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67
CHAPTER - 3
SYNTHESIS OF SUBSTITUTED 1,2,4-TRIAZOLE, 1,3,4-
THIADIAZOLE, 1,3-THIAZINE-2-AMINE AND
HYPOXANTHINE, DERIVATIVES.
3.1 INTRODUCTION:
Substituted 1,2,4-triazole [100-102], 1,3,4-thiadiazole [103],
1,3-thiazine [104] and hypoxanthine [105] derivatives have been
reported to possess diverse biological activity like anti-inflammatory,
antifungal, antiglaucoma, diuretic etc. These are also known to be
used in the treatment of acute mountain sickness, sedative, analgesic,
muscle relaxant and antianginal. Triptan drugs are used for the
treatment of migraine headaches. Many of these triptamines such as
naratriptan [106], almotriptan [107], sumatriptan [108] and avitriptan
[109] have the common feature of possessing a sulfonamide group
attached to the indole ring at 5 position through a methane/ethane
spacer. 2-(4-Aminophenyl)-N-methylethane sulfonamide is a crucial
structural part in naratriptan. However, not much systematic work
has been done on 2-(4-aminophenyl)-N-methylethanesulfonamide.
Hence, it was thought worthwhile to synthesize new heterocycles
containing benzene methane/ethane sulfonamide functionality as
potentially biologically active compounds.
68
3.2 LITERATURE SURVEY:
Several synthetic methods have been reported in the literature
for the synthesis of 1,2,4-Triazole, 1,3,4-thiadiazole, 1,3-thiazine and
hypoxanthine derivatives and few of them are discussed below.
3.2.1. 1,2,4-TRIAZOLE
Bany et. al. [110] reported that the condensation of ethoxy-
carbonylmethyl isothiocyanate (33) with amidrazone salts (34) on
thermal heating gave 1,2,4-triazoline-5-thione (35) (Scheme-3.1).
….. Scheme - 3.1
Hoggarth et. al. [111] reported the synthesis of 3-substituted
1,2,4-triazoline-5-thione derivatives by the reaction of substituted
benzoylisothiocyanate (36) and excess of hydrazine hydrate to give the
corresponding thiosemicarbazide derivatives 37, which on cyclization
yielded 3-aryl-1,2,4-triazoline-5-thione (38) (Scheme-3.2).
….. Scheme - 3.2
Zamani et. al. [112] reported the condensation of 4-
methylphenyl isothiocyanate (39) with pyridinecarboxylic hydrazide
69
(40) giving 1-(4-methyl phenyl)-(pyridoyl) thiosemicarbazide (41)
which on cyclization in the presence of aq.NaOH solution, gave 2,4-
dihydro-4-(4-methylphenyl)-5-(pyridyl)-3H-1,2,4-triazole (42)
(Scheme-3.3).
….. Scheme - 3.3
Iqbal et. al. [113] reported the condensation of 2-phenylmethyl
isothiocyanate (43) with the hydrazide derivative 40 giving N-benzyl-2-
isonicotinoylhydrazine carbothioamide (44), which on cyclization in
the presence of aq.NaOH solution, gave 4-benzyl-5-(pyridin-4-yl)-4H-
1,2,4-triazole-3-thiol (45) (Scheme-3.4).
….. Scheme - 3.4
Dimova et. al. [114] reported that the condensation of
allylisothiocyanate (46) with phenylcarboxylic hydrazide (47) to give
N-allyl-2-benzoylhydrazinecarbothioamide (48), which on cyclization
in the presence of aq.NaOH solution, affords 4-allyl-5-phenyl-4H-
1,2,4-triazole-3-thiol (49) (Scheme-3.5).
70
….. Scheme - 3.5
Hameed et. al. [115] reported the condensation of R-(+)-1-
phenyl propylisothiocyanate (50) with benzohydrazide 47 giving (R)-2-
benzoyl-N-(1-phenylpropyl)hydrazinecarbothioamide (51), which on
cyclization in the presence of aq.NaOH solution gives 3-phenyl-4-(1-
phenylpropyl)-1H-1,2,4-triazole-5(4H)-thione (52) (Scheme-3.6).
….. Scheme - 3.6
Zamani et. al. [116] reported that the condensation reaction of
1-isothiocyanatonaphthalene (53) with acid hydrazide 40 affords
thiosemicarbazide (54) derivative, which on cyclization in aq.NaOH
solution, yields 4-(naphthalen-1-yl)-5-(pyridin-4-yl)-4H-1,2,4-triazole-
3-thiol (55) (Scheme-3.7).
….. Scheme - 3.7
71
3.2.2. 1,3,4-THIADIAZOLE
Zamani et. al. [112] reported that the condensation of 4-
methylphenylisothiocyanate (39) with 4-pyridinecarboxylic acid
hydrazide (40) yield 1-(4-methylphenyl)-4-(isomericpyridoyl)thiosemi
carbazide (41) which on cyclization in the presence of Con. sulphuric
acid, affords 2-(4-methylphenylamino)-5-(isomericpyridyl)-1,3,4-thia -
diazole (56) (Scheme-3.8).
….. Scheme - 3.8
Profire et. al. [117] reported that the condensation of
isothiocyanate derivate 39 with N-(1-hydrazinyl-1-oxo-3-phenyl
propan-2-yl)-4-nitrobenzamide (57) results in the formation of 4-nitro-
N-(1-oxo-3-phenyl-1-(2-(p-tolylcarbamothioyl)hydrazinyl) propan-2-
yl)benzamide (58), which on cyclization in the presence of Con.
sulphuric acid, yields 4-nitro-N-(2-phenyl-1-(5-(p-tolylamino)-1,3,4-
thiadiazol-2-yl)ethyl)benzamide (59) (Scheme-3.9).
72
…..Scheme - 3.9
Hussain et. al. [118] reported the condensation of
arylisothiocynate derivative 39 with 5-amino-2-hydroxybenzo
hydrazide (60) to give 2-(4-amino-2-hydroxy benzoyl)-N-p-tolyl
hydrazinecarboxamide (61), which on cyclization in the presence of
Con. sulphuric acid yields 5-amino-2-(5-(p-tolyl amino)-1,3,4-
thiadiazol-2-yl)phenol (62) (Scheme-3.10).
