- NMP-mediated chlorination of aliphatic alcohols with aryl sulfonyl chloride for the synthesis of alkyl chlorides
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NMP-mediated chlorination of aliphatic alcohols has been developed for the synthesis of alkyl chlorides. This facile, efficient and practical approach used simple and readily available aryl sulfonyl chlorides as the chlorination reagent for the construction of C–Cl bond in good to excellent yields with mild conditions and broad substrate scope.
- Zheng, Dagui,Mao, Liu-Liang,Zhu, Xian-Hong,Zhou, An-Xi
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supporting information
p. 2793 - 2800
(2018/11/06)
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- Synthesis method of 1,2-diphenoxyethane thermosensitive sensitizer
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The invention relates to the field of sensitizers for thermosensitive paper, particularly a synthesis method of a high-purity 1,2-diphenoxyethane thermosensitive sensitizer. The method comprises the following steps: adding phenol and dichloroethane into a reaction kettle, performing heating under reflux, dropwisely adding an acid-binding agent into the reaction kettle, performing reaction until no phenol is detected, performing reduced pressure distillation to remove the dichloroethane, supplementing the acid-binding agent, performing heating, dropwisely adding the phenol, performing tracking detection until 2-chlorophenetole reacts completely, stopping dropwisely adding the phenol, performing water washing to remove the salt, and performing ethanol recrystallization to obtain the product. The reaction condition is mild: the maximum temperature is controlled at 120-150 DEG C, so the condition is accessible. The method has the advantages of short reaction time, accessible raw materials, simple technical operation process, recyclable raw materials and high product purity, and is suitable for industrial production.
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Paragraph 0018; 0019; 0020; 0021; 0022; 0023; 0024
(2017/10/13)
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- Formononetin derivatives and preparation methods and medical application thereof
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The invention relates to the field of pharmaceutical chemistry, and relates to formononetin derivatives and preparation methods and medical application thereof, in particular to formononetin derivatives with the general formula as shown in (I), preparation methods thereof, pharmaceutical compositions containing the compounds and medical application of the derivatives and the pharmaceutical compositions, particularly, application of the derivatives and the pharmaceutical compositions serving as drugs for preventing or treating hyperlipidaemia or obesity or type-II diabetes. Please see the formula in the description.
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- Method for preparing chlorohydrocarbons from alcohols by using aryl sulfonyl chloride as chlorination agent
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The invention provides a method for preparing chlorohydrocarbons from alcohols by using aryl sulfonyl chloride as a chlorination agent. The method comprises the following steps: heating alcohols and aryl sulfonyl chloride in N,N-dialkyl substituted amide to react for 30 minutes, cooling the reaction product to room temperature, adding dichloromethane and water, carrying out extraction and skimming, washing the organic layer with saturated saline water, drying with anhydrous sodium sulfate, steaming to remove the solvent, and carrying out further separation and purification to obtain the chlorohydrocarbons. The method has the characteristics of cheap and accessible chlorination agent, simple technical process, short reaction time and the like, can obtain high reaction under the condition that the aryl sulfonyl chloride consumption is approximate to the stoichiometric quality, and can remove the reaction byproduct aryl sulfonic acid from the reaction mixture.
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Paragraph 0017; 0018
(2017/01/17)
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- TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE
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Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
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Paragraph 0232; 0233
(2016/12/22)
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- Aryl ethers of 4-[(2-hydroxyethyl)sulfanyl]pyrimidine derivatives: Pathways of synthesis and fungicidal activity of their salt forms
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2-Amino-4-[(2-aryloxyethyl)sulfanyl]-6-methylpyrimidines were obtained by S-alkylation of 2-amino-6-methylpyrimidin-4(3H)-thione with 2-aryloxyethyl chlorides. Since 2-amino-4-[(2-chloroethyl)sulfanyl]-6-methylpyrimidine is prone to in situ intramolecular cyclization it cannot be used in Claisen reaction. The bromination of the target compounds provided 5-bromo derivatives; some of their hydrochlorides exhibited fungicidal activity.
