International Journal of Organic Chemistry, 2011, 1, 207-214
doi:10.4236/ijoc.2011.14030 Published Online December 2011 (http://www.SciRP.org/journal/ijoc)
207
Dimethylformamide Dimethyl Acetal (DMFDMA) in
Heterocyclic Synthesis: Synthesis of Polysubstituted
Pyridines, Pyrimidines, Pyridazine and
Their Fused Derivatives
Fathi A. Abu-Shanab1*, Sayed A. S. Mousa1, E. A. Eshak1, Ahmed Z. Sayed2, Ahmed Al-Harrasi3
1Department of Chemistry, Faculty of Science, Al-Azhar University, Assiut, Egypt
2Chemistry Department, Umm Al-Qura University, Makkah Al-Mokaramah, Saudia Arabia
3Department of Biol o gi cal Sciences and Chemis t ry , College of Arts and Sciences, University of Nizwa,
Nizwa, Sultanate of Oman
Received September 29, 2011; revised November 5, 2011; accepted November 13, 2011
Abstract
Reaction of N,N’-dimethylformamide dimethyl acetal (DMFDMA) with malononitrile dimer 8 (1:1) mole
afforded 9 while, this reaction when carried out in (2:1) mole to give amidine 11 which can be used for the
preparation of pyrimidine 13, amidine 14 and pyridine 19 when reacted with 4-nitroaniline, 4-methylaniline
and alkoxide respectively. Malononitrile dimer reacted with diazonium chloride to give pyridazine 21, which
can be reacted with DMFDMA, AcOH/HCl and cyanoacetamide to give pyridazine 22, 23 and pyrido[4,3-c]
pyridazine 24 respectively. The latter reacted with DMFDMA to afford tricyclic compound 25.
Keywords: DMFDMA, Malononitrile Dimer, Pyridazine-3,5-carbonitrile, Pyridine-4-alkoxide
1. Introduction
Formamide acetals are useful reagents in organic synthe-
sis; [1,2] their main application has been used for func-
tional group transformations [3], but they may also be re-
garded as one-carbon synthons in the construction of car-
bon skeletons. One type of reaction, which is potentially
valuable for the future purpose, is the reaction of N,N’-
dimethylformamide dimethyl acetal (DMFDMA) with 1,
3-dicarbonyl compounds 1 to give enamines 2 [2,4].
O
O
R2
R1
MeO
MeO
N
Me
Me
O
O
R2
R1
NMe
Me
R1
CH
3
CH
3
CH
3
CH
3
CH
3
CH
2CO 2C2H5
R2
CH
3
OCH
3
OCH
2CH 3
Ph
OCH
2CH 3
OCH
2CH 3
-(CH
2)3-
12
We have reported that enamines 2 were used as pre-
cursors in the synthesis of pentasubstituted pyridines 3-6
[5-8].
N
H
NH2 R2
R1X
O
N
H
NH2
R2
X
O
N
H
CN
R2
R1X
O
N
H
CN
R2
X
OR
1R1
OO
3456
X = O, S, C(CN)2
Moreover, we have reported that N,N’-dimethylfor-
mamide dimethyl acetal (DMFDMA) is potentially va-
luable as a building block for heterocyclic synthesis [9]
and used for the synthesis of 1,4-pyrazine-2,5-diones 7
[10].
N
N
O
O
Ar
Ar
7
2. Results and Discussion
In conjunction with this work we report here the reaction
of malononitrile dimer 8 [11] with one mole of N,N’-

F. A. ABU-SHANAB ET AL.
208
dimethylformamide dimethyl acetal (DMFDMA) in dry
dioxane afforded only one product that could be formu-
lated as 9 or 10 as result of condensation on either the
amino or active methylene group. The structure of the
isolated product was elucidated based on the spectral
analysis. The 1H-NMR spectrum shows two singlet sig-
nals at δH = 3.2 and 3.25 ppm corresponding to the two
methyl groups of NMe2 moiety, singlet signal at δH=
7.59 ppm corresponding to methylene group or amino
group and singlet signal at δH = 7.99 ppm corresponding
to methine proton. While we could not differentiate be-
tween 9 and 10 by 1H-NMR, DEPT-135 of 13C-NMR
shows a methylene group at –66.78 ppm which indicates
that the isolated product is 9 and not 10. This can be at-
tributed to the fact that the nucleophilicity of the amino
group is greater than that of methylene group.
The treatment of malononitrile dimer 8 with two
moles of N,N’-dimethylformamide dimethyl acetal (DM-
FDMA) afforded amidine 11 in which N,N’-dimethyl-
formamide dimethyl acetal (DMFDMA) reacted with bo-
th the amino group and the active methylene. The mass
spectrum of this compound shows molecular weight at
m/z 242 which corresponds to structure 11. Amidine 11
can also be obtained by treatment of amidine 9 with an-
other one mole of DMFDMA.
