Tosyl Chloride Research Articles

Synthesis of some novel 6′-(4-chlorophenyl)-3,4′-bipyridine-3′-carbonitriles: assessment of their antimicrobial and cytotoxic activity

Abstract A series of novel substituted 6′-(4-chlorophenyl)-3,4′-bipyridine-3′-carbonitriles with incorporated pyrazole and/or triazole moieties have been synthesized using 2-(6′-(4-chlorophenyl)-3′-cyano-3,4′-bipyridin-2′-yloxy)acetohydrazide (3) as starting material. Also, the key intermediate 3 reacted with aromatic aldehydes and tosyl chloride to give the corresponding Schiff bases and tosyl hydrazide derivatives, respectively. The antimicrobial of these newly synthesized compounds was evaluated against Bacillus subtilis as Gram-positive bacteria and Trichoderma viride as a fungus; some of these compounds such as 5, 6, 7, 8, 10, 12, and 14 showed excellent activities as antimicrobial agents. Moreover, the cytotoxic activity of the most active compounds was assessed in vitro against human tumor liver cancer cell line (HEPG2); compounds 8, 10, 13a, and 14 showed potent activities relative to Doxorubicin which was used as a reference standard drug in this study.

Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in folate receptor-positive cancer cells by decorating with folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate

Folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS–FOL) decorated methotrexate (MTX)-conjugated nanoparticles were developed for targeted delivery of MTX to folate receptor-expressed tumor cells. The synthesis of TPGS–FOL followed 3-step process. Firstly, the terminal hydroxyl group of TPGS was converted to sulfonyl chloride using mesyl chloride in comparison with nosyl and tosyl chlorides. The highest conversion efficiency and yield were obtained by mesyl chloride due to the formation of higher reactive intermediate in a presence of triethylamine. Secondly, the substitution of sulfonyl group by sodium azide produced considerably high yield with conversion efficiency of over 90%. Lastly, the coupling reaction of azido-substituted TPGS and propargyl folamide by click reaction resulted in 96% conjugation efficiency without polymer degradation. To fabricate the folate receptor-targeted nanoparticles, 10 and 20%mol MTX-conjugated PEGylated poly(ϵ-caprolactone) nanoparticles were decorated with TPGS–FOL. The size and size distribution of MTX-conjugated nanoparticles relatively increased with %MTX. The MTX release from the nanoparticles was accelerated in acidic medium with an increase of %MTX but retarded in physiological pH medium. The decoration of TPGS–FOL onto the nanoparticles slightly enlarged the size and size distribution of the nanoparticles; however, it did not affect the surface charge. The cytotoxicity and cellular uptake of MCF-7 cells demonstrated that 10% MTX-conjugated nanoparticles and FOL-decorated nanoparticles possessed higher toxicity and uptake efficiency than 20% MTX-conjugated nanoparticles and undecorated nanoparticles, respectively. The results indicated that FOL-10% MTX-conjugated nanoparticles exhibited potential targeted delivery of MTX to folate receptor-expressed cancer cells.

4‐Toluenesulfonamide as a Building Block for Synthesis of Novel Triazepines, Pyrimidines, and Azoles

N‐{(E)‐(dimethylamino)methylidenearbamothioyl}‐4‐toluenesulfonamide (2) was obtained by reaction of N‐carbamothioyl‐4‐toluenesulfonamide (1) with dimethylformamide dimethylacetal or alternatively by the reaction of 1‐(dimethylamino)methylidenethiourea with tosyl chloride. Compound 2 was reacted with substituted anilines to yield anilinomethylidine derivatives 3a, 3b, 3c, 3d, 3e, 3f, 3g. Treatment of 3a, 3b, 3c, 3d, 3e, 3f, 3g with phenacyl bromide gave triazepines 4a, 4b, 4c, 4d, 4e, 4f, 4g and imidazoles 5a, 5b, 5c, 5d, 5e, 5f, 5g. Esterification of compound 3e afforded ester derivative 6, which was subjected to react with hydrazine to yield hydrazide derivative 7. Oxadiazole 8 was obtained by reaction of 7 with CS2/KOH. Compound 3e was treated with o‐aminophenol or o‐aminothiophenol to give benzazoles 9a, 9b. N‐(Diaminomethylidene)‐4‐toluenesulfonamide (10) reacted with enaminones to yield pyrimidines 11, 12, 13, respectively. The structures of the compounds were elucidated by elemental and spectral analyses. Some selected compounds were screened for their in vitro antifungal activity. In general, the newly synthesized compounds showed good antifungal activity.

