Note: Descriptions are shown in the official language in which they were submitted.
~3~3877
Artificial flavoring agents for foodstuffs have received increas-
ing attention in recent years. In many areas, such food flavoring agents ;~
are preferred over natural flavoring agents, at least in part because of
the uniform flavor that may be so obtained. For example, natural food
; flavoring agents such as extracts, essences, concentrates and the like are
often subject to wide variation due to changes in the quality, type, and
treatment of the raw materials. Such variation can be reflected in the end
product and results in unreliable flavor characteristics and uncertainty as
to consumer acceptance and cost. Additionally, the presence of the natural
product in the ultimate food may be undesirable because of increased ten~
dency to spoil. This is particularly troublesome in convenience and snack
food usage where such products as dips, soups, chips, prepared dinners,
canned goods, sauce6, gravies, and the like are ap-t to be stored by the
consumer for some time prior to use.
The fundamental problem in preparing artificial flavoring agents
is that of achieving as nearly as possible a true flavor reproduction.
This generally proves to be a difficult task since the mechanism for flavor
development in many foods is not understood. This is notable in products
having meaty and roasted flavor characteristics.
Reproduction of roasted ana meat flavors and aromas has been the
subject of a long and continuing search by those engaged in the production
of foodstuffs. ~he severe shortage of foods, especially protein foods, in
many parts of the world has given rise to the need for utilizing non-meat
sources of proteins and making such proteins as palatable and as meat-like
as possible. Hence, materials which will closely simulate or exactly re-
produce the flavor and aroma of roasted products and meat products are
required.
Moreover, there are a great many meat-containing or meat-based
foods presently distributed in a preserved form, examples being condensed
soups, dry soup mixes, dried meats, freeze-dried or lyophilized meats,
packaged gravies, and the like. While -these products contain meat or meat
extracts, the fragrance, taste, and other organoleptic factors are very
.~
1~)38877
often impaired by the processing operations, and it is desirable to supple-
ment or enhance the flavors of these preserved meat foods.
The present invention provides furan derivatives having the
formula
I -- S -R
R ~ O ~ R
3 2
wherein R3 is hydrogen or lower alkyl, and where~ is one, Rl is hydro-
gen, R2 is lower alkyl con~aining at least two carbon atoms, and both dashed
lines represent double bonds; or (2) _ is one, Rl is hydrogen, R2 is lower
alkyl, and at least one of the dashed lines represents a single bond; or (3)
n is one, Rl is hydrogen, R2 is methyl, both the dashed lines repres~nt double
bonds, and the furan derivative is substantially pure; or (~) n is one, two,
three or four, Rl is a moiety of the formula
I I
L ~olR~
each dashed line represents a single or double bond, R2 and R~ are lower alkyl,
said lower alkyl containing at least two carbon atoms when _ is two and R5 is
hydrogen or lower alkyl; (5) _ is two, Rl is said moiety, R2 and R~ are methyl,
R3 and R5 are hydrogen or lower alkyl and the furan derivative is substan-
tially pure; or (6) n is two or three, each dashed line represents a double
bond, and Rl and R2 are lower alkyl.
The new compounds have desirable meat, roast meat, and roasted
fragrance and flavor notes.
The present invention also provides flavor compositions comprising
compounds of formula (I) defined above in amounts of from 0.0001 to 10%, and
foodstuffs and food compositions containing such furan derivatives. The
methods for preparing such furan derivatives and such food compositions are
also contemplated within the present disclosure.
;~
~ _ 2 -
-
1~3~877
When R2, R3, R4, R5J R6 and R7 represent alkyl, alkenyl, or al-
kadienyl groups, it is desirable that they be lower alkyl, alkenyl or alkadi-
enyl groups having up to five carbon atoms. Thus, for example, these groups
can be methyl, ethyl, propyl, isopropyl, butyl, secondary butyl, pentyl, vinyl,
allyl, isopropanyl, butenyl, butadienyl, isopentenyl, pentenyl, pentadienyl,
isopentadienyl, and the like. When R5 and R6 and/or R3 and R7, taken together
form cyclialkyl or cyclialkenyl or cyclialkadienyl rings, it is preferred that
they be 5- or 6- membered rings. Thus, for example, the following fused ring
compound is representative of one of such ring materials:
10 ~ 5 ~3
The particularly preferred materials according to the present in-
vention for imparting desirable meat, roast meat, and roasted fragrance and
flavor notes include furan derivatives having the formula:
SnR
R3 R2
wherein R3 is hydrogen or lower alkyl, and where (1) n is one, Rl is hydrogen,
R2 is lower alkyl, at least.one of the dashed lines represents a double bond,
sald furan derivative being substantially pure; or (2) n is one, Rl is hydrogen,R2 is lower alkyl, and at least one of the dashed lines represents a single
bond; or (3) n is one, two, three or four, Rl is a moiety of the formula:
R4 ~ 0 ~ 5
~wherein each dashed line represents a double bond, and R2 and R4 are lower
alkyl, R5 is hydrogen or lower alkyl, said furan derivative being substantially
pure; when n is two and R2 and R4 are methyl; or ~4) n is two or three, each
)38~77
dashed line represents a double bond? and Rl and R2 are lower alkyl.
In this preferred embodiment, when Rl, R2, R3, R4 and R5 reprcsent
alkyl groups it is desirable that they be lower alkyl groups having up to
five carbon atoms. Thus, the alkyl groups can be methyl, ethyl, propyl, iso-
propyl, butyl, secondary butyl, pentyl, and the like. It is especially pre-
ferred that the alkyl groups be methyl or ethyl.
It has been found that when both dashed lines represent double
bonds, that is, when the ring is a furyl ring, the compounds have a desirable
pronounced meat flavor and aroma characteristic. When the furan ring is more
highly saturated, and particularly when the ring is dihydrofuryl, a roasted
flavor and aroma characteristic is more dominant.
Particularly important compoundsof the invention are substantially
pure bis~2-methyl-3-furyl) disulfide having ~ max at 3.22, 6.32, 6.60, 7.22,
11.28 and 13.6 ~ by infrared spectroscopy; substantially pure 2-methylfuran-
3-thiol having ~ max at 3.92, 6.60, 7.26, 7.~0 and 13.58 ~ by infrared spect-
roscopy and methyl (2-methyl-3-furyl) disulfide.
