Reaction of arylhydrazines with an α-alkynyl-carbonylic compound: an unexpected hydration reaction

Article abstract of DOI:10.1016/j.tetlet.2008.03.022

The acid catalyzed reactions of three arylhydrazines with 4-phenyl-3-butynone in order to obtain the corresponding arylhydrazone were realized. The arylhydrazone reaction and an unexpected alkyne hydration reaction product were obtained when diphenylhydrazine was used. This product was identified by spectroscopic methods and X-ray diffractogram. A reaction mechanism is proposed for its formation.

Full text of DOI:10.1016/j.tetlet.2008.03.022

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2942–2945
Reaction of arylhydrazines with an a-alkynyl-carbonylic
compound: an unexpected hydration reaction
a
a
a
´
´
´
Eugenia Josefina Aldeco-Perez , Cecilio Alvarez-Toledano , Alfredo Toscano ,
b
b,
*
´
´
Jose Guadalupe Garcıa-Estrada , Jose Guillermo Penieres-Carrillo
a Instituto de Quı´mica-UNAM, Circuito Exterior-Ciudad Universitaria, Coyoaca´n, Me´xico D.F., C.P. 04510, Mexico
b Facultad de Estudios Superiores Cuautitla´n-UNAM. Seccio´n de Quı´mica Orga´nica, Campo 1, Avenida 1 de mayo s/n,
Cuautitla´n Izcalli, C.P. 54740, Estado de Me´xico, Mexico
Received 13 November 2007; revised 5 March 2008; accepted 5 March 2008
Available online 8 March 2008
Abstract
The acid catalyzed reactions of three arylhydrazines with 4-phenyl-3-butynone in order to obtain the corresponding arylhydrazone
were realized. The arylhydrazone reaction and an unexpected alkyne hydration reaction product were obtained when diphenylhydrazine
was used. This product was identified by spectroscopic methods and X-ray diffractogram. A reaction mechanism is proposed for its
formation.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Arylhydrazines; a-Alkynyl-carbonylic compound; Hydration reaction
1. Introduction
either complexes with several metal compounds or dinucle-
ar compounds.6
Primary and secondary arylhydrazines react with
carbonylic compounds (i.e., aldehydes and ketones) by
standard procedures to yield arylhydrazones. Recently, it
has been reported the synthesis of hydrazones in aqueous
medium using microwaves.1 N-Arylhydrazones are usually
solids and their melting points can be used to identify the
parent carbonyl compounds. Mono- and diarylhydrazones
are also used in organic syntheses to form several hetero-
cyclic compound derivatives, such as pyrrolidione and
indole,2 1,2,4-triazolo[4,3-a]pyrimidine,3 thiazolone, and
oxathiolone.4 For more than a century, it has been known
that hydrazines readily react with acetylenic ketones to
directly afford pyrazoles.5 Moreover, a,b-unsaturated
hydrazone compounds have been used as ligands to form
We herein present the results obtained for the reaction
of 4-phenyl-3-butynone with hydrazine derivatives, in
order to synthesize the corresponding hydrazone com-
pound, where we found that the reaction with N,N-di-
phenylamine results in an unexpected alkyne hydration
reaction in the corresponding hydrazone.
2. Results and discussion
The reaction time, yield, and some physical characteris-
tics for the obtained products are listed in Table 1, and the
overall reaction is outlined in Scheme 1.
Table 1
Results obtained for the reaction of 1.0 with arylhydrazines
Entry
Reaction time (h)
Color/mp (°C)
Yield (%)
1.1
1.2
1.3
2
3
4
Yellow liquid/—
Orange solid/173
Yellow crystals/116
24.4
75.7
70.2
*
Corresponding author. Tel.: +52 55 56 23 20 24; fax: +52 55 56 23 20
56.
E-mail address: peniers@servidor.unam.mx (J. G. Penieres-Carrillo).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.022

