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Патент USA US2410590

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Patented Nomg, i946
STAT
'
2,410,590
CONCENTRATIONOF‘FAT-SOLUBLE
..
VITAMINS
~
Edgar M. Shantz, Rochester, N. Y., assignor to
Distillation Products, Inc., Rochester, N. Y., a‘
corporation of Delaware
No'Drawing.‘ Application January 21, 1944, _
Serial No. 519,203
10 Claims.
(a. 167-81)
2
This invention relates to improved procedure
fat is required. It is more practical and preferred
for the concentration of fat-soluble vitamins and’
in particular for the concentration of vitamin A
tion, from two to ten molecular equivalents of
contained in ?sh liver oils, and fractions thereof.
‘This invention has for its object to provide
Excess reagent may,\of course, be recovered and
to use a slight excess.
To speed up the reac
amine may be used for a given amount of oil. "
used again.- It is also preferred to carry out the
improved procedure for the concentration of fat
reaction in an ,inert atmosphere such as carbon‘
soluble vitamins. Another object is to provide
dioxide or nitrogen.
I,
improved procedure for the concentration of vita
If a diamine is used, it can be made to react
mins contained in. ?sh liver oils and distillates
.or‘fractions thereof, and in particular for the 10 with two molecules of fatty acid to yield a .di-.
amide. One method of doing this is to use just
concentration of vitamin A 'containedin such
enough of the diamine orlpolyamine to provide‘
- oils or fractions. Other objects will appear here
one —NH2 group for each fatty acid radical pres-1
ent in the fat which contains the vitamin. An
These and other objects are accomplished by
my invention which includes reacting a glyceride 15 other method is to react a given quantity of fat
with an‘ excess of the diamine, after which‘the
fat which contains a fat-soluble vitamin with a
excess unused diamine is removed and the reac
member of the group consisting of primary
tion product is then allowed to react with an
amines, secondary amines, and quaternary am
other equal quantity of the same oil or fat. '
monium bases, and then separating the fat-sol
If it is desired, the reaction products may be =
20
uble vitamin from the reaction products.
treated with an esterifying agent suchas acetic
In the following examples and description, I
,anhydride or acetyl chloride before distillation, '
have given several of the preferred embodiments
solvent extraction, or ?ltration of the desired
of my invention, but it is to be understood that
inafter.
,
.
"unsaponiflable” fraction in order to formvita-y
_ these are set forth for the purpose of illustration
25 min esters. Such a reagent would also react with '
and not in limitation thereof.
certain of the fatty acid ‘substituted amides, "as
The amine, or ammonium base, which is used
will be shown below. This is desirable in certain .,
must be one which will substantially completely
cases to decrease their solubility.
react with the glyceride oil under the conditions
The following empirical formulas are for the
of treatment.v Primary ami es are preferred
since they react with the glyceride oil with rela 30 purpose of illustrating and clarifying the .reac-'
tions described above. Speci?c examples are .
tive rapidity. Secondary amines react somewhat
given later.
more slowly but can be used satisfactorily.
Quaternary ammonium bases may be used but
tertiary amines are unsatisfactory. Substituted
amines, or ammonium bases, such as hydroxy, 35
halide, etc., amines can be used and are to .be
understood asbeing included within the expres
_1. Reaction of an oil with a primary amine, '
sions “primary amines,” "secondary amines,” and
“quaternary ammonium bases” as used herein
and in the claims.
. '
2. Reaction of oil with a hydroxy amine, such
40 as ethanolamine:
The reaction takes place over a relatively wide
range of temperature. The preferred range is
about 80° to about 150° C.‘ For most purposes a
' temperature of about 100° C. is quite satisfac
R'COO
Hz
.
glycerol + 3RICONHCHQCHEOH
tory. Too high a temperature causes decompo 45
3. Reaction of above products with esterify
sition of the more labile vitamins whereas low
ing agent such as acetyl chloride:
temperatures decrease the rate of reaction.
The time of reaction depends upon factors such
CHzOI-I
as concentration of the reactants, the tempera
HOH + SR'CONHCHzCHzOF 4- BCHaCOCI —-—v
ture, and the particular ammonium derivative 60
used. In most cases the reaction requires from
about two to twenty hours.
