Chlorination reactions of ephedrines revisited. Stereochemistry and functional groups effect on the reaction mechanisms

The stereochemistry of the chlorination reactions with SOCl₂ of free ephedrine and pseudoephedrine and their hydrochlorides, oxamides and sulfonamides was analyzed. Chlorination of free and hydrochloride erythro isomers occurs with 100% inversion of configuration at C-1 (S_N2 mechanism). Chlorination of oxamides and sulfonamides of erythro isomers occurs with retention of the configuration at C-1, (S_Ni mechanism). Chlorination reactions in all threo isomers and derivatives hydrochlorides, oxamides or sulfonamides gave the same ratio of erythro (40%) and threo isomers (60%) (S_N1 mechanism). Treatment of the isomeric mixture of the chlorodeoxyephedrine and chlorodeoxypseudoephedrine hydrochloride in DMSO with HCl changes the isomeric ratio, increasing the erythro isomer content (65%). Using the erythro ethanolamines it is possible to arrive stereoselectively at the erythro chloroamines if the compound is previously tosylated or converted to the amide, or to the threo chloroamines if the compound is directly chlorinated with SOCl₂.     

1-Bromo-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones as α-bromoglycine templates

The title compounds behaved as α-bromoglycine templates. Radical substitutions and S_N1-type nucleophilic additions proceeded with retention of stereochemistry, while S_N2-type displacements occurred with net inversion of configuration. A homocoupling product was obtained in attempting a Stille cross-coupling reaction.     

Inversion of Configuration at the Phosphorus Nucleophile in the Diastereoselective and Enantioselective Synthesis of P‐Stereogenic syn‐Phosphiranes from Chiral Epoxides

Nucleophilic substitution results in inversion of configuration at the electrophilic carbon center (S_N2) or racemization (S_N1). The stereochemistry of the nucleophile is rarely considered, but phosphines, which have a high barrier to pyramidal inversion, attack electrophiles with retention of configuration at P. Surprisingly, cyclization of bifunctional secondary phosphine alkyl tosylates proceeded under mild conditions with inversion of configuration at the nucleophile to yield P‐stereogenic syn‐phosphiranes. DFT studies suggested that the novel stereochemistry results from acid‐promoted tosylate dissociation to yield an intermediate phosphenium‐bridged cation, which undergoes syn‐selective cyclization.     

Gas chromatographic and mass spectrometric analysis of chlorinated catechols occurring in pulp bleach liquors

Summary Chlorination step (C-step), spent bleach liquor from a kraft pulp mill and the product from the chlorination of guaiacol in aqueous solution have been investigated for their content of chlorinated catechols. After separation the samples were derivatized with diazoethane and analysed by glass capillary gas chromatography with an electron capture detector. The external standard mixture of all ethylated chlorocatechols was used in the measurements. The structures of the compounds identified were confirmed by gas chromatography/mass spectrometry. Eight chlorinated catechols were identified from a sample prepared by chlorination of guaiacol with Cl₂ in aqueous solution. However, only four of these compounds could be detected from a bleach liquor sample.     

Mechanism of Chlorination by Means of Deuterated Model Compounds

β,β-Dideuterated poly(viny1 chloride) (β,β -d2-PVC) was chlorinated under conditions of photochemical suspension chlorination in concentrated hydrochloric acid with addition of chloroform as a swelling agent, and also under conditions of thermal solution chlorination in tetrachloroethane. The ¹H-NMR spectra of chlorinated β,β -d₂PVC (β,β -d₂CPVC) were measured. The deuterium concentration was determined in combustion products of β,β -d₂CPVC as the D₂O:H₂ O ratio by means of mass spectroscopy. It was found that the concentration of CHC1- groups decreases in both the photochemical suspension chlorination and in the thermal solution chlorination. The structural nonidentity of β,β -d₂PVC chlorinated in suspension and in solution was confirmed.     