E. J. Aldeco-Pe´rez et al. / Tetrahedron Letters 49 (2008) 2942–2945
2943
11
12
spectrum, the molecular ion at m/z 328 corresponds to
the molecular formula C22H20N2O and a molecular weight
of 328 g/mol.
10
9
7
6
N N
8
3
4
PhNHNH2
H
2
5
1
1.1
An appropriate single crystal of this compound was
obtained, and then used to collect X-ray intensity data
on a Siemens P4/PC diffractometer. An ORTEP-like
diagram,8 Figure 1,9 shows the molecular geometry, the
thermal ellipsoids (35%), and the numbering scheme.
Selected bond distances and angles are listed in Table 2.
Thus, if it is assumed that the first reaction step in form-
ing this compound is the generation of the corresponding
arylhydrazone, as is shown in the reaction mechanism pro-
posed, Scheme 2, the next reaction step is presumably the
formation of a vinyl-benzylic carbocation that reacts with
water to produce the hydration reaction product of the
alkyne function. This last step must necessarily proceed
from the more stable vinyl-benzylic intermediate shown.
If it is considered that the hydration reaction could take
place for both the phenylhydrazine and 2,4-dinitrophenyl-
hydrazine reactions, then a vinyl-benzylic carbocation
equivalent to that formed for the generation of 1.3, would
have to form for each of those reactions. Therefore, we
realized a molecular dynamics computational study,10 in
order to calculate the activation energy for the vinyl-ben-
zylic carbocation formation, for the three presented reac-
tions. The calculated values are given in Table 3. These
computational results reveal that the intermediate for the
NO2
11
12
13
O2N 10
9
14
O
7
6
2,4-DNPH
Ph2NNH2
N N
8
4
3
H
5
2
1
1.2
7
6
O H
N N
8
5
1
9
10
12
3
H 2
4
11
1.3
Scheme 1. Reaction of 1.0 with arylhydrazines.
As we had expected, the two arylhydrazones 1.1 and 1.2,
were obtained by a classically reported methodology,
although the synthesis of entry 1.1 was previously reported
by Maas et al., by means of the reaction of a 2-propyne
iminium triflate with phenylhydrazine.7 These compounds
were identified by their spectroscopic data, mainly from
those that reveal both the alkyne and imine functions,
and from the corresponding molecular ion by EIMS.
Under the same conditions, the reaction between 1.0 and
diphenylhydrazine resulted in the unexpected product 1.3,
and the spectroscopic data were in agreement with both a
condensation reaction, to form the hydrazone fragment
in equilibrium with the enamine tautomer, and a hydration
reaction of the alkyne function, to form the more stable
keto tautomer, and thus, the Z geometric alkene.
Table 2
Selected bond lengths and angles for 1.3
The following selected spectroscopic data confirm the
formation of 1.3: in the FTIR spectrum, a strong band at
1596 cmꢀ1 is observed due to the carbonyl group, and
the band corresponding to the alkyne function observed
for 1.1 and 1.2 near to 2200 cmꢀ1 is absent for product
Bond distances
Angles
˚
Atoms
A
Atoms
Degrees
O1–C1
N1–C3
C1–C2
C2–C3
C3–C4
N1–N2
1.252
1.346
1.420
1.368
1.495
1.396
C3–N1–N2
O1–C1–C2
O1–C1–C5
C2–C1–C5
C2–C3–C4
C1–C2–C3
122.1
121.6
118.4
119.9
122.2
124.9
1
1.3; in the H NMR technique, the signal at 5.80 ppm is
assigned to the conjugated vinylic proton; in the 13C
NMR spectrum, a signal at 189.2 ppm assigned to the
carbonyl carbon is observed; and finally, in the EIMS
Fig. 1. ORTEP of 1.3.

