Methoxamine hydrochloride: uses and Synthesis method

Introduction

Methoxamine hydrochloride, also known as methoxamine hydrochloride, O-methyl hydroxylamine hydrochloride. Molecular formula CH 30NH 2hCl, molecular weight 83.5, methoxamine hydrochloride is a white crystalline powder. Its fusing point is 149 ~ 152 ℃, soluble in water, dissolved in alcohol, insoluble in ether and toluene, etc., and the solution is in acid.

Methoxyamine Hydrochloride is the hydrochloride salt form of methoxyamine, an alkoxyamine with potential chemotherapeutic adjuvant activity. Methoxyamine covalently binds to apurinic/apyrimidinic DNA damage sites and thereby inhibits the base excision repair (BER) process, which may prevent the repair of DNA strand breaks and result in an induction of apoptosis.  

Importance

Methoxamine hydrochloride is an important chemical and medicine intermediate, can be used for the development and printing of color photography and film, and is widely used in the synthesis of medicine, functional dye, low-toxin farm chemicals, and new herbicides. Methoxamine hydrochloride is mainly used in the synthesis of s-generation cephalosporin product cephalofruxin in medical, and sulfamethoxazole, alkynes promise are bright, the synthesis of hydroxyurea etc.; Agricultural chemicals aspect is then mainly used in the kresoxim-methyl of synthesizing efficient low toxicity. Along with the continuous developmentt of its Application Areas, increasingthe demand foror methoxamine hydrochloride both at home and abroad.

Synthesis method

At present, the main synthetic routes of methoxyamine hydrochloride are as follows:

Use benzaldehyde as raw material to react through oximation and methylation to generate aromatic aldoxime hydroxycarbamate, and then hydrolyze to obtain ;

Use hydroxylamine hydrochloride as raw material, sulfonate with fuming sulfuric acid, and then directly react with sodium alkyl alcohol and its sulfonate to obtain alkoxyamine ;

Use chloroformate and hydroxylamine as raw materials, and the generated hydroxycarbamate is methylated and treated with alkali to obtain ;

Use sodium bisulfite, sodium nitrite, and sulfur dioxide to react to first generate hydroxylamine sodium sulfite and then methylate, hydrolyze, and neutralize to obtain salt;

Use sulfur dioxide, sodium nitrite, and hydroxylamine as main raw materials, and obtain hydroxylamine disulfonate through Schick reaction at a certain temperature and Under the condition of pH value; it reacts with dimethyl sulfate for methylation and hydrolyzes to obtain the product methoxyamine;

Using hydroxylamine hydrochloride as raw material, it first reacts with acetone to generate oxime, then reacts with an alkylating agent, and then hydrolyzes with acid to obtain alkoxyamine hydrochloride;

Ethyl acetate first reacts with hydroxylamine hydrochloride under alkaline conditions to obtain acetylhydroxylamine. Acetylhydroxylamine reacts with dimethyl sulfate for methylation to obtain acetylmethoxyamine; the obtained acetylmethoxyamine is hydrolyzed under acidic conditions to obtain methoxyamine; finally, methoxyamine is salified with hydrochloric acid to obtain the product methoxyamine hydrochloride.

Sun et al. disclose a method of preparation for methoxyamine hydrochloride. According to the method, sulfur dioxide gas, sodium nitrite, sodium hydroxide, and dimethyl sulfate have a cascade one-pot reaction in a water phase, and methoxyamine hydrochloride is prepared. The specific synthesis steps are as follows: in a 500 ml three-necked flask, add 100 ml of water, 69 g (1 mol) of sodium nitrite, 80 g (2 mol) of sodium hydroxide, pass 128 g (2 mol) of sulfur dioxide at 20°C, control the reaction for 1 hour, add 40 g (1 mol) of sodium hydroxide, add 126 g (1 mol) of dimethyl sulfate, react for 1 hour, add 40 g (1 mol) of sodium hydroxide, add 126 g (1 mol) of dimethyl sulfate, react for 1 hour, add sulfuric acid to adjust pH=1, distill under reduced pressure, add concentrated HC1 to the distillate to adjust pH=4~5, let stand to precipitate crystals, filter, and dry to obtain 56.1 g Methoxamine hydrochloride with a yield of 67.2%. Melting point: 148 ~ 151°C.

References

[1] CN105330564A - Preparation method of methoxyamine hydrochloride - Google Patents

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