Showing posts with label beta-hydroxy esters. Show all posts

Thursday, 2 April 2015

Glycerol as solvent green obtain efficient beta-hydroxy esters

Quim. New 2014 , 37 (3) , 545-548

Glycerol as solvent green obtain efficient beta-hydroxy esters

Simone de Sousa Santos Oliveira ^I ; Sorele Baptist Fiaux ^I ; Igor Ramon Barreto Lomba ^I ; Estela Maris Freitas Muri ^I ; Maria da Conceição Klaus V. Ramos ^II ; Francisco Radler de Aquino Neto ^II ; Luiza Rosaria Sousa Dias ^{I *}

^I School of Pharmacy, Federal Fluminense University, Mario Viana Street, 523, Santa Rosa, 24241-000 Niterói - RJ, Brazil ^II Institute of Chemistry, Federal University of Rio de Janeiro, Technology Center, Block A, University City, 21949- 909 Rio de Janeiro - RJ, Brazil * e-mail: ldias@vm.uff.br\

http://dx.doi.org/10.5935/0100-4042.20140088 http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-40422014000300026&lng=en&nrm=iso&tlng=en

In this work, we report a new method for Obtaining racemic β -hydroxyesters by reduction of β -ketoesters. The use of glycerol as a reactional medium in selective reduction of β -ketoesters into the Corresponding alcohols was shown to be a viable and more efficient alternative Compared with the conventional methodology, taking into account green chemistry prerogatives. Keywords: β -ketoesters; β -hydroxyesters; glycerol.

Accordingly, presented here is a synthesis methodology β -hidroxiésteres by chemical reduction of β -cetoésteres with NaBH ₄ ( above) using glycerol as Solvent Green compared to conventional methodology using methanol. Compounds β -hidroxiésteres (RC (OH) CH ₂ CO ₂ R ') are important building blocks of other organic molecules,^1-5 being the reduction of keto carbonyl β -cetoésteres one of the main ways of obtaining these compounds.Among the synthetic procedures which may be used to reduce the carbonyl grouping, often metal hydrides are used. Of these, especially borohydrides are indicated due to the low cost, simplicity of use, and is generally used as a means for reducing an organic solvent of medium polarity such as methanol. ^6-10 Sodium borohydride (NaBH ₄ ) is used as reagent, reaction selectivity due to the keto carbonyl. ^11-12 However, the selectivity of this reagent in ketoesters compounds appears to be dependent on the reaction conditions, with the possibility of reducing the carbonyl and the carboxyl when using methanol as reaction medium. Research in Green Chemistry has expanded the search for processes that contribute to the sustainability of the environment. This concept, introduced in the US in the 90s, proposes new approaches to the synthesis, processing and application of chemicals in order to prevent or reduce pollution caused by these activities. The use of glycerol as a solvent in syntheses falls within the Green Chemistry concept and has attracted the attention of researchers. This alcohol triidroxilado has good compatibility with organic compounds, high boiling point, low volatility, and therefore environmental friendly. It resembles other polar organic solvents (DMF and DMSO) for their ability to dissolve organic compounds that are poorly water-miscible and facilitate the dissolution of inorganic salts. glycerol characteristics provide the use as Solvent Green in chemical synthesis reactions, given at least three principles of the Green Chemistry concept:. safer chemical synthesis, solvent insurance, and use of renewable raw materials

