U.S. patent number 3,875,140 [Application Number 05/365,356] was granted by the patent office on 1975-04-01 for process for the preparation of fructose.
This patent grant is currently assigned to Boehringer Mannheim G.m.b.H.. Invention is credited to Sidney Alan Barker, Brian William Hatt, Peter John Somers.
United States Patent |
3,875,140 |
Barker , et al. |
April 1, 1975 |
Process for the preparation of fructose
Abstract
Fructose is produced by the isomerization of glucose and/or
mannose by a process comprising isomerizing the glucose or mannose
in an alkali solution containing an aryl boric acid.
Inventors: |
Barker; Sidney Alan
(Birmingham, EN), Somers; Peter John (Birmingham,
EN), Hatt; Brian William (Bromsgrove, EN) |
Assignee: |
Boehringer Mannheim G.m.b.H.
(Mannheim, DT)
|
Family
ID: |
5847774 |
Appl.
No.: |
05/365,356 |
Filed: |
May 30, 1973 |
Foreign Application Priority Data
|
|
|
|
|
Jun 15, 1972 [DT] |
|
|
2229064 |
|
Current U.S.
Class: |
536/125; 127/30;
127/42; 127/46.2 |
Current CPC
Class: |
C13K
11/00 (20130101); H02J 13/00004 (20200101) |
Current International
Class: |
C13K
11/00 (20060101); C13k 009/00 () |
Field of
Search: |
;127/42,46R,46A,30
;260/29R |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Chemical Abstracts, 67:117205v (1967)..
|
Primary Examiner: Wolk; Morris O.
Assistant Examiner: Marantz; Sidney
Attorney, Agent or Firm: Burgess, Dinklage & Sprung
Claims
What is claimed is:
1. Process for the production of fructose by the isomerization of a
sugar selected from the group consisting of glucose, mannose and
mixtures thereof comprising isomerizing said sugar in an alkali
solution containing an aryl boric acid.
2. Process as claimed in claim 1, wherein the solution has a pH
value of between 10 and 14.
3. Process as claimed in claim 2, wherein the solution has a pH
value of between 11 and 12.5.
4. Process as claimed in claim 1, wherein the process is carried
out in aqueous solution at a temperature of between 20.degree. and
80.degree.C.
5. Process as claimed in claim 4, wherein the process is carried
out at a temperature of between 45.degree. and 50.degree.C.
6. Process as claimed in claim 1, wherein the aryl boric acid is a
component of an insoluble organic polymer.
7. Process as claimed in claim 6, wherein the polymer is a polymer
or copolymer of vinylphenyl boric acid or of a derivative
thereof.
8. Process as claimed in claim 6, wherein the polymer is an ion
exchanger resin loaded with a phenyl boric acid derivative.
Description
The present invention relates to a process for the production of
fructose by the isomerization of glucose or mannose in alkaline
solution.
The base-catalyzed isomerization of glucose, mannose and fructose
has been known for a long time; it is known by the name of its
discoverers as the "Lobry de Bruyn-Alberda van Ekenstein
rearrangement" (see Rec. trav. chim. Pays-Bas, 14, 203/1895 and 15,
92/1896). Since that time, the reaction has been thoroughly
investigated by many workers. It has been ascertained that a large
variety of bases, for example, sodium hydroxide, sodium carbonate,
basic ion exchangers, ammonia and the like, catalyze the adjustment
of the equilibrium but that the yield of fructose formed is only
about 20-30% (see Gottfried and Benjamin, Ind. Eng. Chem., 44,
141/1952).
It is also known that in the case of the alkaline isomerization of
glucose, the yield of fructose can be considerably increased when
working in the presence of borates (see Mendicino, J.A.C.S., 82,
4975/1960). However, a disadvantage of this reaction is that only
relatively dilute sugar solutions can be used and the high
concentrations of the reagents employed make the working up of the
solution for obtaining pure fructose uneconomical.
We have now found that the base-catalyzed isomerization of glucose
and mannose to give fructose can be favorably influenced by using
the process of the invention.
Essentially, the present invention comprises a process for the
isomerization of glucose and/or mannose in alkaline solution,
wherein the solution contains an aryl boric acid. Depending upon
the alkali content, the temperature and the amount and nature of
the aryl boric acid added, fructose yields of up to and beyond 80%
can be obtained.
