- Molecular Orbital Calculations and 13C NMR Studies To Explain a Regiospecific Demethylation of 3-Alkyl-1,2-dimethoxybenzenes
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This study was performed to explain a regiospecific demethylation of 3-alkyl-1,2-dimethoxybenzenes.PRDDO-MO calculations show that the low-energy conformation of the carbon of a methoxy group having two ortho neighbors on a benzene ring is located out of the plane of the aromatic ring, whereas a methoxy group with only one ortho neighbor executes restricted rotation in the plane of the ring.The carbon portion of the methoxy group is turned away from the neighboring substituent.These calculations also show that the atomic charge on the oxygen atom in the former caseexceeds that in the latter.The carbon of a methoxy group with two ortho neighbors yields 13C NMR T1 relaxation times longer than those with only one ortho neighbor, also suggesting that the methoxy group with two ortho neighbors is crowded out of the plane of the aromatic ring. 13C NMR chemical shifts of these ortho-substituted methoxybenzenes did not correlate well with shifts predicted from published additive parameters; this again suggests an unusual methoxy group orientation and distribution of electrons.The forced rotation of a methoxy group out of the plane of the benzene ring diminishes the release of electrons from the methoxy group to the benzene ring.The resulting higher atomic charge on the oxygen and the orientation of the oxygen orbitals facilitate complexation with Lewis acids and methoxy group cleavage.
- Jardon, Phillip W.,Vickery, Euin H.,Pahler, Leon F.,Pourahmady, Naser,Mains, Gilbert J.,Eisenbraun, Edmund J.
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- Methylation of Alcohols, Phenols, and Carboxylic Acids, and Selective Monomethylation of Diols and Dicarboxylic Acids with Dimethyl Sulfate by Use of Alumina
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Alcohols in cyclohexane give their methyl ethers in high yields by the use of a combination of dimethyl sulfate and alumina.Some diols and dicarboxylic acids adsorbed on alumina react with dimethyl sulfate and produce the corresponding monomethyl ethers and esters in high selectivities.
- Ogawa, Haruo,Ichimura, Youko,Chihara, Teiji,Teratani, Shousuke,Taya, Kazuo
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- Selective catalytic conversion of guaiacol to phenols over a molybdenum carbide catalyst
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An activated carbon supported α-molybdenum carbide catalyst (α-MoC1-x/AC) showed remarkable activity in the selective deoxygenation of guaiacol to substituted mono-phenols in low carbon number alcohol solvents. Combined selectivities of up to 85% for phenol and alkylphenols were obtained at 340°C for α-MoC1-x/AC at 87% conversion in supercritical ethanol. The reaction occurs via consecutive demethylation followed by a dehydroxylation route instead of a direct demethoxygenation pathway.
- Ma, Rui,Cui, Kai,Yang, Le,Ma, Xiaolei,Li, Yongdan
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- AGGREGATION OF LITHIUM PHENOLATES IN WEAKLY POLAR APROTIC SOLVENTS.
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The aggregation of lithium phenolate, 3,5-dimethylphenolate, 2,6-dimethylphenolate, and 2,6-di-tert-butylphenolate in dioxalane, dimethoxyethane, and pyridine has been investigated by a variety of methods including studies of vapor pressure barometry, **1**3C chemical shifts, **7Li nuclear quadrupole coupling constants, and **1**3C spin-lattice relaxation times. The phenolates with no ortho substituents from tetramers under most conditions. In pyridine at low concentrations and temperature the tetramers coexist with dimers. Lithium 2,6-dimethylphenolate forms dimers under all conditions studied, and lithium 2,6-di-tert-butylphenolate exists as a monomer or an oligomer depending on conditions. Attempts to establish solvation numbers for the aggregates from solvent **1**3C relaxation times have not been successful, and the reason for the failure, very fast solvent exchange, is discussed. The kinetics and thermodynamics of exchange between dimers and tetramers of lithium 3,5-dimentylphenolate in pyridine have been investigated, and the mechanism of interconversion is shown to involve additional solvation of the tetramer prior to dissociation.
- Jackman,DeBrosse
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- Methylation of phenol and its derivatives with dimethyl carbonate in the presence of Mn2(CO)10, W(CO)6, and Co2(CO)8
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Aryl methyl ethers were synthesized by reactions of phenol, substituted phenols, and α- and β-naphthols with dimethyl carbonate in the presence of manganese, tungsten, and cobalt carbonyls. Optimal reactant and catalyst ratios and reaction conditions were found to ensure selective formation of aryl methyl ethers.
