FIELD OF INVENTION
The present invention relates a process for the preparation of 3-methyl-5-phenylpentanol. More
particularly this invention relates to the synthesis of industrially important perfumery compound .
' 3-methyl-5-phenylpentanol which is also known as Mefrosol. 3-methyl-5-phenylpentanol find its
use in broad spectrum of applications including'pharmaceuticals, flavours, fragrances, and
agricultural chemicals. This invention discloses the simplest two steps.synthetic route for the
preparation of Mefrosol starting from the readily available chemicals like aldehyde and - - . ,
unsaturated alcohol with high yield and selectivity.
BACKGROUND OF THE INVENTION
Process for the synthesis of 3-methyl-5-phenylpentanol involves two steps. The first step relates
t0.a process for producing a dihyropyran compound which is also an important fragrant. The
second step involves the hydrogenation followed by hydrogenolysis of the dihyropyran
compound. ,
. - The diydropyran slceleton is a synthetically useful handle and considered to be an important
synthon because of its presence in various natural products such as Laulimalide and (-)-
Dactylolide. Moreover, the synthesis of dihydropyrans are comparatively more attractive since
the olefin function can be further functionalized to obtain polysubstitutedpyrans. (S. Bondalapati,
U. C. Reddy, P. Saha, A. I<. Sailcia, Org. Biomol. Chem., 201 1, ,9, 3428-3438; L.Yet, Chem.
Rev., 2000, 100, 2963-3007).The possibility of obtaining the medium sized oxacycle (pyran)' in a
single step is a challenging task. Though there are several interesting methodologies reported for
the synthesis of oxacycle lilce dihydropyran compound including hetero-Diels-Alder method,
Prins cyclization,, intramolecular Michael reactions and so on. In this context, the synthesis of 4- .
substituted pyrans like 4-halo-, 4-thio-, 4-azido-, and 4-011-, have been reported in the literature.
Among these the synthesis of disubstituted-4-allcyl-tetrahydropyrans is found to be still in its
infant stage or very few reports based on it.Following are the literature reports based on it.
The reaction of aldehydes with conjugated dienes or 3-butene-1-01 compounds in the presence of
catalytic amount of acid re'sults in the formation of isomers of dihydropyran compound (Scheme
1) like 4-methyl-2-p'heny~-3,6-dihydro-2~-pyr4a-nm,e thyl-6-phe~yl-3,6-dihydro-2~-pyraannd
HO -.**-....
+
(or) Acid Catalys , &
R
R
/'
R '
Scheme 1: Synthesis of dihydropyran compound
In the patent, JP-A 1-238578 disclosed a process using aluminium chloride or tin tetrachloride as ,
. .
Lewis acid catalysts in presence of aliphatic and aromatic nitro compound as co-catalyst for
preparation of dihydropyran compounds, but this method generates wastes in large amount and
the reaction yield was also very low 50%.
In 1999, Nishioka et al inventcd the process for the synthesis of dihidropyran compound using
aromatic and aliphatic aldehydes using conjugated diene,'isoprene in presence of Lewis acids like
aluminium trichloride ur iron trichloride' or tin tetrachloride or titanium triltetrachloride or boron
., . trifluoride as a catalyst and achieved the dihydropyran compound with 48 to 84% yield.
S. Oi et al. in Tetrahedron Lett., 1996, 37, 6351 used cationic pd2+ catalyst for the reaction of
unactivated aldehydes with dienes to form dihydropyran compounds.
V. K. Aggarwal et al. in Tetrahedron Lett., 199'1, vol. 38, No. 14, pages 2569-2572 reported
hetero Diels-Alder . reaction of aromatic aldehydes with excess of diene 'using
trifluoromethanesulfonic acid as a catalyst for the preparation of pyran compounds with low to
.. . good yield (5-72%).
J. Inanaga et al. in New J. Chemistry., 1995, vol. 19, 707 used Ianthanide(II1) salts of superacids
such as triflic acid, perfluorooctanesulfonic acid as a catalyst for hetero Diels-alder reaction of
I benzaldehyde and 2,3-dimethylbutadiene. Sc(OP03 and Yb(OPO3(30 mol%) resulted in high
I yields of 2-phenyl-4,5-dimethyl-2,3-dihydropyran and only moderate yield were obtained with
Sc(OT03,but the catalyst system is highly expensive and thus makes the method economically
and .industrially unfavourable.
.. -
In the patent, JP-A 8-127577 a method for the production of pyran compounds using dehydration
I in presence of sulfates were reported.
I . ,
A. Umada et. al in US 2005/0004210 A1 disclosed the method for the preparation of pyran ' . .
I compounds in two steps. The first step involves the reaction of aldehydes withdiehes in presence
I of acid catalyst like methane sulphonic acid, p-toluenesulfonic acid, sulphuric acid, hydrochloric
I . '
acid etc. to form pyran as well a's hydroxypyran.ln the next step, the byproduct hydroxypyran
. . .
compound was subjected to dehydration process in presence of acids like phosphoric acid,
sulphuric acid, methanesulfonic acid, p-toluene sulfonic acid and sulphates like ,potassium
hydrogen sulphate, sodium hydrogen sulphate, copper sulphate, sodiurn sulphate, nickel sulphate, ' .
magnesium sulphate and zirconium sulphate, alumina etc to give the dihydropyran compound.
~ o sotf t he processes have limitations for the preparation ofdihyropyran compounds such as need
for stoichiometric amount of Lewis acid initiatorlcatalysts and external additives, requires strictly
, . anhydrous conditions and pressure, low temperatures which makes the process industrially
unfavourable (Y. Lian and R. J. Hinkle J. Org. Chem. 2006, 71, 7071-7074). Moreover, in most
of the cases isoprene were used, but due to the toxic nature it is not viable for further scale up
processes. (EP 0 834 '509 B 1, US 20051000421 0 A1 ).
