Note: Descriptions are shown in the official language in which they were submitted.
Numerous methods for adding flavorants to tobacco smoke
are known in the art. N~ne of these methods, however, has proven
completely satisfactory, particularly where the desired flavorant
is menthol.
The addition of menthol ~E se to tobacco has been found
to be ineffective. The highly volatile nature of this compound
results in a relatively high loss factor incident to the storage
and manufacturing stages required for the production of a smoking
product. Quite clearly, such loss is undesirable ~rom an economic
standpoint.
In an attempt to alleviate these problems, it has been
suggested that menthol might be adsorbed on a suitable support,
such as activated charcoal or fuller's earth, and that the re-
sultant composition might then be added to the tobacco. Attempts
to pursue this method have not, however, met with complete success.
, 1
The menthol yields from such adsorbents have been found to be very
low. Moreover, this method obviously necessitates incorporation
;~ o the adsorbent into the tobacco, and such a foreign material may
., .
¦ result in an undesirable appearance as well as give rise to uneven
.~
, 20 burning of the tobacco.
In order to overcome these difficulties it has been sug-
gested that the menthol could be incorporated into the tobacco as
a part of a compound - i.e. a menthol release agent - in such form
$ ~ .
~ that upon burning of the tobacco, the compound would be decomposed
. ~ ~
to yield the desired menthol flavorant. While considerably more
satisfactory than earlier attempts, even this technique has evi-
denced certain drawbacks.
Bavley et al, U.S. Letters Patent 3,312,226, describes a
' ~
-1-
,., ~, , . . . . . - - "
~ 5 3
process whereby menthol is incorporated into tobacco as the
carbonate ester of various alcohols, particularly one such as
linalool, which were themselves useful flavorants. Upon pyrolysis
of these carbonate esters, incident to the normal burning temper-
ature of the tobacco, the menthol is released to flavor the smoke.
Unfortunately, these simple carbonate esters have not
proven wholly satisfactory. They retain one of the difficulties
of menthol itself, in that they are somewhat susceptible to mig-
ration in the tobacco, and tnereby prevent the strict control of
quantitative release of menthol to the tobacco smoke during burn-
ing, Additionally, the second alcohol of the carbonate ester can
prove susceptible to chemical alteration during pyrolysis, thus
giving rise to undesirable chemical fragments which may add a
chemical after-taste to the smoke.
The Mold et al patents, 3,332,428 and 3,419,543, offer a
slightly different approach to the problem of adding menthol fla-
vor to a tobacco smoke. m ese patents, like that of Bavley et al,
rely upon the formation o~ a carbonate ester to bind the menthol
in a release agent. Here, however, a polyhydroxy compound such
as a monosaccharide, disaccharide, trisaccharide, polysaccharide,
or glycol ~s used to fix the menthol in the tobacco. Again there
are certain draw~aoks.
Because the alcohol linkages of these saccharides and
g~ycols are only primary or secondary in character, the efficiency
with which the menthol can be regenerated upon ~,olysis is limit-
ed, owing to the opportunity for dehydration of the menthol
moiety. Additionally, where attempts were made to utilize menthol-
release agents of h~gh menthol proportion -- i.e., agents which
-2-
:
1(~5~53
would release a high proportion of menthol per unit weight --
it was discovered that menthenes were often produced in addition
to menthol elimination thereby resulting in a bitter tasting
tobacco smoke.
It is the object of this invention to permit the
incoxporation into tobacco of a compound which will release
menthol to the tobacco smoke.
It is a further object of the present invention to
utilize a menthol-release compound characterized by a substantial
lack of volatility and/or mobility at ambient temperatures within
a tobacco composition. Such properties insure the uniformity of
the flavor of tobacco smoke both within each individual tobacco
product and from product to product.
It is a further object of the present invention to
ensure that any non-menthol residue resultant from the pyrolysis,
incident to normal smoking, of a composition containing a
menthol-release agent will be non-deleterious to the flavor
of the resultant tobacco smoke.
It is a still further object of the present invention
2Q to provide a menthol-release agent for tobacco smoking com-
positions, characterized by an optimal efficiency of release
of menthol, incident to normal smoking of the compositions.
In this manner, the amounts of such additive required to be
added to a tobacco composition may be minimized.
The objects of the present invention have been
- satisfied by the discovery of a class of oligomers and lower
molecular weight polymers.
~ - 3 -
1~5i;~4~3
The present oligomers and polymers cannot here be
prec:isely identified individually - in view of their occurrence
as mixtures; possible minor rearrangements in the units incident
to polymerization; and other variables with which those of
ordinary skill in the art are familiar. Based upon some
experience and testing, however, it is believed that the
additives of this invention may be characterized by the
following molecular formula:
-- 4 --
~;
105~53
. 1~3
~2CI~cH2 I T3
C ~ o-11-O- I - (CH2)N
/1\
CH3 H CH3
. 1 3
D I (CH2)N
Iq
.'~ ' .