The reaction of amidine 11 with one mole of aromatic
amines (1:1) afforded the corresponding pyrimidine de-
rivative 13. while the treatment of amidine 11 with two
moles of aromatic amines (1:2) afforded formamidine 14
(Scheme 1). This suggests that the isolated pyrimidine
13 was formed through the intermediate 12. The struc-
ture of these compounds was confirmed by elemental
analysis as well as spectral analysis. The IR spectrum of
compound 14 shows the appearance of two bands of υmax
at 3286.3 cm–1, 3208.2 cm–1 corresponding to two (NH)
groups, while the IR spectrum of compound 13 shows
the disappearance of NH groups. The mass spectrum of
compound 14 shows the molecular ion peak at m/z 366
which is in agreement with the proposed structure 14.
We expected that the treatment of amidine 11 with so-
dium alkoxide (sodium ethoxide, sodium methoxide, so-
dium n-propoxide or sodium isopropoxide) in the corre-
sponding alcohol would afford pyrido[4,3-d]pyrimidine
derivatives 16 [12] through the cyclization of the inter-
mediate 15 in which, two molecules of alcohol were
added on the two cyano groups. However, the mass spec-
tra of the isolated products shows a molecular weight whi-
ch does not agree with the expected structure 16. Also
the 1H-NMR spectra shows three exchangeable protons
corresponding to NH and NH2 groups as well as only one
aromatic proton. This means that the isolated product is
not 16 and the reaction takes place by another pathway in
which the intermediate 15 is attacked by the alkoxide to
give intermediate 17 in which N,N’-dimethylformami-
dine moiety is replaced by alkoxide group followed by
hydrolysis and cyclization to give 4-alkoxy-5-cyano-
pyridine-2(1H)-one-3-carboxylic acid amide 19. The str-
ucture of the isolated product was confirmed by elemen-
tal analysis as well as spectral data in which the IR spec-
tra show the presence of NH, NH2 and cyano group. Also
1H-NMR spectra show two exchangeable protons for NH
& NH2 and one aromatic proton. Sodium isopropoxide
cannot react with amidine 11. This is due to the fact that the
isopropoxide group is a bulkynucleophile. Since it does not
replace the N,N’-dimethylamidine moiety because of the
steric hindrance, we could not isolate pyridine isopropo-
xide derivative (19d) (Scheme 2).
The reaction of malononitrile dimer 8 with diazo-
nium salts of aromatic amines 20a-e furnished the corre-
sponding pyridazine derivatives 21a-e. The structure of
the isolated products was confirmed by elemental analy-
sis as well as spectral data. The IR spectra of these com-
pounds show the appearance of amino and imino groups.
Also the 1H-NMR spectra of these compounds 21a-e
show the appearance of aromatic protons and two exchan-
geable broad singlet signals corresponding to NH2 and
NH groups.
The pyridazine derivatives 21a-e were found to be a good
intermediate for the formation of fused heterocyclic com-
pounds. Reaction of pyridazine derivatives 21a-e with N,N’-
dimethylformamide dimethyl acetal (DMFDMA) afforded
H
2
N
CNNC
CN H
2
N
CNNC
CN
NMe
Me
N
CNNC
CN
NMe
Me
N
Me
Me
N
CNNC
CN
N
Me
Me
N
CNNC
CN
NH
Ar
HN
Ar
N
CNNC
CN
NH
N
Me
Me Ar
N
CNNC
CN
NMe
Me
HN
Ar
N
N
CN
NC
CN
Ar
ArNH
2
ArNH
2
DMFDMA
DMFDMA
or
(9)(10)
(11)
(14)
(12)
or
(1:1)
(1:2)
(8)
(13)
(1:1)
(1:2)
Ar = C
6
H
4
CH
3
-pAr = C
6
H
4
NO
2
-p
DMFDMA
(1:1)
Scheme 1. The reaction and treatment of amidine 11.

F. A. ABU-SHANAB ET AL.
209
N
CNNC
(11)
CN
NN
Me
Me
Me
Me N
CN
NN
Me
Me
Me
Me
RONa
ROH
OROR
NHHN - 2NMe2
NN
N
OROR
CN
OR
RO
CN
N
Me
Me
OROR
NHHN H2O
RO
CN
N
Me
Me
OO
NH2
H2N- NHMe2N
O
H
CN
O
H2N
RO
(15)(16)
(17)(18)(19)
a, R = CH2CH3
b, R = CH3
c, R = n-C3H7
d, R = iso-C3H7
Scheme 2. The treatment of amidine 11 with sodium alkoxide.
3. Experimental
the corresponding amidine 22a-e. IR spectra of these
compounds show the disappearance of the amino group,
and the 1H-NMR spectrum of compound 22b (as an ex-
ample) shows two singlet signals for 6 protons at δH =
3.10, 3.21 ppm corresponding to the two methyl groups
of NMe2 moiety, a singlet signal at δH = 8.41 ppm cor-
responding to CH=N proton and the disappearance of the
amino group.
