Modern Chemistry 2018; 6(1): 1-5

http://www.sciencepublishinggroup.com/j/mc

doi: 10.11648/j.mc.20180601.11

ISSN: 2329-1818 (Print); ISSN: 2329-180X (Online)

Letter

Reactivities Involved in the Seliwanoff Reaction

Francisco Sánchez-Viesca*, Reina Gómez

Organic Chemistry Department, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City (CDMX), México

Email address:

*Corresponding author

To cite this article: Francisco Sánchez-Viesca, Reina Gómez. Reactivities Involved in the Seliwanoff Reaction. Modern Chemistry. Vol. 6, No. 1, 2018, pp. 1-5.

doi: 10.11648/j.mc.20180601.11

Received: January 2, 2018; Accepted: January 10, 2018; Published: January 23, 2018

Abstract: The Seliwanoff Reaction, a well-known colour reaction for ketoses, is based in the fact that ketoses are dehydrated

more rapidly than aldoses to give a furfural derivative. Further condensation with resorcinol in dilute hydrochloric acid gives the

colour product. But a problem has remained unsolved for many years: why the ketoses are dehydrated faster than aldoses? Based

on recent experimental results, as well as in ab initio methodology on the chemistry of aldoses and ketoses, we studied the

reactivities involved in dehydrations and isomerizations of these compounds and propose an explanation of why ketose require

less reaction time in the Seliwanoff Test.

Keywords: Aldoses, Especial Reactivities, Ketoses, Reaction Mechanisms, Reactive Intermediates

1. Introduction

Fructose is an important and interesting ketose. It is

well-tolerated by diabetics [1]. Unlike glucose, fructose does

not stimulate a substantial insulin release. Fructose glycemic

index is only 19, compared to 100 for glucose or 65 for table

sugar [2].

Fructosuria is a rare disorder from liver malfunction. Fructose

in urine can be detected by the Seliwanoff’s Test [3, 4].

Continuing our studies on fructose [5-7], we have turned

our attention to the Seliwanoff’s Reaction. It is a colour test

for ketose identification, giving a cherry-red or Burgundy-red

colour with resorcinol in dilute HCl.

This test showed that fructose reacts faster than glucose in

order to give a positive result: patent with fructose and

slightly pink with glucose. When the test was extended to

ketoses and aldoses the same chemical deportment was

observed.

This indicates that ketoses are dehydrated more rapidly

than aldoses to give a furan derivative that finally reacts with

the reagent producing the observed colouration.

However, a question has remained unanswered until now:

why ketoses react faster than aldoses in the same reaction

conditions?

In order to clear-up this interesting academic theme we

reviewed the recent advances in Carbohydrate Chemistry

related with the monosaccharides, especially dehydrations

and isomerizations. Experimental results as well as ab initio

theoretical studies were examined. So, on the basis of the

new information we propose a theoretical explanation on the

subject.

2. The Seliwanoff Reaction

The Seliwanoff colour reaction for fructose is due to the

Russian chemist Feodor Feodorovich Selivanov (Russian

transliteration), and known as Theodor Seliwanoff (German

phonetics) [8]. A memorial article is available [9].

The test, 0.1% resorcinol in 4M HCl, has been extended to

ketohexoses which also give the deep cherry-red colour.

Ketopentoses can also been identified since they provide

bluish-green solutions [10].

The reaction consists in the triple dehydration of the

monosaccharide to 5-hydroxymethylfurfural (ketohexoses) or

to furfural (ketopentoses). Finally, the furan derivative reacts

with resorcinol to give the coloured condensation product.

Figure 1.

2 Francisco Sánchez-Viesca and Reina Gómez: Reactivities Involved in the Seliwanoff Reaction

Figure 1. The Seliwanoff’s Test.

Several structures have been proposed for the red

compound. The most simple has been given in Ukraine, a two

ring semiquinone structure [11]. Figure 2a.

Other structure involves two resorcinol molecules,

affording a three ring derivative [12]. Figure 2b.

