1-allyl-2-(2-bromoethoxy)benzene | 59825-59-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-allyl-2-(2-bromoethoxy)benzene
• 英文别名: 1-(2-Bromoethoxy)-2-(prop-2-en-1-yl)benzene；1-(2-bromoethoxy)-2-prop-2-enylbenzene
• CAS: 59825-59-1
• 化学式: C₁₁H₁₃BrO
• mdl: MFCD12095720
• 分子量: 241.128
• InChiKey: WAIBTUCLMZSEOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-allyl-2-(2-bromoethoxy)benzene 在 palladium dichloride 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 以90 %的产率得到1-(2-bromoethoxy)-2-(trans-1-propenyl)benzene
  参考文献：
  名称：

  新型合成乙氧基苯基苯磺酰胺的抗增殖活性、分子对接研究与计算

  摘要：

  在此说明中，我们合成了新型苯磺酰胺并检查了其生物学评价。首先，2-烯丙基苯酚( 1 )与1,2-二溴乙烷( 2 )反应得到相应的1-烯丙基-2-(2-溴乙氧基)苯( 3 )，它很容易被PdCl 2异构化得到(E )-1-(2-溴乙氧基)-2-(prop-1-en-1-yl)苯 ( 4 )。此外，利用化合物 4 与邻乙酰氨基苯酚的Williamson反应得到不同的乙酰胺衍生物 6。此外，化合物 6的酸水解 得到相应的 2-[2-(2-丙烯基-苯氧基)-乙氧基]-苯胺 ( 8)与对甲苯磺酰氯反应得到相应的(E)-4-甲基-N-(2-(2-(2-(prop-1-en-1-yl)苯氧基)乙氧基)苯基)苯磺胺类药物 ( 10 )。化合物10与溴代衍生物的反应性利用 100°C 下的微波辐射，得到相应的苯磺酰胺衍生物 11a-c。苯磺酰胺衍生物11a-c对 HepG2 和 MCF-7 肿瘤细胞表现出体

  DOI：

  10.1016/j.molstruc.2022.134871
• 作为产物：
  描述：

  1,2-二溴乙烷 、 2-烯丙基酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78 %的产率得到1-allyl-2-(2-bromoethoxy)benzene
  参考文献：
  名称：

  新型合成乙氧基苯基苯磺酰胺的抗增殖活性、分子对接研究与计算

  摘要：

  在此说明中，我们合成了新型苯磺酰胺并检查了其生物学评价。首先，2-烯丙基苯酚( 1 )与1,2-二溴乙烷( 2 )反应得到相应的1-烯丙基-2-(2-溴乙氧基)苯( 3 )，它很容易被PdCl 2异构化得到(E )-1-(2-溴乙氧基)-2-(prop-1-en-1-yl)苯 ( 4 )。此外，利用化合物 4 与邻乙酰氨基苯酚的Williamson反应得到不同的乙酰胺衍生物 6。此外，化合物 6的酸水解 得到相应的 2-[2-(2-丙烯基-苯氧基)-乙氧基]-苯胺 ( 8)与对甲苯磺酰氯反应得到相应的(E)-4-甲基-N-(2-(2-(2-(prop-1-en-1-yl)苯氧基)乙氧基)苯基)苯磺胺类药物 ( 10 )。化合物10与溴代衍生物的反应性利用 100°C 下的微波辐射，得到相应的苯磺酰胺衍生物 11a-c。苯磺酰胺衍生物11a-c对 HepG2 和 MCF-7 肿瘤细胞表现出体

  DOI：

  10.1016/j.molstruc.2022.134871

文献信息

• Alkenylphenol-based pyridinium salts as hydrogen sulfide corrosion inhibitors and agents for inhibiting the growth of sulfate-reducing bacteria in oil production
  作者：G. M. Mekhtieva、A. M. Magerramov、M. R. Bairamov、M. A. Agaeva、Sh. B. Khoseinzade、G. M. Gasanova

