Download PDF
Synlett 2005(16): 2453-2456  
DOI: 10.1055/s-2005-872703
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of S-Pixyl Derivatives for Mass Spectrometric Applications

Safraz Khana, Pablo L. Bernada, Vladimir A. Korshunb, Edwin M. Southerna, Mikhail S. Shchepinov*a
a Tridend Technologies (a Division of OGT) Hirsch Building, Begbroke Business & Science Park, Sandy Lane, Yarnton, Oxford, OX5 1PF, UK
Fax: +44(1865)841916; e-Mail: misha@tridend.com;
b Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, Moscow, 117 997, Russia
Further Information

Publication History

Received 7 July 2005
Publication Date:
21 September 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

Synthesis of novel S-pixyls based on the thioxanthyl skeleton is described. Thioxanthone derivatives were prepared by a regioselective intramolecular Friedel-Crafts acylation reaction and converted into S-pixyl derivatives by Grignard synthesis. S-Pixyl carbocations stabilised by electron donating groups on the thioxanthyl backbone produced exceptional mass spectra under (MA)LDI conditions (laser desorption ionisation, both with and without ­matrix), and can be detected down to femtomol levels.

Key words

S-pixyls - regioselective Friedel-Crafts acylation - (MA)LDI analysis - functionalised thioxanthen-9-ones - 2-aroylpyrene

12

General Procedure for the Copper-Mediated Ullmann Reaction, Selected Compounds 9a and 20. To a solution of thiosalicylic acid (0.2 mol) in 300 mL of DMF was added aryl halide (0.2 mol), K2CO3 (0.2 mol) and Cu powder (0.2 equiv), the mixture was warmed to reflux. After 16-24 h the mixture was cooled to r.t., filtered and poured into 1 N HCl and then extracted with EtOAc (4 ×). The combined organic phases were then washed with H2O (4 ×), and dried over Na2SO4, filtered and concentrated in vacuo. The product was dried under high vacuum and used with out further purification (78-95%).
Analytic data of 9b: 1H NMR (200 MHz, DMSO-d 6): δ = 8.30-7.50 (d, J = 9.2 Hz, 1 H), 7.50-7.35 (dd, J = 9.6 Hz, 1 H), 7.30-7.18 (t, J = 7.5 Hz, 1 H), 7.15-7.00 (m, 3 H), 6.85-6.74 (d, J = 9.0 Hz, 1 H), 3.8 (s, 3 H). 13C NMR (400 MHz, DMSO-d 6): δ = 168.00, 160.99, 142.35, 134.16, 133.26, 131.79, 131.68, 128.51, 127.88, 125.59, 120.77, 115.98, 56.15. HRMS (ESI): m/z calcd for C14H12NaO3S [M + Na+]: 283.0405; found: 283.0416.
Analytic data of 20: 1H NMR (400 MHz, DMSO-d 6): δ = 8.50-8.30 (m, 8 H), 8.25-8.12 (t, J = 7.65 Hz, 1 H), 8.10-8.00 (d, J = 8.7 Hz, 1 H), 6.80-6.70 (d, J = 8.8 Hz, 1 H), 5.70-5.60 (d, J = 2.4 Hz, 1 H), 3.50-3.40 (br OH, 1 H), 3.35 (s, 3 H). 13C NMR (400 MHz, DMSO-d 6): δ = 167.95, 162.98, 145.59, 135.73, 134.73, 134.04, 133.23, 131.49, 131.15, 130.22, 129.75, 128.12, 127.74, 127.12, 126.76, 126.44, 125.48, 125.18, 124.34, 119.95, 113.49, 109.61. HRMS (ESI): m/z calcd for C24H16NaO3S [M + Na+]: 407.0718; found: 407.0717.

