A convenient synthesis of 1-alkyl-1-phenylhydrazines from N-aminophthalimide

Article abstract of DOI:10.1081/SCC-120015563

N-Alkylaminophthalimides were synthesized by condensation of N-aminophthalimide with aldehydes, and subsequent reduction of the intermediate with pyridine-borane in acetic acid. N-Phenylation and removal of the phthalimide group gave 1-alkyl-1-phenylhydrazines in high yield.

Full text of DOI:10.1081/SCC-120015563

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A Convenient Synthesis of 1-Alkyl-1-phenylhydrazines
from N -Aminophthalimide
Shigeru Nara a , Takeshi Sakamoto a , Etsuko Miyazawa a & Yasuo Kikugawa a b
a Faculty of Pharmaceutical Sciences , Josai University , Sakado, Saitama, Japan
b Faculty of Pharmaceutical Sciences , Josai University , 1-1 Keyakidai, Sakado, Saitama
350-0295, Japan
Published online: 20 Aug 2006.
To cite this article: Shigeru Nara , Takeshi Sakamoto , Etsuko Miyazawa & Yasuo Kikugawa (2003) A Convenient Synthesis
of 1-Alkyl-1-phenylhydrazines from N -Aminophthalimide, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:1, 87-98, DOI: 10.1081/SCC-120015563
To link to this article: http://dx.doi.org/10.1081/SCC-120015563
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 1, pp. 87–98, 2003
A Convenient Synthesis of
1-Alkyl-1-phenylhydrazines from
N-Aminophthalimide
Shigeru Nara, Takeshi Sakamoto, Etsuko Miyazawa,
*
and Yasuo Kikugawa
Faculty of Pharmaceutical Sciences, Josai University,
Sakado, Saitama, Japan
ABSTRACT
N-Alkylaminophthalimides were synthesized by condensation of
N-aminophthalimide with aldehydes, and subsequent reduction of
the intermediate with pyridine-borane in acetic acid. N-Phenylation
and removal of the phthalimide group gave 1-alkyl-1-phenylhydra-
zines in high yield.
Key Words: Phenylhydrazine; Pyridine-borane; N-aminophthali-
mide; Reductive amination.
*Correspondence: Yasuo Kikugawa, Faculty of Pharmaceutical Sciences, Josai
University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. Fax: +81 49 271
7981; E-mail: kikugawa@josai.ac.jp.
87
DOI: 10.1081/SCC-120015563
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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88
Nara et al.
In the course of our investigation of the chemistry of electron-
deficient nitrogen, we required 1-substituted 1-phenylhydrazines.
For the synthesis of substituted hydrazines, mono-,[1] di-,[2] and tri-[3]
protected hydrazines are used for starting compounds. Among the
protecting groups, tert-butoxycarbonyl (BOC), benzyloxycarbonyl (Z),
and tosyl (Ts) groups are commonly used. Very recently, N-BOC-
aminophthalimide (1) was used for the synthesis of 1,1-disubstituted
hydrazines.[4] In this case, 1, which has three electron-withdrawing
carbonyl groups in the molecule, is ideally suited for a subsequent
Mitsunobu reaction. This is the first example in which a phthalimide
group has been used for the protection of hydrazine. However,
compound 1 is notaccessible by directbenzyloxycarbonylaiot n of
N-aminophthalimide (2).[4]
For the introduction of alkyl groups on hydrazine, reductive and
catalytic alkylations of protected hydrazines are often carried out. For
example, tosylhydrazones have been reduced by pyridine-borane
(pyrBH3),[5] NaBH3CN[6] or HSiEt3 to tosylhydrazines, and phenyl-
[7]
hydrazones have been catalytically alkylated by alkylating agents in the
presence of quaternary ammonium salts.[8]
Previously, pyrBH3 was used for reductive alkylation of amines[9]
instead of NaBH3CN.[10] PyrBH3 does not suffer from severe toxicity
that is associated with NaBH3CN. In previous work, we investigated
pyrBH3 reduction of various functional groups.[11] In an extension
of this work, we now have studied the reductive alkylation of 2 with
aldehydes as a convenient route to phthalimide-protected hydrazines.
