盐酸肼屈嗪论文：盐酸肼屈嗪富马酸比索洛尔邻苯二甲酸酐对甲基酚对羟基苯甲醇合成

盐酸肼屈嗪论文：盐酸肼屈嗪 富马酸比索洛尔 邻苯二甲酸酐

对甲基酚 对羟基苯甲醇 合成

【中文摘要】本文由以下两部分组成：Ⅰ盐酸肼屈嗪的合成Ⅱ富马酸比索洛尔的合成第一部分：盐酸肼屈嗪,化学名称为1-肼基-2,3-二氮杂萘。最早由美国NitroMed公司研制成功,是一种舒张血管药,它可以直接作用于血管平滑肌从而可以有效地治疗高血压症而且对心脏和静脉系统没有影响。如果与单硝酸异山梨酯联用,对中度原发性高血压有更好的疗效,可以有效延长心力衰竭患者生存期。本文通过对盐酸肼屈嗪几种合成路线的比较,探索出一条全新的合成方法：以硼氢化钠

【英文摘要】This paper is made up of the synthesis of hydralazine hydrochloride and bisoprolol fumarate.The first part is on the synthesis of hydralazine hydrochloride, whose chemical name is 1-hydrazinophthalazine hydrochloride, which was developed successfully by the American company named NitroMed. Hydralazine hydrochloride is a drug which can relax blood vessel directly. Hydralazine hydrochloride can act on the vascular smooth muscle directly so it can cure the high blood pressure effectively while it has no side effect on the heart and venous system. If it can be combined with isosorbide 5-mononitrate it will have better curative effect on the high

blood pressure and prolong the survival time of the heart failure patient effectively.Several synthetic methods were compared in this paper and we proposed a novel approach to the synthesis of hydralazine hydrochloride:Firstly, in order to synthesize intermediate 1 (2H)-phthalazinone economically, cheap phthalic anhydride was selected as starting material and reacted with sodium borohydride, bromine and hydrazine hydrate respectively. Sodium borohydride reduced phthalic anhydride to form phthalide and it can be used directly in the next step without any further purification. Bromination under the light irradiation and substitution with hydrazine hydrate were carried out respectively but in one pot to afford

1(2H)-phthalazinone in high yield. By adjusting the pH=9 and washing with cold water, pure 1 (2H)-phthalazinone was obtained in 79.3% yield. The yield was high and the post-treatment was simple. In conclusion, the paper has developed a practical method to synthesize hydralazine hydrochloride from cheap and easily accessible phthalic anhydride. In the present method, the yield was high, the post-treatment was easy, the reaction condition was not harsh, the cost was low and the damage to the devices was minor. So this method has a bright future for application in industry.The second part is on the synthesis of

bisoprolol fumarate, whose chemical name is (1-[4-[[2-(1-methy lethoxy)ethoxy]

methyl])phenoxy]-3-[(1-methylethyl)amino]-2-propanol fumarate). Bisoprolol fumarate is a high selective long-actingβ1-blocker of heart. Clinically, it is used to cure the angina, arrhythmia and high blood pressure. It can lower the blood pressure and expand blood vessel because of its high selective feeding ofβ1-recepter of the bronchus and vascular smooth muscle. The expanded left ventricle can return to normal gradually because bisoprolol fumarate can block the nervous endocrine system and improve the diastolic function of the left ventricle evidently. While the blood pressure is lowering the heart function can be fully protected and contractive and diastolic function of the heart can be improved by long-term usingβ1-blocker to cure high blood pressure.This paper proposed a new synthetic route that suit for industrial production through comparing several former synthetic methods. We carried out daring improve and attempt to the synthetic method of bisoprolol fumarate by using 4-methylphenol and p-hydroxybenzyl alcohol as starting material respectively and the structure of the products was characterized by 1H-NMR and IR successfully.