  DOI：10.1134/s0965544115030081

  日期：2015.5

  St 3. The best protective properties have been shown by 1-(2-propenylphenoxytetramethylene)-N-pyridinium bromide (III) and 1-(2-allylphenoxytetramethylene)-N-pyridinium bromide (VI): the corrosion protection by III and VI is respectively 87 and 83% at a concentration of 50 mg/L or 96 and 93% at a concentration of 150 mg/L. The pyridinium salts synthesized in this study also exhibit bactericidal activity

  据报道，对重金属盐和恒电位研究结果进行了研究，该结果来自烯基酚的吡啶鎓盐作为St 3钢在水盐和碳氢化合物体系中的硫化氢腐蚀抑制剂，并测试了盐对硫酸盐还原细菌（SRB）的杀菌活性。已经发现，浓度为50–150 mg / L的测试化合物会减慢St和3的阴极和阳极反应，并显着提高St 3的极化电阻（R p）。1-（-）显示出最佳的保护性能。 2-丙烯基苯氧基四亚甲基）-N-溴化吡啶鎓（III）和1-（2-烯丙基苯氧基四亚甲基）-N-溴化吡啶鎓（VI）：在50 mg / L的浓度下，III和VI的腐蚀防护分别为87％和83％，在150 mg / L的浓度下分别为96和93％。在这项研究中合成的吡啶鎓盐还具有50-200 mg / L的杀菌活性。已经发现1-（2-丙烯基苯氧基四亚甲基）-N-溴化吡啶鎓具有高的杀菌性能。浓度为50或75 mg / L时SRB的生长抑制分别为75％或100％。
• Highly efficient Ru(<scp>ii</scp>)–alkylidene based Hoveyda–Grubbs catalysts for ring-closing metathesis reactions
  作者：Mariam Y. Al-Enezi、Elizabeth John、Yehia A. Ibrahim、Nouria A. Al-Awadi

  DOI：10.1039/d1ra07428h

  日期：——

  Three novel phosphine-free Ru-alkylidenes (7a–7c) have been synthesized and utilized as efficient catalysts for ring closing metathesis (RCM) reaction. Spectroscopic data, i.e. NMR and HRMS, along with single crystal X-ray diffraction analysis, were used to confirm their chemical structures. The tosylated carbenoid 7b showed the highest efficiency in cyclizing different acyclic diene substrates. RCM

  已经合成了三种新型的不含膦的 Ru-亚烷基 ( 7a-7c )，并将其用作闭环复分解 (RCM) 反应的有效催化剂。光谱数据，即NMR 和 HRMS，以及单晶 X 射线衍射分析，用于确认它们的化学结构。甲苯磺酰化的类胡萝卜素7b在环化不同的无环二烯底物方面表现出最高的效率。与众所周知的 Grubbs 相比，仅使用催化量 (0.5–2.0 mol%) 的添加剂催化剂 ( 7b ) 就可以很好地耐受各种（未）取代的N、N-二烯丙基苯胺衍生物的 RCM 和不同大分子二烯的立体选择性 RCM (II) 和 Hoveyda-Grubbs (II) 催化剂。
• Arylethers and pharmaceutical compositions
  申请人：Science Union et Cie