The novel compounds of the present invention are oily liquids or
crystalline solids and are, in general, characterized by pronounced pleasant
meat, roasted meat and/or roasted food fIavor and aroma at the levels taught
herein. The dominant note is one of roasted protein with a notable absence
of any pungency or lachrymost factor.
It will be understood that some of the novel compounds of this in-
vention can exist in various isomeric forms, and the formulas given herein in-
clude such isomers. By way of example, the 2-methyl-[2,3H]-dihydrouran-3-
thiols exist as geometric isomers and as optical isomers. A representation
of one of the isomers of this compound is as follows:
'': ~0
HS H
Another isomer is:
\ H
CH3
- 4 -
1~38~77
Exemplary of 3-sulfur substituted furans contemplated herein
are:
bis-(2-methyl 3-furyl) tetrasulfide
2-methylfuran-3-thiol
2-methyldihydrofuran-3-thiol
2-methyltetrahydrofuran-3-thiol
2-ethylfuran-3-thiol
4a -
1~3E~877
2-ethyldihydrofuran-3-thiol
2-ethyltetrahydrofuran-3-thiol
2-propylfuran-3-thiol
2-isopropylfuran-3-thiol
2-isopropyldihydrofuran-3-thiol
2-isopropyltetrahydrofuran-3-thiol
2-propyldihydrofuran-3-thiol
2,5-dimethylfuran-3-thiol
2,5-dimethyldihydrofuran-3-thiol
2,5-dimethyltetrahydrofuran-3-thiol
2,5-diethylfuran-3-thiol
2,5-diethyldihydrofuran-3-thiol
2,5-diethyltetrahydrofuran-3-thiol
2-ethyl-5-methylfuran-3-thiol
2-methyl-5-ethylfuran-3-thiol
2-ethyl-5-methyldihydrofuran-3-thiol
2-ethyl-5-methyltetrahydrofuran-3-thiol
2,5-dipropylfuran-3-thiol
2,5-diisopropylfuran-3-thiol
5-isopropyl-2-methylfuran-3-thiol
2-butylfuran-3-thiol
2-ethyl-5-propyltetrahydrofuran-3-thiol
bist2-methyl-3-furyl) sulfide
. bist2-methyl-3-furyl) disulfide
bis~2-ethyl-3-furyl) sulfide
bist2-ethyl-3-furyl) disulfide
bis(2,5-dimethyl-3-furyl) sulfide
bis(2,5-dimethyl-3-furyl) disulfide
bis(2-methyl-3-dihydrofuryl) sulfide
bis(2-methyl-3-tetrahydrofuryl) sulfide
bis(2-methyl-3-tetrahydrofuryl) disulfide
bis(2-methyl-3-dihydrofuryl) disulfide
-- 5 --
~)38877 `bis(2,5-diethyl-3-dihydrofuryl) sulfide
bis(2,5-diethyl-3-furyl) sulfide
bis(2-ethyl-5-methyl-3-furyl) disulfide
bis(2,5-diethyl-3-furyl) disulfide
; bis(2,5-dipropyl-3-furyl) disulfide
bis(2,5-dipropyl-3-furyl) sulfide
bis(2,5-dibutyl-3-furyl) disulfide
bis(5-ethyl-2-methyl-3-dihydrofuryl) disulfide
bis(2-isopropyl-3-furyl) sulfide
bis(2-isopropyl-3-furyl) ai sulfide
bis(2-isopropyl-3-dihydrofuryl) sulfide
bls(2-isopropyl-3-tetrahgdrofurgl) disulfide
It wlll be understood ~rom the present dlsclosure that the derlv-
atlves of dlhydrofuran can be 2,3H or 11,5H. Thus, 2-methyldlhydroruran-3-
thiol includes 2-methyl- ~1,5H7-dihydrofuran-3-thiol and 2-methyl-L~,3H7-
dihydrofuran-3-thiol, and bis(5-ethyl-2-methyl-3-dihydrofuryl) disulfide
~i includes bis {5-ethyl-2-methgl-3-(Lh,5 ~-dihydrofuryl)l disulfide and bis
~5-ethyl-2-methyl-3-(~,3~--dihydrofuryl)~ disulfide.
In accordance with a furthsr aspect of this invention, the novel
sulfur compounds are utillzed slngly, in admixture, or in comblnation wlth
other edible materlals to impart a meaty or roasted organoleptic lmpresslon
to foods or edible materials. Thus, the compounds hereln described can
comprise flavoring compositions and flavor-enhancing compositions. It will
be understood herein that a flavoring composition is one capable of im-
parting a definite flavor to a tasteless or bland foodstuff, and a flavor-
enhancing composition is one capable of reinforcing one or more flavor
notes of a natural or other material which is deficient in flavor. A
flavor-enhancing composition would be useful for improving the flavor of,
say, a canned meat product, the flavor of which was diminished or
undesirably altered by the processing. It will accordingly be understood
that the disclosed sulfur-containing compounds can be mixed with other
- flavoring ingredients, carriers, vehicles and the like to form compositions
-- 6 --
1~)38877
suitable for imparting a flavor to, enhancing the flavor in, or altering
the flavor of, a food composition, and such food compositions and the
methods for preparing them are included in this disclosure. The furyl
monosulfides, disulfides, and mercaptans of this invention generally impart
a meat or cooked meat flavor and aroma. The dihydrofuryl sulfides,
disulfides, and mercaptans impart a roasted flavor and odor which is even
redolent of roasted sesame seeds in some instances. Their flavor charac-
teristics are sufficiently pronounced and persistent that a desirable
flavor and odor can be developed by simply using the undiluted compound or
compounds; for example, by addition of the undiluted compound to a pro-
cessed fi8h meal.