Functional polymers and sequential copolymers by phase transfer catalysis. XXII. Vinylidene fluoride–trifluoroethylene copolymers by surface modification of polyvinylidene fluoride

Polyvinylidene fluoride films and powders have been used to synthesize vinylidene fluoride-trifluoroethylene copolymers. The synthetic procedure involves a phase transfer catalyzed heterogenous dehydrofluorination, followed by electrophilic chlorination or bromination. A phase transfer catalyzed displacement of bromine or chlorine by fluoride ion completes the synthesis. Dehydrofluorinations were up to 40% complete at room temperature and up to 100% complete at 90°C. Electrophilic chlorination of the resulting carbon–carbon double bonds were complete on both powder or films. The bromination of dehydrohalogenated polymers does not go to completion even when the reaction is carried out in solution. Displacement reactions were incomplete and resulted in further dehydrohalogenation when tetrabutylammonium hydrogen sulfate (TBAH) or 18-crown-6 and KF were used in organic solvents. Using TBAH, KHF₂, and water, high degrees of displacement were achieved only on the brominated compounds. The chlorinated products gave both displacement and elimination.     

Differences in retention of dioxin-like compounds and organochlorinated insecticides on an immunochromatographic column. Interpretation and applicability

The retention of organochlorinated compounds on an immunochromatographic column is studied. The compounds considered are usually found together in real samples of environmental concern, and include chlorinated biphenyls, chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and organochlorinated insecticides. The different retention observed for different compounds is interpreted in light of the structural similarities of the compound studied with that used as a hapten to raise the antibodies employed as ligands in the immunochromatographic column. Differences in retention of the organochlorinated compounds on the immunocolumn make it possible to fractionate them. Mixtures of phosphate buffer solution and ACN in different ratios were used as desorption agents. Depending on the percentage of ACN employed, different fractionations of the organochlorinated compounds are obtained. The use of 20% ACN allows fractionation of most insecticides from chlorinated biphenyls, dioxins, and furans. Besides, chlorinated biphenyls of different chlorination degree can be separated. Moreover, pentachlorinated dioxins and pentachlorinated furans are separated from hexachlorinated biphenyls. Fractionation is of critical importance from a practical point of view, as it avoids some of the interferences that otherwise take place during the subsequent gas chromatography/mass spectrometry (GC/MS) analysis of these compounds. In this way, immunochromatography makes it possible to perform in a single step all the processes (extraction, clean-up, concentration, and fractionation) that are needed prior to the GC/MS analysis of these analytes in aqueous samples. An additional advantage of this method is the reusability of the immunoaffinity chromatography column for more than 500 times.     

Structure of chlorinated poly(vinyl chloride). I. Determination of the mechanism of chlorination from infrared and NMR spectra

Infrared and NMR spectra of chlorinated poly(vinyl chloride) (CPVC) and of chlorinated α-deuterated poly(vinyl chloride) (α-d-CPVC) have been measured. It was found that the CDCl unit of α-d-PVC does not undergo chlorination. By assuming an analogous mechanism of chlorination in normal PVC, the populations of all the three possible types of two-carbon sequences (? CH₂? CHCl? , ? CHCl? CHCl, ? CHCl? CCl₂) in CPVC could be determined. The mechanism of chlorination of PVC is discussed from the viewpoint of the previous findings on the conformational structure of this polymer. Differences in structure between suspension- and solution-chlorinated PVC have been established.     

The structure of chlorinated poly(vinyl chloride). VI. Comparison of the chlorination of poly(vinyl chloride) and β,β-d2-poly(vinyl chloride) with 1H-NMR and 13C-NMR spectroscopy

Samples of chlorinated poly(vinyl chloride) (CPVC) and chlorinated β,β-dideuterated poly(vinyl chloride) (β,β-d₂-CPVC) were prepared under identical reaction conditions. The microstructure of CPVC and β,β-d₂-(CPVC) was characterized by a combination of ¹H-NMR, ¹³C-NMR spectroscopy, and analytically determined chlorine content. A difference was observed in the reaction rates of chlorination of PVC and β,β-d₂-PVC, and, in their thermal chlorination in solution, also in the structure of the chlorinated products. It was proved that in the chlorination of β,β-d₂-PVC a new chlorine atom can also enter the original? CHCl? group. The results are discussed from the standpoint of the chlorination mechanism.     