For the synthesis of 1-alkyl-1-phenylhydrazines we have designed the
route shown in Sch. 1.
Scheme 1.

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1-Alkyl-1-phenylhydrazines
89
We have performed
a
2
step sequence for the synthesis
of N-(alkylamino)phthalimide (4), that involves the initial formation
of N-(alkylideneamino)phthalimides (3) and subsequentreduicotn
with pyrBH3. The condensation reaction was carried out with
2 and aldehydes in 1,4-dioxane by addition of 2-3 drops of conc. HCl
to give the corresponding 3 in good yields. The results are presented
in Table 1.
Initially, the reduction of 3a to 4a was examined in EtOH-20%HCl
(3:1) or in CF3CO2H (TFA), and 4a was obtained in moderate yields
along with 5 (Sch. 2). Formation of 5 can be rationalized by assuming
a nucleophilic addition of 4a to 3a and subsequenteliminaiot n of
a N-aminophthalimide group (Sch. 3). The pyrBH3 reduction of 3a in
the presence of 4a was performed as a control experiment and 5 was
obtained in increased yield (47%). Carrying out the reduction of 3a–g
in acetic acid suppressed the side reaction and compounds 4a–g were
obtained in good yields (Table 2).
For the synthesis of 1-alkyl-1-phenylhydrazines (7a–g), N-phenyla-
tion of 4a–g was performed with triphenylbismuth and cupric acetate,
initially at room temperature and then in refluxing CH2Cl2, to give 6a–g
in 82–97% yields.[12] Compounds 7a–g were obtained in 90–99% yields
by deprotection of the phthalimide group with hydrazine hydrate in
ethanol under the usual conditions[12,13] (Sch. 4) (Table 3).
In conclusion N-aminophthalimide (2) was successfully used for
the synthesis of 1-alkyl-1-phenylhydrazines (7a–g) by reductive alkylation
Table 1. Condensation reaction of 2 with aldehydes in 1,4-dioxane.
Molar ratio
aldehyde/reagent
Temp.
(ꢀC)
Time
(min)
Productyield
(%)
Entry
1
2
3
4
5
6
7
1.05
1.05
1.05
1.05
1.05
1.05
1.05
25
0
3
30
35
30
30
30
15
3a (76)
3b (55)
3c (90)
3d (81)
3e (87)
3f (71)
3g (80)
25
25
25
25
25

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90
Nara et al.
Scheme 2.
Scheme 3.
Table 2. Reduction of 3 with pyrBH3.
Starting PyrBH3
Entry material (equiv.)
Temp. Reaction Product
(ꢀC)
time (h) yield (%)
Solvent
1
2
3a
3a
3
5
EtOH–20%HCl
(3:1)
TFA–CH2Cl2
(1:2)
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
0
1
1
4a (76)
5a (11)
4a (45)
5a (13)
4a (86)
4b (78)
4c (86)
4d (81)
4e (82)
4f (92)
4g (80)
0
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
5
5
5
5
5
5
5
25
25
25
25
25
25
25
0.25
1
2.5
0.5
1
1
0.25
3g
of 2 with carbonyl compounds using pyrBH3 and subsequent
N-phenylation. Deprotection of phthalimide group was performed as
usual in high yield.
EXPERIMENTAL
All melting points were determined with a Yanagimoto hot-stage
melting point apparatus and are uncorrected. 1H NMR spectra
were measured at 270 MHz on a JEOL JNM-EX270 spectrometer with

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1-Alkyl-1-phenylhydrazines
91
Scheme 4.
Table 3. N-Phenylation of 4.
Entry
Starting material
Reaction time (h)
Product yield (%)
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
7
7
8
15
7
7
14
6a (97)
6b (89)
6c (84)
6d (86)
6e (89)
6f (86)
6g (82)
4g
tetramethylsilane (Me4Si) as an internal reference and CDCl3 as the sol-
1
vent. H NMR spectral data are reported in parts per million (ꢀ) relative
t o M4eSi. IR spectra were recorded on a JASCO IR 810 spectropho-
tometer. Mass spectra were obtained with a JEOL JMS-700 spectrometer
with a directinletsystem at70 eV. Elemental analyses were performed in
the Microanalytical Laboratory of this University.
