Aryl-aryl cross-couplings that avoid the preparation of haloaromatics
3.1 Introductionshodhganga.inflibnet.ac.in/bitstream/10603/34272/7/07_chapter 3.pdf · The...
Transcript of 3.1 Introductionshodhganga.inflibnet.ac.in/bitstream/10603/34272/7/07_chapter 3.pdf · The...
-
3.1 Introduction :-
Pyrazoles are very important well known nitrogen containing five member heterocyclic
compounds. The derivatives of pyrazole have played a crucial role in the history of
heterocyclic Chemistry and used extensively as important pharmacophores and synthons
in the field of Organic chemistry and Drug designing. The pyrazole meoity constitutes the
core structure of numerous biologically active compounds including drugs Viagra1 an
inhibitor of 5- phosphodiesterase used for the treatment of erectile disfunction, Celebrex2,
an inhibitor of cyclooxygenase-2 (COX-2) used as patent antinflammatory and antagonist
of the CB-1 cannabinoid receptor3, used for the treatment of obesity in addition to this
pyrazole. Pyrazoles have diverse biological activities such as anti-microbial4-7
, anti-
inflammatory8, analgesic
9, anti-cancer
10 anti-convulsant
11, anti-viral
12 and herbicidal
13
etc.
The first pyrazole derivatives was isolated by Japanese workers14
3-n-nonyl pyrazole (1)
from Houttuynia Cordata (a plant) and observed its antimicrobial activity. A pyrazolic
amino acid-levo- -(1-pyrazolyl)-alanine (2) has been isolated from water-melon-seeds15-
16.
Pyrazole is a five membered heterocyclic compound having three carbon atoms and two
nitrogen atoms in adjacent position. The molecular formula of Pyrazole is C3H4N4.
Pyrazole contains a pyrrole-like and a pyridine like N-atom at-1 and -2 positions (1, 2-
diazole).
The nuclevs of pyrazole (3) ring is planer.
(CH2)8CH3
N
N H
(1) (CH2)8CH(NH2)COOH
N
(2)
N
3
N2
4
5
-
The bond lengths of N1-N2 bond in the ring is 1.349 A°, N2-N3 bond is 1.331 A
°, C5-N1
bond is 1.359 and N1-H=0.998 A°. The bond angles in pyrazole ring (3) are C-N-
N=113.1°, N-N-C=104.1
°, N-C-C=119.1
°, C-C-C=104.5
°, and C-C-N=104.1
°.
The pyrazole (3) has been represented by the following three tautomers (4,5,6) with H-
prefixes to rationalize to nomenclature of the compound containing this basic skeleton17-
18.
The pyrazole (3) exists in three partially reduced forms-1-pyrazoline (7), 2-pyrazoline (8)
and 3-pyrazoline (9) with different positions of double bond.
The oxoderivatives of pyrazolines were described as pyrazolinones19
and later on
pyrazolones20
.
According to the older system of nomenclature whon the carbonyl group is adjacent to
nitrogen atoms in the ring, these were named as 5-pyrazolone, pyrazolone-5. pyrazolin-5-
one (10) and the later tavtomer-3-pyrazolin-5-one. (11)
(4H- Pyrazole)
(6)
N
N
(5)
(3H- Pyrazole)
N
N
(IH- Pyrazole)
N
N H
(4)
N
(7)
N N H
N
(8) (9)
N H
NH
(10) (11)
NH O
N H
N O
N H
N1 H
(3)
-
The first known 5-pyrazolone is represented by Ludwing knorr21
who carried out the
condensation of acetoaceticester with phenyl hydrazine (in 1883) and synthesized a
compound with m.p.-127°C. The correct structure
22 (12) was propounded in (1887).
The pyrazolones confirming to the structure (12), according to IUPAC system of
nomenclature are termed as 2,4-dihydro-3H-Pyrazol-3-ones.
Preparation of Pyrazoles :-
Pyrazole (14) was obtained for the first time by Buchner in 1889, on heating pyrazole-
3,4,5-tricarboxlic aced (13) at 230-240°C
23.
The most widely used method for the synthesis of pyrazole (17) is the reaction of -
dikitone (15) with hydrazine (16) or mono substituted hydrazine in the presence of an
acid24
.
(12)
CH3
N
N O
C6H5
(13)
HOOC
HOOC
COOH
COOH N
N H
230°C
(14)
+ 3CO2 N
N H
(15)
C
H2C
O
C
H3C
O
H2C
+ H2N NH2 - H2O N
CH3
H3C N H
(16) (17)
-
The reaction of methyl hydrazine with acetylacetaldehyde dimethylacetal (18) give
hydrazone (19). This was subsequently cyclized in acidic medium to yield a dimethyl
pyrazole (20) 25
.
Benzoylacetone (21) reacts with phenyl hydrazine to give a monophenyl hydrazone (22).
On heating with acid the phenyl hydrazone is converted into a single product 3-methyl-
1,5-diphenyl pyrazole26-27
. (23)
CH3
(18)
CO CH2
OCH3
OCH3
(19)
N
CH3 C CH
OCH3
CH
OCH3
NH CH3
CH3 NH NH2
CH3
N
(20)
N
CH3
C6H5–CO–CH2–CO–CH3 C6H5–NH–NH2 C6H5 – CO – CH2
C6H5–NH–N
C – CH2 (21)
(22)
CH3
N
(23)
H5C6
H5C6
N
-
The reaction between -keto ester and hydrazine results in the formation of 5-pyrazolone
(24). Howerver under favoarable experimental conditions a 5-alkoxy pyrazole (25) is
obtained along with pyrazolone28,29
.
Cyclocondensation of cyanoacetamide (27) with sodium salt of 3-hydroxyl-1-(pyridine-
3-yl)-prop-2-en-1-one (26) gave 6-oxo/thiooxo-[2,3] pyridine (28) which on reaction with
iodomethane gave bipyridine, which cyclocondensed with hydrazine to give pyrazolo [3,
4-b] pyridine30
. (29)
R-CO-CH2-COOR + R” NH-NH2 R – C – CH2 – COOR
1
N – NH – R
R1 – OH +
+ H2O
R
R ”
O N
R
(25)
R ”
N
(24)
R1
N N
N
(26)
O
O Na
NH2 H2O
i) Pip. acetate
ii) H+
(27)
EtOH NH2NHR
N N
(29)
NH2
R
+ NC N N
H
X
(28)
CN
N
X
N
-
The Vilsmeier –Haack reaction of the aryl hydrazones of aryl methyl Ketones is a
convenient method for the preparation of 1, 3- diaryl 4 –formyl pyrazole31
. (30)
Dimethyl-1-aryl (benzyl)-4,5-dioxo-4, 5-dihydro-1H-pyrol -2,3-dicaraboxylates (31)
reacted with phemyl hydrazine and benzyl hydrazine to give dimethyl -1 – aryl (benzyl)-
5-[aryl or benzyl] carbamoyl)-1H-pyrazole-3, 4-dicaraboxylate32
. (32)
The reaction of hydrazine and allene carbonyl compounds gives pyrazoles33
. (33)
CH2 C CH CO R N2H4 +
R N
N
H
CH3
(33)
N N
Me
N
H
N
Me
Me
DMF, POCl3 Me
N
O
N
Me
Me
Me
Me
O
(30)
Me N – N
O
Me
+
N N
Me
(32)
R2
H
NH2
N
+ -H2O
COOMe
CONHR1 N
R1
MeOCO
N
COOMe
COOMe
R1
O
O
(31)
N
-
Arylhydrazones of aliphatic and aromatic aldehydes condense with - ketoesters in
presence of anydrous zinc chloride at temperature ranging from 120° to 140
°C to yield the
esters of pyrazol-4-carboxylic acids34-35
.
