SciELO - Scientific Electronic Library Online

 
vol.56 número4HPLC DETERMINATION OF ETOPOSIDE IN INJECTABLE DOSAGE FORMSSYNTHESIS OF β-DIKETIMINATE DERIVATIVES OF ZINC ALKOXIDES: CATALYTIC PROPERTIES FOR RING OPENING POLYMERIZATION índice de autoresíndice de assuntospesquisa de artigos
Home Pagelista alfabética de periódicos  

Serviços Personalizados

Journal

Artigo

Indicadores

Links relacionados

Compartilhar


Journal of the Chilean Chemical Society

versão On-line ISSN 0717-9707

J. Chil. Chem. Soc. vol.56 no.4 Concepción dez. 2011

http://dx.doi.org/10.4067/S0717-97072011000400013 

J. Chil. Chem. Soc., 56, No 4 (2011), págs: 884-886

 

HIGHLY EFFICIENT AND VERSATILE ACETYLATION OF ALCOHOLS, PHENOLS AND AMINES CATALYZED BY METHYLENEDIPHOSPHONIC ACID (MDP) UNDER SOLVENT-FREE CONDITIONS

 

MINHAO XIE*, HONGYONG WANG, JUN WU, YONGJUN HE, YALING LIU, PEI ZOU

*Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, P. R. China. e-mail: hxydc@swu.edu.cn


ABSTRACT

Methylenediphosphonic Acid (MDP) was found to be a simple, cheap and reusable heterogeneous catalyst for the acetylation of structurally diverse alcohols, phenols and amines with acetic anhydride under solvent-free conditions at room temperature. This method showed preferential selectivity for the acetylation of the amino group in the presence of hydroxyl group. The method is very mild and the yields were in excellent.

Keywords: Bisphosphonic acid, MDP, Solvent-free, Acetylation.


INTRODUCTION

With increasing environmental concerns and the regulatory constraints faced in the synthesis of valuable industrial and pharmaceutical compounds, the development of new synthetic methods and reactions using new and environmental friendly reagents is becoming more attractive. The acetylation of alcohols is an important and _E-mail: xiemh0704@sina.com Fax number: +086 510 85513113 frequently used transformation in organic synthesis 1. The most commonly used reagent combination for this reaction uses an acid anhydride in the presence of an acid or base catalyst 2. The various catalysts developed for acetylation include the use of Bu3P 3, metal triflates such as Sc(OTf)3 4, TMSOTf 5, Sc(NTf2)3 6, Cu(OTf)2 7, In(OTf)3 8, Bi(OTf)3 9, ZrO(OTf)210; p-toluenesulfonic acid 11, Nafion-H 12, Montmorillonite K-10 and KSF clay 13, yttria-zirconia 14, NBS 15, Zeolites 16, 3-nitrobenzeneboronic acid 17, La(NO3)3 18 (NH4)25H05PW12O40 19, H5PV2W10O40 20 and molecular iodine 21. The catalysts suffer from certain drawbacks. They are rather expensive or moisture sensitive. Nevertheless, there is still a great demand for acid catalysts to generate esters under mild conditions.

Bisphosphonic acids are commonly used as antiresorptive agents for the treatment of osteoporosis. Methylenediphosphonic Acid (MDP) is cheap, stable and the simplest organic bisphosphonic acid with usefulness in a wide range of applications, such as a coordination ligand of inorganic meterials 22, a bone imaging agent to delineate areas of altered osteogenesis in clinic 23 and a heavy-metal decorporating agents 24. Due to its unique physical and chemical properties such as acidity, selectivity, thermal stability, solubility and security, we have explored its catalytic activity and discovered it can catalyze acetylation of alcohols, phenols and amines very efficiently. Here we report a mild, efficient and environmentally friendly method for the acetylation of alcohols, phenols and amines using acetic anhydride in the presence of MDP under solvent-free conditions at room temperature. The catalyst was reused five consecutive times giving excellent yields.

