19578-74-6

Upstream product

• 576-26-1 2.6-dimethylphenol 
• 100-39-0 benzyl bromide 
• 16081-16-6 sodium 2,6-dimethylphenolate 
• 100-44-7 benzyl chloride 
• 1004-66-6 2-methoxy-1,3-dimethylbenzene 
• 60-29-7 diethyl ether 
• 6711-19-9 benzylium cation 
• 100-51-6 benzyl alcohol 
• 533-58-4 2-Iodophenol 
• 142523-69-1 1-benzyloxy-2-iodobenzene 
• 616-38-6 carbonic acid dimethyl ester 
• 42790-42-1 4-aza-1-benzylazoniabicyclo<2.2.2>octane chloride 
• 13326-10-8 benzyl methyl carbonate 
• 95414-83-8 benzyl 2,6-dimethylphenyl carbonate 

Downstream Products

• 576-26-1 2.6-dimethylphenol 
• 108-88-3 toluene 
• 41772-31-0 4‐benzyl‐2,6‐dimethylphenol 

Relevant academic research and scientific papers

Towards ortho-selective electrophilic substitution/addition to phenolates in anhydrous solvents

Alkyl-substituted Li-phenolates with BnBr in water solution lead to a mixture of o- and p-Bn-substituted phenols together with a substantial amount of phenol Bn ether. In CPME, and especially in toluene with 1–2 equivalents of ether or alcohol additives, ortho-selective alkylation is achieved. In the case of o,o,p-tri- and o,o-di-substituted phenols dearomatization occurs affording o-Bn-substituted alkyl cyclohexadienones with yields up to 92% with an o/p ratio up to 90/1.

Pd-Catalyzed ipso, meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source

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.

Ring-opening reactions of 1,4-diazabicyclo[2.2.2]octane (DABCO) derived quaternary ammonium salts with phenols and related nucleophiles

1,4-Diazabicyclo[2.2.2]octane (DABCO) has been evaluated as a starting material for the synthesis of 1-alkyl-4-(2-phenoxyethyl)piperazines and related derivatives. We found that 1-alkyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, resulting from the alkylation of DABCO, efficiently react with a variety of nucleophiles in polyethyleneglycol (PEG) or diglyme at high temperatures to give piperazine products resulting from the nucleophilic ring-opening reaction. The benzylation side reaction was found to be relevant with softer nucleophiles when using 1-benzyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, while other types of alkylations were not observed. One-pot methodologies allow for the synthesis of piperazines directly from primary alcohols, alkyl halides or sulfonates, using phenols, or other nucleophile sources, and DABCO. The Royal Society of Chemistry 2012.

Benzyl protection of phenols under neutral conditions: Palladium-catalyzed benzylations of phenols

Benzyl protection of phenols under neutral conditions was achieved by using a Pd(n3-C3H5)Cp-DPEphos catalyst. The palladium catalyst efficiently converted aryl benzyl carbonates into benzyl-protected phenols through the decarboxylative etherification. Alternatively, the nucleophilic substitution of benzyl methyl carbonates with phenols proceeded In the presence of the catalyst, yielding aryl benzyl ethers.

Efficient methods for the preparation of alkyl-aryl and symmetrical or unsymmetrical dialkyl ethers between alcohols and phenols or two alcohols by oxidation-reduction condensation

Oxidation-reduction condensation via alkoxydiphenylphosphines (diphenylphosphinite esters) (1), generated in situ from chlorodiphenylphosphine (2) and alcohols, 2,6-dimethyl-1,4-benzoquinone (3), and phenols proceeds smoothly to afford alkyl-aryl ethers in good to high yields under neutral conditions. In a similar fashion, a new and efficient method for the preparation of symmetrical or unsymmetrical dialkyl ethers in good to high yields is established via tetrafluoro-1,4-benzoquinone (fluoranil) (4), alcohols, and 1 formed in situ from nBuLi-treated alcohols and 2. This method is applicable also to the etherification of chiral secondary or tertiary alcohols with retention or inversion of configurations. The inverted ethers are afforded by treating chiral alkoxydiphenylphosphines and achiral alcohols, while the reaction of achiral alkoxydiphenylphosphines and chiral alcohols forms retained ethers.