Physical Properties:-
Pyrazole is a colourless solid, with m.p. 69-70°C. The boiling point of pyrazole is 186-
188°C at 757.9mm. It is very stable to heat and can be distilled at atomospheric pressure
without decomposition. Pyrazole shows weak basic properties with a pka value of 2.5336
.
The dipole moment of pyrazole was determined by Huckel and Coworkers,37
found a
value of 2.64D in dioxane and 1.6D ib benzene38
. Pyrazole is soluble in water and much
less soluble in benzene and cyclo haxane. The IR Spectra are generally characterized by
bands at 3485cm-1
(N-H), 1037-974cm-1
(C-H in plane) 935 and 790cm-1
(C-H. out of
plane). The U.V. region of alkyl pyrazole absorb at 210-225nm,. The pyrazole shows a
1H-NMR signal in CDCl
3 at .=13.6ppm. for CN-H-proton. The C-3 and C-5 protons
appear as a doublet (coupling with H-4) at 7.54 ppm, while the C4-proton itself appears as
a triplet at 6.24ppm in carbon tetrachlorides39
.
Chemical Reaction :-
The pyrazole ring is normally very resistant to oxidation only side chains are attacked by
oxidizing agents. Potassium permanganate, is usually in neutral or alkaline medium
converts side chains on any position of the pyrazole ring into carboxylic groups40-41
.
(34)
R
H5C2OOC R1
N
N
Ar
C2H5OOCCH2 CH
CO
R
N +
NH Ar
R1
ZnCl2
CH3
N
N
COOH
N
N
KMnO4
OH-
-
Nitric acid is a convenient oxidizing agent for converting 4-nitroso-pyrazoles (37) into 4-
intropyrazoles42
. (38)
Nitration of pyrazole with nitrating mixture of concentrated nitric acid and sulfuric acid
occurs at the position-4.
Pyrazoles undergo sulfonation only under vigorous reaction conditions with introduction
of sulfonic acid group at the position-4.
N
O2N
(40)
H
N H
+ HNO3 H2SO4
(39)
N
N
N
ON
H5C6
C6H5
N
N
H
C6H5
N
N
HNO3
(38)
H5C6
O2N
(37)
(H2SO4+SO3)
20% Oleum
R
Prolonged
heating
N
(41)
H
N
R HO3S
R
(42)
H
N
N
R
-
Halogenation of pyrazole (43) occurs at position-4. Pyrazole can be chlorinated by
chlorination reagent i.e., chlorine in carbon tetrachloride.
Pyrazoles are brominated by bromine in chlaro form give 4- bromo pyrazole. (44)
Pyrazoles are chloromercurated at the position-4 by the reaction with mercury (II)
chloride providing (45).
Cl2 in CCl4 (60ºC)
Cl
N
(43)
H N
N
N H
H N
Br2
(CCl4)
(44)
H N
Br
N
N N
H N
+ HgCl2
(45)
H N
ClHg
N
N N
-
The reduction of pyrazole with sodium and alcohol or by catalytic hydrogenation over
palladium results in 2-pyrazolines. (46).
3-methyl-carboxy-5-metheyl pyrazole (47) on akylation with dimethyl sulfate yields N-
alkyl-3-methyl-carboxy-5-methyl pyrazole43-44
. (48)
The irradiation of pyrazoles with nucleophilic reagents results in nucleophilic photo
substitution with the replacement of hydrogen atom by nucleophile from the position -4.
If the position-4 is already occupied, the hydrogen atom is substituted from position-545-
46.
H N
Na/C2H5OH
(46)
H N N
N N
or
H2/Pd
(48)
H
N N
N
COOH
H3C H3C
COOH
H
(47)
N
N
(CH3)2 SO4
N
N
R1 NC R1
R R
(50) (49)
N
N
CN
hυ
N
N
CH3 NC
R R
(52) (51)
N
N
NC
CN
hυ
CH3
-
Biological Activity and its importance :-
Pyrazoles have diverse biological activities such as antimicrobial, anti-bacterial,
antifungal, anti-inflammatory, analgesic, anticonvulsant, anti-cancer, antioxidant,
insecticide and herbicidal. Pyrazole derivatives have huge applications in agrochemical
and pharmaceutical industry as herbicides and active pharmaceuticals.
Antimicrobial Agents :-
A series of 4-chloro-2-{4-[(E)-(substituted phenylimino) methyl]-1-pyrazol-3yl}-phenols
(52) have antimicrobial activity against E. coli and S. aureus. and C. albicans47
.
Vertika Gautam et.al. synthesized 1-(4-Azidophenyl)-5-(4-chlorophenyl)-3-methyl-1H-
Pyrazoles (53) have been reported as antimicrobial agents48
.
CH3
N
C6H4Cl
N=N+=N-
N
R = C6H5,C6H4NO2
(52)
OH
HC = N–R
Cl
N NH
-
1-phenyl-3-(3a,6,7-trimethyl-3a,4,5,6,7-7a-hexa-hydro-1H-inden-3-yl)-1H-pyrazole (54)
have been reported as antimicrobial agents49
.
1-carbonamidipyrazolo [3,4-b] quinolines (55) were reported as antimicrobial agents50
.
Abdel-Rahman et.al. synthesized a series of pyrazole i.e., 5-(1-benzyl-1H-indol-3-yl)-2,
4-dihydro-3H-pyrazole-3-thione (56) have antimicrobial activities against S. aureus and
A. parasiticus51
.
(55)
N H
O
N
N
N
(54)
CH3
H3C
CH3
N
N
-
S maail Radi et.al., synthesized a series of pyrazole (57) derivatives, were evaluated for
their antimicrobial activity against E. coli and Fusarium oxysproum52
.
