Chloroform Adduct Research Articles

Tuning the Regioselectivity of Topochemical Polymerization through Cocrystallization of the Monomer with an Inert Isostere

AbstractRegiochemistry of topochemical reactions depends on the crystal packing and biasing the regiochemistry necessitates precise crystal engineering. The pristine crystals of monomer 1 upon topochemical azide‐alkyne cycloaddition (TAAC) reaction give a 1 : 1 blend of 1,4‐ and 1,5‐triazole‐linked polymers due to the presence of two self‐sorted reactive conformers in the crystal. We designed a binary isomorphous cocrystal of monomer 1 and a structurally similar dummy molecule 2 to limit the number of reactive conformers of 1 to one and thus to get one type of polymer. Equimolar solution of 1 and 2 in chloroform‐acetone mixture gave two 1 : 1 cocrystals Co‐I and Co‐II. The Co‐II, a chloroform adduct, on heating undergoes desolvation and polymorphic transition to Co‐I. Co‐I is isomorphic to 1 and 2 and possess self‐sorted arrays of 1 and 2. Heating Co‐I results in the TAAC polymerization giving 1,4‐triazolyl‐linked polymer of 1 selectively, showing the power of crystal engineering in regiocontrol.

Tuning the Regioselectivity of Topochemical Polymerization through Cocrystallization of the Monomer with an Inert Isostere.

Regiochemistry of topochemical reactions depends on the crystal packing and biasing the regiochemistry necessitates precise crystal engineering. The pristine crystals of monomer 1 upon topochemical azide-alkyne cycloaddition (TAAC) reaction give a 1 : 1 blend of 1,4- and 1,5-triazole-linked polymers due to the presence of two self-sorted reactive conformers in the crystal. We designed a binary isomorphous cocrystal of monomer 1 and a structurally similar dummy molecule 2 to limit the number of reactive conformers of 1 to one and thus to get one type of polymer. Equimolar solution of 1 and 2 in chloroform-acetone mixture gave two 1 : 1 cocrystals Co-I and Co-II. The Co-II, a chloroform adduct, on heating undergoes desolvation and polymorphic transition to Co-I. Co-I is isomorphic to 1 and 2 and possess self-sorted arrays of 1 and 2. Heating Co-I results in the TAAC polymerization giving 1,4-triazolyl-linked polymer of 1 selectively, showing the power of crystal engineering in regiocontrol.

Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with N,N‐Dialkylformamide Acetals

AbstractWe developed a protocol for the palladium‐catalyzed aminocarbonylation of aryl halides using less‐toxic formamide acetals as bench‐stable aminocarbonyl sources under neutral conditions. Various aryl (including heteroaryl) halides reacted with N,N‐dialkylformamide acetals in the presence of a catalytic amount of tris(dibenzylideneacetone)dipalladium(0)‐chloroform adduct and xantphos to give the corresponding aromatic carboxamides at 90–140 °C without any activating agents or bases in up to quantitative chemical yield. This protocol was applied to aryl bromides, aryl iodides, and trifluoromethanesulfonic acid, as well as to relatively less‐reactive aryl chlorides. A wide range of functionalities on the aromatic ring of the substrates were tolerated under the aminocarbonylation conditions. The catalytic aminocarbonylation was used to prepare the insect repellent N,N‐diethyl‐3‐methylbenzamide as well as a synthetic intermediate of the dihydrofolate reductase inhibitor triazinate.

Metalation behavior of a bis-saturated NHC ligand with a flexible m-xylyl linker.

Saturated N-heterocyclic carbenes have unique ligand properties that differ even from their unsaturated analogs. While the unsaturated version has been extensively used in multidentate ligand scaffolds, the incorporation of the saturated version is less common. Here we report the straightforward synthesis of a new bis-saturated N-heterocyclic carbene ligand wherein the carbene moieties are linked by a flexible meta-xylyl unit. Carbene metal complexes of the proligand can be generated by direct metalation, transmetallation or base assisted metalation all of which lead to monodentate coordination modes of silver or iridium. Attempts at direct metalation using zirconium tetrakis-dimethylamide did not lead to complex formation but to the chloroform adduct or amide addition product. As yet, a method to generate pincer complexes from this ligand has not been found. The flexible nature of the xylyl linker as well as the higher σ-bacisity and π-acidity are postulated to contribute to these results.

