potassium 2-ethylhexanoate - CAS号 3164-85-0

物化性质

物理描述：

Liquid
稳定性/保质期：

遵照规定使用和储存，则不会分解。

计算性质

辛醇/水分配系数(LogP)：

-2.04
重原子数：

11
可旋转键数：

5
环数：

0.0
sp3杂化的碳原子比例：

0.88
拓扑面积：

40.1
氢给体数：

0
氢受体数：

2

安全信息

安全说明：

S26,S36/37/39
危险类别码：

R36/37/38
海关编码：

2915900090
危险性防范说明：

P261,P280,P301+P312,P302+P352,P305+P351+P338
危险性描述：

H302,H315,H319,H335
储存条件：

存放于阴凉干燥处即可。

SDS

SDS：022c15acbe93520fbc7ae2d48fa80245

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2-乙基己酸钾水合物 修改号码：6

模块 1. 化学品
产品名称： Potassium 2-Ethylhexanoate Hydrate
修改号码： 6

模块 2. 危险性概述
GHS分类
物理性危害未分类
健康危害
皮肤腐蚀/刺激 第2级
严重损伤/刺激眼睛 2A类
环境危害未分类
GHS标签元素
图标或危害标志
信号词警告
危险描述造成皮肤刺激
造成严重眼刺激
防范说明
[预防] 处理后要彻底清洗双手。
穿戴防护手套/护目镜/防护面具。
[急救措施] 眼睛接触：用水小心清洗几分钟。如果方便，易操作，摘除隐形眼镜。继续冲洗。
眼睛接触：求医/就诊
皮肤接触：用大量肥皂和水轻轻洗。
若皮肤刺激：求医/就诊。
脱掉被污染的衣物，清洗后方可重新使用。

模块 3. 成分/组成信息
单一物质/混和物 单一物质
化学名(中文名)： 2-乙基己酸钾水合物
百分比： >90.0%(T)
CAS编码： 3164-85-0
俗名： 2-Ethylhexanoic Acid Potassium Salt Hydrate
2-乙基己酸钾水合物 修改号码：6

模块 3. 成分/组成信息
分子式：
C8H15KO2·xH2O

模块 4. 急救措施
吸入： 将受害者移到新鲜空气处，保持呼吸通畅，休息。若感不适请求医/就诊。
皮肤接触： 立即去除/脱掉所有被污染的衣物。用大量肥皂和水轻轻洗。
若皮肤刺激或发生皮疹：求医/就诊。
眼睛接触：用水小心清洗几分钟。如果方便，易操作，摘除隐形眼镜。继续清洗。
如果眼睛刺激：求医/就诊。
食入： 若感不适，求医/就诊。漱口。
紧急救助者的防护：救援者需要穿戴个人防护用品，比如橡胶手套和气密性护目镜。

模块 5. 消防措施
合适的灭火剂：干粉，泡沫，雾状水，二氧化碳
特定方法：从上风处灭火，根据周围环境选择合适的灭火方法。
非相关人员应该撤离至安全地方。
周围一旦着火：如果安全，移去可移动容器。
消防员的特殊防护用具：灭火时，一定要穿戴个人防护用品。

模块 6. 泄漏应急处理
个人防护措施，防护用具， 使用个人防护用品。远离溢出物/泄露处并处在上风处。
紧急措施：泄露区应该用安全带等圈起来，控制非相关人员进入。
环保措施：防止进入下水道。
控制和清洗的方法和材料：清扫收集粉尘，封入密闭容器。注意切勿分散。附着物或收集物应该立即根据合适的
法律法规处置。

模块 7. 操作处置与储存
处理
技术措施：在通风良好处进行处理。穿戴合适的防护用具。防止粉尘扩散。处理后彻底清洗双手
和脸。
注意事项：如果粉尘或浮质产生，使用局部排气。
操作处置注意事项：避免接触皮肤、眼睛和衣物。
贮存
储存条件：保持容器密闭。存放于凉爽、阴暗处。
存放于惰性气体环境中。
防湿。
远离不相容的材料比如氧化剂存放。
易湿
包装材料：依据法律。