When the sulfur compounds of this invention are used in flavoring
compositions to enhance existing flavors in, or to provide the entire fla-
vor impression to, a foodstuff, they can be combined with organic acids
including fatty, saturated, unsaturated and amino acids, alcohols, in-
cluding primary and secondary alcohols, esters, carbonyl compounds in-
cluding aldehydes and ketones, lactones, cyclic organic materials including
benzene derivatives, alicyclics, heterocyclics such as furans, pyridines,
~ pyra~.ines and the like, sulfur-containing materials including thiols,
; 20 sulfides, disulfides and the like, proteins, lipids, carbohydrates, and
so-called flavor potentiators such as monosodium glutamate, gu&nylates,
inosinates, natural flavoring materials such as vanillin, and the like.
It will be appreciated that the types and amounts of materials selected
from the foregoing groups of materials will depend upon the precise
organoleptic character desired in the finished product and, especially in
the case of flavoring compositions used to enhance other flavors, will
vary according to the foodstuff to which the flavor and aroma are to be
imparted. Inorganic materials such as sodium chloride and freshness pre-
servers such as butylated hydroxyanisole, butylated hydroxytoluene and
propyl gallate can be added for their adjuvant or preservative effects on
the flavoring composition or on the final food composition itself.
As noted above, it can also be desirable to utilize carriers such
-- 7 --
1~38877
as gum arabic and carrageenen or vehicles such as ethyl alcohol, water,
propylene glycol. When the carrier is an emulsion, the fla~oring composi-
tion can also contain emulsifiers such as mono- and diglycerides of fatty
acids and the like. With these carriers or vehicles the desired physical
form of the composition can be prepared. It will be understood that the
compounds of this invention can be used in spray-dried, liquid, encap-
sulated, emulsified and other forms in which flavorings are added to food-
stuffs. The compounds can be so used alone or in combination with the
other ingredients set forth therein. In the case of a foodstuff which is
prepared from a combination of ingredients the furyl sulfur derivatives,
flavor enhancers and flavoring compositions of this invention can be added
to one of the ingredients and thereby be incorporated into the composition
as a whole.
The amount of novel sulfur-containing compound or compounds used
should be sufficient to impart a meaty or roasted flavor and aroma note to
the ultimate foodstuff in which they are used. Thus, a small but effec-
- tive amount of 3-sulfur substituted furan sufficient to provide the meaty
flavor note in or to round out the meat, roasted, or other flavor note in,
the ultimate foodstuff is used. The amount will vary depending upon the
2Q ultimate food composition to be flavoredj for example, more may be required
in producing a full, rounded meat flavor in an unflavored material and
less may be required when this invention is used to enhance a meat or
roasted foodstuff or flavoring material which is deficient in natural fla-
vor or aroma.
Those skilled in the art will appreciate that the amount of
furyl sulfur derivatives according to this invention can be varied over a
range to provide the desired flavor and aroma. The use of too little of
the derivative or derivatives will not give the full benefit, while too
much will make the flavor cornpositions and foodstuffs needlessly costly,
and in extreme cases will unbalance the flavor and aroma so that optimum
results are not obtained.
It is accordingly preferred that the ultimate food composition
-- 8 --
~38877
contain at least about 1.0 part per billion of the sulfur derivatives,
based on total composition, and it is not generally desirable to use more
than about 500 parts per million (ppm) in the finished composition. Thus,
the desirable range for use in the practice of this invention is from about
0.001 to about 500 ppm of the furyl sulfur compound or compounds. When
these compounds are added to the foodstuff in the form of a meat flavor
composition, the amount should be sufficient to impart the requisite flavor
and/or aroma note to the composition so that the flavor and aroma will be
balanced in the finished foodstuff. Accordingly, the flavoring composi-
tions of this invention preferably contain from about 0.0001% to 10% of
sulfur derivatives based on the total weight of said flavoring composition.
Unless otherwise indicated, all parts, proportions, percentages, and ratios
herein are by weight.
The flavoring compositions o~ this invention can be added to thefoodstuffs by conventional methods known in the art. The flavor material
~ of this invention, together with any other liquids if desired, can be
i~ admixed with a carrier, such as gum arabic, gum tragacanth, carrageenen
and the like, and spray-dried to obtain a particulate solid flavoring
material. Where a powdered prepared flavor mix is being made, the dried
solids and flavoring compositions or furyl sulfur derivatives of this
invention are mixed together in a dry blender to attain uniformity.
When liquid materials are involved in the preparation of food-
stuffs, the flavoring materials of this invention can be combined with
either the liquid to be used in the finished composition, or alternatively
they can be added with a liquid carrier in which they are dissolved, emul-
sified, or otherwise dispersed.
It has been found that the bis(2,5-dialkyl-3-furyl) sulfide can
readily be prepared by reacting a 2,5-dialkyl furan with the appropriate
sulfur chloride in the presence of a catalyst. Thus, a bis(2,5-dialkyl-3-
furyl) sulfide is produced by the reaction of a 2,5-dialkyl furan with
sulfur dichloride, SC12, and a bis(2,5-dialkyl-3-furyl) disulfide can be
obtained by the reaction of such a 2,5-dialkyl furan with sulfur
_ g _
~3~3877
monochloride, that is, S2C12
While the reaction can be carried ou-t in the absence of catalysts,
it is preferred to use as catalysts Lewis acids including metal salts such
as stannic chloride, ferric chloride, ferric bromide, zinc chloride, boron
trifluoride, and boron trifluoride complexes such as boron trifluoride
diethyl etherate, and the like.
It has been found that the time of reaction for obtaining suit-
able results is between 15 minutes and 2 hours; that the desirable tem-
perature range is between -30 C and +50 C; that a reaction vehicle is
preferable for controlling the reaction, and that such reaction vehicle
can be a hydrocarbon solvent such as hexane, cyclohexane, and the like or
dimethyl furan used in large excess. The reactant proportions are such
that the dlmethyl furan compound is used in large molar excess over the
; particular sulfur chloride. The reaction is preferably run at atmospheric
pressure.
It has also been discovered that furan-3-thiols and alkyl-
substituted furan-3-thiols can be produced by the reaction of an appropri-
ate dihydrofuranone-3 or tetrahydrofuranone-3 with hydrogen sulfide in the
; presence of anhydrous hydrogen chloride at temperatures of -60 to -100C.
This reaction provides furan-3-thiols; dihydrofuran-3-thiols; and
tetrahydrofuran-3-thiones as well as alkyl-substituted derivatives thereof.
