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Патент USA US3076014

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United States Pateut O " ice
Patented Jan. 29, 1953
2
Amongst advantages that might be mentioned are a re
duction in the reaction period from 48 hours to about 6
3,076,604
‘PREPARATHQN @F Z-MEJTHYLé-PHYTYL-lA
NAPHTHQHYDRUQUENQNE ESTER
Raiph Franz .Hirschmann, Westheld, N.J., assignor to
hours in some cases, and even as little as 15 minutes. Be
sides reducing the reaction time, the process of this in
vention, consistently gives yields of the desired reaction
gderek dz (10., inc, Rahway, NJ" a corporation oi New
product which are in most cases about 2 times larger
ersey
than those previously attained. Thus, yields by prior art
No Drawing. Filed Jan. 21, 1959, Ser. No. 7%,059
2 Qiaims. (Cl. 259-41tl.5)
methods usually average about 25% whereas with the
novel process of this invention yields of 50% or more of
This invention relates to vitamin K1. More particu 10 those theoretically obtainable of the desired product are
attainable.
boxylic acid esters of 2-methyl-3-phytyl-l,4-naphthohydro
Furthermore, the resulting novel l-monocarboxylic acid
quinone and processes of producing these compounds.
esters of Z-methyl-B-phytyl-1,4-naphthohydroquinone can
Such compounds possess vitamin K1 activity and are use
be hydrolyzed to 2-methyl-3-phytyl-l,4-naphthohydro
ful intermediates in the synthetic production of vitamin 15 quinone as more fully appears in copending US. appli~
K1 and derivatives thereof.
cation, Serial No. 403,638, ?led January 12, 1954, and
This application is a continuation-in-part of applica
the latter compound can then be oxidized to vitamin K1
by'the usual procedures with substantially quantitative re
tions Serial Nos. 403,638, now U.S. Patent 2,906,780,
sults.
and 403,640, now abandoned, each ?led January 12, 1954.
In the usual method for the commercial production 20
In general, any suitable l-monocarboxylic acid ester
of vitamin K1, Z-methyl-1,4-naphthohydroquinone is re
of Z-methyl-l,4-naphthohydroquinone can be employed
larly, this invention is concerned with novel monocar
acted with phytol at about 86° C. for about 48 hours in
the presence of oxalic acid to produce 2-methyl-3-phytyl
1,4-naphthohydroquinone which is subsequently oxidized
quantitatively to Z-methyl-B-phytyl-1,4-naphthoquinone
as a reactant in this new process.
Thus the acyloxy sub
stituent present at the 1 positioned the naphthohydro—
quinone nucleus may be an alkylacyloxy, arylacyloxy or
25 aralkylacyloxy group derived from a monocarboxylic acid.
(vitamin K1). The described condensation not only re
Ordinarily, however, it is preferred to effect the described
quires an undesirably long reaction period which seriously
novel condensation using a l-monocarboxylic acid ester
limits production but also restricts the use of equipment
of Z-methyl-l,4-naphthohydroquinone in which the acyloxy
employed in the reaction from use in other operations.
group contains 8 carbons or less. Speci?c examples
in addition, this reaction results in formation of appre 30 of such compounds which can be used in this invention
ciable quantities of the undesirable angular by-product,
thatmight be mentioned are Z-methyl-1,4-naphthohydro
2-methyl-2-phytyl-l,4-naphthohydroquinone. Most seri
ous, however, is the low yield obtained in this reaction
which seldom exceeds about 25% of the desired product.
Besides these disadvantages, the resulting 2-methyl-3 35
phytyl-l,4-napht‘iohydroquinone must be isolated from
various contaminating side products formed in the
reaction mixture by tedious and time consuming methods.
An ultimate object of this invention is to provide a
quinone
quinone
quinone
quinone
quinone
quinone
quinone
- 1 - acetate, 2 - methyl - 1,4 - 1 - propionate, 2 - methyl - 1,4 - 1 - butyrate, 2 - methyl - 1,4 - 1 - valorate, 2 - methyl - 1,4 ~
- 1 caproate, 2 - nethyl - 1,4 - 1 - caprylate, 2 - methyl - 1,4 - 1 - phenylacetate, Z - methyl -
naphthohydro
naphthohydro
naphthohydro
naphthohydro
naphthohydro
naphthohydro
1,4 - naphtho
hydroquinone - l - benzoate and the like.
