- Activator free, expeditious and eco-friendly chlorination of activated arenes by N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI)
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N-Chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI) has been explored for the first time as a chlorinating reagent for direct chlorination of various activated arenes and heterocycles without any activator. A comparative in-silico study was performed to determine the electrophilic character for NCBSI and commercially available N-chloro reagents to reveal the reactivity on a theoretical viewpoint. The reagent was prepared by an improved method avoiding the use of hazardous t-butyl hypochlorite. This reagent was proved to be very reactive compared to other N-chloro reagents. The precursor of the reagent N-(phenylsulfonyl)benzene sulfonamide was recovered from aqueous spent, which can be recycled to synthesize NCBSI. The eco-friendly protocol was equally applicable for the synthesis of industrially important chloroxylenol as an antibacterial agent.
- Misal, Balu,Palav, Amey,Ganwir, Prerna,Chaturbhuj, Ganesh
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supporting information
(2021/01/04)
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- Method for preparing 4-chloro-3, 5-dimethylphenol
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The invention relates to a method for preparing 4-chloro-3, 5-dimethylphenol. The method comprises the following specific steps: fully dissolving 3, 5-dimethylphenol by using a protonic solvent, and dropwise adding sulfuryl chloride to perform chlorination reaction under the action of a directional chlorination catalyst to obtain the 4-chloro-3, 5-dimethylphenol, wherein the directional chlorination catalyst is Fe-MOFs. A directional catalyst/protic solvent combined system adopted by the method is applied to directional chlorination of 3, 5-dimethylphenol, so that the selectivity of chlorination reaction is effectively improved, and a 4-chloro-3, 5-methylphenol product is efficiently prepared; and a final product with the content of 94% and the purity of 99.7% is obtained through one-step synthesis without purification. The method has the characteristics of simplicity and convenience in operation, high product selectivity and the like, and has very high industrial application value.
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Paragraph 0043-0044; 0047-0084
(2021/07/14)
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- Method for preparing 4 -chloro -3 and 5 -dimethylphenol by low-temperature chlorination
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The invention discloses a method for preparing 4 -chloro -3-5 -dimethylphenol by low-temperature chlorination, which comprises (1) 3,5 -dimethylphenol and a chlorination agent carrying out chlorination reaction at low temperature, and carrying out solid-liquid separation to obtain the solid crude product 1 and the intermediate mother liquor. (2) The mother liquor is further subjected to chlorination reaction at low temperature, and the final solid-liquid separation is carried out after the reaction is completed to obtain the solid crude product 2 and the final mother liquor. The solid crude product 1 and the solid crude product 2 are post-treated to give said 4 - chloro -3, 5 - dimethylphenol. To the method, the precipitated crystals are separated in time in the reaction process, the wrapping of the raw materials is reduced on the one hand, and the conversion rate is improved.
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Paragraph 0032-0035; 0036-0039; 0040-0043; 0044-0047; ...
(2021/11/06)
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- para-Selective chlorination of cresols and m-xylenol using sulfuryl chloride in the presence of poly(alkylene sulfide)s
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Chlorination of o-cresol, m-cresol, and m-xylenol using sulfuryl chloride in the presence of a range of poly(alkylene sulfide)s and a Lewis acid (aluminum or ferric chloride) has been studied. The sulfur containing catalysts used led to the production of para-chlorophenols in high yields and higher para/ortho ratios than for reactions in the absence of such poly(alkylene sulfide)s. The effectiveness of the polymers was found to be dependent on the length of the spacer groups between the sulfur atoms. For example, polymers with shorter spacers provided high yields of 4-chloro-o-cresol (ca. 97%), while polymers with at least one longer spacer provided high yields of both 4-chloro-m-cresol (up to 94.6%) and 4-chloro-m-xylenol (up to 97.6%).
- Smith, Keith,Hegazy, Amany S.,El-Hiti, Gamal A.