All melting points are uncorrected. IR spectra were re-
corded on a Perkin-Elmer 17100 FTIR spectrometer as
KBr disks. NMR spectra were recorded on Bruker AC-
300 spectrometer at 400 MHz for solutions in CDCl3 or
DMSO with tetramethylsilane (TMS) as an internal stan-
dard unless otherwise recorded at Department of Chem-
istry, College of Science, Sultan Qaboos University, P.O.
Box 36, Al-Khod23, Oman. Mass spectra were obtained
on Finnigan 4500 (low resolution) spectrometers using
electron impact (EI) at Micro-analytical Center Cairo
University Giza Egypt. N,N’-Dimethylformamide dime-
thyl acetal (DMFDMA) was purchased from MERCK.
Further treatment of pyridazine derivatives 21b,c,e wi-
th acetic acid in the presence of small amounts of hydro-
chloric acid afforded the corresponding pyridazinone de-
rivatives 23a-c. The IR spectra of these compounds show
disappearance of cyano groups and the appearance of
amide carbonyl groups. N’-(2,2-Dicyano-1-cyanomethyl-vinyl)-N,N-dimethyl
-formamidine (9)
Also, the treatment of pyridazine derivatives 21a,b,e
with cyanoacetamide afforded pyrido[4,3-c]pyridazine
derivatives 24a-c. Consequently, pyridopyridazine de-
rivatives 24a-c were treated with N,N’-dimethylforma-
mide dimethyl acetal (DMFDMA) to afford the tricyclic
heterocycle 25a-c (Scheme 3). The IR spectra of com-
pounds 25a-c show the disappearance of amino group.
Also, 1H-NMR spectra of compounds 25a-c show the
disappearance of amino group and the appearance of
(NH) group and methine protons at δH = 7.45 and 8.71
ppm respectively. 1H-NMR Spectra of these compounds
also show two exchangeable broad signals at δH = 7.45
and 10.50 ppm The sum of the two integrations of both
signals is equivalent to one proton which indicates that
these compounds 25a-c may exist as a mixture of three
tautomers 25A,B,C.
In a dry flask, a mixture of malononitrile dimer 8 (1.32
g, 10 mmol) in dry dioxane (30 mL) as solvent and N,N’-
dimethylformamide dimethyl acetal (DMFDMA) (1.32
ml,10 mmol) was left stirring at room temperature for 24
h and the solvent was evaporated. The solid product was
recovered and recrystallised from ethanol as yellow
crystals (1.63 g, 87.17%); mp. 199˚C - 201˚C; 1H-NMR
(DMSO-d6): δ 3.20, 3.25 (6H, 2s, NMe2), 7.59 (2H, s,
CH2), 7.99 (1H, s, CH); 13C-NMR (DMSO-d6): δ 44.93,
47.94 (2CH3), 69.00 (CH2), 158.0 (CH), 118.5, 169.21
(C free of hydrogen); DEPT-135 δ +38.72, +47.51
(2CH3), –66.78 (CH2), +157.20 (CH); Anal. Calcd for
C9H9N5 (187.21): C, 57.74; H, 4.85; N, 37.41. Found: C,
57.55; H, 4.78; N, 37.22.

F. A. ABU-SHANAB ET AL.
210
CN
H
2
N
NC CN
Ar N
2
Cl
NaOAc
NN
Ar
NH
2
NC CN
NH
Ar
NN
N
NC CN
NH
NMe
2
DMFDMA
NN
Ar
NH
2
O
NH
2
H
2
N
OO
CONH
2
CN
NN
Ar
NH
2
NC N
NH
H
O
CN
NN
Ar
NC NH
O
CN
NN
DMFDMA
Ar
O
CN
N
H
NN
NC N
N
NN
Ar
NC N
CN
NN
OH
A
BC
(24)
a, Ar= Ph
b, Ar= C
6
H
4
Br-p
c, Ar= C
6
H
4
Cl-p
d, Ar= C
6
H
4
Me-p
e, Ar= C
6
H
4
NO
2
-p
(8)
(20)
(21)
(22)
AcOH
HCl
(23)
(25)
a, Ar= C
6
H
4
Br-p
b,Ar= C
6
H
4
Cl-p
c, Ar= C
6
H
4
NO
2
-p
a, Ar= Ph
b, Ar= C
6
H
4
Br-p
c, Ar= C
6
H
4
NO
2
-p
a, Ar= Ph
b, Ar= C
6
H
4
Br-p
c, Ar= C
6
H
4
NO
2
-p
Scheme 3. The treatment of pyridazine derivatives 21a,b,e with cyanoacetamide.