C ~ ICH2 R4 C}
0 1c-(cH2)N2 - CH2 ~_
; ~ C ~
.CH3 H CH~
Where~n: N, N2 and each Nl have values from O to 8 and R, Rl,
~R4, R5 an~ oa~h ~2 ~na R3 are each selected fr the ~roup
consisting of saturated aliphatic hydrocarbons having 1 to 10
carbons, ~at~rated alicyclic hydrocarbons having 5 to 10
carbons, ~nd aromatic hydrocarbons having 6 to 10 carbons
with ~u~stituents
E~' ..
.~ ,.
....
ll3~ 3
which will not interfere with the desired polymerization; and
M has a value of from O to 98.
A preferred class of additive of this invention which
maximizes the weight percent of menthol available for release
includes those oligomers and lower molecuiar weight polymers which
are !prepared solely from monomers or mixtu.res of monomers selec-
ted from the l-menthyl l,l-dimethyl-alkenyl carbonates as are
more fully described below.
Preferably the compounds are characterized by having
a molecular weight between about 550 to about 30,000.
The addition of from about 1.0 to about 10.0 weight
percent of members of the above-indicated classes of polymers
to a natural or reconstituted tobacco smoking product will
result, through the pyrolysis of the polymers under smoking
conditions, in the addition of an appropriate amount of menthol
to the tobacco smoke to meet the subjective demands of educated
consumers. Such flavoration of the tobacco smoke results in
modifications of taste and flavor, so as to result in a gentle
cooling effect on the mouth and throat and in a spice-like
2~ cooling and taste effect which will linger on aftex e~ch puff,
It is believed that the instant production of menthol
during smoking takes place in accordance with a simple pyrolysis
reaction; the byproducts of which consist essentially of only
carbon dioxide.
. ~ _ 5~a) -
and an ordinary, non-gaseous hydrocarbon. ~ccordingly, only the
menthol itself is consequential with respect to flavoring the
tobacco smoke, and one of the major drawbacks of the prior art
adiditives thereby is avoided.
It has additionally been discovered that incident to the
present use of a tertiary alcohol ester attachment of the menthyl
carbonates to the hydrocarbon backbone in the present polymeric
menthol-release agent, the efficiency of menthol release is im-
proved. The present mode of attachment of the menthyl radical
renders de-esterification the greatly preferred decomposition
mechanism under ordinary smoking conditions. Accordingly, ~his
invent~on offers not only a method whereby substantially all the
incorporated menthol may be released to the tobacco smoke, but
further does so in such manner as to result almost exclusively in
the desired menthol product.
In addition to the aforementioned ease and selectivity of
production of menthol, the instant oligomers and low molecular
weight polymers are further characterized by their substantial
lack of volatility and/or mobility with~n tobacco at temperatures
beneath those encountered upon combustion of the smoking composi-
tion. AccordLngly, the use of the present polymeric menthol-
release agen~s avoids the pitfalls encountered in the processing
; and storage of tobacco prod~cts containing prior art flavoring
agents.
In accordance with this invention, there are substantially
no losses of menthol through sublimation or volatilization there-
of during the ma~ufacturing and storage operations incident to
-6-
.. . .
t~
the production of a useful smoking composition. Additionally, the
drawbacks of diffusion of menthol, or of a menthol-release agent,
within the tobacco are successfully eliminated, and the control of
quality and uniformity within the product tobacco compositions is
successfully maintained.
The present polymeric menthol release agent may be produced
from monomers having the formula:
(B) l R
~ O-~-O-~-(CH~ CH=CH~
Such compounds, per se, also constitute an important part of the
present invention, although their produc~ion may be accomplished
by means within the skill in the art, see for example Bavley et
al, U.S. Patent 3,312,226.
In the foregoing formula, the values represented by "N",
"R", and "Rl" may be varied considerably without substantial ad-
verse effect on the utility of the present monomers or of their
product menthol release agents. Thus, for example, '~ hich
merely reflects the linear separation between the menthol releasing
radical and the eventual polymeric backbone of the release agent -
should usually be maintained within the limits of from O to about
8 carbo~s ~n length, although most preferably this value resides
between O and 2~
The side chains of the present monorners (R and Rl) and of
the eventual polymeric release agent (R and Rl, or R, Rl, R2, R3...
etc. where mixtures of monomers are polymerized) may also be
- 1051;?tS3
varied within wide limits without detrimental effect~ As
ha~ been noted previously, each of these side chains must
minimally comprise at least one carbon in order to satisfy
the discovered requirement that the carbon to which each pair
is commonly attached in each monomer be tertiary. The maximum
size of the hydrocarbon side chains, on the other hand, is
limited essentially through the steric effects of their
presence in each monomer. They may therefore be selected in
accordance with parameters well known in the prior art.
