Cyanoacetanilides intermediates in heterocyclic synthesis. Part 5: Preparation of hitherto unknown 5-aminopyrazole and pyrazolo[1,5-a]pyrimidine derivatives containing sulfamoyl moiety

Article abstract of DOI:10.1002/jccs.200900154

Novel 5-aminopyrazole and pyrazolo[1,5-a]pyrimidine derivatives have been synthesized from the readily accessible cyanoacetanilide derivative (2).

Full text of DOI:10.1002/jccs.200900154

1064
Journal of the Chinese Chemical Society, 2009, 56, 1064-1071
Cyanoacetanilides Intermediates in Heterocyclic Synthesis.
Part 5: Preparation of Hitherto Unknown 5-Aminopyrazole and
Pyrazolo[1,5-a]pyrimidine Derivatives Containing Sulfamoyl Moiety
Yousry A. Ammar,a Mohsen M. Aly,a Abd Allah G. Al-Sehemi,b
Mohamed A. Salema and Mohamed S. A. El-Gabyc*
aChemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt
bChemistry Department, Teachers College at Abha, Abha, Saudi Arabia
cChemistry Department, Faculty of Science, Al-Azhar University at Assiut, 71524 Assiut, Egypt
Novel 5-aminopyrazole and pyrazolo[1,5-a]pyrimidine derivatives have been synthesized from the
readily accessible cyanoacetanilide derivative (2).
Keywords: 5-Aminopyrazole; Pyrazolo[1,5-a]pyrimidines; Sulfonamides; Cyanoacetamide.
INTRODUCTION
5-Aminopyrazole1-3 and pyrazolo[1,5-a]pyrimidine4-6
Treatment of cyanoacetanilide 2 with carbon disul-
fide in dimethylformamide in the presence of potassium
hydroxide gave the non-isolated potassium salt of geminal
dithiole 3 which was then allowed to react with dimethyl
sulfate to give 2-cyano-N-(4-sulfamoylphenyl)-3,3-bis-
(methylsulfanyl)acrylamide 4. The molecular structure of
compound 4 was established by analytical and spectral
data. Its 1H NMR spectrum in DMSO-d6 revealed the pres-
ence of a singlet at d = 2.52 and 2.66 ppm characteristic for
two methylsulfanyl groups in addition to the expected sig-
nals attributed to the NH, SO2NH2 and aromatic protons.
Cyclo-condensation of compound 4 with hydrazine hy-
drate in refluxing ethanol furnished the novel 5-amino-
pyrazole derivative 5. The isolated product 5 was con-
firmed by analytical and spectral data. Its infrared spectrum
indicated the absence of the CºN group. The formation of 5
is assumed to proceed via Michael addition of the amino
group of hydrazine to the ethylenic bond in 4 with elimina-
tion of methyl mercaptan followed by intramolecular cy-
clization16 at the cyano group to form 5. The reaction of
compound 2 with phenyl isothiocyanate in the presence of
potassium hydroxide gave the non-isolated adduct 6 which
was then treated with dimethyl sulfate to furnish the 2-cy-
ano-3-methylsulfanyl-3-phenylamino-N-(4-sulfamoylphe
nylacrylamide 7. Cyclization of compound 7 with hydra-
zines in ethanol at reflux temperature afforded the 5-ami-
nopyrazole derivatives 8a-c, Scheme II. The mass spec-
derivatives are biologically important compounds. Sul-
famoyl moiety has been reported to furnish antimicrobial,7
antifungal,8 insulin releasing9 and carbonic anhydrase in-
hibitory`properties. Prompted by these observations and as
a continuation of our research program on the chemistry of
cyanoacetanilide derivatives,11-14 we report herein the syn-
thesis of the versatile hitherto unknown 5-aminopyrazole
and pyrazolo[1,5-a]pyrimidine derivatives containing sul-
famoyl moiety using readily accessible cyanoacetanilide
derivative 2 and simple experimental procedures.
RESULTS AND DISCUSSION
The starting material 4-(sulfamoyl)cyanoacetanilide
2 was achieved in good yield (92%) via the reaction of sul-
fanilamide 1 with ethyl cyanoacetate in m-xylene at reflux
temperature,15 Scheme I.