N’-[2,2-Dicyano-1-(1-cyano-2-dimethylamino-vinyl)-
vinyl]-N,N-dimethyl-formamidine (11)
(A) In a dry flask a mixture of malononitrile dimer 8
(1.32 g, 10 mmol) in dry dioxane (30 mL) as solvent and
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(2.64 mL, 20 mmol) was left stirring at room temperature
for 24h and the solvent was evaporated. The solid prod-
uct was recovered and recrystallised from ethanol as
yellow crystals (2.1 g, 86.4%), Mp. 149˚C - 151˚C; (B)
In dry flask a mixture of N’-(2,2-dicyano-1-cyanome-
thylvinyl)-N,N-dimethylformamidine 9 (1.87 g, 10 mmol)
in dry dioxane (30 mL) as solvent and N,N’-dimethylfor-
mamide dimethyl acetal (DMFDMA) (1.32 mL, 10 mmol)
was left stirring at room temperature for 24 h and the
solvent was evaporated. The solid product was recovered
and recrystallised from ethanol as yellow crystals (1.9 g,
79.34%); mp. and mmp. 149˚C - 151˚C; 1H-NMR
(DMSO-d6): δ 3.06, 3.19, 3.26, 3.34 (12H, 4s, 2NMe2),
7.67, 8.07 (2H, 2s, 2CH); MS (EI)+: m/z 242 (90.7%) M+;
Anal. Calcd for C12H14N6 (242.29): C, 59.49; H, 5.82; N,
34.69. Found: C, 59.31; H, 5.76; N, 34.48.
2-[5-Cyano-1-(4-nitro-phenyl)-1H-pyrimidin-4-ylide
ne]-malononitrile (13)
In a dry flask a mixture of N’-[2,2-dicyano-1-(1-cya-
no-2-dimethylamino-vinyl)-vinyl]-N,N-dimethyl-formam
idine 11 (2.42 g, 10 mmol) in dry xylene (30 mL) as solvent
and 4-nitroanilne (2.9 g, 10 mmol) was refluxed for two
hours, cooled, and the solvent was evaporated. The solid
product was recovered and recrystallised from ethanol as
brown crystals (2.12 g, 73.10%); mp. 206˚C - 208˚C; IR
(KBr) υ 2195.2 cm–1 (CN); Anal. Calcd. for C14H6N6O2
(290.24): C, 57.94; H, 2.08; N, 28.96. Found: C, 57.76;

211 F. A. ABU-SHANAB ET AL.
H, 2.02; N, 28.79.
N-[2,2-Dicyano-1-(1-cyano-2-p-tolylamino-vinyl)-vin
yl]-N’-p-tolyl-formamidine (14)
In a dry flask a mixture of N’-[2,2-dicyano-1-(1-cya-
no-2-dimethylamino-vinyl)-vinyl]-N,N-dimethyl-formam
idine 11 (2.42 g, 10 mmol) in dry xylene (30 mL) as sol-
vent and p-toluidine (2.14 g, 20 mmol) was refluxed for
two hours, cooled and the solvent was evaporated. The
solid product was recovered and recrystallised from eth-
anol as dark brown crystals (2.61 g, 71.31%); mp. 289˚C -
291˚C; 1H-NMR (DMSO-d6): δ 2.12, 2.24 (6H, 2s,
2CH3), 6.42, 6.82 (8H, 2d, Ar-AB), 7.05, 7.09 (2H, 2s,
2NH), 7.54, 7.56 (2H, 2s, 2CH); IR (KBr) υ 3286.3,
3208.2 (2NH), 2225.2, 2204.3 cm–1 (3CN); MS (EI)+:
m/z 366 (10.7%) M+; Anal. Calcd. for C22H18N6 (366.43):
C, 72.11; H, 4.95; N, 22.93. Found: C, 71.92; H, 4.84; N,
22.70.
Genera l proced ure for the prepara tion of comp ounds
19a-c
A mixture of Compound 11 (10 mmol) and sodium al-
koxide (10 mmol) in corresponding alcohol (30 mL) was
refluxed for two hours. The mixture was left to cool then
poured onto ice cold water. The solid product was re-
covered by filtration and recrystallised from ethanol.
5-Cyano-4-ethoxy-2-oxo-1,2-dihydro-pyridine-3-carb
oxylic acid amide (19a):
Obtained from 11 (2.42 g, 10 mmol) with sodium
ethoxide (Na 0.23 g, EtOH 30 mL, 10 mmol); mp. 219˚C -
221˚C as brown crystals (1.46 g, 70.53%); 1H-NMR
(DMSO-d6): δ 1.28, 1.32, 1.35 (3H, t, CH3), 4.36, 4.39,
4.43, 4.47 (2H, q, CH2), 7.49 (1H, s, NH), 8.05 (2H, s,
NH2, br), 8.47 (1H, s, ring-H); MS (EI)+: m/z 207 (39.9%)
M+; Anal. Calcd. for C9H9N3O3 (207.19): C, 52.17; H,
4.38; N, 20.28. Found: C, 52.02; H, 4.25; N, 20.03.
