See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/323229127

Reactivities Involved in the Seliwanoff Reaction

Article · January 2018

DOI: 10.11648/j.mc.20180601.11

CITATIONS READS

16 44,068

2 authors, including:

Francisco Sánchez-Viesca
Universidad Nacional Autónoma de México
84 PUBLICATIONS   438 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Theoretical Advances in Aromatic Nitration View project

Osazone Chemistry View project

All content following this page was uploaded by Francisco Sánchez-Viesca on 16 February 2018.

The user has requested enhancement of the downloaded file.

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

In order to clear-up this interesting academic theme we

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?
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:
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.
Reactivities Involved in the Seliwanoff Reaction
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
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,
3
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:
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
Reactivities Involved in the Seliwanoff Reaction
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
[1] L. O’Brien Nabors, Ed., Chapter 20, J. S. White and T. F.
Osberger, Crystalline Fructose, New York: Marcel Dekker, Inc.,
2001, pp. 367-390.
[2] Calorie Control Council, https://caloriecontrol.org/fructose/.
[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.
 Modern Chemistry 2018; 6(1): 1-5
[5] F. Sánchez-Viesca, and R. Gómez, “On the regiochemistry in
the Heyns rearrangement”, Am. J. Chem., vol. 5 (3), pp. 86-89,
2015.
[6] F. Sánchez-Viesca, and R. Gómez, “On Fructosazone
Regiochemistry”, Modern Chemistry, vol. 4 (1), pp. 1-5, 2016.
[7] F. Sánchez-Viesca, and R. Gómez, “Reactivities Involved in the
Regioselectivity of Osazone Formation”, World J. Org. Chem.,
vol. 5 (1), pp. 11-16, 2017.
[8] Th. Seliwanoff, “Notiz über eine Fruchtzuckerreaction”. Ber.
Deutsch. Chem. Ges., vol. 20 (1), pp. 181-182, 1887.
[9] I. A. Shuklov and G. Boeck, “The Seliwanoff’s test for fructose:
A memorial for Fédor Fédorovic Selivanov”, Chemie in
Unserer Zeit, vol. 49 (2), pp. 106-112, 2015.
[10] Seliwanoff’s Reagent,
http://faculty.mansfield.edu/bganong/biochemistry/reagents.ht
m.
[11] Department of Organic and Bioorganic Chemistry, Zaporozhye
State Medical University, Lecture: Carbohydrates, mono-, di-,
polysaccharides, Zaporozhye, Ukraine: Ministry of Public
Health, s/d, p. 18.
[12] J. Mohan, Organic Analytical Chemistry, Theory and Practice,
Pangbourne, England: Alpha Science International, 2003, pp.
25-26.
[13] M. Ohta, M. Iwasaki, K. Kouno and Y. Ueda, “Study on the
color reaction mechanism of the Seliwanoff reaction with
4-ethyl-resorcinol as the color-developing reagent”, Chem.
Pharm. Bull., vol. 33 (6), pp. 2421-2424, 1985.
[14] Seliwanoff’s test,
https://en.wikipedia.org/wiki/seliwanoff%27s_test.
[15] D. J. S. Gray, “Critical factors in the resorcinol reaction for the
determination of fructose”, Analyst, vol. 75, issue 891, pp.
314-317, 1950.
[16] R. K. Maurmeyer, E. M. Livingston and H. Zahnd, “A color test
for fructose”, J. Biol. Chem., vol 185 (1), pp. 347-348, 1950.
[17] Resorcinarene, https://en.wikipedia.org/wiki/Resorcinarene.
View publication stats
5
[18] L. A. Paquette, Principles of Modern Heterocyclic Chemistry,
New York, USA: W. A. Benjamin, Inc., 1968, pp. 107-108.
[19] W. A. Bonner and M. R. Roth, “The conversion of
D-xylose-1-C14 into 2-furaldehyde-α-C14”, J. Am. Chem.
Soc., vol. 81 (10), pp. 5454-5456, 1959.
[20] Sugars to HMF and Furfural Reaction Mechanism,
http://biorefinery.utk.edu/technical_reviews/Bassem-Data%20
Review%20 (2).pdf
[21] J. B. Binder, J. J. Blank, A. V. Cefali and R. T. Raines,
“Synthesis of furfural from xylose and xylan”, Chem Sus
Chem., vol. 3 (11), 1268-1272, 2010.
[22] D. W. Harris and M. S. Feather, “Evidence for a C-2 to C-1
intramolecular hydrogen-transfer during the acid-catalyzed
isomerization of D-glucose to D-fructose”, Carbohydrate
Research, vol. 30 (2), 359-365, 1973.
[23] N. Shi, Q. Liu, L. Ma, T. Wang, Qi Zhang, Q. Zhang and Y.
Liao, “Direct degradation of cellulose to
5-hydroxymethyl-furfural in hot compressed steam with
inorganic acidic salts”, Royal Society of Chemistry: RSC Adv.,
vol. 4, 4978-4984, 2014.
[24] D. Murzin and O. Simakova, Eds., Biomass Sugars for
Non-Fuel Applications, Chapter 1, P. Bhaumik and P. L. Dhepe,
Conversion of Biomass into Sugars, Cambridge, U. K.: Royal
Society of Chemistry, 2015, pp. 1-53.
[25] F. C. de Melo, R. F. de Souza, P. L. A. Coutinho and M. O. de
Souza, “Synthesis of 5-hydroxymethylfurfural from
dehydration of fructose and glucose using ionic liquids”, J.
Braz. Chem. Soc., vol. 25 (12), 2378-2384, 2014.
[26] R. S. Assary, T. Kim, J. J. Low, J. Greeley and L. A. Curtiss,
“Glucose and fructose to platform chemicals: understanding
the thermodynamic landscapes of acid-catalyzed reactions
using high-level ab initio methods”, Phys. Chem. Chem. Phys.,
vol. 14, 16603-16611, 2012.
[27] X. Lin, Y. Qu, Y. Lv, Y. Xi, D. L. Phillips and Ch. Liu, “ The
first dehydration and the competing reaction pathways of
glucose homogeneously and heterogeneously catalyzed by
acids”, Phys. Chem. Chem. Phys., vol. 15, 2967-2982, 2013.