The reaction of the di- or tetrahydrofuranone-3 or alkylated
counterparts with hydrogen sulfide in the presence of gaseous hydrogen
chloride will take place in from about 5 up to about 25 hours at tempera-
tures of about -60 down to about -100C. The reaction vehicle can be any
polar solvent having a melting point below about -100C and a viscosity
such that the reaction mass can be turbulently mixed at that temperature.
Desirable polar solvents having the above properties are Diglyme,
tetrahydrofuran, methanol, ethanol and the like. The hydrogen sulfide
reactant is preferably in about a 5- to lO-fold excess over the furanone-3.
It will be understood that the thione can readily be converted
to the corresponding thiol with a reducing agent such as lithium aluminum
-- 10 --
1~38877
hydride, diethoxy aluminum hydride, ethoxy aluminum dihydride and the like.
The vehicle for this reduction can be an oxygenated solvent such as diethyl
ether, tetrahydrofuran, Diglyme (dimethyl ether of diethylene glycol), and
the like. The temperature of the reaction can vary from about O C up to
the reflux temperature of the reaction medium. Although the reaction can
be carried out over a range of pressures, it is preferred that the pressure
be atmospheric. The reducing agent is preferably in excess molar propor-
tion relative to the thione.
It will be understood that the corresponding bis(3-furyl),
bis(3-dihydrofuryl), and bis(3-tetrahydrofuryl) disulfides can be produced
by oxidizing the corresponding thiols under mild oxidizing conditions.
Thus, the thiols can be oxidized with an air stream bubbled through them
at 20 C and 760 mm Hg pressure for 8 hours. Stirring of the reaction mass
with use of baffles during the bubbling is adequate to maintain suitable
contact between the reactants. Other suitable mild oxidizing agents in-
clude ferric chloride, iodine-potassium iodide, dimethyl disulfide,
dimethylsulfoxide and the like.
The time of this mild oxidation reaction will vary from substan-
tially instantaneous up to 20 hours at temperatures from about 10 C to 50 C
and atmospheric pressure. The pH of the reaction mass depends upon the
nature of the oxidizing agent, as does the time of reaction which is a
function of the net oxidation reduction potential of the reactants and the
concentrations and relative proportions of -the reactants. It is preferred
that stoichiometric quantities of thiol and oxidizing materials be used
unless such easy-to-remove oxidizing agents as dimethyl sulfoxide, dimethyl
sulfide and the like are employed, in which case an excess of such oxi-
dizing agents can be utilized.
In another process contemplated herein a 2-alkyl-5-furoic acid,
2-alkyl-5-cyanofuran, or a 2-alkyl-5-halofuran is treated with oleum
(fuming sulfuric acid) to produce the 3-sulfo derivative. When the 5-
furoic acid is used, the barium salts of the resulting acid are then
obtained by treatment of the acid with barium carbonate which is used in
-- 11 --
~3E~877 ~
excess so as to eliminate any unreacted sulfuric acid. The barium salt is
converted to the sodium salt which is then decarboxyla-ted with an equiva-
lent amount or an excess of mercuric chloride in a refluxing aqueous solu-
tion. The resulting sodium sulfonate is reacted with a 7-8 fold excess of
thionyl chloride, the excess of thionyl chloride being used as a solvent
in the presence of a trace of dimethyl formamide. In place of excess
thionyl chloride, other inert solvents may be used, for example, benzene,
::'
hexane or diethyl ether. The resulting 3-chlorosulfo group is reduced to
the thiol (-SH) group by reaction with a reducing agent used in excess to
insure total reduction. Agents such as lithium aluminum hydride, mono-
alkoxy a}uminum dihydride, dialkoxy aluminum hydride or zinc in hydro-
chlorie aeid wherein each o~ these reducing agents is in a vehicle can be
used. Such a reduction can be earried out at room temperature to reflux
! ~ under atmospheric pressure. The vehicle carrying the reducing agent can
be oxyeenated vehicles such as diethyl ether, tetrahydrofuran, Diglyme,
and the like.
Saturated furan-3-thiols can also be produced by treating alkyl-
3-halotetrahydrofurans with sodium hydrosulfide under reflux conditions
in the presence of ethanol, methanol, or like vehicles. The mercaptans of
this invention ean, if desired, be reaeted with various chlorosulfur
eompounds to obtain di- or tri- or tetrasul~ides. Thus, a thiol sueh as
2-methyl-3-furan thiol ean be reaeted with an equimolar amount of methyl
disulfur ehloride, CH3S2C1, at a temperature of from -60 C up to about
0 C to produce methyl (2-methyl-3-furyl) trisulfide. This reaction can be
carried out in a solvent such as diethyl ether, cyclohexane, hexane carbon
tetrachloride, benzene and the like. Similarly, a thiol such as 2-methyl-
3-furanthiol can be reacted with an equimolar amount of methanesulfenyl
chloride, CH3SCl, to produce methyl(2-methyl-3-furyl) disulfide. This
reaction also can be carried out in a solvent such as diethyl ether,
cyclohexane, hexane carbon tetrachloride, benzene and the like. The reac-
tion temperature is preferably from -60 C up to 0 C at atmospheric pressure.
The di- and tetrahydro materials according to this invention are
- 12 -
~38~377
also conveniently prepared directly from the appropriate alkyl or dialkyl
di- or tetrahydrofurans, under reaction conditions similar to the condi-
tions used in the analogous reactions described heretofore.
The bis(2-methyl-3-furyl) disulfide and 2-methyl-3-furan thiol
of this invention can also be obtained by: (a) forming a mixture of
thiamine, cysteine, hydrolyzed vegetable protein and water and heating the
mixture to reflux for a period of from about 2 to about 10 hours as shown
in United States Patent 3,394,016; (b) removing the distillate at inter-
vals; (c) treating the distillate in an extractive process using as an
extractant a low boiling solvent such as methylene chloride and the like,
whereby the bis(2-methyl-3-furyl) disulfide and 2-methyl-3-furan thiol of
; this invention are obtained; (d) separating -the furyl sulfur compounds
~rom the mixture by means of, for example, a gas-liquid chromatographic
column or column chromatographic techniques.