Preferably, however, each such side chain should not exceed
about 10 carbons in number.
Representative of the side chains which have been
discovered to be useful in the present invention are the
aliphatic and alicyclic hydrocarbons from the group consisting
of saturated alkyl hydrocarbons having from 1 to 10 carbons
and saturated alicyclic hydrocarbons having from 3 to 10
carbons with substituents which will not interfere with the
requisite polymerization. The most preferred of the aliphatic
radicals are chains of 1 to 6 carbons in length, which may
comprise either normal or branched aliphatics such as the
methyl, ethyl, propyl and isopropyl moieties. Preferred ali-
cyclics contain from about 5 to 10 carbons and include the
cyclohexyl moiety and lower (e.g. methyl and ethyl) homologs
thereof.
In order to avoid interference of complications
during the polymerization of the present invention, the side
` chains should preferably be restricted to groups which will
not enter into the reaction.
Preferentially, the synthesis of monomers and
polymers within the scope of the instant invention is performed
in accordance with the followin~ sequence of equations:
-- 8 -
..; ~ ,~:
~...
1~51453
(1) I
[ ~ _ 013 + COC12 > ~ _ O-l-Cl
OH OLi
~2) CH2=CH-(CH2)N- C-R + R6Li-~ CH2=CH-(CH2)N- C-R
Rl Rl
Wherein: R6 may be alkyl (e.g. CH3, C2H5, n-C3H7,
n-C4Hg etc.) or aryl (e.g. C6H5).
- - OLi
~3) ~ _ O-C-Cl CH2 C~ (C~2)~ I R ~ Mbnomer (B)
(4) Monomer (B)- ~ Polymer (A)
Equation 1 illustrates the preparation of a halo-
, carbonate which can be employed in accordance with the present
invention. The reaction may, for example, be carried out at
a temperature of from about 5 to about 35C in a common solvent
for the menthol and carbonyl chloride - e.g. benzene. The
carbonyl chloride is preferably added in substantial molar
excess of the menthol, and an appropriate catalyst - e.g.
pyridine - may be employed in such an amount as to facilitate
t~e reaction. The reaction mass should be stirred for a
total of about 3 hours and then allowed to stand overnight.
At the end of this time, l-menthyl chloro-
:`
~, .
'
~ _ g _
formate may be recovered as a slightly yellow liquid.
Equa~ion No. 2 merely illustrates the activation of theumsaturated tertiary alcohol which will eventually constitute
tlhe backbone of the present polymeric menthol-release agent.
The production of the metal alkoxide may best be accomplished
through the addition, at ice temperatures and under an inert
atmosphere, of approximately 1:1 proportions of a lower alkyl
lithium compound to an appropriate, unsaturated tertiary alcohol.
After a few minutes, the reaction mixture may be brought to room
temperature and the metal alkoxide, if desired, isolated.
Equation No. 3 illustrates the preparation of the
l-menthyl l,l-substituted alkenyl carbonate monomers of the
present invention. This synthesis may be accomplished through
the addition of the l-menthyl chloroformate produced in accord-
a~ce with Equation 1 to a solution of the metal alkoxide product
of Equation 2. Both ingredients should be in appropriate sol-
vents, for example anhydrous tetrahydrofuran, and the addition
should be performed at close to ice temperature. The resultant
admixture should then be heated at reflux temperatures (60 to 80C)
for from 10 to 20 ho~rs, cooled to ice temperature, and then
slowly hydrolyzed with wat~r. Separation o~ layers is followed
by extraction of the aqueous layer with anhydrous ether. Wash-
ing of the combined organic layers, followed by drying and sol-
vent evaporation will yield the desired product as a liquid
residue.
The vinyl unsaturation of the present monomers permits
homopolymerization in the presence o~ conventional initiators
of vinyl polymerization - e.g. peroxides (preferably benzoyl
-10-
peroxide) azo compounds and the like - in accordance with the
reaction set forth in Equation 4. The reaction of this equation
may be performed at ambient temperature, but preferably from 50
to 90C, under an inert atmosphere. After from 2Q to 100 hours,
the reaction mass may be dissolved in an appropriate solvent,
washed and separated.
The present polymeric, men~hol-release agents may vary
greatly in molecular weight. Thus, for example, the number of
monomeric units may range from 2 to 100 yield~ng molecular
weights of from about 550 to 30,000. All such polymers are use-
ul within the scope of this invention, however, it is pre-
ferred that polymerization be controlled - through modification
of the catalyst concentration, temperature, time of reaction,
etc. - in order to obtain reaction products having from about
6- to about 40 monomeric units or molecular weights of from about
1600 to about 12,000.