- Khusnutdinov,Shchadneva,Mayakova, Yu. Yu.
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- Pd-Catalyzed ipso, meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source
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A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of ortho-substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of K2CO3 as a base, iodoarenes are dimethylated at the ipso- and meta-positions of the iodo group, which represents a novel strategy for meta-C-H methylation. With KOAc as the base, subsequent oxidative C(sp3)-H/C(sp3)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.
- Wu, Zhuo,Wei, Feng,Wan, Bin,Zhang, Yanghui
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supporting information
p. 4524 - 4530
(2021/05/04)
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- Trialkylammonium salt degradation: Implications for methylation and cross-coupling
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Trialkylammonium (most notably N,N,N-trimethylanilinium) salts are known to display dual reactivity through both the aryl group and the N-methyl groups. These salts have thus been widely applied in cross-coupling, aryl etherification, fluorine radiolabelling, phase-transfer catalysis, supramolecular recognition, polymer design, and (more recently) methylation. However, their application as electrophilic methylating reagents remains somewhat underexplored, and an understanding of their arylation versus methylation reactivities is lacking. This study presents a mechanistic degradation analysis of N,N,N-trimethylanilinium salts and highlights the implications for synthetic applications of this important class of salts. Kinetic degradation studies, in both solid and solution phases, have delivered insights into the physical and chemical parameters affecting anilinium salt stability. 1H NMR kinetic analysis of salt degradation has evidenced thermal degradation to methyl iodide and the parent aniline, consistent with a closed-shell SN2-centred degradative pathway, and methyl iodide being the key reactive species in applied methylation procedures. Furthermore, the effect of halide and non-nucleophilic counterions on salt degradation has been investigated, along with deuterium isotope and solvent effects. New mechanistic insights have enabled the investigation of the use of trimethylanilinium salts in O-methylation and in improved cross-coupling strategies. Finally, detailed computational studies have helped highlight limitations in the current state-of-the-art of solvation modelling of reaction in which the bulk medium undergoes experimentally observable changes over the reaction timecourse. This journal is
- Assante, Michele,Baillie, Sharon E.,Juba, Vanessa,Leach, Andrew G.,McKinney, David,Reid, Marc,Washington, Jack B.,Yan, Chunhui
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p. 6949 - 6963
(2021/06/02)
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- Selective O-methylation of phenols and benzyl alcohols in simple pyridinium based ionic liquids
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Synthesis of pyridinium based ionic liquids were reported and applied as catalyst for the selective O-methylation of phenols and benzyl alcohols. The reactions were carried out by using dimethylcarbonate (DMC) as the methylating agent. High selectivity, high yield and recyclability of the ionic liquids are important features of the reactions.
- Das, Pranab Jyoti,Das, Jupitara
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- Microwave mediated protection of hindered phenols and alcohols
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Hindered phenols and alcohols were protected as their corresponding ethers using different alkylating agents in presence of KOH/DMSO under microwave irradiation.
- Pothi, Tejas,Dawange, Mahesh,Chavan, Kamlesh,Sharma, Rajiv,Deka, Nabajyoti
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p. 706 - 711
(2013/03/28)
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- Development of bis(2-picolyl)amine-zinc chelates for imidazole receptors
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New phenyl and phenol bis(2-picolyl)amine (Dpa) derivatives have been synthesized in order to generate zinc chelates for imidazole anion receptors. Previously, binuclear phenolic zinc and copper chelates have shown affinity for pyrophosphate and guanidine anions, respectively. Herein we report significant imidazole affinity increasing from 2.38 × 106 to 2.90 × 107 for phenol-bridged binuclear zinc-Dpa chelates, as evidenced by dynamic and titration 1H NMR studies. Among the Dpa chelates investigated, the zinc-coordinated phenol group plays a crucial role in the mechanism of anion binding. Low-temperature 1H NMR experiments suggest a σν-symmetric geometry for the imidazole chelate. Computational DFT studies at the B3LYP level of theory imply that imidazole binding displaces the phenol bridge between the zinc ions. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Routasalo, Taina,Helaja, Juho,Kavakka, Jari,Koskinen, Ari M. P.
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experimental part
p. 3190 - 3199
(2009/04/07)
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- Development of Dpa-based imidazole zinc anion receptors
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A synthetic route for a new, phenolic Dpa-based aza ligand is presented and its chelation with zinc ions and imidazole were studied using UV/vis and mass spectrometry. A bathochromic shift of 30 nm was observed for the 2*Zn complex of the ligand in UV/vis
- Salo, Taina M.,Helaja, Juho,Koskinen, Ari M.P.
