Fluoro-2,l,3-benzoxadiazole

4-Fluoro-2,l,3-benzoxadiazole 174, by reaction with chlorosulfonic acid (eight equivalents) in boiling chloroform for 2 hours afforded the 7-sulfonyl chloride 175, 78% (Equation 45).  

By treatment with ammonia, the sulfonyl chloride 175 was converted into 7-(aminosulfonyl)-4-fluoro-2,l,3-benzoxadiazole 176, which is used as a new fluorogenic reagent for thiols in HPLC. ° 

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Figure 14 Representative fluorescence derivatization reagents used for PO-CL detection. DNS-CI, dansyl chloride DBD-F, 4-(A,A-dimethylaminosulphonyl-7-fluoro-2,l, 3-benzoxadiazole NDA, naphthalene-2,3-dicarboxaldehyde DNS-H, dansyl hydrazine DBD-H, 4-(iV,iV-dimethylaminosulphonyl-7-hydrazino-2,l,3-benzoxadiazole).

In different types of condensed polycyclic systems, mostly nitrogen-containing systems, the elimination of attached fluorine by thiols has proved a valuable synthetic tool for the introduction of sulfur moieties. In 4-(aminosulfonyI)-7-fluoro-2,l,3-benzoxadiazole(l) the reactivity of the fluorine towards sulfur nucleophiles is sufficiently high that it can be used analytically for the detection of thiols14 (c.g., in peptides). The reaction proceeds almost quantitatively. 

Fluoro-l, 3-benzothiazoIe reacts with sodium methanethiolate to give 2-(mclhylsulfanyl)-1,3-benzothiazole under very gentle conditions,17 as given for 4-(aminosuIfonyl)-7-fluoro-2,l, 3-benzoxadiazole (vide supra). 

Sample preparation Sample + 400 pL 5 mM DBD-PZ -i- 70 mM diethylphosphorotyan-idate in MeCN, react for 6 h, inject a 1 xL aliquot. (DBD-PZ prepared from 123 mg 4-(N, N-dimethylaminosulfonyl)-7-fluoro-2,l,3-benzoxadiazole in 20 mL MeCN added dropwise to 129 mg piperazine in 20 mL Me(DN at room temperature, stir for 30 min, evaporate under reduced pressure, dissolve residue in 50 mL 5% HCl, extract three times with 20 mL ethyl acetate, discard ethyl acetate extracts, adjust pH of aqueous solution to 13-14 with 5% NaOH, extract five times with 50 mL ethyl acetate, combine extracts, wash with 20 mL water, dry over anhydrous sodium sulfate, evaporate under vacuum to give DBD-PZ as orange crystals, mp 121-2°.)... 

Uzu, S. Imai, K. Nakashima, K. Akiyama, S. Use of 4-(N,N-dimethylaminosulphonyl)-7-fluoro-2,l,3-benzoxadiazole as a labelling reagent for peroxyoxalate chemiluminescence detection and its application to the determination of the p-blocker metoprolol in serum by high-performance liquid chromatography. Analyst, 1991, 116, 1353-1357... 

Halogenobenzofurazan, e.g., 7-fluoro-2,l,3-ben-zoxadiazole-4-sulfonate (SBD-F), 4-(aminosulfonyl)-7-fluoro-2,l,3-benzoxadiazole (ABD-F), and 4-(N, N-dimethylaminosulfonyl)-7-fluoro-2,l,3-benzoxadia-zole (DBD-F), having reactive fluorine groups are synthesized. The application studies of these reagents on the determination of cysteine, GSH, and other thiol compounds by LC-FL detection have been reported with detection limits at the subpicomole level. 

Sample preparation Mix 100 jaL plasma, 500 p,L water, 560 p.L 100 mM pH 9.3 borate buffer, 10 p.L 100 p,M IS in water, and 420 p,L 762 (xg/mL DBD-F in MeCN, let stand at room temperature for 30 min (to derivatize thiol in metabolites and IS), evaporate the MeCN under reduced pressure, add 2 mL ethyl acetate to the remaining solution, mix vigorously, centrifuge at 3000 rpm for 2 min. Wash the aqueous layer three more times with ethyl acetate. Adjust the pH of the aqueous layer to 1-2 with ca. 1.5 mL 100 mM HCl, extract three times with 2 mL portions of ethyl acetate. Combine the organic layers and evaporate them to dr5Uiess under reduced pressure, reconstitute the residue with 100 xL MeCN. Remove a 50 p.L aliquot, add 5 p.L DPP A, add 45 xL 17.8 mg/mLi -(—)-DBD-Apy in MeCN, let stand at room temperature for 2 h (to derivatize carboxylic acid), inject an aliquot. (DBD-F is 4-()V,IV-dimethylaminosulfonyl)-7-fluoro-2,l,3-benzoxadiazole. i -(—)-DBD-Apy is i -(—)-4-( V,IV-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-l-yl)-2,l,3-benzoxadiazole. DPPA is diphenyl phosphoryl azide. They are all available from Tokyo Kasei or TCI America (www.tciamerica.com).)... 

