Technological method for synthesis of optically pure L-/D-lactide catalyzed by biogenic guanidine

Abstract

A technological method for synthesizing optically pure L-/D-lactide by using a biogenic guanidine catalysis method. The method of the present invention comprises: by using biogenic guanidine creatinine (CR) as a catalyst and L-/D-lactic acid (90% of mass content) as a raw material, synthesizing optically pure L-/D-lactide by using a reactive reduced pressure distillation catalysis method. The method of the present invention has advantages that the used catalyst is biogenic guanidine creatinine and free of toxicity, metal, and cytotoxicity; the synthesized lactide is high in optical purity (the specific rotation of the L-lactide []25D=276280, and the specific rotation of the D-lactide []25D=280), and does not contain any metal; the amount of the catalyst used in reaction is low, the technological process is simplified (a process for rectifying and purifying a crude lactide product by using a conventional method is avoided); and the technological method is simple and convenient to operate and easy in industrial implementation.

Claims

1. A method for synthesizing L-lactide or D-lactide comprising the following steps: (1) carrying out dehydration and polycondensation of L-lactate or D-lactate by: (1a) heating L-lactate or D-lactate at a temperature of 130 C.-170 C., at ambient pressure for 1-4 h, and (1b) heating the L-lactate or the D-lactate at a temperature of 130 C.-170 C. for 2-8 h at a pressure of 30-60 torr, to produce lactic acid oligomers with a weight-average molecular weight of 600-1500 Da; (2) carrying out catalytic distillation of the lactic acid oligomers from step (1) to form crude L-lactide or D-lactide by: (2a) mixing the lactic acid oligomers from step (1) with creatinine catalyst; and (2b) reacting the mixture for 1-4 h at a temperature of 150-260 C. and a pressure of 2-15 torr, to produce distilled white crude L-lactide or D-lactide; (3) washing the crude L-lactide or D-lactide from step (2) with an alkaline solution having a mass concentration of 1-10% alkali, then washing to neutral using deionized water, and (4) vacuum drying the washed L-lactide or D-lactide at 20 C.-40 C. for 24-36 h to thereby obtain L-lactide or D-lactide.

2. The method according to claim 1, wherein the specific rotation []25D of L-lactide is 276 to 280, and the specific rotation []25D of D-lactide=280.

3. The method according to claim 1, wherein the mass ratio of creatinine catalyst to lactic acid oligomers in step (2) is within the range of 1:100-1:10000.

4. The method according to claim 1, wherein the alkaline solution with mass concentration of 1-10% in step (3) is a solution of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium or potassium bicarbonate; and wherein washing with the alkaline solution removes impurities in the crude L-lactide or D-lactide.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

Example 1

(1) {circle around (1)} A reactor was charged with 100 g of L-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 130 and subjected to dehydration for 4 h. The pressure in the reactor was then reduced to 60 Torr, reacting at 130 C. for 8 h, to get the lactic acid oligomer (OLLA), with a weight average molecular weight of 1500 Da.

(2) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to L-lactic acid at 1:100, and the reaction temperature at 180, vacuum degree of 2 torr, to react 1 h; then the distilled white crude L-lactide was collected.

(3) The collected crude L-lactide was washed with 1% alkali (sodium hydroxide) solution, cleaned with the deionized water to neutral, vacuum dried 24 h at 20 C., to get white needle L-lactide, with the yield of 35.5% and specific rotation [] 25D=276.

Example 2

(4) {circle around (1)} A reactor was charged with 100 g of L-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 170 and subjected to dehydration for 1 h. The pressure in the reactor was then reduced to 30 torr, reacting at 170 C. for 2 h, to get the lactic acid oligomer (OLLA), with a weight average molecular weight of 600 Da.

(5) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to L-lactic acid at 1:10000, and the reaction temperature at 260, vacuum degree of 15 torr, to react 4 h; then the distilled white crude L-lactide was collected.

