Synthesis of hindered hydrazones and their reaction with thionyl chloride

Article abstract of DOI:10.1002/hc.10125

Hydrazones 12a-c and ketazines 13a-c were prepared by the reaction of ketones 11a-c with hydrazine hydrate depending on the temperature and the reaction time. Some ketone (aryl)hydrazone derivatives 14a,c,e reacted with thionyl chloride to afford the chlo

Full text of DOI:10.1002/hc.10125

Heteroatom Chemistry
Volume 14, Number 3, 2003
Synthesis of Hindered Hydrazones
and Their Reaction with Thionyl Chloride
Mohamed I. Hegab, Nasser A. Hassan, Emad M. El-Telbani,
Ibrahim S. Ahmed Farag, and Farouk M. E. Abdel-Megeid
Department of Photochemistry, National Research Centre, Dokki, Cairo, Egypt
Received 26 March 2002; revised 7 June 2002
directly from the reaction of the corresponding 4-
ABSTRACT: Hydrazones 12a–c and ketazines 13a–c
were prepared by the reaction of ketones 11a–c with
hydrazine hydrate depending on the temperature and
the reaction time. Some ketone (aryl)hydrazone deriva-
tives 14a,c,e reacted with thionyl chloride to aff-
ord the chlorothiadiazoline derivatives 15a–c. Surpris-
ingly, the chlorine atom in the latter compounds was
found to undergo smooth nucleophilic substitution,
and by boiling these compounds in absolute ethanol
gave the corresponding ethoxythiadiazoline deriva-
tives 16a–c. The structure of the ethoxythiadiazoline
16b was confirmed by single crystal X-ray determi-
chromanone derivative with hydrazine hydrate, but
could be formed from the reaction of ylidene mal-
ononitrile 2 with hydrazine hydrate.
ꢀ
C
nation. 2003 Wiley Periodicals, Inc. Heteroatom Chem
14:223–228, 2003; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.10125
INTRODUCTION
Harradence et al. [1] have reported that when an
ethanolic solution of 4-chromanone was refluxed
with an aqueous solution of hydrazine sulfate and
sodium acetate, the ketazine 1a was formed. In a
similar reaction of the corresponding 4-chromanone
derivatives with hydrazine hydrate, the ketazine
derivatives 1b–d were obtained as hydrates, which
were converted into the anhydrous ketazines on boil-
ing with acetic acid [2]. Recently, El-Desoky [3] re-
ported that the ketazine 1e could not be formed
Also, it has been reported [4–7] that the reac-
tions of thionyl chloride with some types of ke-
tone (aryl)hydrazones 3–6 gave the 1,2,3-thiadiazol-
S-oxides 7, 8 or the 1,2,3-thiadiazole derivatives 9,
10, respectively (Scheme 1).
These results prompted us to study such
reactions with some hindered [8] ketones, namely 3-
ethyl-1,2,3,4-tetrahydro-3-methylnaphthalen-1-one
Correspondence to: Farouk M. E. Abdel-Megeid; e-mail:
faroukezat@yahoo.com.
2003 Wiley Periodicals, Inc.
c
ꢀ
223

224 Hegab et al.
R1
O
S
X
R2
SO C H Me-4
N
2
6 4
S
S
N
NNHSO2C6H4Me-4
N
N
SOCl2
Z
Z
3
7
R2
Z = CH2, O, S
X
R1
13a-c
N
NNHSO2C6H4Me-4
N
in closed vial
at room temp.,
4 weeks
N2H4 (99%)
SO
Me
abs. EtOH,
brisk reflux,
6h.
S
S
SOCl2
N
N
Me
N
N
O
X
NNH2
Me
Me
4
8
N2H4 (99%)
abs. EtOH,
gentle reflux,
3h.
R1
S
R1
n
X
X
n
R2
N
R2
X
R1
R
R1
R
N
11a-c
12a-c
SOCl2
NNHR2
a, X = CH2, R = CH3, R = C2H5
1
2
1
2
b, X = O, R = R = CH3
1
2
c, X = O, R + R = (CH2)5
5
9
X = S, O, CH2; R = H, OMe,
R1 = H; RR1 = CH=CHCH=CH;
R2 = CONH2, tosyl; n = 1,2
ArNHNH2
abs.EtOH,
AcOH,
6h.