Scheme I
* Corresponding author. E-mail: m_elgaby@hotmail.com

Synthesis of 5-Aminopyrazoles and Pyrazolo[1,5-a]pyrimidines
J. Chin. Chem. Soc., Vol. 56, No. 5, 2009 1065
firmed on the basis of its elemental and spectral data. Its in-
frared spectrum showed the characteristic absorption bands
for the NH2 and CºN groups. The mass spectrum of com-
pound 13 revealed a molecular ion peak at m/z = 473
(15.67%) which is characteristic for the molecular formula
C21H15N9O3S, Chart (I). Formation of pyrazolopyrimidine
13 takes place as depicted in Scheme III, via an initial Mi-
chael addition of the endocyclic NH in 8a to the double
bond in 11 to yield the non-isolable intermediate 12 fol-
lowed by intramolecular cyclization17 to afford the corre-
Scheme II
Scheme III
trum of compound 8a showed a molecular ion peak at m/z =
372 (35.71%) which is characteristic for the molecular for-
mula C16H16N6O3S.
The reactivity of aminopyrazole derivative 8a to-
wards some electrophilic reagents was investigated. Con-
densation of compound 8a with 4-methoxybenzaldehyde
in ethanol in the presence of piperidine under reflux fur-
nished azomethine derivative 9. Also, bis(azomethine) de-
rivative 10 was obtained by condensation of compound 8a
with terephthalaldehyde (2 : 1 molar ratio) in refluxing eth-
anol in the presence of piperidine. A molecular ion peak at
m/z = 842 (4.93%) was observed in the mass spectrum of
compound 10 with base peak at m/z = 56. In compound 8a
the endocyclic NH is highly reactive and is more nucleo-
philic than the exocyclic amino group.17,18 Reaction of
compound 8a with tetracyanoethylene 11 in refluxing
dioxane in the presence of a catalytic amount of piperidine
afforded the 5-aminopyrazolo[l,5-a]pyrimidine derivative
13. The molecular structure of compound 13 was con-

1066 J. Chin. Chem. Soc., Vol. 56, No. 5, 2009
Chart I Fragmentation pattern of compound 13
Ammar et al.
sponding pyrazolopyrimidine derivative 13. Cyclization of
8a to the corresponding pyrazolo[1,5-a]pyrimidine deriva-
tives 16a,b was achieved upon refluxing 8a with aryl-
idenemalo-nonitriles 14a,b in ethanol in the presence of
piperidine. The structure of 16 was established by examin-
ing spectral and elemental analysis. The infrared spectra of
compounds 16a,b indicated the presence of NH2 and CºN
absorption bands. The mass spectrum of compound 16b re-
vealed a molecular ion peak at m/z = 554 (3.48%) with base
peak at m/z = 57. The formation of 16 is assumed to proceed
via an initial Michael addition of the endocyclic NH in 8a
to the double bond in 14 to yield the non-isolable interme-
diate 15 followed by intramolecular cyclization and aro-
matization by loss of hydrogen17 to afford 16, (Scheme III).
When compound 8a was treated with 3-aminocrotono-
nitrile 17 in glacial acetic acid, the corresponding pyr-
azolopyrimidine derivative 18 was obtained. The forma-
tion of 18 is assumed to proceed via the condensation of the
endocyclic NH in 8a with 17 followed by intramolecular
cyclization. The reaction of compound 8a with a,b-unsatu-
rated ketone 19 in refluxing glacial acetic acid yielded the
pyrazolo[1,5-a]pyrimidine derivative 20. Its mass spec-
trum revealed a molecular ion peak at m/z = 560 (11.76%).
The formation of 20 is assumed to proceed through an ini-
tial Michael addition of the endocyclic NH in 8a to the dou-
ble bond in 19 followed by intramolecular cyclization via
dehydration and aromatization by loss of hydrogen to af-
ford 20, (Scheme III).
The present investigation was extended to study the
reaction of compound 8a with 1,3-dicarbonyl compounds.
