Spotlight: Synthesis and applications of sulfones viz β-keto-sulfones, α-halo β-keto-sulfones α-halo methyl sulphones and α, α-dihalo methyl sulphones

Authors

• Suryakiran Navath Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Habsiguda, Hyderabad 500007, India.

Abstract

 The review summarizes an analysis of recent advances and contributions to the methods of synthesis, chemical and spectral properties and application of β-keto sulfones with the main focus on the their increasingly growing demand as starting substrates and intermediates incorporated in the syntheses of various classes of organic compounds and other synthetic applications.

Compiled by Dr. Suryakiran Navath, Ph. D.

Dr. N. Suryakiran. He obtained M.Sc. and Ph. D. in Organic Chemistry from Jawaharlal Nehru Technological University, Hyderabad India, and his research interest is organic synthesis of bioactive Natural Products, medicinal chemistry, drug delivery systems and controlled release and development of new synthetic methodologies.

Introduction

Sulfones are chemical compounds containing a sulfonyl functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of two carbon atoms, usually in two separate alkyl or an aryl hydrocarbon substituents. They are very important and fascinating branch of chemistry.¹ The presence of sulfone group, in an organic compound adds variety to its chemical architecture and also enhances the biological activity of the compound. Among sulfones, β-keto-sulfones are very important group of intermediates. β-keto-sulfones are readily obtained from various routes.^2-8 In β-keto-sulfones the presence of both electron withdrawing groups, the methylene group readily enalises in the presence of bases such as pipridine, pirrolidine, triethylamine, and also in the presence of acids such as acetic acid and ammonium acetate with carbonyl group but not with sulfone group, the effect by sulfone is purely inductive effect only.⁹ The β-keto-sulfones are important building blocks in potentially bioactive molecules,¹⁰ and also used as precursors in various organic transformations, such as, Michael and Knoevenagel reactions and in the preparation of allenes, chalcones, polyfunctionalized 4H-pyrans and ketones. In addition, β-keto-sulfones can be converted into synthetically as well as biologically important optically active β-hydroxy-sulfones and α halomethyl sulfones and α, α dihalomethyl sulfones.

Makosza¹¹ have been utilized chloromethyl phenyl sulfones and chloromethyl p-tolyl sulfones in vicarious nuclephilic substitution (VNS) reactions with nitro arenes to afford VNS adducts. These adducts have been elaborated into both 3-sulfonyl substituted indole derivatives and the analogues indazoles.¹² Halo alkyl sulfones are useful preventing aquatic organisms from attaching to fishing nets and shiphulls,¹³ in herbicides compositions,¹⁴ bactericidal,¹⁵ anti fungal,¹⁶

Scheme 1

algaecides,¹⁷ and insecticides.18 Several methods of synthesis of α-halo methyl sulfones and α, α-dihalo methyl sulfones have been reported in literature.^19-23

(A) As the importance of -keto-sulfones in organic synthesis, various authors have been reported different routes to synthesis of -keto-sulfones.^2-8

Scheme 2

(B) The α-chloro/bromo β-keto-sulfone do not undergo Finkelstein reactions to obtain corresponding α-iodo β-keto-sulfone. However, the α-iodo β-keto-sulfone have been synthesized by treatment with iodine monochloride, further on treatment with aqueous alkali underwent base-induced cleavage afforded α-iodomethyl sulfones, which are excellent carbanion stabilizing substituents.²⁴

Scheme 3

(C) The chemoselective mono halogenation was achieved by treatment with potassium halide in the presence of hydrogen peroxide as en efficient and non polluting halogention reagent, further on treatment with SO₂Cl₂/Br₂ followed by base induced cleavage afforded α,α-symmetrical and asymmetrical dihalo β-keto-sulfone and α,α-symmetrical and asymmetrical dihalomethyl sulfones respectively.²⁵

(D) The controlled mono and di sulfenylation of β-keto-sulfone was achieved by on treatment with N-thiotpthalimide in the presence of triethyl amine in DCM.²⁶

Scheme5

(E) Dalip Kumar et. al have been reported the facile synthesis of novel α-tosyloxy β-keto-sulfone using [hydroxy (tosyloxyiodo]benzene under solvent free conditions.²⁷

Scheme 6

(F) Grossert et. al. have been reported the preparation, spectral properties, structures and base-induced cleavage of α-halo β-keto-sulfones.²⁸

Scheme 7

H) β-keto-sulfones on enzymatic or catalytic reduction yield optically active β-hydroxy-sulfones, which are important key constituents in organic synthesis. Recently, compounds of this class have proved its efficiency as a chiral controller in asymmetric Diels-Alder and alkylation reactions.²⁹

Scheme 8

(I) Nakada et. al. have been reported asymmetric catalysis on the intramolecular cyclopropanation of a-diazo β-keto-sulfones.³⁰

Scheme 9

(J) β-keto-sulfones are precursor for Michael reactions; β-keto-sulfones on treatment with substituted acrylonitrile in the presence of pipridine yields sulfonyl substituted amino pyrans.³¹

Scheme 1 0

(K) β-keto-sulfones on alkylation followed by facile elimination of sulfone group yields the α-alkylated ketones.³²

Scheme 1 1

(L) β-keto-sulfones are useful for the facile synthesis of allenes; α,α-dialkyl β- acetyleno β-keto-sulfones on treatment with Al(Hg) yields substituted allenes.³³

Scheme 1 2

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