Synthesis of N-(Phenylpropylideneamino)phthalimide (3a):
Typical Procedure
To a solution of 2 (1.00 g, 6.17 mmol) and phenylpropionaldehyde
(867 mg, 6.46 mmol) in 1,4-dioxane (100 mL) was added concentrated
hydrochloric acid (2 drops) at room temperature. After the mixture
was stirred for 3–5 min, the solvent was evaporated under reduced pres-
sure and the crude product was chromatographed on a column of silica
gel with AcOEt–hexane (1:3) as an eluent to give 3a (1.31 g, 76%). Other
N-(alkylideneamino)phthalimides (3b–g) were prepared similarly.

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Nara et al.
3a: Yield 76%; yellow crystals: m.p. 94–96ꢀC (Et2O/hexane); IR
1
(KBr) 1795, 1785, 1720; H NMR 2.81–2.90 (2H, m, CH2), 3.00 (2H, t,
J ¼ 7.4, CH2), 7.19–7.36 (5H, m, Ar-H), 7.73–7.79 (2H, m, Ar-H),
7.86–7.93 (2H, m, Ar-H), 8.70 (1H, t, J ¼ 5.1, CH¼N); EIMS m/z (%)
278 (Mþ, 12), 130 (100). Anal. Calcd for C17H14N2O2: C, 73.37; H, 5.07;
N, 10.07. Found: C, 73.30; H, 4.88; N, 10.14.
3b: Yield 55%; colorless crystals: m.p. 111–112ꢀC (benzene/hexane);
1
IR (KBr) 1790, 1775, 1720 cmꢁ1; H NMR 3.86 (2H, d, J ¼ 6.0, CH2),
7.25–7.39 (5H, m, Ar-H), 7.75–7.80 (2H, m, Ar-H), 7.86–7.91 (2H, m, Ar-
H), 8.08 (1H, t, J ¼ 5.9, CH¼N); EIMS m/z (%) 264 (Mþ, 100), 173 (22).
Anal. Calcd for C16H12N2O2: C, 72.72; H, 4.58; N, 10.60. Found: C,
72.71; H, 4.42; N, 10.75.
3c: Yield 90%; lightyellow crysatls: m.p. 165–166 ꢀC (benzene/hex-
ane); IR (KBr) 1785, 1765, 1710 cmꢁ1; 1H NMR 7.41–7.52 (3H, m, Ar-H),
7.74–7.80 (2H, m, Ar-H), 7.87–7.94 (4H, m, Ar-H), 9.39 (1H, s, CH¼N);
EIMS m/z (%) 250 (Mþ, 44), 105 (100). Anal. Calcd for C15H10N2O2: C,
71.99; H, 4.03; N, 11.19. Found: C, 72.07; H, 4.02; N, 11.13.
3d: Yield 81%; lightyellow crystals: m.p. 200 ꢀC (AcOEt/hexane); IR
(KBr) 1780, 1760, 1725 cmꢁ1 1H NMR 7.13–7.15 (2H, m, Ar-H),
;
7.36–7.44 (3H, m, Ar-H), 7.51 (1H, d, J ¼ 7.7, CH), 7.54 (1H, dd,
J ¼ 7.7, 1.8, CH), 7.76–7.79 (2H, m, Ar-H), 7.90–7.93 (2H, m, Ar-H),
9.27 (1H, dd, J ¼ 7.7, 2.0, CH¼N); EIMS m/z (%) 276 (Mþ, 20), 199
(22), 129 (100). Anal. Calcd for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14.
Found: C, 73.83; H, 4.32; N, 9.93.