P-Toluenesulfonyl Azide

p-Toluenesulfonyl azide (TsN3, CAS: 941-55-9) can be prepared in good yield from the reaction of p-toluenesulfonyl chloride (TsCl) and sodium azide (NaN3) (Scheme [1]).[1] TsN3 is a colorless oil with a melting point of 21–22 ºC and boiling point of 110–115 °C at 0.001mmHg.[2]

Reactivity of 1,2,3-triazoles towards sulfonyl chlorides. A novel approach to 1- and 2-sulfonyl-4-azolyl-1,2,3-triazoles

The reactions of N-unsubstituted triazoles with sulfonyl chlorides afforded mixtures of regioisomeric 1- and 2-sulfonyl-1,2,3-triazoles. In some cases, pure regioisomers were obtained by crystallization of mixtures of isomers. 1,2,3-Triazoles bearing thiadiazole, isoxazole and benzene rings react with mesyl chloride and tosyl chloride to form mainly 1-substituted 1,2,3-triazoles. Conversely, reactions of triazoles 1a,b and oxadiazolyl triazole 1h with more bulky 1-(2,4-dimethylphenyl)sulfonyl chloride affords mainly 2-substitued products. Oxadiazole 1b furnishes an equal mixture of the regioisomeric products 3 and 4 as a result of the reaction with mesyl and tosyl chlorides. Higher temperatures increase the ratio of isomers in favor of the 2-substituted triazole. The ratio of isomers depends on both the nature of the azolyl ring and on the size of the substituent in the sulfonyl chloride. Based on the results of experimental and theoretical data, 1-substituted and 2-substituted 1,2,3-triazoles can be considered as the kinetic and thermodynamic products.

Triethylamine–Mesyl Chloride/Thionyl Chloride: A Reagent for Hydrodebromination of Diquinane-Based α-Bromo-γ-Lactones

A selective debromination of tetracyclic dibrominated bis-γ-lactones in the presence of triethylamine and mesyl chloride is reported. Both mesyl chloride and triethylamine are essential for the debromination process. The reduction is proposed to proceed through halophilic substitution of electrophilic bromine. The source of the halophile in this reaction is believed to be triethyl(mesyl)ammonium chloride. The nonoccurrence of debromination in dibromo bis-γ-lactones with tosyl chloride and triethylamine as reagents suggests that the formation of a source of well-dissociated chloride ions during the reaction is necessary. Furthermore, selective debromination of dibrominated bis-γ-lactones was also achieved by using pyridine–thionyl chloride as a reagent. Alternatively, potassium chloride–[18-crown-6] was demonstrated to be a suitable source of chloride ion for the reduction of bromolactones.

Ionic Liquids: Additives for Manipulating the Nucleophilicity

Kinetic investigations of the SN2 reaction at the sulfur atom of p-toluenesulfonyl chloride with sodium azide in dried methanol in the presence of varying amounts of room temperature ionic liquids (RTILs), 1-butyl-3-methylimidazolium acetate ([C4C1im][CH3COO]), 1-butyl-3-methylimidazolium chloride ([C4C1im]Cl) and 1-butyl-3-methylimidazolium hexafluorophosphate ([C4C1im][PF6]), were carried out in order to explore and understand the impact of these additives on the rate of such reactions. The observed results indicate that the rate constant of the reaction increase appreciably with increases in the concentration of RTILs in RTIL–methanol binary solvent systems. The results were analyzed in light of a Kamlet–Taft model system, which established that the observed impact of RTILs can be attributed to the cumulative effects of increase in the β value (hydrogen bonding acceptor ability) which is expected to enhance the reactivity of p-toluenesulfonyl chloride as well as the nucleophilicity of the azide ion and decrease in the π* value (solvent dipolarity/polarizability) which is expected to enhance the reactivity of the azide ion. Of the three ionic liquids used in the presented studies, [C4C1im][CH3COO] was observed to be more effective in accelerating the rate constant; this we attribute to its comparatively stronger ability to increase the β value and decrease the π* value in the mixed solvent system.