…..Scheme - 3.10
Shashikanth et. al. [119] has reported the condensation of
phenyl isothiocyanate (63) with 2-(2-(3-chlorobenzoyl)-4-methyl
phenoxy)acetohydrazide (64), to give 2-(2-(2-(3-chlorobenzoyl)-4-
methyl phenoxy)acetyl)-N-phenylhydrazinecarbothioamide (65), which
on cyclization in the presence of phosphoric acid, results in the
73
formation of (3-chlorophenyl)(3-((5-(phenylamino)-1,3,4-thiadiazol-2-
yl) methoxy) phenyl) methanone (66) (scheme-3.11).
…..Scheme - 3.11
Zamani et. al. [116] reported that condensation of 1-
isothiocyanatonaphthalene (53) with acidhydrazide derivative 40 to
give 1-(4-methylphenyl)-4-(isomericpyridoyl) thiosemicarbazide (54)
which on cyclization in the presence of Con. sulphuric acid, yields N-
(naphthalen-1-yl)-5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine (67)
(Scheme-3.12).
……….Scheme - 3.12
74
Karale et. al. [120] reported the condensation of
phenylisothiocynate 63 with substituted phenoxyaceto hydrazide (68)
to give the corresponding substituted thiosemicarbazide (69), which
on cyclization in the presence of Con. sulphuric acid, affords the
substituted 1,3,4-thiadiazol-2-amine (70) (Scheme-3.13).
……….Scheme - 3.13
Vosooghi et. al. [121] reported the condensation of substituted
isothiocyanate (71) with substituted 2-(4-nitro-1H-imidazol-1-
yl)acetohydrazide (72) to give the corresponding substituted
thiosemicarbazide (73), which on cyclization in the presence of Con.
sulphuric acid, affords the substituted 1,3,4-thiadiazol-2-amine (74)
(Scheme-3.14).
75
……….Scheme - 3.14
3.2.3. 1,3- THIAZINE-2-AMINE
Ruehle et. al. [122] described a method for the condensation of
2,6-dimethylphenylisothiocyanate (75) with 3-amino-1-propanol (76)
to afford 1-(2,6-dimethylphenyl)-3-(3-hydroxypropyl)urea (77), which
on cyclization in the presence of Con. HCl, yields N-(2,6-
dimethylphenyl)-5,6-dihydro-4H-1,3-thiazin-2-amine (78) (Scheme-
3.15).
…….Scheme - 3.15
76
Hiroyukai et. al. [123] described a method for the condensation
of (2-isopropylphenyl)isothiocyanate (79) with 3-amino-2,2dimethyl
propanol (80) gives N-(2-isopropylphenyl)-N’-(1-hydroxy-2,2-dimethyl)
propylthiourea (81) which on cyclization in the presence of Con. HCl
afforded (2-isopropylphenyl)imino-5,5-dimethyl-5,6-dihydro-4H-1,3-
thiazine (82) (Scheme-3.16).
……….Scheme - 3.16
Caujolle et. al. [124] described a method for the condensation of
1-naphthaleneisothiocynate (53) with 3-aminopropanol (76) to give 1-
(3-hydroxypropyl)-3-(naphthalen-1-yl) urea (83), which on cyclization
in the presence of Con. HCl, affords N-(naphthalen-1-yl)-5,6-dihydro-
4H-1,3-thiazin-2-amine (84) (scheme-3.17).
……….Scheme - 3.17
Audia et. al. [125] describes a novel method for the
condensation of 2-(3-bromophenyl)-4-methylpent-4-en-2-amine (87)
with benzoyl isothiocyanate (88) gives (S)-N-(2-(3-bromophenyl)-4-
77
methylpent-4-en-2-ylcarbamothioyl) benzamide (89), which on
treatment with excess of iodine yields the N-((4S)-4-(3-bromophenyl)-
6-(iodomethyl)-4,6-dimethyl-5,6-dihydro-4H-1,3-thiazin-2-yl)benz
amide (90). Finally addition of tri-n-butyl amine and AIBN in the
presence of THF solvent affords (S)-N-(4-(3-bromophenyl)-4,6,6-
trimethyl-5,6-dihydro-4H-1,3-thiazin-2-yl)benzamide (91) (Scheme-
3.18).
……….Scheme - 3.18
3.2.4. HYPOXANTHINE
Mckenzie et. al. [126] prepared another purine derivative from
benzyl amine (92) and 2-aminocyanoacetamide (93) in the presence of
triethyl orthoformate in acetonitrile gave 5-amino-1-benzyl-1H-
imidazole-4-carboxamide (94), which on acetylation with
trifluoroacetic anhydride gave acetyl derivative 95 that cyclized on
heating yielded 9-benzyl-2-(trifluoromethyl)-4,9-dihydro-1H-purin-
6(5H)-one (96) (Scheme- 3.19).
78
……….Scheme - 3.19
Glasky et. al. [127] reported that the condensation of ethyl 4-(3-
aminopropanamido)benzoate (97) and 2-aminocyanoacetamide (93)
with triethylorthoformate in acetonitrile gave ethyl 4-(3-(5-amino-4-
carbamoyl-1H-imidazol-1-yl)propanamido)benzoate (98), which on
cyclisation with triethylorthoformate gave 2-ethyl-4-(3-(6-oxo-1H-
purin-9(6H)-yl)propanamido)benzoate (99). Subsequently on
hydrolysis with aq.NaOH solution gave 4-(3-(6-oxo-1H-purin-9(6H)-
yl)propanamido)benzoic acid (100) (scheme-3.20).
……….Scheme - 3.20
Terret et. al. [128] reported the reaction of N-propylamine (101)
with 93 in the presence of triethylorthoformate in acetonitrile yielded
5-amino-1-propyl-1H-imidazole-4-carboxamide (102), which on
79
treatment with 2-ethoxybenzoyl chloride (103), gave 5-(2-
ethoxybenzamido)-1-propyl-1H-imidazole-4-carboxamide (104). This
derivative 104, on cyclisation with hydrogen peroxide, resulted in 2-
(2-ethoxyphenyl)-9-propyl-1H-purin-6(9H)-one (105) (scheme-3.21).
……….Scheme - 3.21
3.3. PRESENT WORK
It is obvious from the references cited above that a good number of
researchers have synthesized substituted 1,2,4-triazole, 1,3,4-
thiadiazole, 1,3-thiazines and hypoxanthines which are biologically
active molecules.
