- 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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- 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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- Examination of Selectivity in the Oxidation of ortho- and meta-Disubstituted Benzenes by CYP102A1 (P450 Bm3) Variants
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Cytochrome P450 CYP102A1 (P450 Bm3) variants were used to investigate the products arising from the P450 catalysed oxidation of a range of disubstituted benzenes. The variants used all generated increased levels of metabolites compared to the wild-type enzyme. With ortho-halotoluenes up to six different metabolites could be identified whereas the oxidation of 2-methoxytoluene generated only two aromatic oxidation products. Addition of an ethyl group markedly shifted the selectivity for oxidation to the more reactive benzylic position. Epoxidation of an alkene was also preferred to aromatic oxidation in 2-methylstyrene. Significant minor products arising from the migration of one substituent to a different position on the benzene ring were formed during certain P450-catalysed substrate turnovers. For example, 2-bromo-6-methylphenol was formed from the turnover of 2-bromotoluene and the dearomatisation product 6-ethyl-6-methylcyclohex-2,4-dienone was generated from the oxidation of 2-ethyltoluene. The RLYF/A330P variant altered the product distribution enabling the generation of certain metabolites in higher quantities. Using this variant produced 4-methyl-2-ethylphenol from 3-ethyltoluene with ≥90 % selectivity and with a biocatalytic activity suitable for scale-up of the reaction.
- Munday, Samuel D.,Dezvarei, Shaghayegh,Lau, Ian C.-K.,Bell, Stephen G.
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p. 2512 - 2522
(2017/07/12)
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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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- The phototransformation of 4-chloro-2-methylphenoxyacetic acid under KrCl and XeBr excilamps irradiation in water
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The effect of UV radiation of a KrCl and a XeBr on the photodegradation of 4-chloro-2-methylphenoxyacetic acid (MCPA) was studied. The main photoproducts were identified by gas chromatograph/mass spectrometry (GC/MS). The variation of chlorine-ion and active chlorine in MCPA aqueous solution exposed to excilamp radiation was also defined by analytical methods. Irradiation of MCPA solution with a KrCl excilamp emitting mainly at 222 nm yield 2-methylhydroquinone and lactone of 2-hydroxy-3-methyl-5-chlorophenoxyacetic acid as the main photoproducts. Irradiation of MCPA solution with a XeBr excilamp emitting mainly at 283 nm yield 2-methylhydroquinone as the main photoproduct. Biological processes are not suitable for MCPA removal due to low or total absence of biodegradability of this class of pollutants. Estimation of biodegradability of phototreated MCPA solution was carried out according to ratios of biological oxygen demand (BOD5) to chemical oxygen demand (COD). The biodegradability of MCPA solutions increased after irradiation.
- Tchaikovskaya, Olga N.,Karetnikova, Elena A.,Sokolova, Irina V.,Mayer, Georgy V.,Shvornev, Dmitry A.
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experimental part
p. 8 - 14
(2012/04/10)
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- Cu-Mn spinel oxide catalyzed regioselective halogenation of phenols and N-heteroarenes
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A novel simple, mild chemo- and regioselective method has been developed for the halogenation of phenols using Cu-Mn spinel oxide as a catalyst and N-halosuccinimide as halogenating agent. In the presence of Cu-Mn spinel oxide B, both electron-withdrawing and electron-donating groups bearing phenols gave monohalogenated products in good to excellent yields with highest para-selectivity. The para-substituted phenol gave monohalogenated product with good yield and ortho-selectivity. N-Heteroarenes such as indoles and imidazoles also gave monohalogenated products with high selectivity. Unlike the copper-catalyzed halogenation, the present method works well with electron-withdrawing group bearing phenols and gives comparatively better yields and selectivity. The Cu-Mn spinel catalyst is robust and reused three times under optimized conditions without any loss in catalytic activity. Nonphenolics did not undergo this transformation.