ChemInform Abstract: Aqueous MW Eco‐Friendly Protocol for Amino Group Protection

Abstractwith Boc2O, Fmoc‐Cl, Ac‐Cl and Tos‐Cl

Chemistry of cobalt bis(1,2-dicarbollide) ion; the synthesis of carbon substituted alkylamino derivatives from hydroxyalkyl derivatives via methylsulfonyl or p-toluenesulfonyl esters

In this paper we report the synthetic procedures providing the C-substitution of the cobalt bis(dicarbollide) sandwich anion [(1,2-C2B9H11)-3,3′-Co]− with primary, secondary and tertiary alkylamine groups of different length of the aliphatic spacer attached to the carbon C(1) or C(1) and C(1′) cage positions. Reaction pathways leading to these compounds proceed via synthesis of mono [(1-X-O-(CH2)n-1,2-C2B9H10) (1′,2′-C2B9H11)-3,3′-Co]Me4N (where n = 1–3 and X = –SO2CH3 or –SO2(-C6H4-4-CH3) esters (2a–f) and diesters [(1,1′-X-O-(CH2)n-1,2-C2B9H10)2-3,3′-Co]Me4N (3a-c) (n = 1 and 2). These compounds are readily accessible in good to excellent yields by reactions of trimethylammonium salts of alkylhydroxy derivatives (1a–e) of the parent ion with methylsulfonyl or p-toluenesulfonyl chloride. The esterifications proceeded with lower conversions only for methylene hydroxy derivatives. The series of primary amines of general formulation [(1-1R2RN-(CH2)n-1,2-C2B9H10) (1′,2′-C2B9H11)-3,3′-Co]− (where n = 1–3 and 1R = 2R = H) (4a–c), along with the diamine [(1,1′–NH2–C2H5)2-1,2-C2B9H10)2-3,3′-Co]− (5), and compounds comprising secondary and tertiary amino functions (1R = nBu, 2R = H, 1R = Bn, 2R = H and 1R = 2R = Et) (6a–h) were prepared in generally good yields by reactions of the esters with ammonia and primary or secondary amines. However, the reactions of the bis(methylene methylsulfonyl) diester resulted in almost quantitative in situ dialkylation of the amine group leading to the formation of a triatomic bridge between two carbon atoms of the cage [(1,1′-μ-(-CH2NRCH2-) (1,2-C2B9H10)2-3,3′-Co]− (R = H or Bu) (7a, b). We believe this observation contributes further to rich evidence on the preference of bridge substitutions at the cobalt bis(dicarbollide) cage.

Fluorous Analogue of Chloramine-T: Preparation, X-ray Structure Determination, and Use as an Oxidant for Radioiodination and s-Tetrazine Synthesis.

A fluorous oxidant that can be used to introduce radioiodine into small molecules and proteins and generate iodinated tetrazines for bioorthogonal chemistry has been developed. The oxidant was prepared in 87% overall yield by combining a fluorous amine with tosyl chloride, followed by chlorination using aqueous sodium hypochlorite. A crystal structure of the oxidant, which is a fluorous analogue of chloramine-T, was obtained. The compound was shown to be stable for 7 days in EtOH and for longer than three months as a solid. The oxidant was effective at promoting the labeling of arylstannanes using [(125)I]NaI, where products were isolated in high specific activity in yields ranging from 46% to 86%. Similarly, iodinated biologically active proteins (e.g., thrombin) were successfully produced, as well as a radioiodinated tetrazine, through a concomitant oxidation-halodemetalation reaction. Because of its fluorous nature, unreacted oxidant and associated reaction byproducts can be removed quantitatively from reaction mixtures by passing solutions through fluorous solid phase extraction cartridges. This feature enables rapid and facile purification, which is critical when working with radionuclides and is similarly beneficial for general synthetic applications.

ChemInform Abstract: Synthesis of Furoxan Derivatives: DABCO‐Mediated Cascade Sulfonylation/Cyclization Reaction of α‐Nitro‐Ketoximes.

AbstractThe cascade reaction proceeds best with tosyl chloride as mediator.

Cervical Spondylotic Myelopathy: Does Surgical Approach Influence Postoperative Sagittal Alignment and Outcomes?

