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(KAJ)Kurdistan Academation JournalSept 2003, 2(1) Part ,A A

20032(1)

The cyclo condensation of 3-(N-methyl

acetamido) -2- chloro pyridine gives

N- methyl-2-arylpyrido [2,3-b] [1,5]

thiazepin-4[5H] ones[10]. Treatment of

2-chloronicotinic acid with methyl amino

acetonitrile hydrochloride and carbon

disulphide gave pyrido [3,2-f- [1,4]

thiazepine derivateves[11]. Cylic mono

sulphidediamideNN, - ethylen thio

diacetamide prepared in good yields from

the reaction ofNN, -ethylene bis-

(chloro acetamide) with hydrous sodium

sulphide[12]. Unsubstituted 10,11 and 13-

membered ring cyclic disulphide

diamides result from reaction of ethylene

diamine and -3, 3- dithiodipropionic acid

in the absence of solvent[13,14] .

High yeild medium ring of

thiocycloalkanes were obtained from the

reaction of sodium sulphide with

dibromo alkanes[15]. Herein, we describe

in detail the synthesis of a novel nine

membered ring cyclic mono

sulphidediamide, and its sulphone. From

the reaction ofNN, (o-phenylene) bis

(chloro acetamide) (II) and hydrous

sodium sulphide Na2S.9H2O

Scheme (I).

Results and DiscussionNN, -(o-phenylene) bis (chloro

acetamide)(II) was synthesized from

treatment of ethylchloroacetate (I) with

(o-phenylene diamine).

The I.R. Spectrum [Tab. (1)]

showed bands at 3310 and 1580 cm-1

corresponding to N-H stretching and

bending respectively, indicates that

primary amine was converted to

secondary amine. Whilst a second bandat 1670 cm-1 could be attributed to the

carbonyl group of the secondary amide

this low absorption frequency due to the

meseomeric effects in amide .

The 1H-N.M.R. spectrum [Tab.(2)]

gave a singlet at (3.7) ppm for four

protons of two methylene groups with

a broad single at (4.4) ppmcorresponding to one proton of N-H

group, while the ortho substituted protons

of two phenyl groups appeared as a

multiplet at (6.6)ppm. Therefore,

according to spectral studies and

elemental analysis the product could be

NN, -(o-phenylene) bis (chloroacet

amide)(II).The reaction of compound (II) with

hydrous sodium sulphide (Na2S.9H2O)

leads to formation of a cyclic mono

sulphidediamideNN, -(o-phenylen)

thiodiacetamide (III) in good yield.

The I.R. spectrum for the product (III)

[Tab(1)] gave a strong absorption band

at 1670 cm

-1

for C=O Stretching of

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20032(1)

secondary amide, another strong band

was appeared at 3310 cm-1 for N-H

stretching .In this spectrum, the

absorption peaks for C-Cl was

disappeared and a new weak band

appeared at (600,700) cm-1 for C-S

Stretching .

The 1H-N.M.R spectrum [Tab.(2)]

gave a singlet at (3.0) ppm for four

protons of two methylene groups with a

multiplet at (6.6) ppm for four protons

of phenyl group, while a broad singlet at

(4.4) ppm due to N-H proton.

25

I

II

Scheme (1)

IIIIV

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20032(1)

of the compound (III) with potassium

permanganate in %80 acetic acid , after it

was noted that other oxidizing agent,

sodium periodate and hydrogen peroxide

provided a mixture of sulphoxide and

sulphone.

The sulphone was indicated by

the I.R. and elemental analysis . The I.R.

spectrum showed two extra bands at 1320

cm-1 and 1035 cm-1 indicating the

formation of sulphone (SO2).

Table (1) : The I.R. data of the prepared compounds in (cm

-1

)

Compounds N-H C=O C-O C-Cl O=S=O

I .. 1760 1220 750

II 3300,1580 1670 . 750 ..

III 3300,1580 1970 . .

IV 3300,1580 1670 .. . 1320,1035

Table (2) : 1H.n.m.r data of the prepared Compounds

Solvent DMSO-d6

compounds PPM Intensity Multiplicity Assignment

I 1.2

4.0

3

4

t

m

-CH- of methyl groups

-CH2- of two methylen groups

II 3.7

4.4

6.6

2

1

2

s

b

m

-CH2- of two methylen groups

-NH- proton

4-H aromatic protons

III 3

4.4

6.6

2

1

2

s

b

m

-CH2- of two methylen groups.

-NH- proton

4-H aromatic protons

Hetrocyclic compound containing

sulphur and amide group known to have

antibacterial activity [16].

The prepared compounds are

similar to these compounds and they were

showed antibiotic activity .It has been

noted that the sulphone compound (IV)

was more sensitive than thio compound

(III) [Tab(3)].

This difference in biological

activity could be due to the attachment of

sulphur atom to two oxygen atoms with

high electronegativity, which make the

carbonsulpher bond, in sulphon

derivative, weaker than corresponding

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20032(1)

thio compound. Therefore, we were

proposed a simplified mechanism for

inactivation of microbial organism by the

prepared thiol and sulphone compounds

(scheme (2)).