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p. 2977 - 2980
(2007/10/03)
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- A minimalist approach to C-H activation by copper
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The complex [Cu2(1)2]2+ (1=1,3-bis(1-methyl-1H-benzimidazol-2-yl)benzene) undergoes slow oxidation by dioxygen in DMF solution to give the hydroxylated product [Cu 2(2-H)2]2+ (2=2,6-bis(1-methyl-1H-benzimidazol- 2-yl)phenol) characterized by an X-ray crystal-structure analysis. The oxidation occurs much faster when CuII is mixed with 1 in the presence of H2O2, with 80% hydroxylation observed within a few minutes. The mononuclear complex formed with 1-methyl-2-phenyl-1H-benzimidazole (3) shows no hydroxylation under these conditions. It is concluded that the hydroxylation requires the presence of a ligand capable of stabilizing a binuclear species, but no special coordinative activation of the copper is required.
- Kuebel-Pollak, Anita,Ruettimann, Stephane,Dunn, Nichola,Melich, Xavier,Williams, Alan F.,Bernardinelli, Gerald
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p. 841 - 853
(2007/10/03)
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- ρ-heteroatom-substituted phenols and uses thereof
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The present invention provides an antiproliferative p-heteroatom-substituted phenol compound having the structure formula STR1 wherein m is 0 to 3, n is 0 to 4 when Het is nitrogen, wherein R is selected from the group consisting of hydrogen, alkyl, arylmethyl and acyl; R1 is alkyl; R2 is selected from the group consisting of hydrogen and alkyl; R3 is selected from the group consisting of alkyl and acyl when Het is nitrogen, R4 is selected from the group consisting of hydrogen and alkyl; R5 is selected from the group consisting of hydrogen and alkyl; and R6 and R7 are selected from the group consisting of hydrogen, alkyl and R6 and R7 together may represent oxygen. Also provided are various methods for the treatment of a pathological cell proliferative disease comprising administering to an animal) a pharmacologically and therapeutically effective dose of a pharmaceutical composition comprising a p-heteroatom-substituted phenols or an analog thereof.
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- Pyridinium N-Phenoxide Betaines and Their Application to the Characterization of Solvent Polarities, XX Synthesis, Solvatochromism, and Halochromism of Chromoionophoric Crown Ether-Substituted Pyridinium N-Phenolate Betaine Dyes
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Synthesis, negative solvatochromism (Table 1, Figure 1), and negative halochromism (Tables 2-3, Figures 2-3) of the new crown ether-substituted pyridinium N-phenolate betaine dyes 3-6 are described.In contrast to other known chromoionophores, 3-5 exhibit
- Reichardt, Christian,Asharin-Fard, Siamak,Schaefer, Gerhard
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- A New Rearrangement of Alkoxybenzyl Anions
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Alkyl groups migrate from oxygen to carbon in alkyl aryl ethers which have been metalated in benzylic positions. 2,6-Dimethylanisole provides a variety of 2,6-dialkylphenols and their ethers in 45-80percent yields.Rearrangement products are obtained in 10-30percent yields from other dimethylanisoles and from methylanisoles.The reactions appear to proceed, like Wittig rearrangements, by homolytic cleavage of the alkyl-oxygen bond followed by recombination of the resulting radical pair in a different way.The rearrangements can be avoided by using methyl ethers and working at or below room temperature.
- Bates, Robert B.,Siahaan, Teruna J.,Suvannachut, Kessara
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p. 1328 - 1334
(2007/10/02)
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- Pentaalkylguanidines as etherification and esterification catalysts
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Several pentaalkylguanidines have been prepared and found to be superior catalysts for the preparation of aryl and aralkyl ethers from carbonates and for the methylation of phenols with dimethylcarbonate.They also act as effective catalysts for esterification of acids with alkyl chloroformates but not for the acetylation of tertiary alcohols with acetic anhydride.