These and
method of producing vitamin K1 in greatly increased yield. 40 similar esters can be prepared by the application of pro
Another object is to provide novel chemical compounds
cedures in the literature, one source being US. Patent No.
which are useful intermediates in the synthetic production
2,334,669.
Pursuant to the subject invention it has been found that
of vitamin K1 and its derivatives and processes of prepar
the condensation of a l-monocarboxylic acid ester of 2
ing such intermediates. A further object of this inven
tion is to substantially reduce the over-all time required 45 methyl-l,4-naphthohydroquinone with phytol to produce
to produce vitamin K1 synthetically. Other objects will
the corresponding l-monocarboxylic acid ester of Z-meth.
appear from the following description of the invention.
These and other objects have been realized according
to the present invention by the discovery that phytol can
about by the use of a suitable acidic condensing agent as
yl-3-phytyl-l,4-naphthohydroquinone can be brought
catalyst. The acidic condensing agent may be more fully
be condensed with a l-monocarboxylic acid ester of 2~ 50 described as a dehydrating catalyst, i.e. a compound which
is capable of splitting out Water. > Among such compounds
methyi-l,4-naphthohydroquinone in the presence of cer
which may be utilized in the reaction are those which are
tain catalysts to produce the corresponding novel l-mono~
preferably substantially insoluble, i.e. heterogeneous, in
carboxylic acid ester of 2-methyl-3-phytyl-1,4-naphthohy
droquinone.
This reaction may be illustrated as “follows:
the reaction medium, are strongly acidic and preferably
55 ‘have a pH of about 2 to 4.5 in water and which do not
'form esters with phytol. included among the preferred
dehydrating catalysts which are considered suitable for
‘effecting this reaction that might be mentioned are alkali
metal bisulfates such as sodium bisulfate and potassium
‘bisulfate and cation exchange resins on the hydrogen
cycle such as those of the phosphonic and phosphonous
acid type, illustrations of which are Duolite C—60 and
I —CH3
CHQCH=L 01320151131
Duolite C-6l manufactured by Chemical Process Co.,
Redwood City, California.
65
Reaction between the l-rnonocarboxylic acid ester of 2—
methyl-1,4-naphthohydroquinone and phytol is conveni
ently achieved by contacting the reactants and catalyst
in the presence of a suitable reaction medium at an ele
wherein R represents an acyl group.
I
This reaction possesses several noteworthy advantages
over the prior art procedure previously described.
vated temperature, preferably from about 65 to 90° C.
0 Broadly, any inert organic solvent in which the reactants
are soluble may be used asgthe reaction medium although,
since the reaction is ordinarily etfected at elevated tem
3,076,004
4
3
acid ester of Z-methyl-1,4-naphthohydroquinone with
phytol is conveniently achieved by contacting the react
peratures, it is desirable to employ a solvent which boils
above the reaction temperature. Furthermore, to obtain
the advantages of this novel process when a preferred de
hydrating catalyst is used, a solvent should be employed
for the reaction in which the catalyst is substantially in
soluble. Solvents such as benzene, toluene, dioxane and
ants with boron tri?uoride in the presence of a suitable
reaction medium.
Broadly, an inert organic solvent in
which the reactants are soluble may be used as the re
action medium although it is desirable to employ a sol
vent which boils above the reaction temperature. Sol
vents such as tetrahydrofuran, dioxane, and ethylene gly
reaction media in which the condensation may be ef
col dimethyl ether are examples of suitable reaction
fected.
As previously indicated this condensation is readily 10 media in which the condensation may be effected.
In effecting this variation reaction, a solution of the
effected at temperatures of 65-90“ C. By carefully con
reactants may be conveniently contacted with boron tri
trolling the temperature within the range of 70-85” C.
?uoride as a gas or, more conveniently, in the form of a
optimum conditions in terms of time and yield are real
complex such as a boron trii'luoride etherate. Only cat
ized. Within the range of 70-85 ° C., using a preferred
ethylene glycol dimethyl ether are examples of suitable
dehydrating catalyst, a reaction time of l to 3 hours is en
15 alytic amounts of boron tritiuoride are necessary to pro
tirely adequate whereas with lower temperatures reaction
mote the reaction.