3e: Yield 87%; colorless crystals: m.p. 165–167ꢀC (hexane); IR (KBr)
1800, 1770, 1720 cmꢁ1; 1H NMR 2.41 (3H, s, CH3), 7.75–7.80 (6H, m, Ar-
H), 7.89–7.93 (2H, m, Ar-H), 9.32 (1H, s, CH¼N); EIMS m/z (%) 264
(Mþ, 30), 117(100). Anal. Calcd for C16H12N2O2: C, 72.72; H, 4.58; N,
10.60. Found: C, 73.01; H, 4.68; N, 10.63.
3f: Yield 71%; colorless crystals: m.p. 206ꢀC (AcOEt); IR (KBr)
1
1800, 1780, 1730 cmꢁ1; H NMR 7.44 (2H, d, J ¼ 8.5, Ar-H), 7.78–7.81
(2H, m, Ar-H), 7.84 (2H, d, J ¼ 8.5, Ar-H), 7.92–7.94 (2H, m, Ar-H), 9.43
(1H, s, CH¼N); EIMS m/z (%) 286 (Mþ þ 2, 10), 284 (Mþ, 30), 105
(100). Anal. Calcd for C15H9ClN2O2: C, 63.28; H, 3.10; N, 9.84.
Found: C, 63.40; H, 2.92; N, 9.84.
3g: Yield 80%; yellow crystals: m.p. 193–195ꢀC (AcOEt); IR (KBr)
1790, 1765, 1720 cmꢁ1; 1H NMR 3.88 (3H, s, CH3O), 6.97 (2H, d, J ¼ 8.8,
Ar-H), 7.76–7.79 (2H, m, Ar-H), 7.85 (2H, d, J ¼ 8.8, Ar-H), 7.90–7.93
(2H, m, Ar-H), 9.25 (1H, s, CH¼N); EIMS m/z (%) 280 (Mþ, 31), 133
(100). Anal. Calcd for C16H12N2O3: C, 68.56; H, 4.32; N, 9.99. Found: C,
68.43; H, 4.21; N, 9.96.

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1-Alkyl-1-phenylhydrazines
93
Synthesis of N-(3-Phenylpropylamino)phthalimide (4a):
Typical Procedure
To a solution of 3a (200 mg, 0.719 mmol) in CH3CO2H (5 mL)
was added pyrBH3 (334 mg, 3.60 mmol) at room temperature. After the
reaction mixture was stirred for 15 min, the solvent was evaporated under
reduced pressure and 10% HCl (2 mL) was added with ice cooling. After
the solution was stirred for 30 min, 5% Na2CO3 (20 mL) was added to the
mixture. The mixture was extracted with AcOEt (20 mL ꢂ 2) and the
combined organic layer was washed with brine, dried (Na2SO4), and
concentrated. After removal of solvent under reduced pressure, the
residue was chromatographed on a column of silica gel with AcOEt–
hexane (1:3) as an eluentto give 4a (174 mg, 86%). Other N-(alkylamino)
phthalimides (4b–g) were prepared similarly.
4a: Yield 86%; lightyellow crystals: m.p. 55–57 ꢀC (Et2O/hexane); IR
(KBr) 3300, 1785, 1770, 1720 cmꢁ1; 1H NMR 1.85–1.94 (2H, m, CH2), 2.75
(2H, t, J ¼ 8.0, CH2), 3.08 (2H, m, CH2), 4.59 (1H, br s, NH), 7.17–7.30
(5H, m, Ar-H), 7.71–7.76 (2H, m, Ar-H), 7.81–7.86 (2H, m, Ar-H); EIMS
m/z (%) 280 (Mþ, 47), 175 (100). Anal. Calcd for C17H16N2O2: C, 72.84;
H, 5.75; N, 9.99. Found: C, 72.67; H, 5.83; N, 9.95.
4b: Yield 78%; lightyellow crystals: m.p. 79–80 ꢀC (benzene/hexane);
IR (KBr) 3250, 1780, 1765, 1715 cmꢁ1; 1H NMR 2.93 (2H, t, J ¼ 7.5, CH2),
3.36 (2H, dd, J ¼ 7.5, 6.0, CH2), 4.62 (1H, t, J ¼ 6.0, NH), 7.16–7.36 (5H,
m, Ar-H), 7.71–7.75 (2H, m, Ar-H), 7.80–7.85 (2H, m, Ar-H); EIMS m/z
(%) 266 (Mþ, 3), 175 (100). Anal. Calcd for C16H14N2O2: C, 72.16; H,
5.30; N, 10.52. Found: C, 72.06; H, 5.27; N, 10.45.
