Feb. 2, 1965
3,168,550
_1. H. BLUMENTHAL
ALIPHATIC AND ALICYCLIC NITRILES
Filed May 26, 1961
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J. H. BLUMENTHAL
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ALIPHATIC AND ALICYCLIC NITRILES
Filed May 26. 1961
4 Sheets-Sheet 2
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INVENTOR.
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Feb. 2, 1965
3,168,550
J. H. BLUMENTHAL
ALIPHATIC AND ALICYCLIC NITRILES
Filed May 26. 1961
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Feb. 2, 1965
J. H. BLUMENTHAL
3,168,550
ALIPHATIC AND ALICYCLIC NITRILES
Filed May 26. 1961
op
4 Sheets-Sheet 4
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INVENTGR
JÈCKHBLUMENTHAL.
3,168,550
4
Example 4
gave 827 grams of methyl geranylcyanoacetate boiling
from 132-142° C.
As in Example 2, 0.5 liter of benzene and 1.5 moles
(B) To 2400 grams (10.24 moles) methyl geranyl
of powdered sodamide were mixed in a ñask and heated
cyanoacetate was added with cooling and stirring, 4500
to redux with stirring. A solution of 1 mole geranyl
grams (11.26 moles) of 10% sodium hydroxide in one Ul bromide (trans-isomer) and 1.5 moles of isobutyronitrile
hour at 20-25" C. After stirring for another hour at
was added at such a rate with stirring that rellux was
20-25° C., the mixture was poured with stirring into a
mixture of 2400 grams of water, 632 grams of sulfuric
maintained without external heating.
acid (96%) and‘l025 ml. of cumene. After stirring for
washed, and solvent and unreacted nitrile stripped off as
ten minutes, the vupper layer was separated and washed
with saturated salt solution (3 X300() grams) at 40-50° C.
The organic layer was then added with stirring in about
4 hours to a reñuxing mixture of 1025 ml. of cumene, 3.4
grams of sodium acetate and 6.8 grams of copper powder.
in Example 2. The residual oil was distilled under vac
uum, and the distillate washed as in Example 2 with sul
furic acid and water. The product, geranyl isobutyro
nitrile (trans-isomer) is a perfume material and has a
unique, fragrant, woody, peach odor. It showed only one
major peak by GLPC, as will appear in FIG. 7, showing
After refluxing for an additional hour, the cumene was
distilled off at 15 mm. The residue was flash distilled
it to be a single isomer. The trans-isomer had the follow
and the ’distillate fractionated through a Vigreux column
at 4 mm. Hg. There was obtained 1215 grams (78% of
ing physical constants: boiling point 114° C. at 3.7 mm.
Hg; nDZU 1.4676, D202“ 0.8592.
theory; HD2@ 1.4700; d4” 0.8675; boiling point 100° at
4 mm. Hg) of geranyl actonìtrile.
The mixture was
then refluxed, Water added, the benzene layer separated,
The geranyl bromide (trans-isomer) used »in this ex
GLPC (gas-liquid 20 ample was prepared by the following procedure:
>partition chromatogram) showed two major peaks with
a shoulder estimated to be about 6% linalyl isomer. The
'geranylacetonitrile has the formula:
To 472 grams of geraniol (98%) and 80 ml. of pyri
dine, cooled by a Dry-lce-alcohol bath, was added, with
good stirring, over a period of two hours 115 grams of
phosphorous tribrornide while maintaining the reaction
temperature between -10 to _15° C. The mixture was
allowed to warm to room temperature and then was
distilled rapidly at 3 mm. Hg to yield 550 grams of dis
tillate.
.
'
The crude product was combined with 800 rnl. of
In a dry flask was placed five liters of benzene and 15 30 petroleum ether and then washed with 600 ml. of a cold
(5° C.) 3% sodium carbonate solution, followed by two
moles of powdered sodamide. TheV mixture was stirred
water washes of 500 ml. each.
andgheated to reñux. A solution of 8.7 moles of the
After drying over sodium sulfate, the petroleum ether
was stripped olf to yield 518 grams of geranyl bromide
myrcene hydrochloride prepared as in Example l, and l5
« moles of isobutyronitrile were added to the benzene and
sodamide at such a rate with stirring that reflux was main
(trans-isomer) .