(6) The collected crude L-lactide was washed with 10% alkali (sodium carbonate) solution, cleaned with the deionized water to neutral, vacuum dried 36 h at 40 C., to get white needle L-lactide, with the yield of 40.3% and specific rotation [] 25D=280.

Example 3

(7) {circle around (1)} A reactor was charged with 100 g of L-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 150 and subjected to dehydration for 2 h. The pressure in the reactor was then reduced to 40 Torr, reacting at 150 C. for 4 h, to get the lactic acid oligomer (OLLA), with a weight average molecular weight of 1100 Da.

(8) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to L-lactic acid at 1:1000, and the reaction temperature at 200, vacuum degree of 10 torr, to react 3 h; then the distilled white crude L-lactide was collected.

(9) The collected crude L-lactide was washed with 8% alkali (sodium bicarbonate) solution, cleaned with the deionized water to neutral, vacuum dried 30 h at 35 C., to get white needle L-lactide, with the yield of 45.8% and specific rotation [] 25D=277.

Example 4

(10) {circle around (1)} A reactor was charged with 100 g of L-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 160 and subjected to dehydration for 2 h. The pressure in the reactor was then reduced to 50 Torr, reacting at 160 C. for 4 h, to get the lactic acid oligomer (OLLA), with a weight average molecular weight of 1300 Da.

(11) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to L-lactic acid at 1:2000, and the reaction temperature at 220, vacuum degree of 8 torr, to react 2 h; then the distilled white crude L-lactide was collected.

(12) The collected crude L-lactide was washed with 5% alkali (potassium bicarbonate) solution, cleaned with the deionized water to neutral, vacuum dried 26 h at 30 C., to get white needle L-lactide, with the yield of 40.8% and specific rotation [] 25D=280.

Example 5

(13) {circle around (1)} A reactor was charged with 100 g of L-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 150 and subjected to dehydration for 1 h. The pressure in the reactor was then reduced to 30 Torr, reacting at 130 C. for 3 h, to get the lactic acid oligomer (OLLA), with a weight average molecular weight of 900 Da.

(14) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to L-lactic acid at 1:5000, and the reaction temperature at 240, vacuum degree of 5 torr, to react 3 h; then the distilled white crude L-lactide was collected.

(15) The collected crude L-lactide was washed with 2% alkali (potassium hydroxide) solution, cleaned with the deionized water to neutral, vacuum dried 35 h at 30 C., to get white needle L-lactide, with the yield of 38.8% and specific rotation [] 25D=277.

Example 6

(16) {circle around (1)} A reactor was charged with 100 g of L-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 140 and subjected to dehydration for 2 h. The pressure in the reactor was then reduced to 30 Torr, reacting at 140 C. for 3 h, to get the lactic acid oligomer (OLLA), with a weight average molecular weight of 1200 Da.

(17) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to L-lactic acid at 1:2000, and the reaction temperature at 250, vacuum degree of 3 torr, to react 4 h; then the distilled white crude L-lactide was collected.

(18) The collected crude L-lactide was washed with 1% alkali (potassium carbonate) solution, cleaned with the deionized water to neutral, vacuum dried 24 h at 40 C., to get white needle L-lactide, with the yield of 42.4% and specific rotation [] 25D=280.

Example 7

(19) {circle around (1)} A reactor was charged with 100 g of D-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 130 and subjected to dehydration for 3 h. The pressure in the reactor was then reduced to 60 Torr, reacting at 130 C. for 8 h, to get the lactic acid oligomer (ODLA), with a weight average molecular weight of 1500 Da.

(20) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to D-lactic acid at 1:100, and the reaction temperature at 150, vacuum degree of 2 torr, to react 2 h; then the distilled white crude D-lactide was collected.

(21) The collected crude D-lactide was washed with 1% alkali (potassium hydroxide) solution, cleaned with the deionized water to neutral, vacuum dried 24 h at 20 C., to get white needle D-lactide, with the yield of 41.7% and specific rotation [] 25D=280.

