Preparations of Trisubstituted Hydrazines and Pyrazolidines from N-(1-Benzotriazolylalkyl)hydrazines

Article abstract of DOI:10.1021/jo9709110

Reactions of N,N'-disubstituted hydrazines with benzotriazole and aldehydes give N-(α-benzotriazoylalkyl)-N,N'-disubstituted bydrazines which on treatment with organometallic reagents form N-alkyl-N,N'-disubstituted hydrazines in good yields. N-(Benzotriazolylalkyl)-N,N'-disubstituted hydrazines and electron-rich olefins, in the presence of zinc bromide catalyst, generate N,N'-disubstituted pyrazolidines in moderate to good yields.

Full text of DOI:10.1021/jo9709110

8210
J . Org. Chem. 1997, 62, 8210-8214
P r ep a r a tion s of Tr isu bstitu ted Hyd r a zin es a n d P yr a zolid in es fr om
N-(1-Ben zotr ia zolyla lk yl)h yd r a zin es
Alan R. Katritzky,* Guofang Qiu, and Baozhen Yang
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received May 22, 1997X
Reactions of N,N′-disubstituted hydrazines with benzotriazole and aldehydes give N-(R-benzotria-
zoylalkyl)-N,N′-disubstituted hydrazines which on treatment with organometallic reagents form
N-alkyl-N,N′-disubstituted hydrazines in good yields. N-(Benzotriazolylalkyl)-N,N′-disubstituted
hydrazines and electron-rich olefins, in the presence of zinc bromide catalyst, generate N,N′-
disubstituted pyrazolidines in moderate to good yields.
In tr od u ction
benzotriazolyl (Bt) group by nucleophiles such as Grig-
nard reagents or electron-rich alkenes. We now report
new preparations of (i) trisubstituted hydrazines in high
yields by the reactions of N-(1-benzotriazolylalkyl)-N,N′-
disubstituted hydrazines with Grignard reagents or
organozinc reagents and (ii) substituted pyrazolidines by
the reactions of N-(1-benzotriazolylalkyl)-N,N′-diarylhy-
drazines with electron-rich alkenes. We recently re-
ported the preparation of trisubstituted and tetrasubsti-
tuted hydrazines in yields of 32-57% by additions of
R-lithio-1-alkylbenzotriazoles to the NdN bond of azoben-
zenes, followed by substitution of the benzotriazole
residue by Grignard reagents.19 The present investiga-
tions comprise a significant generalization and extension
of this methodology.
Hydrazines are important because of their many
applications in organic synthesis and industry. Trisub-
stituted hydrazines are usually prepared by (i) carbanion
addition to the NdN bond of an azo compound using a
silyl ester enolate1 or a lithium amide enolate2,3 or of an
alkyl- or aryllithium,4 routes which are limited by the
type and accessibility of the appropriate nucleophiles; (ii)
the alkylation of mono- or disubstituted hydrazines,
which rarely gives good yields;5 (iii) electrophilic amina-
tions of amines;6,7 and (iv) additions of organometallic
reagents to hydrazones.8
Pyrazolidines have been widely investigated as fungi-
cides, herbicides, antiinflammatories, antibacterials, an-
esthetics, and anticonvulsants.9,10 General methods for
the synthesis of pyrazolidines include (i) 1,3-dipole
azomethine-imine additions to carbon-carbon double
bonds;11-13 (ii) reductions of pyrazolines, pyrazoles, pyra-
zolones, and pyrazolium salts;14,15 and (iii) cyclizations
of hydrazines with halogenated compounds.
Resu lts a n d Discu ssion
Syn t h esis of N-(1-Ben zot r ia zolyla lk yl)-N,N′-d i-
su bstitu ted Hyd r a zin es. N-(1-Benzotriazolylalkyl)-
N,N′-diphenylhydrazines 2a -d were prepared in good
yields from N,N′-diphenylhydrazine (1a ), benzotriazole,
and the appropriate aldehyde in methylene chloride at
rt in the presence of molecular sieves as dehydrating
agent. These reactions gave mixtures of benzotriazol-1-
yl and benzotriazol-2-yl isomers, and these two isomers
are in equilibrium in solution.20 The ratio of Bt-1 and
Bt-2 isomers was 8 to 1, according to the integration of
Benzotriazole has been extensively used as a synthetic
auxiliary in organic synthesis.16-18 N-Alkylbenzotriazoles
with an electron-donor group at the R-position of the
N-alkyl group can undergo facile replacement of the
X Abstract published in Advance ACS Abstracts, October 1, 1997.
(1) Gennari, C.; Colombo, L.; Bertolini, G. J . Am. Chem. Soc. 1986,
108, 6394.
(2) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J . F. J . Am.
Chem. Soc. 1986, 108, 6395.
(3) Trimble, L. A.; Vederas, J . C. J . Am. Chem. Soc. 1986, 108, 6397.
(4) Katritzky, A. R.; Wu, J .; Verin, S. V. Synthesis 1995, 651.
(5) Askani, R.; Taber, D. F. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6,
p 116.
(6) Boche, G.; Sommerlade, R. H.; Bosold, F. Angew. Chem., Int. Ed.
Engl. 1986, 25, 562.
(7) Linke, K.-H.; Turley, R. Z. Naturforsch, B 1973, 28, 829.
(8) Huddleston, P. R.; Coutts, I. G. C. In Comprehensive Organic
Functional Group Transformations; Katritzky, A. R., Meth-Cohn, O.,
Rees, C. W., Eds.; Pergamon: Oxford, 1995; Vol. 2, p 371. Enders, D.;
Lochtman, R.; Raabe, G. Synlett 1996, 126.
(9) Searching MEDLINE EXPRESS from 1966 to 1996, 59 records
were found.
(10) Elguero, J . In Comprehensive Heterocyclic Chemistry; Katritzky,
A. R.; Rees, C. W., Eds.; Pergamon Press: New York, 1984; Vol. 5, p
297.