The most known designer drugs are carphedone 4-chloro-2,5-dimethoxyphenethylamine (2C-C) i 5-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yM-methylpiperazine-l-carboxylate (zopiclone or Z-drug) 4-(N,N-dimethylamino sulfonyl)-7-fluoro-2,l,3-benzoxadiazole (DBD-F) dimethyltryptamine (DMTA) diphenydramine 4-ethyl-2,5-dimethoxyphenethylamine (2C-E) 4-ethylthio-2,5-dimethoxyphenethylamine (2C-T-2) 4-fluoroamphetamine (4-FMP) indan-2-amine 4-iodo-2,5-dimethoxyphenethylamine (2C-I) 1 -(4-iodo-2,5-dimethoxyphenyl)propan-2-amine (DOI) 4-isopropylthio-2,5-dimethyoxyphenethylamine (2C-T-4) meperidine 2-methylamino-l-(3,4-methylenedioxyphenyl)butan-l-one (Bk-MBDB) l-(3,4-methylenedioxybenzyl)piperazine (MDBP) 1 -(3,4-methylenedioxyphenyl)butan-2-amine (BDB) N-methyl-3,4-methylenedioxymethamphetamine (MMDA-2) N-methyl-1 -(3,4-methylenedioxyphenyl)butan-2-amine (HMDMA) N-methyl-l-(3,4-methylenedioxyphenyl)butan-3-amine (HMDMA) methylphenidate 4-methoxymethamphetamine (PMMA) l-(4-methoxyphenyl)piperazine (4-MPP) 2-(6-methyl-2-p-tolylimidazol[l,2-9]pyridine-3-yl)acetamide (zolpidem) normeperidine 4-phenylbutylamine (4-PBA) 3-phenyl-1-peopyTamine (3-PPA) and 2,4,6-trimethoxyamphetamine (TMA-6). 

Amide [91366-65-3]. 7-Fluoro-4-benzofurazansulfonamide, 9CI. 4-Aminosulfonyl- 7-fluoro-2,l,3-benzoxadiazole C6H4FN3O3S M 217.180 Fluorogenic reagent for thiols. Mp 145-146°. 

Hu S, Li PCH (2000) Micellar electrokinetic capillary chromatographic separation and fluorescent detection of amino acids derivatized with 4-fluoro-7-nitro-2,l,3-benzoxadiazole. J Chromatogr A 876 183-191... 

Zhang H, Le Potier I, Smadja C et al (2006) Fluorescent detection of peptides and amino acids for capillary electrophoresis via on-line derivatization with 4-fluoro-7-nitro-2,l, 3-benzoxadiazole. Anal Bioanal Chem 386 1387-1394... 

The chiral purity of amino acids at large enantiomeric excess can be determined automatically by derivatization with 4-fluoro-7-nitro-2,l,3-benzoxadiazole (127b) followed by CE with cyclodextrin chiral selectors and detection of the LIF excitation at 488 nm. Lod 140 ppm of L-phenylalanine in D-phenylalanine324. 

Mobile phase 5mM citric acid in methanol DNB=4-fluoro-7-nitro-2,l,3-benzoxadiazole. Source Ref. 20. 

Toyo oka T, Mantani T, Kato M. Reversible labeling of tyrosine residue in peptide using 4-fluoro-7-nitro-2,l,3-benzoxadiazole 131. and N-acetyl-L-cysteine. Analyt. Sci. 2003 19 341-346. 

James KJ, Sherlock IR (1996) Determination of the cyanobacterial neurotoxin, anatoxin-a, by derivatisation using 7-fluoro-4-nitro-2,l,3-benzoxadiazole (NBD-F) and HPLC analysis with fluorimetric detection. Biomed Chromatogr 10 46-47. doi 10.1002/(SICI)1099-0801(199601)10 l<46 AID-BMC551>3.0.CO 2-7 [pii]... 

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