5-Cyano-4-methoxy-2-oxo-1,2-dihydro-pyridine-3-ca
rboxylic acid amide (19b):
Obtained from 11 (2.42 g, 10 mmol) with sodium me-
thoxide (Na 0.23 g, MeOH 30 mL, 10 mmol); mp. 229˚C -
231˚C as brown crystals (1.43 g, 74.09%); IR (KBr) υ
3383.7, 3350.9 (NH2), 3237.5 (NH), 2230.1 (CN),
1670.5 cm–1 (C=O); Anal. Calcd. for C8H7N3O3 (193.16):
C, 49.75; H, 3.65; N, 21.75. Found: C, 49.48; H, 3.56; N,
21.62.
5-Cyano-2-oxo-4-propoxy-1,2-dihydro-pyridine-3-car
boxylic acid amide (1 9c):
Obtained from 11 (2.42 g, 10mmol) with sodium
n-propoxide (Na 0.23 g, n-propanol 30 mL, 10 mmol);
mp. 210˚C - 212˚C as yellow crystals (1.91 g, 86.43 %);
IR (KBr) υ 3325.64, 3202.22 (NH2) and (NH), 2214.84
(CN), 1659 cm–1 (C=O); MS (EI)+: m/z 219 (31.3%)
[M-2]+; Anal. Calcd. for C10H11N3O3 (221.22): C, 54.30;
H, 5.01; N, 18.99. Found: C, 54.14; H, 4.90; N, 18.76.
Genera l proced ure for the prepara tion of comp ounds
21a-e
A mixture of ice cold diazonium salts of aromatic ami-
nes 20 [conc. HCl (20 mL) added to aromatic amine (10
mmol), cooled then added sodium nitrite (0.69 g, 10
mmol)] was added to malononitrile dimer 8 (1.32 g, 10
mmol) in ethanol (30 mL) as solvent in presence of so-
dium acetate. The precipitate was collected by filtration
and recrystallised from ethanol.
4-Amino-6-imino-1-phenyl-1,6-dihydro-pyridazine-3,
5-dicarbonitrile (21a):
Obtained from malononitrile dimer 8 (1.32 g, 10 mmol)
and aniline (0.93 g, 10 mmol); mp. > 300˚C as yellow
crystals (2.20 g, 93.22%); 1H-NMR (DMSO-d6): δ 7.63
- 8.04 (5H, m, Ar), 8.85 (2H, s, NH2, br), 9.4 (1H, s, NH,
br); IR (KBr) υ 3432.2, 3333.8 (NH2), 3306 (NH), 2207
(CN); Anal. Calcd for C12H8N6 (236.24): C, 61.01; H,
3.41; N, 35.57. Found: C, 60.83; H, 3.27; N, 35.35.
4-Amino-1-(4-bromo-phenyl)-6-imino-1,6-dihydro-py
ridazine-3,5-dicarbonitrile (21b):
Obtained from malo- nonitrile dimer 8 (1.32 g, 10
mmol) and 4-bromoaniline (1.725 g, 10 mmol); mp. >
300˚C as yellow crystals (2.91 g, 92.38%); 1H-NMR
(DMSO-d6): δ7.41, 8.09 (4H, 2d, Ar-AB), 9.15 (2H, s,
NH2, br), 9.94 (1H, s, NH, br); IR (KBr) υ 3423, 3337.21
(NH2), 3295.2 (NH), 2210.02 cm–1 (CN); Anal. Calcd.
for C12H7BrN6 (315.13): C, 45.74; H, 2.24; N, 26.67.
Found: C, 45.52; H, 2.10; N, 26.48.
4-Amino-1-(4-chloro-phenyl)-6-imino-1,6-dihydro-py
ridazine-3,5-dicarbonitrile (21c):
Obtained from malononitrile dimer 8 (1.32 g, 10 mmol)
and 4-chloroaniline (1.275g, 10 mmol); mp. > 300˚C as
yellow crystals (2.49 g, 92.22%); 1H-NMR (DMSO-d6):
δ 7.52, 7.98 (4H, 2d, Ar-AB), 9.18 (2H, s, NH2, br), 9.88
(1H, s, NH, br); IR (KBr) υ 3415.6, 3326.61 (NH2),
3308.3 (NH), 2209.06 (CN); Anal. Calcd. for C12H7ClN6
(270.68): C, 53.25; H, 2.61; N, 31.05. Found: C, 53.07;
H, 2.55; N, 30.89.