An interesting work with a cognate reagent,

4-ethyl-resorcinol, permitted isolate the reaction product. The

structure assigned is of xanthene type [13]. Figure 2c is for the

classical reaction [14].

Figure 2. Structures that have been assigned to the red product.

We provide a reaction mechanism for the formation of the

final product, Figure 3.

Figure 3. Condensation steps.

In the ketohexoses the bathochromic shift (red shift) is due

to the 5-hydroxymethyl group present in the furan derivative.

A method has been described for the colorimetric

determination of fructose in fermentation media by the use of

Seliwanoff’s colour reaction [15].

In a related reaction for fructose identification, fructose in

glacial acetic acid is treated with phenol in the same solvent

containing sulphuric acid. A green colour is developed after

heating in a boiling water bath. The test is also positive for

those substances yielding fructose on hydrolysis [16].

A very different chemical deportment is observed in the

condensation of resorcinol with other aldehydes yielding

resorcinarenes, macrocycles formed from four units of each

reactant [17].

3. The Involved Mechanisms

Looking for an explanation why the ketohexoses are

dehydrated more readily than the aldohexoses, molecular level

understanding of acid-catalyzed conversion of sugar

molecules into hydroxymethylfurfural (HMF) and furfural is

essential.

Several reaction mechanisms have been proposed through

the years. In the obtention of furfural the reaction was believed

to start from the open structure of the pentoses. Paquette [18]

dehydrates an aldopentose to the α-keto-aldehyde via the enol.

A second dehydration affords an α, β-unsaturated ketone.

Modern Chemistry 2018; 6(1): 1-5 3

Finally, acid catalyzed cyclization and dehydration gives

furfural. Figure 4.

Figure 4. Erroneous open-chain dehydrations.

This point of view had been mentioned earlier [19], though

not cited, and it is faulty. First, it is improbable since the

percentage of open chain structure is very low. The

mechanism is faulty since there is no hydroxide evolution to

the proton, but hydroxyl protonation affording the oxonium

ion, followed by water elimination. Besides the proposed

double bond would yield a trans-product which is not prone to

cyclization. These errors are still online from industrial

sources, not academic [20].

A better alternative would be cyclization before any double

bond, then hemiketal dehydration to the dihydrofuran ring and

finally dehydration to 2-furaldehyde. This way the resulting

double bonds are Z. Figure 5. However, this sequence is also

based in the open chain structure.

Figure 5. Correct cyclization and dehydrations.

Recently, the formation of furfural from a pentose is

considered to take place starting from the pyranose form of the

pentose, by protonation at O-2 of the pyranose ring. Water

elimination is followed by ring contraction, then

neutralization of the resulting carbocation yields an enol that

isomerizes to the aldehyde. This tetrahydrofuran derivative is

a 2, 5-anhydride, the pair of locants identifying the two

hydroxy groups involved in the formation of the

intramolecular ether. A second dehydration gives the α,

β-unsaturated compound and the third water loss affords

furfural [21]. An example with xylose is in Figure 6.

Figure 6. From α-D-xylopyranose to furfural.

Since glucose reacts much slower than fructose as observed

in the Seliwanoff’s Test, we thought that this delay could be

attributed to a previous isomerization of glucose to fructose.

Thus, we looked for the current trends on this isomerization.

We found that there is evidence for a C-2 to C-1

intramolecular hydrogen-transfer during the acid-catalized

isomerization of D-glucose to D-fructose [22]. The reaction

from β-D-glucopyranose to α-D-fructofuranose is depicted in

Figure 7, from a novel method of direct degradation of

cellulose in to 5-hydroxymethylfurfural with sodium or

potassium salts of acidic salts (sulphates and phosphates), a

green HMF production [23].

Figure 7. Reaction sequence from β-D-glucopyranose to α-D-fructofuranose

via a 1, 2-hydride transfer in an open-chain intermediate.

