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STUDIES ON THIAZOLOPYRIDINES. PART 2. SYNTHESIS AND
ANTIMICROBIAL ACTIVITY OF NOVEL THIAZOLO[3,2–a] PYRIDINE
AND THIAZOLO[3,2 – a] [1,8] NAPHTHYRIDINE DERIVATIVES HAVING
TWO DIFFERENT ARYL MOIETIES
G. A. M. El-Hag Ali,a A. Khalil,b A. H. A. Ahmed,a M. S. A. El-Gabyc*
aChemistry Department, Faculty of Science, Al – Azhar universitY, Nasr City, Cairo, Egypt. bChemistry
Department, Faculty of Science, Ain Shams university, Cairo, Egypt. cChemistry Department, Faculty of
Science, Al -Azhar university, at Assuit, Assuit 71524 , Egypt.
Received 24-10-2001
Abstract Condensation of thiazolinone 1 with aromatic aldehydes in ethanol / piperidine solution furnished the novel thiazolidinone derivatives 2a-e. Ternary condensation of 2, malononitrile and aromatic aldehydes (1: 1: 1 molar ratio) in absolute ethanol containing a catalytic amount of piperidine yielded the thiazolo[3,2–a]pyridines 3a-h in good yields. Thiazolo[3,2 – a][1,8]naphthyridines 6a-c were obtained by treatment of 3a, d,h with malononitrile in ethanol in the presence of piperidine as a basic catalyst. Refluxing of compounds 3b, g, h in formic acid furnished the novel thiazolo[2`,3`:1,6] pyrido[2,3– d]pyrimidines 8a–c. Interaction of 8c with malononitrile in ethanol / piperidine solution produced the pyrano[2`,3`:4,5]thiazolo[3`,2:1,6]pyrido[2,3-d]pyrimidine 9. Structures of the synthesized compounds have been established by elemental analyses and spectral data. Compounds 3a-h, 6a-c and 8a-c have been screened for antimicrobial activity.
Introduction
Our search of the literature revealed that, some thiazolo[3,2–a]pyridine derivatives
have been reported to possess antibacterial,1 bactericide,2 coronary dilator, antihypertensive and muscle relaxant3 activities. Also, it is observed from the literature4-7 that,7H-thiazolo[3,2-a] pyridines were synthesized from 2-alkoxycarbonyl -methylidene-5-(arylmethylidene)-1,3-thiazolidin-4-one and arylmethylidenemalono-nitriles . In view of the above and in continuation of our research programme8-12 on the synthesis of heterocyclic compounds for antimicrobial activity, we reported here the synthesis and antimicrobial activity of some novel thiazolo[3,2 –a]pyridine, thiazolo[3,2 –a][1,8]naphthyridine and thiazolo[2`,3` :1,6]pyrido[2,3 – d]pyrimidine derivatives.
Results and discussion Thiazolidinones 2a-e were obtained by refluxing of 2-cyanomethyl-4- thiazolinone
1 with aromatic aldehydes in ethanol / piperidine mixture. Ternary condensation of 2,
malononitrile and aromatic aldehydes (1:1:1 molar ratio) in absolute ethanol containing
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a catalytic amount of piperidine furnished the novel 5-amino–2–arylmethylidene-7– aryl–6,8-dicyano-3-oxo-2,3–dihydro–7H–thiazolo[3,2–a]pyridines 3a-h in good yields. The structures of the synthesized compounds 3a-h are in agreement with analytical and spectroscopic data (IR, 1H NMR and MS). The IR spectra of compounds 3a-h exhibited characteristic absorption bands for NH2, C?N and C=O (thiazolidinone) groups. 1H-NMR spectrum of 3b recorded in deuterated dimethylsulfoxide revealed a signal in the region ? 4.67 ppm, attributed to the pyridine –H. The molecular ion of thiazolopyridine 3b was observed at m/z = 479 (5; 7%) corresponding to the molecular formula C22H12BrFN4OS, (Chart 1). Also, a further conformation of the prepared compounds 3a– h was obtained by an independent synthetic route by treatment of compounds 2 with arylidene malononitriles 4 in refluxing ethanol and triethylamine (Scheme 1).