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p. 345 - 356
(2020/03/23)
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- Synthesis method of 4-chloro-3, 5-dimethylphenol
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The invention provides a synthesis method of 4-chloro-3, 3, 3-tetrafluoropropene. A bivalent copper salt is used as a catalyst, 3, 5-dimethylphenol reacts with a chlorinating agent and an oxidizing agent under the condition of an organic solvent to obtain 4-chloro-3, 5-dimethylphenol, and the synthesis method is good in reaction selectivity, high in yield, recyclable in solvent, easy to separate the catalyst, capable of being repeatedly used, mild in reaction condition, environmentally friendly and quite beneficial to industrial production in the production process.
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Paragraph 0023-0059
(2020/08/02)
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- Method for preparing 4-chloro-3, 5-dimethylphenol
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The invention discloses a method for preparing 4-chloro-3, 5-dimethylphenol. The method comprises the following step: carrying out a chlorination reaction on a 3, 5-dimethylphenol by taking phosgene as a chlorination reagent and a saturated nitrogen-oxygen heterocyclic compound as an accelerant to obtain 4-chloro-3, 5-dimethylphenol. The method has the advantages of no generation of gas sulfide, high para-position selectivity, simplicity and convenience in operation and the like.
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Paragraph 0037-0079
(2020/08/30)
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- Regioselective chlorination of phenols in the presence of tetrahydrothiopyran derivatives
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Four six-membered cyclic sulfides, namely tetrahydrothiopyran, 3-methyltetrahydrothiopyran, 4-methyltetrahydrothiopyran and 4,4-dimethyltetrahyrdrothiopyran have been used as moderators in chlorination reactions of various phenols with sulfuryl chloride in the presence of aluminum or ferric chloride. On chlorination of phenol, ortho-cresol and meta-cresol the para/ortho chlorination ratios and yields of the para-chloro isomers are higher than when no cyclic sulfide is used for all of the cyclic sulfides, but chlorination of meta-xylenol is less consistent, with some cyclic sulfides producing higher p/o ratios and others producing lower ratios than reactions having no sulfide present.
- Smith, Keith,Williams, Des,El-Hiti, Gamal A.
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p. 529 - 538
(2019/06/13)
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- Regioselective synthesis of important chlorophenols in the presence of methylthioalkanes with remote SMe, OMe or OH substituents
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Various methylthio alcohols, methoxy(methylthio)alkanes and bis(methylthio)alkanes have been used as regioselectivity modifiers in the chlorination reactions of various phenols at room temperature. The process involves the use of a slight excess of sulfuryl chloride in the presence of aluminum or ferric chloride as an activator. Methylthio alcohols, methoxy(methylthio)alkanes and bis(methylthio)alkanes having 2 and 3 methylene groups as a spacer were found to be good for the para-selective chlorination of o-cresol and phenol. On the other hand, methylthio alcohols, methoxy(methylthio)alkanes and bis(methylthio)alkanes having 6 and 9 methylene groups were found to be good for the selective para-chlorination of m-xylenol and m-cresol. Calculations using density functional theory on bis(methylthio)alkanes have suggested two different types of stable chlorinated intermediates depending on the number of methylene units as a spacer.
- Smith, Keith,Al-Zuhairi, Ali J.,Elliott, Mark. C.,El-Hiti, Gamal A.
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p. 607 - 621
(2018/07/13)
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- Ammonium Salt-Catalyzed Highly Practical Ortho-Selective Monohalogenation and Phenylselenation of Phenols: Scope and Applications
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An ortho-selective ammonium chloride salt-catalyzed direct C-H monohalogenation of phenols and 1,1′-bi-2-naphthol (BINOL) with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as the chlorinating agent has been developed. The catalyst loading was low (down to 0.01 mol %) and the reaction conditions were very mild. A wide range of substrates including BINOLs were compatible with this catalytic protocol. Chlorinated BINOLs are useful synthons for the synthesis of a wide range of unsymmetrical 3-aryl BINOLs that are not easily accessible. In addition, the same catalytic system can facilitate the ortho-selective selenylation of phenols.