(11) Huisgen, R.; Grashey, R.; Laur, P.; Leitermann, H. Angew.
Chem. 1960, 72, 416.
1
the H NMR spectrum recorded immediately after dis-
1
solving the solid in CDCl3. When the H NMR spectrum
of the same sample was recorded 30 min later, the ratio
had changed to 2 to 1. Considering that both Bt-1 and
Bt-2 groups are good leaving groups, the mixture of the
two isomers was directly used for further reactions
without separation.
1,4-Diphenyl-4-[(benzotriazol-1-yl)methyl]semicarba-
zide (2e) and N-phenyl-N-[(benzotriazol-1-yl)methyl]-N′-
propionylhydrazine (2f) were prepared from correspond-
ing hydrazines, benzotriazole, and paraformaldehyde
under reflux in benzene, with a Dean-Stark trap to
remove the water produced, and both of them gave only
(12) Oppolzer, W. Tetrahedron Lett. 1970, 2199.
(13) Sun, B.; Adachi, K.; Noguchi, M. Tetrahedron 1996, 52, 901.
(14) Behr, L. C.; Fusco, R.; J arboe, C. H. In Chemistry of Heterocyclic
Compounds: Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and
Condensed Rings; Wiley, R. H., Ed.; Interscience Publishers: New
York, 1967; p 279.
(16) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron
1991, 47, 2683.
(17) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis 1994, 445.
(18) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. V. Chem.
Rev. 1997, submitted.
(19) Katritzky, A. R.; Verin, S. V.; Yang, B. Org. Prepr. Proced. Int.
1996, 28, 97.
(20) Katritzky, A. R.; Fan, W.-Q. J . Org. Chem. 1990, 55, 3205.
(15) Banuelos, L. A.; Cuadrado, P.; Gonzalez-Nogal, A. M.; Lopez-
Solera, I.; Pulido, F. J .; Raithby, P. R. Tetrahedron 1996, 52, 9193.
S0022-3263(97)00911-0 CCC: $14.00 © 1997 American Chemical Society

Trisubstituted Hydrazines and Pyrazolidines
J . Org. Chem., Vol. 62, No. 23, 1997 8211
Sch em e 1
Sch em e 2
Ta ble 1. P r ep a r a tion of
N-(1-Ben zotr ia zolyla lk yl)-N,N’-d isu bstitu ted
Hyd r a zin es 2
Ta ble 3. Syn th esis of P yr a zolid in es 4 a n d 5
time yield
Bt-1/
compd
R1
R
(h)
(%)
mp (°C) Bt-2a
time yield
compd
R1
X (for 4) or n (for 5)
(h)
(%)
mp (°C)
2a
2b
2b
2d
2e
2f
Ph
Ph
Ph
Ph
H
Et
24
120
120
88
69
64
70
137-138 97:3
127-132
122-126
153-156
5:2
2:1
2:1
4a
4b
4c
5a
5b
5c
5d
Ph
Ph
2-pyrrolidonyl
N-methylacetamidyl 24
30
53
43
60
84
83
60
39
107-109
142-143
118-120
139-142
168-171
221-224
124-126
n-C3H7
Cyclohexyl 120
PhNHCO OEt
Ph
Ph
PhNHCO n ) 2
C2H5CO n ) 2
50
24
24
48
48
PhNHCO
C2H5CO
H
H
48
48
61b 183-184
61b 157-158
n ) 1
n ) 2
a
b
The ratio of Bt-1/Bt-2 observed just after concentration. In
refluxing benzene with Dean-Stark trap.
of N-(1-benzotriazolylmethyl)-N,N′-disubstituted hydra-
zines 2a with electron rich alkenes in the presence of
Lewis acids gives pyrazolidines 4a ,b. Rather than the
ortho-carbon of the phenyl ring, the nitrogen atom in
hydrazines 2 readily attacks the cationic intermediates
6 formed from starting material 2 and the alkene
(Scheme 2 and Table 3). In these reactions, 2 f 4, 2
equiv of alkene was needed because 1 equiv was con-
sumed by the benzotriazolyl anion which is formed
simultaneously.
Ta ble 2. P r ep a r a tion of Tr isu stitu ted Hyd r a zin es 3
compd
R
R2
yield (%)
mp (°C)
oil
3a
3b
3c
3d
3e
3f
H
Et
79
81
80
70
68
99
91
62
53
Et
Et
Et
Et
Ph
Allyl
Allyl
2-furyl
69-70
59-60
117-119
117-118
oil
oil
59-60
60-62
n-C3H7
cyclohexyl
n-C3H7
H
n-C3H7
H
3g
3h
3i
H
2-thiophenyl
Treatment of 2a with cyclic vinyl ethers gave cis-fused
bicyclic compounds 5a and 5b exclusively; the cis rela-
tionship of H-3 and H-4 was determined by NOE experi-
ments and the coupling H-3/H-4 constants in the 1H
NMR. These are 6.1 Hz for 5a and 1.7 Hz for 5b,
consistant with literature reports24-26 for furan five:five
and five:six ring system, respectively. Similarly 2e was
reacted with vinyl ethyl ether and 3,4-dihydropyran
under similar conditions to give good yields of the
expected cyclic pyrazolines 4c and 5c, respectively.
Bt-1 isomers. The results of these reactions are listed
in Scheme 1 and Table 1.
P r epar ation of Tr isu bstitu ted Hydr azin es 3. N-(1-
Benzotriazolylalkyl)-N,N′-diphenylhydrazines 2a -d re-
acted with Grignard reagents at 0 °C followed by warm-
ing to room temperature to give trisubstituted hydrazines
3a -g in good yields. Treatments of compound 2a with
2-furyl and 2-thiophenyl organozinc reagents gave 3h and
3i in 62% and 53% yields, respectively (Table 2).