‘
As a check on the configuration of the bromide, it was
tained without external heating. The mixture was reconverted back to geraniol via the acetate by reaction with
ñuxed until the evolution of ammonia creased. An equal
potassium acetate in acetone at room temperature [(see
Volume of water was added and the benzene layer was
Ruzicka and Firmenich, Helv., 22, 396 l939)], followed
separated, washed with water, >and the solvent and un
40 by saponiñcation to the alcohol. The'alcohol was identi
reacted nitrile stripped off. The residual oil was distilled
fied by GLPC by comparison of its retention time with a
>under vacuum and the‘distillate washed with twice its
standard sample of geraniol.
’Volume ofV 10% sulfuric acid, then with water until neu
tral. The organic layer was fractionated under vacuum .
Example 5
to yield 1000> grams (4.85'moles) (56% of theory based
on rnyrcene` hydrochloride) of geranyl isobutyronitrile 45
which is a perfume material having a line peach note with
floral perfume quality. The product,
In a dry flask was placed 7.3 moles of acetonitrile and
1 mole of geranyl chloride. The mixture was heated to
50° C. with stirring. Heating was discontinued and l
mole of powdered sodamide was added in small portions
(with vigorous evolution of ammonia) over a period of
50 35 minutes at 50-60" C. with cooling and vigorous stir
ring. After stirring for another half hour at 60° C., the
excess acetonitrile was distilled olf.
had the following physical constants: boiling point 118°
The residue was
washed twice with an equal volume of water, dried and
distilled under vacuum. The distillate was washed with
at 5 mm. Hg, nm, 1.4642, D2020 0.8552.
FIG. 8 shows by GLPC two peaks, representing the cis 55 dilute sulfuric acid, then washed neutral with water,
saturated bicarbonate solution and water. The washed
and trans isomers.
Example 3
As in Example 2, 4.0 liters of benzene and 10.5 moles
oil was dried and fractionated under vacuum to yield
a product which had a sweet, rosy, fruity odor.
There were no vinyl absorption peaks in the infrared
Vof powdered sodamide were mixed in a ñask and heated
to reflux while stirring. A solution of 6.7 moles of the 60 spectrum of geranyl acetonitrile produced in this manner,
ïmyrcene hydrochloride prepared as in Example l and 18
moles of propîonitrile were added at a rate with stirring
such that reflux was maintained without external heating.
’ The mixture was refluxed, water added, the benzene layer
and GLPC showed only two peaks in a 75:25 (trans-cis)
ratio. The product had the following physical constants:
boilingv point 84° C. at 0.4 mm. Hg; HD2@ 1.4707, D2020
0.8697.
The geranyl chloride used in this example was
separated, washed and stripped. This was followed by 65 prepared as follows:
To a solution of 3 l. of dry ethyl ether and l3 kg. of
Y >distillation under vacuum, washing and fractionation of
linalool cooled to 0° C., was added with stirring and
cooling a solution of 1.8 kg. of phosphorous trichloride in
3 liters of ether over a period of four hours while main
70 taining the temperature between -5 to +5" C.
The reaction mixture was poured into 15 liters of ice
cold water, the oil layer separated and washed with 6
'A had the following physical constants: boiling point 100°
liters of cold water, followed by 6 liters of cold 5% sodi
um hydroxide solution and then with water again. After
at l mm. Hg, HD2“ 1.4689, D2020 0.8629. The perfume
l material had a floral, fruity, peach odor.
75 drying the solvent was stripped olf and the crude product
the organic layer, all as in Example 2. The product
3,168,550
5
fractionated under vacuum. A cut boiling at 68° C. at
g 2 mm. Hg; nDZO 1.4790, D1515 0.9254, was used for the
FIG. 5 shows an infrared chart for cyclogeranyl aceto
nitrile as produced by Example 6.
reaction with acetonitrile. The infrared spectrum of the
geranyl chloride used indicated the presence of about
FIG. 6 shows an infrared chart for cyclogeranyl iso
butyronitrile as produced by Example 7.
,
10% of linalyl isomer.
FIG. 7 is a GLPC (gas-liquid partition chromatogram)
5
chart of geranyl isobutyronitrile trans-,isomer as produced
Example 6
by Example 4, and
To arefluxing mixture of 200 grams of 85% phosphoric
FIG. 8 is a GLPC chart of> geranyl isobutyronitrile as
acid and 240 grams of ‘benzene was added with stirring
produced by Example 2.