The variation reaction proceeds at room temperature
but to obtain maximum yields of the desired product in a
temperatures the reaction goes to completion much quick
minimum of time, elevated temperatures up to about
er, often in about 15 minutes, but the reaction is some
what more dif?cult to control.
20 120° C., but preferably about 40 to 60° C., are employed.
At such elevated temperatures periods of one-half hour
The quantity of reactants is not critical but it has been
to two hours are usually su?icient to complete the re-'
found advantageous to use an excess of the l-monocar
action.
boxylic acid ester of Z-methyl-1,4-naphthohydroquinone
Following completion of the reaction according to this
and preferably at least two and up to ten moles of this
reactant to each mole of phytol. Excess starting mate 25 variation, the desired l-monocarboxylic acid ester of 2
times up to 6 hours are sometimes needed. At higher
methyl-3~phytyl-1,4-naphthohydroquinone is recovered.
rial may be recovered unchanged by ordinary methods
Thus, the reaction mixture ?rst may be diluted with
after the reaction has been completed. The catalyst may
ether and washed with aqueous sodium bicarbonate to
be employed in any concentration suitable for promoting
remove the boron triiluoride. After washing with water,
the reaction but to insure maximum reaction large
amounts should be utilized.
30 the ether solution may then be dried, e.g. over magnesium
sulfate. The product is then readily isolated by evapo
Following completion of the reaction the desired 1
rating the ethereal solution to dryness under reduced pres—
monocarboxylic acid ester of 2-methyl—3-phytyl-1,4
sure. The product may be puri?ed further by triturating it
naphthohydroquinone is recovered and puri?ed. Thus,
the reaction mixture may be cooled to about room tem
with low boiling petroleum ether, extracting the pe
perature and ?ltered to remove the catalyst where the
catalyst is insoluble in the reaction medium. The ex
cess l-monocarboxylic acid ester of 2-methyl-1,4-naph
hydroxide, washing the petroleum ether extract with
water, drying it and evaporating the petroleum ether to
troleum ether solution with dilute aqueous potassium
isolate the product.
The described condensation according to this variation‘
may be speci?cally illustrated by the reaction of 2~
methyl-1,4-naphthohydroquinone-l-acetate with phytol in
thohydroquinone used in the reaction is conveniently sepa
rated by evaporating the ?ltrate ‘to a small volume and
extracting the residue with low boiling petroleum ether
(B.P. 30—60° C.). The excess starting material is insolu—
ble in petroleum ether and is separated by ?ltration. The
‘the presence of boron tri?uoride to form 2-methyl-3
petroleum ether solution is extracted with dilute aqueous
potassium hydroxide to remove impurities, and by evapo
phytyl-l,4~naphthohydroquinoneé1-acetate. Similarly, 2
quinone-l-acetate with phytol in the presence of an alkali 50
metal salt such as potassium bisulfate to form Z-methyl
3-phytyl-1,4-naphthohydroquinone-l-acetate. Similarly 2
rnethyl-1,4-naphthohydroquinone-l-propionate is reacted
naphthohydroquinone-l-butyrate, 2-methyl-3~phytyl-l,4
naphthohydroquinone-l-caproate, 2-methyl-3-phytyl-L4
naphthohydroquinone-l-caprylate, 2-methyl—3-phytyl-l,4~
naphthohydroquinone-l-phenylacetate, 2-methyl-3-phy
duce 2 - methyl - 3 - phytyl-l,4-naphthohydroquinone-l
naphthohydroquinone which possess vitamin K1 like
methyl-l,4-naphthohydroquinone—l-propionate is reacted
rating the petroleum ether fraction, the desired l-mono 45 with phytol in the presence of boron tritluoride to pro
duce 2-methyl-3-phytyl-1,4-naphthohydroquinone-l-pro
carboxylic acid ester of 2-methyl-3-ph.ytyl-l,4-naphtho
pionate. In a like manner but starting with other appro
hydroquinone is isolated.