The following examples are given to illustrate embodiments of
the invention as it is presently preferred to practice it. It will be
unders-tood that these examples are illustrative, and the invention is not
to be considered as restricted thereto except as indicated in the appended
claims.
EXAMPLE I
Preparation of bis(2,5-Dimethyl-3-furyl) sulfide
and bis(2,5-Dimethyl-3-furyl) disulfide
Into a l-liter three-néck, round bottom flask equipped with
addition funnel and magnetic stirrer are introduced 175 g of 2,5-
dimethylfuran and 0.4 g of stannic chloride. After cooling to -20 C 75.3
g of sulfur dichloride, SC12, is added during 33 minutes while main-
taining a temperature of -20 C. The reaction mixture is stirred for 1 hour
and 40 minutes and allowed to warm to +34C. Pouring the reaction mixture
into 1 liter of ice-water, and extraction with hexane gives, after drying
with sodium sulfate and solvent removal, 64.8 g of residue. Column
chromatography of the residue on 1625 g of silicic acid with 5% diethyl
ether in hexane glves 14.4 g of a mixture of mono- and disul-~ides.
- 13 -
~38!3~7
Distillation of 11.0 g of mixture provides 3.8 g of bis(2,5-dimethyl-3-
furyl) sulfide, b.p. 81-85 C at 0.15 mm Hg, and 5.1 g of bis(2,5-dimethyl-
3-furyl) disulfide, b.p. 112-116 C at 0.45 mm Hg.
Repeating the above experiment using 98.5 g of sulfur
monochloride, S2C12, in place of sulfur dichloride produces a 54.2 g
residue. Chromatography on 1355 g of silicic acid with 5% ether in hexane
yields 13.9 g of mono- and disulfide. Distillation of 11.0 g of the mix-
ture gives 1.96 g of a 40/60 mixture, as determined by proton magnetic
resonance (PMR) of mono- and disulfide and 6.6 g of bis(2,5-dimethyl-3-
furyl) disulfide, b.p. 115 C at o.l~5 mm Hg.
The data on the bis(2,5-dimethyl-3-furyl) sulfide are as follows:
Proton Magnetic Resonance
In carbon tetrachloride:
2.2 (singlet, 6 protons)
2.3 (singlet, 6 protons) and
5.78 (singlet, 2 protons) ppm.
Infra-red:
~max. Interpretation
3.22 CH stretch of aromatic ring
6.21, 6.36 C=C stretch of aromatic furan ring
7.26 Methyl group
12.05 CH bond of aromatic ring.
Mass Spectrum
Pattern
Ratio of Mass ~et Peak Intensity
to ChargeHeight %
43 1100. - 100.01
53 130. - 11.8
140. - 12.7
96 280. - 25.56
126 390. _ 35.53
127 310. - 28.25
128 220. - 20.0
-- 1~ --
)
~038877
179 320. - 29.14
207 210. - 19.1
222 800. - 72.72
Both compounds impart a distinct meaty flavor to a soup base
at a concentration of 0.2 ppm. The bis(2,5-dimethyl-3-furyl) disulfide is
preferred and both 3-furyl sulfides are preferred over bis(5-methyl-2-
furyl) disulfide which is found to have only a chemical, rubbery taste and
aroma under the same conditions.
EXAMPLE II
,i
I Pre~aration of bis( 15-Dimethyl-3-
!
furyl) Monosulfides.
Into a 25 ml three-neck, round-bottom flask equipped with an
addltion funnel, magnetic stirrer and ice bath are lntroduced 9.o g of
2,5-dimethylfuran and 1.104 g of stannic chloride. At a temperature of
; 0 C 2 g of sulfur dichloride, SC12, is added during 33 minutes. The reac-
tion mixture is then poured into 50 cc of ice-water slurry, and the reac-
tion mass is extracted twice with 20 cc of isopentane and once with 40 cc
of diethyl ether. About three grams of brown oil is recovered after sol-
vent removal. This brown oil has an odor of roast meat. Column
chromatography on 50 g of silicic acid with 5% ether in hexane gives o.6 g
of material having a roast meat aroma. Re-chromatography of this material
on 25 g of silicic acid initially using hexane and then 1% ether in hexane
as eluent gives 0.22 g of a mixture of 2,5-dimethyl-3-furyl monosulfide and
2,5-dimethyl-3-furyl disulfide.
The resulting mixture of bis(2,5-dimethyl-3-furyl) sulfide and
disulfide is recovered after the combined solvent extracts have been evap-
orated. The sulfide and disulfide have a meat aroma and a cooked meat
taste.
EXAMPLE III
Preparation of bis(2,5-Dimethyl-3-furyl) Disulfide
Into a 500 cc three-neck, round bottom flask equipped with a
thermometer and addition funnel, and immersed in an ace-tone-dry ice bath
- 15 -
- - :
: ~38~77
are added: 78.6 g 2,5-dimethylfuran, 0.1 g anhydrous stannic chloride,
and 100 cc hexane. Over a period of one hour, 27 cc of sulfur monochloride,
S2C12, is added while the pot temperature is maintained between -22 C and
O C. During the last 20 minutes a vacuum is applied to the reaction flask
to remove the hydrogen chloride gas which evolves.
At the end of the reaction the reaction mass is poured onto 200
- cc of a water-ice slurry. Hexane-insoluble solids are then filtered and
the aqueous layer is separated from the hexane layer. The hexane layer is
washed with one volume of 10% aqueous sodium bicarbonate and then with
100 cc of water. This is followed by washes with 200 cc water, 5% aqueous
sodium carbonate and 200 cc water. The hexane solution is then dried over
anhydrous sodium sulfate and filtered, and the hexane is evaporated to
produce 21.9 g of a dark oil. This dark oil, on standing, deposits a
solid. The residual oil is taken up in 50 cc hexane and the hexane solu-
tion is washed twice with 50 cc and once with 100 cc of water. After
drying over sodium sulfate and solvent removal, 11.~ g of oil is recovered.
