International Journal of Basic & Applied Sciences IJBAS-IJENS Vol: 11 No: 06

Synthesis, Spectral Behavior and Biological Activity of Some New Fused/Isolated Polyfunctionally Heterocyclic Compounds
Abduallah Suliman Al-Ayed(a) and Hussain Ali Soleiman(a, b)
(a)

Department of Chemistry, Al-Rass Faculty of science and Arts, Qassim University, Kingdom of Saudi Arabic (b) Department of Chemistry, Aswan Faculty of science, South Valley University, Egypt salayedabdualla1@yahoo.com

ABSTRACT
Synthesis and increase the degree sensitization of some new fused/isolated polyfunctionally heterocyclic compounds via interaction of 4,5-dihydro-2-ethylacetate-4-oxothiazole with aryl or alkyl cinnamonitrile, quinoline (isoquinoline) or pyridine and/or quinoline or ()-picoline ethiodide .The structure of the synthesized compounds have been characterized on the basis of their elemental analysis in IR, 1H NMR and Mass spectral data. The synthesized compounds have been screened in vitro for their antimicrobial activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus.

Keywords: Pyranopyridothiazole, Apocyanine, monomethine

INTRODUCTION
Pyranopyridothiazole derivatives are biologically interesting molecules that have established utility in the pharmaceutical and the industries compounds with these ring systems have a wide application range of biological activities and pharmacological actions [1-5] , antibacterial [6, 7] inhibitory activity [8-10] . Otherwise Pyranopyridothiazole derivatives found a wide uses in the chemistry of dyes and pigments such as laser technologies [11-13] , in colour and non colour photographic processes [14] , in optical disk as recording media [15] and inks [16[ . However, the structure activity relationship studies revealed that synthesized compounds is also an important in the many different fields. In connection of our previous work [17], in this article the attempts have been made to synthesize a new fused and isolated heterocyclic compounds, beside the some compounds of cyanine dyes such as apocyanine and monomethine cyanine dyes.

RESULTS & DISCUSSION

In continuation of our programmer to synthesis some new fused/isolated polyfunctionally heterocyclic compounds the interaction of 4, 5-dihydro-2-ethylacetate-4-oxothiazole with aryl and/or alkyl cinnamonitrile to yield compound 1, 2, 3 and 4 respectively. The structure of compounds 1, 2, 3 and 4were established based on ir spectrum[18 ] which revealed bands for NH, NH2 at 3500-3400 cm-1 , for CN at 2220 cm-1 , for C=O at 1700-1680 cm-1 . The 1H NMR spectra[19] revealed a signals at = 87,5 ppm for (m, 11H, Ar-H+ ); at =4.5-4 ppm for NH2 , NH; at =8-7.5 ppm for (m, 11H, Ar-H+ ); at =8-7.5 ppm (m, 10H, Ar-H+ ), at =4.5-4 ppm for (br, 8H, 2NH2 , 2CONH2 ) ; and at =8-7.5 ppm for (m, 2H, Ar-H+ ), at =4.5-4 ppm for (br, 8H, 2NH2 , 2CONH2 ) of compounds1, 2, 3 and 4 respectively. The mass spectrum [20] of compounds 1, 2, 3 and 4 showed a molecular ions at m/z=449, 449, 485 and 333 which are agreement with its molecular formula C25 H11 N3 O4 S, C25 H15 N5 O2 S, C25 H19 N5 O4 S and C13 H11 N5 O4 S respectively (C.F. Table 2). On other hand we desired to increase the degree of sensitization of 4,5-dihydro-2-ethylacetate-4-oxothiazole through the interaction with quinoline (isoquinoline) and /or pyridine in ethanolic solution and under few drops triethylamine as catalyst to yield 4[4(3)]apocyanine dyes (5, 6, 7). The structure of 5, 6 and 7 were established based on IR spectrum[18 ] which revealed bands for C=O at 1700 cm-1 , 1H NMR [19] revealed a signals at =8.5-7 ppm (m, 6H, Ar-H+ , and/or m, 4H, Ar-H+ ), at =5.6 ppm for (s, 1H, CH olefinic), at =3.2 ppm for (q, 2H, CH2 ), at =2.3 ppm for (s, 2H, CH2 ) and at =2.0 ppm for (t, 3H, CH3 ) . The mass spectrum [20] of compounds 5, 6 and 7 showed a molecular ions at m/z =454, 454 and 404 which are agreement with its molecular formula C18 H19 N2 O2 SI, C18 H19 N2 O2 SI and C14 H17 N2 O2 SI, respectively (C. F. Table 2) . Similarly 4, 5-dihydro-2-ethylacetate-4-oxothiazole reacts with quinoline and/or ()-picoline ethiodide in ethanolic solution under few drops of triethylamine as catalyst to yield 4[2(3)]monomethine cyanine dyes (8, 9 and 10) . The structure of 8, 9 and 10 were established based on IR spectrum [18] which revealed bands for C=O at 1700 cm-1 . The 1H NMR spectra[19]revealed a signals at =8.5-7 ppm (m, 5H, and/or 4H, Ar-H+ ), at =5.8 ppm (s, 1H, CH olefinic), at =4.4-4.2

