(4-fluoro-2-iodophenyl)acetic acid | 70931-61-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-fluoro-2-iodophenyl)acetic acid
• 英文别名: 4-fluoro-2-iodophenyl acetic acid；4-Fluoro-2-iodophenylacetic acid；2-(4-fluoro-2-iodophenyl)acetic acid
• CAS: 70931-61-2
• 化学式: C₈H₆FIO₂
• 分子量: 280.037
• InChiKey: KUORKOPHMADFKV-UHFFFAOYSA-N

物化性质

• 沸点：
  342.1±27.0 °C(Predicted)
• 密度：
  1.956±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-fluoro-2-iodophenyl)acetic acid 在 盐酸 、 氢氧化钾 、 sodium hydroxide 、 sodium tetrahydroborate 、 PPA 、 铜 、 calcium chloride 作用下， 以 乙醇 、 甲苯 、 苯 为溶剂， 反应 7.0h， 生成 11-chloro-2-ethyl-7-fluoro-10,11-dihydrodibenzothiepin
  参考文献：
  名称：

  Fluorinated tricyclic neuroleptics with prolonged action: 8-Alkyl derivatives of 3-fluoro-10-piperazino-10,11-dihydrodibenzo[b,f]thiepins

  摘要：

  (4-氟-2-碘苯基)乙酸或(2-溴-4-氟苯基)乙酸与4-甲基硫代苯酚、4-乙基硫代苯酚和4-异丙基硫代苯酚在不同条件下反应，生成酸IIIa-c，再通过多聚磷酸环化得到8-烷基-3-氟二苯并[]噻吩-10(11H)-酮IVa-c。用硼氢化钠还原酮得到醇Va-c，再经氯化氢处理得到氯代衍生物Via-c。它们与1-甲基哌嗪和1-(2-羟乙基)哌嗪的取代反应生成目标化合物Ib、Ic和IIa。相应的2-烷基-7-氟二苯并[]噻吩VIIa-c作为副产物获得。将酮IVc与1-甲基哌嗪在四氯化钛存在下反应得到烯胺VIII。制备的哌嗪衍生物在其急性活性方面具有很强的神经酰胺类药物作用。发现其效果的重要延长主要是由异丙基化合物Ic和VIII引起的。

  DOI：

  10.1135/cccc19842638
• 作为产物：
  描述：

  在 水 、 silver(I) acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以900 mg的产率得到(4-fluoro-2-iodophenyl)acetic acid
  参考文献：
  名称：

  Phosphodiesters as GPR84 Antagonists for the Treatment of Ulcerative Colitis

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c01813

文献信息

• 3 Fluoro-10-piperazino-8-substituted 10,11-dihydrodibenzo-(bf) thiepins
  申请人：SPOFA, spojene podniky pro zdravotnickou vyrobu

  公开号：US04243805A1

  公开（公告）日：1981-01-06

  Techniques for the preparation of 3-fluoro-10-piperazino-8-substituted 10,11-dihydrodibenzo-(b,f) thiepins and their addition salts with organic and inorganic acids are disclosed. The described compositions evidence psychotropic activity and low toxicity and are characterized as neuroliptics with a high degree of cataleptic, anti-apomorphine and central depressant action.

  本文揭示了制备3-氟-10-哌嗪基-8-取代的10,11-二氢二苯并[b,f]噻吩及其与有机和无机酸的加合盐的技术。所述组合物具有精神活性和低毒性，并被描述为神经立平剂，具有高度的猫病性、抗阿波莫啡和中枢抑制作用。
• Potential metabolites of tricyclic neuroleptics and their fluorinated analogues; 3-Hydroxy-, 3-methoxy- and 3-fluoro-10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin
  作者：Miroslav Protiva、Karel Šindelář、Zdeněk Šedivý、Jiřina Metyšová

  DOI：10.1135/cccc19792108

  日期：——

  4-Methoxy-2-(phenylthio)benzoic acid (V) was transformed in four steps to the homologous acid IXa which was cyclized to 3-methoxydibenzo[b,f]thiepin-10(11H)-one (Xa). The 3-methoxy derivative III of perathiepin (I) was synthesized via the intermediates XIa and XIIa, and demethylated with boron tribromide to the phenolic compound II. The analogous 3-fluoro derivative IV was synthesized from (4-fluoro-2-iodophenyl)acetic acid (XVII), the preparation of which by several procedures is described. Whereas III has only mild tranquilizing activity, II is more potent than perathiepin (I) in the tests for central depressant and cataleptic effects. The 3-fluoro derivative IV, while lacking the properties of a neuroleptic agent, is highly central depressant and this effect shows some prolongation after oral administration.