At least one molecular equivalent of amine
should be used based on the fatty acid content of
the glyceride treated if complete removal of the 65
HzQH
CHaOCOCHB
CEOCOCH: + 3R'CONHGH1CH4OCOH; +‘ GHCI
(IJHiOCOCHa
2,410,590
3
4
.
7a. Reaction of two equivalents oi’ vitamin
esters with a polyamine such as ethylenediamine:
4. Reaction of oil with an excess of a poly
amine such as ethylenediamine:
.
alcoocni .
a + NmcmcmNn, --.
" R'COO
8a. Reaction of vitamin esters with ‘a quater
nary ammonium base:
glycerol + aa'c ONHCHICHzNHt
5. Reaction of above products with another
equal amount of oil:
The following 'are speci?c examples of the
methods outlined above.
Example 1
190 grams of ?sh liver oil distillate containing
3R'd0NHCHICHiNH: + R'COOCHI
R'COO
a'coo
In
, _
210,000 units per gram of vitamin A ester were
glycerol + SR'CO'NHCHSCHSNHCOR' 15 heated at 100° C. under nitrogen for twenty
hours with 700 cc. of ethanolamine. At the end
8. Reaction of products of illustration 4 with
of this time the excess ethanolamine was re
an esterifying agent such asacetyl chloride:
moved under reduced pressure. The product was
20 a waxy solid at room temperature but became
onion
'
.
completely liquid at 50° to 60° C. 183 grams of
non + 3R'CONHCH:CH2NH| + acmooci —-i_»
H103’
this material were distilled in a cyclic molecular
still. A fraction weighing 32.2 gms. was obtained
GHQOCOCHI
‘
which distilled between 100° and 140° C. at a
HOCOCH; + 3R'CONHOH2CH2NHCOCHI + 6H0]
25 pressure of 3 to 10 mp. This fraction, a light
HrOCOCH;
yellow oil which became solid at room tempera
ture, contained 900,000 units per gram of vita
7. Reaction of two equivalents of oil with a
polyamine such as ethylenediamine:
min A alcohol.
80
n'coocm
2 R'COO H + aNmcmcmNm --$
R'cooom
.
Example 2
230 grams of ?sh liver oil distillate containing
200,000 units per gram of vitamin A ester were ,
heated for 15 hours at 100° C. under nitrogen
with 320 grams of ethanolamine. After removal
'
8. Reaction of an oil with ‘a quaternary am
monium base:
'
a'coocrn
,
35 of the excess ethanolamine under reduced pres
sure, the residual product was distilled in a cyclic
molecular stilL The fraction distilling between
100° C. and 145“ C. at a pressure of 3 to 10a
.
R'c'oocir + auz'mNon —-o glycerol + an'ooomn'qi
a'coo H:
-'
weighed 52 grams and contained 610,000 units of
40 vitamin A alcohol per gram.
This distillate was then dissolved in 200 cc. of
methyl alcohol and chilled to ~60° C. to freeze
The esters of other valuable substances such
‘out the fatty acid ethanolamides which had dis
as vitamin A, vitamin D, sterols. etc., occurring
in the oils react in an analogous manner to give
tilled with the vitamin A. After ?ltration in
the free alcohols. vThese are shown empirically 45 the cold, the methyl alcohol was evaporated and
in the following formulae where ROI-I stands for
the residue was found to consist of 20 grams of a
dark red oil containing 1,300,000 units of vita
the ‘alcohol. such'as vitamin A.
min A per gram.
la.» Reaction of- vitamin esters with a primary
amine, RfiNHz:
'1
Example 3
150 grams of ?sh liver oil distillate containing
200,000 units of vitamin A per gram were heated
2c.-Reactionof vitamin esters with a hydroxy
for 16 hours at 100° C. under nitrogen with 450
amine, such as ethanolamine:
cc. of ethanolamine.