4-Amino-6-imino-1-p-tolyl-1,6-dihydro-pyridazine-3,
5-dicarbonitrile (21d):
Obtained from malononitrile dimer 8 (1.32 g, 10 mmol)
and 4-methylaniline (1.07 g, 10 mmol); mp. > 300˚C as
yellow crystals (2.27 g, 90.8%); 1H-NMR (DMSO-d6):
δ = 2.10 (3H, s, CH3), 7.57, 7.69 (4H, 2d, Ar-AB), 9.16
(2H, s, NH2, br), 9.88 (1H, s, NH, br); IR (KBr) υ
3413.25, 3318.8 (NH2), 3298.5 (NH), 2209.63 cm–1 (CN);
Anal. Calcd. for C13H10N6 (250.26): C, 62.39; H, 4.03; N,
33.58. Found: C, 62.11; H, 3.88; N, 33.37.
4-Amino-6-imino-1-(4-nitro-phenyl)-1,6-dihydro-pyri
dazine-3,5-dicarbonitrile (21e):
Obtained from malononitrile dimer 8 (1.32 g, 10 mmol)
and 4-nitroaniline (1.38 g, 10mmol); mp. > 300˚C as
brown crystals (2.57 g, 91.46%); 1H-NMR (DMSO-d6):
δ = 7.58, 7.72 (4H, 2d, Ar-AB), 9.23 (2H, s, NH2, br),

F. A. ABU-SHANAB ET AL.
212
9.89 (1H, s, NH, br); IR (KBr) υ 3433.2, 3340.25 (NH2),
3300.5 (NH), 2211.03 cm–1 (CN); Anal. Calcd. for
C12H7N7O2 (281.24): C, 51.25; H, 2.51; N, 34.86. Found:
C, 51.04; H, 2.43; N, 34.69.
Genera l proced ure for the prepara tion of comp ounds
22a-e
Compound 21 (10 mmol) and N,N’-dimethylforma-
mide dimethyl acetal (DMFDMA) (10 mmol) in dry di-
oxane (30 mL) was refluxed for two hours, cooled and
evaporated. The precipitate was collected by filtration
and recrystallised from ethanol.
N’-(3,5-Dicyano-6-imino-1-phenyl-1,6-dihydro-pyrid
azin-4-yl)-N,N-dimethyl-formamidine (22a):
Obtained from Compound 21a (2.36 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. 203˚C - 205˚C as yellow crys-
tals (2.24g, 76.98%); 1H-NMR (DMSO-d6): δ 3.29,
3.42 (6H, 2s, NMe2), 6.85 (1H, s, NH, br), 7.34 - 7.94
(5H, m, Ar), 8.27 (1H, s, CH); IR (KBr) υ 3306.9 (NH),
2208.9 cm–1 (CN); Anal. Calcd for C15H13N7 (291.32): C,
61.85; H, 4.50; N, 33.66. Found: C, 61.63; H, 4.37; N,
33.49.
N’-[1-(4-Bromo-phenyl)-3,5-dicyano-6-imino-1,6-dih
ydro-pyridazin-4-yl]-N,N-dimethyl-formamidine (22b):
Obtained from Compound 21b (3.15 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. 209˚C - 211˚C as deep brown
crystals (2.85 g, 77.03%); 1H-NMR (DMSO-d6): δ 3.10,
3.21 (6H, 2s, NMe2), 6.98 (1H, s, NH, br), 7.46, 7.72 (4H,
2d, Ar-AB), 8.41 (1H, s, CH); IR (KBr) υ 3302.8 (NH),
2202 cm–1 (CN); Anal. Calcd. for C15H12BrN7 (370.21):
C, 48.67; H, 3.27; N, 26.48. Found: C, 48.44; H, 3.12; N,
26.22.
N’-[1-(4-Chloro-phenyl)-3,5-dicyano-6-imino-1,6-dih
ydro-pyridazin-4-yl]-N,N-dimethyl-formamidine (22c):
Obtained from Compound 21c (2.7 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol) mp. 197˚C - 199˚C as brown crys-
tals (2.40 g, 73.85%); 1H-NMR (DMSO-d6): δ 3.22,
3.31 (6H, 2s, NMe2), 6.86 (1H, s, NH, br), 7.34, 7.68 (4H,
2d, Ar-AB), 8.46 (1H, s, CH); IR (KBr) υ 3312.8 (NH),
2213.8 cm–1 (CN); Anal. Calcd. for C15H12ClN7 (325.76):
C, 55.31; H, 3.71; N, 30.10. Found: C, 55.15; H, 3.60; N,
29.93.
N’-(3,5-Dicyano-6-imino-1-p-tolyl-1,6-dihydro-pyrid
azin-4-yl)-N,N-dimethyl-formamidine (22d):
Obtained from Compound 21d (2.5 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. 221˚C - 223˚C as yellow crys-
tals (2.34 g, 76.72%); 1H-NMR (DMSO-d6): δ 2.35 (3H,
s, CH3), 3.08, 3.20 (6H, 2s, NMe2), 6.65 (1H, s, NH, br),
7.40, 7.82 (4H, 2d, Ar-AB), 8.45 (1H, s, CH); IR (KBr) υ
3301.8 (NH), 2209.7 cm–1 (CN); Anal. Calcd. for
C16H15N7 (305.34): C, 62.94; H, 4.95; N, 32.11. Found:
C, 62.75; H, 4.84; N, 31.90.