  4-甲氧基-2-(苯硫基)苯甲酸（V）经过四步转化为同系物酸IXa，后者被环化为3-甲氧基二苯并[bf]噻吩-10(11H)-酮（Xa）。过硫噻吩（I）的3-甲氧基衍生物III，通过中间体XIa和XIIa合成，并用三溴化硼去甲基化为酚化合物II。类似的3-氟衍生物IV是由(4-氟-2-碘苯基)乙酸（XVII）合成的，其制备过程描述了几种方法。尽管III仅具有轻微的镇静活性，II在中枢抑制和痉挛效应测试中比过硫噻吩（I）更有效。3-氟衍生物IV虽然不具有神经阻滞剂的特性，但具有很强的中枢抑制作用，并且这种效果在口服后有一定延长。
• Fluorinated tricyclic neuroleptics with prolonged action: 3-Fluoro-8-halogeno derivatives of 10-piperazino-10,11-dihydrodibenzo[b,f]thiepins
  作者：Miroslav Protiva、Karel Šindelář、Jiřina Metyšová、Jiří Holubek、Miroslav Ryska、Emil Svátek、Zdeněk Šedivý、Josef Pomykáček

  DOI：10.1135/cccc19811788

  日期：——

  Reactions of (4-fluoro-2-iodophenyl)acetic acid with 4-fluoro and 4-bromothiophenol gave the acids IIIa and IIIc which were cyclized to 3-fluoro-8-halogenodibenzo[b,f]thiepin-10(11H)-ones IVa and IVc. The title compounds Ia and IIc were obtained via the intermediates VIac and VIIac. Reactions of (4-fluoro-2-mercaptophenyl)acetic acid or 6-fluorobenzo[b]thiophen-2(3H)-one with 4-chloronitrobenzene afforded the nitro acid IIIe which was reduced to the amino acid IIIf. Cyclization gave the amino ketone IVf which was transformed to the iodo ketone IVd. Proceeding via the intermediates VId and VIId led to the final product IId. Compounds Ia and IIcd have strong central depressant and cataleptic activity; prolongation of the effect is connected merely with the central depressant component of the action.

  (4-氟-2-碘苯基)乙酸与4-氟和4-溴噻吩酚反应，得到酸IIIa和IIIc，它们被环化成3-氟-8-卤代二苯并[ b,f ]噻吩-10(11H)-酮IVa和IVc。通过中间体VIac和VIIac得到了标题化合物Ia和IIc。(4-氟-2-巯基苯基)乙酸或6-氟苯并[ b ]噻吩-2(3H)-酮与4-氯硝基苯反应，得到硝基酸IIIe，再还原成氨基酸IIIf。环化反应得到氨基酮IVf，转化为碘代酮IVd。通过中间体VId和VIId得到最终产物IId。化合物Ia和IIcd具有强烈的中枢抑制和僵硬作用；效果的延长仅与中枢抑制成分有关。
• Fluorinated tricyclic neuroleptics with prolonged action: 3-Fluoro-8-trifluoromethyl derivatives of 10-(4-methylpiperazino)- and 10-[4-(2-hydroxyethyl)piperazino]-10,11-dihydrodibenzo-[b,f]thiepin
  作者：Karel Šindelář、Miroslav Ryska、Jiří Holubek、Emil Svátek、Jiřina Metyšová、Jiří Protiva、Miroslav Protiva