模块 8. 接触控制和个体防护
工程控制：尽可能安装封闭体系或局部排风系统，操作人员切勿直接接触。同时安装淋浴器和洗
眼器。
个人防护用品
呼吸系统防护：防尘面具。依据当地和政府法规。
手部防护：防护手套。
眼睛防护：安全防护镜。如果情况需要，佩戴面具。
皮肤和身体防护：防护服。如果情况需要，穿戴防护靴。
2-乙基己酸钾水合物 修改号码：6

模块 9. 理化特性
固体
外形（20°C）：
外观： 晶体-块状
颜色：白色
气味：无资料
pH: 无数据资料
熔点：无资料
沸点/沸程 无资料
闪点：无资料
爆炸特性
爆炸下限：无资料
爆炸上限：无资料
密度：无资料
溶解度：
[水] 无资料
[其他溶剂] 无资料

模块 10. 稳定性和反应性
化学稳定性：一般情况下稳定。
危险反应的可能性：未报道特殊反应性。
须避免接触的物质氧化剂
危险的分解产物: 一氧化碳, 二氧化碳

模块 11. 毒理学信息
急性毒性：无资料
对皮肤腐蚀或刺激：无资料
对眼睛严重损害或刺激：无资料
生殖细胞变异原性：无资料
致癌性：
IARC = 无资料
NTP = 无资料
生殖毒性：无资料

模块 12. 生态学信息
生态毒性：
鱼类：无资料
甲壳类：无资料
藻类：无资料
残留性 / 降解性： 无资料
潜在生物累积（BCF): 无资料
土壤中移动性
log水分配系数： 无资料
土壤吸收系数（Koc）： 无资料
亨利定律无资料
constaNT(PaM3/mol):

模块 13. 废弃处置
如果可能，回收处理。请咨询当地管理部门。建议在可燃溶剂中溶解混合，在装有后燃和洗涤装置的化学焚烧炉中
焚烧。废弃处置时请遵守国家、地区和当地的所有法规。
2-乙基己酸钾水合物 修改号码：6

模块 14. 运输信息
联合国分类：与联合国分类标准不一致
UN编号： 未列明

模块 15. 法规信息
《危险化学品安全管理条例》（2002年1月26日国务院发布，2011年2月16日修订）: 针对危险化学品的安全使用、
生产、储存、运输、装卸等方面均作了相应的规定。

模块16 - 其他信息
N/A

制备方法与用途

概述

异辛酸钾又名2-乙基己酸钾，化学名称为2-乙基己酸钾。这是一种浅黄色的粘稠液体或固体，容易吸湿。它主要用于合成头孢类抗生素克拉维酸钾的成盐剂，以及作为塑料制品的热稳定剂、聚合反应的催化剂和高分子材料的交联剂。

合成工艺

将氢氧化钾溶解于水中，制备成溶液备用。
将异辛酸加入反应瓶中，在10～20分钟内将上述溶液滴入异辛酸中，并保持pH值在9-12之间。随后逐步升温至60℃～90℃，保温反应2～3小时。
在反应后的混合液中，加入混溶剂进行搅拌萃取30分钟后分相，取出重相。
将上述重相溶液与脱色剂在一定温度下保温脱色30分钟。
过滤物料后送入喷雾干燥器进行干燥。
最终得到异辛酸钾。

用途

主要用作树脂涂料的催干剂和聚氨酯硬泡催化剂等。

反应信息

作为反应物：

描述：

potassium 2-ethylhexanoate 以 4-甲基-2-戊酮为溶剂，生成 potassium p-hydroxymandelate

参考文献：

名称：

p-Hydroxymandelic acid

摘要：

一种分离p-羟基曼德酸固体盐的方法，包括在氢氧化钠或氢氧化钾存在下，将苯酚与乙酰乙酸反应，酸化至pH小于3，用不溶于水的溶剂提取所得溶液以提供p-羟基曼德酸的溶液，并从中沉淀盐。

公开号：

US04368334A1
作为产物：

描述：

2-乙基己醇在 palladium on activated charcoal 氢氧化钾作用下，反应 18.0h，生成 potassium 2-ethylhexanoate

参考文献：

名称：

Chiusoli, Gian Paolo; Giroldini, William; Salerno, Giuseppe, Gazzetta Chimica Italiana, 1980, vol. 110, # 7/8, p. 371 - 374

