Indi an Journal of Chemistry Vol. 428. January 2003. pp. 173-179

Synthesis and reactions of some new 2,3-dihydro-5H-5,7-diarylthiazolo­[3,2-a]pyrimidine-3-one derivatives and their antibacterial and fungicidal activity

M A Salama* & S A EI-Essa*t

*National Research Centre. Dokki. Cairo. Egypt. t*Girls College of Education. in Riyadh. Saudi Arabia

Received 2 June 2000; accepted (revised) 13 March 2002

Arylmethylene acetophe none derivatives (chalcones) la-d react wi th thiourea in glacia l acetic ac id CH3COOH/Ac20 in the presence of anhydrous sodi um acetate to yield I ,4-dihydro-4.6-diarylpyrimidine-2-thione 2a-d which on treatment wi th chloroacetic acid furnish 2.3-dihydro-5H-5.7-di ary l thiazolo[3 .2-aJpyrimidine-3-one derivatives 3a-d. Compou nds 3a-d on condensation with aromatic aldehydes yield 2(ary I methy le ne )-2.3-dihydro-5H-5. 7 -diary l-thiazolo[3.2-a ]pyrimidi ne-3-one deri vatives 4a-f. Also compo unds 4a-d have been prepared directly from 2a,b by the reaction with chloroacetic acid and the aromatic aldehyde. Coupling of 3a-d with aryl diazonium salts in pyridine yields 2-(aryl hydrazo)-2.3-di hydro-5 .7-diaryl-5H-thiazolo[3.2-a]pyrimidine-3-ones Sa-f. Compounds 2a-d on reaction with 2-bromopropionic or 3-bromopropionic acid give 2.3-dihydro-2-methyl-5H-5.7-diary l-thiazolc[3.2-aJpyrimidine-3-one 6a-d and 2.3-di hydro-6H-6.8-diaryl-pyrimido­[3.2-b]- 1.3-thi azin-4-ones 7a-d respectively. A number of 3,4-dihydro-4.6-diaryl pyrimidine-2yl-thio)acetahydrazide 8a-c. 2-(3,4-di hydro-4.6-diary I-pyri midine-2y I-thi o )acetani I ide derivati ves 8d-g. 2-(3,4-dihydro-4.6-diary I-pyrimidi ne-2y I-thio)­propiony Ih ydrazide 9a-c. 2-(3.4-di hydro-4.6-diary I-pyri midine-2y I-thio )propiony lanil ide 9d-f and 3-(3,4-dihydro-4,6-diary 1-pyrimidine-2yl-thio)propionamide lOa-e derivatives are readily obtained in good yield by the ac tion of the corresponding amines on compounds 3 . 6 or 7 successively . The anilide 8d also has been obtai ned by the reaction of compound 2a with chloroacetanilide.

Recently , the chemistry of thiazolopyrimidinones has received considerable attention due to their biological activities' -4. Now we report the synthesis of new analogous series involving si mple pyrimidinethione and thiazolopyrimidine derivatives for the biological evaluation .

Compounds la-d were prepared5.6 and reacted with

thiourea in presence of ethanolic potass ium hydroxide or sodium ethoxide to give 1,4-dihydro-4,6-diaryl-2(1 H)-pyrimidinethione 2,7.8 which on treatment with chloroacetic acid in acetic acid-acetic anhydride in presence of fused sodium acetate gave 2,3-dihydro­SH-S,7-diaryl-thiazolo[3,2-a]pyrimidin-3-ones 3. Compounds 3 were condensed with aromatic alde­hyde in refl uxing acetic anhydride or at ISOaC in the presence of piperidine to give 2-(arylr'1ethylene)-2,3-dihydro-SH-S,7-diarylthiazolo[3,2-a]pyrimidine-3-ones 4. However, the ary lmethylene 4 were prepared di­rectly from 2 by the action of chloroacetic ac id, the aromatic aldehyde and sodium acetate in the presence of acetic acid-acetic anhydride. Also, compound 3 coupled with aryldiazonium salts in pyridine to give 2-arylhydrazono-2,3-dihydro-S,7-diaryl-thiazolo[3, 2-a]pyri midine-3-ones 5 . Compounds 2 reacted with 2 or 3-bromopropionic ac id in refluxing acetic acid­acetic anhydride in presence of fused sodium acetate