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ppm (q, 4H, 2 CH2 ), at =2.4-2.2 ppm (s, 4H, 2CH, 2CH2 ) and at =1.6 ppm (t, 3H, CH3 ). The mass spectrum[20] of compounds 8, 9 and 10 showed a molecular ions at m/z=468, 418 and 418 which are agreement with its molecular formula C19 H21 N2 O2 SI, C15 H19 N2 O2 SI and C15 H19 N2 O2 SI, respectively, (C. F. Table 2) .

EXPERIMENTAL
All melting points are uncorrected; IR spectra were measured as KBr pellets on a pye Unicam sp 1000 spectrophotometer. 1H NMR spectra were recorded in DMSO- d6 at 200 MHz on a varian Gemini NMR spectrometer, using TMS as internal reference; the chemical shifts are expressed as Values (ppm). Mass spectra were obtained on a Shimadzu GCMS- Qp 1000 EX mass spectrometer at 70 ev. Elemental analyses were carried out at the micro analytical center of Cairo University.

Synthesis of cyanopyranopyridothiazole derivative (1)

Equimolar ratios of ethanolic solution of 4, 5-dihydro-2-ethylacetate-4-oxothiazole (0.01 mol) and benzylidene ethylcyanoacetate (0.01 mol) in the presence of triethylamine as catalyst was refluxed for 4h. The reaction mixture was filtered, cooled and solid product that was separated upon concentrating was filtered and crystallized from ethanol, Table (1).

Synthesis of aminothiazole derivative (2)

Equimolar ratios of ethanolic solution 1 (0.01mol) and benzylidene malononitrile (0.01mol) in the presence of triethylamine as catalyst was refluxed for 5h. The reaction mixture was filtered, cooled and solid product that was separated upon concentrating was filtered and crystallized from ethanol, Table (1).

Synthesis of iminothiazole derivative (3)

Equimolar ratios of ethanolic solution 1 (0.01mol) and amidoacrylonitrile (0.01mol) in the presence of triethylamine as catalyst was refluxed for 5h. The reaction mixture was filtered, cooled and solid product that was separated upon concentrating was filtered and crystallized from ethanol, Table (1).

Synthesis of phenyliminothiazole derivative (4)

Equimolar ratios of ethanolic solution 1 (0.01mol) and amidocinnamonitrile (0.01mol) in the presence of triethylamine as catalyst was refluxed for 5h. The reaction mixture was filtered, cooled and solid product that was separated upon concentrating was filtered and crystallized from ethanol, Table (1).

