Preparation of enantiopure biimidazoline ligands and their use in asymmetric catalysis

A convenient new method for the preparation of 2,2'-biimidazolines is reported. Amino alcohols were reacted with dimethyl oxalate, and the product hydroxy amides converted into chloroamides by reaction with thionyl chloride. Treatment with PCl5, followed by diamines (ethanediamine, propane-1,3-diamine, 2,2-dimethylpropane-1,3-diamine) furnished a series of enantiopure tricyclic biimidazolines. Complexes of two of the ligands with PdCl2 were prepared and their X-ray crystal structures were determined. The biimidazolines were tested as ligands for asymmetric Pd-catalysed allylations. Moderate enantioselectivity (up to 80% ee) was found for the reaction of dimethyl malonate with diphenylallyl acetate, with the 5,7,5 fused tricyclic systems outperforming the 5,6,5 analogues. The corresponding reaction of pentenyl acetate gave lower enantioselectivity (44-57% ee), and proved very sensitive to the donor strength of the ligands, the stronger donors giving lower yields. The results provide a further demonstration of the value of the 'tunability' of imidazoline ligands.     

Thionylamides and thionylamidines of carboxylic acid

Amidines of carboxylic acids react with thionyl chloride to form thionylamidines which are converted spontaneously into 2H-1, 2, 4-benzothiadiazine 1-oxides. Carbimidic esters react with thionyl chloride to give thionylamides as final products.     

Simple spectrophotometry method for the determination of sulfur dioxide in an alcohol-thionyl chloride reaction

Thionyl chloride is often used to convert alcohols into more reactive alkyl chloride, which can be easily converted to many compounds that are not possible from alcohols directly. One important reaction of alkyl chloride is nucleophilic substitution, which is typically conducted under basic conditions. Sulfur dioxide, the by-product from alcohol-thionyl chloride reactions, often reacts with alkyl chloride to form a sulfonyl acid impurity, resulting in yield loss. Therefore, the alkyl chloride is typically isolated to remove the by-products including sulfur dioxide. However, in our laboratory, the alkyl chloride formed from alcohol and thionyl chloride was found to be a potential mutagenic impurity, and isolation of this compound would require extensive safety measures. As a result, a flow-through process was developed, and the sulfur dioxide was purged using a combination of vacuum degassing and nitrogen gas sweeping. An analytical method that can quickly and accurately quantitate residual levels of sulfur dioxide in the reaction mixture is desired for in-process monitoring. We report here a simple ultraviolet (UV) spectrophotometry method for this measurement.     

Reagents and Synthetic Methods 21. Thionyl Chloride /4-(N,N-Dimethylamino) Pyridine Complex. A Simple One-Pot Method for Esterification of Carboxylic Acids

Esters are obtained by a one-pot method, in which the carboxylic acid is first converted into its acyl chloride by means of thionyl chloride/4-(N,N-dimethylamino)pyridine complex as a new activating reagent.     

Imidazolinium sulfonate and sulfamate zwitterions as chiral solvating agents for enantiomeric excess calculations

The synthesis of enantiopure unsymmetrical N-heterocyclic based zwitterions incorporating imidazolinium and alkylsulfonate or sulfamate groups is described. The desired compounds were prepared in good yields from 1,3-propanesultone or cyclic sulfamidates and imidazolines. The imidazolinium based zwitterions proved to be versatile chiral solvating agents for Mosher’s acid, alcohols, cyanohydrins, amino alcohols, nitro alcohols, thiols, and carboxylic acids with very high shifts in the ¹H and ¹⁹F NMR.     

4-Functionally Substituted 3-heterylpyrazoles: XII. 4-Chlorothieno[2,3-c]pyrazole-5-carbonyl Chlorides

3-(4-Pyrazolyl)acrylic acids reacted with excess thionyl chloride in the presence of benzyltriethylammonium chloride affording 4-chlorothieno[2,3-c]pyrazole-5-carbonyl chlorides which were converted into the corresponding acids, esters, and amides.     

Desulfurizing agent for thioamides

Russian Chemical Bulletin - Thioamides treated with thionyl chloride in an ionic liquid were successfully converted into amides.     

Synthesis of N-phthalimido β-aminoethanesulfonyl chlorides: the use of thionyl chloride for a simple and efficient synthesis of new peptidosulfonamide building blocks

N-Phthalimido β-aminoethanesulfonyl chlorides, new building blocks for the synthesis of peptidosulfonamide peptidomimetics, were prepared in a straightforward manner from amino acids. In the crucial synthetic step, sulfonic acids or their sodium salts were converted into the corresponding sulfonyl chlorides using an excess of refluxing thionyl chloride or thionyl chloride/DMF. This simple and effective chlorinating method is also applicable to β-aminoethane sulfonic acids and their sodium salts with other N-protecting groups.     