to give 2,3-dihydro-2-methyl-SH-S,7-diaryl thia­zoI0[3,2-a]pyrimidin-3-ones 6 and 2,3-dihydro-6H, 6,8-diaryl-l ,3-thiazino[3,2-a]pyrimidine-4-ones 7 res­pectively. The sulfur hetero ring of compounds 3,6 or 7 is readily opened by the action of hydrazi ne hydrate or aromatic amine and afford 3,4-dihydro-4,6-diaryl­pyrimidine-2-yl-thio)acetahydrazide 8a-c, 2-(3,4-dihydro-4,6-diaryl-pyrimidine-2-yl-thio)acetanilide deri­vatives 8d-g, 2-(3,4-dihydro-4,6-diaryl-pyrimidine-2-yl-thio)propionylhydrazide 9a-c, 2-(3,4-dihydro-4,6-diaryl-pyrimidine-2-yl-thio)propionylanilide 9d-f and 3-(3 ,4-dihydro-4,6-diary l-pyri midi ne-2 y 1- th i 0 )propan­amide lOa-e derivatives successively. Also, the ani­lide 8d has been obtained by the action of compound 2a with chloroacetanilide (Scheme I).

The structure of the products were confirmed by elemental analyses and spectral data (Tables I, II ).

Antimicrobial screening The antimicrobial activity of some of these com­

pounds were assayed against Gram negative and Gram positive organisms, Bacillus subtilis, Es­cherichia coli, Fungi, Pseudomonas aeruginosa, Pro­teus mirabilis, Klebisella pneumonia, Saccharomyces cerevisiae and Staphylocoecus aureus using the cup­plate" in the nutrient agar media by measuring the

174

Compd

2a

2b

2c

2d

3a

3b

3c

3d

4a

4b

4c

4d

INDIAN J. C HEM., SEC B, JA NUARY 2003

o II

CII I,C-C- NHC.H,

9a-c & 9d-f

,.

8d

Ar '~Nvsl I "~~ A r,NH.

H 0 Hd Arz

3a-d

Sa-f

Scheme I

8a-c and lid-g

Table I - Physical and analyt ica l data of the products 2a -d, 3a-d, 4a-f, 6a-d, 7a-d, Sa-g, 9a-f and IOa-e

Ar l/Arz AT) Mol. fo rmula m.p. oC Yie ld Found/(Caled) % (Mo l. WI. ) (solvent ) (%)

C H N S C6H, /4-FC6H4 CI6H I3FNzS 72 80 67.53 4.49 9.67 11.50

(284) (EtOH) (67 .50 4.57 9.85 11.2 1 ) 4-B rC6H41 C6HS C I6H 13BrNzS 87 74 55.7 1 3.8 1 8.30 9.53

(344) (AcOH ) (55.66 3.76 8. 11 9.27) C6Hs/3-N02 CoH4 C I5H 13N)02S 185 72 6 1.66 4 .10 13.40 10.20

(31 1 ) (AcOH) (6 1.73 4.18 13.50 10.21) C6HS/4-NOz C6H4 C I6H 13N)OzS !30 85 6 1.60 4.00 13. 10 10. 10

(3 11 ) (MeOH) (6 1.73 4. 18 13.50 10.2 1) C(, H s/4- FC6H4 C IsH 13FNzOS 105 87 66.R8 4. 11 8.9 1 9.9 1

(324) (MeOH) (66.66 4.0 1 8.64 9.87) 4-BrCoH41 C6HS C I8H I3BrNzOS 130 78 56.32 3.60 7 . 11 8.22

(384.9) (EtOH) (56. 11 3.37 7 .27 8.3 1) C6HS/3-NOz C6H 4 C l sH I.1N3O)S 192 81 6 1.73 3.5 1 ) 1.67 9.00

(35 1 ) (AcOH) (6 1.53 3.70 ! ) .96 9. 11 )

C6H5/4-NOz CoH4 C I8H L,N)O)S 157 85 6 1.44 3.8 1 11.96 9. 10 (351) (AcOH) (6 1.53 3.70 11.96 9.11 )