  公开号：US04027028A1

  公开（公告）日：1977-05-31

  This invention relates to amino piperidines bearing on the endocyclic nitrogen atom an aryloxy alkyl side chain and the acid addition salts thereof. This invention also relates to processes for making the same. The compounds of this invention have therapeutical utility namely in the cardiovascular field. They may be used in the form of pharmaceutical compositions. DESCRIPTION OF THE PRIOR ART The prior art may be illustrated with the following references French drug Patents Nos. 2429 M; 2430 M; 2431 M; Belgian Patent No. 615,350. SUMMARY OF THE INVENTION This invention relates to new 4-amino piperidines and more particularly to N-aralkoxy 4-phenylamino piperidines. The aryl and phenyl nuclei may be unsubstituted or substituted by one or several substituents. This invention also provides processes for producing such compounds. Namely they may be produced by condensing an aryloxy alkyl halide with a 4-phenylamino piperidine. This invention also relates to pharmaceutical compositions including as active ingredient at least one 4-phenylamino N-aryloxy alkyl piperidine or an acid addition salt thereof in admixture with an inert carrier. This invention further relates to a method for treating hypertension in hypertensive humans or animals. DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention relates to novel arylethers, to the processes for their preparation and to pharmaceutical compositions incorporating them as active ingredient. More particularly the present invention provides aryloxy lower alkyl piperidines of the general formula I: ##STR1## in which R.sub.2 is a hydrogen or a lower alkyl radical R.sub.3 is the acyl residue of an organic alkylcarboxylic acid having up to 10 carbon atoms. R.sub.4 is a phenyl radical selected from the group consisting of unsubstituted phenyl and a substituted phenyl radical of the formula ##STR2## WHEREIN R.sub.1 is a radical selected from the group consisting of halogen, lower alkoxy and lower alkylene dioxy AND Q IS AN INTEGER OF 1 TO 3 WITH THE PROVISO THAT WHEN R.sub.1 is a lower alkylene dioxy, Q IS 1 OR 2, X is an alkylene radical selected from the group consisting of ##STR3## in which R is a lower alkyl radical N IS 1 OR 2 AND Ar is an aromatic homo-or hetero cyclic radical selected from the group consisting of (a) a phenyl radical of the general formula ##STR4## IN WHICH X.sub.1 is a radical selected from the group consisting of halogen atom, lower alkyl, lower alkenyloxy, lower alkynyloxy, lower alkylthio, carboxyl, lower alkoxy carbonyl, lower alkenyl, lower alkylene-dioxy, nitro, amino, lower alkylamino, di(lower alkyl) amino, lower acylamino, sulfamido, lower alkylamino sulfonyl, di(lower alkylamino) sulfonyl, lower alkyl sulfonyl, aminocarbonyl, cyano and trifluoromethyl m is zero or an integer from 1 to 5 with the proviso that when X.sub.1 is a lower alkylene dioxy m is 1 or 2 (b) a bicyclic radical of the general formula ##STR5## in which (1) Z and A together form an ethylidene radical, B and D together form an ethylidene radical and p is 1 (2) Z is an imino radical-- NH-- , A and B together form an ethylidene radical, D is a methylene radical and p is zero, 1 or 2 (3) Z is a sulphur atom, A and B together form an ethylene or an ethylidene radical, D is a methylene radical and p is zero or an integer from 1 to 3 The invention also provides acid addition salts of the compounds of the general formula I Due to their basic character, mineral or organic acids may be added to the compounds of general formula I. Such acids are preferably therapeutically compatible mineral or organic acids and there are mentioned as example of preferred salts, those with hydrobromic acid, sulphuric acid, phosphoric acid, acetic acid, propionic acid, maleic acid, fumaric acid, methylsulphonic acid, isethionic acid, glucose-1 phosphoric acid and hydrochloric acid. Among the compounds of general formula I they are presently preferred the aryloxy lower alkyl piperidines of the general formula I'. ##STR6## in which R is a hydrogen atom or a lower alkyl radical, n is an integer from 2 to 4, R.sub.2 is a hydrogen atom or a lower alkyl radical, R.sub.3 is the acyl radical of an alkane carboxylic acid having up to 10 carbon atoms, R.sub.4 is a phenyl radical, and Ar is (a) a phenyl radical of the general formula ##STR7## in which X is a substituent selected from halogen atoms and lower alkyl, lower alkenyloxy, lower alkynyloxy, lower alkylthio, carboxyl, lower alkoxycarbonyl, nitro, amino, lower alkyl amino, di (lower alkyl) amino, lower acylamino, sulfamido, lower alkylaminosulfonyl, (di lower alkyl amino) sulfonyl, lower alkylsulfonyl, amino carbonyl, cyano and trifluoromethyl radicals, and m is zero or an integer from 1 to 5, or (b) a homo -or heterobicyclic radical of general formula ##STR8## in which (i) Z and A together form an ethylidene radical, B and D together form an ethylidene radical and p is 1; or (ii) Z is an imino radical-- NH-- , A and B together form an ethylidene radical, D is a methylene radical and p is zero, 1 or 2; or (iii) Z is a sulphur atom, A and B together form an ethylene radical or an ethylidene radical, D is a methylene radical and p is zero or an integer from 1 to 3, and the acid addition salts thereof. The term "lower alkyl" is used herein to designate a hydrocarbyl group having from 1 to 6 carbon atoms in a straight or branched chain and which