priate reactants, there is obtained 2-methyl-3-phytyl-1,4
The described condensation may be speci?cally illus
naphthohydroquinone-l-valcrate, 2-methyl-3-phytyl-l,4
trated by the reaction of Z-methyl-1,4-naphthohydro
tyl-l,4-naphthohydroquinone-l-benzoate and other simi
with phytol in the presence of an alkali metal bisulfate
or an equivalent acidic condensing agent catalyst to pro 55 lar l-monocarboxylic acid esters of 2-methyi-3-phytyl-L4
propionate. In a like manner starting with other appro
priate reactants there is obtained 2-rnethyl-3-phytyl-1,4
naphthohydroquinone-l-valerate, 2 - methyl-3-phytyl-L4
naphth-ohydroquinone-l-butyrate, 2-methyl-3-phytyl-l,4
naphthohydroquinone-l-caproate, 2-methyl-3-phytyl-1,4
naphthohydroquinone-l-caprylate, 2-methyl-3-phytyl-l,4
naphthohydroquinone-l-phenylacetate, 2-.methyl-3-meth
activity.
These l-monocarboxylic acid esters of 2-methyl-3
phytyl-l,4-naphthohydroquinone prepared in accordance
60 with the present invention may be converted to vitamin
K1 as more fully appears in copending U.S. application
Serial No. 403,638, ?led January 12, 1954. In the ?rst
step of the conversion, the l-monocarboxylic acid ester of
2-methyl-3-phytyl-1,4-naphthohydroquinone is dissolved
other similar l-monocarboxylic acid esters of 2-methyl-3 65 in a suitable solvent such as low boiling petroleum ether
yl - 3 - phytyl-1,4-naphthohydroquinone-l-benzoate and
phytyl - 1,4 - naphthohydroquinone.
These compounds
possess the activity of vitamin K1 itself.
According to a variation upon the invention ‘so far de
and the resulting solution is extracted with Claisen’s
alkali. In this manner, puri?cation and unexpected sol
volysis of the acyl group is achieved simultaneously to
give an alkaline solution of essentially pure 2-Inethyl-3
scribed, phytol and a .l-monocarboxylic acid ester of 2~
methyl-1,4-naph-thohydroquinone also can be condensed 70 phytyl-1,4-naphthohydroquinone. To separate the prod
net, the resulting alkaline solution is diluted with 3%
in the presence of boron tri?uoride to produce the corre
aqueous sodium hydrosul?te and extracted with ethyl
sponding l-monocarboxylic acid ester of 2-methyl-3
phytyl-l,4~naphthohydroquinone in yields of 70% and
higher.
ether. The ethyl ether solution of 2-methyl-3-phytyl-l,4
naphthohydroquinone is treated with an oxidizing agent
In this variation, the reaction of a l-monocarboxylic 75 such as silver oxide to produce 2-methyl-3-phytyl-1A
3,076,004
5
6
naphthoquinone or vitamin K1. The vitamin is conven
iently isolated, after removal of solids from the reaction
The mixture is ?ltered and by evaporating the ?ltrate
under reduced pressure to remove the solvent there is
mixture, by evaporating the solvent.
The following examples are added to illustrate spe
ci‘ic applications of the invention when using the pre
ferred dehydrating catalysts as well as boron trifluoride,
but it should be recognized that the scope of the inven
tion is not to be restricted to the particular embodiments
of the invention as disclosed in these examples, nor to the
particular acidic condensing agent employed.
EXAMPLE 1
obtained 2-rnethyl-3-phytyl-1,4-naphthoquinone.
EXAMPLE 3
Z-IlLIeIhyZd-PhySyZ-Z ,4-Naphthohydroquinone-I-Butyrate
1.480 gm. of phytol, 11.60 g. of 2-methyl-1,4-naph
thohydroquinone-l~butyrate and 3.02 g. of sodium acid
sulfate is added to 20‘ ml. of toluene and the mixture is
10 stirred well. The mixture is then heated at 80° C. for
one hour, cooled and filtered. The toluene solution is
evaporated to a small volume, triturated, with petroleum
ether, cooled and filtered. The petroleum ether ?ltrate
is puri?ed by extraction with 2% aqueous potassium hy
21Aethyl-3 -?lzytyZ-I ,4-Naphz‘lzolz ydroquinone-I -A cetate
To 15 ml. of dioxane is added 1.48 g. of phytol, 6.03 g.
of Z-methyl-l,4-naphthohydroquinone-l-acetate and 3.02 15 droxide. The desired 2~methyl - S-phytyl - 1,4-naphtho
g. of ground potassium acid sulfate. After stirring to
hydroquinone-l-butyrate is recovered -by evaporating the
effect solution of the organic compounds, the mixture is
ether under reduced pressure.
heated at about 75° C. for one hour and twenty minutes.