A NEW METHOD FOR PREPARING 6-NITRO-2-(4-BOC-PIPERAZIN-1-YL)-3H-QUINAZOLIN-4-ONE

The 2-amino-3H-quinazolin-4-one scaffold is found in a large number of molecules with physiological significance and pharmaceutical utility. Previously we synthesized a series of potent antagonists of fibrinogen receptor, derivatives of 2-(piperazin-1-yl)-3H-quinazolin-4-one. The key building block for preparing the above series of compounds is 6-amino-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one, which was synthesized by hydrogenation of 6-nitro-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one. In turn, the nitro derivative was obtained starting from isatoic anhydride in four stages, by a method that can be considered classical, but difficult. The purpose of this work is to simplify the preparation of 6-nitro-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one. We proposed an effective method for the synthesis of 6-nitro-2-(4-Boc-piperazin-1-yl)-3H-quinazolin-4-one based on a sequential process, C-N cross-coupling and intramolecular amidation. As the arylhalogenide, 2-bromo-5-nitrobenzoic acid methyl ester was used, as the N-nucleophile, 4-Boc-piperazine-1-carboxamidine, a guanidine derivative, was used. In the study, we used two types of catalytic systems, which both gave good results. The application of the third generation of Palladacycleprecatalyst –[(4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene)-2-(2′-amino-1,1′-biphenyl)] palladium(II) methanesulfonate, leads to the production of the target product in a high yield, in comparison with the use of the catalytic system: precatalyst – Tris(dibenzylideneacetone) dipalladium(0) chloroform adduct and Buchwald Ligands – 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene. The structure of the title compound was confirmed by spectroscopy 1H and 13C NMR, and FAB mass spectrometry methods, purity was controlled by HPLC. This method has potential implications for the design of various 2-amino-3H-quinazolin-4-ones.

1,3-Bis(2,6-diisopropylphenyl)-2-trichloromethylimidazolidine

A new chloroform adduct of the N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene (SIPr) has been prepared via C–H bond activation of the chloroform at the carbene carbon. This redox product was crystallized and was characterized by 1H and 13C-NMR spectroscopy, elemental analysis (EA), and single-crystal X-ray diffraction. The 1H and 13C-NMR spectroscopic data are in agreement with the crystal structure. Density functional theory (DFT) calculations were performed as a means for comparison to experimental data and the computational results are in agreement with those obtained experimentally.

On the role of noncovalent interactions in electrocatalysis. Two cases of mediated reductive dehalogenation

Two cases of mediated electron transfer are presented: chloroform reduction catalysed by MoII/I alkoxy scorpionates and debromination of hexabromocyclododecane (HBCD) in the presence of free-base tetraphenylporphyrin (H2TPP). Although H2TPP should act as a typical outer-sphere mediator, it is not active towards analogous dehalogenation of 1,2-dibromocyclododecane. The observed phenomena can be rationalised by considering the catalytically relevant transient adducts formed owing to noncovalent interactions (CH hydrogen bonds and dispersive Chalogen⋯π interactions or directional halogen bonding), which warrants the close and prolonged contact between the catalyst and its substrate, thus increases the probability of electron transfer, and decisively accelerates the reaction. Crucial for this action is thermodynamic stability of the adducts, which can only be explained if dispersive van der Waals interactions are properly accounted for, e.g., as by dispersion-corrected density functional theory (DFT-D) calculations. The structures involving strong and anisotropic interactions, like the surprisingly short CH⋯Oalkoxide H-bonding in the MoI–chloroform adduct, may be reasonably well described by standard DFT calculations and the energy needs only be corrected for dispersion without the need for structure re-optimisation at the DFT-D level. The latter is, however, a method of choice for the prediction of supramolecular structures chiefly controlled by weak non-directional van der Waals forces.