P r ep a r a tion of Su bstitu ted P yr a zolid in es 4 a n d
5. We have reported reactions of N-(1-benzotriazolyla-
lkyl)aniline both with electron-rich21 and unactivated
alkenes in the presence of Lewis acid22,23 to give tetrahy-
droquinolines. In contrast, we now find that treatment
(22) Katritzky, A. R.; Nichols, D. A.; Qi, M.; Yang, B. J . Heterocycl.
Chem. 1997, submitted.
(23) Katritzky, A. R.; Abonia, R.; Yang, B.; Qi, M.; Insuasty, B.
Unpublished work.
(24) Elslager, E. F.; Worth, D. F. J . Heterocycl. Chem. 1969, 6, 597.
(25) Kametani, T.; Takeda, H.; Suzuki, Y.; Kasai, H.; Honda, T.
Heterocycles 1986, 24, 3385.
(21) Katritzky, A. R.; Rachwal, B.; Rachwal, S. J . Org. Chem. 1995,
60, 3993.
(26) Kametani, T.; Furuyama, H.; Fukuoka, Y.; Takeda, H.; Suzuki,
Y.; Honda, T. J . Heterocycl. Chem. 1986, 23, 185.

8212 J . Org. Chem., Vol. 62, No. 23, 1997
Katritzky et al.
Sch em e 3
Sch em e 4
Sch em e 5
Compound 5c also has the cis configuration, which was
confirmed by NOE, and the coupling constant of H-3 and
H-4 is 3.8 Hz.
When excess of vinyl ethyl ether was reacted with 2a ,
4-et h oxy-{1-ph en yl-[2,3-a ]-pyr a zolido}t et r a h ydr o-
quinoline (8) was obtained in 31% yield. The formation
of 8 can be explained as depicted in Scheme 3: N-(1-
benzotriazolylmethyl)-N,N′-diphenylhydrazine and vinyl
ethyl ether in the presence of zinc bromide first gave
compound 7, which is unstable under acidic conditions,
and then reacted further with a second equivalent of vinyl
ethyl ether followed by ring-closure to give compound 8.
1
From the H NMR of 8, the proton of the ring 4-position
CH to which the ethoxy group is attached is assigned to
the signal at 4.45 ppm. This signal is a double-doublet
with J ) 4.1 and 10.2 Hz. This means that there is one
axial-axial coupling and thus that the ethoxy group is
equatorial and trans to the proton at the ring junction.
Treatment of N-(1-benzotriazolylcyclohexylmethyl)-
N,N′-diphenylhydrazine (2d ) with 3,4-dihydrofuran
in the presence of zinc bromide gave 2-cyclohexyl-
2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinoline (9) (39%), with
cleavage of the N-N bond and the phenylamino group
In conclusion, N-(1-benzotriazolylalkyl)-N,N′-disubsti-
tuted hydrazines 2 are useful intermediates which pro-
vide convenient and novel methods for preparation of
trisubstituted hydrazines 3 and substituted pyrazolidines
4 and 5.
1
acting as a leaving group (Scheme 4). In the H NMR
spectrum of 9, the doublet (J ) 8.0 Hz) at 5.11 ppm was
assigned to the 4-position proton. The coupling indi-
cates26 that the configuration between the 3- and 4-posi-
tion protons is cis. Furthermore, the 2-position proton
was at 3.11 ppm as a doublet (J ) 2.5 Hz), which showed
that the configuration between 2- and 3-position is also
cis.26
Treatment of 2f with electron-rich alkene under the
above conditions gave two products, 5d and 10, in 39%
and 44%, respectively (Scheme 5). 5d is also of cis
configuration, as the coupling constant of H-3 and H-4
is 3.9 Hz. Compound 10 has a trans configuration,
coupling constant of H-3 and H-4 being 10.2 Hz. In this
reaction, the nucleophilicities of the amide nitrogen and
ortho-carbon at the phenyl ring are comparable.
Exp er im en ta l Section
Gen er a l Com m en ts. Melting points were determined with
a Koefler hot-stage apparatus without correction. The 1H
NMR and 13C NMR spectra were recorded on a 300 MHz
spectrometer in CDCl3 with tetramethylsilane or the solvent
as the internal reference. Tetrahydrofuran (THF) was distilled
from sodium/benzophenone prior to use. Grignard reactions
were carried out under an atmosphere of dry nitrogen. All
glassware was oven-dried. All moisture-sensitive reagents
were transferred by means of predried syringes.
Gen er a l P r oced u r e for th e Syn th esis of N-(1-Ben zot-
r ia zolyla lk yl)-N,N′-d isu bstitu ted Hyd r a zin es 2. Meth od
A (2a -d ). A mixture of benzotriazole (23.8 g, 0.2 mol),
aldehyde (0.2 mol), and 1,2-diphenylhydrazine (18.4 g, 0.1 mol)

Trisubstituted Hydrazines and Pyrazolidines
J . Org. Chem., Vol. 62, No. 23, 1997 8213
in methylene chloride (400 mL) was stirred at rt in the
presence of molecular sieves (3 Å, 10 g) for an appropriate time
until no hydrazine was left. The mixture was washed with
aqueous NaOH (2 N, 2 × 100 mL) and water (2 × 100 mL)
and the aqueous phase was extracted with ethyl acetate. The
combined organic layers were dried over anhydrous sodium
sulfate. After the removal of the solvent, the residue was
recrystallized from ether to give the expected compounds.