摘要：

DOI：
作为试剂：

描述：

Boc-L-蛋氨酸、 alkaline earth salt of/the/ methylsulfuric acid 在盐酸、氯化亚砜、 potassium 2-ethylhexanoate 、 4-甲基-2-戊酮作用下，以甲醇、苯为溶剂，反应 1.0h，生成

参考文献：

名称：

Sankar; Raghuraman; Sulthana, Pharmazie, 2001, vol. 56, # 7, p. 588 - 589

摘要：

DOI：

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文献信息

Stereospecific production of 6- or 7-carbon-substituted-.beta.-lactams

申请人：Schering Corporation

公开号：US04237051A1

公开（公告）日：1980-12-02

Reaction of 6- or 7-diazo-.beta.-lactams with allylic halides in the presence of a catalytic amount of metallic copper or a copper salt affords 6- or 7-carbon-substituted-.beta.-lactams with the desired stereochemical configuration at the 6- or 7-position. Subsequent reduction with a trialkyl stannane affords useful intermediates for further syntheses affording 6- or 7-carbon-substituted-.beta.-lactams. The present invention relates to a process for the production of 6- or 7-carbon-substituted-.beta.-lactams having the desired stereochemical configuration at the 6- or 7-position. More particularly, this invention provides a process for the preparation of a .beta.-lactam of the formula ##STR1## wherein R.sub.1 is cyano or COOR.sub.2 wherein R.sub.2 is a readily removable ester-forming moiety, hydrogen or an alkali-metal cation; R.sub.3 and R.sub.4 are independently hydrogen, lower alkyl, aryl or aralkyl; Z is a group of the formula ##STR2## wherein R.sub.5 is hydrogen, lower alkyl or aralkyl; and the dotted line indicates the optional presence of a double bond; which comprises (1) reacting a diazo-.beta.-lactam of the formula ##STR3## wherein Y is a sulfur or an oxygenated sulfur atom and Z, R.sub.1, R.sub.3, and R.sub.4 are as hereinbefore defined; with an allyl halide of the formula ##STR4## wherein R.sub.3 and R.sub.4 are as hereinbefore defined and X is bromo or iodo; in the presence of a catalytic amount of metallic copper or a copper salt; and where Y is an oxygenated sulfur atom, followed by transformation of the resultant oxygenated sulfur intermediate to a compound wherein Y is a sulfur atom; and (2) subjecting the resultant intermediate of the formula ##STR5## wherein X, Z, R.sub.1, R.sub.3, and R.sub.4 are as hereinabove defined, to reduction with a trialkyl stannane to afford the compound of formula I. The lower alkyl groups referred to contain 1 to 6 carbon atoms and are exemplified by methyl, ethyl, propyl, butyl, pentyl, hexyl and the corresponding branched-chain isomers thereof. The lower alkoxy groups referred to above likewise contain 1 to 6 carbon atoms and are exemplified by methoxy, ethoxy, propoxy, and the like. The term "aryl" as used herein refers to phenyl substituted by one or more substituent groups selected from among chloro, bromo, fluoro, lower alkyl, hydroxy, nitro, amino, aminomethyl, lower monoalkylamino, lower dialkylamino, lower alkoxy and carboxy. Such aryl groups represented by R.sub.1 can be, for example, 4-hydroxyphenyl, 3,4-dichlorophenyl, 2,6-dimethoxyphenyl, 4-methylphenyl, 2-fluorophenyl, 4-carboxyphenyl, 3-nitrophenyl, 4-aminophenyl, 3-aminophenyl, 4-dimethylaminophenyl, 4-aminomethylphenyl and 4-ethoxyphenyl. The term "aralkyl" encompasses aryl-substituted lower alkyl groups such as benzyl, phenethyl, p-fluorobenzyl, o-tolylethyl and m-hydroxy-phenethyl. The process of this invention initially involves the reaction of a diazo-.beta.-lactam of formula II and the allyl halide of formula III in the presence of a catalytic amount of metallic copper or a copper salt to induce the decomposition of the diazo-.beta.-lactam at temperatures of about 0.degree.-50.degree. C. to provide the intermediate of formula IV. The diazo-.beta.-lactam utilizable in this step of the invention may be any type of readily removable ester-blocked acid, i.e., the compound of formula II wherein R.sub.1 is COOR.sub.2 or a nitrile, i.e., the compound of formula II wherein R.sub.1 is cyano. Preferably, benzyl or benzhydryl esters are employed in the reaction wherein R.sub.1 is COOR.sub.2. The starting materials of formula II wherein Y is oxygenated sulfur are preferred due to the stability of the starting compound. However, the reaction using the equivalent sulfide also proceeds with good yields and avoids the need for a subsequent deoxygenation step. The allyl halides of formula III utilizable in the present invention are those wherein the halogen is iodine or bromine with iodine being most particularly preferred. The allyl halide of formula III may be substituted by lower alkyl, aryl or aralkyl groups. Those compounds wherein R.sub.3 and R.sub.4 are methyl or phenyl are preferred. The copper compound utilizable as a catalyst for this step of the instant invention may be