A series of 4,6-disubstituted-3-cyano-2-pyridones derivatives are reported antimicrobial
agents53
.
R=CH3, CO2Et
(57)
N
X OH
R
N H3C
(56)
N
S
N
N H
R= Thienyl
R1= H, 4-F, 4-Cl, etc.
R1
H N N
R O
N
N H
(58)
-
The compound 2-(( 1,3-Diphenyl-1H-pyrazol-4-yl) methylone)-5-5-dimethyl
cyclohexane-1, 3-dione (59) shows antimicrobial activity against A. niger, A. flavus and
E. coli and B. subtilis54
.
The compound 3 - [3 - (5-bromo-1-benzofuran-2-yl) -1H-pyrazole - 4 – yl] -1-
(substituted phenyl) prop-2-en-1-ones (60) have antimicrobial activity against. S.
epidermidis B. subtitis and. A. niger, C. albicans55
.
Ar = C6H5, OCH3C6H4 O
(60)
N NH
Br
HC=CH-C-Ar
O
(59)
O
O
C6H5
Me
X Me
N X = H
N
-
A series of 6/8 substituted –1N-(amido/thiocarboxamido) pyrazolo[4,5-b] quinolines
have been reported as antimicrobial agents56
.
Samir Bondock et.al., synthesized a series of substituted pyrazole derivatiues, exhibited
antimicrobial activity57
. The compound 2-(5-(4-hydroxyphenyl)-3-phenyl-4,5-
dihydropyrazol-1-yl)-N-(4-phenylthiazol-2-yl) acetamide have been reported as
antimicrobial agents58
. A series of arylazopyrazoles derivatives have been reported as
antimicrobial agents against S. aureus, E. coli and C. albican, A. niger59
. A series of
pyrazole derivatives bearing quinoline derivatives showed antimicrobial activity60
.
Ujjwall sahoo et.al., synthesized a series of bipyrazole derivatives, there derivatives have
antimicrobial activity against. E.coli, C. albicans and A. niger61
. A series of sulphur
bridged pyrazole derivatives have been reported as antimicrobial agents62
. A series of 3-
methyl-4-phenyl-5(p-substituted phenyl)-1-(p-sulphamyl-phenyl) pyrazoles have
antimicrobial activity against E. coli and C. albicans63
. The compound 4-arylazo-1-
benzothiazolyl-3,5-dimethyl pyrazoles were showed antimicrobial activity64
.
Antibacterial Agents :-
A series of 4-aryl-5-hydroxypyrazoles (61) have been reported as antibacterial agents65
.
The compound 6-Amino-3-methyl-1-phenyl-1H-pyrazolo-[3,4-b] pyridine-5-
carboxamide (62) have been reported as anti bacterial agents66
.
(61)
CH3
OH
R2
N
N
R1
CONH2
N
N
Me
-
A series of substituted ethyl 4-amino-1-(3-substituted-4-fluorophenyl)-5-cyano-1H-
pyrazole-3-carboxylate (63) have anti bacterial activity against S. aureus and E. colis67
.
A series of 1-(furan-2-carbonyl)-3-methyl-4-(2-phenyl hydrazono)-1H-pyrazol-5(4H)-
one have been reported as anti bacterial agents68
.
A series of N-substituted 3-benzyl-5-phenyl pyrazole (64) have antibacterial activity
against B. subtilis and B. aureus69
.
(63)
H2N COOC2H5
NC
N
R
N
F
CH2
CH3
CO
N
N
-
The compounds 1(unsubstituted/substituted)-3,5-dimethyl-1H-pyarazoles (65) have been
reported as anti bacterial agents70
.
Vijay V. Dabholkar et.al., synthesized a series of pyrazole derivatives as antibacterial
agents71
. A series of [CN-cinnamoyl)-2,3-dichloroanilinomalonyl] 3, 5-dimethyl-4-
(unsubstituted/substituted phenylazo) pyrazole derivatives have been reported as
antibacterial agents72
. A series of pyrazole derivatives have been reported as antibacterial
agents73
. A series of 5-amido-1-(2,4-dinitrophenyl)-1H-4-pyrazole carbonitriles exhibited
anti bacterial activity against S. aureus74
. The compound 1, 1-methyl enedipyrazole
(AM1), showed antibacterial activity75
.
Antifungal Agents :-
Radhakrishnan Sridhar et.al., synthesized a series of 1-Hpyrazole derivatives (66) showed
antifungal activity against Rhizochonia solani, F. oxysperum76
.
CH3
R
H3C
R=H, CH3 C6H5
(65)
N
N
CH3 (NO2)2
CHO
C2H5O2C
(66)
N
N
-
The compound 3-(2-hydroxyphenyl)-5-(4-chloro-styryl)-1H-pyrazoles have been
reported as antifungal agents77
.
A series of pyrazolyl-2, 4-thiazolidinediones have been reported as antifungal agents78
.
Antiinflammatory Agents :-
A series of 2,3- dimethyl-1-(substituted phenyl) pyrazol-5-ones showed anti-
inflammatory activity79
. The compound 1-(1,5-diphenyl-4, 5-dihydro-1H-pyrazol-3-yl)-5-
phenyl-1H-tatrazole have been reported as anti-inflammatory agent80
. The compound 5-
[(3-anilino-5-phenyl-1H-pyrazol-1-yl) carbonyl] cyclohexane-3, 5-diene-1, 2,3 triol,
showed anti-inflammatory activity81
. Flora F. Barsoum et.al., synthesized bis (3-aryl-4, 5-
dihydro-1H-pyrazol-thio carboxamide derivative have anti-inflammatory activity82
.
A series of thiazolyl and thiadiazolyl derivatives of 1H-pyrazole showed significant anti-
inflammatory activity83
. A series of pyrazole derivatives have been reported as anti-
inflammatory agents84
. A series of pyrazole incorporated 1, 2-diazonaphthalene
derivatives have been reported as anti-inflammatory agents85
. 1-acetyl/propanoyl-5-aryl-
3-(4-morpholinophenyl)-4, 5-dihydro-1H-pyrazole derivatives have anti-inflammatory
activity86
. A series of pyrazole derivatives containing benzene sulfonamides, 1, 3, 4-
oxadiazole-2-thiones have been reported as anti-inflammatory agents87
.
Anticonvulsant Agents :-
3-(4-Aminophenyl)-5-(4-chlorophenyl)-4, 5-dihydro-pyrazole-1-carbothioic acid amide
(67) have anti convulsant activity88
.