ethyl 3-oxobutanoate

For the sample of ethyl 3-oxobutanoate ( 1 ) and their reduction products was employed BGB-176B capillary column (25 mx 0.25 mm x 0.25 microns) to 90 ° C isotherm, T _inj = 250 ° C, T _det = 250 ° C (DIC). Reduction products of 3-oxopentanoate and ethyl 3-oxopentanoate Methyl ( 2 and 3 , respectively) were separated with the use of the same column. The column temperature initially at 40 ° C was increased at a 5 ° C / min rate to 150 ° C, t _CH4 = 51 cm / s, split 1:20 flow rate, column flow 1.35 ml / min. T _inj = 250 ° C, T _det = 250 ° C (DIC). To ethyl 3-oxohexanoate ( 4 ) and 3- (4-chlorophenyl) -3-methyl oxopropanoate ( 8 ) and their reduction products was performed using the HP-10B CHIRAL column (30 mx 0.25 mm x 0 25 microns). To 3- (4-chlorophenyl) -3-methyl oxopropanoate ( 8 ) and the respective products, the column temperature was maintained initially for 10 min at 150 ° C, and elevated at a rate of 1.5 ° C / min to 190 ° C, t _{CH 4} = 61.7 cm / sec 1:20 split flow rate, column flow 2.39 ml / min, T _inj = 250 ° C T _det = 270 ° C (FID). Reduction product 4-chloro-3-oxobutanoate Methyl ( 5 ) were separated with the use of Lipodex E column (25 mx 0.25 mm). The column temperature initially at 70 ° C was increased at a rate of 5 ° C / min to 130 ° C (5 min) t _{CH 4} = 51.1 cm / s, flow split ratio 1: 100 Column Flow 2 57 ml / min., T _inj = 250 ° C T _det = 270 ° C (FID). For the 4,4,4-trichloro-3-oxobutanoate Ethyl ( 6 ) and their reduction products was also used to Lipodex E column (25 mx 0.25 mm). The column temperature initially at 70 ° C was increased at a rate of 5 ° C / min to 170 ° C (2 min) t _{CH 4}= 50.5 cm / sec, column flow 2.58 ml / min., split 1 : 20; T _inj = 250 ° C, T _det = 250 ° C (DIC). To 4,4,4-trifluoro-3-oxobutanoate Ethyl ( 7 ) and reduction products, BGB-176 column was used (25 mx 0.25 mm x 0.25 microns) at 120 ° C isotherm (5 min ) t _{CH 4} = 50.1 cm / s, flow rate of division. 1: 100, column flow 1.06 ml / min, T _inj = 250 ° C T _det = 250 ° C (FID).

Obtaining the compounds β -hidroxiésteres (1st to 8th) Method A: the reaction mixture of β corresponding -cetoéster (7.92 mM), NaBH ₄ (7.92 mM) and methanol (10 mL) maintained in an ice bath at a temperature of 0 ° C and under constant magnetic stirring. Method B: Reaction mixture of β corresponding -cetoéster (7.92 mM), NaBH ₄ (7.92 mM) and glycerol (10 ml), kept at room temperature and under constant magnetic stirring. In both methods, the end of the reaction was monitored by TLC and after acidification of the medium with hydrochloric acid solution (10% v / v), the reaction is carried out isolation. The reaction can be performed by isolation extraction with organic solvents immiscible in the reaction medium such as dichloromethane or ethyl acetate (4 x 20 ml), the ethyl acetate less aggressive to the environment and more suited to the principles of green chemistry. ²⁹ Phase The organic layer was washed with saturated NaCl solution and then dried over MgSO ₄ anhydrous, filtered and the solvent evaporated initially on rotary evaporator and then in high vacuum system with variable pressure. Th data of the corresponding B-ketoester compound.

Ethyl 3-hydroxybutanoate (1a). ³⁰ Colorless liquid. IR (KBr, cm ^-1 ): 3440 (C-OH), 1730 (C = O).

NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 1.22 [3H, C H ₃ -CH-OH]; 1.26 [3H, O-CH ₂ -C H ₃ ]; 2.44 [2H, CHOH-C H ₂ -C = O]; 4.14 to 4.21 [3H, CH ₃ C H OH, OC H ₂ -CH ₃ ]. GC (RT): 3.8 and 3.9; 3.6 th.