R1
NNHAr
N
SOCl2
R
C NNHCONH2
R
N
S
R1
R1
10
X
R2
6
14a-f
R = H, Me, OMe, Cl, NO2, Br, CN;
R1 = Me, CH2Ph
a, X = CH2, R1 = CH3, R2 = C2H5, Ar = 4-NO2C6H4
b, X = CH2, R1 = CH3, R2 = C2H5, Ar = 2,4,6-Cl3C6H2
c, X = O, R1 = R2 = CH3, Ar = 4-NO2C6H4
d, X = O, R1 = R2 = CH3, Ar = 2,4,6-Cl3C6H2
e, X = O, R1R2 = (CH2)5, Ar = 4-NO2C6H4
R1 = H, Ph
SCHEME 1
f, X = O, R1R2 = (CH2)5, Ar = 2,4,6-Cl3C6H2
SCHEME 2
(11a) [9], 3,3-dimethylchroman-4-one (11b) [10],
and spirochroman (2,1ꢁ)cyclohexane-4-one (11c)
[11].
spectra showed the molecular ion peak as the parent
peak.
Five new ketone arylhydrazone derivatives
14a,b,d–f were prepared by the reaction of the ke-
tones 11a–c with arylhydrazines in ethanol contain-
ing acetic acid. The preparation of the hydrazone 14c
was reported previously by Auwers and Mauss [12].
The 1H NMR spectra of 14a–f showed the NH signals
at δ 10.01–10.38, which are exchangeable with D2O.
When compounds 14a,c,e were treated with
thionyl chloride at 20◦C, they afforded the corre-
sponding chlorothiadiazolines 15a–c, respectively
(Scheme 3).
RESULTS AND DISCUSSION
When the ketones 11a–c were treated with hy-
drazine hydrate (99%) in absolute ethanol under
gentle reflux for 3 h they gave the corresponding hy-
drazones 12a–c in moderate yields (Scheme 2). The
structures of the hydrazones 12a–c were confirmed
by spectral data and microanalytical data. The IR
spectra showed absorption frequencies at 3325–
3285 cm−1 (νNH2) and 1605–1595 cm−1 (νC N), the 1H
NMR spectra showed the signal at δ 5.34–5.37 ppm
(br s, 2H, NH2, exchangeable with D2O), and the MS
spectra showed the molecular ion peak as the base
peak (M+, 100%).
It was noticed that when the hydrazone deriva-
tives 12a–c were stored in a closed vial for four
weeks at room temperature, they were converted into
the corresponding ketazines 13a–c. However, the lat-
ter could be obtained in good yields from the reac-
tion of the ketone and hydrazine hydrate in abso-
lute ethanol under brisk reflux for 6 h (Scheme 2).
The spectral data and microanalytical data verified
the structures of the ketazine derivatives. The MS
Ar
Ar
N
N
N
N
S
S
SOCl2
EtOH
boiling
Cl
1
R
14a,c,e
OC2H5
1
R
X
X
2
R
R2
15a-c
16a-c
a, X = CH2, R1 = CH3, R2 = C2H5, Ar = 4-NO2C6H4
b, X = O, R1 = R2 = CH3, Ar = 4-NO2C6H4
c, X = O, R1R2 = (CH2)5, Ar = 4-NO2C6H4
SCHEME 3

Synthesis of Hindered Hydrazones and Their Reaction with Thionyl Chloride 225
TABLE 1 Crystal Data, Bond Lengths, and Bond and Torsion
Angles of 16b
Crystal data
Crystal system
Space group
Triclinic
P1
7.3610 (5)
11.3212 (6)
13.1357 (7)
103.445
˚
a (A)
˚
b (A)
˚
c (A)
α (◦)
β (◦)
γ (◦)
105.962
108.238
3
˚
V (A )
936.79 (9)
2
1.366
0.048
0.057
Z
Dx(g cm−3
)
R
wR
FIGURE 1 Single crystal X-ray structure of 16b.
˚
Bond length (A)
O2 C17
N4 N7
N4 C13
N5 O6
1.4072 (6)
1.3615 (6)
1.2877 (6)
1.2255 (6)
1.2226 (6)
1.3833 (6)
The structures of 15a–c were established by the
spectral data as well as the microanalytical data.
N5 O12
N5 C16
1
The H NMR spectra indicated the absence of the
1
Bond and Torsion angles (◦)
NH and the methylene protons. The H NMR spec-
trum of compound 15a showed the presence of the
N7 N4 C13
N4 C13 C8
111.11 (4)
125.11 (5)
118.77 (5)
111.80 (5)
121.23 (4)
119.37 (6)
119.27 (5)
−176.44 (8)
−168.47 (7)
6.06 (5)
two diasteriomers (see Experimental Section). The
MS spectra of 15a–c showed the ion M+
Cl as
N4 C13 C17
O2 C17 C13
N4 N7 C15
N5 C16 C11
N5 C16 C20
N7 N4 C13 C8
C13 N4 N7 C15
N7 N4 C13 C7
the base peak (100%). Surprisingly, when 15b was
crystallized from ethanol it gave the ethoxythiadi-
azoline 16b. This means that the chlorine atom
can be easily replaced by a nucleophile. So, when
1
2
15a–c were boiled in ethanol for h they gave the
ethoxythiadiazolines 16a–c (Scheme 3). The struc-
tures of the latter compounds were verified by mi-
croanalytical data and spectral data. By X-ray anal-
ysis of a single crystal, the S configuration of 16b
(Fig. 1, Table 1) was established. The 1H NMR spec-
trum of the compound 16a showed the presence of
the two diasteriomers (see Experimental Section).