- Barcelo, Gerard,Grenouillat, Denis,Senet, Jean-Pierre,Sennyey, Gerard
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p. 1839 - 1848
(2007/10/02)
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- METALATION REACTIONS. XIV. REGIOSPECIFIC PREPARATION OF POLYSUBSTITUTED BENZENES VIA MONO- OR DI-LITHIATION REACTIONS OF AROMATIC THIOETHERS
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The preparation of polyfunctionalized aromatic thioethers either by one-step dilithiation or by two successive one-flask monometalation reactions is described.By acting on 1 two equal or different electrophiles one on the thiomethyl group and one in the ortho-position with respect to it are introduced; by acting on 11 and on 35 the substitution involves the thiomethyl carbon atom and that in the ortho-position with respect to the alkoxy group.In the case of the homologeous isopropylthio (23) the substitution involves the two aryl carbon atoms in the ortho-position to both functions.In the case of the p-disubstituted isomers (49, 59) analogous behaviour to ortho isomers in one-step metalation reaction is observed, while the two hydrogen atoms in the ortho-positions to the methoxy group are substituted when two successive monometalations are employed.The metalation of 40 results low selective.The behaviour of 79 and 93 is analogous to 1, while 72, 88 and 96 undergo only one-step monometalation reactions.
- Cabiddu, Salvatore,Fattuoni, Claudia,Floris, Costantino,Gelli, Gioanna,Melis, Stefana,Sotgiu, Francesca
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p. 861 - 884
(2007/10/02)
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- The photocyclization of o-alkoxy phenyl ketones
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Several o-alkoxybenzophenones and o-(benzyloxy)benzophenones and -acetophenones photocyclize to 3-hydroxy-2,3-dihydrobenzofurans. Quantum yields generally are quite high, except for o-(benzyloxy)acetophenone. The o-ethoxy and o-benzyloxy ketones form two diastereomeric products, the Z isomer being highly preferred in hydrocarbon solvents, the E isomer being formed in comparable yield in methanol or with added pyridine. The reaction involves δ-hydrogen abstraction by the ketone triplets followed by cyclization of the 1,5-biradical intermediates. The biradicals have such short lifetimes that they usually cannot be detected by flash spectroscopy or trapped by thiols. Triplet state lifetimes, determined both by steady-state quenching studies and by flash kinetics, reveal that hydrogen abstraction rate constants are quite low. Arrhenius plots for triplet decay indicate activation energies of 3-5 kcal/mol and A values of 109 for the δ-hydrogen abstraction. MMX calculations and spectroscopic data all indicate that the ketones exist primarily in conformations with the carbon α to the ether oxygen twisted well away from the carbonyl. The low observed rate constants are ascribed to even lower equilibrium populations of conformers in the geometry required for reaction in the triplet state than in the ground state. 2,6-Diacylphenyl ethers show ten times the triplet reactivity of their monoacyl equivalents. In these cases, the ether function is twisted 90° such that the target C-H bond is much closer to a carbonyl. The large solvent effects on the stereochemistry of cyclization despite short biradical lifetimes suggest that bond rotations may induce intersystem crossing of the triplet biradicals. The low cyclization quantum yield from o-(benzyloxy)acetophenone and the formation of o-benzoylacetophenone as a major side product suggest that the 1,5-biradicals partially cyclize into the benzene ring to generate spiroenol intermediates. Rate constants for quenching of the triplet ketones by 2,5-dimethyl-2,4-hexadiene were measured. The kq values are ≥5 × 109 M-1 s-1 for the o-methoxy ketones but only 1-3 × 109 for the o-benzyloxy ketones. This rare steric effect on triplet energy transfer is attributed to twisting of the benzoyl chromophores caused by steric congestion.
- Wagner, Peter J.,Meador, Michael A.,Park, Bong-Ser
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p. 5199 - 5211
(2007/10/02)
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- SYNTHESIS OF SOME FUNCTIONALIZED PHOSPHINOCARBOXYLIC ACIDS
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Various functionalized phosphinocarboxylic acids have been prepared by a number of complementary methods.Reactions of relatively electron-poor secondary phosphides with electron-rich halocarboxylates in liquid ammonia give high yields of phosphinocarboxylates.The substitution reactionmay proceed by a classical SN2 mechanism or by an SN rad mechanism.Reduction of the carboxilate can be a deleterious side reaction in the preparation of phosphinoacetic acids.Several phosphinopropionic acids are prepared by the Michael adition of diphenylphosphine to unsaturated esters.A valuable method proved to be the reaction of dichlorophosphinoacetic ester with functionalized organometallic reagents. Key words: Phosphine; carboxylic acid; ligand; functionalized; synthesis; NMR data.
- van Doorn, J. A.,Meijboom, N.
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p. 211 - 222
(2007/10/02)
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- A FACILE AND DIRECT CONVERSION OF ARYL-ACETATE TO ALKYL-ARYL ETHER.
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Arylacetate was directly converted to the corresponding alkyl-aryl ether by treatment with sodium hydride and alkyl halide in THF and HMPA.
- Yamashita, A.,Toy, A.
