- (2-Ethylhexyl)sodium: A Hexane-Soluble Reagent for Br/Na-Exchanges and Directed Metalations in Continuous Flow
-
We report the on-demand generation of hexane-soluble (2-ethylhexyl)sodium (1) from 3-(chloromethyl)heptane (2) using a sodium-packed-bed reactor under continuous flow conditions. Thus, the resulting solution of 1 is free of elemental sodium and therefore suited for a range of synthetic applications. This new procedure avoids the storage of an alkylsodium and limits the handling of metallic sodium to a minimum. (2-Ethylhexyl)sodium (1) proved to be a very useful reagent and undergoes in-line Br/Na-exchanges as well as directed sodiations. The resulting arylsodium intermediates are subsequently trapped in batch with various electrophiles such as ketones, aldehydes, Weinreb-amides, imines, allyl bromides, disulfides and alkyl iodides. A reaction scale-up of the Br/Na-exchange using an in-line electrophile quench was also reported.
- Annapureddy, Rajasekar Reddy,Harenberg, Johannes H.,Hoefer, Carla A.,Knochel, Paul,Weidmann, Niels,Wiegand, Alexander J.
-
supporting information
p. 14296 - 14301
(2021/05/07)
-
- 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.
- Huy, Peter H.,Filbrich, Isabel
-
supporting information
p. 7410 - 7416
(2018/04/30)
-
- 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.
- Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
-
supporting information
p. 2980 - 2983
(2018/05/28)
-
- Ni-Catalyzed Carboxylation of Unactivated Alkyl Chlorides with CO2
-
A catalytic carboxylation of unactivated primary, secondary, and tertiary alkyl chlorides with CO2 at atmospheric pressure is described. This protocol represents the first intermolecular cross-electrophile coupling of unactivated alkyl chlorides, thus leading to new knowledge in the cross-coupling arena.
- B?rjesson, Marino,Moragas, Toni,Martin, Ruben
-
supporting information
p. 7504 - 7507
(2016/07/06)
-
- 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.
- -
-
Page/Page column 53; 132; 139; 140
(2017/01/02)
-
- 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.
- Huy, Peter H.,Motsch, Sebastian,Kappler, Sarah M.
-
supporting information
p. 10145 - 10149
(2016/08/16)
-
- Process for preparing alkyl chlorides
-
The invention relates to a process for preparing alkyl chlorides by reacting alcohols with gaseous hydrogen chloride in the presence of a catalyst, wherein the catalyst comprises at least one compound of the structure: wherein R1 is a linear alkyl group having from 1 to 20 carbon atoms, R2, R3, and R4 is selected from a hydrogen, an alkyl, an alkenyl, an aralkyl or an alkylaryl group from 1 to 20 carbon atoms, wherein the substituents of R2, R3, and R4 are all identical, are all different or two of the substituents of R2, R3, and R4 type are identical.
- -
-
Page/Page column 5
(2008/06/13)
-
- Process to prepare alkyl phenyl phosphates
-
The present invention relates to a process to prepare dialkyl monophenyl phosphate, monoalkyl diphenyl phosphate or mixtures thereof wherein dichloromonophenyl phosphate and/or monochlorodiphenyl phosphate is reacted with an aliphatic alcohol in the presence of a Lewis acid catalyst and in the absence of solvent at a temperature of 40 to 200°C and a pressure of 0 to 1 bar. The present invention further relates to mixtures of monoalkyl diphenyl phosphates and dialkyl monophenyl phosphates obtainable from the above process and the use of such mixtures as a plasticiser and/or a flame retardant.
- -
-
Page/Page column 5-6
(2008/06/13)
-
- Method for converting organic chloroformate to the corresponding organic chloride
-
Organic haloformate, e.g., chloroformate, compounds are converted to their corresponding halides, e.g., chlorides, by heating the haloformate, e.g., between 90° C. and 150° C., in the presence of a catalytic amount of a carbon catalyst for a time sufficient to convert the haloformate to the corresponding halide.
- -
-
-