- Erkin,Klaptyuk,Gurzhii,Yuzikhin,Krutikov
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p. 1274 - 1281
(2016/08/10)
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- Nanosized ferric hydroxide catalyzed c-o cross-coupling of phenol and halides to generate phenoxy ether
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The iron-based catalyst can effectively catalyze the phenolic hydroxyl C-O bond formation reaction to give the corresponding phenoxy ethers. The reaction of phenol and methyl chloroacetate, for example, gives phenoxy acetic acid methyl ester in 98 % yield under the optimal reaction conditions. Among the iron-based catalysts, nanosized ferric hydroxide prepared through sol-gel method gives the best catalytic activity.
- Sun, Hongbin,Sun, Yuanhua,Tian, Xiaohua,Zhao, Yunxia,Qi, Xuan
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p. 6189 - 6191
(2013/07/26)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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p. 2692 - 2698,7
(2012/12/12)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener. Georg Thieme Verlag KG Stuttgart · New York.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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p. 2692 - 2698
(2013/01/15)
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- A new and more efficient synthesis of methylene acetals
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A new and efficient synthesis of benzyl chlorides and methylene acetals by use of 2,4-dichloro-6-methoxy[l,3,5]triazine (MeOTCT) and dimethyl sulfoxide has been developed. Chlorides are the major products for benzyl alcohols, while methylene acetals are the major products for secondary alcohols. This procedure provides the highest yields so far for methylene acetals of steroids. A plausible mechanism is proposed on the basis of the experiments. Georg Thieme Verlag Stuttgart.
- Chu, Guobiao,Zhang, Yanqiao,Li, Chunbao,Zhang, Yuqing
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experimental part
p. 3828 - 3832
(2010/03/03)
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- MRI CONTRAST AGENTS FOR DIAGNOSIS AND PROGNOSIS OF TUMORS
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The invention relates to bifunctional conjugates comprising a receptor ligand moiety and a metal binding moiety and complexes thereof with paramagnetic lanthanide or transition metals, and to the use of the metal complexes as contrast agents in magnetic resonance imaging (MRI) of tumors and other abnormalities.
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Page/Page column 33-34; 53
(2008/06/13)
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- Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists
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It is thought that selective 5-HT4 receptor agonists-such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4-ylmethyl] benzamide (2)-have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects. Modification of 2 was performed. Variation of the piperidin-4-ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT4 receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT4 receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N- (piperidin-4-ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT4 receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT4 receptor agonists, and had a similar effect on defecation to compound 2.
- Sonda, Shuji,Kawahara, Toshio,Katayama, Kenichi,Sato, Noriko,Asano, Kiyoshi
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p. 3295 - 3308
(2007/10/03)
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- Development of an efficient and stereoselective manufacturing route to idoxifene
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A literature route to 1-(2-{4-[(E)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine (idoxifene) has been modified to tackle various scale-up issues and provide initial supplies. A new highly efficient, robust, and stereoselective manufacturing route is described in detail. This route involves diastereoselective synthesis of tertiary alcohol (1RS,2SR)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]butan- 1-ol by Grignard addition to the ketone 1-(4-iodophenyl)-2-phenyl-1-butanone followed by derivatisation and stereoselective syn elimination to provide idoxifene in excellent yield and geometric purity. Evaluation of a more direct route to idoxifene using a McMurry low-valent titanium coupling reaction is also described.
- Ace, Karl W.,Armitage, Mark A.,Bellingham, Richard K.,Blackler, Paul D.,Ennis, David S.,Hussain, Nigel,Lathbury, David C.,Morgan, David O.,O'Connor, Noah,Oakes, Graham H.,Passey, Stephen C.,Powling, Laurence C.
