83972-40-1

Upstream product

• 2344-70-9 (R)-4-phenyl-2-butanol 
• 98-07-7 Benzotrichlorid 
• 2344-70-9 (+)-(S)-4-phenylbutan-2-ol 
• 98-88-4 benzoyl chloride 
• 3760-54-1 1-pyrrolidinecarboxaldehyde 
• 100-07-2 4-methoxy-benzoyl chloride 

Relevant academic research and scientific papers

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

Nucleophilic substitutions (SN) are typically promoted by acid chlorides as sacrificial reagents to improve the thermodynamic driving force and lower kinetic barriers. However, the cheapest acid chloride phosgene (COCl2) is a highly toxic gas. Against this background, phenyl chloroformate (PCF) was discovered as inherently safer phosgene substitute for the SN-type formation of C?Cl and C?Br bonds using alcohols. Thereby, application of the Lewis bases 1-formylpyrroldine (FPyr) and diethylcyclopropenone (DEC) as catalysts turned out to be pivotal to shift the chemoselectivity in favor of halo alkane generation. Primary, secondary and tertiary, benzylic, allylic and aliphatic alcohols are appropriate starting materials. A variety of functional groups are tolerated, which includes even acid labile moieties such as tert-butyl esters and acetals. Since the by-product phenol can be isolated, a recycling to PCF with inexpensive phosgene would be feasible on a technical scale. Eventually, a thorough competitive study demonstrated that PCF is indeed superior to phosgene and other substitutes.

Organocatalytic Chlorination of Alcohols by P(III)/P(V) Redox Cycling

A catalytic system for the chlorination of alcohols under Appel conditions was developed. Benzotrichloride is used as a cheap and readily available chlorinating agent in combination with trioctylphosphane as the catalyst and phenylsilane as the terminal reductant. The reaction has several advantages over other variants of the Appel reaction, e.g., no additional solvent is required and the phosphane reagent is used only in catalytic amounts. In total, 27 different primary, secondary, and tertiary alkyl chlorides were synthesized in yields up to 95%. Under optimized conditions, it was also possible to convert epoxides and an oxetane to the dichlorinated products.

Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency

A practical method for the nucleophilic substitution (SN) of alcohols furnishing alkyl chlorides, bromides, and iodides under stereochemical inversion in high catalytic efficacy is introduced. The fusion of diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride as a reagent allows notable turnover numbers up to 100. Moreover, the use of plain acetyl chloride as a stoichiometric promotor in an invertive SN-type transformation is demonstrated for the first time. The operationally straightforward protocol exhibits high levels of stereoselectivity and scalability and tolerates a variety of functional groups.

A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions

A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.

Halogenation through Deoxygenation of Alcohols and Aldehydes

An efficient reagent system, Ph3P/XCH2CH2X (X = Cl, Br, or I), was very effective for the deoxygenative halogenation (including fluorination) of alcohols (including tertiary alcohols) and aldehydes. The easily available 1,2-dihaloethanes were used as key reagents and halogen sources. The use of (EtO)3P instead of Ph3P could also realize deoxy-halogenation, allowing for a convenient purification process, as the byproduct (EtO)3Pa?O could be removed by aqueous washing. The mild reaction conditions, wide substrate scope, and wide availability of 1,2-dihaloethanes make this protocol attractive for the synthesis of halogenated compounds.

Dehydroxylation of alcohols for nucleophilic substitution

The Ph3P/ICH2CH2I system-promoted dehydroxylative substitution of alcohols was achieved to construct C-O, C-N, C-S and C-X (X = Cl, Br, and I) bonds. Compared with the previous approaches such as the Appel reaction and Mitsunobu reaction, this protocol offers some practical advantages such as safe operation and a convenient amination process.

Stereospecific Electrophilic Fluorination of Alkylcarbastannatrane Reagents

We report the use of isolable primary and secondary alkylcarbastannatrane nucleophiles in site-specific fluorination reactions. These reactions occur without the need for transition metal catalysis or in situ activation of the nucleophile. In the absence of the carbastannatrane backbone, alkyltin nucleophiles exhibit no activity towards fluorination. When enantioenriched alkylcarbastannatranes are employed, fluorination occurs predominately via a stereoinvertive mechanism to generate highly enantioenriched alkyl fluoride compounds. These conditions can also be extended to stereospecific chlorination, bromination, and iodination reactions.

METHOD OF CONVERTING ALCOHOL TO HALIDE

The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.

Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers

A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.

CaF2 catalyzed SN2 type chlorodehydroxylation of chiral secondary alcohols with thionyl chloride: A practical and convenient approach for the preparation of optically active chloroalkanes

A CaF2 catalyzed chlorodehydroxylation of chiral secondary alcohols with thionyl chloride has been developed. The chlorination reaction is effective for a wide range of alcohols, generating the corresponding chloroalkanes in good yield with high optical purity with inversion of the original configuration of the alcohol.