N -(B e n zot r ia zo l-1-y lm e t h y l)-N ,N ′-d ip h e n y lh y d r a -
zin e (2a ): 1H NMR (CDCl3) δ 6.13 (s, 1 H), 6.29 (br s, 2 H),
6.87-6.94 (m, 4 H), 7.19-7.30 (m, 6 H), 7.34 (t, 1 H, J ) 7.5
Hz), 7.43 (t, 1 H, J ) 7.5 Hz), 7.54 (d, 1 H, J ) 8.1 Hz), 8.02
(d, 1 H, J ) 8.1 Hz); 13C NMR (CDCl3) δ 64.0, 109.8, 112.8,
114.5, 120.0, 120.7, 121.2, 124.1, 127.8, 129.4, 129.6, 133.8,
145.9, 146.2, 146.9. Anal. Calcd for C19H17N5: C, 72.35; H,
5.44; N, 22.22. Found: C, 72.32; H, 5.58; N, 22.45.
N-(1-Ben zot r ia zolylp r op yl)-N,N′-d ip h en ylh yd r a zin e
(2b): 1H NMR (CDCl3) δ (NMR data of Bt-2 isomer are listed
in square brackets) 0.94 (t, 3 H, J ) 7.4 Hz) [0.90 (t, 3 H, J )
7.4 Hz)], 2.52-2.65 (m, 2 H) [2.34-2.50 (m, 2 H)], 6.33 (br s,
1 H), 6.57 (t, 1 H, J ) 7.1 Hz) [6.70 (t, 1 H, J ) 7.0 Hz)], 6.80-
7.47 (m, 12 H), 7.49 (d, 1 H, J ) 8.5 Hz), 8.02 (d, 1 H, J ) 8.2
Hz) [7.82-7.86 (m, 2 H)]; 13C NMR (CDCl3) δ 10.6 [10.2], 26.0
[26.9], 78.1 [82.8], 109.9, 112.3 [111.7], 116.3 [115.4], [118.2],
[119.2], 119.6, 120.0, 122.0 [121.4], 123.9, [126.3], 127.5, 129.1,
129.3, 133.3, [143.7], 145.5, 147.7, 147.8 [148.2]. Anal. Calcd
for C21H21N5: C, 73,43; H, 6.17; N, 20.40. Found: C, 73.31;
H, 6.41; N, 20.25.
N -(1-Be n zot r ia zolylb u t yl)-N ,N ′-d ip h e n ylh yd r a zin e
(2c): 1H NMR (CDCl3) δ (NMR data of Bt-1 isomer are listed
in square brackets, the ratio of Bt-2 to Bt-1 isomers is 5) 0.89
(t, 3 H, J ) 7.5 Hz) [0.87 (t, 3 H, J ) 7.3 Hz)], 1.10-1.30 (m,
1 H), 1.32-1.50 (m, 1 H), 2.28-2.41 (m, 1 H), 2.43-2.59 (m, 1
H), 6.27 (br s, 1 H), 6.66 (t, 1 H, J ) 7.2 Hz), 6.75-7.47 (m, 12
H), 7.48 (d, 1 H, J ) 8.2 Hz), 8.01 (d, 1 H, J ) 8.2 Hz) [7.80-
7.86 (m, 2 H)]; 13C NMR (CDCl3) δ 13.4, 19.2 [18.8], 34.5 [35.3],
76.4 [81.2], 109.9, 112.3 [111.8], 116.4 [115.5], [118.2], [119.2],
119.7, 120.0, 122.0 [121.5], 123.9 [126.3], 127.5, 129.1, 129.3
[129.4], 133.2, [143.7], 145.6, 147.8 [147.7], 148.3. Anal. Calcd
for C22H23N5: C, 73,91; H, 6.49; N, 19.60. Found: C, 73.90;
H, 6.53; N, 19.89.
N-(1-Ben zot r ia zolyl-1-cycloh exylm et h yl)-N,N′-d ip h e-
n ylh yd r a zin e (2d ): 1H NMR (CDCl3) δ (NMR data of Bt-2
isomer are listed in square brackets) 0.58-0.70 (m, 1 H), 0.77-
1.45 (m, 6 H), 1.48-1.82 (m, 3 H), 2.18-2.30 (m, 1 H) [2.30-
2.48 (m, 1 H)], 2.90-3.10 (m, 1 H) [2.69-2.86 (m, 1 H)], 6.41
(d, 1 H, J ) 10.0 Hz) [6.41 (d, 1 H, J ) 7.5 Hz)], 6.45 (br s, 1
H), 6.70-7.40 (m, 13 H), [7.80-7.85 (m, 2 H)], 7.97 (d, 1 H, J
) 8.7 Hz); 13C NMR (CDCl3) δ 25.4 [25.3], 26.1 [26.0], 29.2
[28.8], 30.8 [30.6], 39.2 [39.7], 82.9 [87.7], 109.7, 112.5 [112.3],
112.8, 117.8 [117.7], 118.3 [119.1], [119.4], 119.8, 122.8 [122.1],
123.8, [126.3], 127.5, 129.1 [129.0], 129.2 [129.3], 131.2, [143.5],
145.2, 146.9 [147.4], 147.8 [149.0]. Anal. Calcd for C25H27N5:
C, 75.52; H, 6.85; N, 17.63. Found: C, 75.64; H, 6.98; N, 17.63.
Meth od B (for 2e,f). A mixture of benzotriazole (3.57 g,
0.03 mol), paraformaldehyde (0.90 g, 0.03 mol), and the
substituted hydrazine (0.02 mol) was heated to reflux in
benzene (100 mL) for 24 h with a Dean-Stark trap for removal
of the formed water. The reaction mixture was washed with
aqueous NaOH (1 N, 2 × 50 mL) and water (2 × 50 mL) and
extracted with ethyl acetate. The combined organic layer was
dried over anhydrous Na2SO4. After removal of the solvent,
the residue was recrystallized from ethyl acetate and a white
solid was obtained.