may be substituted by a hydroxyl, lower alkoxy or dilower alkyl amino group. Examples of such lower alkyl groups are methyl, ethyl, isopropyl, sec butyl, neo-pentyl, tert.butyl, n-hexyl, hydroxyethyl and diethylaminoethyl groups. The term "halogen" is used herein to designate preferably fluorine or chlorine atoms. It may be, also, bromine or iodine The term "lower alkenyl" is used herein to designate a hydrocarbyl group with one or more olefinic double bonds and having from 2 to 10 carbon atoms in a straight or branched chain. Examples of such alkenyl groups are allyl, methallyl, isopentenyl, dimethyl allyl, butenyl and triallyl methyl group. The term "lower alkynyl" is used herein to designate a hydrocarbyl group having a triple bond and having from 2 to 6 carbon atoms, for example, the ethynyl, propynl-yl, propyn-2-yl and methyl-1 but-2-ynyl groups. Preferred acyl radicals are especially those derived from lower alkanoic acids, for example acetic acid, butyric acid, isovalerianic acid, caproic acid, diethylamino acetic acid, pimelic acid, succinic acid, .beta.-ethoxy-acetic acid and (di n-propyl) acetic acid. The term "lower alkoxy" is used therein to designate a lower alkyloxy radical having from 1 to 6 carbon atoms and which may be substituted in the alkyl chain by a hydroxy, a, acyloxy or a dilower alkylamino radical. The term "lower alkylene dioxy" is intended to designate a methylene dioxy radical, an ethylene dioxy or a propylene dioxy radical. When X is substituted with at least a lower alkyl radical, the carbon atom which bears this substituent is asymmetric; such compounds of general formula I may be resolved into their stereoisomers and the compounds of the present invention can therefore be in racemic or optically-active forms. In addition, when R.sub.2 is a lower alkyl radical, a new center of symmetry is created and the diastereoisomers may be resolved. The amino side chain in the piperidine ring also produces an asymmetric carbon atom. The corresponding diastereoisomers may be separated by resolution by chemical or physical methods. The compounds of the present invention possess interesting pharmacological properties, especially anti-hypertensive properties. Their pharmacological properties are distinct from those of 4-aminopiperidines previously described in the literature (Brevets speciaux de Medicament N.degree. 2429 M, 2430 M and 2431 M) as having potent analgesic and neuroleptic properties. The compounds of the general formula I are devoid of any significant analgesic properties. The compounds of the present invention may therefore be used for therapeutic use in human or veterinary medicine, as drugs for treating hypertension without risk of noxious side-effects. Due to their interesting pharmacological properties the following compounds may particularly be cited: -N-( 2,6 dichlorophenoxy) ethyl 4-(N'-phenyl N' -propionylamino) piperidine -N-( 2,6-dimethyl phenoxyethyl) 4-(N'-phenyl N'-propionylamino) piperidine -N-( 2,6-dimethoxy phenoxyethyl) 4-(N'-phenyl N'propionylamino) piperidine -N-( 2,6-dimethyl phenoxypropyl) 4-(N'-phenyl N'propionylamino) piperidine -N-(.alpha. -naphtoxyethyl) 4-(N'-phenyl N'propionylamino) piperidine -N-[ 2-(2,6-dimethyl phenoxy) propyl]4-N'-phenyl N'-propionylamino) piperidine -N-( 2,6-dimethyl phenoxyethyl) 4-[N'phenyl N'(dipropyl acetylamino)] piperidine -N-( 2,6-dimethyl phenoxyethyl) 4-[N'(3,4-methylene dioxyphenyl) N'propionylamino] piperidine -cis dl N-(2,6 dimethyl phenoxyethyl) 3-methyl 4-(N'-phenyl N'-propionylamino) piperidine For therapeutic use, they can be administered in the form of pharmaceutical compositions including a compound of general formula I as active ingredient and one or more non-toxic inert pharmaceutical carriers suitable for oral, parenteral, sublingual or rectal administration. More specifically, the pharmaceutical compositions may be in the form of ampuls, phials, multidose flasks, autoinjectable syringes, tablets, coated tablets, capsules, powders, granules, syrups, sublingual tablets and suppositories. The useful posology will vary depending on the therapeutic use, the age and the weight of the patient and the seriousness of the illness. It may range from 1 to 250 mg per unit dosage and the administration may be repeated one to four times a day. The present invention also provides a process for producing compounds of general formula I which comprises reacting a 4-aminopiperidine of general formula III ##STR9## in which R.sub.2, R.sub.3 and R.sub.4 have meanings given above with an ester of an aryloxy alkanol of the general formula II ar-- O-- (X).sub.n -- Y (II) in which Ar-- , X, n have the same meanings given above, and Y is a halogen atom or the acyl residue of an alkylsulphonic acid or an arylsulphonic acid, to obtain a compound of general formula I which may, if desired, be salified by addition of a mineral or organic acid or resolved into its optical isomers or diastereoisomers. According to the present invention, the above-described condensation is preferably carried out in an inert solvent in the presence or absence of a basic agent. Preferably the solvent is a polar solvent, such as dimethylformamide, dimethylacetamide, hexamethylphosphoramide or acetonitrile. The solvent may also be a halogenated solvent such as methylene chloride or dichloroethane, an aromatic hydrocarbon such as benzene or toluene, or a cycloalkane such as cyclohexane. Preferred esters