110206-9393-ijbas-ijensff

7/29/2019 110206-9393-IJBAS-IJENSff

1/8

International Journal of Basic & Applied Sciences IJBAS-IJENS Vol: 11 No: 06 1

I J E N S2011 IJENSDecemberIJENS -IJBAS9393-600211

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, [email protected]

ABSTRACTSynthesis 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

INTRODUCTIONPyranopyridothiazole 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 & DISCUSSIONIn 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

. The1H NMR spectra[19] revealed a signals at = 8-

7,5 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 =8.5-7ppm (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

7/29/2019 110206-9393-IJBAS-IJENSff

2/8



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) .

EXPERIMENTALAll 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, cooledand 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).

7/29/2019 110206-9393-IJBAS-IJENSff

3/8



Table 1: Characterization of compounds (1 10).

Comp.

No.

M.p.

C

Yield

%Colour

M. formula

(M.Wt.)

Analysis % calcd (found) M.S.

C H N S

1214-216

65 YellowC25H11N3O4S

(449.44)66.81

(66.80)2.47

(2.42)9.36

(6.38)7.12

(7.15)449

2 284-286

70 Yellow C25H15N5O2S(449.44)

66.80(66.82)

3.37(3.38)

15.15(15.60)

7.12(7.10)

449

3188-

19060

Brownish

yellow

C25H19N5O4S

(485.52)

61.85

(61.86)

3.94

(3.94)

14.42

(14.40)

6.60

(6.62)485

4158-

16010

Pale

yellow

C13H11N5O4S

(333.32)

46.84

(46.85)

3.33

(3.34)

21.01

(21.00)

9.62

(9.60)333

5162-164

30 VioletC18H19N2O2S

(454.42)67.06

(67.04)5.63

(5.65)8.69

(8.70)8.69

(8.70)454

6174-

1768 Violet

C18H19N2O2SI

(454.42)

66.64

(66.69)

6.22

(6.20)

8.64

(8.66)

8.63

(8.60)454

7164-166

15 BrownC14H17N2O2SI

(404.36)41.58

(41.60)4.21

(4.20)6.93

(6.95)7.92

(7.90)404

8

166-

168 50

Pale

violet

C19H21N2O2SI

(468.45)

48.72

(48.70)

4.49

(4.50)

5.98

(6.00)

6.84

(6.80) 468

9154-

15625

Deep

violet

C15H19N2O2SI

(418.29)

43.06

(43.05)

4.54

(4.54)

6.70

(6.70)

7.65

(7.66)418

10146-148

10Deepviolet

C15H19N2O2SI(418.29)

43.06(43.08)

4.54(4.55)

6.70(6.72)

7.65(7.64)

418

7/29/2019 110206-9393-IJBAS-IJENSff

4/8



Table 2: IR and1H NMR spectral data of the prepared compounds

Comp. No. IR, cm-1 1

H NMR, ppm

1 3500-3400(NH, NH2 ),

2220 (CN), 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 ).

2 3490-3400(NH, NH2 ),2210(CN), 1690(C=O),

8-7.5(m, 11H, Ar-H+ ), 4.5-4(br, 3H,NH,NH2 ).

3 3500-3400(NH, NH2 ),

2205(CN), 1695(C=O)

8-7.5(m, 11H, Ar-H+

), 4.5-4(br, 8H,

2NH2 , 2CONH2 ).

4 3495-3410(NH, NH2 ),

2215(CN), 1695(C=O),

8-7.5(m, 2H, Ar-H+

), 4.5-4(br, 8H,

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 5-10The 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 absorptionband 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).

7/29/2019 110206-9393-IJBAS-IJENSff

5/8



Table (3) : Absorption spectra of cyanine dyes in 95% ethanol

Compound No. max (nm) max (mol-1

cm-1

)

5

741.50

514.00

92687

64250

6

300

295

37523

36937

7 30700 38375

8

51850

33400

64812

41750

9

54150

4620032250

67687

5775040313

10

54150

45700

31200

67687

57125

39000

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 McFarlandstandards 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.

7/29/2019 110206-9393-IJBAS-IJENSff

6/8



Table 4: Antibacterial activity of tested compounds against bacteria. *

Microorganism Tested compound

start 1 2 3 4 5 6 7 8 9 10

S. aureus 0 0 0 0 0 8 0 0 0 0 7

E. coli 0 0 0 0 0 0 0 0 0 0 0

K. pneumoniae 0 0 0 0 0 0 0 0 0 6.5 0

Ps. Aerugenosa 0 0 6.5 7 6.5 7 0 0 0 0 6.5

*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, 4-

diamino-6-(2, 5-dimethoxybenzyl)-5-methylpyrido[2, 3-d]pyrimidine. J. Med. Chem. 1980; 23(3): 327-

329.[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.

7/29/2019 110206-9393-IJBAS-IJENSff

7/8



[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.

7/29/2019 110206-9393-IJBAS-IJENSff

8/8



Scheme 1

N

S

O

CN

Ph

O

O

Ph

CN

O

( 1 )

N

SO

CN

Ph

O

NH

Ph

CN

H2N

N

S

O

CONH2

Ph

O

NH2

Ph

CONH2

H2N

N

SO

CONH2

O

NH2

CONH2

H2N

N

S

EtOOC

O

( 2 )

( 3 )

(10)

+

N

S

EtOOC

HC

NI-

N

S

EtOOC

HC NI-

+

N

S

EtOOC

HC N NI-

+

N

S

EtOOC

N I-+

N

S

EtOOC

N I-

+

N

S

EtOOC

NI-

+

( 4 )

( 5 )

( 6 )

( 9 )

( 8 )

( 7 )

CH2C

CONH2

CN

PhCH

C

COOEt

CN

PhCH

C

CN CN PhCH

C CONH2

CN

N

CH3

+

I-

N

CH3

+

I-N

+

I-

+I-N

N+

I-

110206-9393-ijbas-ijensff

Documents