, ~ Ten grams of this crude oil is dissolved in 5% of diethyl ether
in hexane and subjected to colu~n chromatography using a 5.5 X 78 cm
column packed with 200 g of silicic acid and the diethyl ether-hexane mix-
ture as eluent. Analysis of the 5.3 g of product recovered from the col-
umn by means of proton magnetic resonance and infra-red and mass spectro-
scopy confirms the production of bis~2,5-dimethyl-3-furyl) disulfide. This
material has a roasted-meat aroma and a cooked-meat taste.
Analytical data are obtained as follows:
Infra-red:
max Interpretation
3.22 Aromatic CH stretch
; 6.21, 6.38 Aromatic ring C-C stretch
7.23 Methyl group
12.55 CH bond of aromatic ring
Proton Magnetic Resonance:
; In carbon tetrachloride:
- 16 -
1~3~877
2.1 (singlet, 6 protons),
2.27 (singlet, 6 protons), and
6.o ppm (singlet, 2 protons).
Mass Spectrum:
Base Peak 43, Molecular Peak 254. Other peaks in descending
order: 127, 128, 85.
EXAMPLE IV
Production of Furan-3-Thiol Derivatives
A 250 ml flask fitted with a mechanical stirrer, gas inlet tube,
calcium chloride drying tube, thermometer, and Y-tube is charged with 50
ml of distilled Diglyme, and the Diglyme is saturated with gaseous hydrogen
chloride at O - 5 C with constant stirring.
The flask is then immersed in a dry ice-isopropanol bath at -80C.
The cooled flask is charged with 1~.0 g (0.14 mole) of 2-methyl-3-
tetrahydrofuranone, and 28.5 g (o.84 mole) of hydrogen sulfide which has
been chilled to -80C is slowly warmed and allowed to boil over into the
reaction flask.
About one-half hour after the beginning of the hydrogen sulfide
addition a pink-red color begins -to appear in the reaction mixture. By
the end of the 2.5 hours required for the addition of all the hydrogen
sulfide, the reaction mixture is orange in color. At this time stirring
is stopped, and the reaction mixture is permitted to stand 16 hours.
A one-liter Erlenmeyer flask is charged with sufficient sodium
bicarbonate -to cover the bottom of the flask and is placed into a dry ice-
isopropanol bath. The reaction mixture is then poured slowly over the
sodium bicarbonate to minimize foaming. Adaitional sodium bicarbonate is
added until all foaming ceases. The neutralized mixture is treated with
200 ml of water and quickly ex-tracted with 100 ml of methylene chloride.
The organic solution so obtained is dried and concentrated to provide 39.5
grams of an oil. The oil is distilled under vacuum to provide a first cut
taken at 73-80 C at 57 mm Hg and a second cut at 80-83C at the same pres-
sure.
- 17 -
~L~38~77
The 25 ml of the second portion is dissolved in 100 ml of ethyl
ether and extracted four times with 5 ml of 5~ aqueous sodium hydroxide to
remove the pink color. The basic fraction so obtained is acidified with
11.2 cc of hydrochloric acid and extracted twice with 10 ml of ethyl ether,
dried over sodium sulfate, and concentrated.
This concentrate is then chromatographed to separate the 2-
methylfuran-3-thiol and 2-methyl- ~,3X~- dihydrofuran-3-thiol produced.
These thiols have a roast meat aroma with the aroma of the furan-3-thiol
being very similar to that of the aisulfide produced in Example III.
The analytical data on the 2-methylfuran-3-thiol are:
Infra-red:
~max Interpretation
3.92 S-H group con~ugated with
aromatic ring
7.40, 6.60 Aromatic ring C=C bond
7.26 Methyl group
13.58 C-H bond of aromatic ring
Proton Magnetic Resonance:
In carbon tetrachloride:
2.12 (doublet, 3 protons),
2.23 (doublet, 1 proton),
6.o8 (doublet, 1 proton) and
7.04 ppm (doublet, 1 proton).
Mass Spectrum:
Base Peak 43, Molecular Peak 114. Other peaks in descending
order: 41, 45, 85, 47, 113, 71, 75, 74.
EXAMPLE V
Preparation of bis(2-Methyl-3-furyl) disulfide
The thiol produced in Example III is oxidized under mild condi-
tions by dissolving 5 g of the thiol in lOO cc of hexane. The solution is
placed in a 250 cc flask equipped with a sparger supplied by an air ~ource,
a stirrer, and a heater. Air is bubbled in at room temperature at a rate
of 20 ml/minute during 20 hours. Solvent is replaced as required in order
- 18 -
~38877
to maintain the original volume of solution. At the end of the reaction
period the solvent is flash-evaporated and the resulting mixture is puri-
fied by column chromatography to yield 3 g of bis(2-methyl-3-furyl)
disulfide.
The purified bis(2-methyl-3-furyl) disulfide has a full meat
flavor and a cooked meat aroma when used in soup base at a concentration
of 0.2 ppm. In a comparison 5-methyl-2-furyl disulfide is also used in
soup base at a concentration of 0.2 ppm and is found to have only a chem-
ical, rubbery taste and aroma.
The analytical data for the 3-furyl disulfide follow:
Infra-red
~max Interpretation
3.22 Aromatic C-H s-tretch
6.32, 6.6Q Aromatic C~C stretch
7.22 Methyl group
11.28 Furanic ring vibration
13.6 C-H out-of-plane bend of a
2,3-disubstituted furan.
Proton Magnetic Resonance
In carbon tetrachloride:
7.14 (doublet, 2 protons),
6.25 (doublet, 2 protons), and
2.07 ppm (singlet, 6 protons).
Mass Spectrum
Base Peak 113; Molecular Peak 226; Other peaks in descending
order: 43, 45, 51, 114, 85.
EXAMPLE VI
The following ingredients are homogeneously admixed at 25 C:
Ingredient Amoun-t (g)
; 2-Methylfuran-3-thiol 2.0
2-Methyl-Lh,5-~ -dihydrofuran-3-thiol 0.5
bis(2-Methyl-3-furyl) disulfide 93.0
bis(2-Me-thyl-3-furyl) monosulfide 4.0
-- 19 --
1()38~377
bis(2-Methyl-3-furyl) trisulfide 0.5
The mixture has an excellent roasted-meat flavor when used in a soup base
at 10 ppm.