- Xiong, Xiaodong,Yeung, Ying-Yeung
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p. 4033 - 4043
(2018/05/22)
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- Iron(III)-Catalyzed Chlorination of Activated Arenes
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A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.
- Mostafa, Mohamed A. B.,Bowley, Rosalind M.,Racys, Daugirdas T.,Henry, Martyn C.,Sutherland, Andrew
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p. 7529 - 7537
(2017/07/26)
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- Method of synthesizing 4-chloro-3,5-xylenol in continuous flow microtubule reactor
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The invention belongs to the field of organic fine synthesis, and relates to a method of synthesizing 4-chloro-3,5-xylenol in a continuous flow microtubule reactor. The method is that in a microtubule reactor with a certain controlled temperature, raw materials of 3,5-xylenol, a hydrochloric acid solution of copper chloride and hydrogen peroxide are simultaneously and continuously introduced in proportion to prepare the 4-chloro-3,5-xylenol. The method is simple and effects are good. Compared with conventional methods, the method changes batch reactions to continuous reactions and shorten the reaction time from a plurality of hours to about a hundred seconds.
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Paragraph 0016-0018
(2017/10/13)
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- Comparison of cyclic and polymeric disulfides as catalysts for the regioselective chlorination of phenols
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Two cyclic and two polymeric disulfides have been synthesized and established to be useful catalysts for the chlorination of m-xylenol, o-cresol, m-cresol and phenol using freshly distilled sulfuryl chloride in the presence of aluminum or ferric chloride as a co-catalyst at room temperature. The yields of p-isomers and para/ortho ratios were higher compared to cases where no catalyst was used with most catalysts for most phenols even when a very low concentration of disulfide was used.
- Smith, Keith,Al-Zuhairi, Ali J.,El-Hiti, Gamal A.,Alshammari, Mohammed B.
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- Synthesis of deuterated benzopyran derivatives as selective COX-2 inhibitors with improved pharmacokinetic properties
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We designed a series of specifically deuterated benzopyran analogues as new COX-2 inhibitors with the aim of improving their pharmacokinetic properties. As expected, the deuterated compounds retained potency and selectivity for COX-2. The new molecules possess improved pharmacokinetic profiles in rats compared to their nondeuterated congeners. Most importantly, the new compounds showed pharmacodynamic efficacy in several murine models of inflammation and pain. The benzopyran derivatives were separated into their enantiomers, and the activity was found to reside with the S-isomers. To streamline the synthesis of the desired S-isomers, an organocatalytic asymmetric domino oxa-Michael/aldol condensation reaction was developed for their preparation.
- Zhang, Yanmei,Tortorella, Micky D.,Wang, Yican,Liu, Jianqi,Tu, Zhengchao,Liu, Xiaorong,Bai, Yang,Wen, Dingsheng,Lu, Xin,Lu, Yongzhi,Talley, John J.
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p. 1162 - 1166
(2014/12/10)
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- Process for the synthesis of phenols from arenes
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A process to synthesize substituted phenols such as those of the general formula RR′R″Ar(OH) wherein R, R′, and R″ are each independently hydrogen or any group which does not interfere in the process for synthesizing the substituted phenol including, but not limited to, halo, alkyl, alkoxy, carboxylic ester, amine, amide; and Ar is any variety of aryl or hetroaryl by means of oxidation of substituted arylboronic esters is described. In particular, a metal-catalyzed C—H activation/borylation reaction is described, which when followed by direct oxidation in a single or separate reaction vessel affords phenols without the need for any intermediate manipulations. More particularly, a process wherein Ir-catalyzed borylation of arenes using pinacolborane (HBPin) followed by oxidation of the intermediate arylboronic ester by OXONE is described.