N’-[3,5-Dicyano-6-imino-1-(4-nitro-phenyl)-1,6-dihy
dro-pyridazin-4-yl]-N,N-dimethyl-formamidine (22e) :
Obtained from Compound 21e (2.81 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. 223˚C - 225˚C as deep brown
crystals (2.82 g, 83.93%); 1H-NMR (DMSO-d6): δ 3.12,
3.28 (6H, 2s, NMe2), 7.40 (1H, s, NH, br), 7.88, 8.39 (4H,
2d, Ar-AB), 8.50 (1H, s, CH); IR (KBr) υ 3290.8 (NH),
2207.6 cm–1 (CN); Anal. Calcd. for C15H12N8O2 (336.32):
C, 53.57; H, 3.60; N, 33.32. Found: C, 53.35; H, 3.48; N,
33.15.
Genera l proced ure for the prepara tion of comp ounds
23a-c
Compound 21 (10 mol) in acetic acid (20 mL) and hy-
drochloric acid (3 mL) was refluxed for four hours,
cooled, and poured onto ice cold water.. The precipitate
which formed was recovered by filtration and recrystal-
lised from ethanol.
4-Amino-1-(4-bromo-phenyl)-6-oxo-1,6-dihydro-pyri
dazine-3,5-dicarboxylic acid diamide (23a):
Obtained from Compound 21b (3.15 g, 10 mmol); mp.
> 300˚C as deep brown crystals (2.65 g, 75.28%);
1H-NMR (DMSO-d6): δ 7.82; 8.64 (4H, 2d, Ar-AB),
7.98 (2H, s, NH2), 9.79 (2H, s, NH2, br); IR (KBr) υ
3376.3, 3314.6 (NH2), 1701, 1663.9 cm–1 (C=O); Anal.
Calcd. for C12H10BrN5O3 (352.15): C, 40.93; H, 2.86; N,
19.89. Found: C, 40.71; H, 2.74; N, 19.60.
4-Aamino-1-(4-chloro-phenyl)-6-oxo-1,6-dihydro-pyr
idazine-3,5-dicarboxylic acid diamide (23b):
Obtained from Compound 21c (2.7 g, 10 mmol); mp.
> 300˚C as brown crystals (2.23 g, 72.64%); 1H-NMR
(DMSO-d6): δ 7.78, 8.40 (4H, 2d, Ar-AB), 8.01 (2H, s,
NH2), 9.85 (2H, s, NH2, br); IR (KBr) υ 3314.5, 3197.7
(NH2), 1697.7, 1630 cm–1 (C=O); Anal. Calcd. for
C12H10ClN5O3 (307.70): C, 46.84; H, 3.28; N, 22.76.
Found: C, 46.59; H, 3.13; N, 22.61.
4-Amino-1-(4-nitro-phenyl)-6-oxo-1,6-dihydro-pyrid
azine-3,5-dicarboxylic acid diamide (23c):
Obtained from Compound 21e (2.81 g, 10 mmol); mp.
> 300˚C as brownish crystals (2.42 g, 76.10%); 1H-
NMR (DMSO-d6): δ 7.90, 8.55 (4H, 2d, Ar-AB), 8.30
(2H, s, NH2), 9.60 (2H, s, NH2, br); IR (KBr) υ 3381.0,
3272.0 (NH2), 1691.9, 1654.7 cm–1 (C=O); Anal. Calcd.
for C12H10N6O5 (318.25): C, 45.29; H, 3.17; N, 26.41.
Found: C, 45.03; H, 3.06; N, 26.24.
Genera l proced ure for the prepara tion of comp ounds
24a-c
A mixture of Compound 21 (10 mmol) and cyanoa-
cetamide (10 mmol) in ethanol (30 mL) and 3-5 drops of
piperidine as a base was refluxed for two hours, cooled,
and poured onto ice cold water. The precipitate was re-

213 F. A. ABU-SHANAB ET AL.
covered by filtration and recrystallised from ethanol.
4-Amino-5-imino-7-oxo-1-phenyl-1,5,6,7-tetrahydro-
pyrido[4,3-c]pyridazine-3,8-dicarbonitrile (24a):
Obtained from Compound 21a (2.36 g, 10 mmol) with
cyanoacetamide (0.84 g, 10 mmol); mp. > 300˚C as
brown crystals (2.22 g, 73.27%); 1H-NMR (DMSO-d6):
δ 7.23 (2H, s, NH2), 7.61, 10.52 (2H, 2s, 2NH, br), 7.64 -
8.12 (5H, m, Ar); IR (KBr) υ 3420.6, 3382.7 (NH2), 3343
cm-1 (NH), 2210.5 cm-1 (CN), 1683.2 cm–1 (C=O); Anal.