7.41 (t, 1 H, J ) 7.5 Hz), 7.55 (t, 1 H, J ) 7.5 Hz), 7.78 (d, 1
H, J ) 8.4 Hz), 8.04 (d, 1 H, J ) 8.1 Hz); 13C NMR (CDCl3) (at
70 °C) δ 9.4, 26.4, 63.8, 111.0, 112.8, 119.1, 119.7, 124.1, 127.4,
129.1, 132.9, 145.3, 146.6, 172.4. Anal. Calcd for C16H17N5O:
C, 65.05; H, 5.80; N, 23.72. Found: C, 65.31; H, 5.94; N, 23.93.
Gen er a l P r oced u r e for P r ep a r a tion of Tr isu bstitu ted
Hyd r a zin es 3a -g. To a solution of N-(1-benzotriazolylalkyl)-
N,N′-diphenylhydrazine 2a -d (5 mmol) in THF (50 mL) was
added Grignard reagent (10 mmol) dropwise at 0 °C under
nitrogen. The mixture was stirred at 0 °C for 1 h and then
warmed to rt for 2 h. The reaction mixture was washed with
aqueous NaOH solution (2 N, 2 × 25 mL) and water (2 × 25
mL) and extracted with ethyl acetate (2 × 25 mL). The
combined organic layers were dried over anhydrous sodium
sulfate. After the removal of the solvent under vacuum, the
residue was purified by column chromatography on silica gel
to give the pure product.
N-P r op yl-N,N′-d ip h en ylh yd r a zin e (3a ): oil; lit.27 mp
32-34 °C; 1H NMR (CDCl3) δ 0.93 (t, 3 H, J ) 7.5 Hz), 1.63-
1.71 (m, 2 H), 3.42 (t, 2 H, J ) 7.0 Hz), 5.53 (s, 1 H), 6.73-
6.80 (m, 4 H), 6.81-6.90 (m, 2 H), 7.15-7.22 (m, 4 H); 13C NMR
(CDCl3) δ 11.5, 19.4, 53.9, 112.2, 112.8, 118.4, 119.4, 129.2,
129.3, 147.6, 149.8. Anal. Calcd for C15H18N2: C, 79.59; H,
8.02; N, 12.38. Found: C, 79.49; H, 8.04; N, 12.61.
N-3-P en t yl-N,N′-d ip h en ylh yd r a zin e (3b ): 1H NMR
(CDCl3) δ 0.75-1.14 (m, 6 H), 1.48-1.60 (m, 2 H), 1.62-1.75
(m, 2 H), 3.66 (quintet, 1 H, J ) 6.3 Hz), 5.33 (s, 1 H), 6.72-
6.83 (m, 4 H), 6.84-6.90 (m, 2 H), 7.12-7.22 (m, 4 H); 13C NMR
(CDCl3) δ 12.1, 24.3, 65.5, 112.2, 114.1, 118.8, 119.1, 129.2,
148.7, 150.8. Anal. Calcd for C17H22N2: C, 80.26; H, 8.72; N,
11.02. Found: C, 80.51; H, 8.75; N, 10.92.
N-3-Hexyl-N,N′-diph en ylh ydr azin e (3c): 1H NMR (CDCl3)
δ 0.78-1.15 (m, 6 H), 1.16-1.80 (m, 6 H), 3.70-3.80 (m, 1 H),
5.31 (s, 1 H), 6.72-6.82 (m, 4 H), 6.84-6.90 (m, 2 H), 7.15-
7.25 (m, 4 H); 13C NMR (CDCl3) δ 12.1, 14.2, 20.6, 33.7, 33.8,
63.2, 112.2, 114.1, 118.8, 119.1, 129.2, 148.7, 150.8. Anal.
Calcd for C18H24N2: C, 80.54; H, 9.01; N, 10.44. Found: C,
80.55; H, 9.07; N, 10.46.
N-(1-E t h yl-1-cycloh exylm et h yl)-N,N′-d ip h en ylh yd r a -
zin e (3d ): 1H NMR (CDCl3) δ 0.70-0.93 (m, 2 H), 1.00-1.30
(m, 6 H), 1.35-1.90 (m, 8 H), 3.48-3.58 (m, 1 H), 5.41 (s, 1
H), 6.70-6.90 (m, 6 H), 7.12-7.24 (m, 4 H); 13C NMR (CDCl3)
δ 12.7, 22.2, 26.3, 26.5, 32.0, 40.9, 69.2, 112.4, 113.4, 118.2,
119.1, 129.1, 129.2, 148.3, 152.0. Anal. Calcd for C21H28N2:
C, 81.77; H, 9.15; N, 9.08. Found: C, 81.70; H, 9.26; N, 9.08.
N-(R-Propylbenzyl)-N,N′-diphenylhydrazine (3e): 1H NMR
(CDCl3) δ 0.93 (t, 3 H, J ) 7.5 Hz), 1.38-1.62 (m, 2 H), 1.88-
2.01 (m, 1 H), 2.07-2.19 (m, 1 H), 5.00 (t, 1 H, J ) 7.4 Hz),
5.09 (br s, 1 H), 6.71-6.83 (m, 4 H), 6.92-6.96 (m, 2 H), 7.10-
7.28 (m, 9 H); 13C NMR (CDCl3) δ 14.1, 20.4, 33.6, 66.0, 112.3,
115.2, 119.1, 119.6, 127.6, 128.3, 129.2, 138.7, 148.5, 150.3.
Anal. Calcd for C22H24N2: C, 83.49; H, 7.65; N, 8.86. Found:
C, 83.76; H, 7.90; N, 8.98.
N-3-Bu t en yl-N,N′-d ip h en ylh yd r a zin e (3f): 1H NMR
(CDCl3) δ 2.43 (q, 2 H, J ) 6.9 Hz), 3.59 (t, 2 H, J ) 6.9 Hz),
5.06 (d, 1 H, J ) 11.4 Hz), 5.11 (d, 1 H, J ) 17.1 Hz), 5.63 (s,
1 H), 5.77-5.95 (m, 1 H), 6.72-6.94 (m, 6 H), 7.14-7.27 (m, 4
H); 13C NMR (CDCl3) δ 30.9, 51.3, 112.4, 112.9, 116.9, 118.7,
119.7, 129.4, 129.5, 136.1, 147.6, 149.6. Anal. Calcd for
C16H18N2: C, 80.62; H, 7.62; N, 11.76. Found: C, 80.82; H,
7.25; N, 11.89.