Scheme 1
NC
H
Ar CHO   Mc        /
------------*-            iS
O
2     N 3
Ar2 CH=C
_^CN
O
Ar.CH 2a-e
CH2(CN)2 Arl *  H
Ar2CHO
y
iS        N4      NH
1     -/2 ArCH
A3
O
CN
Ar^
CN CN
O
NC      >=N Ar1CH
NC    N)—NH
3a-h
S
Ar1CH
O
2a; Ar1 = C6H4 Br-p
2b; Ar1 = C6H4 F-p
2c; Ar1=C6H3 (OCH3)(OH)-3,4
2d; Ar1 = C6H4 Cl-p
2e; Ar1 = C6H4 CH3 -p
3a; Ar1 = C6H4 Br-p
3b; Ar1 = C6H4 F-p
3c; Ar1 = C6H3 (OCH3)(OH)-3,4
3d; Ar1 = C6H4Cl-p
3e; Ar1 = C6H4CH3 -p
3f; Ar1 = C6H4 F-p
3g; Ar1 = C6H4 F-,p
3h; Ar1 = C6H4 F-p
Ar2 = C6H4 F-p
Ar2 = C6H4 Br-p
Ar2 = C6H4 F-p
Ar2 = C6H4 F-p
Ar2 = C6H4 F-p
Ar2 = C6H3 (OCH3) (OH) –3,4
Ar2 = C6H4 Cl-p
Ar2 = C6H4 CH3 - p
4
1
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Chart 1
Br
A   NC
CN
S        N        NH2
^A      ^-----V
o
F—<f   ^C
Br
NC
S'     ~N'    ^NH
CH                O
m/z 384 (64%)
-C6H4F-p    C22H12BrFN4OS m/z 459 (5.7% )
-C6H4Br
Br
-CO
CN
NC S'     ^N
NC-
S'    "N"    "NH2 CH m/z 356 (16%)
/T^v         ^-------^
CN NH,
/   \
O
m/z180 (4.5%)
-66H4F-p S
-CO
m/z 323 (100%; base peak) -CO
//
"\\
CH                 O
m/z 85 (1%)
m/z 295 (38%)
-CN
m/z 269 (4%)
Fragmentation pattern of compound 3b
The reactivity of thiazolopyrimidines 3, which contains chalcone and o-aminonitrile moieties, towards malononitrile was investigated. When compounds 3a,d,h were allowed to react with malononitrile in ethanol/piperidine solution under reflux, for which three possible structures 5, 6 and 7 can be formulated, Scheme 2. The structure of 7 was established and the other possible structures were easily discarded on the basis of spectral data. The IR spectrum of compound 7a showed a cyano stretch at 2214 cm-1, C=O (thiazolidinone) at 1720 cm-1 and a primary amino bands at 3479 and 3363 cm-1. 1HNMR spectrum of 7c in DMSO–d6 displayed a singlet at ? 4.12 ppm, attributed to 5H and a broad singlet at ? 3.36 ppm due to the amino group, in addition to a multiplet in the region ? 7.23–7.56 ppm, which was assigned to the aromatic protons, methine proton and amino group. The formation of 7 is assumed to proceed via the addition of




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amino group in 3 to the cyano group of malononitrile to give the intermediate A, which cyclized to yield 7 ( Scheme 2 ).