C6Hs/4-FC6H4 C6HS C~sH I7 FNzOS 105 87 72.73 4.22 6.7 1 7.96 (4 12) (MeOH) (72.8 1 4. 12 6.79 7.76)

4-B rC6H4/ChH, C6H, C2sH 17BrNzOS 90 78 63.55 3.71 5.97 6.82 (472.9) (EtO H) (63.43 3.59 5.92 6.72)

4-BrCoH4/C6HS 4-C IC6H4 C2sHI6C IN20S !02 67 59.77 3.40 5 .63 6.34 (507.4) (EtOH) (59. 12 3. 15 5.5 1 6.30)

C6HS/3-N02 C6 H4 C6HS C2sH I7N)O)S 105 65 68.2 1 3.25 9.58 7.33 (439) (AcOH) (68.33 3.87 9.56 7.28)

(-Collld)

SALAMA el al.: SYNTHESIS OF THIAZOLOPYRIMIDINON ES 175

Table I - Phys ical and analytical data of the products 2a-d, 3a-d, 4a-f, 6a-d, 7a-d, Sa-g, 9a-f and lOa-e (-Col1ld)

Compd Arl/Arz Ar) Mo l. formula m.p.oC Yield Found/(Caled) % (Mol. Wt. ) (solvent) (%)

4e C6HS/3-NOz C6H4 C6HS CzsHI7N)O)S 90 76 68.0 3.89 9.52 7.7 1 (439) (AcOH) (68.33 3.87 9.56 7.28)

4f C6HS/3-NOz C6H4 4-C IC6H4 C2sH 16CIN)O)S 197 56 63.0 3.9 1 8.00 6.99 (473.5) (AcOH ) (63.35 3.37 8.87 6.75)

Sa C6HS/4-FC6H4 4-BrC6H4 C24H loFBrN4OS 160 70 56.9 1 3.22 11.00 6.5 1 (506.9) (EtOH ) (56.8 1 3. 15 11.04 6.3 1)

51> 4- B rC6H4/C6H s 4- BrC6H4 C24 H 16Br2N40S 90 6 1 50.66 2.87 9. 11 5.34 (567 .8) (MeOH) (50.72 2.8 1 9.86 5.63)

5c 4-B rC6H4/C6H S 3-N02 C6H4 C24HI 6Br2NsO)S 90 75 53.13 2 .51 13. 14 5.6 1 (533.9) (EtOH/ (53.94 2.99 13. 11 5.99)

Dioxane) 5d C6HS/3-NOz C6H4 4- BrC6H4 Cz4 HloBrNsO)S 123 77 54.01 3.3 1 13.00 5.7 1

(533.9) (Dioxane) (53.94 2.99 13. 11 5.99) 5e CoHs/4-N02 C6H4 C6HS C24 H 17NsO)S 123 73 63.0 3.77 15. 11 7.33

(455) (AcOHl (63.29 3.73 15.38 7.03) H2O)

Sf C6HS/4-N02 C6H4 4- BrC6H4 C24 HI6BrNsO)S 155 78 54.0 2.8 1 13.00 5.71 (533 .9) (AcOH) (53.94 2.99 13.l t 5.99)

6a C6HS/4-FC6H4 C 19H IsFN20S 120 86 67.1 1 4 .60 8.1 1 9.50 (388) (Dioxane) (67 .45 4.43 8.28 9.46)

6b 4-B rC6H4/C6H s C I ~HI SBrN20S 102 72 57.23 3.50 7. 11 8.00 (398.9) (EtOH ) (57. 15 3.76 7.0 1 8.02)

6e C6HS/3-NOz C6H4 C I9Hl sN)O)S 142 94 62. 11 4 . 13 11.60 8.60 (365) (EtOH/ (62.46 4 .10 11 .50 8.76)

Dioxane) 6d C6HS/4-NOz C6H4 C I9H IsN)O)S 125 82 62. 11 4 . 11 11.60 8.50

(365) (EtOH) (62.46 4 .10 11.50 8.76) 7a C6HS/4-FC6H4 CI9HISFNzOS 96 88 67.0 4.43 8.80 9. 11

CB8) (EtOH) (67.45 4.43 8.28 9.46) 7b C6HS/4-BrC6H4 C 19H IsBrN20S 100 80 57.65 3.70 7.50 8. 11