2944
E. J. Aldeco-Pe´rez et al. / Tetrahedron Letters 49 (2008) 2942–2945
Ph Ph
N
NH2
were used as purchased. Column chromatography was per-
formed on silica gel (70–230 mesh) and alumina.
O
OH
NH
N
N
N
Ph Ph
Ph Ph
4.2. Reaction of 4-phenyl-3-butynone with arylhydrazines
(1.1–1.3)
H+
4.2.1. General procedure
H
H2O
H
H
To a solution of 4-phenyl-3-butynone 1.0, CAUTION:
tear-producing liquid (3.5 mmol) in ethanol (100 mL), the
corresponding hydrazine (3.5 mmol) and acetic acid (three
drops) were slowly added. This mixture was magnetically
stirred and placed under reflux until the alkynyl-ketone
could no longer be detected by thin layer chromatography.
After the lapse of the reaction time (Table 1), the solvent
was distilled under vacuum, and the remaining mixture
purified by column chromatography over alumina, using
several gradients of hexane/ethyl acetate mixture. The cor-
responding reaction product was obtained as either a liquid
or solid compound, as shown in Table 1.
+
O
N
HO
N
H
N
N
Ph
N
Ph
Ph
N
Ph
Scheme 2. Reaction mechanism proposed for the formation of 1.3.
Table 3
Calculated Eact values for the formation of vinyl-benzylic carbocations
Entry
Eact (kcal/mol)
1.1
1.2
1.3
13.4076
13.3668
11.8687
4.2.2. 4-Phenyl-3-butynone phenylhydrazone (1.1)
FTIR (CHCl3, cmꢀ1): 3311, 3055, 3025, 2919, 2202,
1601. H NMR (CDCl3, d): 2.23 (3H, s, H1), 6.86–7.53
reaction of 1.3 is more easily formed, and is, in fact, the
only one formed under the reaction conditions used.
1
(10H, m, Harom), 8.28 (1H, s, NH). 13C NMR (CDCl3,
d): 22.1 (C1), 81.0 (C3), 101.2 (C4), 113.0–133.1 (Carom),
141.1 (C2). EIMS (70 eV, m/z(%) ): 234 (100) [M+Å], 233
(61.3) [M+ÅꢀH], 218 (6.9) [M+ÅꢀCH4], 129 (12.5)
½C8H5Nþꢁ, 91 (18.1) [C6H5N+Å], 77 (13.8) ½C6Hþꢁ.
3. Conclusion
The reaction of alkynone 1.0 with either phenylhydr-
azine or 2,4-dinitrophenylhydrazine produces the expected
arylhydrazone. However, with diphenylhydrazine, under
the same reaction conditions, an additional hydration
reaction on the alkyne function is observed.
2
5
4.2.3. 4-Phenyl-3-butynone 2,4-dinitrophenylhydrazone (1.2)
FTIR (CHCl3, cmꢀ1): 3313, 3272, 3104, 2217, 2186,
1617, 1595, 1514. 1H NMR (300 MHz, CDCl3, d): 2.35
(3H, s, H1), 7.42–9.13 (8H, m, Harom), 11.98 (1H, s, NH).
13C NMR (75 MHz, CDCl3, d): 22.6 (C1), 80.4 (C3),
104.3 (C4), 116.9–138.2 (Carom), 144.2 (C2). EIMS (70 eV,
m/z(%) ): 324 (100) [M+Å], 232 (28.1) [M+Åꢀ2NO2], 127
4. Experimental
4.1. General
(19.4) [M+ÅꢀC9H5N], 77 (8.8) [C6Hþ].
5
FTIR spectra were recorded on a Perkin–Elmer 283
spectrophotometer using a dissolution technique. CHCl3,
1H, 13C, DEPT, and HETCOR NMR spectra were
obtained on either a VARIAN ST 200 MHz or Jeol Eclipse
300 MHz instrument, using CDCl3 as solvent and TMS as
internal reference. The EIMS spectra were obtained using a
Hewlett Packard 5953 spectrometer. A suitable crystal was
examined on a Siemens P4/PC diffractometer, and the
structure was solved by direct methods using program
SHELXS86, and refined by full matrix least-squares with
SHELXL.11 The position of the hydrogen atom on nitrogen
atom was obtained from a difference Fourier map, and
those hydrogen atoms attached to carbon atoms were
assigned on idealized positions and forced to ride on parent
atoms.
4.3. 3-(N0,N0-Diphenylhydrazino)-1-phenylbut-2Z-en-1-one
(1.3)
FTIR (CHCl3, cmꢀ1): 3066, 2927, 1596, 1581, 1492
1
cmꢀ1. H NMR (300 MHz, CDCl3, d): 2.12 (s, H4), 5.80
(s, H2), 7.06–7.96 (15H, m, Harom), 12.6 (s, NH); 13C
NMR (75 MHz, CDCl3, d): 18.8 (C4), 92.6 (C2), 119.5–
146.3 (Carom), 166.4 (C3), 189.2 (C1) EIMS (70 eV,
m/z(%) ): 328 (100) [M+Å], 169 (33.1) [C12H11N+Å], 168
(64.4) [C12H10N+], 105 (7.5) [C7H5O+], 77 (9.4) ½C6Hþꢁ.
5
References and notes
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E. J. Aldeco-Pe´rez et al. / Tetrahedron Letters 49 (2008) 2942–2945
2945
´
´
6. Ortega, C.; Gutierrez, R.; Sharma, P.; Gomez, E.; Toscano, A.;
9. Crystal data for 1.3 at 293 K: C22H20N2O, monoclinic, space group
˚
´
´
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