The product, polymeric menthol-release-agent, may be in-
corporated into the tobacco in accordance with any of the methods
customary in ~he art. Thus, it is possible merely to mix the
polymer with the free tobacco prior to the manufacture of the
product smoking composition.
Preferably, however, the polymer will be dissolved in
an appropriate solvent such as acetone and then sprayed or in-
jected into free tobacco. Such method insures a proper distri-
bution of the polymer throughout the tobacco itself, and thereby
permits the production of a more uniform smoking composition.
In the foregoing discussion, it is understood that in
the various formulae the figure, ~ has been employed to
-11-
- : . .
. ~ ,
represent the 2-isopropyl - 5-methyl cyclohexyl radical. Addi-
tionally an unsatisfied valence in a orn~1a - such as polymer
(A) - merely indicates the position for similar attachment to
another monomer or to a chain terminator such as a methyl
radical.
Specific examples of the preparation of the present mono-
mers and polymers, as well as of their use in a smoking product,
are as follows:
EXAMPLE 1
Preparation of the Monomer
A solution of 2-methylbut-3-en-2-ol (0.2 mole, 17.2 g)
in anhydrous tetrahydrofuran (THF, 300 ml) was degassed with
nitrogen and cooled to ice temperature. N-Butyllithium (0.23
mole, 2.38M, 100 ml in hexane) was added to the ice-cold stirred
; solution during 8 minutes and a slow evolution of butane was
observed. The reaction mixture was stirred at room temperature
; (27C) for 2 hours (gas evolution s~opped by this time). After
cooling the mixture to ice temperature l-menthyl chloroformate
(43.8 g, 0.2 mole) in anhydrous THF (150 ml) was added over a
14-minute period, The solution changed from a yellow to an
orange-red color. The solution was heated at reflux temperature
(65~C) for 1~5 hours, cooled to ice temperature and slowly hydro-
lyæed with water (400 ml). The aqueous layer was washed with
two volumes each o 75 ml and then 100 ml of anhydrous ether.
The combined organic layers were dried over anhydrous Na2S04
for 16 hours. After filtration and solvent evaporation, an
orange-red liquid residue was obtained. A number of gas
chromatographs were taken o the residue and a peak (menthol)
-12-
increased as the injection port temperature gas was increased.
The residue was fractionally distilled through a spinning-band
column and 4 fractions were obtained. An IR spectrum was taken
of each fraction. (See below)
Fraction Wt. bP (mm) IR
1 1.60g 27-80 & (0.5 - 0.9) strong CH, wk. C=O
2 3.48 80-82 (0.95 - 1.0) no OH, strong C=O
3 19.47 94 (0.55) no OH, strong C=O
4 1.82 90-80 (0.7) no OH, strong C-O
Samples of fractions 2, 3, and 4 were submitted for NMR analyses.
Data from NMR indicated that fraction 3 was the desired
l-menthyl l,l-dimethylallyl carbonate.
Yield 19.47g
% Yield = 19.47 (100) = 36.3%
Elemental Analysis: Found: C, 71.67; H, 10.71
Calc~: C, 71.60; H, 10.52
EXAMPLE 2
Polymerization
Benzoyl peroxide (BPO, 0.5g) was placed in a 100 ml round
bottom flask which was purged with nitrogen for 15 minutes.
-menthyl l,l-dimethylallyl carbonate (11.05g) was added via a
syringe to the BPO while the system was flushed with nitrogen.
The stoppered suspension (light yellow) was placed in an oven
at 75 + 2C. The mixture was swirled at 30 minute intervals for
:
1.5 hours, and the BPO dissolved within 1 hour. After the mix-
ture had been in the oven for 65 hours, it was cooled to room
temperature. The reaction mixture was a pale yellow gelatinous
mass.
The gel was dissolved in methylene chloride (2 x 50 ml) and
washed into a 1 liter Erlenmeyer flask. After adding 99%
isopropyl alcohol (300 ml), methyl alcohol (450 ml) was added
with vigorous stirring. A fine white precipitate formed, and
~fter 30 minutes, it was filtered and dried.
Yield 5.52g
% Yield 5,52 (100) = 50%
11.05
A small sample was heated and emitted a strong menthol-like
odor.
Elemental Analysis: Found: C, 71.60; H, 10.54 0, 18.04
Calc.: C, 71.60; H, 10.52; 0, 17.88
; Molecular weight determination by the ebulliometric method
in dichloromethane gave a value of approximately 2500 (i.e.
M = 9). Polymers prepared with slight variations in procedure,
such as increased catalyst concentration, showed values of about
5000 ~M 3 18) and 7500 ~M = 25).