(398.9) (AcOH ) (57. 15 3.76 7.0 1 8.02) 7e C6HS/3-N02 C6H4 C I9H1SN)O)S 162 8i 62. 17 4.67 11.22 8.80

(365) (Ac)H) (62.46 4. 10 11 .50 8.76) 7d C6Hs/4-N02 C6H4 C I9H IsN)O)S 125 R3 62 .63 4.22 11.00 8.99

(365) (AcOH) (62.46 4. 10 11.50 8.76) Sa C6HS/4-FC6H4 NHz C 1sH17FN4OS 120 79 60.45 4.7 1 15.30 8.7 1

(356) (EtOH) (60.67 4 .77 15.73 8.98) 8b C6HS/3-N02 C6H4 NHz C 1SHI 7NsO)S 178 65 56.4 1 4.43 18.70 8. 11

(383) (EtO H) (56.39 4 .5 1 18.27 8.35) 8e C6HS/3-NOz C6H4 NH2 C lsH I7NsO)S 170 6 1 56. 11 4.30 18.70 8.00

(383) (EtOH) (56.39 4.43 18.27 8.35) 8d C6HS/4-FC6H4 C6HS C24 H20FN)OS 98 79 69. 11 4.50 10.30 7.77

(417) (EtOH) (69.06 4 .79 10.07 7.67) Se C6Hsl3-N02 C6H4 CoHs Cz4H20N. O)S 172 79 64.50 4 .18 12.00 7. 11

(444) (EtO H) (64.86 4 .50 12.6 1 7 .20) 8f C6HS/3- N02 C(,H., 4-BrCJ 14 C24 H 19BrN4O)S 235 71 55.15 3.51 10.70 6.51

(522.9) (MeOH) (55 .07 3.63 10.70 6.11 ) 8g C6HS/4-N02 COH4 4-BrC6H4 C2"HI9BrN4O)S 152 75 55. 11 3.90 10.2 1 6.00

(522.9) (EtOH/ (55.07 3.63 10.70 6.(1) H2O)

9a 4- B rC6H4/C6H S NHl C 1'lH I9BrN4OS 150 80 53 .0 4.50 12.37 7.50 (430.9) (EtO H) (52.91 4.40 12.99 7.42)

9b C6HS/3-N02 C6H4 NH2 CI9HI~NsO)S 165 75 57.0 4.33 17.90 8.00 (397) (MeOH) (57.43 4 .78 17.63 8.06)

ge C6HS/4- N02 C6H4 NH2 C I9 HI9NSO)S 160 79 57.21 4 .90 17. 10 8.30 (397) (EtOH) (57.43 4 .78 17.63 8.06)

(-Col1ld)

176 INDIAN J. CHEM., SEC B, JANUARY 2003

Table I-Physical and analytical data of the products 2a-d, 3a-d, 4a-f, 6a-d, 7a-d, 8a-g, 9a-f and lOa-e (-Col1ld)

Compd Arl/Ar2 Ar) Mol. formula m.p.oC Yield Found/(Caled) % (Mol. Wt.) (solvent) (%)

9d 4-BrC/)H4/C/)H5 C6H5 C25 H22BrN)OS 152 65 61.0 4.34 8.62 6.62 (491.9) (AcOH) (60.98 4.47 8.53 6.50)

ge C6H5/3-N02 C6H4 C6H5 C25H22N4O)S 156 76 65.12 4.36 12.17 7.00 (458) (EtOH) (65.50 4.80 12.22 6.98)

9f C/)H5/3-N02 C6H4 4-BrC6H4 C2s H21 BrN4O)S 235 70 55.50 4.00 10.05 5.90 (536.9) (EtOH) (55 .87 3.91 10.43 5.96)

lOa 4-BrC6H4/C6HS NH2 CI9HI9BrN40S 163 80 53.01 53.01 4.37 12.75 (430.9) . (EtOH) (52.91 4.40 12.99 7.42)

lOb C6H5/3-N02 C6H4 NH2 CI9HI9NsO)S 145 89 57.0 4.70 17.20 8.70 (397) (EtOH) (57.43 4.78 17.63 8.06)

lOe 4-BrC/) H4/C/)H5 C6HS C2s H22BrN)OS 170 78 60.34 4.10 8.25 6.51 ( 491.9) (Dioxane) (60.98 4.47 8.53 6.50)