Alkylation of phenols by oxidation-reduction condensation using 2,6-dimethyl-1,4-benzoquinone and alkoxydiphenylphosphine

Various alkyl phenyl ethers were obtained in high yields by way of oxidation-reduction condensation where alkoxydiphenylphosphine, prepared easily from chlorodiphenylphosphine and corresponding alcohols, was treated with various phenols in the co-existenc

Efficient method for the preparation of carboxylic acid alkyl esters or alkyl phenyl ethers by a new-type of oxidation-reduction condensation using 2,6-dimethyl-1,4-benzoquinone and alkoxydiphenylphosphines

A new-type of oxidation-reduction condensation proceeded smoothly to afford carboxylic acid alkyl esters or alkyl phenyl ethers in good to high yields by combined use of alkoxydiphenylphosphines (1) having primary, bulky secondary or tertiary alkoxy groups, a mild quinone-type oxidant such as 2,6-dimethyl-1,4-benzoquinone (DMBQ) and carboxylic acids or phenols. Generally, alkoxydiphenylphosphines were prepared easily from chlorodiphenylphosphine (2) and alcohols in the presence of pyridine, and were isolated by distillation. On the other hand, the phosphines 1 were also prepared in situ from N,N-dimethylaminodiphenylphosphine (3a) and primary or secondary alcohols while primary, bulky secondary or tertiary alkoxydiphenylphosphines were alternatively formed in situ by adding 2 to the "BuLi-treated alcohols in order to perform the above reactions by a one-pot procedure from alcohols and nucleophiles. The reaction of thus formed 1, DMBQ and carboxylic acids or phenols afforded the corresponding alkylated products, including hindered secondary and tertiary alkylated ones, in good to high yields at room temperature. In the case of using chiral secondary alcohols, the corresponding carboxylic acid alkyl esters were obtained as well in high yields with perfect inversion of stereochemistry by SN2 replacement.

Novel Synthesis of N,N-Diarylarylmethanamines from N-(Arylmethylene)arenamines and (Arylmethoxy)arenes

Various N,N-diarylarylmethanamines were synthesized by the reaction of N-(arylmethylene)arenamines with (arylmethoxy)arenes in dimethylformamide solution in the presence of a strong base as a catalyst which is obtained in situ by reacting metallic sodium with this solvent.In general, the reaction may be depicted as the reduction of the imine and addition, on the original imino nitrogen atom, of the aryl group (of the aryloxy moiety) of the ether and presumably oxidation of the arylmethoxy group of the ether to its corresponding aldehyde.Side reactions and a proposed reaction mechanism are discussed.

PREDOMINANT O-ALKYLATION IN THE ATTACK OF FREE BENZYL CATION ON 2,6-DIMETHYLANISOLE

Labelled benzyl cation from the decay of side-chain multitritiated toluene has been allowed to react with 2,6-dimethylanisole in n-hexane, nitromethane, and diethyl ether solutions at room temperature The nuclear-decay formed (nucleogenic) benzyl cation displays high selectivity toward the n-type centre of the nucleophiles present, leading to predominant formation of benzyl 2,6-dimethylphenyl ether in n-hexane and nitromethane, via the O-benzylated oxonium intermediate.In n-hexane, the oxonium intermediate undergoes partial isomerization, yielding the corresponding ring-substituted products (0.5 meta/para = 1.3).A mechanism involving a tight sandwich ? complex is proposed to account for the solvent effect on product distribution.The mechanistic features of the benzylation process, deduced from the decay experiments, are discussed and compared with those of related gas-phase and conventional Friedel-Crafts data.

Meta Substitution in Electrophilic Benzylations of 2,6-Dimethylphenol and Alkyl 2,6-Dimethylphenyl Ethers: Product Distributions and Mechanism

Electrophilic benzylations of 2,6-dimethylphenol and 2,6-dimethylanisole under a variety of conditions yield ca. 40 percent and 70percent, respectively, of the meta substitution products, although other electrophilic substitution reactions appear to proce