R2
N
N
R1
R1 = 4 – amino
R2 = 4 - chloro
-
1-[(4,5-dihydro-5-phenyl-3-(phenylamino)pyrazol-1-yl)ethanone derivatives have been
reported as anti convulsant agents89
. A series of 3, 5-dimethyl pyrazole derivatives have
anticonvulsant activity90
. 1-(unsubstituted/substituted)-3, 5-dimethyl-1H-pyrazole
derivatives have anti convulsant activity91
. A series of 3-[3-substituted phenyl)-1-
isonicotinoyl-1H-pyrazole-5-yl]-2H-Chromen-2-one derivative have anti-convulsant
activity92
.
H2N S
(67)
-
Analgesic Activity :-
2-{3-[(4-hydroxyphenyl) amino]-4,5-dihydro-1H-pyrazol-5-yl}phenol (68) have
analgesic activity93
.
A series of (4Z)-3-methyl-1-[2-oxo-2H-chromen-4-yl) carbonyl]-1H-pyrazol-4, 5-dione,
4-[(4-substituted phenyl)hydrazone] have analgesic activity94
.
A series of 1, 2, 4-triozole derivatives containing pyrazole ring have analgesic activity95
.
Anticancer Agents :-
N-1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives showed anti cancer activity96
. 5-
benzyl-2-phenyl-pyrazolo [1,5-a] pyrazin-4, 6- (5H, 7H)-dione showed anticancer
activity97
. A series of polysubstituted fused heterocyclic ring viz pyrano [4, 3c] pyrazoles
and pyrazolo [4, 3-c] pyridines have been reported as anticancer agents98
. The compound
5-[1-aryl)-5-phenyl-1H-pyrazol-3-yl]-4-phenyl-2, 4-dihydro [1,2,4] triazole -3-thione
derivatives have anti cancer activities against breast carcinoma (MCF7) 99
. A series of
pyrazole and pyrazoline derivatives have anti cancer activity100
. 2-[3-(2-chlorophenyl)-
1Hpyrazol-5-yl]-1H-benzimidazole have been reported as anti cancer agents101
.
Xiao Hong Wang et. al., synthesized a series of pyrazole derivatives having anticancer
activity102
.
Antiviral Agents :-
A series of substituted pyrazole derivatives (69) have promising antiviral activity against
hepatitis A virus103
.
OH
NH
N
N H
(68)
OH
-
A series of 4, 5-disubstituted pyrazole derivatives have anti-viral activity104
.
Pyrazole compound BPR1P0034 have potent anti-influenza virus activity105
.
Antitumor Agents :-
3-(4-chlorophenyl)-4-substituted pyrazoles (70) have antitubercular activity against
Mycobacterium tuberculosis H37 Rv Strain106
.
The compound 1, 5-dimethyl-2-phenyl-4-([5-(arylamino)-1, 3,4-oxadiazol-2-yl]-methyl-
1,2-dihydro-3H-pyrazol-3-one have been reported as antitubercular agents107
. N-phenyl
acctyl (sulfonyl) 4, 5-dihydro-pyrazole derivatives have been reported as potential
antitumor agents108
. A series of (6-substituted-pyrazolo[3, 4-b] quinolin-1-yl)-(4-pyrrol-
1-yl-phenyl) methanones were reported as antitubercular agents109
. Peng-cheng LV et.al.,
synthesized a series of pyrazole derivative, having antiproliferative activity110
. A series of
trisubstituted pyrazole derivatives have been reported as antitumor agents111
. 3, 4-
disubstituted pyrazole derivatives have antitumor activity112
.
R1=CN
R2= NH2, COOEt
R
R2
R1
(69)
N
N
N NH
O N H
Cl
N
(70)
-
Mislleaneous Activities :-
Pyrazole as antimalarial agents :-
The compound 3-phenyl-1-(p-tolyl)-1H-pyrazole-4-carboxaldehy-e have antimalarial
activity113
.
Antihelmintic Agent :-
A series of pyrazole derivatives have been reported as antihelmintic agents114
.
Anti-oxidant Agents :-
The compound 5-methyl-5-(trifluromethyl)-4,5-dihydro-1 H-pyrazole-1-carboxamide
(72) have been reported as antioxidant agents115
.
Herbicidal & Insecticidal agents :-
The compound methyl 4-chloro-1-(2, 5-difluorophenyl)-5-(4-fluorophenyl)-pyrazole-3-
carboxylate have herbicidal activity116
.
H
O
R
N
N
(71)
H2N O
(72)
HC3
F F
F
N
N
-
5-amino-1-)5-chloropyridine-2-yl)-1H-pyrazole-4-carboxyl amino acids have been
reported as potent insecticidal agents117
.
The compound 3-(2-hydroxy-3, 5-dichlorophenyl)-4-benzoyl-5-butyl-1-phenyl pyrazole
have been reported, to effect the flowering plants118
.
Other activities of pyrazole derivatives :-
Benzofuran based 1, 3, 5-substituted pyrazole have been reported as anti oxidant and
antimicrobial agents119
. 4-alkynyl pyrazoles showed is inhibitors of PDE4120
. 5-(2, 3-
dihydro-1,4-benzodioxane-6-yl)-3-substituted-phenyl-4, 5-dihydro-1H-pyrazole
derivatives have been reported as anti-hepatotoxic agents121
.
1-aryl-4-(4, 5-dihydro-1H-imidazol-2-yl)-1H-pyrazole have been reported as
antileishmanial active compounds122
. 4-5-dihydro-1, 5-diaryl-1H-pyrazole-3-substituted-
heteroazole derivative have anti-inflammatory activity123
. 4-amino methylidine
derivatives of pyrazo1-5-ones have anti cancer activity124
. A series of (cyano-NNO-
azoxy)pyrazole derivatives have anti-fungal activity125
. A series of Novel pyrazolyl
chalcones and pyrazolines have been reported as antimicrobial agents126
. A series of
fluorinated pyrazoline have been reported as antifungal and antitubercular agents127
. A
series of pyrazole derivative have ACE-inhibitory activity128
. A series of pyrazolone
derivatives have anti-inflammatory and analgesic agents129
. 1-substituted-3-aryl-5-aryl
(hetaryl)-2-pyrazolines have been reported as antitumor agents130
. A series of pyrazolone
derivatives have been reported as antimicrobial agents131
. The compounds 2-
Benzylthiopyrimidinyl-4-pyrazolone have been reported as antimicrobial agents132
.
-
3.2 Experimental :-
All melting points of the compounds were determined in open capillary tubes and are
uncorrected. The I. R. spectra were recorded on a Perkin –Elmor-720 Spectrophotometer.
The 1H-NMR spectra were recorded in CDCl3/DMSO-ds on Varian A-60D
spectrophotometer. The chemical shifts are recorded in ppm downfield from TMS
which was used as on internal standard. The elemental analysis of C, H and N were
carried out by Coleman-carbon, hydrogen and nitrogen analyzers.