Synthesis of 4[4(3)apocyanine dyes (5, 6, 7)

Equimolar ratios of ethanolic solution of 1 (0.01mol) and quinoline (isoquinoline) and / or pyridine ethiodide under three drops of triethylamine as catalyst was refluxed for 6h. The reaction mixture was filtered, cooled and solid product that was separated upon concentrating was filtered and crystallized from ethanol, Table (1).

Synthesis of 4[2(3)]monomethine cyanine dyes (8, 9, 10)

Equimolar ratios of ethanolic solution of 1 (0.01mol) and quinaldine and / or () picoline ethiodide under three drops of triethylamine as catalyst was refluxed for 6h. The reaction mixture was filtered, cooled and solid product that was separated upon concentrating was filtered and crystallized from ethanol, Table (1).

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Table 1: Characterization of compounds (1 10).

Analysis % calcd (found) M.S. Comp. M.p. Yield M. formula Colour No. % (M.Wt.) C H N S C 214C25H11N3O4S 66.81 2.47 9.36 7.12 1 449 65 Yellow 216 (449.44) (66.80) (2.42) (6.38) (7.15) 284C25H15N5O2S 66.80 3.37 15.15 7.12 2 70 Yellow 449 286 (449.44) (66.82) (3.38) (15.60) (7.10) 188Brownish C25H19N5O4S 61.85 3.94 14.42 6.60 3 60 485 190 yellow (485.52) (61.86) (3.94) (14.40) (6.62) 158Pale C13H11N5O4S 46.84 3.33 21.01 9.62 4 10 333 160 yellow (333.32) (46.85) (3.34) (21.00) (9.60) 162C18H19N2O2S 67.06 5.63 8.69 8.69 5 30 Violet 454 164 (454.42) (67.04) (5.65) (8.70) (8.70) 174C18H19N2O2SI 66.64 6.22 8.64 8.63 6 454 8 Violet 176 (454.42) (66.69) (6.20) (8.66) (8.60) 164C14H17N2O2SI 41.58 4.21 6.93 7.92 7 15 Brown 404 166 (404.36) (41.60) (4.20) (6.95) (7.90) 166Pale C19H21N2O2SI 48.72 4.49 5.98 6.84 8 50 468 168 violet (468.45) (48.70) (4.50) (6.00) (6.80) 154Deep C15H19N2O2SI 43.06 4.54 6.70 7.65 25 9 418 156 violet (418.29) (43.05) (4.54) (6.70) (7.66) 146Deep C15H19N2O2SI 43.06 4.54 6.70 7.65 10 10 418 148 violet (418.29) (43.08) (4.55) (6.72) (7.64)

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International Journal of Basic & Applied Sciences IJBAS-IJENS Vol: 11 No: 06

