29268-64-2

Upstream product

• 75295-98-6 1-(p-methoxyphenyl)ethanol-2,2,2-d3 
• 123-11-5 4-methoxy-benzaldehyde 
• 768-60-5 4-methoxyphenylacetylen 
• 13422-77-0 3-(4-methoxy-phenyl)-3-oxo-propionic acid 
• 100-06-1 1-(4-methoxyphenyl)ethanone 

Downstream Products

• 75295-98-6 1-(p-methoxyphenyl)ethanol-2,2,2-d3 
• 75296-08-1 C₉H₈⁽²⁾H₃O⁽¹⁺⁾ 
• 313945-09-4 1-(p-methoxyphenyl)ethanol-1,2,2,2-d4 

Relevant academic research and scientific papers

Bismuth subnitrate-catalyzed markovnikov-type alkyne hydrations under batch and continuous flow conditions

Bismuth subnitrate is reported herein as a simple and efficient catalyst for the atom-economical synthesis of methyl ketones via Markovnikov-type alkyne hydration. Besides an effective batch process under reasonably mild conditions, a chemically intensified continuous flow protocol was also developed in a packed-bed system. The applicability of the methodologies was demonstrated through hydration of a diverse set of terminal acetylenes. By simply switching the reaction medium from methanol to methanol-d4, valuable trideuteromethyl ketones were also prepared. Due to the ready availability and nontoxicity of the heterogeneous catalyst, which eliminated the need for any special additives and/or harmful reagents, the presented processes display significant advances in terms of practicality and sustainability.

Spontaneous conversion of prenyl halides to acids: application in metal-free preparation of deuterated compounds under mild conditions

Here we reveal a simple generation of deuterium halide (DX) from common and inexpensive reagents readily available in a synthetic chemistry laboratory,i.e. prenyl-, allyl-, and propargyl halides, under mild conditions. We envisaged thatin situgeneration of an acid, deuterium halide, would be useful for acid-catalyzed reactions and could be employed for organocatalytic deuteration. The present work reports a metal-free method for deuterium labeling covering a broad range of substrate including phenolic compounds (i.e. flavonoids and stilbenes), indoles, pyrroles, carbonyl compounds, and steroids. This method was also applied for commonly used drugs such as loxoprofen, haloperidol, stanolone, progesterone, androstenedione, donepezil, ketorolac, adrenosterone, cortisone, pregnenolone, and dexamethasone. A gram-scale chromatography-free synthesis of some deuterated compounds is demonstrated in this work. This work provides a simple, clean and by-product-free, site-selective deuteration, and the deuterated products are obtained without chromatographic separation. When applying these initiators for other acid-catalyzed reactions, the deuterium isotope effects of DX may provide products which are different from those obtained from reactions using common acids. Although the mechanism of the spontaneous transformation of prenyl halides to acid is unclear, this overlooked chemistry may be useful for many reactions.

Organocatalytic Deuteration Induced by the Dynamic Covalent Interaction of Imidazolium Cations with Ketones

In this article, we suggest a new organocatalytic approach based on the dynamic covalent interaction of imidazolium cations with ketones. A reaction of N-alkyl imidazolium salts with acetone-d6 in the presence of oxygenated bases generates a dynamic organocatalytic system with a mixture of protonated carbene/ketone adducts acting as H/D exchange catalysts. The developed methodology of the pH-dependent deuteration showed high selectivity of labeling and good chiral functional group tolerance. Here we report a unique methodology for efficient metal-free deuteration, which enables labeling of various types of α-acidic compounds without trace metal contamination. (Figure presented.).

3,4-Alkadienyl ketones: Via the palladium-catalyzed decarboxylative allenylation of 3-oxocarboxylic acids

In this communication, we report a palladium-catalyzed decarboxylative allenylation of benzyl carbonates and tert-butyl carbonates of 2,3-allenols with 3-oxocarboxylic acids. The reaction provides a new and straightforward approach to 3,4-dienyl ketones under mild conditions.

Organocatalytic Imidazolium Ionic Liquids H/D Exchange Catalysts

Simple 1,2,3-trialkylimidazolium cation associated with basic anions, such as hydrogen carbonate, prolinate, and imidazolate, is an active catalyst for the H/D exchange reaction of various substrates using CDCl3 as D source, without the addition of any extra bases or metal. High deuterium incorporation (up to 49%) in acidic C-H bonds of ketone and alkyne substrates (pKa from 18.7 to 28.8) was found at room temperature. The reaction proceeds through the fast and reversible deuteration of the 2-methyl H of the imidazolium cation followed by D transfer to the substrate. The IL acts as a neutral base catalyst in which the contact ion pair is maintained in the course of the reaction. The basic active site is due to the presence of a remote basic site in the anion namely, OH of bicarbonate, NH of prolinate, and activated water in the imidazolate anion. Detailed kinetic experiments demonstrate that the reaction is first order on the substrate and pseudozero order relative to the ionic liquid, due to the fast reversible reaction involving the deuteration of the ionic liquid by the solvent.