Impact of synthesis conditions on surface chemistry and structure of carbide-derived carbons

Carbide-derived carbons produced by chlorination of titanium carbide at 600, 800, or 1100 °C were subjected to a post-treatment at 600 °C in Ar, H₂, or NH₃ atmosphere. Experimental results suggest that the chlorination temperature influences the ordering of carbon in a manner that impacts specific surface area and porosity. Higher chlorination temperatures lead to higher total pore volume and increased ordering, but lower microporosity. The effect of post-treatments on surface chemistry is pronounced only for samples chlorinated at 600 °C; post-treatments in Ar are shown to be less effective for chlorine removal than those performed in H₂ or NH₃. Post-treatments in Ar result in a lower total pore volume compared to the ones in H₂ or NH₃ for the same chlorination temperature. Samples chlorinated at higher temperatures contained less oxygen functionalities than samples chlorinated at 600 °C, and showed correspondingly less desorption of H₂O, possibly due to diminished uptake of ambient water.     

Stereochemistry of Substitution of the α-Dimethylamino Group by Dialkylzinc in Chiral Benzylferrocene

The stereochemistry of the substitution of the α-dimethylamino group by dimethylzinc in the presence of acetyl chloride in the chiral benzylferrocene backbone was examined. The reaction with the benzylferrocene bearing an o-bromo substituent at both ferrocene and the phenyl ring proceeded with inversion of configuration, while the reaction with the benzylferrocene bearing an o-bromo substituent at either ferrocene or the phenyl ring proceeded with retention of configuration.     

Gas chromatographic identification of chlorination products of aliphatic ketones

Chlorinated derivatives of aliphatic ketones are a class of organic compounds poorly characterized by both mass spectra and chromatographic retention indices up to present. It is caused by objective difficulties of isolation of individual products from reaction mixtures formed in the result of non-selective chlorination of parent carbonyl compounds. Nevertheless the differences of GC retention indices for structurally analogous chlorination products of different ketones and initial substrates indicate the constancy depending on the number and position of chlorine atoms in the molecules. This feature permits us to use the simplest kind of additive schemes in identification of such chlorinated derivatives, including diastereomeric α,α'-dichloro-k-alkanones (k>2). Hence, the identification of chlorination products of aliphatic ketones becomes possible for any compounds of this class without using mass spectrometric data only in the result of accurate measurement of their GC retention indices.     

Synthesis and bulk characterization of new P(CB‐b‐S) diblock copolymers

Strongly asymmetric chlorinated polybutadiene‐b‐polystyrene, [P((CB)_x‐b‐(PS)_y)] diblock copolymers with increasing x/(x + y) ratios (up to 5.2 mol %) have been synthesized by the selective chlorination of the polybutadiene (PB) block in solution. Chlorination has been performed in anhydrous dichloromethane added with an antioxidant [2,2′‐methylenebis‐(6‐tert‐butyl‐4‐methyl‐phenol)], at −50°C, under a continuous Ar flow and in the dark. Under the optimized experimental conditions, the PB chlorination is not complete, but the PS block is left unmodified. Even in the presence of a large chlorine excess (Cl₂/butene unit molar ratio of 2.5), the experimental degree of chlorination of homo PB does not exceed 85%. The chlorinated copolymers have been characterized by ¹H‐NMR, IR spectroscopy, size‐exclusion chromatography, and elemental analysis. The chlorinated copolymers have also been studied by DSC and SAXS after annealing at 150°C. Although at this temperature the parent homopolymers are immiscible, no microphase separation has been observed for the block copolymers. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 233–244, 1999     

Chromatographic Identification of Cyclohexane Chlorination Products by an Additive Scheme for the Prediction of Retention Indices

Identification of the products of free-radical chlorination of cyclohexane seems to be a complex analytical problem due to the following principal reasons: (1) the available reference information (both standard mass spectra and gas chromatographic retention indices, RI) is strongly restricted to the data for only few simplest congeners, (2) mass spectra of isomeric chlorinated derivatives are practically indistinguishable, and (3) the number of isomers increases with the growing number of chlorine atoms in the molecule until six. To solve this problem, the modified additive scheme for precalculation of the RIs of chlorinated cyclohexanes on standard non-polar polydimethyl siloxane stationary phases was proposed and used. This approach is based on the data for congeners with fewer number of chlorine atoms in the molecule; the principal feature is its applicability to a diastereomers. The final set of both experimental and precalculated RI values permits us to identify unambiguously more than 20 products of cyclohexane chlorination in reaction mixtures. Different modes of the quality control of evaluated retention indices are discussed.     