Table 2: IR and 1H NMR spectral data of the prepared compounds 1 IR, cm-1 H NMR, ppm Comp. No. + 1 3500-3400(NH, NH2 ), 8-7.5(m, 8H, Ar-H ), 5.6(s, 1H, CH 2220 (CN), 1700(C=O) olefinic), 3.2(q, 4H, 2CH2), 2.3(s, 2H, CH2 ), 2.0(t, 6H, 2CH3 ). 2 3490-3400(NH, NH2 ), 8-7.5(m, 11H, Ar-H+ ), 4.5-4(br, 3H, 2210(CN), 1690(C=O), NH,NH2 ). 3 3500-3400(NH, NH2 ), 8-7.5(m, 11H, Ar-H+ ), 4.5-4(br, 8H, 2205(CN), 1695(C=O) 2NH2 , 2CONH2 ). 4 3495-3410(NH, NH2 ), 8-7.5(m, 2H, Ar-H+ ), 4.5-4(br, 8H, 2215(CN), 1695(C=O), 2NH2 , 2CONH2 ). 5 1675(C=O) 8-7.5(m, 8H, Ar-H+ ), 5.6(s, 1H, CH olefinic), 3.2(q, 4H, 2CH2), 2.3(s, 2H, CH2 ), 2.0(t, 6H, 2CH3 ). 6 1700(C=O) 8-7.5(m, 8H, Ar-H+ ), 5.6(s, 1H, CH olefinic), 3.2(q, 4H, 2CH2), 2.3(s, 2H, CH2 ), 2.0(t, 6H, 2CH3 ). 7 1685(C=O) 8-7.5(m, 6H, Ar-H+ ), 6(s, 1H, CH olefinic), 3.4(q, 4H, 2CH2), 2.5(s, 2H, CH2 ), 2.2(t, 6H, 2CH3 ). 8 1670(C=O) 8-7.5(m, 8H, Ar-H+ ), 3.3-3.1(q, 4H, 2CH2 ), 2.4(t, 6H, 2CH3 ), 2(s, 2H, CH2 ). 9 1700C=O) 8-7.5(m,7H, Ar-H+ ), 3.3-3.1(q, 4H, 2CH2 ), 2.4(t, 6H, 2CH3 ), 2(s, 2H, CH2 ). 10 1690(C=O) 8-7.5(m, 7H, Ar-H+ ), 3.3-3.1(q, 4H, 2CH2 ), 2.4(t, 6H, 2CH3 ), 2(s, 2H, CH2 ). Relation between molecular structure and spectral behavior of the synthesized compound dyes 5-10
The electronic absorption spectra of apocyanine dyes (5, 6, 7) in ethanol showed absorption bands with strong hyposochromic shift on increasing the conjugation of the heterocyclic quaternary residue . Thus, the absorption spectra of apocyanine dyes 5, 6 and 7 showed an absorption band hyposochromically shifted respectively .This can be attributed to a more extensive delocalization within the respective heterocyclic quaternary system, Scheme (1) Table (3). On the other hand, the electronic absorption spectra of monomethine cyanine dyes (8, 9 and 10) in 95% ethanol showed absorption bands bathochromically shifted depending upon the nature heterocyclic quaternary salts. Thus, the absorption spectra of compounds 8 showed an absorption band bathochromically shift if compare with compounds 9 and 10. This can be attributed to lower extensive -delocalization within the respective heterocyclic quaternary salt, Scheme (1), Table (3).

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Table (3) : Absorption spectra of cyanine dyes in 95% ethanol Compound No. max (nm) 741.50 514.00 300 295 max (mol-1 cm-1 ) 92687 64250 37523 36937

30700 51850 33400 54150 46200 32250 54150 45700 31200

38375 64812 41750 67687 57750 40313 67687 57125 39000

10

Antibacterial activity
Four pathogenic clinical isolates ( Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus) were provided from Al-Rass General Hospital, Department of Microbiology. 1 ml of fresh nutrient broth culture (18 h) was adjusted to 0.5 McFarland standards corresponding to approximately 1.0 x 108 CFU/ml and loaded into sterile Petri dish, and then 19 ml of sterile nutrient agar at 40oC was added. Plate was set to solidify. The antimicrobial activity was determined by the paper disc diffusion method [21] with slight modification. Sterilized filter papers (6 mm diameter) were soaked in desired compound (in methanol as solvent) for 24 h to saturate. Then left for 6 h to dry. Sterile filter paper discs were placed on each of the nutrient agar plates earlier seeded with the different test bacteria. Plates containing disc saturated with methanol, were used as negative controls. All the plates were then incubated at 37C for 24 h. Following incubation, antimicrobial activity was determined by measurement of the zone diameters of inhibition against the test organisms. The data in Table (4) indicate that the synthesized compounds 2, 3, 4and10 are active against the Ts. Acrugenosa, the synthesized 5and 10 are active against the S. aureus and the synthesized compound 9 is active against the K. pneumonia.

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Table 4: Antibacterial activity of tested compounds against bacteria. * Microorganism start 1 S. aureus E. coli K. pneumoniae Ps. Aerugenosa 0 0 0 0 0 0 0 2 0 0 0 Tested compound 3 0 0 0 4 0 0 0 5 6 7 8 8 0 0 0 0 0 0 0 9 0 0 10 7 0 0 6.5

0 0 0 0 6.5 0

0 6.5 7 6.5 7 0 0 0

*diameter of disk=6 mm, No inhibition zone=0 (6 mm). The authors are thankful to Research Center, Scientific Research Deanship, QASSIM UNIVERSITY.