EXAMPLE 3
Polymer as Tobacco Flavorant
Reconstituted tobacco was prepared as handsheets by a con-
ventional method, with 6.0 percent by weight of the powdered
polymer product of Example 2 incorporated in it at the slurry
stage. There was no odor of menthol observed during casting,
drying, or æhredding of ~he sheets,
The shredded product was mixed with an equal portion of
cased commercial filler containing no menthol. Cigarettes
85 mm long with 20 mm commercial cellulose acetate filters
were prepared from this mixture by use of a manual cigarette
-14-
,~ . :. . : - .
~ 3
maker. The total weight of filler per cigarette was 900 mg, con-
taining 27 mg (3.0%) of the polymer.
The cigarettes were smoked according to the standard FTC
method and menthol was ound to be present in the mainstream
smoke. m e puff count was 12.1 and a total 0.59 mg of menthol
was measured. The theoretically availab~e menthol was 58% of
the polymer weight, or 15.7 mg; the amount found in mainstream
smoke was 3.8% of this. Similar cigarettes were paekaged and
stored under the various con~itions indicated below. Changes in
menthol delivery upon smoking were regarded as not significant.
Mainstream
Storage Menthol,
Period Conditions m~/ciRarette
7 days Ambient humidity, room temperature 0,45
1 month Ambient humidity, room temperature 0.53
1 mon~h 15% Relative humidity, 110F, 0.59
1 month 85% Relative humidity, 90F. 0.50
Cigarettes prepared in accordance with the example were
; also smoked by a panel of expert smokers who found acceptable to
excessive menthol cooling with no off notes.
EXAMPLE 4
Preparation of l-Menthyl l.l-DimethYlundec-10-enYl Carbonate
A soluti~n of 2-me~hyldodec-11-en-2-ol (39.70g, 0.20 mole)
in anhydrous THE (300 ml) was cooled to ice temperature and nitro-
gen was passed through the system for 20 minutes. n-Butyllithium
(2,1 M in hexane, 120 ml, 0~24 mole) was added via a syringe to
the cold, st~rred solution over a period of 10 minutes. An
evolu~ion of butane was noted d~ring the addition. The lemon
-15-
yellow solution was then stirred a~ room temperature for 2 hours.
Because the gas evolution had not ceased, the solution was warm-
ed to about 35 & and held there for 45 minutes. After the solu-
tion had been cooled to ice temperature, l-menthyl chloroformate
(45.9 g, 0.21 mole) in anhydrous THF (150 ml) was added over a
9~minute period. The color of the reaction ~ixture went from lemon
yellow to wine-red. The reaction mixture was heated at reflux
temperature for 2 hours, was cooled to ice tempera~ure, and was
then hydrolyzed with 700 ml water. The aqueous layer was ex-
tracted with 4 x 100 ml anhydrous ether. The combined organic
layers were filtered and then dried for 16 hours over anhydrous
Na2S04. After filtration the solvents (ether and THF) were
stripped ~rom the reaction product with the aid of a rotary eva-
porator. The residue was a deep red, oily liquid. It was dis-
tilled under reduced pressure through a six-inch Vigreux column
and four fractions were taken; IR and NMR spectra indicated that
the product was concentrated in fractions 3 and 4, particularly
the latter, and probably in the residue. (see below)
Fraction
Wei ht bp NMR
1 3.48g 28-85C (0.2-0.3) strong oH,
no C=O
2 14~85 77 87 (0,2-0.35) strong OH,
no C=O
3 4.3 87-100 ( 1 ) OH and C=O Estim. 50%
menthol
4 32.35 103-117Q t 1 ~ OH and C=O Estim, 35%
menthol
Residue Carbonate,
no menthol
-16-
EXA~PLE 5
Preparation of l-Menthyl l-Renzyl-l-methylbut-3-enyl Carbonate
N:l R:CH3 R':benzyl
,
The method of Grignard and Chambret, Compt. rend. 182, 299
(1926) was used to prepare 2-benæylpent-4-en-2-ol. The alcohol
was converted to the l-menthyl carbonate by a procedure like that
of Example 4. Distillation of the extracted product through an
8-inch Vigreux column gave fractions boiling 25-110/0.04-0.6 mm,
all having strong aH absorption in the infra-red. The residue
was distilled through a short path and the fraction boiling 16S-6/
0.6-0.7 mn showed the following IR absorptions: no ~, strong
carbonate (1750 and 1255 G~m ), vinyl (1655, 978, 913 cm 1),
monosubstituted aromatic (750 shoulder, 697 cm 1). N~ analysis
indicated 80% of the expected mixed ester, a yield of 18.0% from
the alcohol. This product had very little odor, but on heating
produced a menthol odor.