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- Hydrolysis of 4-chloro-3,5-dimethylphenyl phosphate monoester in acid solutions
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Hydrolysis of 4-chloro-3,5-dimethylphenyl phosphate monoester has been carried out in HCl solution at 98 +/-5 deg C and the inorganic phosphate obtained during hydrolysis has been estimated colorimetrically.Pseudo-first order rate coefficients have been calculated.Neutral species have been found to be reactive and contribute to overall hydrolysis in the acid region.The calculated rate coefficients are in good agreement with the experimentally observed ones.The effects of temperature, solvent and on the rate have been studied.The results suggest that the hydrolysis of monoester occurs by the cleavage of P-O bond.
- Mhala, M. M.,Kushwaha, R. S.
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p. 420 - 421
(2007/10/02)
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- Method of disinfecting premises from coccidial oocysts using generated ammonia
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A method of disinfecting premises from coccidial oocysts in which surface to be disinfected is thoroughly wetted with a first aqueous solution of ammonium salt containing approximately 0.5 to 1.5 molar of ammonium together with non-ionic surfactant and indicator having a color change in the region of pH 8 to pH 10 and the wetted surface is then covered with sufficient of a second aqueous solution of alkali metal hydroxide containing approximately 0.75 to 2.3 molar of hydroxide toether with phenolic bactericide to cause the indicator to change color on the treated surface. A preparation for use in such a method comprises a first package containing ammonium salt together with non-ionic surfactant and indicator and second package containing alkali metal hydroxide and phenolic bactericide, the molar amount of hydroxide in the second package being greater than the molar amount of ammonium in the first package.
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- Highly Selective Aromatic Chlorinations. Part 2. The Chlorination of Substituted Phenols, Anisoles, Anilines, and Related Compounds with N-Chloroamines in Acidic Solution
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Phenols, anisoles, anilines, and related compounds are chlorinated in trifluoroacetic acid at room temperature by N-chlorodialkylamines and N-chlorotrialkylammonium salts.With monsubstituted compounds and their 2- and 3-substituted derivatives the reaction occurs efficiently and selectively at the 4-position.The reactivity of these substrates and the selectivity of their chlorinations are determined by electronic rather than steric effects of the substituent.Blocking the reaction with a substituent at the 4-position generally leads to only poor or moderate yields of the 2-chlorinated product.Evidence for radical and cation radical intermediates has been obtained in the reactions of some of the 4-substituted reactants and the mechanism of chlorination is discussed in the light of these findings.The reactions of selected substrates have been scaled up to give laboratory syntheses.
- Smith, John R. Lindsay,McKeer, Linda C.,Taylor, Jonathan M.
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p. 385 - 392
(2007/10/02)
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- ACID BASE REACTIONS BETWEEN ACRIDINE ORANGE AND SUBSTITUTED PHENOLS IN BENZONITRILE. PART I. THERMODYNAMICS OF ASSOCIATION AND IONIC EQUILIBRIA.
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Proton transfer reactions of the five substituted phenols 3-Cl-4-nitrophenol CNP, 4-nitrophenol NP, 3-methyl-4-nitrophenol MNP, 4-Cl-3,5-dimethylphenol CMP, and 3,5-dimethylphenol DMP with acridine orange, and the formation of hydrogen bonded complexes AHA** minus of the anions A** minus of CNP, NP, and MNP with the respective phenols AH in benzonitrile solution were investigated by means of absorption spectroscopy. The formation enthalpies of the hydrogen bonded anions AHA** minus are much larger than DELTA H//1, so that DELTA H//2 is mainly determined by this association. On the other hand there is no significant difference between DELTA H//2 and DELTA H//3; thus the hydrogen bond formed between a phenol and a complexed anion AHA** minus is very weak. Substituent effects on the acidity of phenols are about twice as large in benzonitrile as in aqueous solution.
- Suettinger,Strohbusch
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p. 744 - 750
(2007/10/02)
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- Process for chlorinating xylenols
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Chlorination of xylenols with a chlorinating agent such as sulfuryl chloride in the presence of a metal chloride catalyst is conducted in further presence of 0.001 to 1% by weight of a sulfur compound, based on the xylenols, whereby industrially useful xylenols are obtained safely with a high selectivity and high yield.
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