4c: Yield 86%; lightyellow crystals: m.p. 114 ꢀC (AcOEt/hexane); IR
1
(KBr) 3300, 1780, 1760, 1720 cmꢁ1; H NMR 4.21 (2H, d, J ¼ 5.5, CH2),
4.79 (1H, t, J ¼ 5.5, NH), 7.26–7.37 (3H, m, Ar-H), 7.44–7.47 (2H, m, Ar-
H), 7.70–7.75 (2H, m, Ar-H), 7.79–7.84 (2H, m, Ar-H); EIMS m/z (%)
252 (Mþ, 12), 91 (100). Anal. Calcd for C15H12N2O2: C, 71.42; H, 4.79;
N, 11.10. Found: C, 71.38; H, 4.51; N, 11.13.
4d: Yield 81%; colorless crystals: m.p. 138–139ꢀC (benzene/hexane);
1
IR (KBr) 3300, 1780, 1760, 1720 cmꢁ1; H NMR 3.86 (2H, t, J ¼ 5.5,
CH2), 4.73 (1H, br s, NH), 6.33 (1H, dt, J ¼ 16.1, 6.6, CH), 6.55 (1H,
d, J ¼ 16.1, CH), 7.21–7.35 (5H, m, Ar-H), 7.69–7.73 (2H, m, Ar-H),
7.82–7.85 (2H, m, Ar-H); EIMS m/z (%) 278 (Mþ, 10), 117 (100). Anal.
Calcd for C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: 73.36; H,
4.96; N, 9.91.
4e: Yield 82%; yellow crystals: m.p. 104ꢀC (hexane); IR (KBr) 3300,
;
1770, 1760, 1710 cmꢁ1 1H NMR 2.32 (3H, s, CH3), 4.17 (2H, d,

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Nara et al.
J ¼ 5.9, CH2), 4.76 (1H, t, J ¼ 5.9, NH), 7.13 (2H, d, J ¼ 8.1, Ar-H), 7.33
(2H, d, J ¼ 8.1, Ar-H), 7.70–7.75 (2H, m, Ar-H), 7.79–7.84 (2H, m, Ar-H);
EIMS m/z (%) 266 (Mþ, 4), 105 (100). Anal. Calcd for: C16H14N2O2: C,
72.17; H, 5.30; N, 10.52. Found: C, 72.27; H, 5.42; H, 10.53.
4f: Yield 92%; colorless crystals: m.p. 140ꢀC (benzene/hexane); IR
(KBr), 3300, 1780, 1760, 1720 cmꢁ1; 1H NMR 4.20 (2H, d, J ¼ 5.1, CH2),
4.31 (1H, t, J ¼ 5.1, NH), 7.30 (2H, d, J ¼ 8.4, Ar-H), 7.40 (2H, d, J ¼ 8.4,
Ar-H), 7.71–7.73 (2H, m, Ar-H), 7.83–7.85 (2H, m, Ar-H); EIMS m/z
(%) 288 (Mþ þ 2, 2), 286 (Mþ, 6), 125 (100). Anal. Calcd for
C15H11ClN2O2: C, 62.84; H, 3.87; N, 9.77. Found: C, 62.62; H, 4.09;
N, 9.71.
4g: Yield 80%; yellow crystals: m.p. 132ꢀC (benzene/hexane); IR
1
(KBr) 3280, 1780, 1760, 1720 cmꢁ1; H NMR 3.79 (3H, s, CH3O), 4.15
(2H, d, J ¼ 5.1, CH2), 4.74 (1H, t, J ¼ 5.1, NH), 6.87 (2H, d, J ¼ 8.5,
Ar-H), 7.36 (2H, d, J ¼ 8.5, Ar-H), 7.70–7.73 (2H, m, Ar-H), 7.80–7.84
(2H, m, Ar-H); EIMS m/z (%) 282 (Mþ, 2), 121 (100). Anal. Calcd
for C16H14N2O3: C, 68.07; H, 5.00; N, 9.92. Found: C, 68.34; H, 4.86;
N, 9.83.
5a: A pale yellow oil: IR (Neat) 1785, 1720 cmꢁ1; 1H NMR 1.74 (4H,
quint, J ¼ 7.7, CH2), 2.72 (4H, t, J ¼ 7.7, CH2), 3.26 (4H, t, J ¼ 7.7, CH2),
7.12–7.26 (10H, m, Ar-H), 7.71–7.74 (2H, m, Ar-H), 7.80–7.83 (2H, m,
Ar-H); EIMS m/z (%) 398 (Mþ, 39), 189 (100). HRMS calcd for
C26H26N2O2 398.1994, found 398.1994.