X = Ph

n= 0,2

Table: (3) Antimicrobial activity of

prepared compounds

Compounds E. coil Sta. Aur

Control - -

III + -

IV ++ -

Control =KBr

+= inhibition (3.5)mm

++ = inhibition(5.5)mm

- = not inhibition

Experimental

Melting point were determined

with a Gallenkamp electrothermal

melting point apparatus .Infrared spectra

were recorded by using Unicam Model

Sp3-300S Spectrometer. The proton

nuclear magnetic resonance were obtained

using Varian A-60 instrument with

tetramethyl silane were performed by theanalyzer MOD 110 6 supplied by Carlo

Erba type.

1.NN, -(o-phenylene)bis(chloro

acetamide) [12] II

A solution of (o-phenylendiamine

(4gm, 0.036 mole) in ethanol

(60 ml,99%)was added to a solution of

ethylchloro acetate (1) (8 ml. 9.06 gm.

0.075 mole) heating the mixture under

reflex for 9 h . after cooling crush ice

was added until the green precipitate was

formed. The precipitate was filtrated and

washed with water and dried in a

vacuum desicator over CaCl2, , yielding

the product as a green solid after

recrestalized in water. (1gm. 25%),m.p= (160-161)Co ; I.R. (KBr), max .

3300, 1580, 1970, 760 cm-1; Elemental

analysis: Calculated for C10H10O2N2Cl2:

C,44;H,4.03;N,10.7Found:C,44.02;H,4.03

;N,10.5%.

2.

NN, -(o-Phenylene)

thiodiacetamide[12]

(III)

27

Scheme (2)

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20032(1)

To a stirred hot solution

(7080 Co )ofNN, -(o-phenylene) bis

(chloro acetamide)(II), (0.65 gm., 0.0025

mole ) in ethanol (13.9 ml) , a solution of

Na2S.9H2O (0.6 gm ,0.0025 mole) in

distilled water (4ml) was added. The

mixture was stirred with heating till

yellow precipitate formed. The solid

product was filtered off, and dried in

vacuo over CaCl2 yielding the product as

yellow Solid after recrestalized in water.

(0.2 gm , 36% ) m. p. (280 Co dec.), I.R.

(KBr) max(3300), 1580,1970 cm-1,

Elemental analysis: Calculate for

C10H10O2N2S: C, 54.05; H, 4.5, N, 12.6:Found: C, 53.09; H,4.20; N, 12.5%.

3.NN, -(o-phenylene)Sulphone

diacetamide[12]. (IV)

A solution of potassium permanganate

(0.18gm, 0.0012 mole) in water (5 ml)

was added to a stirred solution of

NN, -

(o-phenylene) thiodiacetamide (0. 11 gm )

0.0005 mole in acetic acid (5 ml , 80%)

during 30 minutes at room teperature .

The mixture was neutralized with 10%

Na2 CO3, A brown solid was provided

after recrestalized in water. (0.05 gm,

25%), m.p= 300C0 dec., I. R.(KBr) max

3300, 1580 , 1670 , 13 20 , 1035 cm

-

;Elemental analysis: Calculated for

C10H10O4N2S;C,47.24;H,3.93,N,11.02:

Found : C, 47.03; H, 3.35; N, 11.01 % .

References

1. Lawson J. K.; Easley W. K.and Wanger W. S., five-membered

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heterocyclic compounds, Organic Synthesis, IV, 1963, 892.

2. Tarbell D. S and Weaven C., Chemistry of five-membered

Heterocyclic compounds,J.Am. Chem. Soc, 1941, 63, 2939.

3. Sumrell G. and Hornbaker E. D., chemistry of five-membered

Heterocyclic compounds,J. Org. chem. 1953, 23, 1219.

4. Crombie R. L. and Ridey D. D., Chemistry of seven-membered

Heterocyclic compounds,J. chem., 1976, 32, 2777.

5. Ando W. and Huang L. An Efficien, one-pot synthesis,J. Synth.

1986, 139.

6. Rauter S. and Clarke H. T. Thhe Action of formal dehyde upon Cystein,

J. Am. Chem. Soc. 1937, 59, 200.

7. Kyrides L. p., phthalyl chloride,J. org. chem. 1982, 47, 4005.

8. Hawaizy F. E. M. Sc. Thesis, University of Salahadin (1998).

9. Rahimzadeh M., Heravi M. M. and Abedince A. Synthesis of Novel

Heterocyclic system,J. Sci. I. R. Iran 1998, 9, 163.

10. Couture A. and Grand C. A New synthetic RouteJ. org. chem. 1990,

55, 4337.

11. Dolling W. and Hartung H. A facile Synthesis.Eur.J. org. chem.

1998, 1237.

12. Hussain F. H. and Hadi K. S. Chemistry of Nine-membered

Heterocyclics.Zanco, 1990, 3, 7.

13. Owen T. C and Fayad J. M. A ten-membered RingJ. org. chem, 1970,

35, 3198.

14. Owen T. C and Fayad J. M., Heterocyclic compounds.J. org. chem.

1973, 36, 937.

15. Singh A. and Regen S. L, Heterocyclic Compounds. Synthetic

Communication; II. 1981, 5, 409.

16. Al-Hamadi F. M., M. Sc. Thesis, University of Baghdad 1993.

( - )

/ / /

/ / /

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20032(1)

NN,- - ) (

NN, ) ( - - )(

( Na2S.9H2O ( NN,- ) -(

.

.

NN, ) - ( -

/ / / / / /

NN,) ( -

NN, ) ( ) (

Na2S.9H2O ) )NN,) ( -

.

.

30

20/8/20021/6/2003.Received 20/8/2002 Accepted 11/6/2003.

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