2-dimethylaminoethyl Chloride Research Articles

Preparation, and antibacterial activity of chitosan derivative containing double quaternary ammonium salt and hydantoin structures

Chitosan quaternary ammonium salt antibacterial agents with a single structure have the drawbacks of slow bactericidal speed and poor bactericidal effect, which cannot meet the practical usage requirements. To address the problem, in this study, we designed and synthesized a novel chitosan derivative containing double quaternary ammonium salt and chloride hydantoin structures (QCS-CA-DEADH-Cl) by using chitosan, 5,5-dimethyl hydantoin, methyl iodide, and 2-Dimethylaminoethyl chloride hydrochloride as the main raw materials, and then used as antibacterial agent. The structure of QCS-CA-DEADH-Cl was characterized by Fourier transform infrared spectra, X-ray photoelectron spectroscopy, Thermogravimetric, and Scanning electron microscopy. The antibacterial activity of QCS-CA-DEADH-Cl, and the renewability and stability of N-Cl structure in QCS-CA-DEADH-Cl were explored. The results indicated that the N-Cl structure of QCS-CA-DEADH-Cl has strong renewability and storage stability. Moreover, the synergistic effect of quaternary ammonium salt structure and N-Cl structure endowed QCS-CA-DEADH-Cl with excellent antibacterial activity. This work does not only provide a new perspective for the preparation of novel chitosan antibacterial agents but also contributes to expanding the comprehensive utilization of biomass resources.

Preparation of novel multifunctional monomers

ABSTRACT Novel reducing emulsifier monomers 2-(dimethylamino)ethyl dodecyl maleate (DMAEDM) and 2-(dimethylamino)ethyl dodecyl itaconate (DMAEDI) containing polymerisable double bonds, tertiary amine and long-chain aliphatic hydrocarbons were creatively designed and synthesised. Reducing emulsifier monomers (REM) were prepared using dodecanol, acid anhydride and 2-dimethylaminoethyl chloride hydrochloride through a two-step reaction process. The optimum reaction temperature and ratio of chemicals were determined to achieve higher yield and purity of REM products. The product purity was above 95% as determined by gas chromatography. The structure of the products was confirmed by infrared spectroscopy (IR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The novel reducing emulsifier monomers have been determined to have good emulsifying performance.

Effect of pH on the physicochemical properties of 2-dimethylaminoethyl starch and its desizability

Tertiary amine groups can exhibit and lose cationic properties at different pH levels, and this group can be introduced to starch chains to satisfy the demand for sizing and desizing. However, the effect of pH on tertiary amine groups in toughening starch film and improving adhesion is still unclear. Therefore, 2-dimethylaminoethyl starch (DMAES) was prepared via tertiary aminated starch with 2-dimethylaminoethyl chloride hydrochloride. The influences of pH on the mechanical properties of DMAES films and the adhesion to cotton fiber were investigated. In addition, the desizability and biodegradability of DMAES were measured. It was found that introducing the group of 2-dimethylaminoethyl could toughen the starch film and increase the adhesion to cotton fiber. DMAES has a higher zeta potential and the adhesion to cotton fibers in acidic conditions than in alkaline conditions. In addition, it is easy to remove the DMAES from the yarns and obtain higher desizing efficiency with alkali desizing. Tertiary amination of starch with the 2-dimethylaminoethyl group was a good way for starch to improve adhesion and obtain a higher desizing efficiency.

Tertiary Amination/Hydroxypropylsulfonation of Cornstarch to Improve the Adhesion-to-Fibers and Film Properties for Warp Sizing

To investigate the effects of tertiary amination/hydroxypropylsulfonation on the adhesion-to-fibers and film properties of corn starch for warp sizing, a series of tertiary aminated and hydroxypropylsulfonated corn starch (TAHPSS) samples were prepared by the tertiary amination and hydroxypropylsulfonation of acid-hydrolyzed corn starch (AHS) with 2- dimethylaminoethyl chloride hydrochloride (DMC-HCl) and 3-chloro-2-hydroxy-1-propanesulfonic acid sodium salt (CHPS-Na) simultaneously. The adhesion was evaluated by measuring the bonding force of starch to the fibers. The film properties were investigated in terms of tensile strength, breaking elongation, degree of crystallinity, and moisture regain. The results showed that tertiary amination/hydroxypropylsulfonation was able to increase bonding forces of starch to cotton and polyester fibers, enhance breaking elongation and moisture regain of the starch film and to decrease the tensile strength and degree of crystallinity of the film, thereby improving the adhesion and reducing film brittleness. Increasing the level of tertiary amination/hydroxypropylsulfonation was favorable for gradually improving the adhesion and decreasing the brittleness. The TAHPSS showed potential for use in cotton warp sizing.