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p. 479 - 490
(2013/09/07)
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- Synthesis and reactivity of a potential carcinogenic metabolite of tamoxifen: 3,4-Dihydroxytamoxifen-o-quinone
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Although tamoxifen is approved for the treatment of hormone-dependent breast cancer as well as for the prevention of breast cancer in high-risk women, several studies in animal models have shown that tamoxifen is heptocarcinogenic, and in humans, tamoxifen has been associated with an increased risk of endometrial cancer. One potential mechanism of tamoxifen carcinogenesis could involve metabolism of tamoxifen to 3,4- dihydroxytamoxifen followed by oxidation to a highly reactive o-quinone which has the potential to alkylate and/or oxidize cellular macromolecules in vivo. In the study presented here, we synthesized the 3,4-dihydroxytamoxifen, prepared its o-quinone chemically and enzymatically, and studied the reactivity of the o-quinone with GSH and deoxynucleosides. The E (trans) and Z (cis) isomers of 3,4-dihydroxytamoxifen were synthesized using a concise synthetic pathway (four steps). This approach is based on the McMurry reaction between the key 4-(2-chloroethoxy)-3,4-methylenedioxybenzophenone and propiophenone, followed by selective removal of the methylenedioxy ring of (E,Z)-1-[4-[2-(N,N-dimethylamino)ethoxy]phenyl]-1-(3,4- methylenedioxyphenyl)-2-phenyl-1-butene with BCl3. Oxidation of 3,4- dihydroxytamoxifen by activated silver oxide or tyrosinase gave 3,4- dihydroxytamoxifen-o-quinone as a mixture of E and Z isomers. The resulting o-quinone has a half-life of approximately 80 min under physiological conditions. Reaction of the o-quinone with GSH gave two di-GSH conjugates and three mono GSH conjugates. Incubation of 3,4-dihydroxytamoxifen with GSH in the presence of microsomal P450 gave the same GSH conjugates which were also detected in incubations with human breast cancer cells (MCF-7). Reaction of 3,4-dihydroxytamoxifen-o-quinone with deoxynucleosides gave only thymidine and deoxyguanosine adducts; neither deoxyadenosine nor deoxycytosine adducts were detected. Preliminary studies conducted with human breast cancer cell lines showed that 3,4-dihydroxytamoxifen exhibited cytotoxic potency similar to that of 4-hydroxytamoxifen and tamoxifen in an estrogen receptor negative (ER-) cell line (MDAMB-231); however, in the ER+ cell line (MCF-7), the catechol metabolite was about half as toxic as the other two compounds. Finally, in the presence of microsomes and GSH, 4-hydroxytamoxifen gave predominantly quinone methide GSH conjugates as reported in the previous paper in this issue [Fan, P. W., et al. (2000) Chem. Res. Toxicol. 13, XX- XX]. However, in the presence of tyrosinase and GSH, 4-hydroxytamoxifen was primarily converted to o-quinone GSH conjugates. These results suggest that the catechol metabolite of tamoxifen has the potential to cause cytotoxicity in vivo through formation of 3,4-dihydroxytamoxifeno-quinone.
- Zhang, Fagen,Fan, Peter W.,Liu, Xuemei,Shen, Lixin,Van Breemen, Richard B.,Bolton, Judy L.
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- The total synthesis of a technetium chelate - Tamoxifen complex
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A potential agent for imaging breast cancer has been synthesized by derivatization of the anti-estrogen tamoxifen. A multistep synthesis was required to conjugate a technetium chelate to tamoxifen in such a fashion that the biodistribution of the complex should mimic that of the parent compound.
- Bell, Russell A.,Dickson, Kieran C.,Valliant, John F.
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p. 146 - 154
(2007/10/03)
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- Fungicidal 2-aryl-2-cyano-2-(aryloxyalkyl)ethyl-1,2-4-triazoles
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2-aryl-2-cyano-2-(aryloxyalkyl)ethyl-1,2,4-triazoles of the formula STR1 wherein Ar1 and Ar2 are optionally substituted aryl groups which may or may not be different, R is hydrogen or alkyl, n is an integer of at least one, and the agronomically acceptable enantiomorphs, acid addition salts and metal salt complexes thereof, compositions containing these compounds and their uses as fungicides, particularly against phytopathogenic fungi.
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- Structure-activity studies of 3-benzoylpropionic acid derivatives suppressing adjuvant arthritis
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3-Benzoylpropionic acid derivatives possess an immunomodulative activity and suppress adjuvant arthritis. To understand how substituents affect the biological activity, the quantitative structure-activity relationships of 30 compounds were analyzed by the adaptive least-squares method. For the suppressing activity in rats, the electronic effects and the structural feature of the substituent on benzene ring were suggested to be important. To reinforce and confirm the correlation, 4 additional compounds of phenoxybutyric acid derivatives were synthesized and tested with the rat adjuvant-induced arthritis. These compounds were found to have potent suppressing activity.