In this chapter we have synthesized some substituted
sulfonamide derivatives of 1,2,4-triazole, 1,3,4-thiadiazole, 1,3-
thiazine and hypoxanthine from substituted amino benzene
methane/ethane sulfonamide derivatives as new chemical entities
(NCES).
80
3.4 RESULTS AND DISCUSSION:
The required starting materials, 26a, 26d and 26e were
synthesized by using the reported procedure [95] as described in
chapter-1. The synthetic scheme is depicted in scheme- 3.22. Thus,
treatment of 24 with excess of amines like pyrrolidine, and
monomethylamine, gave the corresponding 4-(secondary amine-1-
sulfonylmethyl)-nitrobenzene (26a, 26d, 26e). These later
compounds were then hydrogenated using palladium on carbon as a
catalyst in methanol to yield the corresponding aminoderivatives 26a,
26d and 26e.
……….Scheme - 3.22
3.4.1. Conversion of amine to isothiocyanate 106:
2-(4-Aminophenyl)-N-methylethanesulfonamide (26e) (i.e. 26, R
= -NHCH3, n=2) was reacted with thiophosgene in chloroform at reflux
temperature to obtain a new product 1-(4-isothiocyanatophenyl)-N-
methylethane sulfonamide (106c) (i.e. 26, R = -NHCH3, n=2)
(Scheme-3.23). The structure of the product was established by its
spectral data. The characteristic peaks at 2185 and 2140 cm−1 in the
IR spectrum of 106c (Fig. 3.1) have been attributed to N=C=S group.
81
The peaks at 1310 cm-1 and 1122 cm-1 confirming the asymmetric and
symmetric stretchings of –SO2 group. Its 1H NMR (DMSO-d6/TMS)
spectrum (Fig. 3.2) showed signals at 2.51 (d, J=4.1 HZ, 3H, -
NHCH3), 3.00-3.20 (t, 2H, Ar-CH2), 3.40-3.50 (t, 2H, -SO2CH2), 7.00
(m, 1H, -NHCH3, D2O exchangable), 7.60 (d, J=8.05 HZ, 2H, Ar-H),
8.20 (d, J=8.05 HZ, 2H, Ar-H). Its APCI mass spectrum (Fig. 3.3)
showed M++1 ion peak at 257 corresponding to a molecular mass of
256.
……….Scheme - 3.23
The above reaction of arylamino derivatives 26e with
thiophosgene has been found to be a general one and has been
extended to other substituted sulfonyl phenyl amine 26a and 26d.
The products obtained have assigned structures 106a-c on the basis
of their spectral data.
3.4.2. Condensation of 106 with Pyridine-4-carboxylic acid
hydrazide 107:
106c (i.e. 106, R=-NHCH3, n=2) was reacted with 40 in
refluxing methanol to yield 2-isonicotinoyl-N-(4-(2-(N-methylsulfamoyl)
ethyl) phenyl) hydrazinecarbothioamide (107c) (i.e. 107c, R=-NHCH3,
n=2) (Scheme-3.24). Its IR (KBr) spectrum (Fig. 3.4) showed a
characteristic peak at 1292 cm−1 which can be attributed to C=S
82
group and a peak at 1693 cm−1 conforming the carbonyl group. Peaks
at 1292 cm-1 and 1141 cm-1 have been attributed to the asymmetric
and symmetric stretchings of –SO2 group. It’s 1H-NMR spectrum
showed signals at δ 9.7 and 9.8 confirming the protons of –NH-NH-
grouping. The signal at δ 10.8 is –NH proton between thio ketone and
aromatic groups. Its 1H NMR (DMSO-d6/TMS) spectrum (Fig. 3.5)
showed signals at 2.50 (d, J=4.8 HZ, 3H, -NHCH3), 2.9-3.00 (t, J=7.6
HZ, 2H, Ar-CH2), 3.40-3.50 (t, 2H, J=7.6 HZ, -SO2CH2), 7.00 (m, 1H, -
NHCH3), 7.30 (d, J=8.0 HZ, 2H, Ar-H), 7.50 (d, J=8.0 HZ, 2H, Ar-H,),
7.90 (d, J=4.8 HZ, 2H, pyridine ring protons,), 8.80 (d, J=4.8 HZ, 2H,
pyridine ring protons,), 9.90 (br, s, 2H, -NH-NH- portons), 10.90 (s,
1H, NH, D2O exchangable). Its APCI mass spectrum (Fig. 3.6) showed
M++1 ion peak at 394 corresponding to a molecular mass of 393. Its
13C NMR spectrum (Fig. 3.7) showed signals at δ 28.97, 29.06, 50.70,
122.06, 126.45, 128.44, 137.86, 139.96, 150.53, and 164.84. Based
on the above spectral data, the compound was assigned the structure
107c.
……….Scheme - 3.24
The above reaction of aryl isothiocyanate derivative 106c with acid
hydrazide derivative 40 has been found to be a general one and has
83
been extended to other substituted isothiocyanates. The products
obtained have been assigned structures 107a-b on the basis of their
spectral data
3.4.3. Cyclization of 107 in sodium hydroxide 108:
Cyclisation of the aryl thiosemicarbazide derivative 107c (i.e.
107, R=-NHCH3, n=2) in aq. sodium hydroxide solution yielded 2-(4-
(3-mercapto-5-(pyridin-4-yl)-4H-1,2,4-triazol-4-yl)phenyl)-N-methyl
ethanesulfonamide (108c) (i.e. 108, R=-NHCH3, n=2) (Scheme-3.25).
Its IR (KBr) spectrum (Fig. 3.8) showed a peak at 2726 cm−1
attributed to SH and peaks at 1322 cm-1 and 1130 cm-1 confirming the
asymmetric and symmetric stretchings of –SO2 group. The signal at δ
14.20 in its 1H-NMR confirmed the proton of -SH. Its mass spectrum
showed molecular ion at m/z 376 which further confirmed the
structure. Its 1H NMR (DMSO-d6/TMS) spectrum (Fig. 3.9) showed
signals at 2.50 (d, J=4.1 HZ, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2),
3.40-3.50 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NHCH3, D2O exchangable),
7.20-7.40 (m, 4H, Ar-H), 7.60 (d, J=5.0 Hz, 2H, pyridine ring
protons), 8.70 (d, J=5.0 Hz, 2H, pyridine ring protons), 14.20 (s, 1H,
SH, D2O exchangable). Its APCI mass spectrum (Fig. 3.10) showed
M++1 ion peak at 376 corresponding to a molecular mass of 375. Its
13C NMR spectrum (Fig. 3.11) showed the peaks at 28.94, 29.20,
50.28, 122.25, 128.94, 129.92, 132.88, 133.60, 140.68, 148.79,
150.43 and 159.60. Based on the above spectral data, the compound
was assigned as structure 108c.
84
……….Scheme 3.25
The above cyclisation reaction of 107c in aq.NaOH was found to
be a general one and has been extended to substituted
carbothioamide. The products obtained have been assigned structures
108a-b on the basis of their spectral and analytical data.
3.4.4. Cyclization of 107 in sulphuric acid 109:
Cyclization of 107c (i.e. 107, R=-NHCH3, n=2) in Con.sulphuric
acid medium at 25-30ºC yielded N-methyl-2-(4-(5-(pyridin-4-yl)-1,3,4-
thiadiazol-2-ylamino)phenyl)ethanesulfonamide (109c) (i.e. 109, R=-
NHCH3, n=2) (Scheme-3.26). Absence of carbonyl absorption in its IR
spectrum (Fig.3.12) supported the assigned structure of 109c which
was further confirmed by 1H-NMR and mass spectral data. Its 1H NMR
(DMSO-d6/TMS) spectrum (Fig. 3.13) showed signals at 2.60 (d,
J=4.8 Hz, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.30-3.40 (t, 2H, -
SO2CH2), 7.00 (m, 1H, -NHCH3, D2O exchangable), 7.2 (d, J=6.0 Hz,
2H, pyridine ring protons ), 7.3 (d, J=8.4 Hz, 2H, Ar-H), 7.4 (d, J=8.4
Hz, Ar-H), 8.50 (d, J= 6.0 Hz, 2H, pyridine ring protons), 10.80 (s, 1H,
NH D2O exchangable). Its APCI mass spectrum (fig. 3.14) showed
M++1 ion peak at 376 corresponding to a molecular mass of 375. Its
13C NMR spectrum (Fig. 3.15) showed the peaks at 28.94, 29.20,
85
50.88, 118.36, 120.91, 129.55, 132.98, 137.57, 139.17, 150.97,
155.42 and 165.78. Based on the above spectral data, the structure of
the compound was assigned the structure 109c.
……….Scheme - 3.26
The above cyclisation reaction of 107c in sulphuric acid has
been found to be a general one and has been extended to substituted
carbothioamide. The products obtained have all been assigned
structures 109a-b on the basis of their spectral and analytical data.
3.4.5. Conversion of 106 to 110:
Condensation reaction of 106c (i.e. 106, R=-NHCH3, n=2) with
3-aminopropanol (76) in refluxing tetrahydrofuran to give 1-(4-(3-(4-
hydroxybutyl)thioureido)phenyl)-N-methyl ethane sulfonamide, which
on cyclisation in hydrochloric acid yielded 2-(4-(5,6-Dihydro-4H-1,3-
thiazin-2-ylamino)phenyl)-N-methylethanesulfonamide (111c) (i.e.
110, R=-NHCH3, n=2) (Scheme - 3.27). Its IR (KBr) spectrum (Fig.
3.16) showed a peak at 3288 cm−1 attributed to -NH and peaks at
1322 cm-1 and 1130 cm-1 confirmed the asymmetric and symmetric
stretchings of –SO2. Its 1H NMR (DMSO-d6/TMS) spectrum (Fig.3.17)
showed signals at 1.70 (m, 2H, CH2 Thiazine ring), 2.60 (d, J=4.5 HZ,
3H, -NHCH3), 2.80 (m, 2H, CH2 Thiazine ring), 3.00 (m, 2H, -Ar-CH2)
3.10 (m, 2H, CH2 Thiazine ring), 3.40 (m, 2H, -SO2CH2), 6.90 (m, 1H, -
86
NHCH3), 7.00-7.20 (m, 4H, Ar-H), 8.50 (s, 1H, NH, D2O exchangable).
Its APCI mass spectrum (Fig.3.18) showed M++1 ion peak at 314
corresponding to a molecular mass of 313. Its 13C NMR spectrum (Fig.
3.19) showed peaks at 21.02, 26.35, 28.60, 43.79, 50.64, 119.93,
128.33, 130.93, 142.54 and 147.10. Based on the above spectral data,
the compound was assigned structure 110c.
……….Scheme - 3.27
The above cyclisation reaction of 106c with 76 in hydrochloric
acid has been found to be a general one and has been extended to
substituted isocyanates. The products obtained have been assigned
structures 110a-b on the basis of their spectral data.
3.4.6. Condensation of 26e with 2-amino-2-cyanoacetamide 111:
Reaction of 26e (i.e. 26, R=-NHCH3, n=2) with 2-amino-2-
cyanoacetamide (93) and triethylorthoformate in acetonitrile to give a
compound whose structure was established by its spectral data as 5-
amino-1-(4-(N-methyl sulfamoyl ethyl) phenyl)-1H-imidazole-4-
carboxamide (111c) (i.e. 111, R=-NHCH3, n=2) (Scheme - 3.28).
Thus, its IR (KBr) spectrum (Fig. 3.20) showed peaks at 3423 cm-1
(due to the –NH2 stretching), 1640 cm-1 (due to the amide carbonyl)
and at 1315 and 1143 cm-1 (due to the -SO2). Its 1H NMR (DMSO-
d6/TMS) spectrum (Fig. 3.21) showed signals at 2.60 (d, J=4.4 HZ,
87
3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.30-3.40 (t, 2H, -SO2CH2),
5.70 (s, 2H, NH2, D2O exchangable), 6.8-6.9 (d, 2H, NH2) 7.00 (m, 1H,
-NHCH3, D2O exchangable), 7.35 (s, 1H, CH imidazole) 7.40-7.60 (m,
4H, Ar-H). Its APCI mass spectrum (Fig.3.22) showed M++1 ion peak
at 324 corresponding to a molecular mass of 323. Its 13C NMR
spectrum (Fig. 3.23) showed peaks at 28.99, 29.11, 50.44, 113.36,
124.93, 130.04, 130.23, 133.37, 139.04, 142.93 and 167.10.