To our knowledge, these types of chlorothiadiazoline
derivatives 15a–c and consequently the ethoxythia-
diazoline derivatives 16a–c have not been reported
in the literature.
The single crystal for the X-ray diffraction analysis of
16b was obtained by slow evaporation of the corre-
sponding ethanol solution. The X-ray determination
was performed by the Central Services Laboratory,
National Research Centre, Cairo.
Preparation of Hydrazones 12a–c
A solution of the ketone 11a–c (0.01 mol) and hy-
drazine hydrate 99% (0.01 mol) in absolute ethanol
(Merck) was heated under gentle reflux for 3 h. Evap-
oration of the solvent under reduced pressure gave
the hydrazones 12a–c.
EXPERIMENTAL
The melting points are uncorrected. Microanalyses
were performed by the Central Services Laboratory,
National Research Centre, Cairo. H NMR spectra
1
were taken in a Varian Gemini 200 MHz spectrome-
ter with CDCl3 and DMSO-d6 as solvents (Cairo Uni-
versity, Faculty of Science). EI (70 eV). Mass spectra
were recorded on a G. C. MSQP 1000 Ex Shmadzu
spectrometer, National Research Centre. IR spectra
were obtained with PU 9712 infrared spectropho-
tometer for neat samples (for liquids) or KBr wafers
(for solid); National Research Centre, Dokki, Cairo).
3-Ethyl-3-methyl-1,2,3,4-tetrahydronaphthalen-1-
one Hydrazone (12a). Colorless oil (1.50 g, 75%)
purified by column chromatography (silica gel,
Merck 60, particle size 0.06–0.20 mm, ethyl ac-
etate/petroleum ether 40–60◦C 1:10). Anal calcd for
C13H18N2 (202.29): C, 77.18%; H, 8.96; N, 13.84%.
Found: C, 77.48; H, 8.79; N, 13.78%. IR (neat): νNH2
3320, 3285; νC 1600 cm−1. 1H NMR (CDCl3): δ 0.89
N

226 Hegab et al.
(t, J = 8.00 Hz, 3H, CH3CH2), 0.98 (s, 3H, CH3), 1.22
(q, J = 8.00 Hz, 2H, CH2CH3), 2.55 (d, J = 18.00 Hz,
1H, 4-CH Hb), 2.63 (d, J = 18.00 Hz, 1H, 4-CHa H ),
315 (18), 301 (32), 287 (15), 186 (62), 158 (100), 143
(91), 128 (85), 115 (86).
a
b
3.45 (s, 2H, CH2), 5.34 (br s, 2H, NH2, exchangeable
with D2O), 7.28–7.42 (m, 3H, ArH), 8.23 ppm (d,
J = 8.00 Hz, 1H, ArH). MS (EI): m/z (%) 202 (M,
100), 187 (8), 173 (37), 156 (30), 143 (13), 128 (16),
116 (13), 91 (60).
2,2-Dimethylchroman-4-azine (13b). Dark yell-
ow crystals (2.60 g, 76%), mp 191–193◦C. Anal calcd
for C22H24N2O2 (348.43): C, 75.83; H, 6.94; N, 8.04%.
Found: C, 75.55; H, 6.82; N, 7.85%. IR (KBr): νC
N
1600 cm−1. 1H NMR (CDCl3): δ 1.40 (s, 12H, 4 CH3),
3.00 (s, 4H, 2 CH2), 6.88–7.01 (m, 4H, ArH), 7.26–
7.35 (m, 2H, ArH), 8.16 ppm (d, J = 8.18 Hz, 2H,
ArH). MS (EI): m/z (%) 348 (M, 41), 333 (100), 173
(24), 160 (29), 120 (11), 91 (19).
2,2-Dimethylchroman-4-one Hydrazone (12b).
Colorless oil (1.10 g, 60%), purified by column chro-
matography (silica gel, Merck 60, particle size 0.06–
0.20 mm, ethyl acetate/petroleum ether 40–60◦C
1:10). Anal calcd for C11H14N2O (190.24): C, 69.44; H,
7.41; N, 14.72%. Found: C, 69.14; H, 7.39; N, 14.65%.
