Chemistry of 1,3-Dithiane

8/2/2019 Chemistry of 1,3-Dithiane

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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 thecharacteristics 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 theoxygen 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 thepresence 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.



In general reaction

Cont..



Synthetic Applications

1. Reaction with Halides and Sulphonates



Example:



2.Reaction with Epoxides

Anion of 1,3-dithiane reacts with epoxides to form β- hydroxycarbonyl in good yield.



3.Reaction with Carbonyl Compounds

Anion of 1,3-Dithiane reacts with Carbonyl group of aldehydes andketones to form tetrahedral carbonyl addition compounds which on

hydrolysis gives α- hydroxy carbonyl compounds



4. Reaction with Nitriles

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



5. Reaction with Acid Chlorides

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



6. Reaction with CO2

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



7.Protection of Carbonyl Compounds

A Lewis acid-surfactant-combined copper bis(dodecyl sulfate) [Cu(DS)2] catalystserved 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,S-

acetals 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 p-

toluenesulfonic 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 removalof solvent in most cases produces pure product.

[M. H. Ali, M. G. Gomes, Synthesis, 2005, 1326-1332.]



Cont..




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..




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

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Chemistry of 1,3-Dithiane