almost any copper salt or finely divided elemental copper. Preferably, 1-10 mole percent of the copper or copper salt is utilized. The most preferred catalysts are cuprous chloride and copper (II)-2,4-pentanedioate. In order to maximize the yield for this step of the instant invention, it is preferable to use a large excess of the allyl halide of formula III. Most preferably, allyl bromide or allyl iodide is used as the reaction medium. Substituted allyl halides of formula III are preferably diluted with a non-polar co-solvent such as methylene chloride. Polar solvents may also be used, e.g., dimethylformamide, dimethylsulfoxide or acetonitrile, but these provide poorer yields. The reaction is preferably carried out at room temperature; however, depending on the nature of the starting materials, the reaction temperatures may range from about 0.degree. to 50.degree. C. Occasionally, warming to about 40.degree. C. is utilized to initiate the reaction which is then continued without further heating. The stereochemistry at C-6 or C-7 of the intermediate of formula IV is generally a mixture of alpha and beta compounds. Generally, use of the bromides gives a higher ratio of beta to alpha compounds, i.e., 5 to 6:1. Use of the iodides gives more approximately equal amounts of the alpha and beta isomers. The reduction of step 2 to afford the cis product of formula I is accomplished using trialkyl stannane (trialkyl tin hydride). Preferably, tri-n-butyl stannane is utilized. The intermediate of formula IV is heated at about 60.degree.-100.degree. C. with 1-2 equivalents of the tin hydride in an inert solvent. Preferred solvents are tetrahydrofuran, benzene and toluene. Typically, the product is separated by chromatography in yields of greater than 80%. The compounds of formula II wherein Y is an oxygenated sulfur atom may be obtained from the corresponding compounds wherein Y is sulfur by any of the conventional oxidation procedures, e.g., ozone, iodobenzene dichloride in aqueous pyridine, etc. An oxygenated sulfur penicillin compound, i.e., wherein Z is ##STR6## may then be converted to the corresponding cephalosporin, i.e., wherein Y is S and Z is ##STR7## by various literature methods. See, for instance, Flynn, "Cephalosporins and Penicillins", Academic Press, pp. 193-199 and 670-673 (1972). By such methods benzyl 6.beta.-allyl-6.alpha.-bromopenicillanate-1.beta.-oxide may be converted to benzyl 7.beta.-allyl-6.alpha.-bromo-3-methyl-3-cephem-4-carboxylate. The sulfoxide compound is also particularly useful wherein it is desired to convert a mixture of 2- and 3-cephem compounds to a pure 3-cephem compound. The 6- or 7-diazo starting materials of formula II are preparable via a variety of literature methods or variations thereof. A preferred method involves degradation of the penicillin or cephalosporin side chain via the N-nitroso derivative as described by Hausler and Sigg, Helv. Chim. Acta., 1327 (1967); and Sheehan, J. Org. Chem., 39, 1444 (1974). This process involves treatment of the penicillin or cephalosporin, e.g., benzylpenicillin benzyl ester or benzhydryl ester, to form the N-nitroso derivative, followed by decomposition of the nitroso amide side chain with methylene chloride-pyridine or methylene chloride at about 40.degree. C. to afford the diazo compound. An improvement of this process, omitting the pyridine and allowing the reaction to proceed at room temperature in a polar solvent, e.g., dimethylsulfoxide or dimethylformamide, affords a cleaner reaction and better conversion, i.e., >90%. This reaction sequence may be represented by the following scheme: ##STR8## wherein Y, Z and R.sub.1 are as hereinbefore defined. Preferable by this route are the following: benzyl 6-diazopenicillanate; benzhydryl 6-diazopenicillanate; 6-diazopenicillanonitrile; and benzyl 7-diazo-3-methylcephalosporanate. Another modification of the decomposition step in the preparation of the starting materials of formula II is to utilize triphenylphosphine and water in place of the methylene chloride and pyridine according to the method of Sheehan, J. Org. Chem., 42, 1012 ( 1977) to afford the hydrazone of the formula: ##STR9## Oxidation of this hydrazone by the method of U.S. Pat. No. 3,880,837 affords the desired diazo compound. This route is particularly preferred for the cephalosporin starting materials of this invention. Preparable by this route are the following: benzhydryl 7-diazo-3-methylcephalosporinate; benzhydryl 7-diazo-3-acetoxymethylcephalosporinate; and benzhydryl 6-diazopenicillanate. An additional method for preparing the 6- or 7-diazo compounds of formula II involves diazotisation of the corresponding amino compounds using nitrous acid according to the procedure originally carried out by Hausler and Sigg, Helv. Chim. Acta., 1327 (1967) and further delineated in J. Amer. Chem. Soc., 94, 1408 (1972) and J. Org. Chem., 41, 1578 (1976). Once prepared, the compounds of formula I are utilizable to prepare various 6- or 7-substituted-.beta.