Scheme 2
CN
S        N        NH
Art
3a,d,h
CH2(CN)2
NC               NH2
5
NC
Ar2x
H     *
NC
CN
CH2CN C-NK
S        N        N'
4
Ar 1 CH               'O
A
NH Ar2     H
Ar2     H    NH2
NC^L
N
,     ,   ,     .   A^                 7S'     ~N'     "N'    "NH0
S        N        N        CHXN           111               2
3^CN
ArW            O
//-------\\
Ar1 CH                O
Ar1 7a; C6H4 Br-p 7b; C6H4 Cl-p 7c; C6H4 F-p
Ar2
C6H4 F-p C6H4 F-P C6H4CH3-p
Heterocyolic o-aminonitriles are well established as versatile starting materials for the synthesis of a wide variety of fused heterocyclic compounds.13 Thus, refluxing of o-aminonitriles 3b,g,h in formic acid yielded the corresponding thiazolo [2`,3` : 6,1]pyrido[2,3-d]pyrimidines 8a-c, (Scheme 3). The formation of 8 is supposed to proceed via intermediate amide formation, resulted from the partial hydrolysis of cyano functionality present at the position 6 of 3, followed by intramolecular cyclization with formic acid.14 The IR spectrum of 8a exhibited stretching vibrations in the region 3193 cm-1 (NH), 2198 cm-1 (C?N) together with characteristic bands for C=O (thiazolidinone)


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at 1700 cm-1 and C = O (pyrimidinone) at 1680 cm-1 . When the a,p-unsaturated ketone 8c was treated with malononitrile in ethanol containing a catalytic amount of piperidine, the pyrano [2`,3` : 4,5]thiazolo[3`,2` :6,1] pyrido[2,3-d] pyrimidine 9 was obtained. The IR spectrum of 9 exhibited stretching vibrations near 3320 and 3201 cm-1 (NH2), 2214 cm-1 (CN) and 1666 cm-1 (C=O). The 1HNMR spectrum of 9 in DMSO-d6 displayed a singlet at 5 4.59 ( pyran-H) .The formation of 9 via initial Michael addition15 to the a,p-
Scheme 3
(3)
HCOOH
(3b,g,h)
Ari    H    O
NC
II C-NK
NH
1     "                O
Ar CH               u
Ari     H    NH2 HCONH2       NC^s^^^ ?
(3b)
7S        N        N'
1
//8
Ar1 CH                O
10
Ar2N    H
NC
PhS02CI
(3d)
8a;Ar1 = C6H4 F-p b;Ar1 = C6H4 F-p c;Ar1 = C6H4 F-p 9a;Ar1 = C6H4 F-p lOandllAr1 = C6H4 F-p
Ai^CH
S        N
11
CN
NHS02Ph
O
Ar2 = C6H4Br-p Ar2 = C6H4Cl-p Ar2 = C6H4CH3-p Ar2 = C6H4CH3 Ar2 = C6H4Br-p
Ar2CH
Ar NC^L
7 S
//8
HO
4   3
NH
O
8a-c
Ar
CH2(CN)2
8c
HO
NC^g-^x^-,^
1
Ar
NC
O 11
A10
2
2
2
2
H
9
9
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370                                Acta Chim. Slov. 2002, 49, 365-376.
unsaturated system followed by nucleophilic attack of hydroxyl group of the heterocyclic ring to one of the cyano groups of malononitrile to yield the pyran derivative 9. Thiazolo[2`,3`:6,1] pyrido [2,3-d]pyrimidine 10 was obtained by cyclocondensation of 3b with formamide under reflux conditions. Finally, treatment of 3b with benzene sulfonyl chloride in benzene furnished the novel sulfonamide derivative 11, (Scheme 3).
Antimicrobial Activity
Fourteen compounds were screened in vitro for their antimicrobial activities against
four strains of bacteria Staphylococcus aureus (NCTC-7447), Bacillus cereus (ATCC-14579), Serratia marcesens (IMRU-70), Proteus mirabilis (NCTC-289) and two strains of fungi Aspergillus ochraceus Wilhelm (AUCC-230) and Pencillium chrysoegenum Thom (AUCC-530) by the agar diffusion technique.16 A l mg/mL solution in dimethylformamide was used. The bacteria and fungi were maintained on nutrient agar and Czapek's-Dox agar media, respectively. DMF showed no inhibition zones. The agar media were inoculated with different microorganisms culture tested. After 24h of incubation at 30 oC for bacteria and 48 h of incubation at 28 oC for fungi, the diameter of inhibition zone (mm) was measured (Table 1). Ampicillin in a concentration 25 µg mL-1 and Mycostatine (30 µg mL-1) used as a references for antibacterial and antifungal activities, respectively. The minimal inhibitory concentration (MIC) of some of the tested compounds was measured by a twofold serial dilution method.17 Most of the synthesized compounds exhibited antimicrobial activity towards all the microorganisms used.