Introduction The effect of surgical approach on outcomes for cervical spondylotic myelopathy (CSM) is controversial. Fehlings et al showed that patients treated with anterior techniques tend to be younger, less impaired, and had more focal pathology. In this study, we compared outcomes of an anterior approach group (AAG) versus a posterior approach group (PAG) with a focus on the effect of sagittal alignment. Patients and Methods Post hoc analysis of a prospective, multicenter database of patients with CSM. A total of 117 patients met inclusion criteria, were nonrandomized to an AAG ( n = 51) or PAG ( n = 62), with postoperative static lateral radiographs, Nurick assessment, and health-related quality of life outcomes at 6 months and/or 1 year. The AAG underwent anterior decompression and fusion, PAG either laminoplasty or laminectomy with fusion. Sagittal regional and focal parameters were compared by multivariate regression. Results At baseline, the groups showed significant age difference (AAG 51 years, PAG 62 years, p < 0.001), rheumatological comorbidity (AAG 3%, PAG 19%, p = 0.011), and modified Japanese orthopaedic association (mJOA). The PAG had significantly more regional malalignment at baseline, but there were no focal alignment differences between the two. Surgical features were significantly different for greater than three levels treated (AAG 27%, PAG 97%, p < 0.001) and blood loss (AAG 152 mL, PAG 380 mL, p < 0.001). After surgery, both AAG and PAG improved significantly in mJOA and Nurick grade, however, there was no statistically significant difference in mJOA postoperatively. AAG had a significant decrease in SVA whereas the PAG had a significant increase in SVA. There were no relevant postoperative focal alignment differences. Conclusion The PAG had older patients with more disability. Even when age, baseline mJOA, and regional parameters were controlled, the PAG cohort still correlated with worse CGH_C7 SVA and TS–CL. It is interesting to note that the PAG had a lower mJOA than the AAG at baseline, they both improved and were not significantly different postoperatively. This suggests that both techniques relieve symptomatic disease, but patients in the posterior group may continue to progress in sagittal misalignment.

Reliability Assessment of a Novel Cervical Deformity Classification System

Introduction Despite the complexity of cervical deformity and the significant impact on patient quality of life, there exists no comprehensive classification. An initial novel classification system has been recently designed with a deformity descriptor and five modifiers that incorporate sagittal regional and global spino-pelvic alignment and neurological status. Our objective was to characterize the intra- and interobserver reliability of this classification. Material and Methods A series of 10 cervical deformity cases, broadly representative of the classification system, were selected and sufficient radiographic and clinical history to enable classification were assembled. A panel of deformity surgeons was queried to classify each case twice, with a minimum of 1 intervening week. Inter- and intrarater reliability measures were based on calculations of Fleiss kappa coefficient values. Results A total of 20 spine deformity surgeons participated in this study. Interrater reliability (Fleiss kappa coefficients) for the deformity descriptor rounds 1 and 2 were 0.489 and 0.280, respectively, and mean intrarater reliability was 0.584. For the modifiers, including the SRS–Schwab components, the interrater (round 1/round 2) and intrarater reliabilities (Fleiss kappa coefficients) were as follows: C2-C7 SVA (0.338/0.412, 0.584), horizontal gaze (0.779/0.430, 0.768), TS–CL (0.721/0.567, 0.720), myelopathy (0.602/0.477, 0.746), curve type (0.590/0.433, 0.564), PI–LL (0.554/0.386, 0.826), PT (0.714/0.627, 0.633), and C7–S1 SVA (0.071/0.064, 0.233), respectively. The parameter with the poorest reliability was the C7–S1 SVA, which may have resulted from differences in interpretation of positive and negative measurements. Conclusion The proposed classification provides a mechanism to assess cervical deformity within the framework of global spino-pelvic malalignment and clinically relevant parameters. The intra- and interobserver reliabilities suggest moderate agreement and serve as the basis for subsequent improvement and study of the proposed classification.