Synthesis of Starting Materials :-
3.2.1- Synthesis of 2-(2, 4-dinitrophenyl)-5-methyl-2, 4-dihydro-3H-pyrazol-3-ones.
(1)
13g (0.1mole) ethyl aceto acetate in 20-30ml. of 95% ethanol was placed in a 100ml.
round bottom flask equipped with a reflux condenser. To this 19.8g (0.1mole) of 2, 4-
dinitrophenyl hydrazine in 20-30ml. of 95% ethanol was added. The reaction was strated
immediately with evolution of heat. It was refluxed for an additional one hour. The 2-(2,
4-dintrophenyl)-5-methyl-2, 4-dihydro-3H-pyrazol-3-one were separated in the reaction
mixture, filtered and washed with a little 95% ethanol (20ml) and recrystallised from
95% ethanol. Yield (66%). This was prepared by reported known methods133-134
.
3.2.2 Synthesis of 4-Arylmethylene-2, 4-dihydro-2-(2, 4-dinitrophenyl)-5-methyl-3H-
pyrazol-3-ones (2):-
General Procedure :-
A mixture of 2-(2, 4 dinitrophenyl)-5-methyl-2,4-dihydro-3H-pyrozol-3-one 3.25g
(0.01mole), (0.01mole) of appropriate aromatic aldehyde and 0.7gm (0.01mole) sodium
acetate were dissolved in glacial acetic acid (15ml) into a beaker. The reaction mixture
was heated for 15 minutes on a sand bath and left overnight at room temperature. The
compound 4-Aryl methylene-2, 4-dihydro-2-(2, 4-dinitrophenyl)-5-methyl-3H-pyrazol-3-
ones were separated out as coloured crystals, fietered dried and recrystallised from
benzene. The physical and analytical data of compounds (2) were recorded in Table-1
-
3.2.3 Synthesis of 1-(2, 4-dintrophenyl)-3-methyl-1-substituted phenyl-6-
imino/phenylimino -4, 7-dihydropyrazolo-[5, 4-d]-1, 3-thiazines. (3):-
General Procedure :-
(0.01mole) of compound (2), (0.01mole) thiourea/phenyl thiourea and (0.02mole) KOH
was taken in a round bottom flask and refluxed in methanol (30ml) for 4-5 hrs. cooled the
reaction mixture at room temperature, and it was acidified with dil hydrochloric acid. The
reaction mixture was diluted by adding (20-30ml) water to get solid materials. The solid
material was filtered dried from methanol this 1-(2, 4-dinitrophenyl)-3-methyl-
4substituted phenyl-6-imino/phenylimino-4, 7-dihydropyrazolo-[5, 4-d]-1, 3, thiazines
(3) was prepared. The similar procedure was adopted in the preparation of the following
particular compounds, viz.
3a. 1-(2, 4-dinitrophenyl)-3-methyl-4-phenyl-6-imino-4, 7-dihydropyrazolo-[5, 4-d]-1, 3
thiazine.
3b. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-nitrophenyl)-6-imino-4, 7 dihydrpyrazolo-[5, 4-
d]-1, 3-thiazine.
3c. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-N, N-dimethyl aminophenyl)-6-imino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine.
3d. 1-(2, 4-dintrophenyl)-3-methyl-4-(4-methoxy phenyl)-6-imino-4, 7-dihydropyrazolo-
[5, 4-d]-1, 3-thiazine.
3e. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-chlorophenyl)-6-imino-4, 7-dihydropyrazolo-[5,
4-d]-1, 3-thiazine.
3f. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-hydroxyphenyl)-6-imino-4, 7-dihydropyrazolo-
[5, 4-d]-1, 3-thiazine.
3g. 1-(2, 4-dinitrophenyl)-3-methyl-4-phenyl-6-phenylimino-4, 7-dihydropyrazolo-[5, 4-
d]-1,3-thiazine.
3h. 1-(2, 4-dinitropyenyl)-3-methyl-4(4-nitrophenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1,3-thiazine.
3i. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-N, N-dimethylaminophenyl)-6-phenylimino-4,
7-dihydro-pyrazolo-[5, 4-d]-1,3-thiazine.
-
3j. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-methoxyphenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1,3-thiazine.
3k. 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-chlorophenyl)-6-phenylimino-4, 7-dihydro
pyrazolo-[5, 4-d]-1,3-thiazine.
3l. 1-(2, 4-dinitrophenyl)-3-methyl-4(4-hydroxy-phenyl)-6-phenylimino-4, 7-dihydro
pyrazolo-[5, 4-d]-1,3-thiazine.
The physical and analytical data are given in Table-2 and the spectral data are recorded in
Table-3.
-
Table-1
4- Arylmethylene-2, 4-dihydro-2(2, 4-dinitrophenyl)-5-methyl-3Hpyrazol-3-ones (2)
Comp. No R1 Molecular
Formula m.p. (°C) Yield (%)
Elemental Analysis (%)
C H N
2a H C17H12N4O5 202 60 57.95
(58.01)
3.40
(3.44)
15.90
(15.80)
2b p-NO2 C17H11N5O7 234 62 52.71
(52.88)
2.84
(2.90)
18.08
(18.00)
2c p-N(Me)2 C19H17N5O5 225 64 56.54
(56.34)
3.66
(3.70)
14.65
(14.50)
2d p-OMe C18H14N4O6 230 69 57.72
(58.01)
4.30
(4.22)
17.72
(17.94)
2e p-Cl C17H11N4O5Cl 252 61 52.84
(53.20)
2.84
(3.02)
14.50
(14.80)
2f p-OH C17H12N4O6 260 70 55.43
(55.33)
3.26
(3.45)
15.21
(15.07)
N
CH3
NO2
O N
CH
R1
O2N
-
Table-2
1- (2,4-dinitrophenyl)-3-methyl-4-substituted phenyl-6imino/phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine (3)
Comp.
No R R1
Molecular
Formula
m.p.