'
~ EXAMPLE VII
,~ :
The monosulfide prepared in Example I is dissolved in propylene
glycol to provide a 0.1% solution. This solution in the amount of o.966 g
is added to 7.3 g of a soup base consisting of:
Ingredient Amount
(Parts/100 total)
Fine ground sodium chloride 35.62
Hydrolyzed ~egetable protein 27.40
Monosodium glutamate 17.81
`/ Sucrose 10.96
Beef fat 5.48
Sethness caramel color (powder B & C) 2.73
The resulting mixture is added to 12 ounces of boiling water to
obtain a soup having an excellent meat flavor.
The composition of Example VI (.005 g) when added to the above
soup base also provides a soup having a good roasted-meat flavor. Similar
results are obtained when the bis(2-ethyl-3-furyl) sulfide or bis(2-propyl-
3-furyl) disulfide is used.
EXAMPLE VIII
One-half gram of the soup base mixture of Example VII is emul-
sified in a solution containing 100 g gum arabic and 300 g water. The
resultant emulsion is spray-dried with a Bowen Lab Model Drier utilizing
, 250 cfs of air with an inlet temperature of 500F, an outlet temperature
of 200 F, and a wheel speed of 50,000 RPM.
Twelve grams of the spray-dried material is mixed with 29.2 g
of the soup base set forth in Example VII. The resulting mixture is then
added to 12 ounces of boiling water, and an excellent roasted-meat flavored
soup is obtained.
EXAMPLE IX
The following ingredients are selected and mixed as described in
- 20 -
1~38~377
Example VI to yield compositions having excellent meat flavor:
MIXTURE A
Ingredient Amount
(Parts/100 total)
2-Methylfuran-3-thiol 5.
2-Methyl-3-thio-C4,5~ -dihydrofuran 5.
bis~2-Methyl-3-furyl) disulfide 1.
bis(2-Methyl-3-furyl) monosulfide 89.
MIXTURE B
bis(2-Methyl-3-furyl) trisulfide 15.
bis(4-Methyl-3-furyl) trisulfide 5.
bis(4-Propyl- ~,5~ -dihydro-3-furyl)
monosulfide 5.
bis(2,5-Dimethyl-3-furyl) monosulflde 25.
Corn oil 50.
MIXTURE C
2-Ethylfuran-3-thiol 9-
2-Butylfuran-3-thiol 9.
bis(2-Pen-tyl-3-furyl) trisulfide 30.
bis(2-Ethyl-5-isopropyl-L~,3H~-dihydro-
3-furyl) trisulfide 1.
bis~2-Butyltetrahydro-3-furyl) monosulfide 1.
Gum arabic 50-
EXAMPLE X
Isolation of bis(Fury~) Disulfides from a Reaction Mixture
A 4,000-pound batch having the following composition:
Thiamine hydrochloride 8.8 parts
L-Cysteine hydrochloride 8.8 parts
Maggi 4 BE protein hydrolysate309.6 parts
Water 672.8 parts
1,000.0 parts
is heated at reflux for four hours. After the first 45 minutes of reflux
a total of 40 gallons of condensate is removed uniformly o~er the next 3
hours and 15 minutes. Each gallon of condensate is extracted with 400 ml
- 21 -
:
~0313877
portions of methylene chloride. After removal of the me-thylene chloride
under very mild vacuum, a 50 ml residue is obtained which possesses an
extremely powerful roast-meat aroma.
Preparative thin-layer chromatography (8x8'! x 1.25 mm, silica-gel
; G, 200 ~/plate) of approximately 2.4 g gave o.o66 g of a pure compoundhaving a good basic roast-meat aroma upon proper dilution. The mass spec-
trum of this compound is as follows: m/e (rel. intensity)
226 (9.6), 227 (1.9), 228 (1.7), 113 (10.0),
,~ 43 (4.7), 114 (4.4), 45 (3.6), 85 (3.1),
51 (2-9), 69 (17.6). Proton magnetic resonance in carbon
tetrachloride shows 2.07 tsinglet,~ -CCH3), 6.25 (doublet,~ furyl protons),
and 7.14 ppm (doublet, ~furyl protons).
The above data are in excellen-t agreement with the proposed
structure of bis(2-methyl-3-furyl) disulfide:
When the crude extract is analyzed by preparative gas/liquid
chromatography a compound having a very lntense pot roast odor is obtained.
This compound has been identified as 2-methyl-furan-3-thiol.
EXAMPLE XI
Prep~ration of 2-Methyl-3-Furanthiol
A 500 cc three-neck round-bottom flask is fitted with a Y-tube,
thermometer, and stirrer and is then charged with 32 g of fuming sulfuric
acid (oleum) containing 20% S03. The temperature is maintained at 24-28 C,
and 40 g (0.318 mol) of 5-methyl-2-furoic acid is slowly added to the oleu~
during a period of 45 minutes. After addition is complete, the reaction
mixture is stirred for an additional 2-l/4 hours and then held for 16
hours.
The reaction mixture is thereupon poured over 600 cc of ice-water
mixture and neutralized to pH 5 with 430 g of barium carbonate, during
- 22 ~
~.~38877
which neutralization a thick paste forms. After addition of 500 cc of
water, the paste is boiled and then vacuum-filtered while hot. The barium
sulfate-containing solids which remain after filtration are boiled with
700 cc of water, and the mixture is vacuum-filtered while hot. Both
filtrates are combined and refrigerated for two days to form crystals which
are recovered. The filtrate is evaporated to a volume of about 500 cc and
cooled in ice to recover further crystals. The remaining filtrate is evap-
orated to a volume of 50 cc, 100 cc of methanol is added~ and the liquid
is chilled to obtain crystals. The yield of solids (barium-2-methyl-3-
sulfo-5-furoic acid) from the three crystallizations is 93.5 g.
Barium-2-methyl-3-sulPo-5-furoic acid in the amount of 98.2 g
and 1800 cc of distilled water is charged to a flask, and the flask is
heated in a steam bath to 70 C until all the solids are dissolved. Then,
116 g of 20% aqueous sul~uric acid is gradually added to precipitate barium
sulfate. The decanted liquid is cooled in ice and filtered. The water is
evaporated from the filtrate, and the remainder is evaporated under high
vacuum at room temperature to obtain 35.1 g of yellow oil which crystallizes
after being held in a desiccator overnight.