The role of solvent in organometallic chemistry — Oxidative addition with dichloromethane or chloroform

Dimethylplatinum(II) complexes [PtMe2(NN)], with NN = diimine ligand, can react with dichloromethane or chloroform solvent to give the corresponding organoplatinum(IV) complexes [PtClMe2(CH2Cl)(NN)] or [PtClMe2(CHCl2)(NN)], respectively. The products can exist in isomeric forms, corresponding to products of cis or trans oxidative addition. The structures of three dichloromethane adducts and one chloroform adduct are reported.

Solid State Structural Evidence of Chloroform−Benzene−Chloroform Adduct Trapped in Hexaanthryl Octaaminocryptand Channels

Structural aspects governing the formation and stabilization of adducts in the organic channels were examined. An unprecedented structural evidence of an inverted sandwich-type benzene/chloroform (1:2) adduct was isolated within the channel formed by close packing of an aromatic substituted aminocryptand 1 host. Interestingly, this adduct was stabilized through several short contacts with the channel wall. Crystallographic study further showed that a channel formed by self-assembly of 1 can also encapsulate chloroform as a guest. Thermal analysis confirms that the chloroform-benzene-chloroform adduct as a guest has better thermal stability than that of the chloroform guest within the channel.

LIVER MITOCHONDRIA ALTERATIONS IN CHLOROFORM-TREATED SPRAGUE-DAWLEY RATS

The formation of a chloroform adduct produced by the reaction of the oxidative chloroform metabolite phosgene with two molecules of phosphatidylethanolamine has been previously demonstrated in liver mitochondria of phenobarbital-pretreated Sprague-Dawley (SD) rats. The aim of our study was to assess the influence of chloroform adduct mitochondrial accumulation on the hepatic mitochondria morphology. Liver mitochondrial ultrastructural alterations were analyzed by electron microscopy in SD rats administered with increasing doses of chloroform. Variation in the morphology of mitochondria, consisting of an increase of intertwined organelles, only rarely seen in control specimens, was observed at the lowest chloroform dose (180 mg/kg). At higher doses, mitochondrial damage progressed with swelling of the organelles and formation of megamitochondria. These megamitochondria were characterized by a dilution of the matrix, and often membranous whorls were found inside the matrix. The two distinct forms of cell death, necrosis and apoptosis, were first observed at 300 mg/kg of chloroform. Our results suggest that the formation and the accumulation of a chloroform-modified phosphatidylethanolamine in mitochondria induce ultrastructural modifications of these organelles. In conclusion, mitochondria are involved in chloroform-induced hepatotoxicity.

Characterization of a phospholipid adduct formed in Sprague Dawley rats by chloroform metabolism: NMR studies.

The formation of a covalent adduct to a single phospholipid by the oxidative chloroform metabolite, phosgene, is demonstrated in liver mitochondria of phenobarbital-pretreated Sprague Dawley (SD) rats treated with CHCl3. The densitometric analysis of the phosphorus stained extracted phospholipids showed that the formation of this adduct in liver mitochondria is accompanied by a decrease of phosphatidylethanolamine and cardiolipin. The characterization of this adduct was performed with a multinuclear NMR approach by comparison with the decreased phospholipids. Treatment of rats with [13C]chloroform resulted in an intense 13C NMR peak from either an esteric or amidic carbonyl. Very strong similarities in fatty acid composition were found between phosphatidylethanolamine and the phosgene-modified PL, using 13C and 1H NMR spectroscopy. A multiplet at 3.91 ppm coupled to a signal at 3.41 ppm was shown by two-dimensional 1H NMR in the adduct spectrum. This cross peak was interpreted as arising from the shifted resonances of the two PE head group methylene groups, due to the binding with phosgene. 31P spectrum of the adduct was identical to that of phosphatidylethanolamine. We concluded that the chloroform adduct is a modified phosphatidylethanolamine, with the phosgene-derived carbonyl bound to the amine of the head group.