Synthesis of N-Phenyl-N-(3-phenylpropyl)aminophthalimide (6a):
Typical Procedure
A mixture of 4a (100 mg, 0.359 mmol), triphenylbismuth (316 mg,
0.718 mmol), cupric acetate (98 mg, 0.539 mmol), and triethylamine
(54 mg, 0.539 mmol) was stirred for 1.5 h at room temperature under
Ar and then refluxed for 15 h. After completion of the reaction, the
solution was diluted with AcOEt (30 mL) and filtered through celite.
The filtrate was evaporated under reduced pressure. The crude product
was chromatographed on a column of silica gel with AcOEt–hexane (4:1)
to give 6a (110 mg, 86%). Other N-alkyl-N-phenylaminophthalimides
(6b–g) were prepared similarly.
6a: Yield 97%; yellow crystals: m.p. 124.5–125ꢀC (Et2O/hexane); IR
1
(KBr) 1790, 1730 cmꢁ1; H NMR 1.94–2.00 (2H, m, CH2), 2.79 (2H, t,
J ¼ 7.3, CH2), 3.76 (2H, t, J ¼ 7.3, CH2), 6.76 (2H, d, J ¼ 7.8, Ar-H), 6.88
(1H, t, J ¼ 7.3, Ar-H), 7.17–7.29 (7H, m, Ar-H), 7.79–7.82 (2H, m, Ar-H),

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1-Alkyl-1-phenylhydrazines
95
7.89–7.93 (2H, m, Ar-H); EIMS m/z (%) 356 (Mþ, 91), 251 (100). Anal.
Calcd for C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found: C, 77.32; H,
5.67; N, 7.59.
6b: Yield 89%; yellow crystals: m.p. 124–124.5ꢀC (benzene/hexane);
IR (KBr) 1790, 1735 cmꢁ1; 1H NMR 3.01 (2H, t, J ¼ 8.1, CH2), 3.99 (2H,
t, J ¼ 8.1, CH2), 6.81 (2H, d, J ¼ 7.7, Ar-H), 6.89 (1H, t, J ¼ 7.3, Ar-H),
7.10–7.27 (7H, m, Ar-H), 7.79–7.84 (2H, m, Ar-H), 7.86–7.91 (2H, m, Ar-
H); EIMS m/z (%) 342 (Mþ, 15), 251 (100). Anal. Calcd for C22H18N2O2:
C, 77.17; H, 5.30; N, 8.18. Found: C, 77.07; H, 5.19; N, 8.02.
6c: Yield 84%; yellow crystals: m.p. 134–136ꢀC (benzene/hexane); IR
1
(KBr) 1790, 1725 cmꢁ1; H NMR 4.93 (2H, s, CH2), 6.83–6.94 (3H, m,
Ar-H), 7.20–7.31 (5H, m, Ar-H), 7.50–7.53 (2H, m, Ar-H), 7.70–7.76
(2H, m, Ar-H), 7.78–7.84 (2H, m, Ar-H); EIMS m/z (%) 328 (Mþ, 25),
181 (100). Anal. Calcd for C21H16N2O2: C, 76.81; H, 4.91; N, 8.53.
Found: C, 76.88; H, 4.81; N, 8.25.