3a, Reaction of abovewproductswwith esterify
ing ‘agent such as acetyl chloride:
‘
'7 L
ROI-1+R'CONHCHaCH2OH+2CI-isC0Cll>
60 again ?ltered. , The ether was removed, the resi
4a. Reaction of vitamin esters with an excess
of a polyamine such as ethylenediamine:
v a'coo'n-i-nmcrnonmm»
ROHi-i-R'CONHCHzCHzNHa
due dissolved in 500 cc. of methyl alcohoL'and
chilled to —35° C. After ?ltration the methyl
alcohol was evaporated and the residue was found
to contain 54 grams‘ of dark red oil having a
65 potency of 508,000 units of vitamin A per gram.
Example 4
5a. Reaction of above products with another
equal amount of oil: '
After removal of the ex
cess ethanolamine by distillation under reduced
pressure, the residue was taken up in 1.5 liters of
warm ethyl ether. About 30% of the material
was insoluble at room temperature and was ?l
tered off. The ?ltrate was chilled to 5° C. and
.
R'CONHCI-IzCHzNHa-l-R'COOR»
ROH-l-R'CONHCI-hCI-IaNHCOR'
6a. Reaction of products of illustration 4 with
an esterifying agent such as acetyl chloride:
200 grams of ?sh liver oil distillate containing
200,000 units per gram‘ or vitamin A were heated
70 for 12 hours with 300 grams of 1-amino-2-bu
tanol at 100° C. under nitrogen. The excess
‘ the
amine
residual
was removed
product distilled
under reduced
in a cyclic
pressure
molecular
and J -
7
still. Four fractions weighing a total of 155
grams were removed between 100° C. and 160° C.
2,410,59o
5
The largest fraction had a potency of 353,000
units of vitamin A per gram.
‘
Example 5
\200 grams of fish‘ liver oil distillate containing
200,000 units per gram of vitamin A were heated.
- for 12 hours at 100° C. under nitrogenwith 275
grams
of
2-amino-2-ethyl-L. 3-propanediol.
The entire mixture was placed in the molecular
tained mainly glycerol and excess aminoethyl
ethanolamine. The fraction distilling between
.4120 and 140° C. at a pressure of 15 microns con
sisted of a light yellow solid having a vitamin A
potency of 5105000 units per gram. ,
Example 11
560 gms. of soup?n shark liver oil distillate '
having a vitamin A potency of 213,000 units per.
still and the excess amine removed at 100° C. at ' 10 gram were heated‘ with- 125 gms. of ethanolamine
a pressure of about 1- mm. .The pressure was
then reduced to 540;‘, and the temperature
. raised to 140° C.
Aldistillate with a vitamin A
potency of 400,000 units per gram was obtained.
Example 6
for 16 hours at 80° C under. nitrogen‘. The re
action mixture was then dissolved in 2.5 liters
of. acetone and the fatty acid ethanolamides
?ltered off after successively chilling the mix-_
15 ture to 0° C., -'35° C., and —50° C. ‘The solvent
was then removed from the ?ltrate under re
duced'pressure and the residue distilled in a.
275 grams of ?sh liver oil distillate were heated
molecular still. The fraction distilling between
for'?ve hours at 100° C. with 2'75 grams of
110° and 135° C. contained vitamin A alcohol a
ethylene diamine. The excess ethylene diamine
.
was removed under reduced pressure, and the 20 a potency of 620,000 units per gram.
residue distilled in the‘ molecular still. _,The dis
Example 12
,
tillate had a potency of 363,000 units per gram
600 gms. of ?sh liver oil having a vitamin
of vitamin A.
potency of 27,000 units per gram were heated
Example 7
under nitrogen for 16 hours at 80° C. with 100
110 grams of ?sh liver oil distillate containing 25 gms. of ethanolamine. The reaction mixture
was .dissolved in 3 liters of warm acetone. This
200,000 units of vitamin A per gram were heated
solution was cooled to —l5° C. and the solid ma
under nitrogen for 10 hours at 100° C. with 100
terial ?ltered o?, washing with 500 ml. of chilled
grams of ethylene diamine. The excess diamine
acetone. The ?ltrate was then chilled to -50° C.
was removed under reduced pressure and 110
grams more of the ?sh liver oil were added to 30' and again the solids which separatedwere ?ltered
off as before. The solvent was removed from
the residue. This mixture was heated for‘ an
the ?ltrate by distillation and the residue dis
other twenty hours under nitrogen after which it
tilled in a molecular still. The main fraction
was distilled in a molecular still. The product
contained 416,000 units per gram of vitamin A.
remained liquid only if heated to about 100° C.