EXAMPLE 6
Preparation of l-Menthyl l-Ethyl-l-methylpent-4-enyl Carbonate
N:2 R:ethYl R':methYl
Alcohol The Grignard reaction was employed to prepare
3-methylhept-6-en-3-ol from 5-hexen-2-one and ethyl bromide by
a conventional procedure. The distilled product showed a yield
of 77% and possessed a boiling point in the range 67-80C at 20 mm
which is the bp and pressure given by Cologne and Clerc, Bull. soc.
chim. France, 1955, 836 for this compound. IR and N~ data shawed
a pure product.
Carbonate To prepare l-menthyl l-ethyl-l-methylpent-4-enyl
carbonate, a so~ution of the alcohol (17.6g, 0.137 mole~ in
-17-
.~, .
~S~ 3
anhydrous tetrahydrofuran (THF, 100 ml) was flushed with nitrogen
for 10 minutes and cooled to ice temperature. n-Butyllithium in
he!xane (0.12 mole, 54 ml of 2.34 M soln.) was added by syringe in
2.5 minutes; there was gas evolution. The mixture was stirred at
room temperature for 1.5 hours and recooled to ice temperature. A
solution of l-menthyl chloroformate (21.0g, 0.10 mole) in 75 ml
anhydrous THF was added in six minutes. The pale yellow solution
was heated at reflux for two hours and then recolled to ice tem-
perature. The solution was carefully hydrolyzed with 300 ml of
water, the layers were separated, and the aqueous layer was wash-
ed with 3 x 75 ml of ether. The combined ether and organic layers
were dried over anhydrous Na2S04 for 17 hours. Filtration and
concentration gave a li~uid residue (35g) which was distilled
under reduced pressure through an eight-inch Vigreux column;
fraction 2 appeared to be menthol and had to be removed from the
cold finger where it condensed as crystals.
Fraction
Wei~ht bpC (mm) IR NMR
1 6.81g 24-6 (0.03) strong oH, med.
2 1.2 26-91 (0.03) (white solid)
3 17.44 92-4 (0.04) strong C=0, C=C,
0-~-0, no OH carbonate
0 high purity
Fraction 3 was clear, colorless liquid with a faint non-menthol
odor; heating caused liberation of a menthol-like odor. Yield
of the mixed carbonate was 56.2%.
-18-
,
EXAMPIE 7
Preparation of l-Menthyl l-Isopropyl-l-phenylbut-3-enyl Carbonate
N:l R:Phenyl R~: isopropYl _
2-Methyl-3-phenylhex-5-en-3-ol
Allylmagnesium bromide was prepared by conventional means
from allyl bromide (90.75g, 0.75 mole) and the ether solution
cooled to ice temperature. Isobutyrophenone (74.1g, 0.5 mole)
in 200 ml ar~ydrous ether was added at a rate to maintain gentle
reflux, over a period of 100 minutes. The mixture was heated to
10 reflux for about 50 minutes and left at room temperature over-
night. It was poured over 500 g of ice and a white precipitate
formed. This was dissolved by adding 500 ml of 10% HCl and the
separated aqueous layer was extracted with 4 x 74 ml of ether.
The combined organic layers were washed with 3 x 125 ml of 5%
sodium bicarbonate and 5 x 100 ml of water and dried over ar~y-
drous Na2S04 four hours. Filtration and concentration gave 84g
of liquid which was then distilled through an eight-inch Vigreux
column under reduced pressure.
Fraction
Wei~eht bpC_ (mm~ IR
4.25 g 92.5-105(5) med. OH, med. C=O
2 11.18 96-105.5~5) med. OH, weaker C=O
3 3.27 100-107(5) med. ()H, less C=O
4 8.91 106-112(5) med. OH, trace C=O
42.25 112-1~8(5-6) strong 0~, no C=O
The yield ~fraction 5) was 44.4%; NMR analysis confirmed it to
be the pure alcohol.
-19-
'' ' ' . ~ ~
Carbonate
A solution of the alcohol (19.0g, 0.10 mole) in 100 ml of
an,hydrous THF, flushed with nitrogen, was cooled to ice tempera-
ture; n-butyllithium (0.12 mole, 54 ml of 2.34 M in hexane) was
added by syringe in six minutes; and gas evolution from the
orange mixture was noted. It was stirred 1.5 hours at room tem-
perature and recooled. A solution of l-menthyl chloroformate
(21.9g, 0.1 mole) in 75 ml of anhydrous THF was added in 6-1/2
minutes, followed by 75 ml more THF to maintain fluidity. The
suspension was heated at reflux for two hours and became an
orange-red solution. It was cooled to ice temperature and hydro-
lyzed with 300 ml of water added slowly. The aqueous layer was
extracted with 4 x 75 ml of ether and the combined organic layers
dried 17 hours over anhydrous Na2S04. Filterin~ and concentrating
gave 37g of liquid product. This was distilled ~hrough an eight-
inch Vigreux column; the distillate (bp 24-92C at 0.08 to 3mm)
had menthol odor and no C=O or ~ absorption in IR. The pot
OCO
residue was a viscous oil having no menthol odor (except when
heated), weak OH and strong C-O, ¦ , and CH=CH2 absorption in
IR, as well as for monosubstituted aromatic. An estimation o~
l-men~hyl l-isopropyl-l-phenylbut-3-enyl carbonate content of
this residue was 70% by NMR, or 50% yield for 26.7g weight.