An Efficient and Improved Process for the Synthesis of Itopride Hydrochloride and Trimethobenzamide Hydrochloride

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.

Confirmation and Quantification of Genotoxic Impurity 2- Dimethylaminoethyl chloride hydrochloride (DMC HCl) by GCMS in Chlorpheniramine/Chlorphenamine Maleate

Confirmation and Quantification of Genotoxic Impurity 2- Dimethylaminoethyl chloride hydrochloride (DMC HCl) by GCMS in Chlorpheniramine/Chlorphenamine Maleate

An efficient etherification of Ginkgol biloba extracts with fewer side effects in a micro-flow system

In this study, etherification of ginkgolide B and dimethylaminoethyl chloride hydrochloride was investigated as a model reaction in a micro-flow system (MFS), providing the resulting ethers in high yield with fewer side effects. Meanwhile, this novel process in MFS worked well for other ginkgolides from Ginkgol biloba and halides, giving moderate yields.

Continuous synthesis of ginkgolide B derivatives in a micro-flow system

In this study, etherification process of ginkgolide B in a micro-flow system was investigated. With calcium carbonate as an acid-binding agent, the optimal result was obtained in such conditions: residence time 3min, temperature 85°C, molar ratio of ginkgolide B to dimethylamino ethyl chloride hydrochloride 1:2, molar ratio of ginkgolide B to potassium iodide 1:0.2, and molar ratio of ginkgolide B to calcium carbonate 1:2.5. Meanwhile, this novel process in MFS could proceed well for the etherification reaction between ginkgolide B and other halides, to afford the target products in moderate yields. Besides, salification reaction was conducted in a valve assisted micromixer by reacting dimethylaminoethyl ginkgolide B with methane sulfonic acid. Compared with conventional drugs, enhanced bioavailability was obtained when nano-scale drugs were dosed.

ChemInform Abstract: Synthesis, Stereochemical Analysis, and Neuromuscular Blocking Activity of Oximino Ether Derivatives of Progesterone.

Abstract This study consists of the synthesis, separation, and stereochemical analysis of oximino ethers, followed by a preliminary pharmacological evaluation for neuromuscular blockade. Synthesis of the compounds began with the double oximation of progesterone, which yielded EE and ZE dioximes as major products. Both stereoisomers were separated and purified by chromatography followed by crystallization. The diether of each dioxime was prepared by O-alkylation with 2-dimethylaminoethyl chloride hydrochloride, using a mixture of potassium tert-butoxide and sodium hydride as base. The diethers were separated from the monoethers by vacuum chromatography. Configurational assignments of all compounds were based on 1 HNMR and 13 CNMR spectroscopy. Quaternization with methyl bromide yielded the salts which were purified via fractional crystallization. A preliminary pharmacological evaluation was conducted by using mice on a treadmill apparatus. Structure–activity relationships are discussed on the basis of similarities to succinylcholine.

Synthesis of Surfactants Based on Pentaerythritol. I. Cationic and Zwitterionic Gemini Surfactants