Risk of Development of New Onset Postoperative Cervical Deformity in Thoracolumbar Adult Spinal Deformity and Effect on Clinical Outcomes at 2-Year Follow-Up

Introduction A high prevalence of residual cervical deformity (CD) has been identified following surgical treatment of adult spinal deformity (ASD). Development of the new onset CD is less understood and its clinical impact unclear. This study quantifies the incidence of new onset CD after ASD surgery, identifies predictors of development, and determines the impact outcomes. Materials and Methods Retrospective review of a prospective multicenter database yielded 215 patients (pts) with complete 2-year follow-up and full length X-rays including the cervical spine. CD was defined by T1S–CL > 20 degrees, C2C7 SVA > 40 mm, or C2C7 kyphosis > 10 degrees. Univariate analysis was performed using t tests or tests of proportion. Multivariate logistic regression was used to determine independent predictors of new CD. The impact of CD on health-related quality of life (HRQL) and satisfaction was measured using repeated measures mixed models or logistic regression as appropriate, accounting for potential confounders. Results Of the 215, 88 pts with ASD did not have CD at baseline and 42 of them (47.7%) developed CD at 2 years' postoperatively. Univariate analysis revealed that pts who developed new CD in the postoperative period had a higher incidence of diabetes (14.29 vs. 2.17%, p = 0.036) increased preoperative C2C7 SVA ( p = 0.04) and C2 slope ( p = 0.038) and smaller diameter rods used at surgery ( p = 0.0328). Independent predictors of new CD at 2 years included diabetes (OR, 10.49; p = 0.046) and increased preoperative TS–CL (OR, 1.08/deg, p = 0.027). Ending instrumentation below T4 was a negative predictor of CD (OR, 0.31; p = 0.019). Pts with and without CD experienced improvements in 2-year SF-36 ( p = 0.0001), ODI ( p = 0.0001), and SRS ( p = 0.0001). Rates and overall improvement were similar. CD was not associated with decreased satisfaction ( p = 0.28). Conclusion Overall, 47.7% of pts without preoperative CD develop new postoperative CD after ASD surgery. Independent predictors of new onset CD at 2 years include diabetes, higher preoperative TS–CL, and ending instrumentation above T4. Significant improvements in HRQL scores occurred despite the development of postoperative CD.

Synthesis of 4-(Dimethylamino)quinazoline via Direct Amination of Quinazolin-4(3H)-one Using N,N-Dimethylformamide as a Nitrogen Source at Room Temperature

An efficient direct amination of quinazolin-4(3<i>H</i>)-ones using <i>N</i>,<i>N</i>-dimethylformamide as a nitrogen source is described that affords the corresponding 4-(dimethylamino)quinazolines in high yields. This transformation proceeds through efficient 4-toluenesulfonyl chloride mediated C–OH bond activation at room temperature.

Cellulose ether derivatives: a new platform for prodrug formation of fluoroquinolone antibiotics

Novel macromolecular prodrugs of the second-generation fluoroquinolone antibiotic ofloxacin were fabricated based on the hydrophilic biopolymers hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). HPC- and HEC-ofloxacin conjugates were synthesized by activation of ofloxacin with p-toluenesulfonyl chloride under homogeneous reaction conditions at 70 °C in a one-pot synthesis. Structures of HPC- and HEC-ofloxacin conjugates were confirmed by spectroscopic and chromatographic techniques. Covalent drug loading was determined by UV/Vis spectrophotometry after hydrolysis of the conjugates. The results indicated significant covalent ofloxacin-loading (degree of substitution, 0.53–0.71 and 0.38–0.47) on HPC and HEC, respectively. All prodrugs were soluble in organic and aqueous solvents. Transmission electron microscopic analysis indicated formation of nanoparticles in the size range 100–250 nm and 150–210 nm for HPC- and HEC-ofloxacin conjugates, respectively. Ofloxacin, HPC-ofloxacin conjugate, and HEC-ofloxacin conjugate were orally administered to healthy male albino rabbits to determine pharmacokinetic parameters. Both HPC- and HEC-ofloxacin conjugates showed sustained release, with an increase in ofloxacin (control 1–3) half-life from 2.59, 4.56 and 4.63 h to 18.07 and 20.71 h, respectively. The relative AUC values clearly indicate ofloxacin oral bioavailability from conjugates that is enhanced, 1.6–1.8 and 2.1–2.3 times that of control.