EXAMPLE 8
Preparation of l-Menthyl l-Methyl-l-phenylbut-3-enyl Carbonate
N l R:CH3 R':phenyl
2-Phenylpent-4-en-2-ol was prepared by the procedure of
Helferich and Lecher, Ber. 34B~ 930(1921); see also German
-20-
Patent 544,388 (1930), C.A~ 26, 24669 ~1932). Literature gives
bp 91-2C/3 rr~n and the fraction used here had bp 98-9/10 mm.
Th~e IR showed a weak to trace C=O and strong OH.
A solution of this alcohol (16.22g, 0.01 mole) in 150 ml of
an~ydrous THF was degassed with nitrogen and cooled to ice tem-
perature. n-Butyllithium (0.12 mole, 53 ml of 2 38 M in hexane)
was added by syringe to the stirred solution in six minutes. A
slow evolution of butane was noted. The lemon yellow solution
was stirred at room temperature for 1.5 hours and recooled to ice
temperature. 75 ml of anhydrous THF containing l-menthyl chloro-
formate (21~9g, 0.01 mole) was then added over 10 minutes. The
orange mixture was heated at reflux for two hours and recooled to
ice temperature. It was carefully hydrolyzed with 400 ml of water;
the aqueous layer was extracted with 4 x 70 ml of ether and the
combined organic layers were dried over anhydrous Na2S04 16 hours.
Filtering and concentrating gave 34g of orange-red oil. This was
distilled through an eight-inch Vigreux column under reduced pres-
sure, and IR spectra were obtained for the fractions,
Fraction
Wei~ht bPC (mm) IR
1 4.42g 24-47 (0.07) Strong OH, weak C-O
2 5.01 52-81 (0.08-0.11) Strong OH, med. C=O
`. ~
O
3 4.11 82-99 (0.7) Med. OH, med. C=O
1~
O
4 5.0 99-104 ~1.0) Weak ~H, strong C=O
3~o
S 4.57 104-120 (1.0) Weak OH, C=O
O O
-21-
Fraction 4 subJected to NMR analysis showed a 45 to 50% content
of the mixed menthyl methylphenylbutenyl carbonate. Its odor
was light and pleasant but non-menthol-like. On heating it gave
a menthol odor.
EXAMPLE 9
Prepara~ion of l-Menthyl 1,1-Diphenylbut-3-enyl Carbonate
N:l R,R':phenyl
The method of Kharasch and Weinhouse, J. Org. Chem. 1, 209
(1936) was used to prepare 1,1-diphenylbut-3-en-1-ol. The pro-
duct boiled at 124C/0,05 mm, while the literature te8ches
150-55/3 mm.
This alcohol (22.4g, 0.10 mole3 in 100 ml anhydrous THF was
flushed with nitrogen and cooled to ice temperature. n-Butyl-
lithium (0.12 mole, 54 ml of 2.34 M soln. in hexane) was added
by syringe in five minutes. There was gas evolution and the
mixture became blood red. It was stirred at room temperature
for 1.5 hours and recooled. A solution of l-menthyl chloroformate
(21.9g, 0.10 mole) in 75 ml of anhydrous THF was added in 10
minutes. The reaction mixture, now light orange, was heated at
reflux for two hours and then cooled to ice temperature.
The mixture was carefully hydrolyzed with 300 ml of water.
The aqueous layer was extracted with 4 x 75 ml of ether and the
combined ~rganic layers were dried over anhydraus Na2S04 for 16
hours. Filtration and concentration gave 38g of a viscous, odor-
less oil. Attempted distillation gave a product wi~h menthol
odor and strong OH absorbence in the IR, indicating decomposition.
The undistilled liquid showed IR evidence for carbonate, aromatic
ring, monosubs~ituted aromatic ring, vinyl, and ~lural methyl
-2~-
~ 3
groups. NMR analysis indicated about 70% content of the expected
carbonate.
