Efficient and ‘green’ microwave-assisted synthesis of haloalkylphosphonates via the Michaelis–Arbuzov reaction

Abstract

This paper deals with a novel, efficient and environmentally friendly synthesis of dialkyl haloalkylphosphonates via a microwave-assisted Michaelis-Arbuzov reaction. The approach is solventless, requires only one equivalent of each of the starting compounds, and provides high yields of pure products from which the impurities are easy to remove. The process has been optimised for batch and flow reactors and is especially profitable for the production of key intermediates in synthesis of Ethephon or acyclic nucleoside phosphonates such as adefovir, tenofovir, and cidofovir.

Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines

“…None of the 6-substituted FPMPA derivatives (13)(14)(15)(16)(17)(18)(19)(20)(21) showed neither anti-HIV nor anti-MSV activity in cell culture (Scheme 2). In contrast, several N 6 -substituted FPMPDAP derivatives were endowed with a moderate anti-HIV/MSV activity (Scheme 2, Table 2).…”

“…Enantiomer 8a was also obtained in the same yield (67%) by an alternative procedure using bromomethylphosphonate 7 instead of tosylate 6 under similar reaction conditions. 20 Detritylation of compounds 8 was carried out in 80% aqueous acetic acid and gave acceptable yields of the derivatives 9. Scheme 1.…”

“…Reagents and conditions: (a) NaH, DMF, À20°C to rt; (b) 80% CH 3 COOH, 90°C; (c) Dowex D50W Â 8 (H + form), aq MeOH, reflux; (d) TsCl, Et 3 N, CH 2 Cl 2, 0°C to rt; (e) TsCl, Py, DMAP, 0°C; (f) 6-chloropurine, NaH, DMF, 60°C (conventional) or 120°C (microwave); (g) 6-chloropurine, Ph 3 P, DIAD, THF, rt to 60°C; (h) 2-amino-6-chloropurine, NaH, DMF, 90°C; (i) amine, CH 3 CN, 70°C or 80°C; (j) TMSBr, CH 3 CN, rt. in acetonitrile, 14b followed by the standard removal of the isopropyl ester groups with TMSBr in acetonitrile at room temperature, 14b afforded the crude products [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Final purification of the products 13-29 was performed by two approaches: (a) standard deionization by means of the ion-exchange resins and subsequent crystallization from aqueous ethanol to get the final free phosphonic acids; 14b (b) reverse phase HPLC chromatography of the corresponding triethylammonium salts of the products followed by the conversion to their sodium salts on Dowex D50 Â 8 (Na + form), which can be either crystallized from aqueous ethanol or lyophilized.…”

Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs

“…Thus, 7-deazapurine compounds 10, 11 and 31, 32 were hydrolysed by the reaction with potassium carbonate and DABCO in water 30,31 to form 6-oxo-7-deazapurine derivatives 16, 17 and 37, 38. 32 was also tried. Thus, 6-chloropurine ester 9 was transformed directly to 6-oxopurine derivative containing free phosphonate functional groups, followed by conversion to the corresponding sodium salt of the final inhibitor 19 (Scheme 1).…”

Simple synthesis of Biphosphonates with Excellent Flameproofing Properties

“…According to the thermogravimetric analysis (TGA) of these biphosphonates and single phosphonates (DEEP Supported by the Jiangsu Natural Science Foundation of China (BK2011369) and Priority Academic Program Development of Jiangsu Higher Education Institutions and DMMP), results showed that biphosphonates had better thermal stability and higher char residue, two important measures of low flammability materials. These flame retardants were synthesized through polycondensation and Arbuzov rearrangement reactions [11] (Scheme 1).…”