(°C)
Yield
(%)
Elemental Analysis (%)
C H N
3a H H C18H14N6SO4 240 54 52.68
(52.56)
3.41
(3.50)
20.48
(20.22)
3b H p-NO2 C18H13N7SO6 264 62 47.47
(47.60)
2.85
(2.80)
21.53
(21.77)
3c H p-N(Me)2 C20H19N7SO4 254 71 52.98
(53.00)
4.19
(4.22)
21.66
(21.84)
3d H p-OMe C19H16N6SO5 251 67 51.81
(52.04)
3.63
(3.77)
19.09
(18.88)
3e H p-Cl C18H13N6SO4Cl 272 65 48.64
(48.20)
2.92
(3.10)
18.91
(18.92)
3f H p-OH C18H14N6SO5 280 70 50.70
(51.00)
3.28
(3.18)
19.71
(19.44)
3g C6H5 H C24H18N6SO4 264 57 59.25
(59.60)
3.70
(3.88)
17.28
(17.10)
3h C6H5 p-NO2 C24H17N7SO6 223 60 54.23
(54.11)
3.20
(3.44)
18.45
(18.65)
3i C6H5 p-N(Me)2 C26H23N7SO4 270 69 58.97
(59.10)
4.34
(4.64)
18.52
(18.64)
3j C6H5 p-OMe C25H20N6SO5 230 62 58.13
(58.43)
3.87
(4.01)
16.27
(16.45)
3k C6H5 p-Cl C24H17N6SO4Cl 282 67 55.38 3.26 16.15
N
NO2
N O2N
N
CH3
NO2
N NR
R1
O2N
S
H
N
-
(55.49) (3.28) (15.90)
3l C6H5 p-OH C24H18N6SO5 288 70 57.37
(57.56)
3.58
(3.60)
16.73
(16.64)
Table-3
1-(2,4-dinitrophenyl)-3-methyl-4-substituted phenyl-6-imino/phenylimino/-4, 7-
dihydro pyrazolo-[5, 4-d]-1, 3-thiazine (3)
Comp.
No R R1
I.R. (KBr.) υmax
cm-1
1H-NMR (CDCl3 (ppm)
3a H H 3595 (NH),
3384 (=NH),1580 (C=N)
1.9(3H,s,CH3), 3.8 (1H,s,S-CH), 6.4-7.2
(8H,m,Ar-H) 9.0 (2H,s,NH is D2Oexchangeable)
3b H p-NO2
3591 (NH),
3385 (=NH),
1574s (C=N)
1.9(3H,s,CH3), 3.6 (1H,s,S-CH), 6.2-7.0
(7H,m,Ar-H) 9.2 (2H,s,NH is D2O exchangeable)
3c H p-N(Me)2
3590 (NH),
3401 (=NH),
1575s (C=N)
2.(3H,s,CH3), 2.9 (6H, S NM2) 3.7 (1H,s,S-CH),
6.1-7.0 (7H,m,Ar-H) 9.2 (2H,s,NH is D2O
exchangeable)
3d H p-OMe
3599 (NH),
3390 (=NH),
1575s (C=N)
2.1(3H,s,CH3), 3.6 (1H,s,S-CH), 3.8 (3H, s,
OCH3), 6.2-7.2 (7H,m,Ar-H) 9.2 (2H,s,NH is
D2O exchangeable)
3e H p-Cl 3585 (NH),
3399 (=NH),1579 (C=N)
2.1 (3H,s,CH3), 3.8 (1H,s,S-CH), 6.8-7.1
(7H,m,Ar-H) 9.1 (2H,s,NH is D2O exchangeable)
3f H p-OH
3580 (-OH),
3590 (NH),3395 (=NH),
1579 (C=N)
2.0 (3H,s,CH3), 3.9 (1H,s,S-CH), 6.6 (1H, s, OH)
6.3-7.3 (7H,m,Ar-H) 9.2 (2H,s,NH is D2O
exchangeable)
3g C6H5 H
3580 (NH),
3401 (=NPh),
1579s (C=N)
1.8 (3H,s,CH3), 3.8 (1H,s,S-CH), 6.2-6.9
(13H,m,Ar-H) 8.9 (1H,s,NH is D2O exchangeable)
O2N
N
NO2
N
N
CH3
NO2
N NR
R1
S
H
N
-
3h C6H5 p-NO2
3586 (NH),
3411 (=Nph),
1577s (C=N)
2.0 (3H,s,CH3), 3.7 (1H,s,S-CH), 6.3-7.2
(12H,m,Ar-H) 9.1 (1H,s,NH is D2O exchangeable)
3i C6H5 p-N (Me)2
3589 (NH),
3410 (=NPh),
1575s (C=N)
2.0 (3H,s,CH3), 2.8 (6H,s,NMe2), 3.8 (1H,s, S-
CH), 6.2-7.1 (12H,m,Ar-H) 8.9 (1H,s,NH is D2O
exchangeable)
3j C6H5 p-OMe
3587 (NH),
3390 (=NPh),
1581s (C=N)
1.9 (3H,s,CH3), 3.7 (1H,s,S-CH), 4.1 (3H, s,
OCH3) 6.1-7.2 (12H,m,Ar-H) 9.2 (2H,s,NH is
D2O exchangeable)
3k C6H5 p-Cl
3575 (NH),
3392 (=NPh),
1576s (C=N)
2.0 (3H,s,CH3), 4.1 (1H,s,S-CH), 6.8-7.5
(12H,m,Ar-H) 9.0 (1H,s,NH is D2O exchangeable)
3l C6H5 p-OH
3580 (NH),
3590 (NH),3392 (=NPh),
1577(C=N)
2.1 (3H,s,CH3), 3.9 (1H,s,S-CH), 6.8 (1H, s,OH)
6.5-7.0 (12H,m,Ar-H) 9.0 (1H,s,NH is D2O
exchangeable)
-
3.3.1 Condensation Reaction :-
2, 4-dinitrophenyl condense with Ethyl acetoacetate in methanol to give 2-(2, 4-
dinitrophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-ones(1).The condensation refeation of
2-(2, 4-dinitrophenyl-5-methyl-2, 4-dihydro -3H-pyrazol-3-ones with different aromatic
aldehydes in the presence of acidic media to give 4-arylmethylene -2, 4-dihydro-2-(2, 4-
dinitrophenyl)-5-methyl-3H-pyrazol-3-ones (2). The compound (2) reacts with
thiourea/phenyl thiourea and KOH in the presence of methanol to give corresponding 1-
(2, 4-dinitrophenyl)-3-methyl-4-substituted phenyl-6-imino/phenyl imino -4, 7-dihydro
pyrazolo-[5, 4-d]-1, 3-thiazines (3). (Scheme - 3)
CH3
O2N
NO2
O
CH
R1
CHO
R1
CH3COONa/gl. AcOH KOH/MeOH
(2)
H2N – C – NR
S
N
N
O2N
NO2
+ O C
NO2
O2N NH – NH2
CH3
CH
2
CH
2
C2H5
O
(1)
N
CH3
O
N
N
N
CH3
O2N
NO2
(3)
R1
H
N
NR
S
(Scheme – 3)
-
Compound No. R R1
3a H H
3b H p-NO2
3c H p-N-(Me)2
3d H p-OMe
3e H p-Cl
3f H p-OH
3g C6H5 H
3h C6H5 p-NO2
3i C6H5 p-N-(Me)2
3j C6H5 p-OMe
3k C6H5 p-Cl
3l C6H5 p-OH
The mechanism of the condensation reaction is well known.