-lactams having useful antimicrobial activity, many of which are known in the art. For instance, ozonolysis of 6.beta.-(allyl)penicillanonitrile, benzyl 6.beta.-(allyl)penicillanate or benzhydryl 6.beta.-allylpenicillanate affords 6.beta.-(formylmethyl)-penicillanonitrile, benzyl 6.beta.-(formylmethyl)penicillanate and benzhydryl 6.beta.-(formylmethyl)penicillanate, respectively. This ozonolysis is carried out according to standard methodology. The aldehyde obtained by the ozonolysis described in the preceding paragraph may then be subjected to reduction utilizing a mild reducing agent such as sodium borohydride to afford the corresponding alcohol. For instance, obtainable by this reaction is 6.beta.-(2-hydroxyethyl)penicillanonitrile, benzyl 6.beta.-(2-hydroxyethyl)penicillanate and benzhydryl 6.beta.-(2-hydroxyethyl)penicillanate. The ester group of the preceding two compounds may, of course, be removed utilizing standard hydrogenolysis typically with a palladium catalyst to afford the resulting free acids. Workup with a weak base, e.g., potassium carbonate or sodium carbonate, will afford the potassium or sodium salts, e.g., potassium 6.beta.-(2-hydroxyethyl)penicillanate or sodium 6.beta.-(2-hydroxyethyl)penicillanate. Oxidation of the aldehydes obtainable by the ozonolysis procedure affords the corresponding carboxylic acids. For instance, benzhydryl 6.beta.-(formylmethyl)penicillanate treated with chromic acid in acetone and water affords benzhydryl 6.beta.-(carboxymethyl)penicillanate. Reaction of the foregoing carboxylic acids with suitable azides provides various homo-penicillanates. For instance, benzhydryl 6.beta.-(carboxymethyl)penicillanate treated with diphenylphosphoryl azide and triethylamine at a reaction temperature of about 80.degree. C. according to the method of Ninomiya, et. al., Chem. Pharm. Bull. Japan, 22, 1398 (1974), affords benzhydryl 6.beta.-(carbonylaminomethyl)penicillanate which is typically not isolated. Treatment of this intermediate with the desired acid or alcohol provides homopenicillanates which then may be optionally deblocked. Obtainable in this method are potassium 6.beta.-(phenylacetamidomethyl)penicillanate and potassium 6.beta.-(ethoxycarbonylaminomethyl)penicillanate. Treatment of benzhydryl 6.beta.-(carbonylaminomethyl)penicillanate with trichloroethanol followed by a zinc/acetic acid reduction affords benzhydryl 6.beta.-(aminomethyl)penicillanate. Conventional deblocking of this compound then affords 6.beta.-(aminomethyl)penicillanic acid. Several of the foregoing compounds are described by Sheehan, et. al. as having useful and interesting antimicrobial activity in German Pat. Nos. 2,416,492 and 2,643,085. However, 6.beta.-(aminomethyl)penicillanic acid has not heretofore been described in any publication and is therefore a novel compound. The 6.beta.-(aminomethyl)penicillanic acid produced by the process of this invention possesses antibacterial activity. Additionally, it is a penicillinase inhibitor which may be used concomitantly with other penicillin-type antibiotics in infection therapy. Thus, when tested in standardized microbiological assays, this compound exhibits activity vis-a-vis such organisms as Staphylococcus aureus, Klebsiella, Bacillus subtilis, and Pseudomonas aeruginosa at test levels of 0.1 to 100 .mu.cg/ml. Thus, as antibacterial agents this compound is conventionally formulated for oral, intramuscular, intravenous or topical therapy. Thus, the present invention includes within its scope pharmaceutical compositions comprising an antibacterially effective amount of the novel 6.beta.-(aminomethyl)penicillanic acid with a compatible pharmaceutical carrier therefor, and a method of using such compositions for the treatment of microbial infections. The dosage administered of this compound is dependent upon the age and weight of the animal species being treated, the mode of administration, and the type and severity of bacterial infection being prevented or reduced. Typically, the dosage administered per day will be in the range of 100-5000 mg with 500-1000 mg being preferred. For oral administration, this compound may be formulated in the form of tablets, capsules, elixirs or the like. For parenteral administration it may be formulated into solutions or suspensions for intramuscular injection. Topical formulations include creams, ointments, gels and the like.