  DOI：10.1135/cccc19810118

  日期：——

  A reaction of (4-fluoro-2-iodophenyl)acetic acid with 4-(trifluoromethyl)thiophenol gave the acid VIII which was cyclized with the reagent consisting from methanesulphonic acid and phosphorus pentoxide and afforded the methanesulphonic enol ester XIX. The alkaline hydrolysis resulted in 3-fluoro-8-trifluoromethyldibenzo[b,f]thiepin-10(11H)-one (XVI) which was transformed via the alcohol XXIV to the chloro derivative XXV. Substitution reactions with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine resulted in the title compounds IV and V. These products are very potent cataleptic neuroleptic agents with a prolongation of duration of the effects comparable to that of isofloxythepin and tefluthixol. A series of further synthetic experiments aimed at alternative syntheses of the acid VIII and the ketone XVI; their results were mostly not of use for preparative purpose but they led to isolation and characterization of a series of interesting heterocyclic products (XVII, XVIII, XXII, XXIII, XXIX-XXXI, XXXVI-XXXIX).

  (4-氟-2-碘苯基)乙酸与4-(三氟甲基)硫代苯酚反应，生成酸VIII，然后与由甲磺酸和五氧化二磷组成的试剂环化，生成甲磺酸烯基酯XIX。碱性水解产生3-氟-8-三氟甲基二苯并[bf]噻吩-10(11H)-酮(XVI)，通过醇XXIV转化为氯衍生物XXV。与1-甲基哌嗪和1-(2-羟乙基)哌嗪的取代反应产生IV和V。这些产物是非常有效的猫病性镇静剂，其效果持续时间延长，与异氟沙替平和替氟西乐相当。一系列进一步的合成实验旨在寻找酸VIII和酮XVI的替代合成方法；它们的结果大多数并没有用于制备目的，但导致了一系列有趣的杂环产物(XVII、XVIII、XXII、XXIII、XXIX-XXXI、XXXVI-XXXIX)的分离和表征。
• 2-Chloro-7-fluoro- and 2-chloro-3,7-difluoro-11-[4-(4-fluoroaralkyl)piperazino]-10,11-dihydrodibenzo-[b,f]thiepins and related compounds; Long acting tranquillizers
  作者：Václav Bártl、Jiřina Metyšová、Miroslav Protiva

  DOI：10.1135/cccc19810141

  日期：——

  Substitution reactions of 2,11-dichloro-7-fluoro-(seriesa) and 2,11-dichloro-3,7-difluoro-10,11-dihydrodibenzo[b,f]thiepin (seriesb) with 1-(4-fluorobenzyl)piperazine, 1-[2-(4-fluorophenyl)-ethyl]piperazine, 1-[2-(4-fluorophenoxy)ethyl]piperazine, 1-[2-(4-fluorophenylthio)ethyl]piperazine, 1-[3-(4-fluorobenzoyl)propyl]piperazine and 1-[4,4-bis-(4-fluorophenyl)butyl]piperazine gave the title compounds Ia,b-VIa,b. Compounds of the series a are little toxic, have low cataleptic activity and display a relatively high central depressant activity, being fully developed only after 4 h and persisting until the 3rd-7th day after the oral administration. Compounds of series b are less active and the protracted depressant effects are shown only by substances IIIb and Vb.

  2,11-二氯-7-氟-(系列a)和2,11-二氯-3,7-二氟-10,11-二氢二苯并[b,f]噻吩（系列b）与1-(4-氟苯基)哌嗪、1-[2-(4-氟苯基)乙基]哌嗪、1-[2-(4-氟苯氧基)乙基]哌嗪、1-[2-(4-氟苯基硫基)乙基]哌嗪、1-[3-(4-氟苯甲酰基)丙基]哌嗪和1-[4,4-双(4-氟苯基)丁基]哌嗪发生取代反应，得到标题化合物Ia,b-VIa,b。系列a化合物毒性较小，具有低的瘫痪活性，并表现出相对较高的中枢抑制活性，仅在口服后4小时后完全发展，并持续到第3-7天。系列b化合物活性较低，仅IIIb和Vb物质显示出持久的抑制效果。