Simple strategies for the synthesis of five series of cationic gemini surfactants and one series of zwitterionic gemini surfactants from pentaerythritol have been developed. Two lipophilic groups were introduced onto pentaerythritol by alkylation of the known compound, O-benzylidenepentaerythritol, with 1-bromooctane, 1-bromodecane, 1-bromododecane, and 1-bromotetradecane. Hydrogenolysis of the benzylidene acetals gave diols which were converted into three different series of trimethylammonium derivatives. The diiodides derived from the diols could be displaced by dimethylamine, even though they are adjacent to a quaternary carbon atom. Alkylation with methyl iodide gave the first series. The iodides were easily displaced by cyanide ion and the resulting dinitriles were hydrolyzed, converted to N,N-dimethylamides, and reduced to give a second series. Oxidation of the diols to dialdehydes under Swern conditions followed by Horner-Wadsworth-Emmons reactions with diethyl N,N-dimethylcarbamoylmethylphosphonate followed by two-stage reduction gave a third series. The dialkoxides derived from the four di-O-alkylpentaerthritol diols were reacted with 2-dimethylaminoethyl chloride and 3-dimethylaminopropyl chloride in neighboring-group assisted double Williamson ether syntheses to give precursors to two more series. As expected because the neighboring group participation occurs through a four-membered-ring intermediate, considerably more vigorous conditions were required for the reactions with 3-dimethylaminopropyl chloride. 2-Diethylaminoethyl bromide was found to be less reactive than 2-dimethylaminoethyl chloride. The products were alkylated with methyl iodide and, in some cases, other alkyl halides to give cationic gemini surfactants. Alkylation of one series with ethyl bromoacetate followed by anion exchange resin catalyzed ester hydrolysis gave zwitterionic gemini surfactants. The members of all series have superior surfactant properties.

Synthesis, antimicrobial, and anti-HIV-1 activity of certain 5-(1-adamantyl)-2-substituted thio-1,3,4-oxadiazoles and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-oxadiazoline-2-thiones

The reaction of 5-(1-adamantyl)-1,3,4-oxadiazoline-2-thione 2 with iodoethane, 2-dimethylaminoethyl chloride hydrochloride or 2-piperidinoethyl chloride hydrochloride in ethanolic potassium hydroxide yielded the corresponding 5-(1-adamantyl)-2-ethyl or substituted ethylthio-1,3,4-oxadiazoles 3a– c. Interaction of 2 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding 5-(1-adamantyl)-3-arylaminomethyl-1,3,4-oxadiazoline-2-thiones 4a– m or 5-(1-adamantyl)-3-(4-substituted-1-piperazinylmethyl)-1,3,4-oxadiazoline-2-thiones 5a– h, respectively. All the synthesized compounds were tested for in vitro activities against certain strains of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 2, 5a, and 5e were found as the most active derivatives, particularly against the Gram-positive bacteria. In addition, the antiviral activity of compounds 2, 4a– m, and 5a– h against HIV-1 using the XTT assay was carried out. Compound 2 produced 100%, 43%, and 37% reduction of viral replication at 50, 10, and 2 μg/mL concentrations, respectively.

Syntheses of Poly(ethylene oxide) Macromonomers Carrying Tertiary Amine and Quaternary Ammonium End Groups

p-Vinylbenzyl alcohol, partially alkoxidated with potassium naphthalene, was used successfully to initiate living polymerization of ethylene oxide to afford α-p-vinylbenzyl-ω-hydroxy poly(ethylene oxide) (PEO) macromonomers. The ω-hydroxy end-groups were quantitatively transformed to tertiary amines either by tosylation followed by reaction with potassium 2-dimethylaminoethoxide or by Williamson synthesis with 2-dimethylaminoethyl chloride in the presence of sodium hydride. ω-Quaternary ammonium-ended PEO macromonomers were also quantitatively obtained by reaction with iodomethane.

Dimethylaminoethylated hydroxypropyl-chitosan: Preparation and application as polymeric ligand to form Rh6 cluster complexes for the reduction of benzaldehyde and nitrobenzene

Hydroxypropyl chitosan and its dimethylaminoethylated derivative were prepared in different conditions. Experimental results indicated that the degree of substitution (DS) of hydroxypropyl chitosan was strongly related to the molar ratio of propylene oxide to the glucosamine unit of chitosan, the used solvent, the reaction temperature and the amount of sodium hydroxide. Moreover, the obtained hydroxypropyl chitosan could be effectively dimethylaminoethylated by the reaction with dimethylaminoethyl chloride in the presence of NaH under DMAC solution. By the combination of dimethylaminoethylated hydroxypropyl chitosan and Rh 6 (CO) 16 , benzaldehyde and nitrobenzene could be converted into correspondingly reductive products in high yields under the WGSR condition.

