Process For Synthesis Of Hydroxyacetophenone And Methoxylamine

O-hydroxyacetophenone and p-hydroxyacetophenone are important organic chemical raw materials, which can be used for making spice, synthesizing a variety of drug intermediates in pharmaceutical industry, synthesizing Schiff base, determining the trace amounts of rare earth metal ions in food, etc. In the annual demand of tens of thousands of tons, methoxy amine is a kind of important intermediate in current pesticide and pharmaceutical industries. However, this product still remains can not been prepared in large scale.In our work,(o-and p-) hydroxy acetophenone were synthesized by Fries-Rearrangement by utilizing AICl3as the catalyst, and furthermore, the parameters of the synthesis process were optimized. The general syntheses are started with ethyl acetate as the raw reagent, after substitution reaction with hydroxylamine, methylation by dimethyl sulfate, and then hydrolyzation by HC1. Finally, methoxy amine was obtained after purifying process. The main research work is as follows:1、By using p-toluene sulfonic acid as the catalyst, benzyl acetate was synthesized by reaction between phenol and acetic anhydride.The synthesis process is optimized:p-toluene sulfonic acid:phenol:acetic anhydride=1:10:13(mole ratio), and reacted at130℃for1h, the conversion is over99%for phenol, and it reaches94%in terms of benzyl acetate.2、(O-and p-) hydroxy acetophenone were synthesized by Fries-Rearrangement with AICl3as the catalyst, and the process is optimized as follow:toluene as the solvent, AICl3:phenyl acetate=1.3:1(mole ratio), and reacted at120℃for10h, o-and p-hydroxy acetophenone yield was50.88%and23.53%, respectively. The total yield was74,41%.3、Gas chromatographic was employed to proceed the quantitative analysis of phenyl acetate, o-and p-hydroxy acetophenone.The phenyl acetate was analyzed by gas chromatography with flame ionization detection on Φ2.5mmx lm2.5%OV-225chromosorb W-HP (80～100mesh) packed stainless glass column. The inner standard was diethyl oxalate. The linear Regression Equation is Y=1.8821X+1.5293with a correlation coefficient of0.9996. The standard deviation and coefficient of variation were0.19%and0.20%, respectively.The o-hydroxy acetophenone was analyzed by gas chromatography with flame ionization detection on Φ2.5mm×1m2.5%OV-7chromosorb W-HP (80-100mesh) packed stainless glass column. The inner standard was bromotetradecane. The linear Regression Equation is Y=1.0633X-0.0082with a correlation coefficient of0.9989. The standard deviation and coefficient of variation were2.2%and2.1%, respectively.The p-hydroxy acetophenone was analyzed by gas chromatography with flame ionization detection on Φ2.5mmxlm2.5%OV-225chromosorb W-HP (80-100mesh) packed stainless glass column. The inner standard was bromotetradecane. The linear Regression Equation is Y=0.8278X-0.0727with a correlation coefficient of0.9991. The standard deviation and coefficient of variation were0.44%and0.56%, respectively.4、Phenyl acetate, o-and p-hydroxy acetophenone structure were confirmed by IR、1H NMR and the results were in good accordance with the structure of relative compounds.5、With Fries rearrangement reactions catalyzed by self-made new-type heterogeneous modification of zeolite and metavanadate zinc as the catalysts, toluene as the solvent, and reacted at120℃for48h, the selectivity of adjacent hydroxy acetophenone was up to100%; With modified zeolite as catalyst, the yield of hydroxy acetophenone was10%, while using metavanadate zinc as the catalyst, the yield was17%.6、Methoxy amine hydrochloride was synthesized from ethyl acetate by reacting with hydroxylamine sulfate to form acetyl hydroxyl oxime acid, and followed by methylation by dimethyl sulfate, and hydrolysis process by HCl. Finally, methoxy amine was obtained through purifying process. The process was optimized as follows:hydroxylamine sulfate:ethyl acetate=1:1.2(mole ratio), at25℃for4h, the yield was90.1%; Hydroxyl oxime acid sodium:dimethyl sulfate=1:1.3(molar ratio), at15℃for2h，the yield for acetyl hydroxyl oxime acid is less than0.2%. Methoxy amine hydrochloride was gained by the acidolysis process of acetyl methoxy amine with content of98.5%, and a yield of75%.7. A quantitative determination of acetyl hydroxyl oxime acid by UV-vis spectrophotometer has been investigated. The purple complex formed by acetyl hydroxyl oxime acid and ferric ion showed an obvious adsorption peak located at450nm in the UV-vis spectrum. The relationship between the absorbance and concentration is a linear correlation over the concentration range of0.04-0.20mg/mL. The linear regression equation is Y=0.0932A-0.00148with a correlation coefficient of0.99992.