The procedure of this example is repeated starting with
The reaction mixture is then cooled to room temperature
Z-methyl-l,4-naphthohydroquin'one-l-valerate and react
and ?ltered to remove the catalyst. The ?ltrate is evapo 20 ing it with phytol to form 2-methyl-3-phytyl-1,4-naph
rated under reduced pressure to a thin slurry, low boiling
thohydroquinone- l-valerate. Similarly, other l-mono
petroleum ether is added and the mixture is cooled in an
carboxylic acid esters of 2-methyl- 1,4 -naphthohydro
ice bath. The mixture is ?ltered and the petroleum ether
?ltrate is extracted with 2% aqueous potassium hydrox
quinone such as the caproate, caprylate and phenyl
ness under reduced pressure to obtain 2-methyl~3-phytyl
duce the corresponding 2-methyl-3 -phytyl-1,4-naphtho
'hydroquinone-l-caproate, l-caprylate and l-phenylacetate.
acetate are reacted with phytol in the presence of an
ide. The petroleum ether solution is evapoarted to dr‘ - 25 acidic salt such as an alkali metal acid sulfate to pro
l,4-naphthohydroquinone-1~acetate.
The product of this example is converted to vitamin
K1 as follows:
The Z-methyl-S-phytyl - 1,4 - naphthohydroquinone - l
EXAMPLE 4
30
acetate is added to petroleum ether and the resulting
solution is extracted under nitrogen with 50 ml. of
Z-Z‘vlenhyl-3-Phytyl-1,4-Naphthohydroqainone-I-Benz0ate
To 25 ml. of benzene is added 3 g. of 2-methyl-l,4
naphthohydroquinone-l-benzoate, 1 g. of phytol and 2
Claisen‘s alkali (prepared by dissolving 17.5 g. of po
g. of potassium acid sulfate. The mixture is re?uxed
tassium hydroxide in 12.5 ml. of water and diluting to
50 ml. with methanol). The aqueous alkaline solution 35 for 2 hours, cooled and ?ltered. The benzene ?ltrate
is reduced to a small volume by evaporation and low
is diluted with a 3% aqueous solution of sodium hydro
boiling petroleum ether is added to the remaining solu
sulhte, the mixture is extracted with ethyl ether and
tion. The mixture is cooled, ?ltered and the ?ltrate
the ether extract is dried over magnesium sulfate. After
is extracted with 2% aqueous potassium hydroxide. The
concentrating the solution to a small volume 2.0 g. of
petroleum
ether solution is evaporated to dryness to ob
40
silver oxide and 2.0 g. of magnesium sulfate are added
tain 2-methyl-3-phytyl - 1,4 - naphthohydroquinone-l-ben
to the ethereal solution followed by shaking for 30 min
zoate.
utes. After ?ltering, the desired vitamin K1 is recovered
EXAMPLES
by evaporating ‘the ?ltrate to dryness under reduced
2-Methyl-3-Phytyl-1 ,4 -Naphth0hydr0quin0ne-1 -
pressure.
EXAMPLEZ
Z-Methyl-S-Plzytyl-J ,4-Naphth0l1ydroquinone-J -
Propionate
To 16 ml. of dioxane is added 1.48 g. of phytol, 11.60
45
Propionate
11.6 g. of 2-methyl-1,4-naphthohydroquinone-l-pro
pionate and 3.08 g. of Duolite C-60, a cation exchange
resin on the hydrogen cycle, are added to 16 ml. of di
g. of 2-methyl-1,4 - naphthohydroquinone - l-propionate 50 oxane and the mixture heated to 75° C. Then 1.58 g. of
phytol in 4 ml. of dioxane is added over a 1 hour
and 3.02 g. of freshly ground potassium acid sulfate.