A distillate was obtained between 100° and 160°
Example -1 3
C. which was a viscous orange oil containing
600
gms.
of
a
high
vacuum distillate of de
570,000 units per gram of vitamin A.
odorizer scum containing 24% tocopherol were
Example 8
heated for 12 hours at 80° C. with 100 gills. of
150 grams of ?sh liver oil distillate contain 40 ethanolamine. 3.0 liters of acetone were added
to the reaction mixture. The solution was then
ing 200,000 units per gram of vitamin A were
chilled to —50° C. and the separated solids ?ltered
heated at 100° C. with 150 grams of ethylene
I oil". The solid material wasvdissolved in 2 liters
diamine for 15 hours. The excess diamine was
of fresh acetone and again the solids were re
removed under reduced pressure and the residue
moved by ?ltration after chilling to -50° C. The
dissolved in one liter of acetone. 100 grams of
?ltrates were combined and the acetone removed
pyridine, followed by 100 grams of acetic anhy
by distillation. The residue was distilled in a
dride, were added. Upon cooling, the fatty acid
molecular still. The fractiondistilling at 150° C.
acetic acid diamides of ethylene diamine crystal
contained 25% of the starting tocopherol at a
lized out and. were ?ltered o?. Ethyl ether was
added to the ?ltrate and the solution washed 0 concentration of 50%. The fraction distilling
at 170° C. contained 45% of the original toco
several times with water. Upon evaporation of
pherol at a concentration of 72.5%.
the ether, 68 grams of residue remained which
contained 358,000 units per gram of vitamin A
Example 14
acetate.
Ca Ca
400 gms. of a high vacuum distillate of deodor
Example 9
izer scum containing 18% tocopherol were heated
at 80° C. ‘for 15 hours with 70 grams of ethanol
30 grams of ?sh liver oil distillate (200,000 units
per gram), 30 cc. of tetraethanolammonium hy
amine. The reaction mixture was dissolved in 2
droxide (40% aqueous solution) and 30 cc. of
liters of acetone and the solid material removed
ethyl alcohol were re?uxed for 2 hours under 60 by ?ltration after chilling ?rst to -20° C., then
to -5o° o. The acetone was distilled from the
nitrogen. - The mixtureywas dissolved in ether,
washed three times with water to remove the
?ltrate and the residue‘ dissolved in 1 liter of
ethyl ether. The ether solution was washed three
reaction products which are soluble in water and
times with lNHCl, followed by two water washes.
the ether removed by evaporation‘; The residue
consisted’ of 12 grams of red oil which contained 65 This washing was found to improve the taste ‘of '
the ?nal product considerably. The ether was
465,000 units per gram of vitamin A alcohol.
then removed by distillation. The residue then
Example 10
contained 50.3% tocopherol. Upon distillation
' 270 gms. of ?sh liver oil distillate containing
75% of this tocopherol was obtained at a concen
186,000 units of vitamin A per gram were heated 70 tration of 70% or better.
The vitamin can" be separated from the reac
‘at 80° C. for 15 hours with 160 gms. of amino '
tion product in any desired manner. I prefer to'
ethylethanolamine under a stream of nitrogen.‘
use vacuum distillation, and in particular, high-'
The reaction mixture was then placed in a
vacuumunobstructed path or molecular distilla
molecular still and distilled. The ?rst fraction,
removed at 100° C. at a pressure of 1 mm., con 75 tion. However, solvent extraction and ?ltration
2,410,590‘
7 i
.
or pressing of the reaction products may be used.‘v -
Combinations-oi these separation procedures can
be used.
'
While the procedure of my inventionis of par
ticular advantage for the concentration or sep
aration oi’ vitamins, it can also be used to sepa
rials which are present in fats and which dolnot
react with the amines or like compounds dis
10 vacuum unobstructed path distillation and sep
arating a vitamin A concentrate as a distillate.
.
.