Transport of procainamide via H(+)/tertiary amine antiport system in rabbit intestinal brush-border membrane.

Transport characteristics of procainamide in the brush-border membrane isolated from rabbit small intestine were studied by a rapid-filtration technique. Procainamide uptake by brush-border membrane vesicles was stimulated by an outward H(+) gradient (pH(in) = 6.0, pH(out) = 7.5) against a concentration gradient (overshoot phenomenon), and this stimulation was reduced when the H(+) gradient was subjected to rapid dissipation by the presence of a protonophore, FCCP. An outward H(+) gradient-dependent procainamide uptake was not caused by H(+) diffusion potential. The initial uptake of procainamide was inhibited by other tertiary amines with N-dimethyl or N-diethyl moieties in their structures, such as triethylamine, dimethylaminoethyl chloride, and diphenhydramine, but not by tetraethylammonium and thiamine. Furthermore, procainamide uptake was stimulated by preloading the vesicles with these tertiary amines (trans-stimulation effect), indicating the existence of a specific transport system for tertiary amines. These findings indicate that procainamide transport in the intestinal brush-border membrane is mediated by the H(+)/tertiary amine antiport system that recognizes N-dimethyl or N-diethyl moieties in the structures of tertiary amines.

New Highly Stereoselective Synthesis of ( E)-Droloxifene via Selective Protection of 3,4′-Dihydroxybenzophenone and McMurry Reaction

A new, highly stereoselective synthesis of ( E)-droloxifene is reported. Deprotection of 3,4′-dimethoxybenzophenone and selective pivaloylation of the 3′-phenolic position gave 4-hydroxy-3′-(trimethylacetoxy)benzophenone. A McMurry reaction between the preceding benzophenone and propiophenone gave the ( E)-olefin as a major product (14:1 E/ Z ratio in crude reaction), which was then alkylated with 2-dimethylaminoethyl chloride and deprotected to yield ( E)-droloxifene with a >100:1 E/ Z ratio (5 steps, 13%). Attempts to use this strategy as a suitable stereoselective method to obtain ( Z)-droloxifene were not successful.

Dimethylamine Formation in the Rat from Various Related Amine Precursors

Dimethylamine is the immediate precursor of dimethylnitrosamine, a known potent carcinogen in a wide variety of animal species. Although small amounts of dimethylamine are ingested directly, the major dietary source is believed to be via choline and related materials. Owing to quantitative recoveries following oral administration, urinary dimethylamine levels provide good overall measures of body exposure. The oral administration of equimolar amounts (1 mmol/kg body weight) of potential amine precursors to male Wistar rats produced only small increases in urinary dimethylamine after choline (+11%; 0.60±0.36% dose), dimethylaminopropanol (+32%; 1.49±0.30% dose), dimethylaminoethyl chloride (+110% 5.38±1.72% dose) and trimethylamine (+51%; 1.6±0.80% dose) input, whereas significantly larger increases were found following trimethylamine N-oxide ingestion (+355%; 12.93±1.13% dose; t-test, P <0.001). These data suggest that trimethylamine N-oxide is a major dietary source of dimethylamine, by direct conversion and not by sequential reduction (to trimethylamine) and demethylation, and that in this respect it is of greater importance, on a molar basis, than choline.

Synthesis of Deramciclane labelled with radiocarbon in various positions

[U- 14 C]Bromobenzene, prepared from [ 14 C]barium carbonate according to literature procedures, was transformed (Li / diethylether) into [ 14 C]phenyllithium which was condensed with camphor giving rise to [U- 14 C-phenyl]borneol: 2 . The latter, after conversion into its sodium salt, was reacted with dimethylaminoethyl chloride to give [ 14 C-Ar]Deramciclane, which was isolated as the fumarate salt. This 8 step synthesis from [ 14 C]BaCO 3 gave an overall yield of 12 %. [1- 14 C]Sodium acetate, through a standard 5 step literature procedure, was converted to N,N-dimethylaminoethyl-1- 14 C chloride 5 which was condensed with the sodium derivative of 2-phenylborneol giving rise to [1- 14 C-side chain]Deramciclane, again isolated as the fumarate. This 6 step synthesis from [ 14 C]BaCO 3 gave an overall yield of 8 %. The specific radioactivities from the two syntheses were respectively 40 mCi/mmol and 21 mCi/mmol; chemical and radiochemical purities were better than 98 %.