Intramolecular formal [4+2] cycloaddition reactions of secondary and tertiary aryldiacetylene alcohols

Thermal and thionyl chloride induced cycloaromatizations of secondary and tertiary aryldiacetylene alcohols were studied. The secondary alcohol did not respond to thionyl chloride, but in all the other cases presumptive biradical intermediates evolved either by intramolecular radical coupling or, when derived from a xanthene scaffold, by intramolecular radical acylation to a diketone that finally afforded a p-methylene-quinone.     

Synthesis of diamides from 1,4-benzodioxane-2- and isochroman-1-carboxylic acids

1,4-Benzodioxane-2-carboxylic acid and isochroman-1-carboxylic acid were treated with thionyl chloride, and the resulting acid chlorides reacted with p-aminobenzoic acid in dioxane in the presence of pyridine to produce the corresponding amido acids. The latter were converted into acid chlorides which were brought into reaction with various amines to obtain a number of new diamides.     

The synthesis of 2-aryl-3-oxa-1-azaspiro [4.4]non-1-enes

A series of 2-aryl-3-oxa-1-azaspiro[4.4]non-1-enes was prepared by cyclization of the corresponding β-acylamino alcohols (V) with thionyl chloride. Structure proofs for the β-acylamino alcohols and the spiro compounds are given. Infrared and p.m.r. data are reported.     

Synthesis of fused cyclopropanes from γ-stannyl alcohols

Fused cyclopropanes including 3-carene and isosequicarene have been prepared by treatment of γ-stannyl alcohols with thionyl chloride.     

Practical and highly stereoselective technology for preparation of enantiopure sulfoxides and sulfinamides utilizing activated and functionally differentiated N-sulfonyl-1,2,3-oxathiazolidine-2-oxide derivatives

A simple, general, and practical technology to prepare enantiopure 1,2,3-oxathiazolidine-2-oxide derivatives using chiral aryl N-sulfonyl aminoalcohol derivatives and thionyl chloride is reported. The versatility of these novel chiral building blocks (MIOO and TMPOO), was exemplified by the expedient production of a variety of unique chiral sulfoxides and valuable chiral sulfinamides in excellent yields and enantiopurities.     

Fluorous solvent as a new phase-screen medium between reagents and reactants in the bromination and chlorination of alcohols

[reaction: see text] A perfluorohexane layer regulates the rate of reagent transport in the bromination and chlorination of alcohols. A fluorous triphasic U-tube method is effective for lighter reagents; the thionyl chloride layer (yellow) vanishes, and the chlorides are obtained from the right top organic layer in the chlorination of alcohols.     

Cu(I) catalysed cyclopropanation with enantiopure scorpionate type ligands derived from (+)-camphor or (-)-menthone

One-pot syntheses of three new enantiopure heteroscorpionate ligands derived from (+)-camphor or (-)-menthone are described. The ligands are obtained by reacting pyrazoles derived from (+)-camphor or (-)-menthone with sodium hydride and thionyl chloride. Subsequent reactions with pyridine and various aldehydes afford the tripod ligands in multi-gram amounts. Especially the menthopyrazole based ligand 6 showed encouraging ee values up to 69% in the Cu(I) catalysed enantioselective cyclopropanation of styrene with ethyl diazoacetate.     

The preparation of 3-chlorobenzo[b] thiophene derivatives from cinnamie acids

The reaction of cinnamic acid derivatives with thionyl chloride and pyridine is a general procedure for the preparation of derivatives of 3-chlorobenzo[b] thiophene-2-carbonyl chloride from readily accessible starting materials. These compounds are easily converted to the corresponding acids, esters and amines.     

2,2'-Disubstituted F12binaphthyl derivatives: stannanes, boranes, and (R)-F12BINOL

2,2'-Distannyl derivatives of dodecafluorobinaphthalene are converted to a novel D2 symmetric borane dimer, which can be oxidized to (+)-F12BINOL; resolution using (S)-acetoxypropanoyl chloride affords enantiopure material.     

Conversion of Epoxides to β‐Chlorohydrins with Thionyl Chloride and β‐Cyclodextrin in Water

Several epoxides are efficiently converted to the corresponding β‐chlorohydrins in impressive yields with thionyl chloride in the presence of β‐cyclodextrin using water as solvent at room temperature.     

The preparation of 3-chlorothieno[3,2-b] thiophene derivatives from thiophene-2-acrylic acids

Thiophene-2-acrylic acids react with thionyl chloride in the presence of pyridine to form derivatives of 3-chlorothieno[3,2-b]thiophene-2-carbonyl chloride. These compounds are easily converted to the corresponding acids and esters.     

Synthesis of enantiopure imidazolines through a Ritter reaction of 2-(1-aminoalkyl)aziridines with nitriles

The Ritter reaction of enantiopure 2-(1-aminoalkyl)aziridines 1 with different nitriles afford enantiopure tetrasubstituted imidazolines 2. The opening of the aziridine ring takes place with total regio- and stereoselectivity. A mechanism to explain the described addition reaction is proposed. [reaction: see text]