Experimental
All melting points are uncorrected (Stuart Scientific Co., UK). IR spectra were measured as KBr pellets on Shimadzu IR 200 spectrophotometer. 1H-NMR spectra were recorded in deutrated DMSO-d6 at 200 MHz on a Varian Gemini NMR spectrometer using tetramethylsilane as an internal reference. Elemental analyses were carried out at the Microanalytical Center of Cairo University. The characteristic data for prepared compounds are given in Table 2. The spectral data are collected in Table 3. Compound 1 was prepared according to reported method.18
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TABLE (1): Antimicrobial activity of some synthesized compounds and inhibition zones
Compd. No.	Gram positive bacteria		Gram negative bacteria		Fungi	
	Staphyloccus aureus (NCTC 7447)	Bacillus cereus (NCTC-14579)	Serratia marcesens (IMRU-70)	Proteus mirabilis (NCTC-289)	Aspergillus ochraceus Wilhelm (AUCC-230)	Penicillium chrysogenum Thorn (AUCC-530)
3a 3b 3c 3d 3e 3f 3g 3h 6a 6b 6c 8a 8b 8c Standard	+++ ++ +++ + + + ++ ++ ++ ++ +++ +++ ++ + ++++	+ ++ + ++ + + ++ + + ++ ++ + + ++ ++++	++ + +++ ++ + + ++ +++ + ++ + + + + +++ +	+ ++ + + + + ++ + ++ + + + ++ + +++ +	+ + ++ + + + ++ + + ++ ++ ++ + ++ ++++	++ + + + + + + ++ + ++ + + ++ + ++++
+           : Less active (0.2-0.5 cm)
++          : Moderately active (0.6-1.4 cm)
+++        : Highly active (1.5-3.0 cm)
++++      : Very highly activity (over 3.0 cm)
Standard: For Gram positive and Gram negative bacteria: Ampicillin 25 µg mL-1; for fungi: Mycostatine 30 µg mL-1.
Experimental
All melting points are uncorrected (Stuart Scientific Co., UK). IR spectra were measured as KBr pellets on Shimadzu IR 200 spectrophotometer. 1H-NMR spectra were recorded in deutrated DMSO-d6 at 200 MHz on a Varian Gemini NMR spectrometer using tetramethylsilane as an internal reference. Elemental analyses were carried out at the Microanalytical Center of Cairo University. The characteristic data for prepared compounds are given in Table 2. The spectral data are collected in Table 3. Compound 1 was prepared according to reported method.18
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5-Arylmethylidene–2–cyanomethyl–4,5-dihydro-4-thiazolinones (2a-e). A mixture of 1 (0.01 mole), aromatic aldehyde (0.01 mole) and piperidine (0.5 mL) in anhydrous ethanol (30 mL) was heated under reflux at 120 oC for 3h, and then allowed to cool to room temperature. The precipitate was collected by filtration and recrystallized from ethanol / benzene to give 2a-e.
5-Amino–2-arylmethylidene–7-aryl-2,3-dihydro-7H-3-oxothiazolo[3,2-a]pyridin – 6,8- dicarbonitriles (3a-h). Method (A): A mixture of 2 (0.01 mole), malononitrile (0.01 mole), aromatic aldehyde (0.01 mole) and piperidine (0.5 mL) in anhydrous ethanol (30 mL) was heated under reflux for 4h, the solid product which precipitated upon heating was collected by filtration and recrystallized from dioxane to give 2a-h Method B: A mixture of 2 (0.01 mole), arylidenemalononitrile 4 (0.01 mole) and piperidine (0.5mL) in absolute ethanol (30 ml) was heated under reflux for 2 h. The precipitate was collected by filtration and recrystallized to give 3.
5–Aryl-8-arylmethylidene–2,4-diamino-8,9-dihydro-5H-thiazolo[3,2-a][1,8] naphthryidine-3,6-dicarbonitriles (6a-c). A mixture of 3 (0.01 mole), malononitrile (0.01 mole) and piperidine (0.5 mL) in absolute ethanol (30 mL) was heated under reflux for 0.5 h. The solid product which precipitated upon on heating was collected by filtration and recrystallized from dioxane to give 6a-c.
5-Aryl-8-Arylmethylidene-4-oxo–3,4,8,9-tetrahydro-5H-thiazolo[2`,3`:1,6][2,3–d] pyrimidine–6–carbonitriles (8a-c). A mixture of 3 (0.01 mole) and formic acid (15 mL) was heated under reflux for 8h. The reaction mixture was concentrated in vacuo and the precipitate was collected by filtration, washed with water and recrystallized from dioxane to give 8a-c.