The Fanconi Anemia Complementation Group C Protein Corrects DNA Interstrand Cross-Link-Specific Apoptosis in HSC536N Cells

Fanconi anemia (FA) cells are hypersensitive to cytotoxicity, cell cycle arrest, and chromosomal aberrations induced by DNA cross-linking agents, such as mitomycin C (MMC) and nitrogen mustard (HN2). Although MMC hypersensitivity is complemented in a subset of FA cells (complementation group C [FA-C]) by wild-type FAC cDNA, the cytoprotective mechanism is unknown. In the current study, we tested the hypothesis that FAC protein functions in the suppression of DNA interstand cross-link (ISC)-induced cell cycle arrest and apoptosis. Comparison of HN2-induced cell cycle arrest and apoptosis with those of its non-cross-linking analogs, diethylaminoethyl chloride and 2-dimethylaminoethyl chloride, delineated the DNA ISC specificity of FAC-mediated cytoprotection. Overexpression of wild-type FAC cDNA in FA-C lymphoblasts (HSC536N cell line) prevented HN2-induced growth inhibition, G2 arrest, and DNA fragmentation that is characteristic of apoptosis. In contrast cytoprotection was not conferred against the effects of the non-cross-linking mustards. Our data show that DNA ISCs induce apoptosis more potently than do DNA monoadducts and suggest that FAC suppresses specifically DNA ISC-induced apoptosis in the G2 phase of the cell cycle.

Synthesis of Several Hydroxylated 23-(Benzimidazol-2-yl-, Benzoxazol-2-yl and Benzothiazol-2-yl)norcholanes and Some Related Compounds

The bile acids Ia - Id (lithocholic, chenodeoxycholic, deoxycholic, cholic) and their derivatives (O-acetylated acids and O-acetylated acid chlorides) reacted under various conditions with 1,2-diaminobenzene, 2-aminophenol and 2-aminothiophenol and afforded the title benzimidazoles II and VII, benzoxazoles V and benzothiazoles VI. Alkylation of the benzimidazole derivative IIa with 2-dimethylaminoethyl chloride resulted in 3α-hydroxy-23-[1-(2-dimethylaminoethyl)ben zimidazol-2-yl]- norcholane (IVa). The use of 1,2-diamino-4-methylbenzene enabled the preparation of 3α-acetoxy-23-[5(6)-methylbenzimidazol-2-y l]norcholane (VIII). Reactions of the 3α-hydroxy compounds IVa, Va and VIa with succinic anhydride resulted in the hemisuccinates IVi - VIi. The boric acid mediated condensation of O-acetyllithocholic acid (Ie) with 3,4-diaminopyridine gave compound X which was transformed to 3α-acetoxy-23-[1H-imidazo(4,5- c)pyridin-2-yl]norcholane (IX). The structure of the products was corroborated by the mass, IR, 1H NMR and 13C NMR spectra. Some of the compounds were tested for antileukemic and for the anti-HIV activity in vitro.

The base‐promoted dehydration of rac.‐trans‐tetrahydro‐6‐hydroxy‐4‐[(2‐(dimethylamino)ethyl]‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(2H)‐one

AbstractThe base‐catalyzed alkylation of rac.‐trans‐tetrahydro‐6‐hydroxy‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(2H)‐one (1) with dimethylaminoethyl chloride in dimethyl sulfoxide provided predominantly rac.‐trans‐tetrahydro‐6‐hydroxy‐4‐[(2‐dimethylamino)ethyl]‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(2H)‐one (2) and in addition, 2,3‐dihydro‐4‐[2‐(dimethylamino)‐ethyl]‐7‐(4‐methoxyphenyl)‐1,4‐thiazepin‐5(4H)‐one (3). A plausible mechanism is postulated for the dehydration of the rac.‐trans‐amide 2.