Thus, the reaction of compound 8a with acetylacetone 21a
and benzoyl-acetone 21b in refluxing glacial acetic acid
gave the pyrazolo[l,5-a]pyrimidine derivatives 23a and
23b, respectively. The mass spectrum of compound 23a re-
vealed a molecular ion peak at m/z = 436 (27.29%), and the
base peak was found in the spectrum at m/z = 265, Chart
(II). The formation of 23 is assumed to proceed via the con-
densation of the endocyclic NH in 8a with 21 to form 22
followed by intramolecular cyclization through dehydra-
tion,18 Scheme IV. Also, the reaction of compound 8a with

Synthesis of 5-Aminopyrazoles and Pyrazolo[1,5-a]pyrimidines
J. Chin. Chem. Soc., Vol. 56, No. 5, 2009 1067
Pyrazolo[3,4-d]pyrimidine derivative 29 was achieved
by treatment of compound 8a with dimethylformamide-
dimethylacetal (DMFDMA) in m-xylene at reflux tempera-
ture. On the basis of analytical and spectral data the struc-
ture of compound 29 was confirmed. Its 1H NMR spectrum
in DMSO-d6 revealed the absence of the SO2NH2 moiety
and contains the characteristic signals for N(CH3)2, 2CH=N,
2 NH and aromatic protons. The mass spectrum of com-
pound 29 showed a molecular ion peak at m/z = 437 which
is the base peak in the spectrum. The formation of 29 is as-
sumed to proceed through the formation of azomethine 27
followed by intramolecular cyclization by loss of dimethyl-
amine to form 28 which was then condensed with DMFDMA
to yield 29, Scheme (V). Refluxing of compound 8a with
2,3-dichloronaphtho-quinone in dimethylformamide(DMF)
yielded the naphtho[2¢,3¢:4,5]imidazo[l,2-b]pyrazole de-
rivative 30. Its mass spectrum exhibited a molecular ion
peak at m/z = 526 (2%), and the base peak was observed in
the spectrum at m/z = 69.
Chart II Fragmentation pattern of compound 23a
Scheme V
ethyl acetoacetate 24 in glacial acetic acid at reflux temper-
ature afforded the pyrazolopyrimidine derivative 26. The
formation of 26 is assumed to proceed through the conden-
sation of the endocyclic NH in 8a with the ester moiety and
elimination of ethanol to yield 25 followed by in situ het-
erocyclization via loss of water, (Scheme IV).
Scheme IV
EXPERIMENTAL
Melting points are recorded on a Fisher-John melting
points apparatus and are uncorrected. IR spectra were re-
corded on a Shimadzu 470 spectrometer using KBr pellets.
1H NMR spectra were recorded on a Varian Gemini spec-
trometer 200 (200 MHz) using TMS as internal standard
and mass spectra on a Jeol-JMS-600 mass spectrometer. El-
emental analyses were performed on a Perkin-Elmer 240 C

1068 J. Chin. Chem. Soc., Vol. 56, No. 5, 2009
Ammar et al.
micro-analyzer. The physical and spectral data are col-
lected in Tables 1 and 2, respectively.
again to 0 ºC, treated with dimethyl sulfate and stirred at
room temperature for an additional 6 h. Then it was poured
into ice/water; the resulting precipitate was filtered off,
dried and recrystallized to give 4.
Formation of 2-Cyano-N-(4-sulfamoylphenyl)-3,3-bis-
(methylsulfanyl)acrylamide (4)
To a stirred suspension of finely powdered potassium
hydroxide (0.01 mole) in dry dimethylformamide (10 mL)
cooled to 0 ºC, the active methylene 2 (0.01 mole) and next
carbon disulfide (0.01 mole) were added gradually. The re-
action was stirred at room temperature for 3 h, then cooled
Formation of 2-Cyano-3-methylsulfanyl-3-phenyl-
amino-N-(4-sulfamoylphenyl)acrylamide (7)
The experimental procedure used for 4 was carried
out except for the use of phenyl isothiocyanate instead of
carbon disulfide.
Table 1. Physical and analytical data for the synthesized compounds
Elemental analyses
Compd. M.P.
Yield
(%)
Solvent
Cryst
M. F.
(°C)
150-1
190-2
220-2
170-1
200-1
190-2
240-2
>300
>300
280-2
270-1
280-2
>300
300
(M. Wt.)
No.