N-4-(1-Hepten yl)-N,N′-diph en ylh ydr azin e (3g): 1H NMR
(CDCl3) δ 0.82-1.00 (m, 3 H), 1.20-1.80 (m, 4 H), 2.22-2.60
(m, 2 H), 3.90-4.03 (m, 1 H), 5.01 (d, 1 H, J ) 9.9 Hz), 5.08
(d, 1 H, J ) 17.3 Hz), 5.43 (br s, 1 H), 5.76-6.02 (m, 1 H),
6.75-6.92 (m, 6 H), 7.14-7.27 (m, 4 H); 13C NMR (CDCl3) δ
14.1, 20.5, 34.1, 36.2, 61.2, 112.2, 114.0, 116.6, 118.9, 119.2,
129.2, 136.7, 148.6, 150.3. Anal. Calcd for C19H24N2: C, 81.37;
H, 8.63; N, 10.00. Found: C, 81.20; H, 8.83; N, 9.98.
Gen er a l P r oced u r e for P r ep a r a tion of Tr isu bstitu ted
Hyd r a zin es 3h ,i. To a solution of furan (10 mmol, 0.8 mL)
and TMEDA (11 mmol, 1.7 mL) in THF (50 mL) was added
n-butyllithium (11 mmol, 1.6 M, 6.9 mL) dropwise at -78 °C
1,4-Dip h en yl-4-(1-ben zotr ia zol-1-ylm eth yl)sem ica r ba -
zid e (2e): 1H NMR (CDCl3) δ 6.21 (s, 1 H), 6.28 (s, 1 H), 6.99-
7.07 (m, 2 H), 7.18-7.37 (m, 10 H), 7.47 (t, 1 H, J ) 7.5 Hz),
7.58 (d, 1 H, J ) 8.40 Hz), 7.81 (s, 1 H), 8.01 (d, 1 H, J ) 8.2
Hz); 13C NMR (CDCl3) δ 67.2, 109.3, 115.6, 119.7, 120.3, 123.3,
123.6, 124.5, 128.5, 128.9, 129.8, 133.1, 137.5, 145.9, 146.2,
155.2. Anal. Calcd for C20H18N6O: C, 67.01; H, 5.07; N, 23.46.
Found: C, 67.22; H, 5.20; N, 23.23.
N-P h en yl-N-(ben zotr ia zol-1-ylm eth yl)-N′-p r op ion ylh y-
d r a zin e (2f): 1H NMR (CDCl3) (at 70 °C) δ 1.08 (t, 3 H, J )
7.5 Hz), 2.21 (q, 2 H, J ) 7.2 Hz), 6.38 (s, 2 H), 6.86 (t, 1 H, J
) 6.9 Hz), 7.12 (d, 2 H, J ) 8.1 Hz), 7.27 (t, 2 H, J ) 7.5 Hz),
(27) Berg-Nielsen, K.; Bernatek, E. Acta Chem. Scand. 1972, 26,
4130.

8214 J . Org. Chem., Vol. 62, No. 23, 1997
Katritzky et al.
under nitrogen. After stirring for 2 h, the reaction mixture
was warmed to reflux for 0.5 h. The solution was then cooled
to rt for 1 h, and anhydrous zinc bromide (11 mmol, 2.48 g) in
THF (10 mL) was added. The mixture was stirred at rt for 1
h, and a solution of N-(benzotriazol-1-ylmethyl)-N,N′-diphe-
nylhydrazine (5 mmol, 1.58 g) in THF (5 mL) was added. The
formed mixture was stirred at rt for 16 h. The reaction
mixture was washed with aqueous NaOH solution (2 N, 2 ×
25 mL) and water (2 × 25 mL) and extracted with ethyl acetate
(2 × 25 mL). The combined organic layers were dried over
anhydrous sodium sulfate. After the removal of the solvent
under vacuum, the residue was purified by column chroma-
tography on silica gel to give the pure product 3h (0.82 g, yield
62%).
N-2-Fu r yl-N,N′-diph en ylh ydr azin e (3h ): 1H NMR (CDCl3)
δ 4.67 (s, 2 H), 5.79 (s, 1 H), 6.21 (d, 1 H, J ) 3.0 Hz), 6.30 (d,
1 H, J ) 2.4 Hz), 6.80-6.85 (m, 2 H), 7.07 (d, 2 H, J ) 8.1
Hz), 7.25 (t, 4 H, J ) 7.5 Hz), 7.36 (s, 1 H); 13C NMR (CDCl3)
δ 47.3, 108.7, 110.2, 112.8, 113.4, 119.2, 120.0, 129.1, 129.4,
142.4, 147.1, 149.4, 150.7. Anal. Calcd for C17H16N2O: C,
77.24; H, 6.11; N, 10.60. Found: C, 77.62; H, 6.33; N, 10.73.
N-2-Th iop h en yl-N,N′-d ip h en ylh yd r a zin e (3i): 1H NMR
(CDCl3) δ 4.87 (s, 2 H), 5.64 (s, 1 H), 6.82-6.92 (m, 4 H), 6.93-
6.98 (m, 2 H), 7.08 (d, 2 H, J ) 6.3 Hz), 7.18-7.31 (m, 5 H);
13C NMR (CDCl3) δ 49.3, 113.0, 113.8, 119.5, 120.1, 125.4,
126.8, 127.0, 129.3, 129.5, 138.1, 147.0, 149.2. Anal. Calcd
for C17H16N2S: C, 72.83; H, 5.76; N, 10.00. Found: C, 72.71;
H, 5.89; N, 10.01.