As the boric acid, there can be used, for example, phenyl boric
acid, naphthyl boric acid, alkoxyphenyl boric acids, such as
4-methoxyphenyl boric acid, nitrophenyl boric acids or sulfonated
phenyl or naphthyl boric acids. The process can be carried out
especially advantageously when the aryl boric acid is a component
of an insoluble organic polymer. Such insoluble polymers can be
obtained, for example, by polymerizing a vinylphenyl boric acid or
a derivative thereof with itself or with styrene or a similar
compound or by fixing an aryl boric acid, via a further
substituent, on to a reactive carrier material, for example, by
fixing a sulfonylphenyl boric acid on to an anion exchanger
resin.
The process according to the present invention can be carried out
with the use of glucose solutions with a concentration of up to 30
or 40%; it is especially advantageous to use 20-25% glucose
solutions. Instead of pure glucose, there can also be used
appropriate crude starch hydrolyzates or invert sugar solutions
from which a part of the fructose has been removed in known
manner.
The reaction temperature used is usually between about 20.degree.
and 80.degree.C and preferably between 45.degree. and 50.degree.C.
In the case of higher temperatures, the decomposition of the
fructose and of the aryl boric acids becomes more noticeable as a
disturbing side reaction and, at comparatively low temperatures,
the rate of the reaction is, as is to be expected, lower so that
the reaction is uneconomic.
Since it is a base-catalyzed reaction, the rate of the reaction
increases with increasing pH value but, on the other hand, the
irreversible decomposition of the fructose is favored by high pH
values. Consequently, pH values of between 10 and 14 have proved to
be especially favorable because, on the one hand, the rate of
formation of the fructose is great enough and, on the other hand,
the irreversible decomposition of the fructose formed is not
important. pH values between 11 and 12.5 are regarded as being
optimal.
Our investigations have shown that, per mole of glucose, the
reaction solution should contain about 1/2 to 1 mole of aryl boric
acid in order to bring about a maximum formation of fructose. When
using smaller amounts of aryl boric acid, the yield of fructose is
impaired and, when using higher amounts of aryl boric acid, the
rate of reaction drops very considerably, which is surprising and
which naturally impairs the economy of the process.
The separation of the fructose formed from the reaction solution
can be carried out in known manner, for example, by separation by
means of an ion exchanger or by precipitation of the fructose from
a neutral solution in the form of calcium fructosate. When the aryl
boric acid is added to the reaction solution in the form of a
component of an insoluble polymer, the fructose formed is
preponderantly also fixed in complex form on the resin and can be
removed with the resin from the reaction solution. By washing out
the separated resin with dilute hydrochloric acid, there is
obtained a fructose-enriched solution which can then be further
worked up in known manner.
Although aryl boric acids are relatively stable under the
conditions used for the process according to the present invention,
the boric acids included in a polymeric resin are, nevertheless,
partially decomposed at comparatively high temperatures.
Consequently, an especially advantageous variant of the process
according to the present invention is to carry out the
isomerization of glucose at a temperature of about 30.degree. to
60.degree.C in solution in the absence of an aryl boric acid,
subsequently to cool the solution and then to pass it through an
aryl boric acid-containing polymer in which the fructose formed is
almost completely absorbed, whereupon the fructose-impoverished
solution can again be heated up and recycled to the reaction zone.
When the resin used has a sufficient absorption capacity, repeated
passage in this manner enables fructose yields to be obtained which
are similar to those obtained when carrying out the isomerization
in the presence of an aryl boric acid.
The following Examples are given for the purpose of illustrating
the present invention:
EXAMPLE 1
ISOMERIZATION IN THE PRESENCE OF PHENYL BORIC ACID
2.0 g radioactive marked D-glucose were added to a solution of 0.26
g sodium hydroxide, 1.15 g phenyl boric acid anhydride in 4.0 g
water. After the addition of 0.39 ml of a 50% solution of sodium
hydroxide, there was obtained a clear solution with a pH of 12.17
at 24.5.degree.C. The solution was placed in a glass flask under an
atmosphere of nitrogen, further heated for 1.7 hours at 50.degree.C
and thereafter stored at -15.degree.C until analyzed.
An aliquot thereof was diluted and determined according to the
automated resorcinol method (see Yaphe et al., Anal. Biol. Chem.,
13, 143/1965). The analysis gave a fructose content of 49.4% of
theory.