C%
H%
N%
41.98
41.50
40.36
40.00
52.57
52.50
51.61
51.40
58.92
58.70
60.80
60.01
58.77
58.60
57.00
57.10
53.27
53.10
60.22
60.00
58.48
58.30
54.91
54.80
66.42
66.30
57.79
57.80
62.65
62.30
54.79
54.60
54.91
54.70
59.31
59.00
3.79
3.40
3.97
3.80
4.12
4.00
4.30
4.20
4.09
4.00
4.34
4.30
4.48
4.30
4.03
4.00
3.17
3.00
4.08
4.00
3.97
3.80
4.34
4.20
4.28
4.10
4.58
4.40
4.41
4.30
4.10
4.00
4.34
4.30
3.42
3.40
12.24
12.00
21.40
21.30
14.43
14.30
22.58
22.40
18.75
18.60
18.26
18.10
17.14
17.10
19.95
19.70
26.63
26.30
20.81
20.60
20.21
20.10
22.42
22.20
15.00
15.10
19.26
19.00
16.86
16.50
19.17
19.00
22.42
22.20
15.96
15.80
C12H13N3O3S3
(334)
4
75
60
80
80
50
60
70
65
70
70
60
70
75
60
70
75
50
55
EtOH
EtOH
C11H13N5O3S2
(327)
5
C17H16N4O3S2
(388)
7
EtOH
C16H16N6O3S
(372)
8a
8b
8c
9
EtOH
C22H20N6O3S
(448)
Benzene
Benzene
AcOH
C23H20N6O3S
(460)
C24H22N6O4S
(490)
C40H34N12O6S2
(842)
10
13
16a
16b
18
Dioxane
AcOH
C21H15N9O3S
(473)
C27H22N8O3S
(538)
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
EtOH
C27H22N8O4S
(554)
C20H19N7O3S
(437)
C31H24N6O3S
(560)
20
23a
C21H20N6O3S
(436)
C26H22N6O3S
(498)
23b
26
>300
>300
>300
C20H18N6O4S
(438)
C20H19N7O3S
(437)
29
C26H18N6O5S
(526)
30
290
AcOH

Synthesis of 5-Aminopyrazoles and Pyrazolo[1,5-a]pyrimidines
Table 2. Spectral data of the synthesized compounds
J. Chin. Chem. Soc., Vol. 56, No. 5, 2009 1069
Compd.
IR/nmax (cm-1)
No.
1H NMR (DMSO-d6) (d/ppm)
4
3365, 3269, 3107 (NH/NH2), 2207 2.52, 2.66 (2s, 6H, 2CH3), 7.29 (s, 2H, SO2NH2; exchange-
(CºN), 1657 (C=O), 1595 (C=C) able), 7.68-7.80 (m, 4H, Ar-H), 10.88 (s, 1H, NH;
exchangeable).
3440, 3338, 3250 (NH/NH2), 1648 2.49 (s, 3H, SCH3), 6.25 (s, 2H, NH2; exchangeable), 7.28
5
(C=O)
(s, 2H, SO2NH2; exchangeable), 7.78-7.79 (m, 4H, Ar-H),
9.37, 12.11 (2s, 2H, 2NH; exchangeable).
7
3362, 3262 (NH2), 2204 (CºN),
2.28 (s, 3H, SCH3), 7.26 (s, 2H, SO2NH2; exchangeable),
7.33-7.71 (m, 9H, Ar-H), 9.91, 11.54 (2s, 2H, 2NH;
exchangeable).
1636 (C=O), 1588 (C=C)
8a
8b
3340, 3200 (NH2), 1654 (C=O)
6.15 (s, 2H, NH2; exchangeable), 6.78 (s, 2H, SO2NH2;
exchangeable), 7.19-7.80 (m, 9H, Ar-H), 8.56, 9.06, 11.42
(3s, 3H, 3NH; exchangeable).
3462, 3354, 3250 (NH/NH2), 1652 6.51 (s, 2H, NH2; exchangeable), 7.25 (s, 2H, SO2NH2;
(C=O)
exchangeable), 7.28 (s, 1H, NH; exchangeable), 7.57-7.80
(m, 9H, Ar-H), 9.41 (s, 1H, NH; exchangeable).
8c
9
3204, 3180 (NH2), 1668 (C=O,
amide), 1632 (C=O; benzoyl)
3330, 3250 (NH2), 1670 (C=O),
1620 (C=N)
3.91 (s, 3H, CH3), 6.93-8.10 (m, 15H, Ar-H + SO2NH2;
exchangeable), 8.87 (s, 1H, CH=N), 8.99, 10.26, 12.99 (3s,
3H, 3NH; exchangeable).