The mixture is heated under nitrogen at 76° C. for one
hour and twenty minutes. After cooling to room tem
perature the reaction mixture is ?ltered to remove the
catalyst. The ?ltrate is evaporated under reduced pres
period. After the addition of phytol has been com
pleted, heating is continued for 20 minutes more. The
reaction mixture is cooled to room temperature, ?ltered
and the ?ltrate is reduced to a small volume by evapo
ration under reduced pressure. Low boiling petroleum
sure until very little solvent remains. To the residue
ether is added to the residue, the mixture is cooled and
is added 27 ml. of petroleum ether (B.P. 30-60" C.).
?ltered. The ?ltrate is extracted with 2% aqueous po
After cooling for one hour in the refrigerator, excess
tassium hydroxide containing a small amount of sodium
starting material is removed by ?ltration and the ?ltrate
is extracted with 2% aqueous potassium hydroxide con 60 hydrosul?te. The petroleum ether layer is evaporated
to isolate the 2-methyl-3-phyty1-l,4-naphthohydroquinone
taining a small amount of sodium hydrosul?te. The
l-proprionate.
petroleum ether layer is evaporated under reduced pres
EXAMPLE 6
sure to give 2-rnethyl-3-phytyl-1,4-naphthohydroquinone
l-propionate.
2 -M ethy 1-3 -Phytyl-1 ,4-Naph t-hohydroquinone-l -A cetate
The 2-methyl-3-phytyl - 1,4-naphthohydroquinone-1
To 20 ml. of dioxane is added 2.1 g. of phytol, 9.2 g.
65
propionate is added to 30 ml. of petroleum ether and
of Z-methyl-1,4-naphthohydroquinone-l-acetate and 0.30
shaken vigorously with 50 ml. of Claisen’s alkali con
ml. of boron tri?uoride-etherate. After solution is ef
taining 3.0 ml. of aqueous sodium hydrosul?te. The
fected the mixture is heated at about 50° C. for one
alkaline extract is separated and added to a mixture of
hour and twenty minutes under nitrogen. The reaction
200 ml. of cold 3% aqueous sodium hydrosul?te and 70 mixture is then cooled to room temperature and diluted
100 ml. of ether. The ether layer is separated and
with ether. The ethereal solution is extracted with 2%
dried over anhydrous magnesium sulfate. The ether
aqueous potassium hydroxide and washed with water.
solution of 2-methyl-3~phytyl-1,4,-naphthohydroquinone
The ethereal solution is evaporated to dryness under re—
is evaporated to about 10-25 ml. and to it is added 2.08
duced pressure to obtain 2-methyl-3-phy-tyl-1,4-naphtho
g. of silver oxide in the presence of magnesium sulfate.
hydroquinone-l-acetate.
3,073,004
The product of this example is converted to vitamin K1
as follows.
The 2-methyl-3-phytyl-1,4-naphthohydroquinone-l-ace
tate is added to petroleum ether and the resulting solution
is extracted under nitrogen with 50 ml. of Claisen’s meth
anolic alkali (prepared by dissolving 17.5 g. of potassium
hydroxide in 12.5 vml. of Water and diluting to 50 ml. with
methanol). The aqueous alkaline solution is diluted with
a 3% aqueous solution of sodium hydrosul?te, the mix
ture is extracted With ethyl ether and the ether extract is
dried over magnesium sulfate. After concentrating the
quinone-l-butyrate and 0.40 g. of boron tri?uoride ether
ate is added to 20 ml. of toluene and ‘the mixture is
stirred Well. The mixture is then heated at 55° C. for
one hour, cooled and ?ltered. The toluene solution is
evaporated to a small volume and diluted with ether. The
ethereal solution is puri?ed by extraction with 2% aqueous
potassium hydroxide and washing with water. The de
sired Z-methyl-3-phytyl-1,4-naphthohydroquinone-1-butyr
ate is recovered by evaporating the ether under reduced
pressure.