JOd C6Hsl3-N02 C6H4 C6HS C2sH22 N4O)S 120 83 65.61 4.33 12.11 7.00 (458) (EtOH) (65.50 4.80 12.22 6.94)

JOe C6HS/3-N02 C6H4 4-BrC6H4 C2sH21 BrN4O)S 182 81 55.60 3.12 10.00 6.11 (536.9) (MeOH) (55.87 3.9 1 10.43 5.96)

Table Il- IR and IH NMR spectral data of compounds 2,3,4,5,6,7,8,9 and 10

Compd IR (villa. , cm· l) IH NMR (8, ppm) 2a 3410,3200 (NH); 3090 (CH); 1550 (pyrimidine

moity); 1200 (C=S) 2b 3400, 3300 (NH) ; 3090 (C H); 1540 (pyrimidine

moity); 1190 (C=S) fBI 2e 3430 (br. , NH); 3 100 (CH); 1520 (py rimidine

moity); 121 0 (C=S) [B] 2d 34 10, 3180 (2 NH) ; 3 100 (CH) ; 1580 (pyrimidine

moity); 1190 (C=S) fA] 3a 3 100, 2900 (CH), 1740 (C=O) 3b 3100, 2970 (CH), 1730 (C=O) fA I

3e 3080, 2970 (C H), 1720 (C=O) fBI

3d 3060,2900 (CH), 1740 (C=O) fA]

fA] = CDCI); [B] = DMSO-d6

4a 3030,2990 (CH), 1670 (C=O)

4b 3030, 3000 (CH), 1670 (C=O)

4e 4d

4e 4f Sa

5b 5e

5d

5e Sf 6a

3100, 2990 (CH), 17 10 (C=O) 3040, 2950 (CH), 171 0 (C=O)

3100, 2990 (CH), 1710 (C=O) 3090,2940 (CH), 1670 (C=O) 3400 (NH), 3 100 (CH ), 1680 (C=O)

3300 (N H), 3080, 2990 (CH), 1690 (C=O) 3450,3 150 (NH), 3000 (CH), 1700 (C=O)

3450 (NH), 3080 (CH), 1680 (C=O)

3400 (NH), 3 100, 2990 (CH), 1700 (C=O) 3400 (NH). 3 100.2990 (CH), 1700 (C=O) 3090, 2910 (CH), 1730 (C=O)

5.1 (d, I H, H-c), 6.5 (d, I H, H-d), 7.0-8.7 (m, 9H, ArHs), 8.8 and 9.8 (br. s, 2H, 2 NH). 5.1 (d, I H, H-c), 5.2 (br. s, 2H, 2 NH), 6.6 (d, I H, H-d), 6.8-8.4 (m, 9H, ArHs). 4.8 (d, I H, H-c), 6.6 (d, I H, H-d) , 7.0-8.2 (m, 9H, ArHs), 8.9 (br. S, 2H, 2 NH).

3.0 (s, 2H, H-a), 5.3 (d, I H, H-c), 6.6 (d, I H, -d), 7.0-8.0 (m, 9H, ArHs). 3.5 (s, 2H, H-a), 5.4 (d, I H, H-c), 6.5 (d. I H, H-d), 6.8-7.4 (m, 9H, ArHs). 2.9 (5, 2H, H-a), 5.3 (s, I H, H-c), 6.7 (d. I H, H-d), 7.0-8.0 (m. 9H, ArHs).

6. 1 (d, I H, H-c), 6.9 (d, I H, H-d). 7.1-8.0 (m, 15H, ArHs and benzilic proton). 5.8 (d, I H, H-c), 6.7 (d, I H. H-d). 7.1-8.4 (m, 15H, ArHs and benzilic proton).

5.9 (d, IH , H-c), 7.0 (d, 11-1 , H-d), 7.1-8.4 (m, ISH, ArHs and bcnzilic proton) .

5.2 (d, I H, H-c), 6.1 (d, I H, H-d), 7.0-8 .0 (m, 13H, ArHs), 9.0 (br. S, I H, NH).

