Chemistry of 1,3-Dithiane

Suma H.S 2nd Semester (Chemistry) JSS College of Arts, Commerce & Science Ooty road, Mysore 25

Introduction
Majority of reactions in organic chemistry involves reagents and substrate. When reagents are used in the reaction, they bring about various types of changes in organic compound to yield the desire product . The salient features of these reagents is that they can degrade complex molecule to simple known compounds. This has enabled to elucidate the structures of complex molecule . To get a desire product choice of reagents and reactions conditions are very important.

UMPOLUNG PRINCIPLE
This concept was introduced by D.Seebach and E.J.Corey Umpolung or polarity inversion in organic chemistry is the chemical modification of a functional group with the aim of reversal of polarity of that group In several situation, one may reverse temporarily the characteristics reactivity, nucleophilic or electrophilic of an atom or a group( dipole inversion or polarity inversion ) Example:

1,3-Dithiane

A Dithiane is a heterocyclic compound composed of a cyclohexane core structure where in two methylene units are replaced by sulfur centres. The sulphur atom of a thiol is a far better nucleophile than the oxygen atom of an alcohol Dithianes are also employed in unpolung reaction

Preparation:
The Cabonyl group of both aldehydes and ketones reacts with 1,3-propanehithiol in the presence of acid to form cyclic thio acetate called 1,3-Dithiane.

The hydrogen atom of carbon -2 of 1,3-diathiane is weakly acidic. In the presence of strong base like butylithium, it forms 2-lithio- 1,3- Dithiane

Cont..

2- Lithio 1,3-Dithiane mainly exitst an anion which is stabilized by delocalization of negative charge by valence d-orbitals of the two sulphur atoms.

Cont..

In general reaction

Synthetic Applications
1. Reaction with Halides and Sulphonates

Example:

2.Reaction with Epoxides Anion of 1,3-dithiane reacts with epoxides to form - hydroxy carbonyl in good yield.

3.Reaction with Carbonyl Compounds

Anion of 1,3-Dithiane reacts with Carbonyl group of aldehydes and ketones to form tetrahedral carbonyl addition compounds which on hydrolysis gives - hydroxy carbonyl compounds

4. Reaction with Nitriles

Anion of 1,3-Dithiane gives nucleophilic addition with nitriles which on hydrolysis gives dicarbonyl compounds

5. Reaction with Acid Chlorides

Anion of 1,3-Dithiane reacts with acid chlorides, it gives the carbinol product.

6. Reaction with CO2

Anion of 1,3-Dithiane reacts with solid carbon dioxide to give addition product which on hydrolysis gives -keto acid

7.Protection of Carbonyl Compounds

A Lewis acid-surfactant-combined copper bis(dodecyl sulfate) [Cu(DS)2] catalyst served as an efficient and reusable catalyst for the thioacetalization and transthioacetalization of carbonyl compounds and O,O-acetals in water at room temperature. This procedure offers high chemoselectivity, ease of operation and purification without any organic solvent, and high yields. S.-S. Weng, S.-C. Chang, T.-H. Chang, J.-P. Chyn, S.-W. Lee, C.-A. Lin, F.-k. Chen, Synthesis, 2010, 1493-1499.

Cont..
Aldehydes and ketones were protected as their thioacetals in the presence of a catalytic amount of iodine. These mild reaction conditions were also applied in the transthioacetalization of O,O-acetals, O,O-ketals and O,Sacetals and acylals. [H. Firouzabadi, N. Iranpoor, H. Hazarkhani, J. Org. Chem., 2001, 66, 7527-7529.]

Cont..
A new procedure for the protection of aldehydes and ketones as thioacetals promoted by catalytic amount of ptoluenesulfonic acid and silica gel has been developed. This procedure offers versatility, short reaction time, excellent yield, and is easy to carry out. A simple filtration followed by removal of solvent in most cases produces pure product. [M. H. Ali, M. G. Gomes, Synthesis, 2005, 1326-1332.]

Cont..
Aldehydes and ketones were protected as their thioacetals in the presence of a catalytic amount of iodine. These mild reaction conditions were also applied in the transthioacetalization of O,O-acetals, O,O-ketals, O,S-acetals, and acylals. [H. Firouzabadi, N. Iranpoor, H. Hazarkhani, J. Org. Chem., 2001, 66, 7527-7529.]

Other syntheses of dithianes

b-Keto 1,3-dithianes can be generated by the double conjugate addition of dithiols to propargylic ketones, esters and aldehydes in excellent yields. These masked 1,3-dicarbonyl systems can be converted to a range of functionalised oxygen-containing heterocycles that can be used in natural product synthesis. M. J. Gaunt, H. F. Sneddon, P. R. Hewitt, P. Orsini, D. F. Hook, S. V. Ley, Org. Biomol. Chem., 2003, 1, 15-16.

Cont..
Aldehydes and ketones were protected as their thioacetals in the presence of a catalytic amount of iodine. These mild reaction conditions were also applied in the transthioacetalization of O,O-acetals, O,O-ketals, O,S-acetals, and acylals. [H. Firouzabadi, N. Iranpoor, H. Hazarkhani, J. Org. Chem., 2001, 66, 7527-7529.]

Deprotection

1. A simple protocol for the deprotection of 1,3-dithianes and 1,3-dithiolanes showed tolerance for a number of phenol and amino protecting groups using 30% aqueous hydrogen peroxide activated by iodine catalyst (5 mol%) in water in the presence of sodium dodecyl sulfate (SDS) under essentially neutral conditions without any detectable overoxidation. [N. G. Ganguly, S. K. Barik, Synthesis, 2009, 1393-1399.] 2. Chemoselective method for the deprotection of S,S-acetals to the corresponding carbonyl compounds using silicasulfuric acid/NaNO3 [A. R. Hajipour, A. Zarei, L. Khazdooz, A. E. Ruoho, Synthesis, 2006, 1480-1484.]

Cont..

3. Oxidative deprotection of several dithiane-containing alkaloids in the presence of bis(trifluoroacetoxy)iodobenzene and a nonchromatic purification cleanly generates the corresponding ketoamines. The described procedure is ideal for labile alkaloids. [F. F. Fleming, L. Funk, R. Altundas, Y. Tu, J. Org. Chem., 2001, 66, 6502 6504.]

Cont..

Conversion of dithianes to other functional groups

Easily prepared 2-alkyl-1,3-dithiane derivatives were reacted with BrF3 to form the corresponding 1,1-difluoromethyl alkanes in good yield. The reaction proceeds well with primary alkyl halides. The limiting step for secondary alkyl halides is the relatively low yield of the dithiane preparation.
[R. Sasson, A. Hagooly, S. Rozen, Org. Lett., 2003, 5, 3635-3641.]

References:
Reagents in organic synthesis Jagadamb Singh Organic chemistry portal via internet