.02 (s, 1 H, Ar); 8.13 (s, 1 H, Pz)
129.4, 131.6, 133.7, 137.4, 150.2, 172.5
Reductive amination of ferrocenylformylpyrazoles (general
procedure). A solution of ferrocenylpyrazoleꢀ4ꢀcarbaldehyde 2a
or 2b (0.5 mmol) and an amine (0.75 mmol) in 1,2ꢀdichloroꢀ
ethane (35 mL) was stirred at room temperature for 1 h. Sodium
triacetoxyborohydride (0.16 g, 0.75 mmol) was added and the
reaction mixture was refluxed for 30 min and decomposed with
aqueous NaHCO3. The product was extracted with CH2Cl2
(2×30 mL). The organic fractions were washed with brine and
dried over Na2SO4. The solvent was removed in a water aspiraꢀ
tor vacuum and the residue was chromatographed on silica gel
(CHCl3—MeOH, 9 : 1). The spectroscopic and elemental analyꢀ
sis data for the compounds obtained are given in Table 1. Their
1H and 13C NMR and mass spectra are given in Tables 2 and 3.
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This work was financially supported by the Presidium
of the Russian Academy of Sciences (Programs "Support
of Young Scientists" and "Basic Sciences to Medicine"),
the Division of Chemistry and Materials Science of the
Russian Academy of Sciences (Program OKhꢀ10), and
the Russian Foundation for Basic Research (Project
No. 09ꢀ03ꢀ00535).
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Synlett., 2006, 16, 2581.
References
1. A. R. Katritzky, Comprehensive Heterocyclic Chemistry III,
Received December 12, 2008;
Elsevier, 2008, Vol. 4, p. 1.
in revised form December 22, 2009