Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
106ZZ~6
The present in~ention relates to a method for the preparatio~
of 2-alkyl indane.
The ~ethod according to the invention is particulerly
economical on the industrial level in view of its simplicity,
the low number of stages to be carricd out and the excellent
yields obtained.
2-alkyl indanes obtained by the method accordin~ to the
invention may be used in particular as us~ful intermediate products
for carrying out the synthesis of certain medicaments.
In fact, the present invention relates to a method for the
preparation of 2-alkyl indane of formula~IV):
,
. .,
(IV)
in which R represents a group chosen from a straight or branched
lower alkyl group at Cl-C5 and cycloalkyl group at C3-C7,
characterised in that :
a) An aromatic ketone of formula (I) :
. ' O
C - CH2 - R (I)
.::
in which Risasabove-defined, is condensed with formaldehyde or
~-~ a precursor of formaldehyde in a basic medium and in a polar
organic solvent with a view to obtaining a ketol of formula (II)
, .
- 2
- . ~ - :
:. . ~ ~ ~ : .. : -
-. . . ~ : : -.
- .
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1062Z86
o
C - C~ - R
CH20~ (II)
in which R is as defined above.
b) said ketol of formula (I) is cyclized in a strong acid
~ medium with a view to obtaining the indanone of formula (III)
.j O
¦ ~ (III)
in which R is as defined above.
c) said indanone is reduced with a view to obtaining the
desired 2-alkyl indane.
The use, during the condensation stage a) of the method
`~ according to the invention, of a polar organic solvent such as
tetrahydrofuran, dimethylformamide, hexamethylphosphorotriamide
~-~ and dimethylsulphoxide for example, makes it possible to
~j - substantially improve the yield and all other things being equal,
to reduce the initial quantity of ketone used.
Dimethylsulphoxide is one of the preferred polar organic
solvents.
When carrying out stage a), it is possible to use either
formaldehyde or "trioxymethylene" which is the cyclic trimerized
-i form of formaldehyde.
~ he method according to the invention is particularly useful
for preparing 2-alkyl indanes in which the alkyl radical is chosen
from the ethyl and isopropyl radicals.
., .
.~ . _ ~ _
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' ' , , ' " ~ '~ . ' ,
' ' ' ' ' ' ' ,' ' '
' . .' '' ' ' ' ' "''' ' '' ' ' .
106Z286
The strong acid used during stage b) may be chosen more
particularly froul sulphuric acid nnd polyphosphoric acid.
.
The reduction of stage c) may be carried out by using a
conventional Clemmensen or Wolff-Kishner reaction or by
catalytic hydro~enation of the indanone of formula III.
! To produce the baslc medium of stage a), it is possible to
use soda, potash, an alcoholate, a quaternary ammonium hydroxide,
a carbonate etc. for example.
A precursor of formaldehyde is intended to mean a polycondensed
form of formaldehyde which liberates formaldehyde in the conditions
-~ of stage a). Triox~methylene as mentioned above may also be cited
for example.
~ The invention will be better understood on reading the following
-~i non-limiting examples given as an illustration.
. . .
,~ Example 1
i 2-isoprop~ phen~l propan-3-ol-1-one
' 1
~ormula (II) ~ = isoprop~l
184ml normal ethanolic potash at 20 i8 added drop by drop
to a solution of 1800g isovalerophenone and 333g trioxymethylene
in 550ml dimethylsulphoxide. The temperature of the reaction
rises progressively from 20 to 45C and the solution becomes clear.
~, ,
After the end of the addition, the solution is stirred for 3 hours,
thus allowing the reaction to return to ambient temperature. The
latter is left over-night then water and ice are added and an
extraction is undertaken with ether. The ethereal phase is washed
:.
three times with water, then dried over sodium sulphate. ~he ether
; is evaporated under vacuum and 2066g 2-isopropyl-1-phenyl propan-~-ol-
1-one are obtained in the form of white cr~stals, M.P. = 46-48C.