EXPERIMENTAL

All commercial chemicals were used as received. Methylenediphosphonic Acid (MDP) was provided by Jiangyuan Pharmaceutical Factory. Products are all known compounds and their structures were established through IR, MS and 1H NMR by comparing of their physical and spectra data with those in the literature. IR spectra were recorded on BRUKER TENSOR 27 FT-IR spectrometer using KBr pellets. Mass spectra were recorded on a Waters Q-TOF-MS apparatus. 1H NMR spectra were run on a BRUKER AVAVCE 400 spectrometer using CDCl3 or DMSO-D6 as solvent.

General Procedure of Acetylation Reaction

Method A: Alcohol (2.5 mmol), MDP (0.25 mmol) and Ac2O (3.0m mol) were added and stirred continued at room temperature for the appropriate time (monitored by TLC). After completion, the reactant was filtered and water (10mL) was added to the filtrate. The mixture was extracted with ethyl acetate (10mLx2) and the combined organic layer was washed with saturated NaHCO3 (10mLx2), brine (10mL), dried (Na2SO4) and concentrated to give the pure liquid product (Scheme 1).


Method B: Alcohol (2.5 mmol), MDP (0.25 mmol) and Ac2O (3.0 mmol) were added and stirred continued at room temperature for the appropriate time (monitored by TLC). After completion, the reactant was quenched with cold water (10mL). The mixture was filtered to give the pure solid product.

Chemoselective N-acetylation of bifunctional substrates using MDP

The substrate containing -NH2 and -OH groups (2.5 mmol) was treated with Ac2O (2.5 mmol) in the presence of MDP (0.25 mol ) under neat conditions at room temperature. After the end of the reaction, the reactant was quenched with cold water and extracted with ethyl acetate. To concentrate the organic layer, the product was obtained without further purification.

Reuse and Recycling of the Catalyst

The reuse and recycling properties of the catalysts were tested by acetylation of 2-phenylethanol. MDP was filtered from the reaction mixture, reused to catalyse the next reaction without any treatment.

RESULTS AND DISCUSSION

Several examples illustrating the novel and rapid procedure for acetylation of alcohols, phenols and amines are presented in Table 1. The reaction conditions were standardised after conducting the acetylation of 2-phenylethanol with Ac2O using various amounts of MDP at room temperature without any solvent (entries 4, Table 1). The acetylation of 2-phenylethanol with 1.2 equiv. of Ac2O in presence of 1, 2.5, 5, 10 mol % MDP afforded 24, 43, 67, 97% yields in 2 h respectively, while 5% yield was obtained without MDP at the same reaction conditions. Encouraged by the success of this reaction, various primary, secondary and tertiary alcohols, phenols and amine were subjected to acetylation. Several primary and secondary alcohols underwent the acetylation reactions in excellent yields (entries 1-8, Table 1). It is very interesting to note that tertiary alcohols such as t-butanol and 2-methyl-2-butanol (entries 9 and 10, Table 1) can also be acetylated with satisfactory yields and there was no elimination product in the mixture as shown by IR, MS and 1H NMR analysis, the yield of entry 9 is 98%, however, it is 70% using Gd(OTf)3 as a catalyst 25. Phenols are acetylated smoothly without any side products observed (entries 11-18, Table 1). We found that this method was also suitable for the acetylation of amines and they were converted to their corresponding acetamides respectively in excellent yields (entries 19 and 20, Table 1).


To expand the scope of the present reaction further, we performed a new study in which the selective acetylation of the bifunctional substrates containing -NH2 and -OH groups using our catalyst under solvent-free conditions. The results are collected in Table 2. Only N-acetate product was obtained with one equivalent of acetic anhydride and no O-acetate product was discovered under these conditions. The hydroxy group of the substrates did not take part in the acetylation because -NH2 group has more nucleophilicity than -OH group. MDP could be easily recycled, it was utilized repeatedly over five times in acetylation of 2-phenylethanol with the yield being unchanged (Table 3).




CONCLUSION

In conclusion, MDP is an efficient catalyst for the acetylation of various alcohols, phenols and amines under solvent-free conditions. The advantages include low cost, high yields, cleaner products, selective acetylation of bifunctional compounds containing —NH2 and —OH groups, ease of operation, and with increasing environmental concern, absence of organic solvents and no need for energy in the present method will make it environment friendly and promising in practical production.