……….Scheme - 3.28
The above reaction of 26e with 93 has been found to be a
general one and has been extended to substituted amines 26a and
26d. The products obtained have been assigned structures 111a-b on
the basis of their spectral data.
3.4.7. Cyclization of 111 with formic acid. 112:
Cyclization of 111c (i.e. 111, R=-NHCH3, n=2) in formic acid
under refluxing conditions at 120 ºC yielded N-methyl-2-(4-(6-oxo-1H-
purin-9(6H)-yl)phenyl)ethanesulfonamide (112c) (i.e. 112, R=-NHCH3,
n=2) (Scheme-3.29), which was found to be homogeneous on TLC. Its
IR (KBr) spectrum (Fig. 3.24) showed stretching frequencies at 3443
cm-1 (due to the -NH) and at 1712 cm-1 (sharp, strong, due to the
88
carbonyl) and 1309 and 1131 cm-1 (due to -SO2 group). Its 1H NMR
spectrum (Fig.3.25) at 2.60 (d, 3H J=4.8, -NHCH3), 3.00 (t, 2H, -Ar-
CH2), 3.30-3.40 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NHCH3, D2O
exchangable), 7.50 (d, 2H J=8.4 HZ, Ar-H), 7.70 (d, 2H J=8.4 HZ, Ar-
H), 8.10 (s, 1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50
(s, 1H, NH pyrimidine, D2O exchangable); Its mass spectrum (Fig.
3.26) in APCI mode showed the M++1 ion peak at 334 confirming the
molecular mass of the compound as 333. Its 13C NMR spectrum (Fig.
3.27) showed peaks at 28.99, 29.14, 50.52, 124.19, 125.15, 129.93,
133.27, 139.05, 139.76, 146.45, 148.29 and 157.09. Based on the
above spectral data the compound was assigned the structure 112c.
……….Scheme 3.29
The above cyclization reaction of 111c with formic acid has
been found to be a general one and has been extended to substituted
amino amides. The products obtained have all been assigned
structures 112a-b on the basis of their spectral and analytical data.
2-amino-2-cyanoacetamide (93) required in this reaction was
prepared as per the literature method [126]. In this method, ethyl
cyanoacetate (113) reacted with sodium nitrite to yield the nitroso
89
compound 114 which on reduction with sodium dithionite gave the
required 2-amino-2-cyanoacetamide (Scheme-3.30).
……….Scheme - 3.30
4-Pyridinecarboxylic acid hydrazide (40) required in this
reaction was prepared as per the literature method [129]. In this
method, nicotinic acid (115) was converted into ethyl ester to yield
ethyl nicotinate (116), which on reaction with hydrazine hydrate
gave the required 4-pyridine carboxylic acid hydrazide (Scheme-3.31).
……….Scheme - 3.31
All the above sequences of reactions are summarized in Scheme -
3.32 & 3.33
90
……….Scheme - 3.32
……….Scheme - 3.33
91
3.5. EXPERIMENTAL SECTION:
PREPARATION OF 108, 109, 110, 111 & 112:
3.5.1. GENERAL PROCEDURE FOR THE PREPARATION OF 106(a-
c):
A mixture of 26(a, d, e) (0.046 mol), chloroform (60 mL) and
water (50 mL) was cooled to about 10 ºC. Thiophosgene (0.063 mol)
was added dropwise to the reaction mixture with continuous stirring
at 10-20 ºC. After addition, the mixture was stirred at room
temperature for 3 hours. The progress of the reaction was monitored
by TLC. The organic layer was seperated and washed with excess of
water and finally with brine solution. The organic layer was dried over
anh.Na2SO4 and concentrated under reduced pressure. The residue
was stirred with hexane (20 mL) for I hour at room tempreature. The
solid was filtered, washed with hexane to give pure compound 107(a-
c).
106a: R = Pyrrolidine, n=1, Yield: 8.5 gm (65 %), M.R: 141-143 °C; IR
(KBr, cm-1) 2185 and 2140 (-N=C=S), 1310 and 1122 (-SO2); 1H NMR
(DMSO-d6/TMS) at 1.60-1.80 (m, 4H, pyrrolidine), 3.00-3.20 (m,
4H, pyrrolidine), 4.40 (s, 2H, -SO2CH2), 7.60 (d, 2H, Ar-H), 8.20 (d,
2H, Ar-H); M++1: 283; Anal.Calcd for (C12H14N2O2S2) requires: C,
51.04; H, 5.00; N, 9.92. Found: C, 51.00; H, 4.90; N, 9.90.
106b: R = -NHCH3, n=1, Yield: 6.1 gm (55 %), M.R: 146-148 ºC; IR
(KBr, cm-1) 2185 and 2140 (-N=C=S), 1310 and 1122 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2),
7.00 (m, 1H, -NH, D2O exchangable), 7.60 (d, 2H, Ar-H), 8.20 (d, 2H,
92
Ar-H); M++1: 243; Anal.Calcd for (C9H10N2O2S2) requires: C, 51.04; H,
5.00; N, 9.92. Found: C, 51.00; H, 4.90; N, 9.89.
106c: R = -NHCH3, n=2, Yield: 7.0 gm (60 %), M.R: 166-168 ºC; IR
(KBr, cm-1) 2185 and 2140 (-N=C=S), 1310 and 1122 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.50 (d, 3H, -NHCH3), 3.00-3.20 (t, 2H, -Ar-CH2),
3.40-3.50 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NH, D2O exchangable), 7.60
(d, 2H, Ar-H), 8.20 (d, 2H, Ar-H); M++1: 257; Anal.Calcd for
(C10H12N2O2S2) requires: C, 46.85; H, 4.72; N, 10.93. Found: C, 46.80;
H, 4.70; N, 10.90.
3.5.2. GENERAL PROCEDURE FOR THE PREPARATION OF 107(a-
c):
4-Pyridinecarboxylic acid hydrazide (40) (0.004 mol) was
dissolved in absolute ethanol (80 mL). A solution of 106(a-c) (0.004
mol) in absolute ethanol was added into the solution of hydrazide with
continuous stirring. The reaction mixture was refluxed by monitoring
on TLC for completion of reaction. After the completion of the reaction,
the mixture was cooled to room temperature. The resultant white solid
was filtered and recrystallized from methanol to get pure product
107(a-c).
