Disulfur Dichloride (S2cl2) Spotlight 238 Compiled by Bárbara Vasconcellos Da Silva

SPOTLIGHT 1265

SYNLETT Disulfur Dichloride (S2Cl2) Spotlight 238 Compiled by Bárbara Vasconcellos da Silva

This feature focuses on a re- Bárbara Vasconcellos da Silva was born in Rio de Janeiro, Brazil in 1981. She received her Chemistry degree from Universidade Feder- agent chosen by a postgradu- al do Rio de Janeiro in 2007 and she is currently working toward her ate, highlighting the uses and Ph.D. in organic synthesis under the supervision of Dr. Angelo da preparation of the reagent in Cunha Pinto at the same university. Her research interests focus on current research the synthesis of isatins and oxindole derivatives. Centro de Tecnologia, Bloco A, Instituto de Química, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, Brazil E-mail: [email protected]

Introduction S2Cl2 is a smelly, clear, yellowish-red, oily liquid. It should be used with care and proper precautions must be Disulfur dichloride (S2Cl2), also known as sulfur chloride taken because it is toxic, corrosive, and harmful to the en- (SCl), is widely used in organic synthesis as a sulfurizing vironment. and chlorinating agent. Sulfide compounds are found in many natural products and may have useful biological properties.1 This reagent has been explored for the prepa- Preparation ration of heteroaryl disulfides,2 symmetric aryl di-, tri-, 2,3 4 5,6 and tetrasulfides, episulfides and benzopolysulfides. S2Cl2 is synthesized by partial chlorination of elemental 9 Moreover, S2Cl2 is a suitable substrate for the synthesis of sulfur and is also commercially available.

dialkoxy disulfide,7 or for the Herz reaction.8 It decom-

S + 4 Cl

4 S Cl 8 2 2 2 poses into SO2, HCl, and S8 when exposed to wet air due to reaction with water. Scheme 1

Abstracts

S Cl

(A) Korn and Knochel have described the use of S2Cl2 to achieve 2

functionalized aryl and heteroaryl disulfides from functionalized (0.5 equiv)

ZnBr

zinc organometallics. All the reactions were carried out at –80 °C, S

–80 °C

R R producing within ten minutes the expected disulfide in 62–99% R

yield. R = Cl, OMe, EtO C, CN 2

S Cl 2 2

(0.5 equiv)

–80 °C

ZnBr

EtO C

EtO C SS CO Et O O 2 2

(B) An equilibrated equimolecular mixture of S2Cl2 and DABCO S (1,4-diazobicyclo[2.2.2]octane) has been used for treatment of N- S S S S S S substituted 2,5-dimethylpyrroles 1 giving pentathiepinopyrroles 2 in S2Cl2 S S S2Cl2 moderate yields. Further reaction of 2 with the same mixture at room This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. DABCO DABCO S N S temperature has resulted in an extensive reaction cascade, to give Me N Me r.t. 0 °C Me 10 Me N R

bis(dithiolo)pyrrole 3 in high yield. R 12R 3

R = Bn, Me, Et, n-Pr, i-Pr

SYNLETT 2008, No. 8, pp 1265–1266 xx.xx.2008 Advanced online publication: 16.04.2008 DOI: 10.1055/s-2008-1072741; Art ID: V24507ST © Georg Thieme Verlag Stuttgart · New York 1266 SPOTLIGHT

(C) Chiral benzopolysulfides are rarely described in the literature. S S Me S S Sato and co-workers5 have reported the synthesis of axially chiral S S S S benzopentathiepins by treatment of dithiastannole with S Cl . S S 2 2 S Me S S2Cl2 S +

BF3⋅OEt2 CH2Cl2, r.t.

dr = 55:45

(D) Reaction of a diol with S2Cl2 resulted in the first example of a sta- O S Cl ble and fully characterized cyclic dialkoxy disulfide under mild con- OH 2 2 S 11 ditions. S OH Et3N O