10- Amino –5,8-diaryl 3,4-dihydro–4-oxo–5H,8H- pyrano [2`,3`:5,4]thiazolo[3`,2`: 1,6]pyrido[2,3-d]pyrimidine–6,9-dicarbonitrile (9). A mixture of 8c (4.42 g; 0.01 mole), malononitrile (0.66 gm; 0.01 mole) and piperidine (0.5 mL) in anhydrous ethanol (30 mL) was heated under reflux for 3h, then allowed to cool poured into cold water
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(100 mL), and acidified with HCl ( 3 mL; 36%). The solid product was collected by filtration and recrystallized from ethanol to give 9 .
4-Amino–5-aryl-8-arylmethylidene-8,9-dihydro-5H-thiazolo[2`,3`:1,6]pyrido[2,3-d]pyrimidine-6-carbonitrile (10). A mixture of 3b (4.79 g; 0.01 mole) and formamide (10 mL) was refluxed for 4h. The precipitate was collected by filtration    and recrystallized from ethanol to give 10 .
5-Benzenesulfonylamino–2-(4-fluorphenylmethylidene)-7-(4-bromophenyl)-2,3-dihydro-3-oxo-7H-thiazolo[3,2-a]pyridin–6,8-dicarbonitrile (11). A mixture of 3b (4.79 g; 0.01 mole) and benzene sulfonyl chloride (1.77 g; 0.01 mole) in anhydrous benzene (30 mL) was heated under reflux for 1 h. The precipitate was collected by filtration and recrystallized from benzene to give 11.
Table 2: Physical and analytical data for compounds 2, 3, 6, 8, 9, 10 and 11.
Compd. No	Yield (%)	Solvent cryst.	mp (oC)	Mol. Formula (M. Wt)	Calculated / found (%)		
					C	H	N
2a	82	B/H	176-8	C12H7 Br N2 OS	46.92	2.30	9.12
				(307.17)	46.80	2.10	9.30
2b	76	B/E	169-71	C12H7 F N2 OS (246.26)	58.53 58.40	2.87 2.80	11.38 11.40
2c	80	B/E	166-8	C13H10 N2 O3S	56.92	3.67	10.21
				(274.30)	56.70	4.10	10.20
2d	74	B/H	162-4	C12H7Cl N2 OS	54.86	2.69	10.66
				(262.72)	54.70	2.70	10.50
2e	67	B/E	183-5	C13H10 N2 OS	64.44	4.16	11.56
				(242.30)	64.40	4.10	11.50
3a	87	D	258-60	C22H12 Br F N4 OS	55.13	2.52	11.67
				(479.99)	55.20	2.50	13.70
3b	84	D	260-2	C22H12 Br F N4 OS	55.13	2.52	11.67
				(479.99)	55.10	2.60	13.80
3c	82	DMF/E	233-5	C23H15 F N4 O3S	61.88	3.39	12.55
				(446.45)	61.70	3.40	12.60
3d	77	D	248-50	C22H12Cl F N4 OS	60.76	2.78	12.88
				(434.87)	60.60	2.70	12.80
3e	72	DMF/H2O	246-8	C23H15 F N4 OS	66.65	3.65	13.52
				(414.46)	66.70	3.60	13.50
3f	75	DMF/H2O	250-2	C23H15 F N4 O3S	61.88	3.39	12.55
				(446.45)	61.70	3.40	12.60
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Table 2 Continued.