Conclusion:

The electronic absorption spectra of apocyanine dyes showed an absorption band

hyposochromically shifted .This can be attributed to a more extensive -delocalization within the respective heterocyclic quaternary system. On the other hand, the electronic absorption spectra of monomethine cyanine dyes showed an absorption band bathochromically shift. This can be attributed to lower extensive -delocalization within the respective heterocyclic quaternary salt. Also, antimicrobial activity was determined by measurement of the zone diameters of inhibition against the test organisms. The data indicate that the synthesized compounds are active against the Ts. Acrugenosa, the S. aureus and the K. pneumonia.

REFERENCES
[1] Gangjee A, Aldair O, Queene S F. Pneumocystis Carinii and Toxoplasma gondii dihydrofolate reductase inhibitors and antitumor : Synthesis and biological activity of 2,4-diamino-5-methyl-6[(monosubstituted-amino)-methyl]-pyrido[2,3-d]pyrimidines. J . Med. Chem. 1999; 42(13):2447-2455. [2] Grivsky E M, Lee S; Sigal C W, Duch D S, Nichol C A. Synthesis of antitumor activity of 2, 4diamino-6-(2, 5-dimethoxybenzyl)-5-methylpyrido[2, 3-d]pyrimidine. J. Med. Chem. 1980; 23(3): 327329. [3] Matulenko, M. A.; Lee C.-H.; Jiango, M.; Free, R. R.; Cowart, M. D.; Bayburt, E. K.; Didomenico, S. Jr.; Gfesser, G. A.; Gomtsyan, A.; Zheng, G. Z.; Mckie, J. A.; Stewart, A. O.; Yu, H.; Kahlhass, K. L.; Alexander, K. M.; McGaraughty, S.; Wismer, C. T.; Mikusa, J.; Marsh, K. C.; Snyder, R. D.; Diehl, M. S.; Kowaluk, E. A.; Jarvisa, M. F.; Bhagwata, S. S.; Bioorg. Med. Chem. 2005, 13, 3705. [4]Zheng, G. Z.; Lee, C.-H.; Patt, J. K.; Perner, R. J.; Jlang, M. O.; Gonitsyan, A.Matulenko, M. A.; Mao, Y.; Koenig, J. R.; Kim, Muchmore, S.; Yu, H.; Kohlhaas, K.; Alexander, K. M.; McGaraughty, S.; Chu, K. L.; Wismer, C. T.; Mikusu, J.; Jarvis, M. F.; Marsh, K.; Kowaiuk, E. A.; Bhagwata, S. S.; Stewarta, A. O. Bioorg. Med. Chem. Lett.2001, 11, 2071. [5] Gfesser, G. A.; Bayburt, E. K.; Cowart, M.; DiDomenico, S.; Gomtsyan, A.; Lee, C.-H.; Stewart, A. O.; Jarvis, M. F.; Kowaluk, E. A.; Bhagwat, S. S.; Eur. J. Med. Chem. 2003, 38, 245. [6]Soleiman, H. A.; Khalafallah, A. K.; Abdelzaher, H. M.; Synthesis of some new fused/spiro of benzindole derivatives and their biological activity.J. Chin. Chem. Soc., 2000, 47, 1267-1272. [7]Soleiman, H. A.; Koraim, A. I. M.; Mahmoud, N. Y.; Synthesis of new fused heterocyclic compounds of benzpyrid-4-one derivatives and their some biological activity. J. Chin. Chem. Soc., 2004, 51, 553-560.

