Nucleophilic Displacement Of Chlorine Research Articles

Preparation of PolyHIPE monolithic materials functionalization by tris(2-aminoethyl)amine

The developments of monolithic materials rapidly in nowadays hold an impressively strong position in separation science as well as in other areas of chemistry. In this research are presented functionalization of PolyHIPE monolithic materials by tris(2-aminoethyl) amine. Monolithic polymer supports and scavengers were synthesized via nucleophilic displacement of chlorine in poly(4-vinyl benzyl chloride-co-divinylbenzene) as PolyHIPE materials. Porous copolymers of DVB/DVB were prepared by emulsion templating using high internal phase emulsions (HIPEs) as precursors for monoliths. The properties of the final products synthesized were functionalized with an amino group, at a different ratio of amine/chloromethyl groups, in different time refluxed were explored. PolyHIPE functionalized with tris(2-aminoethyl)amine to yield a product with high degrees of conversion. The extent of the functionalization reactions was investigated by a range of qualitative and quantitative techniques: FTIR, CHN analysis, potentiometric measurements, and (BET) measurements have been performed.

Alicyclic β- and γ-Amino Acids: Useful Scaffolds for the Stereocontrolled Access to Amino Acid-Based Carbocyclic Nucleoside Analogs.

Stereocontrolled synthesis of some amino acid-based carbocyclic nucleoside analogs containing ring C=C bond has been performed on β- and γ-lactam basis. Key steps were N-arylation of readily available β- or γ-lactam-derived amino ester isomers and amino alcohols with 5-amino-4,6-dichloropyrimidine; ring closure of the formed adduct with HC(OMe)3 and nucleophilic displacement of chlorine with various N-nucleophiles in the resulting 6-chloropurine moiety.

Synthesis and In Vitro Anti-inflammatory Activity of Some 1-[(2(Methylsulphonyl amino) thiazole-4-yl) methyl]-3-aryl thioureas.

New thioureas (4a-f) bearing 2-methylsulhonyl amino thiazol-4-methyl moiety have been synthesized by multistep synthesis depicted in Scheme.1. Intermediate 2-Amino-4-(isothiocynatomethyl) thiazole (2) has been synthesized from 2-amino-4-chloromethyl thiazole hydrochloride (1) by nucleophilic displacement of chlorine by isothiocynate. The compound (2) on subsequent condensation with methyl sulphonyl chloride carried in the presence of triethyl amine in DCM yielded 2-methylsulphonyl amino-4-(isothiocynatomethyl) thiazole (3) which on addition with aryl amines in refluxed pyridine gave the titled thioueras. Synthesized intermediates and final compounds were characterized by I.R, 1H NMR, MASS spectroscopic techniques and C, H, N and S analysis. Synthesized final compounds were evaluated for in vitro anti-inflammatory activity by HRBC membrane stabilization method. Most of the synthesized compound exhibited good anti-inflammatory activity as compared to standard Diclofenac sodium.

Nucleophilic Displacement Reactions on Sterically Hindered Chloro-Pyridines: Some Optimisation Studies

A Factorial Design has been used to optimise the reaction conditions for the nucleophilic displacement of chlorine in 2-chloro-4,6-diisopropyl-5-nitropyridine (1B) by 4-chlorophenol. The results obtained have been successfully applied to a large variety of phenols and thiophenol.

ChemInform Abstract: Nucleophilic Substitution Reactions of Polyfluoroalkylsulfonamides.

Abstract The sulfonamides CF 3 SO 2 N(CH 3 )Na and CF 3 SO 2 N(H)Na have been reacted with polyfluoro cyclic, acyclic and inorganic chlorine and bromine-containing species. Nucleophilic displacement of chlorine or bromine in 1,2-dichloroperfluorocyclobutene, 1,2-dichloroperfluorocyclopentene, benzyl bromide, cyanuric chloride and oxalyl chloride has been found to occur under mild conditions to give good yields of N-substituted polyfluoroalkyl and polyfluoroaryl sulfonamides. The effects of solvent and substrate structure on the conditions necessary for reaction to occur, and the yields obtained of the desired products are discussed.

Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones

The reactions of glutathione (GSH) with polychlorinated biphenyl (PCB) quinones having different degrees of chlorination on the quinone ring were examined. EPR spectroscopy and MS revealed 2 types of reactions yielding different products: (i) a nonenzymatic, nucleophilic displacement of chlorine on the quinone ring yielding a glutathiylated conjugated quinone and (ii) Michael addition of GSH to the quinone, a 2-electron reduction, yielding a glutathiylated conjugated hydroquinone. The pK(a) of parent hydroquinone decreased by 1 unit as the degree of chlorination increased. This resulted in a corresponding increase in the oxidizability of these chlorinated hydroquinones. The reaction with oxygen appears to be first-order each in ionized hydroquinone and dioxygen, yielding hydrogen peroxide stoichiometrically. The generation of semiquinone radicals, superoxide, and hydroxyl radicals was observed by EPR; however, the mechanisms and yields vary depending on the degree of the chlorination of hydroquinone/quinone and the presence or absence of GSH. Our discovery that chlorinated quinones undergo a rapid, nonenzymatic dechlorination upon reaction with GSH opens a different view on mechanisms of metabolism and the toxicity of this class of compounds.