Spirochroman(2,1ꢁ)cyclohexane-4-azine
(13c).
Dark yellow crystals (3.3 g, 80%), mp 174–177◦C.
Anal calcd for C28H32N2O2 (428.56): C, 78.46; H, 7.52;
N, 6.53%. Found: C, 78.28; H, 7.48; N, 6.51%. IR
IR (neat): νNH2 3310, 3275; νC 1595 cm−1. 1H NMR
N
(CDCl3): δ 1.40 (s, 6H, 2 CH3), 2.70 (s, 2H, CH2), 5.37
(br s, 2H, NH2, exchangeable with D2O), 7.26–7.31
(m, 3H, ArH), 8.14 ppm (d, J = 8.05 Hz, 1H, ArH).
MS (EI): m/z (%) 190 (M, 91), 176 (37), 161 (100), 121
(52), 92 (35).
(KBr): νC 1600 cm−1. 1H NMR (CDCl3): δ 1.24–1.94
N
(m, 20H, 2 (CH2)5), 2.95 (s, 4H, 2 CH2), 6.91–7.00
(m, 4H, ArH), 7.26–7.36 (m, 2H, ArH), 8.13 ppm (d,
J = 8.18 Hz, 2H, ArH). MS (EI): m/z (%) 428 (M,
74), 413 (60), 213 (100), 199 (40), 172 (60), 156 (17),
120 (25), 91 (30).
Spirochroman(2,1ꢁ)cyclohexane-4-one Hydrazone
(12c). Colorless crystals (1.80 g, 80%), crystal-
lized from n-hexane; mp 73–75◦C. Anal calcd for
C14H18N2O (230.30): C, 73.01; H, 7.87; N, 12.16%.
Found: C, 72.91; H, 7.80; N, 12.01%. IR (KBr): νNH2
3295, 3215; νC N 1605 cm−1. 1H NMR (CDCl3): δ 1.16–
1.90 (m, 10H, (CH2)5), 2.70 (s, 2H, CH2), 5.35 (br s,
2H, NH2, exchangeable with D2O), 7.26–7.32 (m, 3H,
ArH), 8.10 ppm (d, J = 8.05 Hz, 1H, ArH). MS (EI):
m/z (%) 230 (M, 66), 214 (100), 199 (13), 187 (30),
172 (44), 156 (17), 135 (15), 120 (20), 91 (19).
Preparation of Arylhydrazones 14a–f
A solution of the ketones 11a–c (0.01 mol) and the
arylhydrazine (0.01 mol) in ethanol (100 ml) con-
taining glacial acetic acid (1 ml) was boiled under
reflux for 6 h. After cooling, the solid was collected
and crystallized from ethanol to give the hydrazones
14a–f.
3-Ethyl-3-methyl-1,2,3,4-tetrahydronaphthalen-1-
one (4-Nitrophenyl)hydrazone (14a). Yellowish-
brown crystals (2.00 g, 62.5%), mp 168–170◦C. Anal
calcd for C19H21N3O2 (323.38): C, 70.56; H, 6.54; N,
Preparation of Ketazines 13a–c
A solution of the ketone 11a–c (0.01 mol) and hy-
drazine hydrate 99% (0.01 mol) in absolute ethanol
(Merck) was heated under brisk reflux for 6 h. Evapo-
ration of the solvent and crystallization of the residue
from ethanol afforded the pure ketazines 13a–c.
12.99%. Found: C, 70.32; H, 6.48; N, 12.69%. IR
1
(KBr): νNH 3345; νC 1608 cm−1. H NMR (CDCl3):
N
δ 0.83 (t, J = 8.00 Hz, 3H, CH3CH2), 0.92 (s, 3H,
CH3), 1.33 (q, J = 8.00 Hz, 2H, CH2CH3), 2.53 (d,
J = 18.00 Hz, 1H, 4-CH Hb), 2.65 (d, J = 18.00 Hz,
a
1H, 4-CHa H ), 3.37 (s, 2H, CH2), 7.17–7.41 (m, 6H,
b
3-Ethyl-3-methyl-1,2,3,4-tetrahydronaphthalen-1-
azine (13a). Dark yellow crystals (3.1 g, 85%), mp
117–119◦C. Anal calcd for C26H32N2 (372.54): C,
ArH), 8.13 ppm (d, J = 8.00 Hz, 2H, ArH), 10.30 (s,
H, NH, exchangeable with D2O). MS (EI): m/z (%)
323 (M, 100), 299 (4), 170 (5), 156 (15), 130 (15), 116
(21), 91 (8).