10
3310, 3300 (NH2), 1684 (C=O),
1650 (C=N)
6.90-8.20 (m, 26H, Ar-H + 2SO2NH2; exchangeable), 8.37
(s, 2H, 2CH=N), 8.90, 9.20, 10.15 (3s, 6H, 6NH; ex-
changeable).
13
3411, 3318, 3252 (NH/NH2), 2200
(CºN), 1648 (C=O)
16a
3450, 3338, 3250 (NH/NH2), 2210 2.46 (s, 3H, CH3), 7.10 (hump, 2H, NH2; exchangeable),
(CºN), 1664 (C=O)
7.20-7.98 (m, 13H, Ar-H), 9.13 (hump, 2H, NH2; ex-
changeable), 9.33, 10.40 (2s, 2H, 2NH; exchangeable).
3.89 (s, 3H, OCH3), 3.92 (s, 2H, NH2; exchangeable), 7.10-
7.90 (m, 15H, Ar-H + NH2; exchangeable), 8.85, 10.19 (2s,
2H, 2NH; exchangeable).
16b
18
3318, 3300 (NH2), 2212 (CºN)
and 1664 (C=O)
3330, 3300 (NH2) and 1654 (C=O) 2.51 (s, 3H, CH3), 6.17 (s, 1H, pyrimidine-H), 6.98 (hump,
2H, NH2; exchangeable), 7.35-7.93 (m, 9H, Ar-H), 9.10
(hump, 2H, NH2; exchangeable), 9.30, 10.60 (2s, 2H, 2NH;
exchangeable).
20
3294, 3220 (NH2), 1670 (C=O)
6.94 (s, 1H, pyrimidine-H), 7.42-7.90 (m, 21H, Ar-H +
SO2NH2; exchangeable), 8.41, 9.30 (2s, 2H, 2NH; ex-
changeable).
23a
23b
26
3326, 3230 (NH2), 1670 (C=O)
2.52, 2.58 (2s, 6H, 2CH3), 6.89 (s, 1H, pyrimidine-H), 6.98
(hump, 2H, NH2; exchangeable), 7.30-7.81 (m, 9H, Ar-H),
9.13, 10.15 (2s, 2H, 2NH; exchangeable).
3350, 3320, 3150 (NH/NH2), 1666 2.51 (s, 3H, CH3), 6.96 (s, 1H, pyrimidine-H), 7.26-8.21
(C=O)
(m, 16H, Ar-H + SO2NH2; exchangeable), 9.25, 10.38 (2s,
2H, 2NH; exchangeable).
3378, 3314, 3250 (NH/NH2), 1654, 2.34 (s, 3H, CH3), 5.81 (s, 1H, pyrimidine-H), 6.90-7.84
1624 (2C=O)
(m, 11H, Ar-H + SO2NH2; exchangeable), 8.76, 10.10 (2s,
2H, 2NH; exchangeable), 12.01 (s, 1H, OH; exchangeable).
2.96 (s, 1H, NH; exchangeable), 3.19 (s, 6H, N(CH3)2),
6.88-7.97 (m, 9H, Ar-H), 8.31, 8.33 (2s, 2H, 2CH=N),
12.07 (s, 1H, NH; exchangeable).
29
3357 (NH), 2981 (CH-aliph.),
1696 (C=O) and 1625 (C=N)
30
3316, 3190 (2NH), 1659 (C=O)

1070 J. Chin. Chem. Soc., Vol. 56, No. 5, 2009
Ammar et al.
Formation of 5-amino-3-methylsulfanyl-4-(4-sulfamo-
ylphenyl)carbamoylpyrazole (5) and 5-amino-3-phen-
ylamino-1-R-4-(4-sulfamoyl-phenyl)carbamoyl-pyra-
zoles (8a-c)
lected and recrystallized to give 18 and 20, respectively.