Example 8

(22) {circle around (1)} A reactor was charged with 100 g of D-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 170 and subjected to dehydration for 1 h. The pressure in the reactor was then reduced to 30 Torr, reacting at 170 C. for 4 h, to get the lactic acid oligomer (ODLA), with a weight average molecular weight of 800 Da.

(23) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to D-lactic acid at 1:10000, and the reaction temperature at 260, vacuum degree of 15 torr, to react 4 h; then the distilled white crude L-lactide was collected.

(24) The collected crude D-lactide was washed with 5% alkali (potassium carbonate) solution, cleaned with the deionized water to neutral, vacuum dried 36 h at 40 C., to get white needle D-lactide, with the yield of 40.3% and specific rotation [] 25D=280.

Example 9

(25) {circle around (1)} A reactor was charged with 100 g of D-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 150 and subjected to dehydration for 2 h. The pressure in the reactor was then reduced to 40 Torr, reacting at 150 C. for 4 h, to get the lactic acid oligomer (ODLA), with a weight average molecular weight of 1100 Da.

(26) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to D-lactic acid at 1:1000, and the reaction temperature at 200, vacuum degree of 10 torr, to react 3 h; then the distilled white crude D-lactide was collected.

(27) The collected crude D-lactide was washed with 6% alkali (potassium bicarbonate) solution, cleaned with the deionized water to neutral, vacuum dried 30 h at 35 C., to get white needle D-lactide, with the yield of 45.6% and specific rotation [] 25D=280.

Example 10

(28) {circle around (1)} A reactor was charged with 100 g of D-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 160 and subjected to dehydration for 2 h. The pressure in the reactor was then reduced to 50 Torr, reacting at 160 C. for 4 h, to get the lactic acid oligomer (ODLA), with a weight average molecular weight of 1300 Da.

(29) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to D-lactic acid at 1:2000, and the reaction temperature at 200, vacuum degree of 8 torr, to react 2 h; then the distilled white crude D-lactide was collected.

(30) The collected crude D-lactide was washed with 1% alkali (sodium hydroxide) solution, cleaned with the deionized water to neutral, vacuum dried 26 h at 30 C., to get white needle D-lactide, with the yield of 46.8% and specific rotation [] 25D=280.

Example 11

(31) {circle around (1)} A reactor was charged with 100 g of D-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 150 and subjected to dehydration for 1 h. The pressure in the reactor was then reduced to 30 Torr, reacting at 150 C. for 3 h, to get the lactic acid oligomer (ODLA), with a weight average molecular weight of 900 Da.

(32) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to D-lactic acid at 1:5000, and the reaction temperature at 200, vacuum degree of 8 torr, to react 2 h; then the distilled white crude D-lactide was collected.

(33) The collected crude D-lactide was washed with 1% alkali (sodium hydroxide) solution, cleaned with the deionized water to neutral, vacuum dried 35 h at 30 C., to get white needle D-lactide, with the yield of 44.5% and specific rotation [] 25D=280.

Example 12

(34) {circle around (1)} A reactor was charged with 100 g of D-lactic acid (90% by mass content). Under an argon atmosphere at normal pressure, the reaction system was then heated to 140 and subjected to dehydration for 2 h. The pressure in the reactor was then reduced to 30 Torr, reacting at 140 C. for 3 h, to get the lactic acid oligomer (ODLA), with a weight average molecular weight of 1200 Da.

(35) The biogenic guanidine creatinine (CR) was added, to control the mass ratio of catalyst CR to D-lactic acid at 1:2000, and the reaction temperature at 250, vacuum degree of 3 torr, to react 4 h; then the distilled white crude D-lactide was collected.

(36) The collected crude D-lactide was washed with 6% alkali (sodium bicarbonate) solution, cleaned with the deionized water to neutral, vacuum dried 24 h at 40, to get white needle D-lactide, with the yield of 43.8% and specific rotation [] 25D=280.