5.1 (d. IH , H-c), 6.1 (d, IH , H-d), 7.1-8.0 (m, 13H, ArHs), 8.5 (br. s, I H, NH). 2.5 (br. s, I H, NH), 5.2 (d, I H, H-c). 6.6 (d, I H, H-d), 7.0-8.0 (m, 13H, ArHs).

1.4 (d, 3H, H-a). 3.2 (q, I H, H-b), 5.4 (d, I H, H-c), 6.2 (d, I H, H-d). 7.0-8.1 (m, 9H, ArHs)

(-CO/lIC/)

SALAMA el al. : SYNTHESIS OF THIAZOLOPYRIMIDINONES 177

Table II- IR and IH-NMR spectral data of compounds 2, 3, 4, 5, 6, 7, 8, 9 and 10 (- COnld)

Compd. IR (vmax , cm· l)

6b 3060, 2930 (CH), 1680 (br.,C=O) 6e 3100, 2910 (CH), 1730 (C=O)

6d 7a

7b

7e

7d

8a

8b 8e 8d 8e 8f

8g

9a

9b ge 9d

ge

lOa lOb 10e

10d

3120, 2930 (CH), 1740 (C=O) 3100,2980 (CH), 1690 (C=O)

3100, 2900 (CH), 1710 (C=O)

31 10, 2980 (CH), 1720 (C=O)

3100,2970 (CH), 171 0 (C=O)

3400 (NH), 3080, 2960 (CH), 1680 (C=O)

3400 (br., NH), 3100, 2980 (CH), 1680 (C=O) 3400 (NH), 3060, 2990 (CH), 1670 (C=O) 3390 (NH), 3060, 2920 (CH), 1680 (C=O) 3400 (NH), 3060, 2920 (CH), 1680 (C=O) 3400 (NH), 3060, 2960 (CH), 1680 (C=O)

3340 (NH), 3100, 2990 (CH), 1690 (C=O)

3400 (NH), 3060, 2980 (CH), 1650 (C=O)

3400 (NH), 3060, 2920 (CH), 1680 (C=O) 3400,3200 (NH), 3060,2940 (CH), 1660 (C=O) 3400, (N H), 3060, 2920 (CH), 1680 (C=O)

3400, (NH), 3090, 2920 (CH), 1690 (C=O)

3400, (br, NH), 3090, 2940 (CH), 1670 (C=O) 3400, 3300, (NH), 2930 (CH), 1680 (C=O) 3400, (NH), 2990, 29 10 (CH), 1680 (C=O)

3410, (NH), 3080, 2920 (CH), 1660 (C=O)

10e 3400, (NH), 3070, 2960 (CH), 1700 (C=O)

inhibition zone in nm (Table III). Whatman No. 2 paper disc (0.5 cm) were impregnated with 200 mg of the tested compound. The disc was pl aced on the sur­face of the cold solid medium in petri dishes, incu­bated with the organisms and the incubated at 5°C for 1 hr to permit good diffusion and then transferred to an incubator at 28°C for 24 hr. .From the antimicrobial activity data it was found that compounds 2a, 2b, 3b, 4b, 4d, Sa, 5b, 5e, 8b and 9b were active against the microorganisms . Compounds 3b, 4b and 5b were the most active (Table III).

Experimental Section l,4-Dihydro-4,6-diaryl-pyrimidine-2-thione 2a-

d. A mixture of (0.02 mole) of the aryl methylene ace-

IH NMR (0, ppm)

1.8 (d, 3H, H-a), 3.4 (q, 1 H, H-b), 5.6 (d, 1 H, H-c), 6.4 (d, I H, H-d), 7.0-7.8 (m, 9H, ArHs)

2.2-2.9 (m, 4H, H-a), 5.4 (d, I H, H-c), 6.6 (d, I H, H-d), 7.0-8.0 (m, 9H, ArHs) 2.4-3.6 (m, 4H, H-a), 5.2 (d, I H, H-c), 6.3 (d, I H, H-d), 6.5-8.0 (m, 9H, ArHs) 2.2-2.9 (m, 4H, H-a), 5.3 (d, I H, H-c), 6.5 (d, I H, H-d), 7.0-8.1. (m, 9H, ArHs) 2. 1-3 .1 (m, 4H, H-a), 5.7 (d, I H, H-c), 6.5 (d, 1 H, H-d), 7.1-8.4 (m, 9H, ArHs) 2.0 (br. s, 2H, 2 NH), 3.6 (s, 2H, H-a), 5.0 (br. s, H, NH), 5.6 (d, IH, H-c), 6.7 (d, IH, H-d), 6.8-7.8 (m, 9H, ArH s)