N,N′-Dip h en yl-2,3,3a ,4,5,6a -h exa h yd r ofu r o[2,3-c]p yr a -
zole (5a ): H NMR (CDCl3) δ 1.58-1.69 (m, 1 H), 1.97-2.22
1
(m, 1 H), 3.07-3.17 (m, 1 H), 3.69-3.91 (m, 4 H), 5.83 (d, 1 H,
J ) 6.1 Hz), 6.80-6.92 (m, 2 H), 6.92-7.00 (m, 2 H), 7.00-
7.10 (m, 2 H), 7.18-7.30 (m, 4 H); 13C NMR (CDCl3) δ 31.2,
46.0, 56.7, 67.5, 100.0, 113.4, 114.0, 119.5, 120.1, 128.9, 129.1,
147.8, 150.6. Anal. Calcd for C17H18N2O: C, 76.65; H, 6.82;
N, 10.52. Found: C, 76.93; H, 7.13; N, 10.57.
N,N′-Dip h en yl-1,2,3,3a ,4,5,6,7a -oct a h yd r op yr a n o[2,3-
c]p yr a zole (5b): 1H NMR (CDCl3) δ 1.38-1.48 (m, 1 H), 1.65-
1.88 (m, 3 H), 2.46-2.58 (m, 1 H), 3.48-3.61 (m, 2 H), 3.82-
3.99 (m, 2 H), 5.12 (d, 1 H, J ) 2.3 Hz), 6.80-6.98 (m, 4 H),
7.10-7.32 (m, 6 H); 13C NMR (CDCl3) δ 20.9, 22.0, 36.8, 52.5,
64.8, 94.3, 113.6, 115.9, 119.0, 121.3, 128.9, 149.2, 151.5. Anal.
Calcd for C18H20N2O: C, 77.10; H, 7.19; N, 10.00. Found: C,
77.27; H, 7.50; N, 10.02.
2-P h en yl-1-(p h en ylca r ba m oyl)-1,2,3,3a ,4,5,6,7a -octa h y-
d r op yr a n o[2,3-c]p yr a zole (5c): 1H NMR (CDCl3) δ 1.29-
1.40 (m, 1 H), 1.53-1.68 (m, 1 H), 1.77-1.96 (m, 2 H), 2.44-
2.58 (m, 1 H), 3.45 (q, 2 H, J ) 9.90 Hz), 3.80-4.00 (m,
2 H), 5.74 (d, 1 H, J ) 3.8 Hz), 6.95-7.12 (m, 4 H), 7.20-
7.33 (m, 4 H), 7.34-7.43 (m, 2 H), 7.97 (br s, 1 H); 13C
NMR (CDCl3) δ 19.9, 21.5, 38.3, 55.3, 65.6, 85.8, 115.0, 119.3,
121.6, 123.3, 128.7, 129.0, 137.9, 152.1, 155.6. Anal. Calcd
for C19H21N3O2: C, 70.55; H, 6.55; N, 13.00. Found: C, 70.75;
H, 6.74; N, 13.04.
2-P h en yl-1-p r op ion yl-1,2,3,3a ,4,5,6,7a -octa h yd r op yr a -
n o[2,3-c]p yr a zole (5d ): 1H NMR (CDCl3) δ 0.97 (t, 3 H, J )
7.5 Hz), 1.26-1.38 (m, 1 H), 1.47-1.58 (m, 1 H), 1.62-1.72
(m, 1 H), 2.14-2.28 (m, 1 H), 2.32-2.50 (m, 1 H), 3.32-3.50
(m, 2 H), 3.66-3.84 (m, 2 H) H), 5.58 (d, 1 H, J ) 3.9 Hz),
6.82-6.90 (m, 3 H), 7.20 (t, 2 H, J ) 8.1 Hz); 13C NMR (CDCl3)
δ 7.9, 19.2, 20.4, 25.2, 36.8, 55.2, 63.7, 83.2, 114.9, 120.0, 127.8,
151.8, 173.6. Anal. Calcd for C15H20N2O2: C, 69.19; H, 7.75;
N, 10.77. Found: C, 69.21; H, 8.02; N, 10.75.
4-Eth oxy-(1,2,3,3a,4,5-h exah ydr o-1-ph en ylpyr azolo[1,5-
a ]qu in olin e (8): mp 113-115 °C; 1H NMR (CDCl3) δ 1.35 (t,
3 H, J ) 6.9 Hz), 1.54-1.69 (m, 1 H), 1.88-1.98 (m, 1 H), 2.28-
2.38 (m, 1 H), 2.52-2.60 (m, 1 H), 3.49-3.88 (m, 5 H), 4.45
(dd, 1 H, J ) 4.1, 10.2 Hz), 6.82-6.97 (m, 5 H), 7.10 (t, 1 H, J
) 7.5 Hz), 7.24 (t, 2 H, J ) 7.8 Hz), 7.37 (d, 1 H, J ) 7.5 Hz);
13C NMR (CDCl3) δ 15.6, 32.6, 34.0, 51.1, 55.0, 65.0, 72.9, 113.7,
114.0, 119.0, 119.7, 123.8, 126.2, 127.9, 128.9, 144.7, 151.5.
Anal. Calcd for C19H22N2O: C, 77.51; H, 7.54; N, 9.52.
Found: C, 77.36; H, 7.72; N, 9.53.