107a: R = Pyrrolidine, n=1, Yield: 1.34 gm (80 %); M.R: 160-163 °C; IR
(KBr, cm-1) 1292 (-C=S), 1693 (C=O), 1310 and 1122 (-SO2); 1H NMR
(DMSO-d6/TMS) at 1.60-1.80 (m, 4H, pyrrolidine), 3.00-3.20 (m,
4H, pyrrolidine), 4.40 (s, 2H, -SO2CH2), 7.00 (s, 1H, -NH, D2O
exchangable), 7.20-7.40 (m, 4H, Ar-H), 7.90 (d, 2H, pyridine ring
protons), 8.80 (d, 2H, pyridine ring protons), 9.90 (s, 2H, -NH-NH
93
portons), 10.90(s, 1H, -NH, D2O exchangable); M++1: 420; Anal.Calcd
for (C18H21N5O3S2) requires: C, 51.53; H, 5.05; N, 16.69. Found: C,
51.50; H, 5.00; N, 16.63.
107b: R = -NHCH3, n=1, Yield: 1.21 gm (80 %), M.R: 182-184 °C; IR
(KBr, cm-1) 1292 (-C=S) 1693 (C=O), 1310 and 1122 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2),
7.00 (s, 1H, -NH, D2O exchangable), 7.20-7.40 (m, 4H, Ar-H), 7.90 (d,
2H, pyridine ring protons), 8.80 (d, 2H, pyridine ring protons), 9.90 (s,
2H, -NH-NH protons), 10.90 (s, 1H, -NH, D2O exchangable); M++1:
380; Anal.Calcd for (C15H17N5O3S2) requires: C, 47.48; H, 4.52; N,
18.46. Found: C, 47.45; H, 4.50; N, 18.43.
107c: R = -NHCH3, n=2, Yield: 1.1 gm (75 %), M.R: 150-155 °C; IR
(KBr, cm-1) 1292 (-C=S) 1693 (C=O), 1310 and 1122 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.50 (s, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2),
3.40-3.50 (t, 2H, -SO2CH2), 7.00 (s, 1H, -NH, D2O exchangable), 7.20-
7.40 (m, 4H, Ar-H), 7.90 (d, 2H, pyridine ring protons), 8.80 (d, 2H,
pyridine ring protons), 9.90 (s, 2H, -NH-NH portons), 10.90 (s, 1H, -
NH, D2O exchangable); M++1: 394; 13C NMR δ 28.97, 29.06, 50.70,
122.06, 126.45, 128.44, 137.86, 139.96, 150.53, 164.84. Anal.Calcd
for (C16H19N5O3S2) requires: C, 48.84; H, 4.87; N, 17.80. Found: C,
48.80; H, 4.83; N, 17.79.
3.5.3. GENERAL PROCEDURE FOR THE PREPARATION OF 108(a-
c):
Thiosemicarbazide 107(a-c) (0.003 mol) was added portion wise
to sodium hydroxide solution (2N, 25 mL). The reaction mixture was
94
refluxed, and the completion of the reaction was monitored by TLC.
The reaction mass was cooled to room temperature and filtered. The
filterate was acidified with 2N hydrochloric acid to pH = 2. The
precipitated solid was filtered, washed thoroughly with water (20 mL),
dried. The crude compound was recrystallized from ethanol/water
(4:1) to get compounds of 108(a-c).
108a: R = Pyrrolidine, n=1, Yield: 0.95 (80 %); M.R: 260-262 °C; IR
(KBr, cm-1) 2726 (-SH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 1.90 (m, 4H, pyrrolidine), 3.20 (m, 4H, pyrrolidine), 4.40
(s, 2H, -SO2CH2), 7.20-7.40 (m, 4H, Ar-H), 7.60 (d, 2H, pyridine ring
protons), 8.70 (d, 2H, pyridine ring protons), 14.20 (s, 1H, -SH, D2O
exchangable); M++1: 402; Anal.Calcd for (C18H19N5O2S2) requires: C,
53.85; H, 4.77; N, 17.44. Found: C, 53.81; H, 4.72; N, 17.43.
108b: R = -NHCH3, n=1, Yield: 0.85 gm (80 %); M.R: 260-262 °C; IR
(KBr, cm-1) 2726 (-SH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2), 7.00 (m,
1H, -NH, D2O exchangable), 7.20-7.40 (m, 4H, Ar-H), 7.60 (d, 2H,
pyridine ring protons), 8.70 (d, 2H, pyridine ring protons), 14.20 (s,
1H, -SH, D2O exchangable); M++1: 362; Anal.Calcd for (C15H15N5O2S2)
requires: C, 49.84; H, 4.18; N, 19.38. Found: C, 49.80; H, 4.14; N,
19.33.
108c: R = -NHCH3, n=2, Yield: 0.90 gm (80 %); M.R: 248-250 ºC; IR
(KBr, cm-1) 2726 (-SH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 2.50 (d, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.40-
3.50 (t, 2H, -SO2CH2), 7.00 (s, 1H, -NH, D2O exchangable), 7.20-7.40
95
(m, 4H, Ar-H), 7.60 (d, 2H, pyridine ring protons), 8.70 (d, 2H,
pyridine ring protons), 14.20 (s, 1H, -SH, D2O exchangable); M++1:
376; 13C NMR 28.94, 29.20, 50.28, 122.25, 128.94, 129.92, 132.88,
133.60, 140.68, 148.79, 150.43, 159.60. Anal.Calcd for
(C16H17N5O2S2) requires: C, 51.18; H, 4.56; N, 18.65. Found: C, 51.11;
H, 4.52; N, 18.60.
3.5.4. GENERAL PROCEDURE FOR THE PREPARATION OF 109(a-
c):
Thiosemicarbazide 107(a-c) (0.0025 mmol) was added portion
wise to Con. sulfuric acid (25 mL) at 0 ºC with continuous stirring. The
reaction mixture was stirred further for 3 hours at room temperature.