,. . . . . ~ ~ -
. -
.
106ZZ86
This ketol is used as such, without ~ny other purification for the
subsequent operations. However, it may be distilled if desired.
B P 2 mm Hg = 145-150,C (~ield 97j~.).
Exam~le 2
2-ethyl-1-phenyl propan-,3-ol-1-one
_ormula (II) R -- ethyl
:`
;~ 232g 2-ethyl-1-phenyl propan-3-ol-1-~ne are obtained according
~ to the method of operation of Example 1, but usin~ 200g butyrophenone.
`,~ B.P. : 135-140C under 2mm Hg. (yield 96~).
' ~xample 3
2-isopro~l indan-1-one
~.,
~ormula (III) R = iso~rop~l
100g 2-isopropyl-1-phenyl propan-3-ol-1-one are poured drop
by drop over a period of 15 minutes, with considerable stirring,
l keeping the temperature less than 60C, into 220ml concentrated
.,!j sulphuric acid having a density of approximately 1.84g/cm3.
After~the end of the addition, the mixture is cooled to a
temperature less than 50C and stirring takes place for 1 hour,
leaving the reaction to return slowly to ambient temperature.
,i .,
, The latter is poured onto ice and extracted with ether.
. .
The formation of a residue is observed, which remains in
' suspension in ether. ~his residue is removed by decantation and
the ethereal phase is washed with :
a) a saturated aqueous sodium chloride solution
'b) a 5/, soda solution
- c) a saturated aqueous sodium chloride solution.
:
The ether is dried then concentrated under vacuum. A residue
., . . .i . .-
- . .. .. .. ..
- . : .
.. . .: - . ~ ~ :
.
1062Z86
of 83.8g (yield 9~) is thus obtained, which is subjected to
distillation under vacuum ~nd which le~ds to 79g (yield 8~/o)
pure 2-isopropyl indan-1-one.
B P 12mm Hg 135 C.
Example 4
2-ethyl indan-1-on
Formula (III) ~ = ethyl
84.5g 2-ethyl indan-1-one are obtained according to the
method of operation of Example 3, but starting with 100g
2-ethyl-1-phenyl propan-3-ol-1-one.
B-P-18mm Hg = 144C- (yield 94%).
Example 5
2-isoprop~l indane
~ormula (IV) R = isopropyl
A mixture of 520g Zn, 52g HgCl2, 520ml distilled water and
26ml concentrated hydrochloric acid is stirred for 5 minutes.
Stirring is stopped and the mixture is then decantered. 330ml
., .
distilled water and 520ml concentrated hydrochloric acid are
thus added with blending and good stirring, the latter is then
refluxed.
A solution of 468g 2-isopropyl indan-1-one in 520ml ethanol
are then added drop by drop, with good stirring, to the reaction
mixture. The reaction is refluxed for 3 hours. 520ml concentrated
hydrochloric acid are then added in small fractions and reflux
is continued for 3 hours.
. . .
`' At the end of these 3 hours, 520ml concentrated hydrochloric
acid are then added in small fractions and the reflux is continued
-- 6
., ~ : , . , , , :
10~2286
for 3 hours. 'l`he re~;ctiorl ;s then cooled, diluted with a mixture
of water (~d ice and the p:roduct i.s extracted with ether, which is
wa~hed with water, with a 550 soda solution c~ld then again with
water. After undertaking drying over sodium sulphate and
evaporating th.e ether, the resi.d.ue obtained, 463g, i5 subjected
to fractionation under vacuum. One thus obtains 3~1.1g
2-isopropyl indane which crystallises in the form of wh.ite needles
(M.P. = 42C).
B.P.1~mm Hg = 118-120C.
xample 6
~ .
~ 2-ethyl indane
'', :
Formula (IV) R = eth~l
. 98.5g 2-ethyl indane are obtained after distillation under
.~
vacuum, according to the method of operation of ~xample 5, but
starting with 119.2g 2-ethyl indan-1-one.
-P-13mm Hg = 97-100C.
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