Novel Synthesis of Norepinephrine Thiocarbamides

 

D.T.Tayade¹, A.A.Dhande^2*

 

ABSTRACT:

A new series of norepinephrine thiocarbamides was synthesized by the interactions of norepinephrine with ethyl and phenyl isothiocyanates in acetone medium, to isolate 1,1-(1R)(3,4-Dihydroxyphenyl)-2-ethylthiocarbamidoethanol [DHPETC] and 1,1-(1R)(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol [DHPPTC] respectively. The products thus synthesized in these reactions were characterized on the basis of conventional elemental analysis, chemical characteristics and through IR, PMR, CMR and Mass spectral analysis.

 

 

 

INTRODUCTION:

The literature survey reveals that from last four decades numerous advances, theories and new concepts in the physical as well as chemical study of benzenoid and non-benzenoid, heteroacyclic and heterocyclic compounds were studied^1-5. These compounds have their own identity and importance in the life sciences due to their variety of applications in medicinal, agricultural, pharmaceutical, industrial, biotechnological and biochemical sciences^6-10. If we think about the drugs we can define the history of medicine by these compounds.

 

 

 

 

 

 

 

 

 

In the view of the utility of these compounds in various fields and as a part of research work, presently being undertaken in this laboratory in the synthesis of nitrogen, nitrogen and sulphur containing heteroacycles and heterocycles and to investigate their medicinal, pharmaceutical, agricultural, industrial, biotechnological and biochemical significance^11-18, hence interactions of norepinephrine was carried out with ethyl and phenyl isothiocyanates to synthesized yet new series of norepinephrine thiocarbamides.

 

 

 

 

NorepinephrineAlkyl Isothiocyanate Norepinephrine                                                                                                thiocarbamide

Where, -R = -ethyl and -phenyl.

 

 

 

RESULT AND DISCUSSION:

A) Synthesis of 1,1-(1R)-(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol:

1,1-(1R)-(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol was synthesized by refluxing norepinephrine with phenyl isothiocyanate in acetone medium for 4 hours. After completion of reaction, two different layers of 1,1-(1R)-(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol and acetone are detected. After distillation of acetone the product is isolated which is recrystalized from ethanol to get white colour crystalline solid flakes with m.p. 64⁰C.

 

 

 

Nroepinephrine         Phenyl1,1-(1R)-(3,4-Dihydroxyphenyl)-
                                        isothiocyanate-2-phenylthiocarbamido                                                                   ethanol

Where, -R = -ethyl and -phenyl.

 

Properties of 1,1-(1R)-(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol:

The compound is white colour crystalline solid flakes, C₁₅H₁₆N₂O₃S with m.p. 64⁰C.It gave positive test for nitrogen and sulphur.Desulphurised with alkaline plumbite solution. Soluble in boiled sodium hydroxide, sulphuric acid, 1,4-dioxane, hydrochloric acid and nitric acid and was sparing soluble in boiled water, ethanol, acetone and benzene.Formedpicrates having melting point 99⁰C. Elemental analysis (%): Found (Calculated) C- 62.78 (66.30), H-7.49 (8.21), N-7.71 (8.81), S-8.82 (11.26), O-13.20 (14.48).FTIR spectrum (v cm^-1):-The IR spectrum of compound was carried out in KBr pellets on Shimadzu IR spectrometer^19-24. 2773.64-2565.33 (Aliphatic C-H stretching), 2902.87 (Aromatic C-H stretching), 1955.82 (N-C=S stretching), 1598.99-1815.02 (C=N stretching), 1897.95 (C=S stretching), 3008.95 (Two N-H stretching), 3201.83 (Alcoholic O-H stretching), 3201.83 (Two phenolic O-H stretching), 1172.72-1244.09 (C-O stretching), 1529.55-1294.24 (Aliphatic –H bending), 1070.49-611.43 (Aromatic –H bending). PMR spectrum :The PMR spectrum of a compound was recorded in CDCl₃+ DMSOd₆ on Bruker Advance-II 400 NMR spectrometer^19-20,25-30. This spectrum distinctly displayed the signals, due to five aromatic protons in the range at δ 7.5093 – δ 7.2882 ppm of phenyl group, three aromatic protons in the range at δ 7.1326 - δ 7.0910 ppm, two phenolic –OHprotons at δ 3.3568 ppm, alcoholic –H at δ 3.65, two amino –NH protons at δ 9.7422 ppm, methyne (-CH) proton at δ 2.5192, two disteriotopic methylene protons at δ 2.5103 ppm.

From the above chemical characteristics, elemental and spectral analysis the compound was assigned the structure as 1,1-(1R)-(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol.

 

 

1,1-(1R)-(3,4-Dihydroxyphenyl)-2-phenylthiocarbamidoethanol.:

 

Similarly, 1,1-(1R-(3,4-Dihydroxyphenyl)-2-ethylthiocarbamidoethanol was synthesized by interacting norepinephrine and ethyl isothiocyanate in acetone medium.

 

B) Synthesis of 1,1-(1R)-(3,4-Dihydroxyphenyl)-2-ethylthiocarbamidoethanol:

The compound is white colour crystalline solid flakes, C₁₁H₁₆N₂O₃S with m.p. 36⁰C. It gave positive test for nitrogen and sulphur.Desulphurised with alkaline plumbite solution. Soluble in boiled sodium hydroxide, sulphuric acid, 1,4-dioxane, hydrochloric acid and nitric acid and was sparing soluble in boiled water, ethanol, acetone and benzene. Formed picrates having melting point 115⁰C. Elemental analysis (%): Found (Calculated) C- 57.11(60.23), H-8.63(10.21), N-8.88(9.82), S-10.16(12.26), O-15.22(18.46). FTIR spectrum (v cm^-1):-The IR spectrum of compound was carried out in KBr pellets on SHIMADZU IR spectrometer^19-24. 2974.23-2756.28 (Aliphatic C-H stretching) 3242.34 (Aromatic C-H stretching) 2052.26 (N-C=S stretching) 1512.19 (C=N stretching) 1678.07 (C=S stretching) 3334.92 (Two N-H stretching) 3444.87 (Alcoholic O-H stretching) 3604.96 (Two phenolic O-H stretching) 1244.09 (C-O stretching) 1369.46 (Aliphatic –H bending) 1066.84-630 (Aromatic –H bending).PMR spectrum : The PMR spectrum of a compound was recorded in CDCl₃+ DMSOd₆ on Bruker Advance-II 400 NMR spectrometer^19-20,25-30. This spectrum distinctly displayed the signals, due to three aromatic protons at δ 7.3219 ppm, two phenolic –OH protons at δ 3.8147 ppm, alcoholic –H at δ 3.3698, two amino –NH protons at δ 8.2708 ppm, methyne (-CH) proton at δ 1.2363, two disteriotopic methylene protons at δ 3.1857 and δ 3.2033, methyl protons at δ 1.0678 and methylene protons at δ 2.5157 ppm.

 

From the above chemical characteristics, elemental and spectral analysis the compound was assigned the structure as 1,1-(1R)-(3,4-Dihydroxyphenyl)-2-ethylthiocarbamidoethanol.

 

 

1,1-(1R)-(3,4-Dihydroxyphenyl)-2-ethylthiocarbamidoethanol.

 

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Received on 21.07.2018         Modified on 19.08.2018

Accepted on 25.08.2018         © AJRC All right reserved