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p. 755 - 762
(2007/10/02)
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- Phenol alkylation and anisole rearrangement on AlPO4, TiO2, and AlPO4-TiO2 catalysts
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Using the microcatalytic pulse technique, the alkylation of phenol with methanol and the conversion of anisole in the presence of methanol were studied at temperatures ranging from 520 to 670 K over TiO2, AlPO4 and AlPO4-TiO2 (with different weight ratios
- Campelo, Juan-Manuel,Garcia, Angel,Luna, Diego,Marinas, Jose-Maria,Moreno, Maria-Sierra
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p. 283 - 292
(2007/10/02)
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- Highly sterically hindered guanidines and process for the production thereof
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Compounds of the formula STR1 in which R1, R1 ', R2, R2 ' and R3 independently represent a C1-6 alkyl radical, in addition to which R3 may represent a hydrogen atom, the alkyl radicals together containing in all at least 8 carbon atoms, are provided for use as highly sterically hindered bases in chemical syntheses.
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- FLUORIDE SALTS ON ALUMINA AS REAGENTS FOR ALKYLATION OF PHENOLS AND ALCOHOLS.
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THE EFFECTIVENESS OF ALKALI METAL FLUORIDES IMPREGNATED ON ALUMINA AS A REAGENT FOR PROMOTING ALKYLATION WAS OPTIMIZED WITH RESPECT TO THE METAL CATION, THE AMOUNT OF IMPREGNATION, AND THE REACTION SOLVENT. POTASSIUM OR CAESIUM FLUORIDE ONALUMINA IN ACETONITRILE OR 1,2-DIMETHOXYETHANE WAS CONCLUDED TO BE THE BEST REACTION SYSTEM FOR GENERAL USE. O-ALKYLATION OF SUBSTITUTED PHENOLS, PRIMARY AND SECONDARY ALCOHOLS, AND A GLYCOL WAS CARRIED OUT MOSTLY IN GOOD YIELDS UNDER MILDCONDITIONS WITH SIMPLE EXPERIMENTAL PROCEDURES.
- ANDO,YAMAWAKI,KAWATE,SUMI,HANAFUSA
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p. 2504 - 2507
(2007/10/02)
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- 13C Nuclear Magnetic Resonance Spectra of Methoxycyclohexane Derivatives. Rotamer Populations about C-OMe Bonds as indicated by 13C Chemical Shifts of Methoxy- and Ring-carbons and 3JC,H Coupling Constants
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Methoxy 13C chemical shifts in methoxycyclohexane derivatives may be rationalized in terms of rotamer populations about the C-OMe bond and δ1-effects caused by steric interaction of the methoxy-group with substituents at the neighbouring 2- and 6-positions.Information on rotamer populations is obtained also from the 13C chemical shifts of C-2 and C-6, and from the three-bond coupling between the proton at C-1 and the methoxy-carbon atom.
- Haines, Alan H.,Shandiz, Mohammad Seyedi
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p. 1671 - 1678
(2007/10/02)
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- Arene-Metal Complexes. 12. Reaction of Substituted (Benzene)tricarbonylchromium Complexes with n-Butyllithium
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Reaction of a series of substituted (benzene)tricarbonylchromium complexes with n-butyllithium has been examined.The reaction appears to proceed via proton abstraction to yield an (aryllithium)tricarbonylchromium intermediate which may then be quenched by the addition of primary alkyl halides,usually methyl iodide.New alkylated complexes may be obtained,or the material may be decomplexed to yield alkylated benzene derivatives.In this manner,(monoalkylbenzene)tricarbonylchromium complexes yield mainly m-dialkylbenzenes;(fluorobenzene)tricarbonylchromium yields o-fluorotoluene;(anisole)tricarbonylchromium yields mainly 2,6-dimethylanisole;and (N,N-dimethylaniline)tricarbonylchromium yields several isomeric N,N-dimethyltoluidines.(Iodobenzene)tricarbonylchromium undergoes metal-halogen exchange with n-butyllithium and may be converted to either toluene or n-butylbenzene depending on the reaction conditions.Comparison with known chemistry of the uncomplexed analogues demonstrates the strongly activating effect of the tricarbonylchromium moiety on these reactions.It is especially interesting that under these conditions reaction of (fluorobenzene)tricarbonylchromium with n-butyllithium results in proton abstraction rather than net nucleophilic displacement,as observed when less basic nucleophiles are used.
- Card, Roger J.,Trahanovsky, Walter S.
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p. 2560 - 2566
(2007/10/02)
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