2.8 (br. s, H-a), 5.0 (br. s, 2H, 2 NH), 5.2 (d, I H, H-c), 6.6 (d, I H, H-d), 7.0-8.0 (m, 13H, ArHs) . 3.1 (br. s, 2H, H-a), 4.7 (br. s, 2H, 2 NH), 5.6 (d, I H, H-c), 6.6 (d, I H, H-d), 7.0-8.0 (m, 13H, ArHs) . 1.6 (br. s, 3H, H-a), 2.0 (br. s, 2H, 2 NH), 3.9 (q , I H, H-b), 4.4 (s, IH , NH), 5.6 (d, IH, H-c), 6.7 (d, IH, H-d), 7.0-8.0 (m, 9H, ArHs).

1.4 (d, I H, H-a), 1.8 (s, I H, NH), 3.5 (s, 1 H, NH), 3.8 (q, I H, H-b), 5.0 (d, IH, H-c), 6.4 (d, IH, H-d), 6.8-7.8 (m, 14H, ArHs). 1.3 (d, 3H, H-a), 2.2 (bu, I H, NH), 3.6 (q, I H, H-b), 5.4 (d, IH, H-c), 6.6 (d, IH, H-d), 7.3-8.3 (m, 14H, ArHs).

1.7 (br. s, 2H, 2 NH), 2.6-3.6 (m, 4H, H-a), 5.6 (d, I H, H-c), 6.6 (d, IH, H-d), 7.0-8.0 (m, 14H, ArHs). 2.4-3.0 (m, 4H, H-a), 4.6 (br. s, 2H, 2 NH), 5.2 (d, I H, H-c), 6.5 (d, IH, H-d), 7.0-8.2 (m, 14H, ArHs).

tophenone derivatives 7.8 la-d, thiourea ( 1.5 g) and KOH (2 g) in ethanol (lOO mL) was heated on a water bath for 4 hr. Ethanol was evaporated to its half and the mixture was left overnight. Ethanol was distilled off and water was added to the precipitate, filtered, washed the product with water until free from alkali (Table I).

2,3-Dihydro-5H -diaryl-thiazolo[3, 2-a ]pyrimidine-3-one 3a-d. A mixture of 2 (0.01 mole), chloroacetic ac id (0.01 mole) fused sodium acetate (2 g) in acetic acid (10 mL) and acetic anhydride (7 mL) was re­fluxed for 2 hr, allowed to cool and then poured gradually while stirring into cold water. The solid ob­tained was filtered off and crystallized from proper solvent (Table I).

178 INDIAN J. CHEM., SEC 8 , JANUARY 2003

Table Ill-The preliminary screening of biological activity for the prepared compounds

Compd B. slibti/is E. coli C. a/bicalls A. niger P. aeruginosa P. mirabi/is K. pneumonia S. cerevisia

2a ++ ++ + 2b +++ ++ ++ 3b ++ ++ + + +++ +++ + + 4b ++ +++ + + + ++ + + 4d ++ + + ++ + +++ +++ Sa ++ + + + + Sb +++ +++ + ++ ++ + + +++ Se + +++ ++ + + 8b ++ + + 9b + + +

(+++) = Highly ~en sit i ve (inhibition zone 1.2-1.5 mm); (++) = Fairly sensi ti ve (inhibit ion zonc 0.Y-l.2 mm); (+) = ~ht ly sensit ivc (inhibition zone 0.6-0.9 mm).

2-(Arylmethylene)-2,3-dihydro-51l-5,7-diaryl-thia­zolo[3,2-a ]pyrimidine-3-ones 4a-f.

Method A: A mixture of 3 (0.01 mole), aromatic aldehyde (0.01 mole) and sodi um acetate (l g) in ace­tic anhydride (6 mL) was refluxed for 1 hr, poured into cold water and the precipitate was filtered and crystallized from the proper solvent (Table I).