Monolithic scavenger resins by amine functionalizations of poly(4-vinylbenzyl chloride-co-divinylbenzene) PolyHIPE materials.

[reaction: see text] Monolithic polymer supports and scavengers were prepared via nucleophilic displacement of chlorine in poly(4-vinylbenzyl chloride-co-divinylbenzene) PolyHIPE materials. Reactions of monolithic PolyHIPE with tris(2-aminoethyl)amine, 4-aminobutanol, tris(hydroxymethyl)aminomethane, morpholine, and hexamethylenetetramine led to functionalized polymers with amino and hydroxy functionalities with high degrees of conversion. 4-Chlorobenzoyl chloride was efficiently and rapidly scavenged from solution by the tris(2-aminoethyl)amine derivative of monolithic poly(4-vinylbenzyl chloride-co-divinylbenzene) PolyHIPE at ambient temperature.

Synthesis of Derivatives of 3-Methylxantheve and 1-Methyl-3-Isobutylxanthine 7-β-D-Ribofuranosides

Methods of synthesis of 7–(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)-8-chloro-3-methylxanthine (5a) and l-methyl-3-isobutylxanthine (5b) were reported. Further nucleophilic displacement of chlorine has provided the corresponding 8-alkylamino and 8-benzylamino derivatives (6a,b-9a,b). Several 5′-acyl analogues of 3-methylxanthine-7–β-D-ribofuranoside (15–18) were synthesized using 7–(2′,3′-di-O-isopropylidene-β-D-ribofuranosyl)-3-methylxanthine (10) as intermediate.

Unsaturated nitrogen compounds containing fluorine. Part 9 [1]. The preparation of 2,5-dichloro-l,l,l,6,6,6-hexafluoro-3,4-diazahexa-2,4-diene and its reaction with amines

2,5-Dichloro-1,1,1,6,6,6-hexafluoro-3,4-diazahexa-2,4-diene ( 1) has been prepared in goodyield (60%) by the reaction of 1,2-bis(trifluoroacetyl)hydrazine with a mixture of N,N-dimethylaniline hydrochloride and phosphoryl chloride. Nucleophilic displacement ofchlorine from azine 1 occurs readily on reaction with primary amines RNH 2 (RPr i, Bu s,Ph, 4-FC 6H 4, 2,6-Cl 2C 5H 2NCH 2-4) and with secondary amines (morpholine and Et 2NH);in general, mono- or di-substitution can be achieved by varying the azine/amine ratio(1:2 or 1:4). The products are the azines CF 3(NRR′)NNCClCF 3 ( 7) (RH, R′Pr i;RR′Et) and CF 3C(NRR′)NNC(NRR′)CF 3 ( 8) (RH, R′=Pr i, Bu s and 2,6-Cl 2pyCH 2-4; RR′: Et; RR′CH 2CH 2OCH 2CH 2) and the imidoyl tautomersPhNC(CF 3)NHNCClCF 3 ( 9a) and ArNC(CF 3)NHNHC(CF 3)NAr ( 110) (ArPh and4-FC 6H 4). On heating at temperatures up to 120 °C, the compounds 10a (ArPh), 10b(Ar4-FC 6H 4) and 9a undergo cyclisation (with elimination of ArNH 2 or HCl) to affordthe corresponding 4-aryl-4 H-1,2,4-triazoles ( 22); the azine 8a (R=Pr i) does not cycliseunder these conditions. The azine 7a (RH, R′Pr i) on hydrolysis (NaOH/EtOH thenH 3O +) gives the trifluoroacetylhydrazine Pr iNC(CF 3)NHNHCOCF 3 ( 20) in excellent yield(92%).

Synthesis of 8-Substituted 7-(α-L-Arabinofuranosyl)theophyllines

Abstract Glycosylation of trimethysilyl theophylline by 1,2,3,5-tetra-O-acetyl-L-arabinofuranose yielding 7-(α-L-arabinofuranosyl)theophylline after deacetylation is reported. A method for the synthesis of 8-chlorotheophylline α-L-arabinofuranoside using N-chlorosuccinimide was found. Further nuc-leophilic displacement of chlorine has provided the corresponding 8-amino-and 8-methylaminotheophylline α-L-arabinofuranosides.