- Singh, Parvinder Pal,Thatikonda, Thanusha,Kumar, K. A. Aravinda,Sawant, Sanghapal D.,Singh, Baldev,Sharma, Amit Kumar,Sharma,Singh, Deepika,Vishwakarma, Ram A.
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scheme or table
p. 5823 - 5828
(2012/09/05)
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- Simple and efficient method for the halogenation of oxygenated aromatic compounds
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An efficient and mild method for the chlorination and bromination of oxygenated aromatics, with good regioselectivity and excellent yields, using a combination of HX/H2O2/AcOH in petroleum ether is presented. The effect of ultrasound was investigated. Georg Thieme Verlag Stuttgart ? New York.
- Koini, Eftychia N.,Avlonitis, Nicolaos,Calogeropoulou, Theodora
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experimental part
p. 1537 - 1542
(2011/08/03)
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- Regioselective supramolecular catalysis. Exploiting multiple binding motifs in propanediurea molecular clips
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Molecular clips derived from 2,4,6,8-tetraazabicyclo[3.3.1]nonane-3,7-dione promote increased regioselectivity in the SO2Cl2-mediated electrophilic aromatic chlorination of ortho-cresol leading to para/ortho ratios (Rp/o) 25; approximately six times larger than in the absence of the clip. Specific recognition events involving hydrogen-bond, π-π and dative covalent interactions are implicated.
- Bugnet, Emmanuelle A.,Nixon, Tracy D.,Kilner, Colin A.,Greatrex, Robert,Kee, Terence P.
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p. 5491 - 5494
(2007/10/03)
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- Two efficient methods for the preparation of 2-chloro-6-methylbenzoic acid
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Two efficient methods for the preparation of 2-chloro-6-methylbenzoic acid were developed: one based on nucleophilic aromatic substitution and the other based on carbonylation. In the first approach, 2-chloro-6-fluorobenzaldehyde was converted to its n-butylimine, then treated with 2 equiv of methylmagnesium chloride in THF to give, after hydrolysis, 2-chloro-6-methylbenzaldehyde. Subsequent oxidation of this compound gave the title compound in 85% overall yield. In the second approach, 3-chloro-2-iodotoluene was efficiently carbonylated in methanol to give methyl 2-chloro-6-methylbenzoate, which after hydrolysis afforded the title compound in 94% yield (84% yield after recrystallization). The carbomethoxylation proceeded smoothly even at a high substrate-to-Pd ratio of 10 000. Both methods do not require isolation of intermediates and are suitable for the preparation of kilogram quantities of 2-chloro-6-methylbenzoic acid.
- Daniewski, Andrzej R.,Liu, Wen,Puentener, Kurt,Scalone, Michelangelo
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p. 220 - 224
(2013/09/06)
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- Highly efficient, para-selective oxychlorination of aromatic compounds using potassium chloride and Oxone
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A highly efficient, regioselective method for oxychlorination of aromatic compounds is possible through electrophilic substitution of chlorine generated in situ from KCl as a chlorine source and Oxone as an oxidant for the first time.
- Narender,Srinivasu,Kulkarni,Raghavan
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p. 279 - 286
(2007/10/03)
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- N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-2,5-dienylideneamine as a mild and highly regioselective chlorinating reagent
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N-Chloro-2,3,4,4,5,6-hexachlorocyclohexa-2,5-dienylideneamine was used as a new, mild and highly regioselective chlorinating reagent in the chlorination of phenol and o-cresol in CCl4, DMF and CH3CN. The effects of C2H5OH, C5H5N, DMF and Et3N on the regioselectivity in CCl4 have also been examined.