3.3.2 1-(2, 4-dinitrophenyl)-3-methyl-4-phenyl-6-imino-4, 7-dihydro-[5, 4-d]-1, 3-
thiazine (3a) :-
1-(2, 4-dinitrophenyl)-3-methyl-4-phenyl-6-imino-4, 7-dihydro-[5, 4-d]-1, 3-thiazine was
synthesized by the reaction of 4-phenylmethylene-2, 4-dihydro-2-(2,4- dinitrophenyl)-5-
N
N
CH3
O2N
NO2
(3a)
H
N
NH
S
-
methyl-3H-pyrazol-3-ones and thiourea is the presence of KOH and methanol. The
molecular formula of the compound (3a) is C18H14N6SO4, and the elemental analysis of
the compound (3a) correspond to the molecular formula. The IR (KBr, max, cm-1) of the
compound (3a) shows 3595 (NH), 3384 (=NH), and 1580 (C=N). The 1H-NMR of the
compound (3a) shows ppm. 1.9 (3H, s, CH3), 3.8 (1H,s, S-CH), 6.4-7.2 (8H,m, Ar-H)
and 9.0 (1H, s, NH).
3.3.3 1-(2,4-dinitrophenyl)-3-methyl-4-(4-nitrophenyl)-6-imino-4,7-
dihydropyrazolo -[5, 4-d]-1, 3, thiazine (3b) :-
1-(2, 4-dinitrophenyl)-3-methyl-4-(4-nitrophenyl)-6-imino-4, 7-dihydropyraz-olo-[5, 4-
d]-1, 3-thiazine was synthesized by the reaction of 4-(4-nitrophenyl)-methylene-2, 4-
dihydro-3H-pyrazol-3H-ones and thiourea in the presence of KOH/methanol. The
molecular formula of the compound (3b) is C18H13N7SO6, and the elemental analysis of
the compound (3b) correspond to the molecular formula. The IR (KBr, max, cm-1) of
the compound (3b) shows 3591 (NH), 3385 (=NH), and 1574 (C=N). The 1H-NMR of the
compound (3b) shows 1.9 (3H, s, CH3), 3.6 (1H,s, S-CH), 6.2-7.0 (7H,m, Ar-H) and 9.2
(1H, s, NH).
3.3.4 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-N, N-dimethyl aminophenyl)-6-imino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3, thiazine (3c) :-
N
N
O2N
NO2
(3b)
H
N
NH
S
NO2
CH3
-
1-(2,4-dinitrophenyl)-3-methyl-4-(4-N, N-dimethyl aminophenyl)-6-imino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine was synthesiged by the reaction of 4-(4-N, N-
dimethyl aminophenyl)-methylene-2, 4-dihydro-3H-pyrazol-3-one and thiourea in the
presence of KOH/methanol. The molecular formula of the compound (3c) is
C20H19N7SO4, and the elemental analysis of the compound (3c) correspond to the
molecular formula. The IR (KBr, max, cm-1) of the compound (3c) shows 3590 (NH),
3401 (=NH), and 1575 (C=N). The 1H-NMR of the compound (3c) shows 2.0 (3H, s,
CH3), 2.9 (6H,s,NMe2) 3.7 (1H,s, S-CH), 6.1-7.0 (7H,m, Ar-H) and 9.2 (2H,s, NH).
3.3.5 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-methoxyphenyl)-6-imino-4,7-
dihydropyrazolo-[5, 4-d]-1, 3, thiazine (3d) :-
CH3
NH N
N
O2N
NO2
(3d)
H
N
S
OMe
N – (Me)2
N
CH3
O2N
NO2
(3c)
H
N
S N
NH
-
1-(2,4-dinitrophenyl-3-methyl-4-(4-methoxyphenyl)-6-imino-4, 7-dihydropyra-zolo-[5,
4-d]-1, 3-thiazine was synthesized by the reaction of 4-(4-methoxphenyl)methylene-2, 4-
dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H-pyrazol-3-one and thiourea in the presence of
KOH/methanol. The molecular formula of the compound (3d) is C19H16N6SO5. The
elemental analysis of the compound (3d) correspond to the molecular formula. The IR
(KBr, max, cm-1) of the compound (3d) shows 3599 (NH), 3390 (=NH), and 1575
(C=N). The 1H-NMR of the compound (3d) shows ppm 2.1 (3H, s, CH3), 3.6 (1H,s, S-
CH), 3.8(3H,s,OCH3), 6.2-7.2 (7H,m, Ar-H) and 9.2 (2H, s, NH).
3.3.6 1-(2,4-dinitrophenyl)-3-methyl-4-(4-Chlorophenyl)-6-imino-4,7-
dihydropyrazolo-[5, 4-d]-1, 3, thiazine (3e) :-
1-(2, 4-dinitrophenyl)-3-methyl-4-(4-Chlorophenyl)-6-imino-4, 7-dihydropyra-zolo-[5,4-
d]-1,3-thiazine was synthesized by the reaction of 4-(4-chlorophenyl)-methylene-2,4-
dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H-pyra -zol-3-one and thiourea in the presence
of KOH/methanol. The molecular formula of the compound (3e) is C18H13N6SO4Cl. The
elemental analysis of the compound (3e) correspond to the molecular formula. The IR
(KBr, max, cm-1) of the compound (3e) shows 3585 (NH), 3399 (=NH), and 1579
(C=N). The 1H-NMR of the compound (3e) shows ppm 2.1 (3H, s, CH3), 3.8 (1H,s, S-
CH), 6.8-7.1 (7H,m, Ar-H) and 9.1 (2H, s, NH).
Cl
NH N
CH3
O2N
NO2
(3e)
H
N
S N
-
3.3.7 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-hydroxyphenyl)-6-imino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3, thiazine (3f) :-
1-(2,4-dinitrophenyl)-3-methyl-4-(4-hydroxyphenyl)-6-imino-4,7-dihydropyra-zolo-[5, 4-
d]-1, 3-thiazine was synthesized by the reaction of 4-(4-hydroxyphenyl)-methylene-2, 4-
dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H-pyrazol-3-one and thiourea in the presence of
KOH/methanol. The molecular formula of the compound (3f) is C18H14N6SO5. The
elemental analysis of the compound (3f) correspond to the molecular formula. The IR
(KBr, max, cm-1) of the compound (3f) shows 3580 (-OH), 3590 (NH), and 3395 (=NH)
1579 (C=N). The 1H-NMR of the compound (3f) shows 2.0 (3H, s, CH3), 3.9 (1H,s, S-
CH), 6.6 (1H,s,OH) 6.3-7.3 (7H,m, Ar-H) and 9.2 (2H, s, NH).
