Synthesis of 4-Amino-5-Substitutedthiocarbamido-N-[2-(Diethylamino)Ethyl]-O-Anisamides

 

R.D. Thombare*, D.T. Tayade

Department of Chemistry, Government Vidarbha Institute of Science and Humanities, Amravati 444 604, Maharashtra State, India.

*Corresponding Author E-mail: rupalidthombare30@gmail.com

Recently in this laboratory a novel series of 4-amino-5-substituted thiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamides was successfully synthesized by the interactions of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-o-anisamide with various thioureas in isopropanol, acetone medium.  The structural determination and justification of the synthesized compounds were done on the basis of chemical characteristics, elemental analysis and spectral studies

 

 

 

INTRODUCTION:

Synthetic chemistry is one of the main streams for progress and expanding a various branch of science in the field of pharmaceutical science.  Throughout the preceding years pharmaceutical chemistry had been huge progress not only on terms of development of novel methodologies for construction of carbon-carbon and carbon-hetero atoms bonds but also in terms of development of new strategies, catalysts, reagents and technologies. It is well-known from the compounds containing amide moiety as a functional group have been β found to acquire donor properties and show a wide range of biological activities. A broad spectrum of biological activity is described to be associated with a number of heterocyclic compounds.

 

3Anisamide nucleus is gainful targeted case of liposome in a potent carrier for targeted doxorubicin to human prostate cancer cells.  An anisamide derivative holds high affinity for sigma receptors and used for the treatment of human malignancies including prostate cancer.  For the prevention and therapy of metabolic diseases o-anisamide equivalent are effective. The solvent free reaction condition had been study in recent years¹. Usually solvent free reactions are economical and take shorter time, easier separation and purification in conventional reaction condition². These reactions are environmental having simple work-up with high product yield and prevent delusive byproducts, so the great task towards chemist is to develop non-hazardous synthetic methodology for the organic synthesis. The main target of these basic principle are to explore an alternative reaction conditions and reaction medium to accomplish the preferred chemical transformations with least byproducts or waste generation as well as to eliminate the conservative organic solvent. The literature survey proved that 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-o-anisamide, benzamide derivatives are known for their anti-inflammatory and immunomodulatory^3-4, anti-tumoral⁵, anti-sychotic⁶ and anti-allergic activities. The antimicrobial activity of various substituted N-[(1-morpholinobezyl)]benzamide compounds studied against various organisms such as s. aureus, b. subtilis, E. coli and p. aeruginosa by disc diffusion method. New series of thiadiazoles, thiadiazines and dithiazines were synthesized by exploring the synthetic applications of -amino, -cyano, -halo etc. and their antimicrobial, antifungal, antibacterial, analgesic physiochemical parameters^7-14 were studied.  4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-o-anisamide, thiocarbamide and their derivatives showed agricultural, medicinal, biological, pharmaceutical, industrial significances and applications.  By considering all this facts this research scheme was designed.  The synthesis of 4-amino-5-substituted-thiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamideswere carried out by the interactions of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-o-anisamide and various thioureain isopropanol medium. The main objective of the work is to synthesize a novel series of 4-amino-5-substitutedthiocarbamido-N-[2-(diethylamino) ethyl]-o-anisamides. The newly synthesized compounds may possess more practical utility and also the new thiocarbamido substituent may enhance the potency of the compound and can also be used as drug. The tentative reaction is depicted below (Scheme-I).

 

Scheme-I

Where R = -H, -methyl, -ethyl, -phenyl, -allyl.

 

 

Synthesis of 4-amino-5-phenylthiocarbamido-N-[2-(diethylamino) ethyl]-o-anisamide

4-Amino-5-phenylthiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamidewas synthesized by interacting4-amino-5-chloro-N-[2-(diethylamino)ethyl]-o-anisamidewith phenylthiourea in isopropanal medium for 4 hours on water bath pale yellow crystals were separated out at room temperature and filtered and dried.  Yield 92 %, m.p.  219˚C  The probable reaction and mechanism is depicted below,

 

REACTION:

 

 

PROPERTIES:

It is yellow crystalline solid having melting point 219˚C.  It gave positive test for nitrogen and sulphur.  It was desulphurized by alkaline plumbite solution which clearly indicate the presence of C=S group¹⁵.  It was soluble in water, ethanol, DMSO-d⁶ while insoluble in carbon tetrachloride, chloroform, benzene, dioxane, petroleum ether.  It formed picrate having melting point 180˚C.

 

Elemental Analysis:

This result of elemental analysis is gives Carbon[60.00%(found),60.72%(calculated)],Hydrogen[06.11%(found),06.98%(calculated)], Nitrogen[16.22%(found),16.86%(calculated)],Sulphur [06.91%(found),07.71%(calculated)]. From the analytical data the molecular formula was found to be C₂₁H₂₉N₅O₂S_.

 

IR Spectrum:

The IR spectrum of compound was carried out in KBr pellets, the important absorption are correlated as (cm^-1) 3354.00 N-H Stretching, 2925.10 C-H stretching, 1643.10 C=O stretching, 1158.00N-C=S stretching, 1019.00 C-N stretching.

 

 

PMR Spectrum: 

The PMR spectrum of compound was carried out in CDCl₃ and DMSO-d₆.  This spectrum distinctly displayed the signals due to Ar-H protons at protons at d 9.7295 ppm, Ar-H (phenyl) protons at protons at d 8.3210-6.4616 ppm, –NH proton at δ 3.8288 ppm, NH₂ protons d 3.3938 ppm, -OCH₃ protons at d 2.5186-2.4854 ppm, -CH₃ protons at d 1.2027-0.9794 ppm. By considering above chemical characteristics and spectral analysis the compound was assigned the structure as 4-amino-5-phenylthiocarbamidomido-N-[2-(diethylamino)ethyl]-o-anisamide.

 

Similarly, 4-amino-5-substitutedthiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamide (IIIb), 4-amino-5-methylthiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamide (IIIc), 4-amino-5-allyl-thiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamide (IIId), were prepared by the interactions of  4-amino-5-chloro-N-[2-(diethylamino)ethyl]-o-anisamide (I), with thiourea(IIa), methylthiourea(IIc), allylthiourea (IId) respectively by the above mentioned method and enlisted in Table No. II-5

 

Table No. I-1

Sr. No.	4-Amino-5-substitutedthiocarb- amido-N-[2-(diethylamino)ethyl]-o-anisamide (III)	Yield (%)	M.P. ˚C
1.	4-Amino-5-thiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamide	200	90
2.	4-Amino-5-methylthiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamide	212	92
3.	4-Amino-5-allylthiocarbamido-N-[2-(diethylamino)ethyl]-o-anisamide	225	84

 

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Received on 26.03.2017         Modified on 30.03.2017

Accepted on 12.04.2017         © AJRC All right reserved