Chloroacetyl Chloride Research Articles

Effect of the Molecular Structure of Acylating Agents on the Regioselectivity of Cellulosic Hydroxyl Groups in Ionic Liquid

Homogeneous functionalization of cellulose with chloroacetyl chloride (CAC), 2-bromoisobutyryl bromide (BrBiB), and 2-chloro-2-phenylacetyl chloride (CPAC) was performed in ionic liquid to evaluate the effect of the molecular structure of the reagents on the reactivity of the cellulosic hydroxyl groups. The results showed that the reaction was very selective for the less hindered C6-OH group, but the substitution of the secondary OH group still occurred, which indicated that the acylation of cellulose was only partly regioselective. The reaction extent and regioselectivity of the cellulosic hydroxyl groups partly depended on the molecular structure of the acylating agents. The reaction rate of the CAC was much faster than the relatively bulky BrBiB and CPAC, but the bulky acylating agents showed a higher C6-OH selectivity. Moreover, the BrBiB was less reactive than the CPAC, although they showed the same regioselectivity for the three hydroxyl groups. The acylation decreased the thermal stability of the cellulose, which decreased further as the bulk of the substituted groups increased.

Facile green one‐pot synthesis of novel thiazolo[3,2‐a]pyrimidine derivatives using Fe3O4@l‐arginine and their biological investigation as potent antimicrobial agents

Thiazolopyrimidine derivatives are well known because of their excellent therapeutic properties. In this investigation, an effective one‐pot three‐component method is described for the synthesis of novel 2‐[(Z)‐1‐(substituted phenyl)methylidine]‐7‐methyl‐3‐oxo‐5‐(substituted phenyl)‐2,3‐dihydro‐5H‐thiazolo[3,2‐a]pyrimidine‐6‐carboxilic acid tert‐butyl ester derivatives by condensation reaction of 3,4‐dihydropyrimidine‐2(1H)‐thiones, various aromatic aldehydes and chloroacetyl chloride under reflux conditions in the presence of Fe3O4@l‐arginine nanoparticles as a magnetically reusable and eco‐friendly catalyst with short reaction times and moderate yields. The chemical structures of all synthesized compounds were determined using infrared, 1H NMR and 13C NMR spectroscopies. In vitro antimicrobial activities of 3,4‐dihydropyrimidine‐2(1H)‐thiones and newly fused thiazolo[3,2‐a]pyrimidine derivatives were examined using the well diffusion method against diverse pathogenic strains, namely Staphylococcus aureus ATCC 6538, S. epidermidis ATCC 12228, Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027 (bacteria), Candida albicans ATCC 10231 (yeast) and Aspergillus niger ATCC 16404 (fungus). The compounds having 2‐hydroxy, 4‐hydroxy, 2‐chloro and 4‐chloro groups attached to the phenyl ring on the pyrimidine and 4‐CH3, 4‐OCH3 and 3‐NO2 groups attached to benzylidine on the thiazolo moiety showed significant antibacterial activity.

Development and Optimization of Dual Drugs (Isoniazid and Moxiflox-acin) Loaded Functional PLGA Nanoparticles for the Synergistic Treatment of Tuberculosis.

The management of TB is difficult due to the resistance developed by Mycobacterium tuberculosis against anti-tubercular drugs causes the new challenges for treating and managing the disease. The objective of the study was to combat multiple drug resistance (MDR) exhibited by mycobacterium species by synthesizing Dual Drug Conjugate nanoparticle (DDC) using Isoniazid (INH) and Moxifloxacin (MOXI). The reaction was nucleophilic substitution using hydrolysable linkers like Chloroacetyl chloride (CAC) & Succinyl chloride (SCL). The drugs were covalently linked as INH-CAC-MOXI (DDC-1) and INH-SCL-MOXI (DDC-2). The DDC-1 & DDC-2 were subjected to hydrolysability tests at different pH solutions. The modified drugs were formulated into Poly (D, L-Lactic-co-Glycolide) nanoparticles using single emulsion technique. Design Expert® (version 8.0.1) software was used for designing, and evaluating the prepared formulation by employing response surface, optimal design of experiment technique. The prepared nanoparticles were characterized for compatibility studies using Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, particle size, size distribution, Zeta potential, drug entrapment efficiency and Scanning Electron Microscopy. Microbiological studies on pure drug and the conjugate indicated better activity of conjugate compared to pure drug alone or 1:1 physical mixture of drug. The nanoparticles were further subjected to drug release studies and accelerated stability studies. The present study offers a key to the challenge of loading different types of drugs onto the same drug delivery vehicle with efficient loading capacity, thus enabling better treatment for TB.

SYNTHESIS AND ANTI-INFLAMMATORY ACTIVITY OF SOME NEW PYRAZOLO[3,4-d] PYRIMIDINES

5-Amino-3-methyl-1-phenyl-1 H -pyrazole-4-carbonitrile ( 5 ) was reacted with chloroacetyl chloride under fusion condition to afford two compounds, which identified as 6-chloromethylpyrazolo[3,4- d ]pyrimdine ( 3 ) and 4-amino-5-chloropyrazolo[3,4- b ]pyridine ( 7 ) ln different ratios. Treatment of compound ( 3 ) with aromatic amines, gave the arylaminomethyl derivatives ( 8a-c ). Compound ( 3 ) was reacted with sodium azide, phosphorous oxychloride, sulphanilamide to give new derivatives ( 9, 10, and 14 ). The 4-chloro derivative ( 11 ) underwent nucleophilic substitution using some reagent such as P 2 S 5 , sodium azide and hydrazine hydrate to furnish novel pyrazolo[3,4- d ]pyrimidines ( 12, 13, 15, 16, 17 ). All synthesized compounds were characterized using elemental analysis and spectral techniques. The anti-inflammatory activity of all the newly synthesized compounds was evaluated using the carrageenan induced paw oedema test in rats using indomethacin as the reference drug.

Synthesis, Characterization & Screening for Anti-Inflammatory & Analgesic Activity of Quinoline Derivatives Bearing Azetidinones Scaffolds.

Non-steroidal anti-inflammatory drugs (NSAIDS) are clinically used as anti-inflammatory, analgesic and antipyretic agents but they have the drawbacks such as gastric irritation and gastric ulceration. Recently, quinoline derivatives have shown significant anti-inflammatory and less ulcerogenic activity. The present study deals with the synthesis and pharmacological assessment of a series of novel quinoline derivatives bearing azetidinones scaffolds as anti-inflammatory and analgesic agents. A series of newer 3-chloro-1-(substituted)-4-(tetrazolo [1,5-a]quinolin-4- yl)azetidin-2-one derivatives (6a-l) was synthesized starting with acetanilide (1). Initially, acetanilide (1) was allowed to react with Vilsmeier-Haack reagent (DMF + POCl3) to form 2- chloro-3-formyl quinoline (2). The 2-chloro-3-formyl quinoline (2) was further treated with p-toluenesulphonic acid and sodium azide which yielded Tetrazolo [1,5-1] quinoline-4- carbaldehyde (3). The reaction of formyl group with various substituted amines (4a-l) formed corresponding Schiff base intermediates (5a-l), which were further allowed to react with chloroacetyl chloride to produce 3-chloro-1-(substituted)-4-(tetrazolo [1,5-a]quinolin-4-yl) azetidin-2-one derivatives (6a-l). The structure of the final analogues (6a-l) has been confirmed on the basis of elemental analysis, IR, 1H NMR, 13C NMR and mass spectra. All the synthesized compounds were evaluated for their anti-inflammatory and analgesic activities by using carrageenan induced rat paw model and Eddy's hot plate method respectively. All the values of elemental analysis, IR, 1H NMR, 13C NMR and mass spectra were found to be prominent. The anti-inflammatory activity test revealed that 3-chloro-1-(4-methoxyphenyl)- 4-(tetrazolo[1,5-a] quinolin-4-yl)azetidin-2-one (6b), 3-chloro-1-(2-methoxyphenyl)- 4-(tetrazolo[1,5-a]quinolin-4-yl)azetidin-2-one (6a) exhibited significant anti-inflammatory and analgesic activity as compared to control group. The results of the current study indicate that substitution at quinoline derivatives bearing azetidinones scaffolds showed potent analgesic and anti-inflammatory activities.

Synthesis, Characterization and Antimicrobial Activity of New Nucleoside Analogues from Benzotriazole

Novel derivatives of 1-(´1, ´3, ´4, ´6-tetra benzoyl-β-D-fructofuranosyl)-1H- benzotriazole and 1-(´1, ´3, ´4, ´6-tetra benzoyl-β-D-fructofuranosyl)-1H-benzotriazole carrying Schiff bases moiety were synthesised and fully characterised. The protection of D-fructose using benzoyl chloride was synthesized, followed by nucleophilic addition/elimination between benzotriazole and chloroacetyl chloride to give 1-(1- chloroacetyl)-1H-benzotriazole. The next step was condensation reaction of protected fructose and 1-(1-chloroacetyl)-1H-benzotriazole producing a new nucleoside analogue. The novel nucleoside analogues underwent a second condensation reaction with different aromatic and aliphatic amines to provide new Schiff bases. The prepared analogues were characterised by FT-IR, 1H NMR, 13C NMR, HRMS(EI+) spectra. These analogues were tested against different bacteria to evaluate them as antimicrobial agents.

Synthesis of Highly Polymerized Water-soluble Cellulose Acetate by the Side Reaction in Carboxylate Ionic Liquid 1-ethyl-3-methylimidazolium Acetate.

In the present study, we describe a novel one-step method to prepare water-soluble cellulose acetate (WSCA) with higher degree of polymerization values (DP = 650–680) by in situ activation of carboxyl group in ionic liquid. First of all, cellulose was dissolved in 1-ethyl-3-methylimidazolium acetate (EmimAc) and reacted with dichloroacetyl chloride (Cl2AcCl) in order to make cellulose dichloroacetate. Under various conditions, a series of water soluble products were produced. Elemental analysis and NMR results confirmed that they were cellulose acetate with DS (degree of substitution) values in the range from 0.30 to 0.63. NMR studies demonstrated that Cl2AcCl reacted with acetate anion of EmimAc producing a mixed anhydride that acetylated cellulose. Other acylating reagents such as benzoyl chloride, chloroacetyl chloride can also work similarly. 2D NMR characterization suggested that 6-mono-O-acetyl moiety, 3,6-di-O-acetylcellulose and 2,6-di-O-acetyl cellulose were all synthesized and the reactivity of hydroxyl groups in anhydro-glucose units was in the order C-6>C-3>C-2. This work provides an alternative way to make WSCA, meanwhile, also services as a reminder that the activity of EmimAc toward carbohydrate as acylating reagents could be a problem, because the expected acylated products may not be resulted and recycling of this ionic liquid could also be difficult.

Synthesis and anticancer activity of new isatin-benzoic acid conjugates

A series of new isatin-benzoic acid conjugates (9a - n) were synthesized via conjugation of isatin (3a) and its derivatives (3b - d, 4, 5 and 6) with 4-amino-5 chloro-2-ethoxybenzoic acid or 4-amino-5-(ethylsulfonyl)-2- methoxybenzoic acid by using chloroacetyl chloride as a bifunctional linker. Compounds 3a - d were prepared by employing Sandmeyer reaction. Compounds 4, 5, and 6 were obtained from isatin (3a) via previously reported methods. Isatin-benzoic acid conjugates were synthesized by halomethylketo alkylation at N-1 position of the isatin nucleus. The newly synthesized compounds were characterized using IR, Mass, 1H NMR and 13C NMR spectral techniques. Anticancer activity of the synthesized compounds was evaluated againstMCF-7 (human breast cancer) and HeLa (human cervical cancer) cell lines by 3-(4,5-dimethylthiazol -2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay using vinblastin as a standard. The results showed compounds 9g and 9d to be more potent than the other compounds synthesized with IC50 values of 5.88 ± 0.88 & 6.57 ± 0.81 μM against MCF-7, and 8.34 ± 0.94 & 9.24 ± 1.06 μM against HeLa, respectively.Keywords: synthesis, isatin-benzoic acid conjugates, in vitro anticancer, human breast cancer cell line, human cervical cancer cell line

Synthesis and antitumor activity evaluation of some N-heterocycles derived from pyrazolyl-substituted 2(3H)-furanone

ABSTRACTPyrazolyl-substituted 2(3H)-furanone was allowed to react with different nitrogen nucleophiles such as hydrazine hydrate, ethylenediamine, ethanolamine, and anthranilic acid to give pyrrolone and benzoxazinone derivatives. The acid hydrazide 3 was reacted with some carbonyl compounds such as 4-chlorobenzaldehyde, chloroacetyl chloride, and acetic anhydride to give thiazolidinone, oxadiazole, and pyridazinone derivatives. Selected examples of the synthesized compounds were evaluated as anticancer agents against three types of carcinoma cell lines (HePG 2, HCT116, and PC3), using Doxorubicin as a reference drug. The result revealed that some of the new compounds showed high activities. Compound 6a was more potent than the standard drug. A docking study using MOE 2008.10 program was performed.

Synthesis of Some Novel 2-Azetidinones/4-Thiazolidinones Bearing 1, 3, 4- Thiadiazole Nucleus and Screening for its Anti-Imflammatory Activity

Objective: The objective of the study was to synthesize a series of 3-chloro-4-(substituted phenyl)-1-(5-styryl-1, 3, 4-thiladiazole-2-yl) azetidin-2-one / 2-(substituted phenyl)-3-(5-styryl-1, 3, 4- thiadiazole-2-yl)-thiazolidin-4-one and screened for their possible anti-inflammatory activity by carrageenan induced paw edema in rats. Method: The synthesis of 2-amino-5-styryl-1, 3, 4-thiadiazole, an intermediate was carried out by oxidative cyclization method. In the current study, thiosemicarbazone (I) was subjected to oxidative cyclization using ferric chloride as an oxidising agent, to get 2- amino- 5- styryl -1, 3, 4-thiadiazole (II). Futhermore, compound (II) was reacted with different aromatic aldehydes in methanol to form N-(4-sustituted)- 5- styryl- 1, 3, 4-thiadiazol-2-amine (III a-h). Compound (III ah) was reacted with chloroacetyl chloride in triethylamine to form 2-azetidinone derivatives bearing 1, 3, 4-thiadiazole nucleus (IV a-h). Compound (III a-h) on cyclocondensation with mercaptoacetic acid leads to the formation of 4- thiazolidinone derivatives bearing 1, 3, 4-thiadiazole nucleus (V a-h). Results: The synthesis of the targeted compounds IVa-h and Va-h was confirmed through their MP, IR, 1H-NMR and mass spectrum studies. Compounds IVa, IVb and IVc (56.32, 61.11 and 58.24 % inhibition) exhibited significant antiinflammatory activity than that of diclofenac (65.13% inhibition). Conclusion: It may be concluded that the presence of methoxy, nitro and hydroxyl phenyl groups substituting 2- azetidinone bearing 1, 3, 4-thiadiazole showed significant anti-inflammatory activity. Keywords: Anti-inflammatory activity, diclofenac, 2-Azetidinone, 4-Thiazolidinone, 1, 3, 4-Thiadiazole, carrageenan induced paw edema.

Dithiocarbamate as an efficient intermediate for the synthesis of 2-(alkylthio)thiazol-4(5H)-ones

ABSTRACT An effective approach for the synthesis of 2-(alkylthio)thiazol-4(5H)-ones from alkyl dithiocarbamates and chloroacetyl chloride in the presence of NaHCO3 has been developed. Good to excellent yields of products, simple reaction conditions and general applicability are the most important advantages of this protocol.

Synthesis of New Some Imidazole Derivatives Containing ?-Lactam Ring

In this work 5-methylene-yl - (2-methy –oxazole-4-one) (1H) imidazole (1) were synthesized from the reaction of L-Histidine with acetic anhydride and which converted to the of 5-methylene-yl-(2-methyl 3-amino imidazole-4-one)-1H-imidazole (2) by reaction with hydrazine hydrate. Schiff bases (3-6) were synthesized from the reaction of compound (2) with different aromatic aldehyde. Reaction of compounds (3-6) with chloroacetyl chloride gives azetidinone one derivatives (7-10). These compounds were characterized by FT-IR and some of them with 1H-NMR and 13C-NMR spectroscopy.

Design and Synthesis of 3‐Substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones as a New Class of Anticonvulsants

A new series of 3‐substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones were synthesized by nucleophilic substitution of p‐substituted‐thiazol‐2‐yl‐chloroacetamides with potassium thiocyanide by cyclization. The starting material p‐substituted‐thiazol‐2‐yl‐chloroacetamides were synthesized from p‐substituted‐thiazol‐2‐yl‐amines with chloroacetyl chloride, which in turn was prepared from one pot reaction of substituted aryl acetophenone and amino group of thiourea. The title compounds were investigated for their anticonvulsant activity. Among the tested compounds, compound 3‐(4‐(4‐fluorophenyl)thiazol‐2‐yl)‐2‐iminothiazolidin‐4‐one (16) emerged as the most active compound of the series, and it is moderately more potent than the reference standard diazepam.

Synthesis of Thiazolinone, Aminopyrazole, Pyrazolopyrimidine, and Pyrazolotriazine Derivatives Starting from 1‐Naphthyl‐2‐Cyanoacetamide

Efficient and suitable methods for the synthesis of novel class of simple and fused heterocyclic compounds were prepared starting with 1‐naphthyl‐2‐cyanoacetamide and commercially available reagents. The cyclocondensation of 1‐naphthyl‐2‐cyanoacetamide with sulfanylacetic acid furnished phenylthiazolinone derivative. Stirring of the starting compound with PhNCS afforded thiocarbamoyl derivative which underwent heterocyclization with chloroacetyl chloride to give thiazolinone derivative. 5‐Aminopyrazole derivative was prepared by following mild procedures via refluxing the last thiocarbamoyl with hydrazine hydrate. Different synthetic approaches were discussed to obtain the novel fused pyrazolo[1,5‐a]pyrimidine, 4H‐pyrazolo[3,4‐d]pyrimidin‐4‐one moieties involving the reaction of the prepared 5‐aminopyrazole with a) 1, 3‐dielectrophilic centers (acetylacetone, acetoacetanilide), b) arylidines of malononitrile, and c) isothiocyanate derivatives. The action of iced sodium nitrite solution in acidic medium on the last 5‐aminopyrazole gave pyrazolo[3,4‐d][1,2,3]triazine. All novel structure were elucidated by different spectroscopic data (IR, MS, 1H, and 13C NMR) and elemental analysis.

Design and synthesis of four steroid-oxirane derivatives using some chemical tools

This study involved the synthesis of several new derivatives of progesterone, 11a-hydroxyprogesterone, 11a-t-butyldimethylsilanyloxyprogesterone, and andrenosterone. The new derivatives were prepared by condensation of the 4-en-3-one moiety of the four steroids with 2-hydroxy-1-naphthaldehyde to afford a series of 4-(R)-hydroxy-(2-hydroxynaphtalen-1-yl) adducts. These adducts were further modified by cyclization reactions of the dihydroxynaphthalenyl moieties with succinic acid, and the resulting cyclic succinates were then condensed with ethylenediamine to form imine derivatives at all available carbonyl groups. These compounds were then derivatized by N-acylation of the 11- and 17-imine nitrogens with chloroacetyl chloride and the resulting chloroacetamides were then condensed with 2-hydroxy-1-napthaldehyde in Darzens-type reactions forming the corresponding epoxy acetamides in the side chains. In addition, the chemical structure of steroid derivatives was confirmed by NMR spectroscopic data.

Synthesis of new substituted acetamide derivatives of 6′,7′-dimethoxy-2′,3′-dihydro-1′H-spiro[isoquinoline-1,4′-cyclopentane]-1′-carboxamide

Reaction of ethyl 6′,7′-dimethoxy-3′Н-spiro[isoquinoline-1,4′-cyclopentane]-1′-carboxylate with ammonia and isopropylamine afforded dihydroisoquinoline carboxamides that were reduced with NaBH4 in amides of 6,7-dimethoxy-4-spirocyclopentane-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid. The reaction of unsubstituted carboxamide with chloroacetyl chloride led to chloroamide that reacted with versatile secondary amines and heterylthiols providing the corresponding substituted amino- and sulfanylamides of tetrahydroisoquinoline series.

Theoretical study on the mechanism of chloroacetyl chloride decomposition

The mechanism of chloroacetyl chloride (CH2ClCOCl) decomposition has never been investigated by theoretical and experimental methods before, which is explored at the BMC-CCSD//BMK/6-311+G(d, p) level in this work. Eight pathways and ten transition states are located to search for more favorable pathways. Some dissociated pathways start from the trans-CH2ClCOCl directly. Alternatively, the trans-CH2ClCOCl would transform to the cis-CH2ClCOCl. Then, the cis-CH2ClCOCl would dissociate into the product with single or multi steps. Starting from the trans-CH2ClCOCl, P1 (CHClCO+HCl) is the most favorable product by the rupture of C1H1 bond and C2Cl2 bond and the formation of H1Cl2 bond (Pathway 1), due to the least step and the lowest barrier height. P2 (CH2Cl2+CO) is the common product of both Pathway 2 and Pathway 4 those start from the trans- and cis-CH2ClCOCl, respectively. Owing to the second lowest rate-determining barrier height, P2 is the second feasible product. P3 (CH2Cl(O)CCl) formed by the migration of O atom from C2 atom to Cl1 atom is the most minor product because of the highest barrier height. Other products P4 (CH2Cl+CO+Cl), P5 (CH2CO+Cl2), and P6 (CH2ClCO(Cl)) formed by the attack of Cl2 atom to C1 atom, Cl1 atom, and O atom, respectively, are not energetically accessible because of higher barrier-consumed and/or complicated process.

Novel biocidal polymers based on branched and linear poly(hydroxystyrene)

ABSTRACTNew biocidal polymers based on branched as well as linear poly(p-hydroxystyrene) were synthesized. Biocidal polymers were synthesized in two steps by creation of active centers via chloroacetylation of linear and branched poly(p-hydroxystyrene) using chloroacetyl chloride. The second step involves the immobilization of onium salts onto the chloroacetylated polymers. All the prepared polymers were characterized using elemental microanalysis, FT-IR, 1H NMR spectra, and TGA. Antimicrobial activity of the prepared polymers was tested against various pathogenic microorganisms. The antimicrobial activity was found to be affected by the active group and the tested microorganism. The phosphonium salts showed higher activity than ammonium salts.

ChemInform Abstract: A New and Facile Synthesis of Novel Pyrazolothienopyrimidines and Imidazopyrazolothienopyrimidines.

4-Amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide (5), which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrazolothienopyrimidines and imidazopyrazolothienopyrimidines compounds. Reaction of amino thienopyrazole carboxamide 5 with triethyl orthoformate afforded thienopyrazolopyrimidine 6. Chlorination of the latter compound, using phosphorus oxychloride afforded the chloro pyrazolothienopyrimidine 7, which underwent nucleophilic substitution reactions with various primary and secondary amines to give the alkyl (aryl) amino pyrimidine compounds 8a–d. On the other hand, the reaction of chloropyrimidine 7 with thiourea afforded the pyrimidine thione compound 9, which was alkylated with α-halogentaed compounds to afford the S-alkylated derivatives 10a–c. Also, chloroacetylation of the amino carboxamide 5 using chloroacetyl chloride yielded the chloromethyl pyrazolothienopyrimidine 12, which underwent nucleophilic substitu- tion reactions with various primary and secondary amines to afford the alkyl (aryl) aminomethyl compounds 13a–f. The latter Compounds underwent Mannich reaction to give imidazopyrimidothieno- pyrazoles 14a–c. The newly synthesized compounds and their derivatives were fully characterized by elemental and spectral analysis.

Synthesis and Characterization of 3 - Substituted Coumarin

The reaction of(2-oxo-2H-chromen-3-Carbonyl chloride)(k1) with hydrazine in boiling ethanol gives the hydrazide(K2).When compound (k2) reacts with various aromatic aldehydes ,the corres ponding Schiff bases(k3–k4) achieve new series of thiazotidines (k5–k6) and azetidinones (k7–k8) obtained from the reactions of appropriate Schiff bases with mercapto acetic acid and chloro acetyl chloride respectively. All the compounds are characterized by FT-IR,1H-NMR and GC-Ms.