Compd. No	Yield (%)	Solvent cryst.	mp (°C)	Mol. Formula (M. Wt)	Calculated / found (%)		
					C	H	N
3g	64	DMF/H20	255-6	C22H12 C/F N4 OS	60.76	2.78	12.88
				(434.87)	60.70	2.70	12.90
3h	68	DMF/H20	240-2	C23H15 F N4 OS	66.65	3.65	13.52
				(41446)	66.70	3.70	13.60
6a	76	D	200-1	C25H14 Br F N6 OS	55.06	2.59	15.41
				(545.39)	55.10	2.10	15.30
6b	72	D	205-7	C25H14 Cl F N6 OS	59.94	2.82	16.78
				(500.94)	59.90	2.80	16.70
6c	70	DMF	> 300	C26H17 F N6 OS	64.99	3.57	17.49
				(480.52)	65.10	3.40	17.60
8a	90	DMF	> 300	C23H12 Br F N4 O2S	54.45	2.42	11.04
				(507.34)	54.40	2.30	11.10
8b	67	D	232-4	C23H12 Cl F N4 O2S	59.68	2.61	12.10
				(462.88)	59.60	2.50	12.20
8c	82	DMF	> 300	C24H15 F N4 O2S	65.15	3.42	12.66
				(442.47)	65.10	3.40	12.70
9	64	E	132-4	C27H17 F N6 O2S	63.77	3.37	16.53
				(508.53)	63.80	3.30	16.40
10	84	DMF	> 300	C23H13 Br FN5 OS	54.56	2.59	13.83
				(506.35)	54.50	2.56	13.80
11	72	B	130	C28H16 Br F N4O3S2	54.29	2.60	9.04
				(619.49)	54.10	2.50	9.10
B = benzene ,  H = n-hexane,        E = ethanol ,        DMF = dimethylformamide , D = dioxane
Table (3): Spectral data for compounds 2, 3, 7, 8, 9, 10,and 11
Cmp. No	IR ( cm-1) (KBr disc)	1HNMR (DMSO-d6) ? (ppm)
2a 2b 2c 2d 2e 3a 3b 3c	2950    (CH-aliph.),    2199    (C=N),1715 (C=0; thiazolidinone ). 2900 (CH-aliph.), 2200 (C=N), 1719 (C=0; thiazolidinone ). 3483-2958  (broad;  OH),  2200  (ON), 1707 (C=0; thiazolidinone) 293 4 (CH-aliph.), 2200 (C=N), 1718 (C=0; thiazolidinone). 2924   (CH-aliph.),   2200   (C=N),   1711 (C=0; thiazolidinone) 3400, 3290 (NH2), 2200 (C=N), 1712 (C=0; thiazolidinone ) 3410, 3350 (NH2), 2200 (C=N), 1708 (C=0; thiazolidinone ) 3400 - 2400 (NH2 + OH), 2200 (C=N), 1705 (C=0; thiazolidinone)	4.04 (s, 2H, CH2CN), 7.12-7.85 (m, 5H, 4H-Ar and methine-H). 3.84 (s, 3H, OCH3),4.76(s, 2H, CH2CN), 6.67-7.89 (m, 4H,   3H-Ar   and   methine–H),  10.00  (s,   1H,   OH; exchangeable). 2.35 (s, 3H, CH3), 4.02 (s, 2H, CH2CN), 7.06 – 7.87 (m, 5H ,4H-Ar and methine-H,) 4.64( s,1H,pyridine –H ), 7.20-7.82 (m, 9H, 8H – Ar and methine –H), 7.87 (s, 2H, NH2 exchangeable) 4.67 (s, 1H, pyridine-H), 7.22 – 7.85 (m, 9H, 8H Ar and methine-H), 7.89 (s, 2H, NH2; exchangeable). 3.83 (s, 3H, OCH3), 4.46 (s, 1H, pyridine-H), 6.80 (s, 1H, OH; exchangeable), 6.93-7.85 (m, 8H, 7H- Ar-and methine-H), 7.87 (s, 2H, NH2; exchangeable).
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Table (3) Continued.
Cmp. No.
3f
3d 3g 3e 3h
7a 7b
7c
8a
8b
8c
IR ( cm-1) (KBr disc)
10
11
3500, 2450 (NH2 + OH), 2200 (C?N),
1700 (C=0; thiazolidinone ).
3430, 3300 (NH2), 2200 (C?N), 1710
(C=0; thiazolidinone )
3390, 3300 (NH2), 2200 (C?N), 1710
(C=0 ; thiazolidinone).
3400, 3200 (NH2), 2200 (C?N), 1705
(C=0; thiazolidinone ).
3400, 3300 (NH2), 2200 (C?N), 1710
(C=0; thiazolidinone)
3479,   3363   (NH2),   2985   (CH-aliph.)
2214 (C?N), 1720 (C=0; thiazolidinone)
3409,   3332   (NH2),   2923   (CH-aliph.)