are those which are derived from readily cleaved acids such as methanesulphonic acid, ethanesulphonic acid, benzenesulfonic acid or p-toluenesulphonic acid. Among the halides, chlorides and bromides are especially referred. When a bromide is used, it is especially suitable to carry out the condensation in the presence of an alkali metal iodide, in the presence of a dilower alkyl ketone such as acetone or methylisobutyl ketone. The basic agent may be a trilower alkylamine such as triethylamine, a dilower alkyl arylamine such as dimethylamino aniline or a pyridine base such as pyridine, collidine or lutidine. The basic agent may also be an excess of aminopiperidine of general formula III or the solvent when it is a disubstituted lower alkylamide or a phosphoramide. The present invention also provides a process for producing compounds of general formula I which comprises submitting a compound of general formula IV ##STR10## in which n, Ar, R.sub.2, R.sub.3 and R.sub.4 have the meanings given above, and X' is a radical selected from the group consisting of -- CH.sub.2 -- CHOH, -- CHOH-- CH.sub.2 --, -- CO-- CH.sub.2 -- and CH.sub.2 -- CO-- to the action of a reducing agent and recovering the desired compound of general formula I Preferably the reducing agent is hydrogen in the presence of a catalyst such as platinum or palladium. The reducing agent is hydrazine in the presence of potassium hydroxide when an oxo group is present in the alkylene chain. According to another aspect of the invention, there is provided a process for producing a compound of general formula I which comprises condensing compound of general formula II ar-- O-- (X).sub.n -- Y (II) in which Ar, X, Y and n have the above-given definitions with a 4-aminopyridine of the formula VI ##STR11## in which R.sub.2, R.sub.3 and R.sub.4 have the meanings give above, to produce a 4-amino pyridinium salt of the formula VII ##STR12## on which the substituents are defined as above specified and reducing the latter by catalytic hydrogenation or by means of mixed alkali metal hydride to an amino piperidine of formula I. The catalyst may be based on a metal of the platinium family such as platinum, palladium, iridium or rhodium. The mixed metal hydride may be an alkali metal borohydride or an alkali metal aluminohydride. A compound of general formula I may also be produced according to the invention by condensing an aryloxy radical of general formula VIII ar-- O-- (X).sub.n -- OH (VIII) in which Ar, X and n have the above-specified meanings with an aminopiperidine of general formula II ##STR13## in which R.sub.2, R.sub.3 and R.sub.4 have the meanings given above, in the presence of a hydrogenation catalyst to produce the desired compound of formula I. More specifically the hydrogenation catalyst is RANEY nickel and, preferably RANEY nickel WR. The compounds of general formula I may further be produced according to the invention by submitting an aryloxy alkylpiperidine of the formula V ##STR14## in which Ar, X, n, R.sub.2 and R.sub.4 are defined as above to the action of an acylating agent derived from an alkane carboxylic acid having up to 10 carbon atoms and recovering the desired compound of formula I. The acylating agent is preferably a halide of the alkane carboxylic acid or the alkane carboxylic acid in the presence of a dehydrating agent such as a dialkyl-or a dicycloalkyl carbodiimide. The compounds of general formula I may also be produced according to the invention by submitting an aminopiperidine of general formula II ##STR15## in which R.sub.2, R.sub.3 and R.sub.4 have the meanings given above to the action of an alkylene difunctional derivative of the formula IX y-- (x).sub.n -- OH (IX) in which R, n and Y have the meanings given above to obtain an (aminopiperidino) alkanol of the formula X ##STR16## treating the latter with an acylating agent derived from a hydrohalic acid, to produce a halide of the formula XI ##STR17## in which Hal is a halogen atom, and reacting the halide with a phenol of the formula XII ar-- OH (XII) in which Ar has the meaning given above to produce a compound of general formula I. Preferably the acylating agent derived from a hydrohalic acid is phosphorous tribromide, phosphorous sxychloride, a sulphuric or sulphonyl halide, such as thionyl chloride or sulphuryl chloride, an aryl sulphonyl halide such as benzene sulphonyl chloride or p-toluene-sulphonyl chloride or a metallic halide such as vanadium chloride. The optically-active reagent which may be used for resolving the compounds of formula I is preferably an optically-active organic acid such as an optically-active carboxylic acid, for example d-tartaric acid, 1-ketogulonic acid, 1-ascorbic acid, 1-menthyloxyacetic acid, abietic acid, d-N,N-diemthyl tartramic acid, an optically-active sulphonic acid for example d-camphosulphonic acid or an optically-active phosphoric acid such as d-glucose-1-phosphoric acid or d-glucose-1,6-diphosphoric acid. The starting materials of general formula III and the starting materials of general formula VIII may be obtained according to the processes described in U.S. Patent No. 3,131,218 and in J. Med. Chem. 6 (1963) 63. The starting materials of general formula II may be obtained according to known processes, for example that disclosed in German Patent No. 1,470,357. The following Examples illustrate the invention. The temperatures are expressed in degrees Centigrade.