在微量金属铜或铜盐的催化下，6-或7-重氮-.beta.-内酰胺与烯丙基卤化物的反应，可得到在6-或7位具有所需立体化学配置的6-或7-碳取代-.beta.-内酰胺。随后使用三烷基锡烷进行还原，可得到适用于进一步合成6-或7-碳取代-.beta.-内酰胺的有用中间体。本发明涉及一种生产在6-或7位具有所需立体化学配置的6-或7-碳取代-.beta.-内酰胺的方法。更具体地，本发明提供了一种制备具有以下公式的.beta.-内酰胺的方法： ##STR1## 其中R1是氰基或COOR2，其中R2是易于移除的酯形成基团、氢或碱金属阳离子；R3和R4独立地为氢、低级烷基、芳基或芳烷基；Z是具有以下公式的基团： ##STR2## 其中R5是氢、低级烷基或芳烷基；虚线表示双键的可选存在；该方法包括：(1)将具有以下公式的重氮-.beta.-内酰胺： ##STR3## 其中Y是硫或氧化的硫原子，Z、R1、R3和R4如前所述；与具有以下公式的烯丙基卤化物反应： ##STR4## 其中R3和R4如前所述，X是溴或碘；在微量金属铜或铜盐的存在下；当Y是氧化的硫原子时，随后将所得的氧化的硫中间体转化为Y为硫原子的化合物；以及(2)将具有以下公式的所得中间体： ##STR5## 其中X、Z、R1、R3和R4如前所述，进行还原，使用三烷基锡烷得到公式I的化合物。所提及的低级烷基含有1至6个碳原子，例如甲基、乙基、丙基、丁基、戊基、己基及其相应的支链异构体。所提及的低级烷氧基同样含有1至6个碳原子，例如甲氧基、乙氧基、丙氧基等。术语“芳基”如本文所用，指的是被一个或多个选自氯、溴、氟、低级烷基、羟基、硝基、氨基、氨基甲基、低级单烷基氨基、低级二烷基氨基、低级烷氧基和羧基的取代基团取代的苯基。代表R1的此类芳基可以是例如4-羟基苯基、3,4-二氯苯基、2,6-二甲氧基苯基、4-甲基苯基、2-氟苯基、4-羧基苯基、3-硝基苯基、4-氨基苯基、3-氨基苯基、4-二甲基氨基苯基、4-氨基甲基苯基和4-乙氧基苯基。术语“芳烷基”包括被芳基取代的低级烷基基团，如苄基、苯乙基、对氟苄基、邻甲苯乙基和间羟基苯乙基。本发明的过程首先涉及在微量金属铜或铜盐的存在下，将公式II的重氮-.beta.-内酰胺与公式III的烯丙基卤化物反应，以在约0°至50°C的温度下诱导重氮-.beta.-内酰胺的分解，提供公式IV的中间体。在本发明这一步骤中可用的重氮-.beta.-内酰胺可以是任何类型的易于移除的酯阻断酸，即公式II的化合物，其中R1是COOR2或腈，即公式II的化合物，其中R1是氰基。优选地，在R1是COOR2的反应中使用苄基或二苄基酯。由于起始化合物的稳定性，公式II的起始材料，其中Y是氧化的硫，是优选的。然而，使用等效硫化物的反应也以良好的产率进行，并避免了随后的脱氧步骤的需要。在本发明中可用的公式III的烯丙基卤化物是那些卤素为碘或溴的，其中碘是最特别优选的。公式III的烯丙基卤化物可以被低级烷基、芳基或芳烷基基团取代。那些R3和R4为甲基或苯基的化合物是优选的。