Method B: A mixture of 2 (0.01 mole) , chloroacetic acid (0.01 mole) and the appropriate aldehyde (0.01 mole) and fused sodi um acetate (2 g) in 20 mL acetic acid and acetic anhydride (14 mL) was refluxed for 3 hr, al lowed to cool, then poured into cold water and the product was filtered and crystallized (Table I).

2-(Arylhydrazino )-2,3-dihydro-5H -5,7 -diaryl­thiazolo[3,2-a]pyrimidin-3-one Sa-f. The aromatic amine (0.0 1 mole)was dissolved in conc. HCI (3 mL) and water (2 mL), cooled to - 10°C and trea ~ed with of sodium nitrite (0.7 g) in water (5 mL). The diazo­tized amine was added gradually while stirring to cooled solution of compound 3 (0.01 mole) in pyri ­dine (20 mL). The reaction mixture was refrigerated fo r 30 min and then diluted with water, the product obtained was filtered off, washed with water and crys­tallized from the proper solvent (Table I) .

2,3-Dihydro-2-methyl-(5H)-5,7-diaryl-thiazolo­[3,2-a]pyrimidine-3-ones 6a-d . Compounds 6 were prepared by [he same method used for compounds 3, but by using 2-bromopropionic acid instead of chloroacetic acid (Table I) .

2,3-Dihydro-6H-6,8-diaryl(1,3)thiazino[3,2-a]pyri­midin-4-ones 7a-d. Compounds 7 were prepared by the same method used for compounds 3, but by using 3-bromopropionic acid instead of chloroacetic acid (Table I).

3,4-Dihydro-4,6-diaryl-pyrimidin-2-ylthio aceta­hydrazide 8a-c. To a mixture of compounds 3 (0.005 mole) and hydrazine hydrate (0.006 mole) was

added ethanol ( 15 mL), and the mix ture refluxed for 2 hr. The reaction mixture ollowed to cool and poured into cold water. The so lid product obtained was col­lected, washed with little ethanol and crystalli zed from the proper solvent (Table I ).

3,4-Dihydro-4,6-diaryl-pyrimidin-2-yl-thio acetanilide 8d-g.

Method A: 5,7-Diaryl-2,3-dihydrothiazolo[3,2-a]pyrimidin-3-ones 3 (0.005 mol ) and the amine (0.005 mole) were reflux ed in ethanol (15 mL) for 2 hr. The reaction mixture was allowed to cool and then poured into water. The solid product obtained was collected, washed with little ethanol and crystal­lized from the proper solvent (Table I ).

Method B: 4,5-Diaryl-pyrimjdine-2-thiol 2 (O.OJ mole) and a-chloroacetanilide9

.tO (0.0 I mole) were

refluxed for 2 hr in ethanolic KOH (3 g in 15 mL), allowed to coo l and filtered to remove KCI. After concentration of the mi xture, the sol id product formed was collected, washed with little water and crystall­lized from the proper solvent (Table I ).

2-(3,4-Dihydro-4,6-diary I-pyrimidin-2-yl-thio )pro­pionyUlydrazide 9a-c. To a mixture of compounds 6 (0.005 mole) and hydrazine hydrate (0.006 mole) was aclded ethanol (15 mL) and the mixture was refluxed for 2 h. The reaction mixture allowed to cool, then poured into water. The solid formed was collected, washed with little ethanol and crystallized from the proper solvent (Table I).

Compounds 9d-f were prepared by the same method used for compounds 9a-c but using aniline or p-bromoanilne instead of hydrazine hydrate (Table I) .

3-(3,4-Dih ydro-4,6-diary 1-pyrimidin -2-Y I-thio )pro­pionylhydrazide lOa-b. To a mixture of compounds 7 (0.005 mole) and hydrazine hydrate was added (15 mL) of ethanol and the mixture refluxed for 2 hr. The reaction mixture was allowed to cool, then

SALAMA el at.: SYNTHESIS OF THIAZOLOPYRIMIDINONES 179

poured into water. The solid product formed was collected, washed with little ethanol and crystallized from the proper solvent (Table I).

3-(3,4-Dihydro-4,6-diaryl-pyrimidin-2-yl-thio)pro­pionylanilide lOc-e. Compounds lOc-e were prepared by the same method used for compounds lOa,b but using aniline or p-bromoaniline instead of hydrazine hydrate (Table I).

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