Ethyl 3-hydroxybutanoate

3-hydroxypentanoate acetate (2a). ³⁰ colorless oily liquid. IR (KBr, cm ^-1 ): 3443 (C-OH), 1732 (C = O).NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 0.94 [3H, C H ₃ -CH ₂ -CH-OH]; 1.25 [3H, O-CH ₂ -C H ₃ ]; 1.50 [2H, CH ₃ -C H ₂ -CH-OH]; 2.43 [2H, C H ₂ -C = O]; 3.91 [1H, CH ₃ -CH ₂ -C H -OH]; 4.15 [2H, OC H ₂ -CH ₃ ].GC (Rt): 12.6 and 12.8; 12.3 th. 3-methyl hydroxypentanoate (3a) . ³⁰ colorless oily liquid. IR (KBr, cm ^-1 ): 3450 (C-OH), 1645 (C = O).NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 0.96 [3H, C H ₃ -CH ₂ -CH-OH]; 1.58 [2H, CH ₃ -C H ₂ -CH-OH];2.48 [2H, C H ₂ -C = O]; 3.71 [3 H, OC H ₃ ]; 3.94 [1H, CH ₃ -CH ₂ -C H -OH]. GC (Rt): 10.8 and 11.2; 10.5 th. 3-hydroxyhexanoate acetate (4a) . ³⁰ colorless oily liquid. IR (KBr, cm ^-1 ): 3433 (C-OH), 1732 (C = O).NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 0.90 [3H, C H ₃ (CH ₂ ) ₂ CH-OH]; 1.22 [3H, O-CH ₂ C H ₃ ]; 1.54 [2H, CH ₃ -C H ₂ -CH ₂ -CH-OH]; 1.71 [2H, CH ₃ -CH ₂ -C H ₂ -CH-OH]; 2.50 [2H, C H ₂ -C = O]; 3.90 [1H, CH ₃(CH ₂ ) ₂ -C H -OH]; 4.15 [2H, OC H ₂ - CH ₃ ]. CG (tr): 16.2 and 16.6. 4-chloro-3-hydroxybutanoate Methyl (5a). ³⁰ colorless oily liquid. IR (KBr, cm ^-1 ): 3415 (C-OH), 1732 (C = O). NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 2.63 [2H, C H ₂ -C = O]; 3.59 [2H, Cl-C H ₂ -CH-OH]; 3.71 [3 H, OC H ₃ ]; 4.25 [1H, Cl-CH ₂ -C H -OH]. CG (tr): 10.7 and 10.9; 9.7 ^a . 4,4,4-trichloro-3-hydroxybutanoate acetate (6a). ³⁰ yellowish oily liquid. IR (KBr, cm ^-1 ): 3430 (C-OH), 1731 (C = O). NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 2.63 [2H, C H ₂ -C = O]; 3.59 [2H, Cl-C H ₂ -CH-OH]; 3.71 [3 H, OC H ₃ ]; 4.25 [1H, Cl-CH ₂ -C H -OH]. GC (Rt): 16.3 and 16.4; 10.9 ^at . 4,4,4-trifluoro-3-hydroxybutanoate acetate (7a). ³⁰ yellowish oily liquid. IR (KBr, cm ^-1 ): 3430 (C-OH), 1725 (C = O). NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 1.30 [3H, O-CH ₂ -C H ₃ ]; 2.70 [2 H, CF ₃ -CHOH-CH ₂ -C = O]; 3.77 [2H, OC H ₂ CH ₃ ]; 4.22 [1H, CF ₃ -C H -OH]. CG (tr): 2.1 and 2.2; 1.8 ^a . 3- (4-chlorophenyl) -3-hydroxypropanoate Methyl (8a). ³⁰ White solid. IR (KBr, cm ^-1 ): 3450 (C-OH), 1732 (C = O). NMR ¹ H (500 MHz) CDCl ₃ / TMS ( δ ppm): 2.71 [2H, C H ₂ -C = O]; 3.73 [3 H, OC H ₃ ]; 5.11 [1H, CH OH]; 7.33 [4H, p -Cl C ₆H ₄ -CH-OH]. GC (Rt): 23.5 and 23.7; 4.3 ^to .

School of Pharmacy, Federal Fluminense University, Mario Viana Street