3.3.8 1-(2, 4-dinitrophenyl)-3-methyl-4-phenyl-6-phenylimino-4, 7-dihydro-
pyrazolo-[5, 4-d]-1, 3- thiazine (3g) :-
OH
N
CH3
O2N
NO2
(3f)
H
N
NH
S N
CH3
N O2N
NO2
(3g)
H
N
S N
NC6H5
-
1-(2, 4-dinitrophenyl)-3-methyl-4-phenyl-6-phenylimino-4, 7-dihydropyrazolo-[5, 4-d]-1,
3-thiazine was synthesized by the reaction of 4-phenylmethylene-2, 4-dihydro-2-(2,4-
dinitrophenyl)-5-methyl-3H-pyrazol-3-one and phenyl thiourea in the presence of
KOH/methanol. The molecular formula of the compound (3g) is C24H18N6SO4. The
elemental analysis of the compound (3g) correspond to the molecular formula. The IR
(KBr, max, cm-1) of the compound (3g) shows 3580 (NH), 3401 (=NPh) and 1579
(C=N). The 1H-NMR of the compound (3g) shows ppm. 1.8 (3H, s, CH3), 3.8 (1H,s, S-
CH), 6.2-6.9 (13H,m, Ar-H) and 8.9 (1H, s, NH).
3.3.9 1-(2, 4-dinitrophenyl)-3-methyl-4(4-nitrophenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3- thiazine (3h) :-
1-(2, 4-dinitrophenyl)-3-methyl-4-(4-nitrophenyl)-6-phenylimino-4, 7-dihydro-pyrazolo-
[5, 4-d]-1, 3-thiazine was synthesized by the reaction of 4-(4-nitrophenyl)methylene-2,4-
dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H- yrazol-3-one and phenyl thiourea in the
presence of KOH/methanol. The molecular formula of the compound (3h) is
C24H17N7SO6. The elemental analysis of the compound (3h) correspond to the molecular
formula. The IR (KBr, max, cm-1) of the compound (3h) shows 3586 (NH), 3411
(=NPh) and 1577 (C=N). The 1H-NMR of the compound (3h) shows ppm. 2.0 (3H, s,
CH3), 3.7 (1H,s, S-CH), 6.3-7.2 (12H,m, Ar-H) and 9.1 (1H, s, NH).
NO2
N
CH3
O2N
NO2
(3h)
H
N
S N
NC6H5
-
3.3.10 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-N,N-dimethylaminophenyl)-6-
phenylimino-4, 7-dihydropyrazolo-[5, 4-d]-1, 3- thiazine (3i) :-
1-(2,4-dinitrophenyl)-3-methyl-4(4-N,N-dimethylaminophenyl)-6-henylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine was synthesized by the reaction of 4-(4-N,N-
dimethylaminophenyl) methylene-2, 4-dihydro-2-(2,4-dinitrophenyl) -5-methyl-3H-
pyrazol-3-one and phenyl thiourea in the presence of KOH/methanol. The molecular
formula of the compound (3i) is C26H23N7SO4. The elemental analysis of the compound
(3i) correspond to the molecular formula. The IR (KBr, max, cm-1) of the compound
(3i) shows 3589 (NH), 3410 (=NPh), 1575 (C=N). The 1H-NMR of the compound (3i)
shows ppm. 2.0 (3H, s, CH3), 2.8 (6H, s, N(NMe)2) 3.8 (1H,s, S-CH), 6.2-7.1 (12H,m,
Ar-H) and 8.9 (1H, s, NH).
3.3.11 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-methoxyphenyl)-6-phenylimino -4, 7-
dihydropyrazolo-[5, 4-d-]-1, 3- thiazine (3j) :-
N
CH3
O2N
NO2
(3i)
H
N
S N
N–C6H5
N Me
Me
N
CH3
O2N
NO2
(3j)
H
N
S N
N – C6H5
OMe
-
1-(2, 4-dinitrophenyl)-3-methyl-4-(4-methoxyphenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine was synthesized by the reaction of 4-(4-
methoxyphenyl) methylene-2, 4-dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H-pyrazol-3-
one and phenyl thiourea in the presence of KOH/methanol. The molecular formula of the
compound (3j) is C25H20N6SO5. The elemental analysis of the compound (3j) correspond
to the molecular formula. The IR (KBr, max, cm-1) of the compound (3j) shows 3587
(NH), 3340 (=NPh), 1581 (C=N). The 1H-NMR of the compound (3j) shows ppm. 1.9
(3H, s, CH3), 3.7 (1H,s, S-CH), 4.1 (3H, s,OCH3) 6.1-7.2 (12H,m, Ar-H) and 9.2 (1H, s,
NH).
3.3.12 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-Chlorophenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d-]-1, 3- thiazine (3k) :-
1-(2, 4-dinitrophenyl)-3-methyl-4-(4-Chlorophenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine was synthesized by the reaction of 4-(4-
Chlorophenyl) methylene-2, 4-dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H-pyrazol-3-one
and phenyl thiourea in the presence of KOH/methanol. The molecular formula of the
compound (3k) is C24H17N6SO4Cl. The elemental analysis of the compound (3k)
correspond to the molecular formula. The IR (KBr, max, cm-1) shows 3575 (NH), 3392
N
CH3
O2N
NO2
(3k)
H
N
S N
N – C6H5
Cl
-
(=NPh), 1576 (C=N). The 1H-NMR of the compound (3k) shows ppm. 2.0 (3H, s,
CH3), 4.1 (1H,s, S-CH), 6.8-7.5 (12H,m, Ar-H) and 9.0 (1H, s, NH).
3.3.13 1-(2, 4-dinitrophenyl)-3-methyl-4-(4-hydroxyphenyl)-6-phenylimino -4, 7-
dihydropyrazolo-[5, 4-d-]-1, 3- thiazine (3l) :-
1-(2, 4-dinitrophenyl)-3-methyl-4-(4-hydroxyphenyl)-6-phenylimino-4, 7-
dihydropyrazolo-[5, 4-d]-1, 3-thiazine was synthesized by the reaction of 4-(4-
hydroxyphenyl)-methylene-2, 4-dihydro-2-(2,4-dinitrophenyl)-5-methyl-3H-pyrazol-3-
one and phenyl thiourea in the presence of KOH/methanol. The molecular formula of the
compound (3l) is C24H18N6SO5. The elemental analysis of the compound (3l) correspond
to the molecular formula. The IR (KBr, max, cm-1) shows 3580 (-OH),3590 (NH), 3392
(=NPh), 1577 (C=N). The 1H-NMR of the compound (3l) shows ppm. 2.1 (3H, s, CH3),
3.9 (1H,s, S-CH), 6.8 (1H,s,OH), 6.5-7.0 (12H,m, Ar-H) and 9.0 (1H, s, NH).
N
CH3
O2N
NO2
(3l)
H
N
S N
N – C6H5
OH
-
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