The reaction mass was poured into crushed ice (100 gm) and stirred
for 30 minutes. The separated product was filtered and recrystallized
from a mixture of acetic acid and water (1:1) to get compounds 109(a-
c).
109a: R = Pyrrolidine, n=1, Yield: 0.80 gm (80 %); M.R: >270 °C; IR
(KBr, cm-1) 3440 (-NH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 1.90 (d, 4H, pyrrolidine), 3.20 (d, 4H, pyrrolidine), 4.40
(s, 2H, -SO2CH2), 7.20-7.60 (m, 4H, Ar-H), 7.80 (d, 2H, pyridine ring
protons), 8.80 (d, 2H, pyridine ring protons), 10.80 (s, 1H, -NH, D2O
exchangable); M++1: 402; Anal.Calcd for (C18H19N5O2S2) requires: C,
53.85; H, 4.77; N, 17.44. Found: C, 53.80; H, 4.73; N, 17.40.
109b: R = -NHCH3, n=1), Yield: 0.71 gm (80 %); M.R: >270 °C; IR
(KBr, cm-1) 3440 (-NH), 1310 and 1122 (-SO2); 1H NMR (DMSO-
d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2), 7.00 (m,
96
1H, -NH, D2O exchangable), 7.20-7.60 (m, 4H, Ar-H), 7.80 (d ,2H,
pyridine ring protons), 8.80 (d, 2H, pyridine ring protons), 10.80 (s,
1H, -NH, D2O exchangable); M++1: 362; Anal.Calcd for (C15H15N5O2S2)
requires: C, 49.84; H, 4.18; N, 19.38. Found: C, 49.81; H, 4.14; N,
19.33.
109c: R = -NHCH3, n=2, Yield: 0.75 gm (80 %); M.R: >300 °C; IR (KBr,
cm-1) 3440 (-NH), 1310 and 1122 (-SO2); 1H NMR (DMSO-d6/TMS) at
2.60 (d, 3H, -NHCH3), 2.9-3.00 (t, 2H, -Ar-CH2), 3.30-3.40 (t, 2H, -
SO2CH2), 7.00 (m, 1H, -NHCH3 D2O exchangable), 7.20-7.60 (m, 4H,
Ar-H), 7.80 (d, 2H, pyridine ring protons), 8.80 (d, 2H, pyridine ring
protons), 10.80 (s, 1H, -NH, D2O exchangable), M++1: 376; Its 13C
NMR spectrum (Fig. 3.14) showed the signals at 28.94, 29.20,
50.88, 118.36, 120.91, 129.55, 132.98, 137.57, 139.17, 150.97,
155.42 and 165.78. Anal.Calcd for (C16H17N5O2S2) requires: C, 51.18;
H, 4.56; N, 18.65. Found: C, 51.12; H, 4.50; N, 18.61.
3.5.5. GENERAL PROCEDURE FOR THE PREPARATION OF 110(a-
c):
Compound 106(a-c) (0.013 mmol) was added portion wise to a
mixture of tetrahydrofuran (35.0 mL) and 4-aminobutane-1-ol (76)
(0.014 mol, 1.08 gm) at room temperature. The reaction mixture was
stirred further for 1 h at 50-55 ºC and completion of the reaction
monitored by TLC. After the completion of the reaction, the mixture
was cooled to room temperature and added Con.HCl (3.8 gm). The
reaction mixture was refluxed by monitoring on TLC for completion of
reaction. After the completion of the reaction, the mixture was
97
concentrated under reduced pressure at 90 ºC. To the resultant crude
was added water (20 mL) and the pH adjusted to neutral with
saturated aq.sodium bicarbonate. The separated product was filtered
and recrystallized from methanol to get pure compounds 110(a-c).
110a: R = Pyrrolidine, n=1, Yield: 3.0 gm (68 %); M.R: 142-145 °C; IR
(KBr, cm-1) 1625 (-C=N), 1310 and 1150 (-SO2); 1H NMR (DMSO-
d6/TMS) at 1.90 (d, 4H, pyrrolidine), 2.00 (m, 2H, CH2), 2.40 (m,
2H, CH2), 3.00 (m, 2H, CH2), 3.20 (d, 4H, pyrrolidine), 4.40 (s, 2H, -
SO2CH2), 7.20-7.60 (m, 4H, Ar-H), 8.80 (s, 1H, -NH, D2O
exchangable); M++1: 340; Anal.Calcd for (C15H21N3O2S2) requires: C,
53.07; H, 6.24; N, 12.38. Found: C, 53.01; H, 6.20; N, 12.33.
110b: R = -NHCH3, n=1, Yield: 2.7 gm (70 %); M.R; 152-155 °C; IR
(KBr, cm-1) 3278 (-NH), 1624 (-C=N), 1310 and 1150 (-SO2); 1H NMR
(DMSO-d6/TMS) at 1.90 (m, 2H, CH2), 2.6 (d, 3H, -NHCH3), 2.90 (m,
2H, CH2), 3.50 (m, 2H, CH2), 4.20 (s, 2H, -SO2CH2), 6.90 (s, 1H, -NH
D2O exchangable), 7.20-7.60 (m, 4H, Ar-H), 8.40 (s, 1H, -NH, D2O
exchangable); M++1: 300; Anal.Calcd for (C12H17N3O2S2) requires: C,
48.14; H, 5.72; N, 14.03. Found: C, 48.11; H, 5.70; N, 14.00.
110c: R = -NHCH3, n=2, Yield: 2.6 gm (65 %); M.R: 184-187 °C; IR
(KBr, cm-1) 3288 (-NH), 1625 (-C=N), 1310 and 1150 (-SO2) ; 1H NMR
(DMSO-d6/TMS) at 1.80 (m, 2H, CH2), 2.6 (d, 3H, -NHCH3), 2.80 (m,
2H, CH2), 3.00 (t, 2H, -Ar-CH2), 3.20 (t, 2H, -SO2CH2), 3.40 (m, 2H,
CH2), 6.90 (s, 1H, -NH, D2O exchangable), 7.20-7.60 (m, 4H, Ar-H),
8.40 (s, 1H, -NH, D2O exchangable); M++1: 314; Anal.Calcd for
98
(C13H19N3O2S2) requires: C, 49.81; H, 6.11; N, 13.41. Found: C, 49.78;
H, 6.08; N, 13.39.