N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes I and II

Sulfonamides represent a significant class of biologically active compounds that inhibit carbonic anhydrase (CA, EC.: 4.2.1.1) isoenzymes involved in different pathological and physiological events. Sulfonamide CA inhibitors are used therapeutically as diuretic, antiglaucoma, antiobesity and anticancer agents. A series of new sulfonamides were synthesized using imides and tosyl chloride as starting materials. These N-acylsulfonamides efficiently inhibited the cytosolic human carbonic anhydrase isoenzymes I, and II (hCA I, and II), with nanomolar range inhibition constants ranging between 36.4±6.0–254.6±18.0 and 58.3±0.6–273.3±2.5nM, respectively.

Synthesis and Characterisation of Phosphazene Derivatives Containing Dioxybiphenyl and 4-Sulfanylquinazoline Groups

2,2-Dichloro-4,4,6,6-bis[spiro(2′,2″-dioxy-1′,1″-biphenylyl)]cyclotriphosphazene was synthesised from the reaction of hexachlorocyclotriphosphazene with biphenyl-2,2′-diol. 2,2-Bis(4-formylphenoxy)-4,4,6,6-bis[spiro(2′,2″-dioxy-1′,1″-biphenylyl)]cyclotriphosphazene was obtained from the reaction of 2,2-dichloro-4,4,6,6-bis[spiro(2′,2″-dioxy-1′,1″-biphenylyl)] cyclotriphosphazene with 4-hydroxybenzaldehyde. 2,2-Bis[4-(4-quinazolinone)phenoxy]-4,4,6,6-bis[spiro(2′,2″-dioxy-1′,1″-biphenylyl)]cyclotriphosphazene was synthesised from the reaction of 2,2-bis(4-formylphenoxy)-4,4,6,6-bis[spiro(2′,2″-dioxy-1′,1″-biphenylyl)]cyclotriphosphazene with anthranilamide in N,N-dimethylformamide. The novel cyclophosphazene derivatives were synthesised under mild conditions from the reaction of 2,2-bis[4-(4-quinazolinone)phenoxy]-4,4,6,6-bis[spiro(2′,2″-dioxy-1′,1″-biphenylyl)]cyclotriphosphazene with 4-chlorobenzenemethanethiol, p-thiocresol, 4-aminothiophenol, and 4-chlorothiophenol in the presence of p-toluenesulfonyl chloride via C-OH bond activation under mild conditions. All products were generally obtained in high yields. Their structures were characterised by HRMS, IR and 1H, 13C spectroscopy.

Chiral supramolecular nanoparticles: The study of chiral surface modification of silver nanoparticles by cysteine and its derivatives

Many studies dealing with modified nanoparticles are based on the assumption that organic molecules form single-layer structure on their surface. In this work, we suggest a novel approach to study the important phenomenon of supramolecular chirality at metal nanoparticle surfaces. Self-assembly layers of several ligands, namely l-cysteine, l-penicillamine and α-methyl-l-cysteine, on different silver nanoparticles were studied by means of absorption and electronic circular dichroism spectroscopy in UV–vis range and surface enhanced Raman scattering spectroscopy. The amount of ligands bonded to the surface of nanoparticles was quantified by absorption spectroscopy. Quantification was performed indirectly by measuring concentration of free ligands in solution after incubation with absorption labels 4-toluenesulfonyl chloride or 1-fluoro-2,4-dinitrobenzene. Data were obtained for ligands at concentration levels from 10−6 to 10−3 mol L−1. The results showed the significantly lower adsorbed molecules of methyl derivatives of cysteine than for cysteine themselves. This fact could explain the unexpected behavior of silver nanoparticles that provide ECD bands in the presence of cysteine and not in the presence of its derivatives.

3-(Dimethylamino)-1-propylamine: a cheap and versatile reagent for removal of byproducts in carbohydrate chemistry.

Inexpensive 3-(dimethylamino)-1-propylamine (DMAPA) was found to be effective in anomeric deacylation reactions giving 1-O deprotected sugars in high yield as precursors for the formation of imidate glycosyl donors. DMAPA was also found to be useful for removing excess reagents such as benzoyl chloride, tosyl chloride, and 2,2,2-trifluoro-N-phenylacetimidoyl chloride. The deacylation reaction could be conducted in moist THF and did not require chromatographic purification since an acidic wash was sufficient to remove excess reagent and the formed byproduct.