Nucleophilic substitution reactions of polyfluoroalkylsulfonamides

The sulfonamides CF 3SO 2N(CH 3)Na and CF 3SO 2N(H)Na have been reacted with polyfluoro cyclic, acyclic and inorganic chlorine and bromine-containing species. Nucleophilic displacement of chlorine or bromine in 1,2-dichloroperfluorocyclobutene, 1,2-dichloroperfluorocyclopentene, benzyl bromide, cyanuric chloride and oxalyl chloride has been found to occur under mild conditions to give good yields of N-substituted polyfluoroalkyl and polyfluoroaryl sulfonamides. The effects of solvent and substrate structure on the conditions necessary for reaction to occur, and the yields obtained of the desired products are discussed.

Electrophilic and nucleophilic approaches to the synthesis of 3-fluorodiazepam

Electrophilic fluorination of diazepam with elemental fluorine or gas phase acetyl hypofluorite gave 3-fluorodiazepam in 20–60% yields. Nucleophilic displacement of chlorine in 3-chlorodiazepam by fluoride ion also gave 3-fluorodiazepam in modest yields (maximum: 21%). Both of these methods were used for the synthesis of 18F-labelled 3-fluorodiazepam.

Modification of polyvinylchloride in solution or suspension by nucleophilic substitution

AbstractNucleophilic displacement of chlorine from polyvinylchloride (PVC) suspended either in water or in solution can be achieved using a nucleophile such as a sodium thiolate (RS−, Na+). The nucleophilicity of the salt increases if an ether linkage exists in a β position to the thiol group [RO(CH2)2S−, Na+]. Addition of a solvent such as cyclohexanone (which is a good solvent for PVC) to the slurry increases substantially the degree of substitution. Elemental analysis shows that every chlorine displaced from the polymer is replaced by a thiolate group; thus almost no dehydrochlorination occurs. It is possible to obtain by this method a grafted polymer in which 33% of the chlorine atoms are replaced by the β‐ether thiolate group. The resulting polymer behaves like an internally plasticized PVC. The higher the degree of substitution of chlorine, the greater the flexibility of the grafted polymer is. Other compounds, such as lauryl thiolate and diethyl dithiocarbamate, also were used as nucleophiles, the latter one resulting in a brittle crosslinked polymer whenever sulfur was above 2%. Grafting of polytetrahydrofuran from PVC also was achieved using tetrahydrofuran as solvent and silver‐perchlorate as catalyst. The resulting flexible grafted polymer is believed to consist of longer chains of polytetrahydrofuran grafted from few displaced chlorine atoms along the PVC chain.

Synthesis and biological activities of some N6-(nitro- and -aminobenzyl)adenosines.

Synthesis and biological activities of 12 analogs of N6-benzyladenosine are described. The compounds were prepared by two methods: (1) direct alkylation of adenosine with an appropriately substituted benzyl bromide to give the N1-substituted derivative which was then rearranged in base to give the N6-substituted compound, and (2) by nucleophilic displacement of chlorine in 6-chloropurine ribonucleoside, 6-chloro-2-aminopurine ribonucleoside, and 6-chloro-2-aminopurine with an amine. These analogs were examined for their growth inhibitory effect in cultured leukemic cells and also for their effect on adenosine aminohydrolase activity. N6-p-Nitrobenzyladenosine and its 2'-deoxy analog were competitive inhibitors (K1 65, 22 MUM). The 2-amino-N6-p-nitrobenzyladenine and its ribonucleoside were found to be noncompetitive inhibitors of adenosine aminohydrolase. In cultured L1210 leukemia, 2-amino-6-p-nitrobenzylaminopurine and the corresponding ribonucleoside were better growth inhibitors than N6-benzyladenosine, while N6-p-nitrobenzyladenosine, its 2'-deoxy analog, and N6-p-fluorobenzyladenosine were as active as N6-benzyladenosine.

Hydroxy-group participation in the chlorination of thian 1-oxides

Chlorination of 4-hydroxythian 1-oxides with hydroxy- and S-oxide groups cis to each other gives 4-chlorosulphones. The reaction proceeds via a cyclic alkoxyoxosulphonium ion formed by nucleophilic displacement of chlorine by the 4-hydroxy-group in an initially formed chloro-oxosulphonium ion in which the S-oxide group is axial. The equatorial chlorine atom is displaced with inversion at sulphur. Nucleophilic attack by chloride ion at C-4 of the cyclic alkoxyoxosulphonium ion with inversion at C-4 causes ring opening with transfer of the C-4 oxygen atom to sulphur. Chlorination of a thian 1-oxide containing a 4-chloro- or a 4-tosyloxy-group, or a 4-hydroxy-group trans to the S-oxide group, proceeds without participation to give the α-chloro-sulphoxide.