83.82; H, 8.66; N, 7.52%. Found: C, 83.72; H, 8.61; N,
1
7.39%. IR (KBr): νC 1605 cm−1. H NMR (CDCl3):
N
δ 0.87 (t, J = 8.00 Hz, 6H, 2 CH3CH2), 0.98 (s, 6H,
3-Ethyl-3-methyl-1,2,3,4-tetrahydronaphthalen-1-
one (2,4,6-Trichlorophenyl)hydrazone (14b). The
compound (purified by column chromatography
on silica gel, Merck 60, particle size 0.06–0.20 mm,
ether/petroleum ether 40–60◦C 1:10) was isolated
(2.20 g, 60%) as a brownish oil. Anal calcd for
C19H19Cl3N2 (381.73): C, 59.77; H, 5.01; N, 7.34%.
2 CH3), 1.20 (q, J = 8.00 Hz, 4H, 2 CH2CH3), 2.54
[d, J = 18.00 Hz, 2H, 2 (4- & 4ꢁ-CH Hb)], 2.63 [d,
a
J = 18.00 Hz, 2H, 2 (4- & 4ꢁ-CHa H )], 3.44 (s, 4H, 2
b
CH2), 7.28–7.44 (m, 6H, ArH), 8.23 ppm (d, J = 8.00
Hz, 2H, ArH). MS (EI): m/z (%) 273 (M + H, 88),
372 (M, 78), 357 (92), 344 (84), 343 (69), 329 (18),

Synthesis of Hindered Hydrazones and Their Reaction with Thionyl Chloride 227
Found: C, 59.38; H, 4.86; N, 7.20%. IR (neat): νNH
Spirochroman(2,1ꢁ)cyclohexane-4-one (2,4,6-Tri-
chlorophenyl)hydrazone (14f). The compound
(purified by column chromatography on sil-
ica gel, Merck 60, particle size 0.06–0.20 mm,
ether/petroleum ether 40–60◦C 1:10) was isolated
(2.80 g, 76%) as brownish oil. Anal calcd for
C20H19Cl3N2O (409.74): C, 58.62; H, 4.67; N, 6.83%.
1
3342; νC 1598 cm−1. H NMR (CDCl3): δ 0.82 (t,
N
J = 8.00 Hz, 3H, CH3CH2), 0.98 (s, 3H, CH3), 1.41
(q, J = 8.00 Hz, 2H, CH2CH3), 2.55 (d, J = 18.00 Hz,
1H, 4-CH Hb), 2.59 (d, J = 18.00 Hz, 1H, 4-CHa H ),
a
b
3.40 (s, 2H, CH2), 7.10–7.43 (m, 5H, ArH), 8.13
(d, J = 8.00 Hz, 1H, ArH), 10.08 ppm (s, H, NH,
exchangeable with D2O). MS (EI): m/z (%) 386 (M, 3
Cl37, 25), 384 (M, 2 Cl37 Cl35, 80), 382 (M, Cl37 2 Cl35,
90), 380 (M, 3 Cl35, 98), 371 (4), 369 (12), 367 (28),
365 (40), 357 (5), 355 (23), 353 (34), 351 (49), 346
(98), 315 (44), 274 (26), 208 (40), 195 (97), 187 (25),
170 (97), 167 (95), 159 (23), 143 (96), 131 (40), 128
(100), 110 (86), 89 (47).
Found: C, 58.35; H, 4.60; N, 6.79%. IR (neat): νNH
1
3315; νC 1600 cm−1. H NMR (CDCl3): δ 1.32–1.77
N
(m, 10H, (CH2)5), 2.68 (s, 2H, CH2), 6.91–7.02 (m,
3H, ArH), 7.19–7.35 (m, 2H, ArH), 8.10 (d, J = 8.00
Hz, 1H, ArH), 10.03 ppm (s, 1H, NH, exchangeable
with D2O). MS (EI): m/z (%) 414 (M, 3 Cl37, 3), 412
(M, 2 Cl37 Cl35, 14), 410 (M, Cl37 2 Cl35, 30), 408 (M, 3
Cl35, 38), 216 (62), 190 (36), 185 (38), 179 (16), 173
(82), 159 (20), 145 (15), 131 (21), 121 (100), 91 (35).
2,2-Dimethylchroman-4-one (4-Nitrophenyl)hyd-
razone (14c). Dark yellow crystals (2.69 g, 85%), mp
192–194◦C (literature [11] 193–194◦C). Anal calcd for
C17H17N3O3 (311.33): C, 65.57; H, 5.50; N, 13.49%.