Other isomerization of glucose to fructose by means of

Lewis acid involves the same hydride transfer from C-2 to C-1

[24].

The dehydration of fructose to 5-hydroxymethylfurfural

occurs through the fructofuranose form. This can be

originated either by glucose isomerization to fructose or more

directly from the fructopyranose form. Dehydration starts at

4 Francisco Sánchez-Viesca and Reina Gómez: Reactivities Involved in the Seliwanoff Reaction

the hemiketal, and the intermediate enol rearranges to the

aldehyde. The second dehydration gives the α, β-unsaturated

derivative. A third water loss affords hydroxymethylfurfural

[25], Figure 8.

Figure 8. Dehydration steps from fructose to HMF.

The route of glucose to 5-hydroxymethylfurfural has been

studied recently using high-level ab initio methods (G4MP2

along with SMD solvation model), [26]. The reaction

mechanism confirms the previous one described for pentoses

to furfural, such as xylose [21], i.e., protonation at O-2, water

elimination, ring contraction, neutralization, deprotonation,

and two more dehydrations.

Other ab initio study using density functional and two-layer

ONIOM calculations found that no dehydration pathway of

open-chain glucose is favoured over its isomerization to

β-glucopyranose or to fructose. The chair conformers are

given in the ring contraction mechanism to

5-hydroxymethylfurfural [27], Figure 9.

Figure 9. Oxygen-assisted ring-contraction.

4. Conclusion

Since 5-hydroxymethylfurfural is the key intermediate that

reacts with resorcinol to give the coloured xanthenoid, and the

fact that ketoses react faster than the aldoses in the Seliwanoff

Test, prompted us to direct our attention to the HMF formation

in order to clear-up the theoretical core that permits an

explanation of the reaction rates involved in the formation of

the key intermediate.

We reviewed the actual information regarding the formation

of furfural and hydroxymethylfurfural from aldopentoses,

aldohexoses and ketohexoses. The isomerization of glucose to

fructose was also revised. All this has been detailed in the

previous section.

If we look at the reactivities involved from fructose to

hydroxymethylfurfural we observe that dehydration is

initiated by protonation of the more reactive OH, the anomeric,

which can be stabilized by resonance, previously to vicinal

deprotonation. Then a tautomerism occurs and two simple

dehydrations of a tetrahydrofuran derivative yield

hydroxymethylfurfural. The first dehydration can be

visualized as an α, β-conjugation but also, prior to

tautomerism, as a very rapid dehydration of the allylic OH,

supported by the enolic electron donation.

On the contrary, in glucose to 5-hydroxymethylfurfural, the

starting protonation does not occur at the most basic OH but at

O-2. Then a cationic rearrangement contraction provides the

five-member ring intermediate. Two further dehydrations

afford HMF. In this route we observe two not common

reactivities, the starting point and the ring contraction.

The isomerization of glucose to fructose, another route to

HMF, also presents an uncommon reactivity, a hydride shift.

Besides, the total course implies more steps to HMF and

obviously more reaction time.

― Thus, in the Seliwanoff’s Test ketoses react via a diverse

reaction mechanism than aldoses, being significative

differences at molecular level.

― Fructose presents common reactivities in the synthesis of

hydroxymethylfurfural, this not being the case with glucose or

glucose isomerization to fructose. This explains the different

reaction times observed in the test and it’s utility for ketose

identification. Slower reactions resulted in accord with less

common reaction steps, i.e., with especial reactivities.

― The theory of the Seliwanoff’s Reaction has been

cleared-up. This is important because generally aldehydes

react faster than ketones but now we are not dealing with

isolated functional groups but with polyfunctional molecules

with mixed groups.

References

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[3] W. Hood, A-Z of Clinical Chemistry: A Guide for the Trainee, Lancaster, U. K.: MTP Press Limited, 1980, p. 142.

[4] Z. Bojanic, Selivanov’s test. A test for fructosuria. http://www.whonamedit.com/synd.cfm/2682.html.

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