Aliquots which had been chromatographed, either directly or after
acidification with sulfuric acid, over a borate ion-charged anion
exchanger gave a fructose yield of 46.7% of theory (also determined
according to the resorcinol method).
A further aliquot was chromatographed over an anion exchanger in
the borate form, the fructose-containing fractions were mixed with
5 g unmarked fructose and the total mixture freed from residual
boric acid by means of "Borasorb" (Borasorb is a registered
trademark for a boron absorbent resin available from Calbiochem,
Los Angeles). In order to remove the residual glucose and mannose,
the di-O-isopropylidene derivative of fructose was prepared
according to the method of Bell (J. Chem. Soc., 1952, 3760) and
purified by extraction with chloroform and recrystallization from
petroleum ether. The radioactive determination corresponds to a
yield of 44.5 % fructose.
EXAMPLE 2
Determination of the important reaction parameters for the
isomerization of glucose to fructose
General process: A precise amount of an aryl boric acid anhydride
was mixed in a reagent glass with a known amount of water and a
known amount of sodium hydroxide. The solution or suspension
obtained was mixed with a definite amount of glucose and stirred
until solution was complete. The pH value of the solution was
measured at ambient temperature and, when necessary, adjusted
precisely by the addition of a small amount of sodium hydroxide
solution. Parts of this solution were placed in small glass flasks
which were closed under an atmosphere of nitrogen. The flasks were
maintained for a definite period of time at a constant temperature
and subsequently cooled to 0.degree. or to -15.degree.C and, at
this temperature, stored until analyzed. The analyses were carried
out according to methods described above in Example 1. The results
obtained from the various experiments are summarized in the
following Table I.
TABLE I
Effects of various reaction conditions on the isomerisation of
glucose to fructose in alkaline solution in the presence of aryl
boric acids in concentrated solutions
aryl boric acid I II III IV V VI
__________________________________________________________________________
phenyl boric acid 1:1 12.05 25.1 50.0 57 120 1:1 12.16 25.7 37.0 55
340 1:1 12.16 25.7 50.5 50 90 1:1 12.16 25.7 61.5 50 15 1:1 10.95
26.5 50.0 34 720 1:1 -- 24.9 50.0 53 21 1:1 11.97 24.8 50.0 55 150
1:1 12.08 24.9 50.0 52 110 2:1 12.50 17.8 50.0 19 60 1:2 12.00 27.9
50.0 55 95 0:1 12.03 30.2 50.0 40 90 sulphonate phenyl boric acid
1:1 12.00 26.4 50.0 46 140 4-methoxy-phenyl boric acid 1:1 12.14
25.1 50.0 55 120 3-nitrophenyl boric acid 1:1 12.04 24.6 50.0 18 90
p-tolyl boric acid 1:1 12.00 3.6 50.0 68 240 1:1 12.00 9.0 50.0 63
250 1:1 12.00 14.4 50.0 61 220 1:1 12.00 23.4 50.0 56 250
__________________________________________________________________________
I = molar ratio of aryl boric acid to D-glucose II = pH of the
solution III = initial concentration of D-glucose (% by weight) IV
= temperature of the reaction in .degree.C. V = maximum yield of
D-fructose (% by weight) VI = time of maximum yield in minutes
EXAMPLE 3
Isomerization of sugars in alkaline solutions in the presence of
aryl boric acids in dilute solution
The results summarized in the following Table II were obtained by
using the experimental procedures described in Example 2
(temperature 50.degree.C):
TABLE II
__________________________________________________________________________
aryl boric starting ratio of sugar pH of % yield reaction acid
material aryl boric content solu- of D- time in acid to in mole
tion fructose min. sugar
__________________________________________________________________________
phenyl boric D-glucose 1:1 0.02 12 73 270 acid D-mannose 1:1 0.02
12 53 270 D-fructose 1:1 0.02 12 77 270 D-glucose 1:1 0.02 13 66
120 D-mannose 1:1 0.02 13 65 120 D-fructose 1:1 0.02 13 51 120
D-glucose 2:1 0.02 12 40 210 D-mannose 2:1 0.02 12 36 210
D-fructose 2:1 0.02 12 83 210 D-glucose 1:1 0.125 12 70 240 73 480
D-glucose 1:1 0.125 11 17 600 21 1200 4-methoxy- D-glucose 1:1 0.02
12.1 81 230 phenyl boric acid 61 720 3-nitrophenyl D-glucose 1:1
0.02 12 81 280 boric acid 70 720 p-tolyl D-glucose 1:1 0.02 12.01 8
240 boric acid 1:1 0.02 11.0 7 500 1:1 0.02 13.0 77 130
__________________________________________________________________________
EXAMPLE 4
Production of poly-(4-vinylphenyl boric acid) resin
1.1 g iminodiethyl-4-vinylphenyl boric acid, 0.17 g
divinyl-benzene/ethyl vinyl benzene (1:1), 0.76 g styrene and 0.045
g azo-bis-isobutyric acid nitrile were dissolved in 10 ml
chloroform, deaerated by passing through nitrogen and heated in a
closed flask for four hours at 70.degree.C. The gel obtained was
dried and washed with 1N hydrochloric acid, until the wash water no
longer gave a yellow coloration with periodate/pentane-2,4-dione.