354 grams (2.0 moles) of geranyl acetonitrile, as prepared 10
I claim:
1. A composition of matter selected from the group
consisting ` of (a) 5,9-dimethy1-4,S-decadienyl nitrile
in Example l. After an additional reñux period of two
hours, the mixture was cooled and separated, at 50° C.
The upper layer was washed neutral with saturated salt
solution, sodium bicarbonate solution, and water. After
stripping oif the benzene, the residue was fractionated
through a Vigreux-oolumn at 5 mm. Hg. Yield: 312
monosubstituted in the 2 position by a methyl; (b) 5,9
dirnethyl-4,S-decadienyl nitrile disubstituted in the 2 position by methyl groups; (c) a mixtureof alpha, beta
and gamma cyclogeranyl acetonitrile; and (d) a mixture
grams (90% of theory) of cyclogeranyl acetonitrile (mix
ture of double bond isomers) having the formula
of alpha and gamma cyclogeranyl isobutyronitrile.`
2. Geranyl isobutyronitrile having the formula:
20
5
GHz-CHgCN
in which a double bond is in‘ one of the dotted positions. 25
> It had the following physical constants: boiling point 108°
l C. at 5 mm. Hg, nr?" 1.4822.
(Fractions bullied had a
range of HD2” 1.4792-l.4829.) It is a perfume material
having a rooty, woody, vetiver-like odor.
4. A mixture of alpha, beta and gamma cyclo'gerauyl
30 acetonitriles having the formulae:
Example 7
CH3 CH3
360 grams of 85% phosphoric acid and 220 grams of
benzene were heated to 65° C. in a ñask.
Cäa CH3
360 grams of
the product from Example 2 were added with good stirring
over a period of ten minutes, and the mixture was refluxed 35
for one hour. 220 grams of benzene were‘added and
the mixture was stirred for one hour without heating. The
benzene'layer was separated and washedrneutral. The
l solvent `was stripped off and the residual oil fractionated
under vacuum. The distillate weighed 290 grams and 40
i Alpha
Beta
Cil-I3 CH3
had the following physicalconstants: boiling point, 90° C.
' at 1 mm. Hg, HD2” 1:4767, D202o 0.9134. The product,
which had a characteristic fruity, woody odor, was shown
by GLPC to consist of two major components. These
were isolated, and were found from their infrared ab
Gamma
" sorption curves to be the alpha (A) and gamma (B)
5. Alpha cyclogeranyl isobutyronitrile having the for- ì
double~bond isomers,
i
CH3 CH3
mula:
»
\/
(ïHS
`
’
. CH3
CHT-(ID-CN
CH3
CH3
CH3
(A)
CH3 CH3
$H3 `
CHg-t‘ì»-GN
Y
’
CH3 CH3
:CH:
ì
`
‘
(B)
(Alpha Cyelogeranyl
55
(Gamma Cyclogerany]
6. Gamma cyclogeranyl isobutyronitrile having the for- l
Isobutyronitrile)
Isobutyronitrile)
‘ It is to be noted that a variation in the relative propor
tions of the various double bond isomers in the above
examples will cause a variation in the‘physical constants
given.v
_
.
All temperatures herein used are expressed in ° Cf
_om ons
In addition to the characteristics of the compounds of
7. The trans-isomer of geranyl isobutyronitrilehaving
the following physical characteristics: boiling point` 114°
the above examples, further ì. characteristics of> the com
pounds are shown in the accompanying drawings, in .
which:
Y
‘
.
.
'
’
.
~
65
C at 3.7 mm Hg, m32“ 1.4676, `13202008592.
‘
p FIG. lshows an infrared chart for gcranyl isobutyro
nitrile` as produced byExample 2.
. FIG. 2 shows-an infrared chartA for geranyl acetonitrile .,
as produced by‘Example 5.
FIG'. 3 shows an infrared chart fortrans-isomer geranyl 70
‘ isobutyronitrile as produced ‘by Example 4.
FIG. ‘,4 shows an infrared chart for alpha geranyl pro~
l ‘v pionitrile‘as producedrby Example 3.
,
References'Cited` in thelfile of this patent
Zeigler: Chemical Abstracts, ">vo1. 26’y (1932), page "l
5573.@
t.
‘
i
V`
Rajzmonqchemicai Abstracts, v51. `43 (1949), page
3798.
`
Y
Í Cornforth et al.: Journal of the` Chemical Society `
(London), page 2540, July 179,59.
¿ '