6d: Yield 86%; yellow crystals: m.p. 137–138ꢀC (benzene/hexane); IR
(KBr) 1780, 1730 cmꢁ1; 1H NMR 4.54 (2H, d, J ¼ 8.0, CH2), 6.87 (1H, dt,
J ¼ 16.1, 8.0, CH), 6.55 (1H, d, J ¼ 16.1, CH), 7.19–7.30 (10H, m, Ar-H),
7.74–7.77 (2H, m, Ar-H), 7.85–7.88 (2H, m, Ar-H); EIMS m/z (%) 354
(Mþ, 20), 117 (100). Anal. Calcd for C23H18N2O2: C, 77.95; H, 5.12; N,
7.90. Found: C, 77.95; H, 5.25; N, 7.90.
6e: Yield 89%; yellow crystals: m.p. 150–151ꢀC (benzene/hexane); IR
1
(KBr) 1780, 1730 cmꢁ1; H NMR 2.26 (3H, s, CH3), 4.89 (2H, s, CH2),
6.84–6.94 (3H, m, Ar-H), 7.07 (2H, d, J ¼ 8.0, Ar-H), 7.20–7.26 (2H, m,
Ar-H), 7.36–7.40 (2H, m, Ar-H), 7.72–7.75 (2H, m, Ar-H), 7.80–7.83 (2H,
m, Ar-H); EIMS m/z (%) 342 (Mþ, 27), 105 (100). Anal. Calcd for
C22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C, 77.31; H, 5.53; N, 7.90.
6f: Yield 86%; yellow crystals: m.p. 145ꢀC (benzene/hexane); IR
(KBr) 1790, 1730 cmꢁ1 1H NMR 4.90 (2H, s, CH2), 6.03 (2H, d,
;
J ¼ 7.7, Ar-H), 6.93 (1H, t, J ¼ 7.7, Ar-H), 7.21–7.27 (4H, m, Ar-H),
7.47 (2H, d, J ¼ 8.4, Ar-H), 7.74–7.77 (2H, m, Ar-H), 7.82–7.85 (2H,
m, Ar-H); EIMS m/z (%) 364 (Mþ þ 2, 8), 362 (Mþ, 23), 215 (100).
Anal. Calcd for C21H15ClN2O2: C, 69.52; H, 4.17; N, 7.72. Found: C,
69.48; H, 4.22; N, 7.73.
6g: Yield 82%; colorless crystals: m.p. 157ꢀC (benzene/hexane); IR
1
(KBr) 1780, 1730; H NMR 3.73 (3H, s, CH3O), 4.86 (2H, s, CH2), 6.79
(2H, d, J ¼ 8.7, Ar-H), 6.86 (2H, d, J ¼ 9.0, Ar-H), 6.92 (1H, t, J ¼ 7.5,
Ar-H), 7.24 (2H, dd, J ¼ 9.0, 7.5, Ar-H), 7.40 (2H, d, J ¼ 8.7, Ar-H),
7.70–7.81 (4H, m, Ar-H); EIMS m/z (%) 358 (Mþ, 10), 121 (100).
Anal. Calcd for C22H18N2O3: C, 73.73; H, 5.06; N, 7.82. Found: C,
73.77; H, 5.12; N, 7.81.

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96
Nara et al.
Synthesis of 1-Phenyl-1-(3-phenylpropyl)hydrazine (7a):
Typical Procedure
To 7a (400 mg, 1.12 mmol) in EtOH (10 mL) was added
NH2NH2ꢃH2O (80%) (0.16 mL, 2.81 mmol) at room temperature. After
refluxing the reaction mixture for 4 h, EtOH was evaporated under
reduced pressure. To the residue benzene (5 mL) was added and insoluble
material was removed by filtration. After evaporation of the filtrate, the
crude productwas chromatographed on a column of silica gel with ben-
zene as an eluentto give 7a (231 mg, 91%). Other 1-alkyl-1-phenylhydra-
zines (7b–g) were prepared similarly.
1
7a: Yield 91%; a pale yellow oil: IR (Neat) 3340, 1600; H NMR
(DMSO-d6) 1.88 (2H, quint, J ¼ 7.7, CH2), 2.62 (2H, t, J ¼ 7.7, CH2),
3.31–3.37 (2H, m, CH2), 4.20 (2H, br s, NH2), 6.59 (1H, t, J ¼ 7.3, Ar-H),
6.91 (2H, d, J ¼ 7.6, Ar-H), 7.08–7.32 (7H, m, Ar-H); EIMS m/z (%) 226
(Mþ, 55), 121 (100). HRMS calcd for C15H18N2 226.1470, found
226.1472.