3.5.6. GENERAL PROCEDURE FOR THE PREPARATION OF 111(a-
c):
A mixture of 2-amino-2-cyanoacetamide (93) (0.018 mol),
triethylorthoformate (0.0321 mol) and acetonitrile (55.0 mL) was
heated to reflux for 30 minutes then allowed to cool to room
temperature. (26a,d,e) (0.018mol) was added portion wise, and then
resulting mixture was stirred at reflux temperature for 3 hours. The
solid which was precipitated was filtered and recrystallized from
methanol to give pure compound (111a-c).
111a: R = Pyrrolidine, n=1, Yield: 5.1 gm (80 %); M.R: 204-207 °C; IR
(KBr, cm-1) 3445 (-NH), 1648 (-C=O) 1315 and 1143 (-SO2); 1H NMR
(DMSO-d6/TMS) at 1.90 (m, 4H, pyrrolidine), 3.20 (m, 4H,
pyrrolidine), 4.40 (s, 2H, -SO2CH2), 5.80 (s, 2H, -CONH2 D2O
exchangable), 6.7-6.9 (d, 2H, -NH2 D2O exchangable), 7.40 (s, 1H,
imidazole ring protons), 7.50-7.60 (d, 4H, Ar-H), M++1: 350;
Anal.Calcd for (C15H19N5O3S) requires: C, 51.56; H, 5.48; N, 20.04.
Found: C, 51.53; H, 5.42; N, 20.01.
111b: R = -NHCH3, n=1, Yield: 4.4 gm (80 %); M.R: 193-196 °C; IR
(KBr, cm-1) 3435 (-NH), 1644 (-C=O) 1315 and 1143 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.70 (d, 3H, -NHCH3), 4.20 (s, 2H, -SO2CH2),
5.80 (s, 2H, -CONH2, D2O exchangable), 6.7-6.9 (d, 2H, -NH2, D2O
exchangable), 7.00 (m, 1H, -NH, D2O exchangable), 7.40 (s, 1H, CH
imidazole), 7.50-7.60 (m, 4H, Ar-H), M++1: 310; Anal.Calcd for
99
(C12H15N5O3S) requires: C, 46.59; H, 4.89; N, 22.64. Found: C, 46.55;
H, 4.87; N, 22.61.
111c: R=-NHCH3, n=2, Yield: 3.4 gm (60 %); M.R: 220-225 °C; IR
(KBr, cm-1) 3423 (-NH2), 1640 (-C=O) 1315 and 1143 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.70 (s, 3H, -NHCH3), 3.00 (m, 2H, -Ar-CH2),
3.40 (m, 2H, -SO2CH2), 5.80 (s, 2H, -CONH2, D2O exchangable), 6.7-
6.9 (d, 2H, -NH2, D2O exchangable), 7.00 (m, 1H, -NHCH3, D2O
exchangable), 7.40 (s, 1H, CH imidazole), 7.50-7.60 (m, 4H, Ar-H),
M++1: 324; 13C NMR 28.99, 29.11, 50.44, 113.36, 124.93, 130.04,
130.23, 133.37, 139.04, 142.93 and 167.10. Anal.Calcd for
(C13H17N5O3S) requires: C, 48.28; H, 5.30; N, 21.66. Found: C, 48.24;
H, 5.28; N, 21.61.
3.5.7. GENERAL PROCEDURE FOR THE PREPARATION OF 112(a-
c):
A mixture of 111(a-c) (0.005 mol) and formic acid (20 mL) was
refluxed for 1 hour. The solution was cooled, and then poured into
water (50 mL). The solid that seperated was collected and crystallized
from suitable solvent gave the pure product 112(a-c).
112a: R = Pyrrolidine, n=1, Yield: 1.4 gm (80 %); M.R: >270 °C; IR
(KBr, cm-1) 3440 (-NH), 1712 (-C=O), 1519 and 1131 (-SO2); 1H NMR
(DMSO-d6/TMS) at 1.90 (m, 4H, pyrrolidine), 3.20 (m, 4H,
pyrrolidine), 4.40 (s, 2H, -SO2CH2), 7.40-7.60 (m, 4H, Ar-H), 8.10 (s,
1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50 (s, 1H, -NH,
pyrimidine, D2O exchangable); M++1: 360; Anal.Calcd for
100
(C16H17N5O3S) requires: C, 53.47; H, 4.77; N, 19.49. Found: C, 53.42;
H, 4.75; N, 19.45.
112b: R = -NHCH3, n=1, Yield: 1.2 gm (80 %); M.R: >270 °C; IR (KBr,
cm-1) 3440 (-NH), 1712 (-C=O), 1519 and 1131 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.60 (d, 3H, -NHCH3), 4.40 (s, 2H, -SO2CH2),
7.00 (m, 1H, -NH, D2O exchangable), 7.20-7.60 (m, 4H, Ar-H), 8.10
(s, 1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50 (s, 1H, -NH,
pyrimidine, D2O exchangable); M++1: 320; Anal.Calcd for
(C13H13N5O3S) requires: C, 48.89; H, 4.10; N, 21.93. Found: C, 48.86;
H, 4.08; N, 21.89.
112c: R=-NHCH3, n=2, Yield: 1.1gm (70 %); M.R: >270 °C; IR (KBr,
cm-1) 3443 (-NH), 1712 (-C=O), 1309 and 1131 (-SO2); 1H NMR
(DMSO-d6/TMS) at 2.60 (d, 3H J=4.8, -NHCH3), 2.9-3.00 (t, 2H, -Ar-
CH2), 3.30-3.40 (t, 2H, -SO2CH2), 7.00 (m, 1H, -NH, D2O
Exchangable), 7.50 (d, 2H J=8.4, Ar-H), 7.70 (d, 2H J=8.4, Ar-H),
8.10 (s, 1H, CH pyrimidine), 8.50 (s, 1H, CH imidazole), 12.50 (s, 1H, -
NH, pyrimidine, D2O exchangable); M++1: 334; 13C NMR 28.99,
29.14, 50.52, 124.19, 125.15, 129.93, 133.27, 139.05, 139.76,
146.45, 148.29 and 157.09. Anal.Calcd for (C14H15N5O3S) requires: C,
50.44; H, 4.54; N, 21.01. Found: C, 50.41; H, 4.51; N, 21.00.
Recommended