2-Cycloh exyl-2,3,3a ,4,5,9b-h exa h yd r ofu r o[3,2-c]qu in o-
lin e (9): mp 148-151 °C; 1H NMR (CDCl3) δ 0.94-1.08 (m, 2
H), 1.15-1.49 (m, 4 H), 1.60-2.10 (m, 7 H), 2.74 (q, 1 H, J )
8.1 Hz), 3.11 (dd, 1 H, J ) 2.5, 9.1 Hz), 3.70-3.82 (m, 3 H),
5.11 (d, 1 H, J ) 8.0 Hz), 6.52 (d, 1 H, J ) 7.8 Hz), 6.74 (t, 1
H, J ) 7.5 Hz), 7.04 (t, 1 H, J ) 8.2 Hz), 7.29 (d, 1 H, J ) 7.5
Hz); 13C NMR (CDCl3) δ 23.9, 25.9, 26.0, 26.3, 28.9, 30.1, 40.3,
40.4, 57.7, 66.5, 76.0, 114.4, 118.6, 122.8, 128.1, 130.0, 145.1.
Anal. Calcd for C17H23N1O: C, 79.32; H, 9.01; N, 5.44.
Found: C, 79.13; H, 9.14; N, 5.44.
N -(P r op ion yla m in o)-3,4,4a ,5,6,10b -h e xa h yd r op yr a -
n o[3,2-c]qu in olin e (10): yield 44%, mp 166-168 °C; 1H NMR
(CDCl3) δ 1.12 (t, 3 H, J ) 7.2 Hz), 1.42-1.54 (m, 1 H), 1.62-
1.84 (m, 2 H), 1.84-1.98 (m, 2 H), 2.17-2.29(m, 2 H), 2.49-
2.54 (m, 1 H), 3.19 (d, 1 H, J ) 10.2 Hz), 3.58-3.72 (m, 2 H),
3.81 (d, 1 H, J ) 10.2 Hz), 4.44 (s, 1 H), 6.65-6.75 (m, 2 H),
7.07-7.19 (m, 2 H), 9.09 (s, 1 H); 13C NMR (CDCl3) δ 8.8, 21.8,
24.4, 26.2, 31.7, 50.0, 65.7, 72.5, 111.3, 117.1, 120.9, 128.0,
129.6, 145.3, 171.4. Anal. Calcd for C17H23N1O: C, 69.19; H,
7.75; N, 10.77. Found: C, 69.23; H, 8.12; N, 10.22.
Gen er a l P r oced u r e for th e P r ep a r a tion of P yr a zoli-
d in e Der iva tives 4 a n d 5 a n d Com p ou n d s 8-10.
A
mixture of N-(1-benzotriazolylalkyl)-N,N′-disubstituted hy-
drazine 2 (2 mmol), alkene (4 mmol), and anhydrous zinc
bromide (20 mg) in dry methylene chloride (30 mL) was stirred
at rt for an appropriate time. After the reaction was com-
pleted, the mixture was washed with aqueous NaOH (2 N, 2
× 15 mL) and water (2 × 15 mL) and extracted with ethyl
acetate. The combined organic layers were dried over anhy-
drous sodium sulfate. After the removal of the solvent under
vacuum, the residue was purified by column chromatography
on silica gel to give the pure products.
3-P yr r olid on yl-1,2-d ip h en ylp yr a zolid in e (4a ): 1H NMR
(CDCl3) δ 1.85-1.98 (m, 2 H), 2.17-2.26 (m, 1 H), 2.36-2.48
(m, 3 H), 3.06-3.16 (m, 1 H), 3.22-3.32 (m, 1 H), 3.56-3.68
(m, 1 H), 3.89-3.98 (m, 1 H), 6.11 (t, 1 H, J ) 6.5 Hz), 6.84-
6.96 (m, 4 H), 7.06 (d, 2 H, J ) 8.1 Hz), 7.23-7.32 (m, 4 H);
13C NMR (CDCl3) δ 18.1, 30.4, 31.6, 43.7, 49.1, 72.9, 113.8,
114.5, 119.7, 120.9, 129.1, 149.8, 150.0, 174.9. Anal. Calcd
for C19H21N3O: C, 74.23; H, 6.89; N, 13.68. Found: C, 74.50;
H, 7.02; N, 13.77.
1,2-Diph en yl-3-(N-m eth ylacetam idyl)pyr azolidin e (4b):
1H NMR (CDCl3) δ 2.01-2.08 (m, 1 H), 2.15 (s, 3 H), 2.39-
2.46 (m, 1 H), 2.76 (s, 3 H), 3.46-3.54 (m, 1 H), 3.96-4.08 (m,
1 H), 6.54 (t, 1 H, J ) 4.5 Hz), 6.84-6.98 (m, 6 H), 7.22-7.28
(m, 4 H); 13C NMR (CDCl3) δ 22.7, 30.8, 31.0, 48.8, 75.2, 113.9,
114.1, 119.5, 120.6, 129.1, 149.9 (overlapped), 170.8. Anal.
Calcd for C18H21N3O: C, 73.18; H, 7.17; N, 14.23. Found: C,
73.48; H, 7.35; N, 14.37.
1-P h en yl-2-(p h en ylca r b a m oyl)-3-et h oxyp yr a zolid in e
(4c): 1H NMR (CDCl3) δ 1.16 (t, 3 H, J ) 6.9 Hz), 2.12-2.26
(m, 1 H), 2.29-2.40 (m, 1 H), 3.52-3.68 (m, 1 H), 3.70-3.85
(m, 2 H), 3.86-4.00 (m, 1 H), 5.81-5.87 (m, 1 H), 6.88-7.10
(m, 2 H), 7.15 (d, 2 H, J ) 8.2 Hz), 7.22-7.36 (m, 4 H), 7.45
(d, 2 H, J ) 8.0 Hz), 8.14 (br s, 1 H); 13C NMR (CDCl3) δ 14.8,
33.6, 53.2, 63.9, 88.4, 115.5, 119.2, 122.0, 123.3, 128.8, 129.0,
138.0, 150.9, 156.6. Anal. Calcd for C18H21N3O2: C, 69.42;
H, 6.80; N, 13.50. Found: C, 69.40; H, 7.15; N, 13.53.
J O9709110