The procedure of this example is repeated starting with
solution to a small volume, 3.0 g. of silver oxide and 3.0
g. of magnesium sulfate are added to the ethereal solution
2-methyl-1,4-naphthohydroquinone-l-valerate and react
ing it with phytol in the presence of boron tri?uoride to
followed by shaking for 30 minutes. After ?ltering, the
"desired vitamin K1 is recovered by evaporating the ?ltrate
form 2-methyl-3-phytyl-1,4-naphthohydroquinone-l-valer
to dryness under reduced pressure.
EXAMPLE 7
ate. Similarly, other l-monocarboxylic acid esters of 2~
methyl-1,4-naphthohydroquinone such as the caproate,
caprylate and phenylacetate are reacted with phytol in the
presence of boron trifluoride to produce the correspond
ing 2-methyl-3-phytyl-1,4-naphthohydroquinone-l-capr0
Z-Methy l-3~Plzytyl-1 ,4-Naphzhohydroquinone-I -Pr0
pionate
20 ate, l-caprylate and l-phenylacetate.
1.481 g. of phytol in 4.0 ml. of dry oxane is added drop
EXAMPLE 9
wvise over a 30 minute interval at 50° C. to 11.65 g. of
2-methyl-1,4-naphthohydroquinone-l-monopropionate in
2 -Methyl-3-Phytyl-1 ,4-Naphth0hydroquinone-l -Benzoate
10.0 ml. of dry dioxane to which about 0.22 ml. of boron
To 20 ml. of benzene is added 2.5 g. of 2-methyl-1,4
tri?uoride etherate has been added. During the addition
naphthohydroquinone-l-benzoate, 0.80 g. of phytol and
the reaction temperature is maintained at about 52° C. and
0.25 g. of borontri?uoride-etherate. The mixture is
the condensation is effected under an inert atmosphere.
heated at 45° C. for two hours and then cooled to room
Stirring is continued With heating until the total reaction
temperature. The benzene solution is extracted with 2%
time is about 1 hour.
The reaction mixture is cooled to room temperature and 30 aqueous potassium hydroxide and washed with Water.
The benzene solution is evaporated to dryness to obtain
‘diluted with 60 ml. of ether. The mixture is washed with
2-methyl-3-phytyl-1 ,4-napl1thohyd roquinone- l-benzoate.
sodium bicarbonate and then ‘with water. The ethereal
Various changes and modifications of the invention can
solution is dried over magnesium sulfate and evaporated
he
made and, to the extent that such variations incorpo
to dryness. The residue is triturated with petroleum ether
rate
the spirit of this invention, they are intended to be
35
and cooled. The solution is ?ltered and the ?ltrate is
extracted with 2% aqueous potassium hydroxide to re
move any remaining unreacted starting material.
The
petroleum ether solution of 2-methyl-3-phytyl-1,4-naph
thohydroquinone-l-propionate is then extracted with
included within the scope of the appended claims.
I claim:
1. The process Which comprises reacting a l-monocar
boxylic acid ester of 2-methyl-l,4-naphthohydroquinone in
Claisen’s alkali and the aqueous alkaline solution is di 40 which the acyl group is derived from a monocarboxylic
acid having from one to and including eight carbon atoms,
luted with a 3% aqueous solution of sodium hydrosul?te.
with phytol in an inert organic solvent in the presence of
The mixture is extracted with ethyl ether and the ether
an alkali ‘metal bisulfate to produce the corresponding 1
extract is dried over magnesium sulfate. The ethereal
monocarboxylic acid ester of 2-methyl-3-phytyl-1,4-naph
solution is concentrated to a small volume. 3.0 g. of
silver oxide and 3.0 g. of magnesium sulfate are added 45 thohydroquinone.
2. The process according to claim 1 wherein the alkali
to the ethereal solution and the mixture is shaken for 20
minutes and ?ltered. The ?ltrate is evaporated to dryness
metal bisulfate is potassium bisulfate.
to give 1.6 g. of vitamin K1 in a 70% yield.
‘References Cited in the ?le of this patent
EXAMPLE 8
50
UNITED STATES PATENTS
2-Methyl-3-Phytyl-1 ,4-Naphthohya'roquinone-Z -Butyrate
1.480 g. of phytol, 5.3 g. of Z-methyl-l,4-naphthohydro
2,839,570
Lindlar ______________ __ June 17, 1958
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