EXAMPLE 10
Preparation of l-Menthyl 1,1-Dimethylpent-4-enyl Carbonate
N:2 R,R': CH3
~ . . . . . ~,_
A solu~i~n of 2-methylhex-5-en-2-ol (22.8g, 0.2 mole) in
400 ml of anhydrous THF was cooled to ice temperature and purged
with nîtrogen; n-butyllithium (100 ml of 2.38 M in hexane) was
added to the stirred solution by syringe in 10 minutes. It was
stirred at room temperature for 1.5 hours, by which time the
evolution of butane had ceased. A solution of 43.8g, 0.2 mole of
l-menthyl chloroformate in 150 ml anhydrous THF was added at ice
temperature during 11.5 minutes. After 2 hours at reflux the
solution became deep orange-red. Hydrolysis and isolation of
product followed the general procedures of earlier examples.
Distillation at reduced pressure through a short-path semi-
micro apparatuæ gave 26.7g of product boiling point 98-106C~
0.17-0.26 mm having no menthol odor. Redistillation gave a fore-
run of 0.8g and 23.3g of product boiling point 92-4/0.12 mm, or
39~2% yield. NMR analysis indicated no hydroxyl, IR spectrum
showed peaks at 1745 and 1270 cm (carbonate), 1390 and 1375 cm
(gem dimethyl) and 3090, 1650, 985, and 912 cm (vinyl).
Analysls:
Calc. Found
% C 72.93 72~9
% H 10.88 10.43
-23-
E~AMPLE 11
Polymerization
The carbonate produced in Example 4, l-menthyl l,l-dimethyl-
undec-10-enyl carbonate, after further distillation at 0.5 mm
pressure (weight 2.0g) was mixed with 0.2g of benzoyl peroxide and
~reated according to the procedure of Example 2. Heating time was
96 hours. A colorless, viscous oil was obtained. When 50 ml of
methanol was added and the mixture was ~riturated, a white oily
mass settled out. A sample o~ this mass was subjected to IR
lo analysis; peaks characteristic of carbonate were present at 1740
and 1260 cm , while peaks characteristic of unsaturation at 1640,
1000, and 910 cm were greatly diminished in comparison ~ith the
monomer. After 5 washings with methanol the oily mass becam~ more
tacky but not firmly solid. Heating the odorless material liber-
ated a menthol odor.
Elemental analysis showed:
Calc. Found
% C 75.74 75.90
% H 11.65 11.57
Molecular weight, osometric method in acetone, was 1750.
EXAMPLE 12
PolYmerization
The carbonate produced in Example 6, fraction 3, was placed
(2.0g) with 0,15g of benzoyl peroxide in a 100 ml flask and
treated as in Example 2, heating for 112 hou¢s. A colorless, very
viscous material was produced, This was dissolved in 40 ml of
methylene chloride, and 60 ml of isopropanol was added, then 200 ml
o~ methanol. A white precipitate formed which was tacky and odor-
-24-
~ 3
less; on standing this lost îts tackiness; its weight was 0 4g.
A small sample when heated liberated a strong odor of menthol.
NMR spectrum of this product ~as consistent with a polymer
structure; no evidence o~ unsaturation appeared. Similarly, IR
examination showed that the bands indicative of unsaturation at
1642 cm 1, 993 cm 1, and 903 cm were not distinguishable.
Elemental analysis showed:
Calc. found
% C 73.50 73.15
% H 11.04 10.96
Molecular weight, osometric method in acetone, was 1730
(ave. degree of polymerization 5.6).
EXAMPLE 13
PolYmerization
A heavy-walled glass polymerization vessel was charged
with the product d Example 10, l-menthyl 1,1-dimethylpent-4-
enyl carbonate and with benzoyl peroxide. The vessel was
purged of air by thP ~reeze-thaw technique and sealed off under
vacuum. In this way, 4.5g of the carbonate was mixed with 300
mg of peroxide. The vessel was maintained at 80C in an oven for
139.5 hours.
The reaction mixture on removal from the vessel was
evaporated to dryness using a rotary evaporator. Methanol (5 ml)
dissolved the polymer and the solution was chilled using dry ice.
Frozen polymer precipitated and the monomer-rich methanol solution
was decan~ed, The polymer was brought to room temperature and
20 ml of methanol was added and then chilled. This procedure
-25-
. , . ,.: - - . .
~ .
was carried through five cycles and yielded a tacky, transparent,
oclorless material. After heating to 90O at 1 mm for one hour,
polymer weighing 0.75g was retained for testing.
Elemental analysis gave C,H,0 values of 72.45, 10.82,
and 16.95, the theoretical values being 72.93, 10.88, and 16.19.
Infrared analysis showed the material to contain only a small
amount of unsaturation. The number average molecular weight as
determined from vapor-phase osometry was 1240 corresponding
roughly to tetramer. The 0.75g of purified polymer represented
a 17% conversion from monomer. However, some polymer was lost
during the methanol decantation steps.
~26-
.