Found: C, 65.35; H, 5.40; N, 13.28%. IR (KBr): νNH
3355; νC N 1616 cm−1. 1H NMR (CDCl3): δ 1.45 (s, 6H,
2 CH3), 2.72 (s, 2H, CH2), 6.98–7.43 (m, 6H, ArH),
8.09 (d, J = 8.01 Hz, 2H, ArH) 10.12 ppm (s, 1H,
NH, exchangeable with D2O). MS (EI): m/z (%) 311
(M, 80), 296 (100), 281 (60), 235 (40), 159 (28), 121
(52), 91 (35).
Preparation of Chlorothiadiazolines 15a–c
Hydrazone 14 (0.01 mol) was added portionwise to
thionyl chloride (20 ml) with stirring. The mixture
was stirred at room temperature for 10 h. The excess
of thionyl chloride was removed under reduced pres-
sure and recrystallization from ethyl acetate afforded
the corrresponding chlorothiadiazolines 15a–c.
(3aRS, 4RS) 3a-Chloro-4-ethyl-4-methyl-2-(4-ni-
trophenyl)-3a,4,5,9b-tetrahydronaphtho[1,2-d]-ꢀ1, 9b
-
[1,2,3]thiadiazoline (15a). Yellow crystalline pow-
der (3.50 g, 91%), mp 272–274◦C. Anal calcd for
C19H18ClN3O2S (387.86): C, 58.83; H, 4.67; N, 10.83;
2,2-Dimethylchroman-4-one (2,4,6-Trichlorophe-
nyl)hydrazone (14d). Yellowish-green crystals (2.90
g, 83%), mp 138–140◦C. Anal calcd for C17H15Cl3N2O
(369.68): C, 55.22; H, 4.09; N, 7.57%. Found: C, 55.01;
S, 8.26%. Found: C, 58.74; H, 4.55; N, 10.62; S,
1
8.16%. IR (KBr): νC 1594 cm−1. H NMR (DMSO-
N
H, 3.98; N, 7.52%. IR (KBr): νNH 3355; νC 1616
N
d6): δ 0.98 (t, J = 8.00 Hz, 3H, CH3CH2), 1.00 (t,
J = 8.00 Hz, 3H, CH3CH2), 1.02 (s, 3H, CH3), 1.31
(s, 3H, CH3), 1.62–1.78 (m, 2H, CH2CH3), 1.81–
2.00 (m, 2H, CH2CH3), 2.97 (d, J = 18.00 Hz, 1H,
CH Hb), 3.00 (d, J = 18.00 Hz, 1H, CH Hb), 3.22 (d,
cm−1. H NMR (CDCl3): δ 1.46 (s, 6H, 2 CH3), 2.72
1
(s, 2H, CH2), 6.84–6.96 (m, 3H, ArH), 7.19–7.34 (m,
2H, ArH), 7.98 (d, J = 8.01 Hz, 1H, ArH) 10.01 ppm
(s, 1H, NH, exchangeable with D2O). MS (EI): m/z
(%) 374 (M, 3 Cl37, 4), 372 (M, 2 Cl37 Cl35, 31), 370
(M, Cl37 2 Cl35, 98), 368 (M, 3 Cl35, 100), 357 (7),
355 (28), 353 (28), 333 (25), 194 (10), 174 (11), 159
(12).
a
a
J = 18.00 Hz, 1H, 5-CHa H ), 3.28 (d, J = 18.00 Hz,
b
1H, 5-CHa H ), 7.12–7.20 (m, 3H, ArH), 7.25–7.31
b
(m, 4H, ArH), 7.42–7.50 (m, 3H, ArH), 7.55–7.61 (m,
4H, ArH), 8.00 (d, J = 8.00 Hz, 1H, ArH), 8.21 (d,
J = 8.00 Hz, 1H, ArH). MS (EI): m/z (%) 389 (M,
Cl37, 0.22), 387 (M, Cl35, 0.62), 352 (M+ − Cl, 100),
337 (50), 330 (35), 323 (60), 306 (10), 294 (4), 170
(5), 156 (15), 130 (20), 91 (40).
Spirochroman(2,1ꢁ)cyclohexane-4-one (4-Nitro-
phenyl)hydrazone (14e). Yellowish-brown crystals
(2.80 g, 80%), mp 245–248◦C. Anal calcd for
C20H21N3O3 (351.39): C, 68.35; H, 6.02; N, 11.96%.
Found: C, 68.10; H, 5.92; N, 11.75%. IR (KBr): νNH
(3aRS) 3a-Chloro-4,4-dimethyl-2-(4-nitrophenyl)-
1
3322; νC 1598 cm−1. H NMR (CDCl3): δ 1.33–1.77
chromane[4,3-d]-ꢀ1, 9b-[1,2,3]thiadiazoline
(15b).
N
(m, 10H, (CH2)5), 2.62 (s, 2H, CH2), 6.90–7.03 (m,
3H, ArH), 7.19–7.27 (m, 3H, ArH), 8.20 (d, J = 8.00
Hz, 2H, ArH), 10.38 ppm (br s, 1H, NH, exchange-
able with D2O). MS (EI): m/z (%) 351 (M, 100), 335
(24), 326 (11), 306 (15), 284 (13), 277 (17), 260 (11),
134 (15), 115 (25), 91 (9).
Yellow crystalline powder (2.20 g, 60%), mp 247–
248◦C. Anal calcd for C17H14ClN3O3S (375.81): C,
54.32; H, 3.75; N, 11.18; S, 8.53%. Found: C, 54.01;
H, 3.68; N, 10.98; S, 8.46%. IR (KBr): νC 1605
N
cm−1. H NMR (DMSO-d6): δ 1.43 (s, 6H, 2 CH3),
1
6.97–7.15 (m, 4H, ArH), 7.48–7.55 (m, 3H, ArH),

228 Hegab et al.
8.25 (d, J = 8.00 Hz, 1H, ArH). MS (EI): m/z (%) 377
(M, Cl37, 0.21), 375 (M, Cl35, 0.64), 340 (100), 325
(30), 310 (25), 308 (8), 264 (65), 194 (20), 174 (11),
159 (15), 89 (70).
calcd for C19H19N3O4S (385.42): C, 59.20; H, 4.96;
N, 10.90; S, 8.31%. Found: C, 58.91; H, 4.91; N,
1
10.81; S, 8.21%. IR (KBr): νC 1587 cm−1. H NMR
N
(DMSO-d6): δ 1.08 (t, J = 8.00 Hz, 3H, CH3CH2O),
1.56 (s, 3H, CH3), 1.68 (s, 3H, CH3), 3.02 (q, J = 8.00
Hz, 2H, CH3CH2O), 7.02–7.08 (m, 3H, ArH), 7.27–
7.39 (m, 4H, ArH), 7.93 (d, J = 8.00 Hz, 1H, ArH).
MS (EI): m/z (%) 385 (M, 56), 356 (24), 340 (18), 325
(23), 295 (16), 252 (17), 145 (19), 139 (11), 127 (78),
111 (36), 97 (55), 83 (59), 73 (50), 55 (100).
(3aRS) 3a-Chloro-2-(4-nitrophenyl)spirochrom-
ane(4,1ꢁ)cyclohexane[4,3-d]-ꢀ1, 9b-[1,2,3]thiadiazoli-
ne (15c). Yellow crystalline powder (3.40 g, 83%),
mp 273–275◦C. Anal calcd for C20H18ClN3O3S
(415.87): C, 57.75; H, 4.36; N, 10.10; S, 7.70%.
Found: C, 57.55; H, 4.33; N, 10.00; S, 7.40%. IR
(KBr): νC
1614 cm−1. 1H NMR (DMSO-d6): δ
(3aRS) 3a-Ethoxy-2-(4-nitrophenyl)spirochroma-
ne(4,1ꢁ)cyclohexane[4,3-d]-ꢀ1, 9b-[1,2,3]thiadiazoline
(16c). Red crystals (3.40 g, 83%), mp 150–152◦C.
Anal calcd for C22H23N3O4S (425.48): C, 62.09;
H, 5.44; N, 9.87; S, 7.53%. Found: C, 61.85; H,
N
1.19–2.22 (m, 10H, (CH2)5), 7.18–7.21 (m, 4H, ArH),
7.59–7.69 (m, 3H, ArH), 8.02 (d, J = 8.00 Hz, 1H,
ArH). MS (EI): m/z (%) 417 (M, Cl37, 0.11), 415 (M,
Cl35, 0.32), 380 (100), 358 (40), 344 (10), 326 (10),
306 (15), 284 (14), 277 (18), 260 (10), 213 (9), 115
(25), 91 (50).
5.34; N, 9.68; S, 7.40%. IR (KBr): νC 1596 cm−1.
N
1H NMR (DMSO-d6): δ 1.07 (t, J = 8.00 Hz, 3H,
CH3CH2O),1.15–2.25 (m, 10H, (CH2)5), 2.92 (q,
J = 8.00 Hz, 2H, CH3CH2O), 7.18–7.22 (m, 4H,
ArH), 7.59–7.69 (m, 3H, ArH), 8.00 (d, J = 8.01 Hz,
1H, ArH). MS (EI): m/z (%) 425 (M, 30), 396 (20),
380 (50), 358 (20), 326 (17), 277 (30), 260 (20), 115
(30), 89 (100).
Preparation of Ethoxythiadiazolines 16a–c
Boiling of chlorothiadiazolines 15a–c (0.01 mol) in
100 ml absolute ethanol was carried out for 1/2 h.
The solvent was evaporated and crystallization of the
residue from ethanol afforded the ethoxythiadiazo-
lines 16a–c.
ACKNOWLEDGMENT
Thanks are due to the National Research Centre,
Dokki, Cairo, Egypt for the financial support and for
all the given facilities.
(3aRS, 4RS)-3a-Ethoxy-4-ethyl-4-methyl-2-(4-ni-
trophenyl)-3a,4,5,9b-tetrahydronaphtho[1,2-d]-ꢀ1, 9b
-
[1,2,3]thiadiazoline (16a). Red crystals (2.7 g,
70%), mp 115–117◦C. Anal calcd for C21H23N3O3S
(397.7): C, 63.45; H, 5.87; N, 10.57; S, 8.06%. Found:
C, 63.15; H, 5.72; N, 10.39; S, 7.89%. IR (KBr):
REFERENCES
[1] Harradence, R. H.; Hughe, G. K.; Lions, F. J Proc Roy
Soc N S Wales 1939, 72, 273–283; Chem Abstr 1939,
33, 68411.
[2] Dann, O.; Volz, G. Ann Chem 1965, 685, 167–176.
[3] El-Desoky, S. I.; Heterocycl Comm 1996, 2, 559–
565.
νC
1600 cm−1. 1H NMR (DMSO-d6): δ 0.99 (t,
N
J = 8.00 Hz, 3H, CH3CH2), 1.00 (t, J = 8.00 Hz, 3H,
CH3CH2), 1.02 (s, 3H, CH3), 1.21 (s, 3H, CH3), 1.30
(t, J = 8.00 Hz, 3H, CH3CH2O), 1.42 (t, J = 8.00
Hz, 3H, CH3CH2O), 1.61–1.79 (m, 2H, CH2CH3),
1.81–2.05 (m, 2H, CH2CH3), 2.40 (q, J = 8.00 Hz,
2H, CH3CH2O), 2.66 (q, J = 8.00 Hz, 2H, CH3CH2O),
[4] Bakthavatchalam, R.; Ramana, D. V.; Ramadas, S. R.
Sulfur Lett 1987, 5, 103–108.
[5] Maiti, S. B.; Chatterjee, A.; Raychaudhuri, S. R. In-
dian J Chem, Sec B 1984, 23b, 203–205.
[6] Flowers, W. T.; Robinson, J. F.; Taylor, D. R.; Tipping,
A. E. J Chem Soc, Perkin Trans 1 1981, 349–355.
[7] El-Bahaie, S.; Bayoumy, B. E. Rev Roum Chim 1991,
36, 209.
[8] Crossland, I. Acta Chem Scand 1976, 30, 787–
789.
[9] Hegab, M. I.; Abdel-Megeid, F. M. E.; Gad, F. A.; Shiba,
S. A.; Søtofte, I.; Møller, J.; Senning, A. Acta Chem
Scand 1999, 53, 133–140.
[10] El-Essawy, F. A. G.; Yassin, S. M.; El-Sakka, I. A.;
Khattab, A. F.; Søtofte, I.; Madsen, J.; Senning, A. J
Org Chem 1998, 63, 9840–9845.
[11] Kabbe, H. J. Synthesis 1978, 886–887.
[12] Auwers, K. von.; Mauss, W. Chem Ber 1928, 61B,
2545–2549.
2.98 (d, J = 18.00 Hz, 1H, 5-CH Hb), 3.02 (d,
a
J = 18.00 Hz, 1H, 5-CH Hb), 3.22 (d, J = 18.00 Hz,
a
1H, CHa H ), 3.28 (d, J = 18.00 Hz, 1H, CHa H ),
b
b
6.99–7.21 (m, 3H, ArH), 7.25–7.31 (m, 4H, ArH),
7.42–7.50 (m, 3H, ArH), 7.55–7.63 (m, 4H, ArH),
8.10 (d, J = 8.00 Hz, 1H, ArH), 8.21 (d, J = 8.00 Hz,
1H, ArH). MS (EI): m/z (%) 397 (M, 35), 368 (21),
352 (15), 323 (20), 294 (10), 170 (15), 130 (35), 91
(100).
(3aRS) 3a-Ethoxy-4,4-dimethyl-2-(4-nitrophen-
yl)chromane[4,3-d]-ꢀ1, 9b-[1,2,3]thiadiazoline (16b).
Red crystals (3.0 g, 80%), mp 135–137◦C. Anal