  本发明涉及带有内环氮原子上的芳氧基烷基侧链的氨基哌啶及其酸加成盐。本发明还涉及制备这些化合物的方法。本发明中的化合物在心血管领域具有治疗功效，可用于制备药物组合物。先前的技术可以通过以下参考文献进行说明：法国药品专利号2429 M、2430 M、2431 M；比利时专利号615,350。本发明涉及新的4-氨基哌啶，尤其是N-芳基氧基4-苯基氨基哌啶。芳基和苯基核可能未经取代或经过一个或多个取代基取代。本发明还提供制备这些化合物的方法。具体而言，它们可以通过将芳氧基烷基卤化物与4-苯基氨基哌啶缩合而制得。本发明还涉及包括至少一种4-苯基氨基N-芳氧基烷基哌啶或其酸加成盐作为活性成分与惰性载体混合的药物组合物。本发明还涉及一种治疗高血压的方法。
• Cation radical chain cycloaddition polymerization: a fundamentally new polymerization mechanism
  作者：Nathan L. Bauld、Daxin Gao、J. Todd Aplin

  DOI：10.1002/(sici)1099-1395(199911)12:11<808::aid-poc207>3.0.co;2-m

  日期：1999.11
• Kuroda; Koyama, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1943, vol. 63, p. 387,389
  作者：Kuroda、Koyama

  DOI：——

  日期：——