The sodium salt of the sulfo furoic acid is prepared by dis-
solving 33.1 g of the crystallized oil (sulfo furoic acid) in 100 cc of
water and gradually adding 6.75 g of sodium bicarbonate. After drying in
a steam bath and then in a vacuum desicca-tor, 37.4 g of the sodium salt
containing water of crystallization is obtained.
The sodium salt is decarboxylated by charging 13.2 g OI` mercuric
chloride (HgC12) in 60 cc of water to a 500 cc three-neck round-bottom
flask fitted with a condenser having a gas outlet and with a Y-tube, a
nitrogen inlet, a stirrer, and a heating mantle. Then 11.1 g of the sulfo
furoic acid sodium salt in 80 cc of water is charged to the flask, and this
is followed by 1.95 g of sodium hydroxide in 20 cc of water. The mixture
is refluxed for 2 hours and 40 minutes while the pH is maintained at 4-5
by addition of aqueous sodium hydroxide or hydrochloric acid as required,
and carbon dioxide evolves. The mixture is then cooled to room temperature
- 23 -
1~3~3877
and filtered. The filtrate is adjusted to pH 7-8 with 10% aqueous sodium
bicarbonate, and hydrogen sulfiae is bubbled through the mixture to precip-
itate mercuric sulfide. The mercuric sulfide is separated by filtration
and the filtrate is concentrated in a rotary evaporator. About 30 cc of
water is added to dissolve all the solids after concentration and the mix-
ture is cooled to crystallize out 4.93 g of 2-methyl furan-3-sulfonic mate-
rial. The crystals are filtered from the supernatant and dried.
The sulfonic acid derivative is converted to the sulfonyl
chloride derivative by treatment of 1.3 g of the sulfonic acid with 33 g
of thionyl chloride and two drops of dimethyl formamide for 75 minutes at
25 C. The excess thionyl chloride is removed on a rotary evaporator, the
residue iB washed with benzene, and the benzene is strlpped off to obtain
o.88 g of amber oil having a sharp, meaty odor.
The amber oil so obtained ls then reacted with 3.8 g of lithium
aluminum hydride in 30 cc of diethyl ether. The reaction is carried out
by adding the hydride to 20 cc of ether, filtering, adding the oil in 10
cc of ether at reflux during a period of eight minutes. The reflux is
then continued for 75 minutes. After reflux the remaining hydride in the
mixture is reacted with methanol in ether, and the product so obtained is
poured into ice water, acidified to p~I 1 with hydrochloric acid, and ex-
tracted with ether to obtain an oil. This oil is dried, filtered, and
~ stripped of ether to obtain 0.27 g of a yellow oil having a good meaty
; aroma.
Proton magnetic resonance of the major peak obtained from this
oil by gas-liquid chromatography shows a thiol. Mass spectroscopy of this
material shows peaks at 114 and 113. These results confirm the production
of 2-methyl-3-furanthiol.
EXAMPLE XII
Preparation of bis-(2-methyl-3-furyl) tetrasulfide
S--S--S--S
- 24 -
1~38877
~ o a flask containing a solution of 2-methyl-3-furanthiol
(1.65 g) in ethyl ether (10 ml.) and solid sodium bicarbonate (3.0 g)
cooled to -30C was added dropwise a solution of sulfur monochloride
(l.Olg) in ethyl ether (10 ml). After standing 45 minutes the reaction
mixture is poured into water (75 ml), the upper layer is separated and
washed with water (25 ml). After back-extracting the aqueous washings with
ethyl ether (25 ml.) the ether solutions are combined and washed with water
(2 x 30 ml.) until the pH of the wash is about 5. Drying the ether solu-
tion with anhydrous sodium sulfate followed by solvent removal in vacuo
; 10 gives 1.6g. of crude bis-(2-methyl-3-furyl) tetrasulfide.
Column chromatography of the amber oil on 60 g. of silicic acid
packed in hexane followed by elution with hexane gives 1.1 g. of analyt-
ically pure bis(2-methyl-3-furyl) tetrasulfide as a light yellow oil. The
puri~ied bis(2-methyl-3-furyl) tetrasulfiae has a full meat flavor and
brothiness when used in soup base at a concentration
- 25 -
lQ3B87'7
of 0.2 ppm. ;
2 . ¦ Infra-red
3 ¦ ~ mas
1 3100 1 .
s 1 2900
s 1 1570
? l 1510
8 1 1435
1380
~o 122.5
t1 1122
12 1086
,13 938
88i
73
645 cm~l
Proton Magnetic ~ ~ nance in carbon tetrachloride.
18 . 2.37 (singlet~ 6 protons)
19 6.38 (doublet, J=2Hz~ 2 protons)
7.20 (doublet~ ~=2~1z, 2 protons)
21 Mass Spectrum .
22 Base Peak 43; Molecular Peak 290. Other peaks
23 in descending order 113, 45, 226, 114, 51,
24 85~ 69.
2s Elemental Analysis: Calculated for CloH1002SI~;
C, 41.35; H, 3.47; S, 44.16. Found: C, 41.52; H, 3.38;
27 S, 43.77-
28 EX~MPLE XIII
29 The followine ingredients are homogeneously ,
30 admlxed at 25C: 2 ~
31 ~ .
. .
Il ' lU;~8l~77
l . ~redient
2 2-Ethyl~uran-3-thiol -~ -- 9
3 2-Butylf'uran-3-thiol ~ 9
bis (2-Pentyl-3-furyl)trisulfide ----~ ^30
bis (2-Ethyl-5-isopropyl-[2,3H~- ,
; 6 dihydro-3-furyl)trisulfide ------------ 1 .
bls (2-Butyltetrahydro-3-furyl)
8 monosul~ide ---~-------------^------- 1
9 bis (2-Methyl-3-furyl) tetrasul~ide ------ 5
Gum arabie ---------_-___________________45
; 1l Total 100
12 . The mlxture has an excellent roasted-meat flavor
23 ~ and moy b dded to n soup bsse st 10 ppm.
7 . ~:
18
19 , .
221
22
23
2~ 27
27
29 .
.31 . '