13

General Procedure for the Intramolecular Friedel-Crafts Acylation Reaction, Selected Compounds 10, 12, 13 and 21.Preparation of Acid Chlorides.
o-(Phenylthio)benzoic acid derivatives (0.1 mol), placed in a dry 250 mL round-bottom flask under a positive pressure of argon. Then, 100 mL of dry CH2Cl2 were added and the reaction cooled to 0 °C. A few drops of DMF were added followed by the dropwise addition of oxalyl chloride (1.5 equiv) with stirring. The reaction was stirred for 1 h or longer until the suspension had completely dissolved. The product was concentrated in vacuo and dried under high vacuum to give the acid chloride, which was used without further purification (90-100%).
Intramolecular Friedel-Crafts Acylation.
The acid chloride (0.1 mol) was placed in a dry 250 mL round-bottom flask under a positive pressure of argon. Then, 100 mL of dry CH2Cl2 were added and the reaction was stirred at r.t., AlCl3 (1.5 equiv) was added slowly and the reaction was stirred for 1-2 h. The reaction was quenched with H2O and extracted with CH2Cl2 (2 ×). The combined organic phases were washed with dilute NaHCO3 and dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by flash chromatography on silica gel, hexane-EtOAc gradient elution to give the desired product (80-95%).
Analytic data of 10: 1H NMR (400 MHz, CDCl3): δ = 8.65-8.58 (d, J = 8.1 Hz, 1 H), 8.55-8.50 (d, J = 9.0 Hz, 1 H), 7.60-7.40 (m, 3 H), 7.05-6.97 (d, J = 11.6 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 3.90 (s, 3 H). 13C NMR (400 MHz, CDCl3): δ = 179.02, 162.48, 139.54, 136.89, 132.88, 131.92, 129.69, 129.27, 126.28, 125.71, 123.02, 115.08, 107.79, 55.66. HRMS (ESI): m/z calcd for C14H11NaO2S [M + H]: 243.0480; found: 243.0473.
Analytic data of 12: 1H NMR (400 MHz, CDCl3): δ = 8.65-8.60 (d, J = 8.3 Hz, 1 H), 8.02 (d, J = 2.8 Hz, 1 H), 7.60-7.45 (m, 4 H), 7.30-7.20 (d, J = 8.9 Hz, 1 H), 3.95 (s, 3 H). 13C NMR (400 MHz, CDCl3): δ = 179.65, 158.35, 137.49, 131.99, 130.19, 129.84, 129.14, 128.55, 127.27, 126.06, 125.97, 122.72, 110.29, 55.67. HRMS (ESI): m/z calcd for C14H11NaO2S [M + H]: 243.0480; found: 243.0469.
Analytic data of 13: 1H NMR (400 MHz, CDCl3): δ = 8.60-8.50 (d, J = 4.5 Hz, 1 H), 7.05-6.98 (d, J = 5.1 Hz, 1 H), 6.90 (s, 1 H), 3.90 (s, 3 H). 13C NMR (400 MHz, CDCl3): δ = 178.30, 162.21, 139.12, 131.75, 123.03, 114.81, 107.98, 55.64. HRMS (ESI): m/z calcd for C15H13NaO3S [M + H]: 273.0585; found: 273.0576.
Analytic data of 21: 1H NMR (200 MHz, CDCl3): δ = 8.90 (s, 1 H), 8.70-8.60 (d, J = 8.9 Hz, 1 H), 8.59-8.48 (d, J = 9.3 Hz, 1 H), 8.35-7.90 (m, 6 H), 7.24-7.00 (m, 2 H), 4 (s, 3 H). 13C NMR (500 MHz, CDCl3): δ = 180.14, 162.71, 138.72, 132.18, 131.98, 131.73, 131.01, 129.15, 128.44, 128.37, 127.79, 127.56, 126.79, 126.50, 126.21, 125.87, 125.78, 125.49, 124.20, 122.58, 122, 115.33, 108.53, 55.84. HRMS (ESI): m/z calcd for C24H15O2S [M + H]: 267.0793; found: 267.0797.