Tipson–Cohen reaction

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The Tipson–Cohen reaction is a name reaction first discovered by Stuart Tipson and Alex Cohen at the National Bureau of Standards in Washington D.C. [1] The Tipson–Cohen reaction occurs when two neighboring secondary sulfonyloxy groups in a sugar molecule are treated with zinc dust (Zn) and sodium iodide (NaI) in a refluxing solvent such as N,N-dimethylformamide (DMF) to give an unsaturated carbohydrate. [2]

A name reaction is a chemical reaction named after its discoverers or developers. Among the tens of thousands of organic reactions that are known, hundreds of such reactions are well-known enough to be named after people. Well-known examples include the Grignard reaction, the Sabatier reaction, the Wittig reaction, the Claisen condensation, the Friedel-Crafts acylation, and the Diels-Alder reaction. Books have been published devoted exclusively to name reactions; the Merck Index, a chemical encyclopedia, also includes an appendix on name reactions.



Unsaturated carbohydrates are desired as they are versatile building blocks that can be used in a variety of reactions. [2] For example, they can be used as intermediates in the synthesis of natural products, or as dienophiles in the Diels-Alder reaction, or as precursors in the synthesis of oligosaccharides. [3] The Tipson–Cohen reaction goes through a syn or anti elimination mechanism to produce an alkene in high to moderate yields. [4] The reaction depends on the neighboring substituents. A mechanism for glucopyranosides and mannooyranosides is shown below. [4]

Scheme 1 Noren Hirani.gif

Scheme 1:Syn elimination occurs with the glucopyranosides. Galactopyranosides follows a similar syn mechanism. [3] Whereas, anti elimination occurs with mannopyranosides. [4] Note that R could be a methanesulfonyl CH2O2S (Ms), or a toluenesulfonyl CH3C6H4O2S (Ts).

Reaction mechanism

Scheme 2 Noren Hirani.gif

Scheme 3: The scheme illustrates the first displacement, the rate determining step and slowest step, where the starting material is converted to the iodo-intermediate. [4] The intermediate is not detectable as it is rapidly converted to the unsaturated sugar. Experiments with azide instead of the iodide confirmed attack occurs at the C-3 as nitrogen-intermediates were isolated. The order of reactivity from most reactive to least reactive is: β-glucopyranosides > β-mannopyranosides > α-glucopyranosides> α-mannopyranosides.

The reaction of β–mannopyranosides gives low yields and required longer reaction times than with β-glucopyranosides due to the presence of a neighboring axial substituent (sulfonyloxy) relative to C-3 sulfonyloxy group in the starting material. [4] The axial substituent increases the steric interactions in the transition state, causing unfavorable eclipsing of the two sulfonyloxy groups. α-Glucopyranosides possess a β-trans-axial substituent relative to C-3 sulfonyloxy (anomeric OCH3 group) in the starting material. The β-trans-axial substituent influences the transition state by also causing an unfavorable steric interaction between the two groups. In the case of α-mannopyranosides, both a neighboring axial substituent (2-sulfonyloxy group) and a β-trans-axial substituent (anomeric OCH3 group) are present, therefore significantly increasing the reaction time and decreasing the yield. [3]

Reaction conditions

Table 1: Reaction times and yield vary on the substrate. The β-glucopyranoside was found to be the best substrate for the Tipson–Cohen reaction as the reaction time and yield were much superior that any other substrate proposed in the study. [3]

Substratea Time (hours) Yield (%)
β-glucopyranoside 0.5 85
β-mannopyranoside 2.5 66
α-glucopyranoside 12 55
α-mannopyranoside 15 10

aSubstrates possess benzylidene protecting groups at C-4 and C-6, OMe groups at anomeric position and OTs groups at C-2 and C-3. Reaction temperature 95–100 ˚C

Reaction scope

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