ABSTRACT
OBJECTIVE:To optimize the synthesis technology of 4-biphenylacetic acid,and to provide technology support to meet the market demand of 4-biphenylacetic acid raw material. METHODS:The synthesis route of 4-biphenylacetic acid from biphenyl by Friedel-Crafts reaction,ketal reaction,rearrangement reaction and hydrolysis was optimized and improved. The effects of different Friedel-Crafts reaction solvents (petroleum ether,dichloromethane,1,2-dichloroethane),ketal reaction ethanol (ethanediol, 1,3-propanediol, dimethyltrimethylene glycol, pentaerythritol), rearrangement reaction catalyzer (zinc biphenyl acetate,zinc oxide,zinc caprylate,zinc acetate) and refined solvent (isopropanol,95% isopropanol,ethanol,acetone,ethyl acetate) on synthesis technology were investigated. The optimal synthesis technology was screened with the purity and yield of intermediate or 4-biphenylacetic acid. RESULTS:The petroleum ether as Friedel-Crafts reaction solvent,ethylene glycol as ketal reaction ethanol,zinc diphenylacetate as rearrangement catalyst and 95% isopropanol as refining solvent were used for the preparation to obtain better effects. The yield of key intermediate 2′-chloroacetophenone reached above 95%. The purity of refined 4-biphenylacetic acid reached 99.9%;the content of single impurity was less than 0.1%;the total yield reached over 70%. CONCLUSIONS:The optimal synthesis technology of 4-biphenylacetic acid has the advantages of simple operation,mild and controllable reaction conditions,low cost,greener reagents and higher safety,and is suitable for industrial production. The purity and yield of the products are in high level and in line with the standards of European Pharmacopoeia and the Japanese Pharmacopoeia.
ABSTRACT
OBJECTIVE:To improve the synthesis technology of sodium picosulfate. METHODS:The synthesis technology of sodium picosulfate was improved by changing reaction solvent,charging sequence,refined method and formation of crystal water. Using phenol as raw material,it was condensed with 2-pyridinecarboxaldehyde to achieve 4,4′-(pyridin-2-ylmethylene)diphenol, and its yield rate was investigated. Sodium picosulfate was obtained after esterification,salification,formation of crystal water, and then its purity was determined. RESULTS:The yield rate of key intermediate 4,4′-(pyridin-2-ylmethylene) diphenol reached above 88%,and the purity of refined products reached over 99.5%. Sodium picosulfate monohydrate was stable,and the content of single impurity was less than 0.1%. CONCLUSIONS:The improved technology is simple with mild conditions,and suitable for large-scale production.
ABSTRACT
Objective To study the expression of epidermal growth factor receptor (EGFR) in cervical car-cinoma and cervical intraepithelial neoplasia(CIN),and to elucidate its relation with the genesis, infiltration, metas-tasis and prognosis of cervical carcinoma. Methods EGFR was determined by means of S-P immunohistochemistry in tissue of 100 cases of cervical carcinoma,60 cases of CIN and 40 cases of controls. Results The overexpression rates of EGFR were 0% (0/40), 51.67% (31/60),78.00% (78/100), respectively in normal cervical epithelium, CIN and cervical tumor tissues. The overexpression rate of EGFR was significantly higher in cervical tumor tissue than in control group(P<0.01). The overexpression of EGFR didn't demonstrate significant association with clinical staging, tumor size, pathological type, differentiation, cervical invasion depth, cervical canal invasion, lymphnode me-tastasis or the prognosis of cervical neoplasm (P>0.05). Conclusion Overexpression of EGFR is worsened with the severity of cervical lesion, suggesting that overexpression of EGFR is correlated with the genesis of cervical neo-plasms,which may be a valuable biological indicator of cervical carcinoma,but is not correlated with clinical patho-logical features and prognosis of cervical carcinoma.