Subsequently, it was washed with distilled water and dried over
phosphorus pentoxide. The yield of poly-(4-vinylphenyl boric acid)
resin was 81%. The dried resin was sieved and the fractions of
60-120 mesh were used for the following experiments.
EXAMPLE 5
Isomerization of glucose and fructose in alkaline solution on
poly-(4-vinylphenyl boric acid) resin
0.68 g of the resin prepared according to Example 4 was stirred at
various temperatures in a thermostatically controlled vessel in an
aqueous solution of glucose, fructose and sodium hydroxide, the
solution having a pH of 12.0. Subsequently, the resin was separated
off from the supernatant solution and the absorbed sugars were
washed out with dilute hydrochloric acid. The supernatant solution
and wash water were investigated for their content of glucose and
fructose according to the cystein-sulfuric acid and according to
the resorcinol method. The results obtained are summarized in the
following Table III.
TABLE III
__________________________________________________________________________
Isomerization and distribution of D-glucose and D-fructose on
poly-(4-vinylphenyl boric acid) resins at pH 12
__________________________________________________________________________
expt. sugar content reaction temper- sugar content sugar content
total of starting time in ature of supernatant of resin (mg) recov-
solution (mg) minutes solution (mg) ery %
__________________________________________________________________________
D-glu- D-fruc- glu- fruc- glu- fruc- cose tose cose tose cose tose
__________________________________________________________________________
A 350 350 15 20.degree.C. 265 83 63 245 94 B 350 0 240 50.degree.C.
77 21 68 155 91.3
__________________________________________________________________________
EXAMPLE 6
Use of poly-(4-vinylphenyl boric acid) resin in a reactor
2 g of a poly-(4-vinylphenyl boric acid) resin prepared according
to Example 4 were placed in a column with a diameter of 1.3 cm,
which was thermostatically controlled at 19.degree.C. The inlet and
outlet of the column were connected via pipes and an appropriate
pump with a reaction circuit. The resin was first washed with 1N
soda lye until the solution running off had a pH of 12.0.
Subsequently, the total system was filled with a 1N aqueous sodium
hydroxide solution to which 0.68 g D-glucose was added. With a pump
capacity of about 0.23 ml per minute, the solution was pumped
around the reaction circuit at various temperatures and
subsequently, the content of glucose and fructose thereof was
investigated. The resin was, after separation of the supernatant
solution, washed out with hydrochloric acid and the fructose and
glucose content of the wash water also investigated. The results of
the various experiments are summarized in the following Table
IV:
TABLE IV
__________________________________________________________________________
Isomerization of D-glucose to D-fructose on poly-(4-vinylphenyl
boric acid) resin in a reactor.
__________________________________________________________________________
expt. D-fructose in D-fructose yield of temp. of reaction no.
supernatant absorbed on D-fructose reaction time in solution (g)
resin (g) (%) circuit hours
__________________________________________________________________________
1 0.161 0.224 56.5 37.degree.C. 22 2 0.219 0.348 56.7 37.degree.C.
46 3 0.018 0.342 52.8 50.degree.C. 6 4 0.652 0.406 42.3
37.degree.C. 21.5
__________________________________________________________________________
It will be understood that the specification and examples are
illustrative but not limitative of the present invention and that
other embodiments within the spirit and scope of the invention will
suggest themselves to those skilled in the art.
* * * * *