Molbank 2005, M401

http://www.mdpi.net/molbank/

 

Synthesis of 4-tert-butyl-2-(thiomorpholin-4-ylmethyl)phenol, and 4-tert-butyl-2,6-bis(thiomorpholin-4-ylmethyl)phenol

 

A. Ma. Vel¨¢zquez1, L.Torres1, R.Gonz¨¢lez1, I.Mart¨ªnez1, A.Valencia1, A.Pecina1, L.Torres, I.Menconi1, L.Mart¨ªnez1, A.Ram¨ªrez1, R.Hern¨¢ndez1, R.L¨®pez-Castañares2 , O.Olvera-Neria3, E.Angeles*1,

 

1) Facultad de Estudios Superiores Cuautitl¨¢n, Universidad Nacional Aut¨®noma de M¨¦xico,

2) Facultad de Qu¨ªmica de la UAEM,

3) Instituto de Ciencias B¨¢sicas e Ingenieria, Universidad Aut¨®noma del Estado de Hidalgo

 

e-mail: [email protected]

 

Received: 2 April 2004 / Accepted: 31 May 2004 / Published: 1 July 2005

 

Keywords: phenol, thiomorpholine

 

 

4-tert-butyl-2-(thiomorpholin-4-ylmethyl)phenol (2) and 4-tert-butyl-2,6-bis(thiomorpholin-4-ylmethyl)phenol (3) were prepared from 4- tert-butylphenol (1) and thiomorpholine and formaldehyde (37%) in methanol as solvent . A solution of methanol (50 mL) and 4-tert-butylphenol (1.49 g, 9.92 mmol) 1 was prepared and and heated at 40 ¡ãC for 15 minutes, after that  a solution of thiomorpholine (2.0 g, 20.7mmol) and formaldehyde (1.50 mL, 20.15 mmol) in methanol were added. When the addition was completed, the reaction mixture was stirred at reflux for 24 hrs. The solvent was eliminated using rotavapor and reaction mixture was poured into water and extracted with ethyl acetate. Chromatography on silica gel (30/70 EtOAc/n-hexane) afforded two crystalline products 2 and 3 (5% and 35 % yield).

 

4-tert-butyl-2-(thiomorpholin-4-ylmethyl)phenol (2)

 

Melting Point: 85-87 C¡ã (methanol, uncorrected).

 

IR (CHCl3 film; cm-1): 3456 (O-H); 3197 (Csp2-H Ar); 2886 (Csp3-H).

 

1H-NMR (300 MHz; CDCl3): ¦Ä= 10.33 (1H, s, OH); 7.18 (1H, dd, J= 8.4Hz, 2.7Hz); 6.94 (1H, d, J=  2.7Hz); 6.74 (1H, d, 8.4Hz); 3.70 (2H, s, Ar-CH2); 2.82 (4H, m, -S-CH2-); 2.71 (4H, m, -N-CH2-); 1.27 (9H, CH3). 

 

13C-NMR (75 MHz; CDCl3): ¦Ä= 155 (C); 141.8 (C); 125.60 (CH); 125.49 (CH); 119.77(C); 115.47 (CH); 62.51 (Ar-CH2); 54.36 (-N-CH2-); 33.84 (C); 31.48 (CH3); 27.79 (-S-CH2-). 

 

MS (FAB; m/z, %): 266(80%); 265 (100%); 163(45%).

 

Elemental Analysis: Calculated for C15H23NOS: C, 67.88%; H, 8.73%; N, 5.28%; O, 6.03%; S, 12.08%. Found: C, 67.58%; H, 8.75%; N, 5.41%; O, 6.09%; S, 12.01%.

 

4-tert-butyl-2,6-bis(thiomorpholin-4-ylmethyl)phenol (3)

 

Melting Point: 95-97 C¡ã (methanol, uncorrected).

 

IR (CHCl3 film; cm-1): 3403 (O-H); 3089 (Csp2-H Ar); 2986 (Csp3-H).

 

1H-NMR (300 MHz; CDCl3): ¦Ä=10.69 (1H, s, OH); 7.09 (2H, s); 3.71 (4H, s, Ar-CH2); 2.86 (8H, m, -S-CH2-); 2.76 (8H, m, -N-CH2-); 1.27 (9H, CH3). 

 

13C-NMR (75 MHz; CDCl3): ¦Ä=153.6 (C); 141.14 (C); 125.79 (CH); 121.22 (C); 58.81 (Ar-CH2); 54.42 (-N-CH2-); 33.78 (C); 31.47 (CH3); 27.74 (-S-CH2-). 

 

MS (FAB; m/z, %): 381 (35%); 278 (100%); 175 (50%).

 

Elemental Analysis: Calculated for C20H32N2OS2:  C, 63.11%; H, 8.47%;  N, 7.36%; O, 4.20%; S, 16.85%. Found: C, 63.42%; H, 8.51%; N, 7.29%; O, 4.25%; S, 16.91%.

 

Acknowledgements

The authors wish to acknowledge to PAPIIT/UNAM Projects No IN205902 and IN207705 and ALPHARMA SA de CV, by partially support this work. We would like to thank C.Barajas, F.Sotres, P.Garc¨ªa, D.Jim¨¦nez from FESC-UNAM and Rosa I.del Villar M., Oscar Yañez and Georgina Duarte from  USAI-UNAM for their skillful technical assistance and DGSCA-UNAM for their support. As a part of Project C¨¢tedra Qu¨ªmica Medicinal of FESC-UNAM.

 

 

References

1. Biava, M., Fioravanti, R., Porretta, G.C., Deidda, D., Maullu, C., Pompei M. Biorg.& Med.Chem.Lett. 1999, 9, 2983-2988.

2. Teipel, S.; Griesar, K.; Haase, W.; Krebs, B. Inorganic Chemistry  1994,  33,  456-64.

3. Hodgkin, J.H., Aust .J. Chem., 1984, 37, 2371-2378.

 

 

 

 

 


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