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Method for preparing o-phthaloyl threonine
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A technology of phthalyl threonine and gram phthalic anhydride, which is applied in the field of preparation of phthalyl threonine to achieve the effect of mild reaction
Inactive Publication Date: 2010-08-25
SHAANXI UNIV OF SCI & TECH
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So this method is not suitable for the preparation of phthalyl threonine
Method used
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Embodiment 1
[0015] In the first step, 2 milliliters of N,N-dimethylformamide, 1.48 grams of phthalic anhydride and 1.19 grams of threonine were added to the reactor, and the reactor was heated to 70° C. for 8 hours;
[0016] In the second step, filter the solution obtained in the first step while it is hot, add the filtrate to 8 ml of distilled water, cool in an ice bath to 3~8°C, adjust the pH to 2~3 with hydrochloric acid, and cool to 3~8°C in an ice bath C, 2.14 g of the solid obtained by filtration is phthalylthreonine, and the yield is 86%. 1H-NMR (DMSO-d6, 400M, TMS internal standard, δ:ppm): 1.38~1.40 (3H, CH3-, doublet), 3.35 (1H, -OH, singlet), 5.20~5.24 (1H, CH-, multiplet), 5.50~5.53 (1H, CH-, doublet), 7.86~8.00 (4H, Ph-H, multiplet), 13.47 (1H, -OH, singlet).
Embodiment 2
[0018] In the first step, 2 milliliters of N,N-dimethylformamide, 1.63 grams of phthalic anhydride and 1.19 grams of threonine were added to the reactor, and the reactor was heated to 90° C. for 6 hours;
[0019] In the second step, filter the solution obtained in the first step while it is hot, add the filtrate to 10 ml of distilled water, cool in an ice bath to 3~8°C, adjust the pH to 2~3 with hydrochloric acid, and cool to 3~8°C in an ice bath C, 2.29 g of the solid obtained by filtration is phthaloylthreonine, and the yield is 92%.
Embodiment 3
[0021] In the first step, 2 milliliters of N,N-dimethylformamide, 1.66 grams of phthalic anhydride and 1.19 grams of threonine were added to the reactor, and the reactor was heated to 120° C. for 5 hours;
[0022] In the second step, filter the solution obtained in the first step while it is hot, add the filtrate to 14 ml of distilled water, cool in an ice bath to 3~8°C, adjust the pH to 2~3 with hydrochloric acid, and cool to 3~8°C in an ice bath C, 2.22 g of the solid obtained by filtration is phthaloylthreonine, and the yield is 89%.
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Abstract
The invention relates to a method for preparing o-phthaloyl threonine, which comprises the following steps: firstly, adding a milliliters of inorganic alkaline solvent, b grams of phthalic anhydride and c grams of threonine into a reactor, heating the reactor to 70 to 150 DEG C, and keeping temperature for 4 to 8 hours; and secondly, filtering hot solution obtained by the reaction in the first step, adding the filtrate into d milliliters of distilled water, cooling the solution to 3 to 8 DEG C, adjusting the pH value of the solution to 2 to 3 by using strong acid, and filtering obtained solid to obtain the o-phthaloyl threonine. The ratio of the a to the b is (1.20 to 2.81):1, the ratio of the b to the c is (1.24-1.50):1, and d is more than or equal to 4a; and the inorganic alkaline solvent is N,N-dimethylformamide, dimethyl sulfoxide or 1,4-dioxane. The method has the advantages that: the heating temperature is between 70 and 150 DEG C; the reaction is performed in solution; the reaction is mild without bumping; and the yield is over 80 percent.
Description
technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a method for preparing phthalyl threonine. Background technique [0002] MargueriteFling etc. reported in J.Am.Chem.Soc., 1947,69 (10) by equivalent phthalic anhydride and amino acidsolidphase reaction synthesis phthalyl amino acid, this method is at 140 ℃-190 Melt phthalic anhydride at °C, then add amino acid to react until the bubbles disappear. The above method includes the preparation of phthaloyl D-valine, phthaloyl L-valine, phthaloyl D-leucine and phthaloyl L-leucine. [0003] However, the method reported by Marguerite Fling requires strict conditions such as high temperature, and the reaction is violent, and it is not easy to control the reaction process. Such conditions are not of high industrial interest as they are environmentally unfriendly and have high reactor requirements and tend to racemize amino acids and products. [0004] Organicsyntheses, coll. Vol.5, p...
Claims
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