Reaction of citral with trimethyl phosphite in the presence of acetic acid

Abstract

Phosphorus-containing polyprenoids play an important role in metabolic processes in living organisms (biosynthesis of glicosylaminoglycanes and glycoproteins, terpenes, and geraniol and nerol pyrophosphates) [134]. There are scarce data in the literature on phosphorus-containing isoprenoids with a P3C bond. Synthesis of such compounds is a challenging problem of natural chemistry, that consist of design of new types of phosphorylated 1,5-polyenes and polyterpenes as promising low-molecular bioregulators. Considering the complex structure of ÄÄÄÄÄÄÄÄÄÄÄÄ natural polyisoprenylaldehydes, we made an attempt to develop methods of phosphorylation of such compounds on the basis of their low-molecular analogs. In the present work we showed that a representative of long-chain unsaturated aldehydes, citral I (a mixture of the E and Z isomers), can unidirectionally react with such normal phosphites as trimethyl phosphite in the presence of acetic acid under mild conditions to give a mixture of the E and Z isomers of dimethyl 1-hydroxy-3,7-dimethylocta-2,6-dienylphosphonate (III) in high yield.

Dimethyl 1-Hydroxy-3,7-dimethyl-2,6-octadienylphosphonate. Development of Synthetic Procedures

“…For this purpose, a dilute solution of triethylamine in ethanol was added to the reaction mixture, and the mixture was heated for 13.5 h at 60°C. As a result, we isolated dimethyl 1-hydroxy-3,7-dimethyl-2,6-octadienylphosphonate (III) as a mixture of E and Z isomers in an overall yield of 71% (Scheme 1); the physical constants and IR, 31 P and 13 C NMR, and mass spectra of the product were in agreement with the data reported in [4].…”

“…For this purpose, a dilute solution of triethylamine in ethanol was added to the reaction mixture, and the mixture was heated for 13.5 h at 60°C. As a result, we isolated dimethyl 1-hydroxy-3,7-dimethyl-2,6-octadienylphosphonate (III) as a mixture of E and Z isomers in an overall yield of 71% (Scheme 1); the physical constants and IR, 31 P and 13 C NMR, and mass spectra of the product were in agreement with the data reported in [4].Taking into account that the formation of compound III in the above reaction involves intermediate conversion of II into dimethyl phosphonate (IV), we examined the reaction of IV with citral I in the presence of triethylamine at a reactant molar ratio of 4 : 2 : 8 in a dilute solution in methanol (Scheme 2). The reaction was complete in 16 h at 40-55°C, and phosphonate III was isolated in 88% yield.…”

“…We previously succeeded in reacting trimethyl phosphite with citral under fairly mild conditions (50°C, 1.5 h) in the presence of acid catalysts, e.g., acetic acid [4]. While developing methods of synthesis of unsaturated α-hydroxy phosphonates we tried to use other initiating agents.…”

“…The mixture was stirred for 4 h at ~20°C, a solution of 8.2 ml of triethylamine in 50 ml of methanol was added, and the mixture was stirred for 13.5 h at 60°C and evaporated under reduced pressure at 40°C (for 1 h at 0.5 mm and for 1 h at 0.02 mm). The residue was subjected to molecular film distillation at 165°C (0.03 mm) to isolate 4.9 g (71%) of phosphonate III, n D 20 = 1.4855; published data [4]: n D 20 = 1.4850. 31 P NMR spectrum, δ P , ppm: 25.8 and 22.5 (intensity ratio ~1 : 1).…”

Applications of Lawesson′s Reagent in Organic and Organometallic Syntheses

“…The reaction of LR with alkyl borates, 195,196 trialkylsilyl and stannyl derivatives, 197,198 and with arsenic(III) alkoxides 199 was examined by Nizamov et al He et al studied the treatment of phenylthiourea and oxamide with LR. 200…”