Synthesis of 5,7-dimethyl-2-phenylamino-3-(4-sulfamo-
ylphenyl)carbamoylpyrazolo[1,5-a]pyrimidine (23a),
7-methyl-7-phenyl-2-phenylamino-3-(4-sulfamoylphen-
yl)carbamoyl-pyrazolo-[1,5-a]pyramidine (23b) and
5-methyl-2-phenyl-3-(4-sulfamoylphenyl)-carbamoyl-7-
oxo-6,7-dihydropyrazolo[1,5-a]pyrimidine (26)
General procedure: Amixture of compound 8a (0.01
mole) and 1,3-dicarbonyl compound (namely, acetylace-
tone, benzoylacetone, ethyl acetoacetate) (0.01 mole) in
glacial acetic acid (10 mL) was heated under reflux for 24
h, then allowed to cool. The solid was collected and recrys-
tallized from the proper solvent to give 23a, 23b and 26, re-
spectively.
General procedure: A mixture of 4 or 7 (0.01 mole)
and hydrazine derivative (0.01 mole) in ethanol (30 mL)
was heated under reflux for 24 h. The reaction was concen-
trated and the obtained product was collected and recrys-
tallized from the proper solvent to give 5 and 8a-c, respec-
tively.
Synthesis of 5-(4-methoxybenzylideneamino)-3-(phen-
ylamino)-N-(4-sulfamoylphenyl)-1H-pyrazole-4-car-
boxamide (9) and 5,5¢-(1,4-phenylenebis(methan-1-yl-
1-ylidene)) bis(azan-1-yl-1-ylidene)bis(3-(phenylami-
no)-N-(4-sulfamoylphenyl)-1H-pyrazole-4-carbox-
amide) (10)
Formation of N,N-dimethyl-N¢-(4-(4-oxo-3-(phenyl-
amino)-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl)phenyl-
sulfonyl)formimidamide (29)
General procedure: A mixture of compound 8a (0.01
mole), aromatic aldehyde (0.01 mole) and piperidine (0.01
mole) in ethanol (30 mL) was heated under reflux for 1 h;
the solid product which was produced on heating was col-
lected and recrystallized from the proper solvent.
Synthesis of 5-amino-6,7-dicyano-2-phenylamino-3-(4-
sulfamoylphenyl)carbamoyl-pyrazolo[1,5-a]pyrimidine
(13)
A mixture of compound 8a (0.01 mole) and dimeth-
ylformamide-dimethylacetal (DMFDMA; 0.02 mole) in
m-xylene (30 mL) was heated under reflux for 6 h; the solid
product which was produced on heating was collected and
recrystallized from the proper solvent to give 29.
Synthesis of 2-phenylamino-3-(4-sulfamoylphenyl)car-
bamoyl-4,5,10-tri-hydro-5,10-dioxo-naphtho[2¢,3¢:4,5]-
imidazo[1,2-b]pyrazole (30)
A mixture of compound 8a (0.01 mole), tetracyano-
ethylene 11 (0.01 mole), and piperidine (0.01 mole) in
dioxane (10 mL) was heated under reflux for 30 min, then
allowed to cool. The solid product was collected and re-
crystallized from the proper solvent to give 13.
A mixture of compound 8a (0.01 mole) and 2,3-di-
chloro-naphthoquinone (0.01 mole) in dimethylformamide
(10 mL) was heated under reflux for 1 hr, then allowed to
cool and poured into cold water (60 mL). The solid product
was collected and recrystallized from the proper solvent to
give 30.
Synthesis of 5-amino-6-cyano-7-(4-substituted-phenyl)-
2-phenylamino-3-(4-sulfamoylphenyl)carbamoyl-pyra-
zolo[1,5-a]pyrimidine (16a,b)
Received November 14, 2008.
General procedure: A mixture of 8a (0.01 mole),
arylidenemalononitrile 14 (0.01 mole) and piperidine (0.5
mL) in ethanol (30 mL) was heated under reflux for 3 h; the
solid product which was produced on heating was collected
and recrystallized from the proper solvent to give 16.
Synthesis of 5-amino-7-methyl-2-phenylamino-3-(4-
sulfamoyl-phenyl)carbamoylpyrazolo[1,5-a]pyrimidine
(18) and 5,7-diphenyl-2-phenylamino-3-(4-sulfamoyl-
phenyl)carbamoylpyrazolo[1,5-a]pyrimidine (20)
General procedure: A mixture of compound 8a (0.01
mole), b-aminocrotononitrile 17 (0.01 mole) or a,b-unsat-
urated ketone 19 (0.01 mole) in glacial acetic acid (10 mL)
was heated under reflux for 1 h, then allowed to cool and
poured into water (100 mL). The solid product was col-
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