A simple method for α-position deuterated carbonyl compounds with pyrrolidine as catalyst

A simple, cost-effective method for deuteration of carbonyl compounds employing pyrrolidine as catalyst and D2O as deuterium source was described. High degree of deuterium incorporation (up to 99%) and extensive functional group tolerance were achieved. It is the first time that secondary amines are used as catalysts for H/D exchange of carbonyl compounds, which also allow the deuteration of complex pharmaceutically interesting substrates. A possible catalytic mechanism, based on the hydrolysis of 1-pyrrolidino-1- cyclohexene, for this pyrrolidine-catalyzed H/D exchange reaction has been proposed. Pyrrolidine has been shown to be an efficient catalyst for deuteration of carbonyl compounds. The method also allowed the deuteration of complex pharmaceutically interesting substrates. Preliminary experiment showed that the enamine and/or iminium activation modes may be involved. Copyright

Acid-catalyzed hydration of alkynes in aqueous microemulsions

Terminal aromatic alkynes are converted rapidly into ketones in a regioselective manner by treatment of their microemulsions with 0.33 M mineral acid between 80 and 140 °C. Internal and aliphatic acetylenes are likewise hydrated, but require longer reaction periods. The products are easily isolated from the reaction mixtures by phase separation. Replacement of H2O by D2O leads to the formation of trideuteriomethyl ketones. Copyright

Mechanism of the [2 + 2] photocycloaddition of fullerene C60 with styrenes

Stereochemical studies on [2 + 2] photoaddition of cis-/trans-4-propenylanisole (cis-1 and trans-1) and cis-1-(p-methoxyphenyl)ethylene-2-d1 (cis-3-d1) to C60 exhibit stereospecificity in favor of the trans-2 cycloadduct in the former case and nonstereoselectivity in the latter. The observed stereoselectivity in favor of the cis-6-d3 [2 + 2] diastereomer by 12% in the case of the photochemical addition of (E)-1-(p-methoxyphenyl)-2-methyl-prop-1-ene-3,3,3-d3 (trans-5-d3) to C60 is attributed to a steric kinetic isotope effect (k(H)/k(D) = 0.78). The loss of stereochemistry in the cyclobutane ring excludes a concerted addition and is consistent with a stepwise mechanism. Intermolecular secondary kinetic isotope effects of the [2 + 2] photocycloaddition of 3-d0 vs 3-d1, and 3-d6 as well as 5-d0 vs 5-d1, and 5-d6 to C60 were also measured. The intermolecular competition due to deuterium substitution of both vinylic hydrogens at the β-carbon of 3 exhibits a substantial inverse α-secondary isotope effect k(H)/k(D) = 0.83 (per deuterium). Substitution with deuterium at both vinylic methyl groups of 5 yields a small inverse k(H)/k(D) = 0.94. These results are consistent with the formation of an open intermediate in the rate-determining step.

Solvolytic Elimination Reactions of Tertiary α-CSNMe2-Substitutedd Systems

The tertiary benzylic α-CSNMe2-substituted p-nitrobenzoates and trifluoroacetates of general structure Ar(CH3)C(CSNMe2)(OCOR), 7 and 8, solvolyze to give exclusively elimination products H2C=C(CSNMe2)Ar.A Hammett study gave a nonlinear correlation.Variation in rate with solvent ionizing power was small for the unsubstituted trifluoroacetate derivative of 8, and the β-CD3 isotope effect on rate was negligible.There is, however, a large isotope effect (2.5-2.8) in formation of the elimination product when Ph(CH2D)C(CSNMe2)(OCOCF3) solvolyzes.It is concluded that an intermediate must be involved sine the product-determining step and the rate-determining step have differing isotope effects.The likely intermediate is an α-CSNMe2-substituted cation as an ion pair), despite the fact that the reaction has few characteristics of a typical E1 reaction.Tertiary noorbornyl, cyclohexyl, and 2-propyl α-CSNMe2-substituted systems also react to give exclusively elimination products at rates far in excess of α-CONMe2 analogues.It is suggested that α-CSNMe2 cations are also intermediates and that these cations undergo proton loss at an early ion pair stage.These cations are proposed to derive substitantial stabilization by charge delocalization onto sulfur of the thiocarbonyl group. By way of contrast, the secondary system CH3CH(CSNMe2)(OCOCF3), 25, solvolyzes to give mainly a rearranged product CH3CH(CONMe2)(SCOCH3) via a KΔ mechanism involving neighboring thiocarbonyl participation leading to a cyclized ion.