Studies on the Chemical Constituents of Rutaceous Plants. Part 70. Re-examination of the Synthesis of 7,8-Dimethoxy-2-methyl-3-(4',5'-methylenedioxy-2'-vinylphenyl)isocarbostyril.

Oxidation of the enamine (6) to the isocarbostyril (7) was re-examined. Simply stirring a dimethylformamide (DMF) solution of 6 provided 7 with good reproducibility, in the presence of KCN under an oxygen atmosphere. The structure of the chloroform adduct (8) was determined by an X-ray analysis.

Conformational differences in dioxouranium(VI) coordination compounds: Crystal structure of the chloroform adduct of N,N′-bis-salicylidene-1,5-diamino-3-oxapentane-dioxouranium(VI)

The title compound (UO 2-saloden·CHCl 3) crystallizes in an orthorhombic system, space group Cmc2 1 with a = 16.938(6), b = 12.440(5) and c = 10.662(4) A ̊ , Z = 4 . The coordination geometry of the uranium atom is bipyramidal pentagonal with the ligand pentadentate in the equatorial plane of the uranyl ion. The chloroform molecule does not interact directly with the ligand. The IR spectral data are also discussed.

Structure of the chloroform adduct of pentakis(phenyl isocyanide)cobalt(I) perchlorate, [Co(CNC6H5)5]ClO4.HCCl3

Structure of the chloroform adduct of pentakis(phenyl isocyanide)cobalt(I) perchlorate, [Co(CNC6H5)5]ClO4.HCCl3

Adducts of co-ordination compounds. Part XI. Isomerism and solvation of dichlorobis(triphenylphosphine)platinum(II)

The complex cis-[Pt(PPh3)2Cl2] forms distinct adducts with chloroform and NN-dimethylformamide. The existence of these adducts, for which X-ray powder results are given, accounts for several discrepancies in the literature. In particular, the product (recrystallised from chloroform–hexane) of reaction of carbon tetrachloride with tetrakis(triphenylphosphine)platinum(0), previously incorrectly formulated as [Pt(PPh3)2(CCl3)Cl], is in fact a partly desolvated sample of the chloroform adduct of the cis-dichloro-complex. In solution, cis–trans-isomerisation is easily set up providing access to the trans-isomer. Two further methods, which give much better yields of the trans-isomer, are described.

The Crystal and Molecular Structure of (PPh3)2PtO2•2CHCl3

The X-ray crystal structure analysis of the chloroform adduct of the bis(triphenylphosphine) platinum di-oxygen complex (PPh3)2PtO2•2CHCl3 is reported. The crystals belong to the monoclinic System a = 15.492(7), b = 13.520(5), c = 19.187(6) Å; β = 98.97(6)°. Space group C2/c. Z = 4 molecules per cell.A total of 2740 independent X-ray reflections were measured and refinement gave a final conventional R of 6.6%.The molecule has a two-fold axis of symmetry through the Pt atom with O—O normal to the axis. The O—O distance of 1.505(16) Å is in accord with that found with other transition elements when oxygen is taken up irreversibly to form di-oxygen complexes.

Conformational influences in copper co-ordination compounds. Part IV. Crystal structure of the chloroform adduct of NN′-ethylenebis(salicylideneiminato)copper(II)

Conformational influences in copper co-ordination compounds. Part IV. Crystal structure of the chloroform adduct of NN′-ethylenebis(salicylideneiminato)copper(<scp>II</scp>)

防已科植物アルカロイド研究 (第208報)

Dauricine (I), the alkaloid of Menispermum dauricum DC. (Japanese name “Kohmori-kazura”), has not been isolated in crystalline form and had been obtained as methiodide or perchlorate crystals. In the present series of experiment, dauricine was obtained as a chloroform adduct, forming colorless prismatic crystals of m.p. 100-103°, [α]D16-129.5° (MeOH), C38H44O6N2⋅CHCl3, in a pure state.

A Stable Chloroform Adduct of 11-Epi-17α-hydroxycorticosterone

A Stable Chloroform Adduct of 11-Epi-17α-hydroxycorticosterone