ACKNOWLEDGMENTS

We acknowledge financial support by the Social Development Foundation of Jiangsu (grant No. BE2008633) and the Medical Research Project of Jiangsu (grant No.H200736).

 

REFERENCES

1. A.S. Frannklin, J. Chem. Soc. Perkin Trans 1, 3537, (1999).         [ Links ]

2. R.C. Larock, "Comprehensive Organic Transformations", VCH, New York, 1989.         [ Links ]

3. E. Vedejs, N.S. Bennett, L.M. Conn, S.T. Diver, M. Gingras, J. Org. Chem. 58 , 7286, (1993);         [ Links ]

E. Vedejs, S.T. Diver, J. Am. Chem. Soc. 115, 3358, (1993).         [ Links ]

4. K. Ishihara, M. Kubota, H. Kurihara H. Yamamoto, J. Am. Chem. Soc. 117, 4413, (1995).         [ Links ]

5. P.A. Procopiou, S.P.D. Baugh, S.S. Flack, G.G.A. Inglis, J. Org. Chem. 63, 2342, (1998).         [ Links ]

6. K. Ishihara, M. Kubota, H. Yamamoto, Synlett 2, 265, (1996).         [ Links ]

7. P. Saravanan, V.K. Singh, Tetrahedron Lett. 40, 2611, (1999).         [ Links ]

8. K.K. Chauhan, C.G. Frost, I. Love, D. Waite, Synlett 2, 174, (1999).         [ Links ]

9. A. Orita, C. Tanahashi, A. Kakuda, J. Otera, J. Org. Chem. 66, 8926, (2001).         [ Links ]

10. M. Moghadam, S. Tangestaninejad, V. Mirkhani, I. Mohammadpoor-Baltork, M. Babaghanbari, M. Zarea, L. Shariati, S.A. Taghavi, J. Iran. Chem. Soc. 6, 523, (2009).         [ Links ]

11. A.C. Cope, E.C. Herrich, Org. Synth. Coll 4, 304, (1963).         [ Links ]

12. R. Kumareswaran, K. Pachamuthu, Y.D. Vankar, Synlett 11, 1652, (2000).         [ Links ]

13. X.A. Li, T.S. Li, T.H. Ding, Chem. Commun. 5, 1389, (1997).         [ Links ]

14. P. Kumar, K.R. Pandey, S.M. Bodas, K.M. Dongare, Synlett 2, 206, (2001).         [ Links ]

15. B. Karimi, H. Seradji, Synlett 4, 519, (2001).         [ Links ]

16. R. Ballini, G. Bosica, S. Carloni, L. Ciaralli, R. Maggi, G. Sartori, Tetrahedron Lett. 39, 6049, (1998).         [ Links ]

17. R.H. Tale, R.N. Adude, Tetrahedron Lett. 47, 7263, (2006).         [ Links ]

18. R.T. Srikanth, M. Narasimhulu, N. Suryakiran, M.K. Chinni, K. Ashalatha, Y. Venkateswarlu, Tetrahedron Lett. 47, 6825, (2006).         [ Links ]

19. R.S. Jitendra, V. Radha, J. Catal. Commun. 9, 2365, (2008).         [ Links ]

20. S. Farhadi, M. Taherimehr , Acta Chimi. Slov. 55, 637, (2008).         [ Links ]

21. J.W.J. Bosco, A. Agrahari, A.K. Saikia, Tetrahedron Lett. 47, 4065, (2006).         [ Links ]

22. G. Qiuming, G. Nathalie, N. Marc, K.C. Anthony, Chem. Mater. 11, 2937, (1999).         [ Links ]

23. B. David, D. Antigoni, V.M. Ralph, D. David, F. Glenn, Cancer Biother Radio 20, 189, (2005).         [ Links ]

24. S. Fukuda, H. Iida, Y. Yan, Y. Xie, W. Chen, Health Phys. 76, 489, (1999).         [ Links ]

25. A. Ramesh, P. Meher, S. Sampak, R. Prakash, J. Mol. Catal. A Chem 226, 57, (2005).         [ Links ]

 

(Received: March 1, 2011 - Accepted: July 12, 2011)

Creative Commons License Todo o conteúdo deste periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons