Tosyl Chloride Research Articles

Cationization of lignocellulosic fibers with betaine in deep eutectic solvent: Facile route to charge stabilized cellulose and wood nanofibers

In this study, a deep eutectic solvent (DES [based on triethylmethylammonium chloride (TEMA) and imidazole]) was used as a reaction medium for cationization of cellulose fibers with trimethylglycine (betaine) hydrochloride in the presence of p-Toluenesulfonyl (tosyl) chloride. Cellulose betaine ester with a cationic charge up to 1.95 mmol/g was obtained at mild reaction conditions (four hours at 80 °C). The reaction was further demonstrated in the fabrication of cationic cellulose nanofibers (CCNFs) by a mild mechanical disintegration of cationized cellulose. In addition to CCNFs, cationic wood nanofibers (CWNFs) were produced directly from groundwood pulp (GWP) with a high lignin content (27 w%). Individualized CCNFs and CWNFs had a fiber diameter of 4.7 ± 2.0 and 3.6 ± 1.3 nm, respectively, whereas some larger fiber aggregates (diameter below 200 nm) were also observed, especially in the case of CWNFs.

Oxazolidine Formation, or Loss of Acid, from Attempted Fluorination of Amide Side‐Chain in 2‐Nitroimidazoles

Reaction of Etanidazole (a 2‐nitroimidazole derivative with an amide side‐chain containing a hydroxyethyl group) with triflic anhydride gives, depending on conditions, a trifluoromethyl(sulfonyl)oxazolidine via a cyclization reaction, or a fluorine‐free formate derivative; reaction with tosyl chloride gives only a chloroethyl derivative. An attempt to replace a Br‐atom in a related propyl‐containing amide side‐chain by a F‐atom forms instead a propylene derivative via loss of HBr. The studies stem from interest in use of 2‐nitroimidazoles with fluorine‐containing amide side‐chains as hypoxia markers.

An Improved Approach to the Direct Construction of 2-Deoxy-β-Linked Sugars: Applications to Oligosaccharide Synthesis.

A next-generation reagent-controlled approach for the synthesis of 2,6-dideoxy and 2,3,6-trideoxy sugar donors in good yield and high β-selectivity is reported. The use of p-toluenesulfonyl chloride and potassium hexamethyldisilazide (KHMDS) greatly simplifies deoxy-sugar glycoside construction, and can be used for gram-scale glycosylation reactions. The development of this approach and its application to the construction of β-linked deoxy-sugar oligosaccharides are described.

Synthesis of 2,2-diaryl-1,1-difluoroethenes via Pd-catalyzed dehydrosulfonylative cross-coupling of α-[difluoro(phenylsulfonyl)methyl]benzyl tosylates with arylboronic acids

By using PhSO2CF2H as the difluoromethylidene equivalent, a novel method for connecting aromatic aldehydes and arylboronic acids via consecutive reactions was developed to obtain structurally diverse 2,2-diaryl-1,1-difluoroethenes. The key step is the palladium-catalyzed dehydrosulfonylative cross-coupling of tosylates that are prepared from PhSO2CF2H, aromatic aldehydes and tosyl chloride. Mechanistic investigations showed that the reaction proceeds mainly through base-mediated dehydrosulfonylation followed by palladium-catalyzed C(sp2)-C(sp2) cross-coupling reaction.

Rational design of novel water-soluble ampholytic cellulose derivatives

The development of new biocompatible, biodegradable functionalized biopolymers that can serve as scaffold for tissue regeneration or work as carriers for different bioactive molecules such as drugs, proteins, and enzymes remains a continuous challenge that need to be extensively explored. For this purpose, three water-soluble cellulose derivatives; namely 4(celluloseamino) butyric acid (CABA) 2(celluloseamino) succinic acid (CASA), and 3(celluloseamino) propane sulfonic acids (CAPSA) were synthesized from microcrystalline cellulose (MCC) via esterification with tosyl chloride that was followed by nucleophilic substitution by the proper aminoalkyl acid derivative. The products were characterized by elemental analyses, FTIR, 13C NMR spectroscopy. The thermal stability, surface morphology, and the elemental composition of the new ampholytic biopolymers were also studied by TGA, EDX-SEM. The new ampholytic cellulose derivatives were evaluated for their in vitro cytotoxicity on normal human retina cell line (RPE1) by MTT assay.

Flurbiprofen conjugates based on hydroxyethylcellulose: Synthesis, characterization, pharmaceutical and pharmacological applications

Present study deals with fabrication of macromolecular prodrugs (MPDs) of flurbiprofen (FLB) with hydroxyethylcellulose (HEC). FLB was activated using p-toluenesulfonyl chloride and reacted with pre-dissolved HEC to yield HEC-FLB conjugates 1–3. Resultant prodrugs showed moderate to high degree of substitution (DS: 0.40–1.74) and assembled into nanoparticles of 220–550 nm at water/DMSO interface. Pharmacokinetic studies of HEC-FLB conjugate revealed a tmax of 4.0 h indicating delayed release of FLB while t1/2 of 10.63 h indicated sustained release characteristics of the conjugate in rabbit model. Pharmacological studies revealed that HEC-FLB conjugates had immunomodulatory potential as results showed 34 and 36% inhibition of Interleukin-6 and tumor necrosis factor-α, respectively. A 79% inhibition of paw edema indicated anti-inflammatory properties of the conjugates. Cell viability studies indicated safety of the conjugates to L929 cell lines up to 24 h in the range of 2–10 mM. Moreover, thermal analysis indicated greater stability of MPDs than FLB.

A Novel Synthesis of N-Sulfonylformamidines from N-Sulfonyl­sulfonamides

N-Sulfonylformamidines were synthesized from N-sulfonylsulfonamides by reacting with p-toluenesulfonyl chloride (TsCl) and N,N -disubstituted formamides. In this reaction, it was expected that mixing TsCl with the N,N-disubstituted formamide would generate an iminium salt (Vilsmeier reagent). The reaction avoids the use of metal catalysts and hazardous reagents, and the desired N-sulfonylformamidines were obtained in 60% to quantitative yields.

Differentiation of isomeric haloanilines by tosylation in combination with electrospray ionization mass spectrometry.

Differentiation of the isomeric haloanilines still remains a challenging andnecessaryanalytic task due to their identical retention time in chromatography and similar mass spectra. In this work, p-tosylation of haloanilines by reaction of haloanilines with p-toluenesulfonyl chloride resulted in the corresponding N-tosyl haloanilines. Fragmentation of protonated N-tosyl haloanilines in electrospray ionization tandem mass spectrometry (ESI-MS/MS) mainly resulted in tosyl cation, haloaniline radical cation, and halohydroxyaniline radical cation. The MS/MS of the three group isomeric derivatives showed significant difference in abundance distribution of these product ions, respectively. Theoretical calculations showed that the stability of the ion-neutral complex (INC) is a key factor influencing the relative intensity of the product ions. The three group isomeric derivatives were also separated by high performance liquid chromatograph (HPLC) at conventional conditions. p-Tosylation combined tandem MS (or HPLC) technique were carried out to realize the differentiation of isomeric haloanilines.

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives

In the present study, a series of new hydrazone and sulfonamide derivatives of 1,2,4-triazole were synthesized. Initially three 4-substituted-5-(2-pyridyl)-1,2,4-triazole-3-thiones ZE-1(a–c) were treated with ethyl chloroacetate to get the corresponding thioesters ZE-2(a–c), which were reacted with hydrazine hydrate to the respective hydrazides ZE-3(a–c). The synthesized hydrazides were condensed with different aldehydes and p-toluene sulfonylchloride to furnish the target hydrazone derivatives ZE-4(a–c) and sulfonamide derivatives ZE-5(a–c) respectively. All the synthesized compounds were characterized by FTIR, 1HNMR, 13CNMR and elemental analysis data. Furthermore, the new hydrazone and sulfonamide derivatives ZE-4(b–c) and ZE-5(a–b) were evaluated for their antiplatelet and anticoagulant activities. ZE-4b, ZE-4c, ZE-5a and ZE-5b inhibited arachidonic acid, adenosine diphosphate and collagen-induced platelets aggregation with IC50 values of 40.1, 785 and 10.01 (ZE-4b), 55.3, 850.4 and 10 (ZE-4c), 121.6, 956.8 and 30.1 (ZE-5a), 99.9, 519 and 29.97 (ZE-5b) respectively. Test compounds increased plasma recalcification time (PRT) and bleeding time (BT) with ZE-4c being found most effective, which at 30, 100, 300 and 1000 µM increased PRT to 84.2 ± 1.88, 142 ± 3.51, 205.6 ± 5.37 and 300.2 ± 3.48 s and prolonged BT to 90.5 ± 3.12, 112.25 ± 2.66, 145.75 ± 1.60 s (P < 0.001 vs. saline group) respectively. In silico docking approach was also applied to screen these compounds for their efficacy against selected drug targets of platelet aggregation and blood coagulation. Thus in silico, in vitro and in vivo investigations of ZE-4b, ZE-4c, ZE-5a and ZE-5b prove their antiplatelet and anticoagulant potential and can be used as lead molecules for further development.

Synthesis of benzaldehyde by Swern oxidation of benzyl alcohol in a continuous flow microreactor system

Preparation of benzaldehyde by Swern oxidation of benzyl alcohol was carried out in a continuous flow microreactor system. Dimethyl sulfoxide (Me2SO) was used as oxidizing agent and oxalyl chloride or p-toluenesulfonyl (p-TsCl) chloride was used as the activating agent. Benzyl alcohol was oxidized to benzaldehyde by the Me2SO-activating agent mixture in the continuous flow microreactor system. The optimized reaction conditions of the Swern oxidation were as follows: oxalyl chloride was used as the activating agent; the mole ratio of Me2SO, oxalyl chloride, and benzyl alcohol was 4:2:1; the ow rate of Me2SO was 1.5 mL/min; the reaction temperature was 15 length of delay loop was 1.5 m; a Caterpillar Split-Recombine Micro Mixer was used; and all of the experiments were completed at atmospheric pressure. The yield of benzaldehyde can reach 84.7% with selectivity of 98.5%. Due to the small reactor volume and short residence times, the Swern oxidation of benzyl alcohol in a continuous flow microreactor system can be operated at nearly room temperature (5–19 ℃) instead of –70 ℃ in a batch reaction, with residence time of reactants in microreactors in milliseconds instead of several hours in a batch reaction.

Syntheses of Amino-Substituted Iridabenzofurans and Subsequent Selective N-Functionalisation.

The first examples of amino-substituted fused-ring metallabenzenes, the cationic iridabenzofuran [Ir(C7 H4 O{NH2 -2}{OMe-7})(CO)(PPh3 )2 ][O3 SCF3 ] (5) and neutral analogue Ir(C7 H4 {NH2 -2}{OMe-7})Cl(PPh3 )2 (6), can be prepared by reduction of the corresponding nitro-substituted iridabenzofurans with zinc and concentrated hydrochloric acid. N-functionalised derivatives of 5 and 6 are formed through alkylation, sulfonylation or acylation. Thus, consecutive treatments with methyl triflate and base gives the corresponding trimethylammonium-substituted iridabenzofurans while sulfonamide derivatives are formed with p-toluenesulfonyl chloride. N-Acylation of 5 or 6 with acid chlorides, however, selectively form either amide or imide products depending on the charge on the metal and the steric size of the acid chloride. Cationic 5 gives amide substituted products regardless of the conditions whereas neutral 6 rapidly undergoes di-N-acylation with excess benzoyl chloride under mild conditions to give the imide-substituted product Ir(C7 H4 O{N[C(O)Ph]2 -2}{OMe-7})Cl(PPh3 )2 (13). Selective mono-acylation of 6 can be achieved with one equivalent of benzoyl chloride or with excess of the sterically congested pivaloyl chloride.

Direct Oxidation of Aldehydes to Methyl Esters with Urea Hydrogen Peroxide and p-Toluenesulfonyl Chloride.

Combination of urea hydrogen peroxide and p-toluenesulfonyl chloride in methanol was proved to be facile and highly efficient for the oxidative methyl esterification of various aldehydes to the corresponding carboxylic methyl esters.

Analytical insight into degradation processes of aminopolyphosphonates as potential factors that induce cyanobacterial blooms

Aminopolyphosphonates (AAPs) are commonly used industrial complexones of metal ions, which upon the action of biotic and abiotic factors undergo a breakdown and release their substructures. Despite the low toxicity of AAPs towards vertebrates, products of their transformations, especially those that contain phosphorus and nitrogen, can affect algal communities. To verify whether such chemical entities are present in water ecosystems, much effort has been made in developing fast, inexpensive, and reliable methods for analyzing phosphonates. However, unfortunately, the methods described thus far require time-consuming sample pretreatment and offer relatively high values of the limit of detection (LOD). The aim of this study was to develop an analytical approach to study the environmental fate of AAPs. Four phosphonic acids, N,N-bis(phosphonomethyl)glycine (GBMP), aminotris(methylenephosphonic) acid (ATMP), hexamethylenediamine-N,N,N′,N′-tetrakis(methylphosphonic) acid (HDTMP), and diethylenetriamine penta(methylenephosphonic) acid (DTPMP) were selected and examined in a water matrix. In addition, the susceptibility of these compounds to biotransformations was tested in colonies of five freshwater cyanobacteria—microorganisms responsible for the so-called blooms in the water. Our efforts to track the AAP decomposition were based on derivatization of N-alkyl moieties with p-toluenesulfonyl chloride (tosylation) followed by chromatographic (HPLC-UV) separation of derivatives. This approach allowed us to determine seven products of the breakdown of popular phosphonate chelators, in nanomolar concentrations and in one step. It should be noted that the LOD of four of those products, aminemethylphosphonic acid (AMPA), N-phosphomethyl glycine (NPMG), N-(methyl)aminemethanephosphonic acid (MAMPA), and N-(methyl) glycine (SAR), was set below the concentration of 50 nM. Among those substances, N-(methylamino)methanephosphonic acid (MAMPA) was identified for the first time as the product of decomposition of the examined aminopolyphosphonates.

Development and validation of an LC\u2013MS/MS method for the determination of biogenic amines in wines and beers

Biogenic amines are group of organic, basic, nitrogenous compounds that naturally occur in plant, microorganism, and animal organisms. Biogenic amines are mainly produced through decarboxylation of amino acids. They are formed during manufacturing of some kind of food and beverages such as cheese, wine, or beer. Histamine, cadaverine, agmatine, tyramine, putrescine, and β-phenylethylamine are the most common biogenic amines found in wines and beers. This group of compounds can be toxic at high concentrations; therefore, their control is very important. Analysis of biogenic amines in alcoholic drinks (beers and wines) was carried out by HPLC–MS/MS after their derivatization with p-toluenesulfonyl chloride (tosyl chloride). The developed method has been applied for analysis of seventeen biogenic amines in twenty-eight samples of lager beers and in twelve samples of different homemade wines (white grape, red grape, strawberry, chokeberry, black currant, plum, apple, raspberry, and quince). The developed method is sensitive and repeatable for majority of the analytes. It is versatile and can be used for the determination of biogenic amines in various alcoholic beverages.Graphical abstract

Reaction of 5-Hydroxymethyl-6-Methyluracil with Toluenesulfonyl Chloride or Methanesulfonyl Chloride and Tertiary Amines

Quaternary ammonium salts were formed or the starting uracil was recovered after the reaction of 5-hydroxymethyl-6-methyluracil with toluenesulfonyl chloride or methanesulfonyl chloride and tertiary amines.

Application of sulfonyl chlorides and chiral amines in the efficient synthesis of nonracemic sulfinamides

A simple protocol that allows the preparation of separable epimeric sulfinamides from chiral amines and sulfonyl chlorides reduced in situ with triphenylphosphine in the presence of KOH is described. Using this method, tosyl chloride and nosyl chloride were successfully reacted with α-substituted primary amines to give five diastereomeric pairs, in certain cases accompanied by a small amount of the corresponding sulfonamide. Enantiopure products were isolated by column chromatography. The obtained enantiomerically pure sulfinamides were tested as organocatalysts in the asymmetric epoxide ring opening.

Tetrakis [N-(2-pyridyl) sulfonamide] di palladium: synthesize, X-ray diffraction, antibacterial properties and as a novel binuclear Pd-complex for coupling reactions

The N-(2-pyridyl) 4-toluene sulfonamide as a free ligand (PTS) was prepared from the reaction of 2-amino pyridine and 4-toluenesulfonyl chloride in the presence of potassium hydroxide solution 1 M as a base and THF was used as a solvent. The complex tetrakis [N-(2-pyridyl) sulfonamide] di palladium (1) (Pd2L4) was also prepared from the reaction of PdCl2(CH3CN)2 using (PTS) in the presence of NaOH 0.5 M and its application in Heck and Suzuki reactions. This complex consists of a binuclear unit consisting of four ligands linked to two palladium atoms via the nitrogen of pyridines ring and the nitrogen of sulfonamides. These compounds were confirmed by FT-IR and 1H NMR spectroscopy. Moreover, the structure of the complex was studied by single-crystal X-ray diffraction method. The green crystal of Pd2L4 [L = N-(2-pyridyl) sulfonamide](1) was found to crystallize in the monoclinic space group C2/c with a = 18.2013(19), b = 19.7544(16), c = 17.2898(19) A, β = 120.179(8) °; V = 5374.0(9) A3; Z = 4; the final R 1 = 0.0894, wR 2 = 0.1754 (or 5867 observed reflections and 318 variables). The Pd–Pd distance is 2.567(2) A. In addition, PTS and Pd2L4 presented different antibacterial behaviors. The free ligand was active against Staphylococcus aureus and Escherichia coli, but the complex was inactive against them.

Ligand versus Complex: C-F and C-H Bond Activation of Polyfluoroaromatics at a Cyclic (Alkyl)(Amino)Carbene.

C-F and C-H bond activation reactions of polyfluoroaromatics at the cyclic (alkyl)(amino)carbene (cAAC) cAACmethyl (1) are reported. Studies on the C-F bond activation using the cAAC-stabilized nickel(0) complex [Ni(cAACmethyl )2 ] (2) have shown that 2 does not react with fluorinated arenes. However, these investigations led to the observation of C-F bond cleavage of perfluorinated arenes by the carbene ligand cAACmethyl (1) itself. The reaction of 1 with C6 F6 , C6 F5 -C6 F5 , C6 F5 -CF3 , and C5 F5 N afforded the insertion products of cAAC into one of the C-F bonds of the substrate, that is, the C-F bond activation products (cAACmethyl )F(Arf ) (Arf =C6 F5 4 a, C6 F4 -C6 F5 4 b, C6 F4 -CF3 4 c, C5 F4 N 4 d). These products decompose readily upon heating to 80 °C within a few hours in solution with formation of ionic iminium salts [(cAACmethyl )(Arf )][X] 6 a-d or neutral alkenyl perfluoroaryl imine compounds 7 a-d. The compounds (cAACmethyl )F(Arf ) 4 a-d readily transfer fluoride, which has been exemplified by the fluoride transfer of all compounds using BF3 etherate as fluoride acceptor. Fluoride transfer has also been achieved starting from (cAACmethyl )F(C6 F4 -CF3 ) (4 c) or (cAACmethyl )F(C5 F4 N) (4 d) to other selected substrates such as trimethylchlorosilane, benzoyl chloride and tosyl chloride. Instead of C-F bond activation, insertion of the cAAC into the C-H bond was observed if 1 was treated with the partially fluorinated arenes C6 F5 H, 1,2,4,5-C6 F4 H2 , 1,3,5-C6 F3 H3 , and 1,3-C6 F2 H4 . The compounds (cAACmethyl )H(Arf ) (Arf =C6 F5 12 e, 2,3,5,6-C6 F4 H 12 f, 2,4,6-C6 F3 H2 12 g and 2,6-C6 F2 H3 12 h) have been isolated in good yields and have been characterized including X-ray analysis. Fluorobenzene C6 FH5 (pKa ≈37), the least C-H acidic fluoroarene used in this study, does not react. In order to investigate the scope and limitations of this type of cAAC C-H bond activation reaction, cAACmethyl (1) was treated with several other reagents of different C-H acidity such as imidazolium salts, imidazoles, esters, and trimethylphosphine. These investigations led to the isolation and characterization of the compounds [(cAACmethyl )H(R2 ImMe2 )]X (13 a,b), (cAACmethyl )H(ImR2 ) (14 a-c), (cAACmethyl )H(CH(COOCH3 )2 ) (15 b) and (cAACmethyl )H(CH2 -PMe2 ) (16). Deprotonation of [(cAACmethyl )H(Me2 ImMe2 )][BF4 ] (13 a) at the cAAC carbon atom using KHMDS as a base led to isolation and structural characterization of the cAACmethyl -NHC heterodimer (17).

Octahedral iridium complex catalyzed α-chlorination of 2-acyl imidazoles with tosyl chloride

An efficient and catalytic α-chlorination of 2-acyl imidazoles with readily available tosyl chloride catalyzed by an octahedral iridium complex under mild condition was reported. A range of 2-acyl imidazoles were converted to their corresponding α-chlorination products in good to excellent yields.

Synthesis and antitumor activity evaluation of some novel pyrazolotriazine derivatives

ABSTRACT6-Aminopyrazolo[1,2-a][1,2,4]triazine-4,8-dione derivative 3 was obtained upon the reaction of the acid hydrazide derivative 2a with ethyl cyanoacetate. The reactions of 3 with several electrophiles such as aldehydes, isatin, acetic anhydride, phenyl isocyanate, benzoyl isothiocyanate, and p-toluenesulfonyl chloride were studied. The structures of the newly synthesized compounds were established on the basis of IR, 1H NMR, mass spectra, and elemental analyses. The antitumor activities of some selective compounds were examined against two cell lines as liver carcinoma cell line (HEPG-2) and human breast cancer cell line (MCF7).