Chemistry of 1,3-Dithiane
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Transcript of 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
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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.
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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:
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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
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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
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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.
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In general reaction
Cont..
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Synthetic Applications
1. Reaction with Halides and Sulphonates
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Example:
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2.Reaction with Epoxides
Anion of 1,3-dithiane reacts with epoxides to form β- hydroxycarbonyl in good yield.
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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
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4. Reaction with Nitriles
Anion of 1,3-Dithiane gives nucleophilic addition with nitriles which onhydrolysis gives dicarbonyl compounds
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5. Reaction with Acid Chlorides
Anion of 1,3-Dithiane reacts with acid chlorides, it gives the carbinolproduct.
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6. Reaction with CO2
Anion of 1,3-Dithiane reacts with solid carbon dioxide to give additionproduct which on hydrolysis gives α-keto acid
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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.
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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.]
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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.]
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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.]
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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.
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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.]
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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.]
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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.]
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Cont..
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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.]