_1. They process of preparing a fat-soluble vi
tamin concentrate which comprises reacting a
'7. The process of preparing a fat-soluble vi~
tamin concentrate which comprises reacting a
glyceride tat which contains a fat-soluble vita
glyceride fat which contains a fat-soluble vita
min with at least approximately stoichiometric
amounts of a member of the group consisting of
primary amines, secondary amines, and quater
nary-ammonium bases, until substantially all the
iatty acids of the glyceride have combined there
with and then separating the vitamin in concen
trated form from the reaction mixture.
'
amines, secondary amines, and quaternary am
monium bases, until substantially all the fatty
acids or the glyceride have combined therewith
and then subjecting the reaction mixture to high
rate or concentrate sterols as well as like mate
What I claim is:
,
trate which comprises reacting a glyceride fat de
rived from a ?shwhich contains vitamin A with
at least approximately stoichiometric amounts
of a member or the group consisting of primary
'
closed herein.
8'
. 6. The process of preparing vitamin A concen.
min with 1 to 10 molecular equivalents of a mem
ber oi’ the group consisting of primary amines,
secondary amines, and quaternary ammomum
bases, until substantially all the fatty acids of
the glyceride have ‘combined therewith and sep
20 arating the vitamin from the reaction product.
'
2. The process 01' preparing a fat-soluble vi
tamin concentrate which comprises reacting a
glyceride fat which contains a‘ fat-soluble vita
min with at least approximately stoichiometric
amounts of a primary amine, until substantially
all the fatty acids of the glyceride have combined
therewith and then separating the vitamin from
the reaction mixture.
3. The process or preparing a fat-soluble vi 30
tamin concentrate which comprises reacting a
glyceride fat which contains a fat-soluble vita;
min with approximately stoichiometric amounts
or a member of the group consisting of primary
' 8. The process‘ of preparing a fat-soluble vi
tamin concentrate which comprises reacting a
glyceride tat which contains a fat-soluble vita
min with at least approximately stoichiometric
amounts of. a member of the group consisting oi’
primary amines, secondary amines, and quater
nary ammonium bases until substantially all the
fatty acids of the glyceride have combined there
with at a temperature of about 100° for a period
of time between about 2 to 20 hours, and then
separating the vitamin from the reaction prod
uct.
'
9. The process of preparing a fat-soluble vi
tamin concentrate which comprises reacting a
- amines, secondary amines, and quaternary am 35 glyceride fat derived from a fish and containing a
monium bases at a temperature of between about
fat-soluble vitamin with l to 10 molecular equiv
80° and 150° C. until substantially all the fatty
alents of a primary amine until substantially all
acids of the glyceride have combined therewith,
the fatty acids of the glyceride have combined
and then separating the vitamin from the reac
therewith at a temperature of about 100° for a
tion mixture.
40 period of time between about 2 to 20 hours, and
4. The process ‘of preparing a fat-soluble vi
‘separating a vitamin in concentrated form from ‘
tamin concentrate which comprises reacting a
the reaction products.
glyceride 'fat which contains a fat soluble vita
10. The process of preparing a concentrate of
min with at least approximately stoichiometric
a substance selected from the group consisting
amounts of a primary amine at a temperature of ' of fat soluble vitamins and sterols present in a
between about 80° and 150°, until substantially all
natural glyceride fat which substance does not
the fatty acids of the glyceride have combined
react with amines or quaternary ammonium bases
therewith, and then separating the vitamin from
which process comprises reacting the fat with at
the reaction mixture.
-
5. The proces of preparing vitamin A concen
trate which comprises reacting a glyceride fat de
rived from a ?sh which contains vitamin A with:
at least approximately stoichiometric amounts of
a member of the group consisting of primary
amines, secondary amines, and quaternary'am- .
monium bases, until substantially all the fatty
acids of the glyceride have combined therewith
and then separating the vitamin A in concen
trated form from the reaction mixture.
least approxlmately stoichiometric amounts of
a member of the group consisting of primary
amines, secondary amines and quaternary am
monium bases until substantially all the fatty
acids of the glyceride have combined therewith
and then separating said substance in concen
trated form from the reaction mixture.
EDGAR M. SHANTZ.
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