2214              (C?N),       1720       (C=0;
thiazolidinone).
3479,   3170   (NH2),   2923   (CH-aliph.),
2214 (C?N), 1720 (C=0; thiazolidinone)
1HNMR (DMSO-d6) ? (ppm)
(C?N),  1700 1680
(C=0; (C=0;
3193, (NH), 2198
thiazolidinone),
pyrimidinone)
3186, (NH), 2206 (C?N), 1705 (C=0);
thiazolidinone), 1658 (C=0;
pyrimidinone)
3200, (NH), 2206 (C?N),  1710 (C=0;
thiazolidinone),           1666           (C=0;
pyrimidinone).
3320, 3201 (NH2), 2931(CH-aliph.) 2214
(C?N), 1666 (C=0; pyrimidinone).
3270, 3200 (NH2), 2200 (C?N), 1704 (C=0; thiazolidinone) .
3350,   (NH),   2923   (CH-aliph.),   2214 (C?N), 1705 (C=Q; thiazolidinone) .
4.67 (s, 1H, pyridine-H), 7.23 – 7.68 (m, 9H, 8H-Ar-and methine-H), 7.88 (s,2H, NH2; exchangeable).
2.34 (s, 3H, CH3), 4.67 (s, 1H, pyridine–H), 7.22-7.71 (m, 9H, 8H-Ar, and methine–H), 7.90 (s, 2H, NH2; exchangeable).
4.00 – 4.51 (broad, 3H, pyridine – H+ NH2), 7.42 – 8.03 (m,11H, 8H-Ar, and methine – H and NH2) 4.08 (s, 1H, pyridine-H ), 4.19 (s,2H, NH2; exchangeable) 7.23-7.66 (m, 9H, 8H-Ar and methine– H) 7.96 (s, 2H, NH2; exchangeable ). 2.39 (s, 3H, CH3), 3.36 (b, 2H, NH2), 4.12 (s, 1H, pyridine–H), 7.23–7.56 (m, 11H, Ar-H+ methine-H+NH2)
4.91(s, 1H, pyridine–H), 7.18-7.79 (m, 9H, 8H- Ar and methine–H) , 8.19 (s, 1H, pyrimidine–H ), 11.50 (s, 1H NH ; exchangeable)
2.37 (s, 3H, CH3), 4.67 (s, 1H, pyridine –H), 7.19 – 7.75 (m, 9H, 8H-Ar, and methine–H), 8.15 (s, 1H, pyrimidine-H), 11.66 (broad, 1H, NH, exchangeable). 2.32 (s, 3H, CH3), 4.59 (s, 1H, pyran–H), 4.67 (s, 1H, pyridine –H), 5.81 (s, 2H, NH2), 7.15 – 7.72 (m, 8H, 8H, Ar), 10.85 (s, 1H, pyrimidine –H), 11.60 (s, 1H, NH; exchangeable)
4.80    (s,    1H,    pyridine–H),    6.21(s,    2H,    NH2; exchangeable), 7.04-7.54 (m, 9H ,8H–Ar and methine-H), 8.00 (s, 1H, pyrimidine – H ) . 4.80 ( s, 1H pyridine –H ), 7.28- 7.67 ( m, 9H, 8H–Ar and methine–H), 8.00 (s, 1H, NH; exchangeable).
References
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Povzetek S kondenzacijo tiazolina 1 z aromatskimi aldehidi in sledečo ternerno kondenzacijo z malononitrilom in aromatskimi aldehidi smo pripravili tiazolo[3,2–a]piridine 3a-h z dobrimi izkoristki. Le-te smo z nadaljnimi reakcijami pretvorili v tiazolo[2`,3`:1,6] pirido[2,3–d]pirimidine 8a–c. Slednji je z malononitrilom v zmesi etanol-piperidin dal pirano[2`,3`:4,5]tiazolo[3`,2:1,6]pirido[2,3-d]pirimidin 9. Spojine 3a-h, 6a-c in 8a-c smo testirali na antimikrobno učinkovanje.
G. A. M. El-Hag Ali, A. Khalil, A. H. A. Ahmed, M. S. A. El-Gaby: Studies on thiazolopyridines. Part 2.