(E) S Cl was reacted with 1,7-s-hydrindacenedione dioximes lead- Cl Cl 2 2 HON NOH ing to the first example of bis[1,2,3]dithiazolo-s-indacene.12 In this example, S Cl has also been found as a chlorinating agent. S2Cl2 2 2 S S i-Bu3N, THF S S N N

(F) Treatment of 1,5-cyclooctadiene with S2Cl2, followed by reaction Cl with sulfuryl chloride (SO2Cl2) provides high yields of 2,6-dichloro- 9-thiabicyclo[3.3.1]nonane in a robust and convenient manner. This 1. S2Cl2, CH2Cl2 product may be used as connector and as a chiral scaffold through 2. SO Cl , CH Cl nucleophilic substitution of chloride.13 2 2 2 2 S Cl

(G) S2Cl2 is a very effective reagent for the preparation of nitrogen- Ph Ph substituted thiosulfinyl compounds (R N) S=S. When the substitut-

2 2 Et2O ed 1,2-ethylenediamine (1) containing electron-withdrawing groups Ts N N Ts 2 Ph Ph on the nitrogen atoms was treated with n-BuLi in Et2O and then with 1. n-BuLi S S Ph Ph S2Cl2, compound 2, a new heterocyclic system, was obtained in 57%

yield. The reaction in THF gave sulfoxide 3 in 27% yield.14 Ts NH HN Ts 2. S2Cl2 THF

Ts N N 3 1 0 °C Ts S

(H) The reaction of aldehyde hydrazones or phenyldiazomethane R S Cl R with S2Cl2 in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7- 2 2 R S R H C NNH2 C N ene) or Et3N gave 1,3,4-thiadiazoles in good to moderate yields. The DBU + 15 N C

azines 4a and 4b were obtained as side products. H CH Cl N N H 2 2 4a 0–5 °C R R = Tol, Ar

Ph Ph S S2Cl2 Ph Ph H C N C N2 + Et N N N N C

H 3 H CH2Cl2 4b Ph 0–5 °C

References (1) Tan, R. X.; Jensen, P. R.; Williams, P. G.; Fenical, W. J. Nat. (9) Dodd, R. E.; Robinson, P. L. Experimental Inorganic This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Prod. 2004, 67, 1374. Chemistry, 2nd ed.; Elsevier Publishing Company: New (2) Korn, T. J.; Knochel, P. Synlett 2005, 1185. York, 1957, 218. (3) Zysman-Colman, E.; Harpp, D. N. J. J. Org. Chem. 2003, 68, (10) Amelichev, S. A.; Aysin, R. R.; Konstantinova, L. S.; 2487. Obruchnikova, N. V.; Rakitin, O. A.; Rees, C. W. Org. Lett. (4) Sugihara, Y.; Noda, K.; Nakayama, J. Tetrahedron Lett. 2005, 7, 5725. 2000, 41, 8913. (11) Zysman-Colman, E.; Nevins, N.; Eghbali, N.; Snyder, J. P.; (5) Sato, R.; Ohta, H.; Yamamoto, T.; Nakajo, S.; Ogawa, S.; Harpp, D. N. J. Am. Chem. Soc. 2006, 128, 291. Alam, A. Tetrahedron Lett. 2007, 48, 4991. (12) Macho, S.; Miguel, D.; Gómez, T.; Rodríguez, T.; Torroba, (6) Aebisher, D.; Brzostowska, E. M.; Mahendran, A.; Greer, A. T. J. Org. Chem. 2005, 70, 9314. J. Org. Chem. 2007, 72, 2951. (13) Díaz, D. D.; Converso, A.; Sharpless, B.; Finn, M. G. (7) Braverman, S.; Pechenick, T.; Gottlieb, H. E. Tetrahedron Molecules 2006, 11, 212. Lett. 2003, 44, 777. (14) Yoshida, S.; Sugihara, Y.; Nakayama, J. Tetrahedron Lett. (8) Koutentis, P. A.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1 2007, 48, 8116. 2002, 315. (15) Okuma, K.; Nagakura, K.; Nakajima, Y.; Kubo, K.; Shioji, K. Synthesis 2004, 1929.