7b: Yield 91%; colorless crystals: m.p. 48–50ꢀC (hexane); IR (Neat)
1
3330, 1600 cmꢁ1; H NMR 2.92 (2H, t, J ¼ 7.7, CH2), 3.55 (2H, br s,
NH2), 3.66 (2H, t, J ¼ 7.7, CH2), 6.78 (1H, t, J ¼ 8.1, Ar-H), 6.95 (2H,
d, J ¼ 7.9, Ar-H), 7.17–7.33 (7H, m, Ar-H); EIMS m/z (%) 212 (Mþ, 16),
121 (100). Anal. Calcd for C14H16N2: C, 79.21; H, 7.60; N, 13.20. Found:
C, 79.16; H, 7.68; N, 13.18.
1
7c: Yield 96%; a pale yellow oil: IR (Neat) 3340, 1600 cmꢁ1; H NMR
3.56 (2H, s, CH2), 4.60 (2H, s, NH2), 6.81 (1H, t, J ¼ 7.3, Ar-H), 7.10
(2H, d, J ¼ 7.8, Ar-H), 7.23–7.38 (7H, m, Ar-H); EIMS m/z (%) 198
(Mþ, 27), 107 (100). HRMS calcd for C13H14N2 198.1157, found, 198.1143.
7d: Yield 99%; yellow crystals: m.p. 53–54ꢀC (pet. ether); IR (KBr)
1
3320, 1620 cmꢁ1; H NMR 3.06 (2H, br s, NH2), 4.19 (2H, dd, J ¼ 6.2,
1.3, CH2), 6.27 (1H, dt, J ¼ 15.8, 6.2, CH), 6.63 (1H, d, J ¼ 15.8, CH),
6.82 (1H, t, J ¼ 7.3, Ar-H), 7.14 (2H, d, J ¼ 7.9, Ar-H), 7.20–7.39 (7H, m,
Ar-H); EIMS m/z (%) 224 (Mþ, 21), 107 (100). Anal. Calcd
for C15H16N2: C, 80.32; H, 7.19; N, 12.49. Found: C, 80.13; H, 7.16;
N, 12.37.
7e: Yield 98%; colorless crystals: m.p. 39–40ꢀC (pet. ether); IR (KBr)
1
3290, 1590 cmꢁ1; H NMR 2.34 (3H, s, CH3), 3.52 (2H, br s, NH2), 4.54
(2H, s, CH2), 6.78 (1H, t, J ¼ 7.3, Ar-H), 7.01–7.30 (8H, m, Ar-H); EIMS
m/z (%) 212 (Mþ, 48), 107 (100). Anal. Calcd for C14H16N2: C, 79.21; H,
7.60; N, 13.20. Found: C, 78.99; H, 7.61; N, 13.20.
7f: Yield 93%; yellow crystals: m.p. 40ꢀC (pet. ether); IR (KBr) 3360,
1600 cmꢁ1; 1H NMR 3.58 (2H, br s, NH2), 4.56 (2H, s, CH2), 6.83 (1H, t,

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1-Alkyl-1-phenylhydrazines
97
J ¼ 7.3, Ar-H), 7.05 (2H, d, J ¼ 7.9, Ar-H), 7.22–7.32 (6H, m, Ar-H);
EIMS m/z (%) 234 (Mþþ 2, 6), 232 (Mþ, 17), 107 (100). Anal. Calcd
for C13H13N2Cl: C, 67.10; H, 5.63; N, 12.04. Found: C, 66.97; H, 5.56;
N, 12.06.
7g: Yield 94%; lightyellow crystals: m.p. 71–72 ꢀC (Et2O/hexane); IR
1
(KBr) 3350, 1600 cmꢁ1; H NMR (DMSO-d6) 3.72 (3H, s, CH3O), 4.23
(2H, br s, NH2), 4.52 (2H, s, CH2), 6.61 (1H, t, J ¼ 7.2, Ar-H), 6.87 (2H,
d, J ¼ 8.6, Ar-H), 6.98 (2H, d, J ¼ 9.2, Ar-H), 7.12 (2H, dd, J ¼ 9.2, 7.2,
Ar-H), 7.20 (2H, d, J ¼ 8.6, Ar-H); EIMS m/z (%) 228 (Mþ, 10), 121
(100). Anal. Calcd for C14H16N2O: C, 73.66; H, 7.06; N, 12.27. Found: C,
73.66; H, 6.89; N, 12.23.
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Received in Japan August7, 2001