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[8] Gfesser, G .A.; Bayburt, E .K.; Cowart, M.; DiDomenico, S.; Gomtsyan, A.; Lee, C H.; Stewart, A .O.; Jarvis, M .F.; Kowaluk, E .A.; Bhagwat, S .S.; Synthesis and structure-activity relationships of 5-heteroatom-substituted pyridopyrimidines as adenosine kinase inhibitors. Eur. J. Med.Chem. 2003, 38, 345. [9] Ravi Kanth, S.; Venkat Reddy, G.; Hara Kishore, K.; Shanthan Rao, P.; Narsaiah, B.; Surya Narayana Murthy, U.; substitutedamino-5-trifluoromethyl 2, 7-disubstituted pyrido[2,3-d] pyrimidines and their antibacterial activity. European Journal of Medicinal Chemistry . Eur. J. Med.Chem. 2006, 41, 1011. [10] Soleiman, H. A., Some fused/isolated heterocyclic of pyrimidine, -lactam, thiazolidine and triazine derivatives. The open catalysis journal, 2010, 3, 107-115. [11] Dgdyusha, G.G.; Zubarovskii, V.M., Moreiko, V.M.; Parhomskaya, O.V.; Sych, E.D.; Tikhonov, E.A. and Khodot, G.P. 1978 USSP Patent 568318: Appln (1975): 215763; Chemical Abstract 1979, 90, 46509j. [12] Inagaki, Y.; Adachi, K. and Yabe, M., 1988 Ger Offen. DE 3819688 (C1G. 11B7124) Appl. 87 143 46809; Chemical Abstract 1988, 111, 68030a. [14] Ikeat, T.; Takei, H. and Yamashita, H., 1985 Eur Pat. Appl. Ep. 144091 (1C031128); Chemical Abstract 1985, 104, 12987p. [15] Sun, Shuqing; Chen Ping; Zheng, Deshui (Proc. SPIE-Int. Soc. Opt. Eng. 1998, 3562 (Optical Storage Technology), 11, 16 (Eng.), SPIE. Chemical Abstract 1999, 130, 175194w. [16] Onodera, Akira; Ninomia, Hidetaka; Ghya, Hidenobu; Ishibashi, Daisuke; Komamura, Tawara, Katoh, Katsunert; Tanaka, Tatsuc; Morimoto, Ritoshi (Konica corporation, Japan). Eur. Pat. Appl. Ep 7C9, 53j (C1CO9B 55100), 23 Apr. 1997. Jp Appl. 96172, 257, 27 Mar 1996, 55 pp. (Eng). Chemical Abstract 1997, 126, 344433t. [17] Alayed, A. S.: Candian Journal on Chemical Engineering& Technology, 2011, Vol. 2, No.5. [18] Silvevstein, R. M.; Bassler, G. C. and Morrill, T. C.: Spectrometric Identification of organic compounds 4th Ed.Jotin Wiley& Sons, New York, 1981. [19] L. G. Wale Jr. Organic Chemistry, 4th Edn (Uper Saddle River, NJ:Prentice Hall, 1999) 544. [20] Porter, G. N. and Baldas, J. : Mass spectrometry of heterocyclic compounds, Wiley, New York, 1971. [21] Doughari, J. H. ; El-mahmood, A. M.and Manzara, S. Studies on the Antibacterial Activity of Extracts of Carica Papaya L. Afr. J. Microbiol. Res., 2008, pp. 37-41.

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CN CN Ph O Ph O N S O CN O Ph H 2N CN CONH2 NH2 N S H2N CONH2 O CH 2 C CN EtOOC CONH2 S EtOOC

+

NH N S Ph O O Ph

CONH2 NH 2 N S H 2N O Ph CONH2

(2)
PhCH CN C CN COOEt CN C CN PhCH C

(1)
PhCH

(3)

CONH2 I N HC N
+

(4)
N S O NI
+

(10)

EtOOC S

N -

N I-

CH 3 EtOOC S N
+

+N

N I

HC

(9) (5)
EtOOC S N
+

N I

N I I -

N -

CH3 EtOOC S N
+

HC

EtOOC

N S

(8)

N I

(6)

(7)

+N

Scheme 1

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