B(C6F5)3‐Catalyzed Selective Chlorination of Hydrosilanes

The chlorination of Si−H bonds often requires stoichiometric amounts of metal salts in conjunction with hazardous reagents, such as tin chlorides, Cl₂, and CCl₄. The catalytic chlorination of silanes often involves the use of expensive transition‐metal catalysts. By a new simple, selective, and highly efficient catalytic metal‐free method for the chlorination of Si−H bonds, mono‐, di‐, and trihydrosilanes were selectively chlorinated in the presence of a catalytic amount of B(C₆F₅)₃ or Et₂O⋅B(C₆F₅)₃ and HCl with the release of H₂ as a by‐product. The hydrides in di‐ and trihydrosilanes could be selectively chlorinated by HCl in a stepwise manner when Et₂O⋅B(C₆F₅)₃ was used as the catalyst. A mechanism is proposed for these catalytic chlorination reactions on the basis of competition experiments and density functional theory (DFT) calculations.     

Nickel(0) triethyl phosphite complex-catalyzed allylic substitution with retention of regio- and stereochemistry

Nickel(0) triethyl phosphite complex-promoted reaction of allylic acetates with thiols produced allylic sulfides with retention of configuration without allylic rearrangement. A similar reaction of allylic acetates with alcohols and phenols also proceeded with retention of regio- and stereochemistry.     

CHLORINATION OF ISOLATED CHLOROPHYLLS in vitro

Abstract— It was shown that chlorophyll a and its epimer chlorophyll a' are chlorinated and hydroxyl-ated during thin layer chromatography with silica gel plates. Hydroxylated chlorophyll a could not be chlorinated. Chlorinated and non chlorinated chlorophylls could be separated and determined by high performance liquid chromatography, because chlorophylls do not alter during this procedure. These findings support the assumption that Chi RC I is a preparation artifact. The extent of chlorination depends on chloride availability on the thin layer and on time. Chlorination and hydroyxlation do not take place under nitrogen atmosphere. The mechanism of chlorination during the thin layer chromatography procedure is discussed.     

Pd-catalyzed regioselective C-H chlorination of disubstituted 1,2,3-triazoles

This paper mainly studied Pd-catalyzed regioselective chlorination of disubstituted 1,2,3-triazoles directed by the 1,2,3-triazole ring. A series of regioselective chlorinated products were synthesized in 47–86% yields using Pd(OAc)₂ as a catalyst and CuCl₂ as a chlorinated reagent. This method provides a new mean for the synthesis of 1,2,3-triazole halides which combines the formation of C-X bond with C-H activation.     

Structure of chlorinated poly(vinyl chloride). X. Conclusions on the chlorination mechanism

The chlorination of poly(vinyl chloride) (PVC) was investigated by using deuterated polymeric models of PVC, viz., α-deuterated PVC (α-d-PVC) and β,β-dideuterated PVC (β,β-d₂-PVC). The chlorinated samples of PVC, α-d-PVC, and β,β-d₂-PVC were examined by combining infrared (IR), ¹H-NMR, ¹³C-NMR, and mass spectroscopy. The results obtained were used in a study of the reaction mechanism of PVC chlorination. The selectivity of chlorination and the extent of the substitution and elimination-addition mechanism of chlorination are discussed with respect to the degree of chlorination and chlorination conditions.     

Highly enantioselective chlorination of β-keto esters and subsequent S(N)2 displacement of tertiary chlorides: a flexible method for the construction of quaternary stereogenic centers

Highly enantioselective chlorination of β-oxo esters and subsequent stereospecific substitution of tertiary chlorides are described. Enantioselective chlorination of β-keto esters and malonates was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline ligand 2 to yield the desired α-chlorinated products with high enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting chlorides proceeded smoothly to afford a variety of chiral molecules such as α-amino, α-alkylthio, and α-fluoro esters, without loss of enantiopurity. The results of X-ray crystallographic analysis proved that Walden inversion occurs at the chlorinated tertiary carbon center. These results supported the fact that the substitution proceeds via an S(N)2 mechanism.