A simple and efficient synthesis of the novel 4-mercapto-6-phenylpyridazin-3(2H)-ones from the reaction of 6-phenyl-4,5-dihydropyridazin-3(2H)-ones with excess thionyl chloride under mild conditions, is described. 3(2H)-Pyridazinone core have an ubiquitous presence in pharmaceuticals and pesticides. Three marketed selective COX-2 inhibitors, Celebrex(celecoxib), Viox(rofecoxib) and Bextra(valdecoxib), effectively treat pain, infamation, and fever with improved gastroindestinal safety. All three of these drugs share a similar structural motif: a core heterocyclic ring substituted with a phenyl and a 4-(sulfonyl)phenyl ring on adjacent atoms. This structural motif was investigated employing 3(2H)-pyridazinone as the core heterocycle, some active regioisomers of this report are under clinical investigation. The same core is present in many pharmaceuticals used as phosphodiesterase inhibitors for treatment of different diseases among them multiple sclerosis, hypertension, Alzheimer disease, and as inhibitors of the production and transduction of cytokines. 3(2H)-Pyridazinone derivatives, have been also recently referred" as drugs for inhibiting vascular intimal hyperplasia. Norflurazon, belongs to this core heterocycle with herbicidal activity inhibiting the biosynthesis of long-chain carotenoids, effecting on protein composition and chlorophyll organization in pigmentprotein complex of photosystem II. Furtermore some 5-mercapto-pyridazinones have been reported as microbiocides and insecticides or for treating/preventing diabetic complications. Given the broad spectrum of biological activity of functionalized pyridazinones, the method desribed here could be used for the synthesis and derivatization of new compounds added to the corporate library, useful as prodrugs and/or as microbiocides or pesticides. After an extensive bibliographic research we did not find 4-mercapto-substituted 3(2H)pyridazinones and in the course of our studies on synthesis of different heterocycles and on abnormal reactions of thionyl chloride, we experimented with the incorporation of the sulfur moiety at the 4position of this core. Based on literature reports""® and our experience, on direct incorporation of chlorosulfenyl moiety, at the α-carbon atom to a carbonyl group, (ketonic or carboxylic acid's chloride), using thionyl chloride ,we proceeded by means of a mechanism which involved oxidation of a methylene carbon to the preparation of the corresponding chlorosulfenyl chloride, >C(SC1)C1. The literature reports""®'··'' refer to such reactions under drastic conditions, in the presence of pyridine, on different carbon atoms as: methyl carbon atoms adjacent to an aromatic ring, " ' methylenes adjacent both, to an aryl and a carboxyl group, active methylenesand methylenes adjacent to enolizable carbonyl groups, (ketonic or carboxylic acid's chloride). '" The former authors suggested a mechanism which proceeded through the transformation of a methylene carbon to the corresponding chlorosulfenyl chloride. The later usually reacts as an intermediate to the formation of sulfur heterocycles"'®' or other nucleophilic displacements while in only few cases it was isolated and characterized by "H NMR, and then heterocyclized. In this letter we wish to disclose a simple and convenient synthesis of 4-mercapto-6-phenylpyridazin3(2H)-ones 6 from the corresponding 6-phenyl-4,5-dihydropyridazin-3(2H)-ones 3, a reaction of mild conditions with excess thionyl chloride, (without any of base), Scheme 1. The used pyridazinones 3 have been reported (except from 3d for which there are no data), by cyclocondensation of ßbenzoylpropionic acid and the proper hydrazine. In order to overcome some experimental obscurities, perhaps connected to and/or the co-formation of the corresponding hydrazides, and to have better yields, we prepared them from the hydrazones 2, (prepared under mild condensation conditions,

中文翻译：

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4-MERCAPTO-6-PHENYLPYRIDAZIN-3(2H)-ONES 的简单高效合成

在温和条件下，通过 6-苯基-4,5-二氢哒嗪-3(2H)-酮与过量亚硫酰氯反应，简单有效地合成新型 4-巯基-6-苯基哒嗪-3(2H)-酮，被描述。3(2H)-哒嗪酮核在药物和农药中无处不在。三种已上市的选择性 COX-2 抑制剂 Celebrex（塞来昔布）、Viox（罗非昔布）和 Bextra（伐地昔布）可有效治疗疼痛、炎症和发烧，并提高胃肠道安全性。所有这三种药物都有一个相似的结构基序：一个被苯基取代的核心杂环和一个相邻原子上的 4-（磺酰基）苯环。该结构基序采用 3(2H)-哒嗪酮作为核心杂环进行研究，本报告的一些活性区域异构体正在临床研究中。相同的核心存在于许多用作磷酸二酯酶抑制剂以治疗不同疾病的药物中，这些疾病包括多发性硬化症、高血压、阿尔茨海默病，以及作为细胞因子产生和转导的抑制剂。3(2H)-哒嗪酮衍生物，最近也被称为“抑制血管内膜增生的药物”。诺氟草酮属于这种核心杂环，具有除草活性，抑制长链类胡萝卜素的生物合成，影响色素蛋白中的蛋白质组成和叶绿素组织光系统 II 的复合物。此外，一些 5-巯基-哒嗪酮已被报道为杀微生物剂和杀虫剂或用于治疗/预防糖尿病并发症。鉴于功能化的哒嗪酮具有广谱的生物活性，这里描述的方法可用于合成和衍生化添加到公司库中的新化合物，用作前药和/或杀微生物剂或杀虫剂。经过广泛的书目研究，我们没有发现 4-巯基取代的 3(2H)哒嗪酮，在我们研究不同杂环的合成和亚硫酰氯的异常反应的过程中，我们试验了硫部分在这个核心的4位置。根据文献报道""® 和我们的经验，使用亚硫酰氯将氯磺基部分在 α-碳原子上直接结合到羰基（酮或羧酸的氯化物）上，我们通过一种机制进行，该机制涉及将亚甲基碳氧化以制备相应的氯亚磺酰氯，>C(SC1)C1。文献报道“”®'··'' 指的是在剧烈条件下，在吡啶存在下，在不同碳原子上的反应，例如：与芳环相邻的甲基碳原子，与两者相邻的亚甲基，芳基和羧基、活性亚甲基和与可烯醇化的羰基相邻的亚甲基（酮或羧酸的氯化物）。'”前作者提出了一种通过将亚甲基碳转化为相应的氯亚磺酰氯的机制。后者通常作为中间体反应形成硫杂环"'®'