在本发明这一步骤中可用的铜化合物可以是几乎任何铜盐或细分的金属铜。优选地，使用1-10摩尔百分比的铜或铜盐。最优选的催化剂是氯化亚铜和铜(II)-2,4-戊二酸酯。为了最大化本发明这一步骤的产率，优选使用大量过量的公式III的烯丙基卤化物。最优选地，作为反应介质使用烯丙基溴或烯丙基碘。公式III的取代烯丙基卤化物优选地用非极性共溶剂如二氯甲烷稀释。也可以使用极性溶剂，例如二甲基甲酰胺、二甲基亚砜或乙腈，但这些提供较差的产率。反应优选在室温下进行；然而，根据起始材料的性质，反应温度可以从约0°到50°C。偶尔，加热到约40°C以启动反应，然后在没有进一步加热的情况下继续进行。公式IV的中间体在C-6或C-7的立体化学通常是α和β化合物的混合物。一般来说，使用溴化物给出β到α化合物的更高比例，即5到6:1。使用碘化物给出α和β异构体更接近相等的量。步骤2的还原以得到公式I的顺式产物是通过使用三烷基锡烷（三烷基锡烷氢化物）完成的。优选地，使用三正丁基锡烷。将公式IV的中间体在约60°至100°C下与1-2当量的锡烷在惰性溶剂中加热。优选的溶剂是四氢呋喃、苯和甲苯。通常，产品通过色谱法分离，产率超过80%。公式II的化合物，其中Y是氧化的硫原子，可以通过任何常规氧化程序从相应的Y为硫的化合物获得，例如臭氧、碘苯二氯化物在水性吡啶中等。氧化的硫青霉素化合物，即Z为： ##STR6## 可以然后通过各种文献方法转换为相应的头孢菌素，即Y为S且Z为： ##STR7## 例如，参见Flynn，“头孢菌素和青霉素”，学术出版社，第193-199页和670-673页（1972）。通过这些方法，苄基6.β.-烯丙基-6.α.-溴青霉烷酸-1.β.-氧化物可以转换为苄基7.β.-烯丙基-6.α.-溴-3-甲基-3-头孢-4-羧酸酯。当希望将2-和3-头孢化合物混合物转换为纯3-头孢化合物时，亚砜化合物也特别有用。公式II的6-或7-重氮起始材料可以通过各种文献方法或其变体制备。优选的方法涉及通过N-亚硝基衍生物描述的青霉素或头孢菌素侧链的降解，如Hausler和Sigg，Helv. Chim. Acta.,1327（1967）；以及Sheehan，J. Org. Chem.,39,1444（1974）。该过程涉及处理青霉素或头孢菌素，例如苄基青霉素苄基酯或二苄基酯，形成N-亚硝基衍生物，然后在大约40°C的甲基氯仿-吡啶或甲基氯仿中分解亚硝基酰胺侧链，得到重氮化合物。对该过程的改进，省略了吡啶并允许反应在极性溶剂如二甲基亚砜或二甲基甲酰胺中在室温下进行，提供了更清洁的反应和更好的转换，即>90%。该反应序列可以由以下方案表示： ##STR8## 其中Y、Z和R1如前所述。通过这条路线优选的是以下：苄基6-重氮青霉烷酸酯；二苄基6-重氮青霉烷酸酯；6-重氮青霉烷腈；和苄基7-重氮-3-甲基头孢菌酸

potassium 2-ethylhexanoate | 3164-85-0

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