Calcd. for C15H9N7O (303.29): C, 59.41; H, 2.99; N,
32.33. Found: C, 59.22; H, 2.87; N, 32.19.
4-Amino-1-(4-bromo-phenyl)-5-imino-7-oxo-1,5,6,7-t
etrahydro-pyrido[4,3-c]pyridazine-3,8-dicarbonitrile
(24b):
Obtained from Compound 21b (3.15 g, 10 mmol) with
cyanoacetamide (0.84 g, 10 mmol); mp. 179˚C - 181˚C
as brown crystals (2.83 g, 74.08%); 1H-NMR (DMSO-
d6): δ 6.70 (2H, s, NH2), 7.68, 10.20 (2H, 2s, 2NH, br),
7.50, 8.20 (4H, 2d, Ar-AB); IR (KBr) υ 3402.0, 3325.1
(NH2), 3175.1 (NH), 2204.8 (CN), 1617.5 cm–1 (C=O);
Anal. Calcd. for C15H8BrN7O (382.18): C, 47.14; H, 2.11;
N, 25.65. Found: C, 46.91; H, 2.02; N, 25.41.
4-Amino-5-imino-1-(4-nitro-phenyl)-7-oxo-1,5,6,7-tet
rahydro-pyrido[4,3-c]pyridazine-3,8-dicarbonitrile
(24c):
Obtained from Compound 21e (2.81 g, 10 mmol) with
cyanoacetamide (0.84 g, 10 mmol) mp. 239˚C - 241˚C as
brown crystals (2.39 g, 68.68%); 1H-NMR (DMSO-d6):
δ 7.19 (2H, s, NH2), 7.55, 10.60 (2H, 2s, 2NH, br), 7.78,
8.34 (4H, 2d, Ar-AB); IR (KBr) υ 3462.0, 3352.3 (NH2),
3228.2 (NH), 2192 (CN), 1630.0 cm–1 (C=O); Anal.
Calcd. for C15H8N8O3 (348.28): C, 51.73; H, 2.32; N,
32.17. Found: C, 51.50; H, 2.19; N, 32.13.
Genera l proced ure for the prepara tion of comp ounds
25a-c:
Compound 24 (10 mmol) and N,N’-dimethylforma-
mide dimethyl acetal (DMFDMA) (10 mmol) in dry di-
oxane (30 mL) was refluxed for two hours, cooled, and
evaporated. The precipitate was collected by filtration
and recrystallised from ethanol.
8-Oxo-1-phenyl-7,8-dihydro-1H-1,2,4,6,7-pentaaza-p
henalene-3,9-dicarbonitrile (25a):
Obtained from Compound 24a (3.03 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. > 300˚C as brown crystals (2.29
g, 73.16%); 1H-NMR (DMSO-d6): δ 7.37 (1H, s, NH, br),
7.81-8.36 (5H, m, Ar), 8.86 (1H, s, CH), 10.30 (1H, s, OH,
br); IR (KBr) υ 3333.7 (NH), 2205.7 (CN), 1629 cm–1
(C=O); Anal. Calcd. for C16H7N7O (313.28): C, 61.34; H,
2.25; N, 31.30. Found: C, 61.18; H, 2.08; N, 31.16.
1-(4-Bromo-phenyl)-8-oxo-7,8-dihydro-1H-1,2,4,6,7-
pentaaza-phenalene-3,9-dicarbonitrile (25b):
Obtained from Compound 24b (3.82 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. > 300˚C as deep brown crys-
tals (2.76 g, 70.41%); 1H-NMR (DMSO-d6): δ 7.51 (1H,
s, NH, br), 7.69, 8.28 (4H, 2d, Ar-AB), 8.84 (1H, s, CH),
10.02 (1H, s, OH, br); IR (KBr) υ 3326.9 (NH), 2206.1
(CN), 1623 cm–1 (C=O); Anal. Calcd. for C16H6BrN7O
(392.18) C, 49.00; H, 1.54; N, 25.00. Found: C, 48.79; H,
1.42; N, 24.85.
1-(4-Nitro-phenyl)-8-oxo-7,8-dihydro-1H-1,2,4,6,7-p
entaaza-phenalene-3,9-dicarbonitrile (25c):
Obtained from Compound 24c (3.48 g, 10 mmol) with
N,N’-dimethylformamide dimethyl acetal (DMFDMA)
(1.32 mL, 10 mmol); mp. > 300˚C as brown crystals
(2.52 g, 70.39%); 1H-NMR (DMSO-d6): δ 7.45 (1H, s,
NH, br), 7.78, 8.32 (4H, 2d, Ar-AB), 8.71 (1H, s, CH),
10.50 (1H, s, OH, br); IR (KBr) υ 3338.4 (NH), 2202.5
(CN), 1618 cm–1 (C=O); Anal. Calcd. for C16H6N8O3
(358.28): C, 53.64; H, 1.69; N, 31.28. Found: C, 53.41;
H, 1.58; N, 31.05.
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