- Kawashima,Kameo,Kato,Hasegawa,Tomisawa,Hatayama,Hirono,Moriguchi
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p. 774 - 777
(2007/10/02)
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- Method of preparing fungicidal intermediates
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N-n-propyl-N-(2,4,6-trichlorophenoxy)-ethyl amine is prepared by reacting 2-phenoxy ethanol with thionyl chloride in the presence of a catalytic amount of tetraalkyl ammonium halide optionally in the presence of a solvent to form 2-phenoxy ethyl chloride; selectively chlorinating the 2-phenoxy ethyl chloride with chlorine at a temperature from 0° C. to 60° C. in the presence of a catalytic amount if urea to form 2-(2,4,6-trichlorophenoxy)-ethyl chloride; reacting the 2-(2,4,6-trichlorophenoxy)-ethyl chloride with n-propyl amine at a temperature of from 20° C. to 150° C., optionally in the presence of water; and recovering the N-n-propyl-N-2-(2,4,6-trichlorophenoxy)-ethyl amine formed.
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- Environmentally safe method of preparing a certain dialkylamine
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N-n-propyl-N-2-(2,4,6-trichlorophenoxy) ethyl amine is prepared by reacting 2-phenoxy ethanol with thionyl chloride in the presence of a catalytic amount of tetra-alkyl ammonium halide optionally in the presence of a solvent to form 2-phenoxy ethyl chloride; reacting the 2-phenoxy ethyl chloride with n-propylamine at a temperature of from 50° C. to 150° C. optionally in the presence of a solvent to form N-n-propyl-N-2-phenoxy-ethyl amine; selectively chlorinating N-n-propyl-N-2-phenoxyethyl amine with chlorine in the presence of a solvent; and recovering the N-n-propyl-N-2-(2,4,6-trichlorophenoxy) ethyl amine formed.
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- Hexitol derivatives having vasodilative activity
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Disclosed is a hexitol derivative represented by the formula (I): STR1 wherein Q represents a formula selected from the group consisting of STR2 wherein a represents NH, O or S; each of b, c and d independently represents CH or N; each of R1, R2, R3 and R4 independently represents hydrogen, lower alkyl, trifluoromethyl, aryl, lower alkanoyloxy, amino, lower alkylamino, lower alkanoylamino, lower alkanoyl, aroyl, halogen, nitro, (CH2)m OR 7, (CH2)m SR7, (CH2)m CO2 R7 where R7 represents hydrogen or lower alkyl and m represents an integer of 0 to 3; each of R5 and R6 independently represents hydrogen or lower alkyl; U represents >N-- or STR3 W represents a single bond, --O-- or --S--; X represents STR4 wherein each of Y1 and Y2 independently represents hydrogen, lower alkyl, hydroxyl, lower alkanoyloxy, nitrile or phenyl; or Y1 and Y2 are combined together to form oxygen; each of Y3 and Y4 independently represents hydrogen or lower alkyl; and l is an integer of 0 to 6, and where l is an integer of 2 to 6, each STR5 may be the same or different; Z represents hydrogen or nitro; and, n is 2 or 3 or a pharmaceutically acceptable salt thereof. The compounds show prominent coronary vasodilative activities, and are useful in treating angina pectoris and myocardial infarction.
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- The Use of the Perfluorotolyl Protecting Group in the Synthesis of Pure Z and E Isomers of 4-Hydroxytamoxifen -1-(4-hydroxyphenyl)-2-phenyl-1-butene>
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The perfluorotolyl protecting group has been used in the synthesis of pure Z and E isomers of 4-hydroxytamoxifen (4a), a potent metabolite of the anticancer drug, tamoxifen (1a). 4-(Perfluorotolyloxy)phenyl magnesium bromide underwent addition to the carbonyl group of the easily prepared versatile ketone, 1--2-phenyl-1-butanone (7), without affecting the chloroethoxy group.Acid catalysed dehydration of the resulting carbinol gave a 1:1 mixture of isomeric ethers, (6a) and (6b), that were easily separated by chromatography and respectively converted to the Z (4a) and E (4b) isomers of 4-hydroxytamoxifen.The property of the perfluorotolyl function in enabling the separation of geometrical isomers is attributed to a combination of its lipophilicity and electron withdrawal.
- McCague, Raymond
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p. 771 - 793
(2007/10/02)
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