- Mamaghani,Zolfigol,Shojaei
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p. 735 - 740
(2007/10/03)
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- Reactions of OH and SO4.- with Some Halobenzenes and Halotoluenes: A Radiation Chemical Study
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The optical absorption and kinetic characteristics of the transients formed in the reactions of OH and SO4.- with bromobenzene, ortho and meta-isomers of chloro- and bromobenzenes, and monobromotoluenes have been studied by pulse radiolysis technique.The rates for OH reaction are generally higher (k = (1.7-4.4)X109 M-1s-1) than those found for the SO4.- reaction (k = (0.4-2.3)x109 M-1s-1). ρ+ values of -0.4 for OH and -1.2 for SO4.- reactions were obtained from the Hammett analysis.The formation of substituted hydroxycyclohexadienyl radicals (λmax = 315-330 nm) is the major reaction channel, and the phenoxyl type radical (λ >/=400 nm) formation is an additional minor process in the SO4.- reaction.Abstraction of H by SO4.- from the -CH3 group is only significant with the para-isomers of bromo- and chlorotoluenes.This result is in accord with the observed yields (70 percent of SO4.-) of the products resulting from the oxidation of the 4-chlorobenzyl radical in the presence of K3Fe(CN)6 under steady-state conditions.The total yields of the phenolic products accounting for >90 percent of OH and SO4.- suggest that the attack at the ipso positions is considerably small.The rate constants for OH reactions relative to benzene at positions 3 and 6 of 2-chlorotoluene and positions 2 and 3 of 4-chlorotoluene are between 1.18 and 1.39, indicating that the directing effects of -CH3 and -Cl groups are comparable.This is also reflected in the additive effects of activation of the ortho and para-positions and deactivation of meta-positions by these substituents in 3-chlorotoluene.
- Merga, Getahun,Rao, B. S. M.,Mohan, H.,Mittal, J. P.
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p. 9158 - 9164
(2007/10/02)
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- HIGH ORTHO-SELECTIVITY IN THE CHLORINATION OF PHENOLS WITH N-CHLORODIALKYLAMINES IN THE PRESENCE OF SILICA.
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Phenols are readily chlorinated by N-chlorodialkylamines in the presence of silica.Furthermore, this approach allows greater selectivity for mono:di and ortho: para chlorination than is possible with many other approaches.
- Smith, Keith,Butters, Michael,Nay, Barry
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p. 1319 - 1322
(2007/10/02)
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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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- HIGH SITE-SELECTIVITY IN THE CHLORINATION OF ELECTRON-RICH AROMATIC COMPOUNDS BY N-CHLORAMMONIUM SALTS.
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N-Chlorammonium salts are efficient and very site-selective monochlorinating agents for electron-rich aromatic compounds.
- Smith, John R. Lindsay,McKeer, Linda C.
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p. 3117 - 3120
(2007/10/02)
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- HALOGENATION REGIOSELECTIVE EN SERIE AROMATIQUE-I CHLORATION DES PHENOLS ET LEURS ETHERS A L'AIDE DE REACTIFS METTANT EN JEU DES INTERACTIONS DONNEUR-ACCEPTEUR
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An efficient regiospecific route for the chlorination of phenol involving hexachlorohexadienones is described.The selectivity is attained by using a reagent tailored in such a way that it is able to participate in charge transfer interactions and hydrogen bonding with the substrate.This recognition between substrate (phenol) and 2,3,4,4,5,6-hexachlorocyclohexa 2,5-dien 1-one 1 which we called "reactif p" allows the chlorination of phenol in the para position.The use of 2,3,4,5,6,6-hexachlorocyclohexa 2,4-dien-1 one 2 we have called "reactif o" permits the chlorination in the ortho position.These two reagents are stable and inexpensive materials, synthetized from pentachlorophenol and chlorine.The chlorination of anisole with these two reagents, gives solely the parachloro derivative, under steric control.
- Guy, Alain,Lemaire, Marc,Guette, Jean-Paul
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p. 2339 - 2346
(2007/10/02)
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- Regiospecific Chlorination of Aromatic Substrates using Donor-Acceptor and Hydrogen Bonding Interactions
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The chlorination of aromatic substances has been achieved with good regioselectivity using 2,3,4,4,5,6-hexachlorocyclohexa-2,5-dien-1-one and 2,3,4,5,6,6-hexachlorocyclohexa-2,4-dien-1-one as chlorinating agents.
- Guy, Alain,Lemaire, Marc,Guette, Jean-Paul
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