To overcome the above said limitations, herewith we have developed a simple and efficient
process for the synthesis of dihydropyran compound using heterogeneous acid basedcatalysts.
The second step involves the hydrogenation reaction followed by subsequent hydrogenolysis of
dihydropyran compound to give the perfume based co~r~poun5d- aryl pentanol (3-methyl-5-
phenylpent~nool r Mefrosol). Mefrosol is a fragrance ingredient used in many cdmpounds.
PdIC (5%)
Temp.
Pressure
Solvent
Scheme 2: Process for the preparation of 3-methyl-5-phenylpentanol .
The core structure is found in medicaments, agricultural chemicals and fragrances used in
decorative -cosmetics, fine fragrances, shampoos as well as in non-cosmetic products such as
household cleaners and detergents (US 200510004210 Al). For the preparation of this
commercially important perfume based compound there are few reports which are discussed as
follows.
Switzerland patent (No. 655932) used palladium based catalyst for the hydrogenation of
dihydropyran compound in presence of inorganic proton acids or acidic diatomaceous earth '
resulted in the formation of 5-aryl-3-methylpentanol. This process involves the use of external
acidic additives for the complete hydrogenation.
R. H. ~Balcer et al. reported in J.' Am. Chem. Soc. 1948, 70, 1490-1492 a method for the
hydrogenolysis of 2-phenyltetrahydropyran using palladium catalyst in an acetic acid solution ,
containing perchloric acid for the preparation of 5-phenylpentanol. This method has the .
drawbaclcs like using the corrosive acids as an additive for the hydrogenolysis step.
U. Matteoli et al. in Chirality 201 1, 23, 779-783 disclosed a method for the preparation of 5- . .
phenyl-2-methylpentanol (Rosaphen) from 5-phenyl-2-methylpentanoic acid using sodium
borohydride and iodine.
A. Umada et al. in US patent 200310060667 A1 reported the process for the preparation of 5-
arylpentanol using mixed metal like supported palladium and platinum carbon powder acid type .
catalysts. Though this method achieved good conversion and yield of the desired product but still
the protocol requires high reaction temperature, bimetallic catalysts, acidic supports, makes the. . ' .
process expensive.
While acknowledging the reported catalytic procedures, these processes requires external acidic
additivies which leads to the corrosion of the process equipment, generates large amount of byproducts/
wastes thereby increasing the environmental load and furthermore the selectivity of the
desired product can be improved. Thus we are interested on developing the process for the
preparation of Mefrosol in two steps from the readily available starting matkials like
. . benzaldehyde and isoprenol in affordable reaction conditions and without using any external .
additivies.
OBJECTIVE OF TIIE INVENTION
The main objective of the invention is to develop a process for the preparation of industrially
important perfumery compound 3-methyl-5-phenylpentanol, which obviates the above said
drawbacks.
Another objective of the present invention is to develop a process for the preparation of a
perfumery compound Rosyrane, which is an active synthon for the synthesis of Mefrosol.
Yet another objective of the present invention is to avoid the use of external additives for the
I preparation of the synthon, Rosyrane.
Another objective of the present invention is to use the heterogeneous based acid catalysts for the
preparation of Rosyrane.
Yet another objective of the present invention is to recycle the catalyst used for the preparation of
I perhmery compound and synthon, Rosyrane.
I Yet another objective of the present invention is to prepare the Rosyrane with the minimum
I amount of catalyst loading.
I not her objective of the present invention is to increase the yield of the synthon Rosyrane.
Another objective of the present invention is to prepare the Rosyrane regioselectively.
Still another objective of the invention is to prepare the Rosyrane without using the toxic
isoprene, which is industrially unfavourable.
Yet another objective of the present invention is to develop a process for the preparation of
1 : perfumery compound, Mefrosol using simple Pd/C catalyst. I Yet another objective of the present invention is to prepare the Mefrosol without using any
external acid additives.
Yet another objective of the present invention is to prepare the Mefrosol withoul using any costly
. . - reducing agents like bimetallic systems.
Another objective of the present invention is to prepare the Mefrosol with high yield and
1
I
: selectivity.
i SUMMARY OF THE INVENTION
A - --
Accordingly the present invention describes, a process for the preparation of 3-methyl-5-
phenylpentane-1-01 comprising the steps of:
(i) adding benzaldehyde and 3-methyl-3-butene-1-01 in the ratib of the range of 1:1.2
to 1:1.4 in the presence of catalyst and organic solvent under stirring at a
temperature range between 40-200°C tu obtain a reaction mixture;
(ii) cooling the reaction mixture as obtained from is step (i) upto 25-30°C' and
separatiilg the catalyst from the reaction mixture by centrifuge followed by
decantation of solvent to obtain 4-methyl-6-phenyl-3,6-dihydro-2H-pyran;
(iii) hydrogenolysing 4-methyl-6-phenyl-3,6-dihydro-2H-pyraans obtained from the
step (ii) in .presence of palladium-carbon as catalyst and organic solvent followed
by stirring at a temperature range in between 40-250°C under hydrogen pressure of
15-800psi wherein the substrate to catalyst ratio is in the range of 10-200w/w to
obtain hydrogenolysed reaction mixture;
(iv) the hydrpgenolysed reaction mixture as obtained from step (iii) is cooled to 25-30°c'and
separating the catalyst from the reaction mixture by filtration and removing the
solvent by evaporation to obtain 3-methyl-5-phenylpentane-1-01.
In an embodiment of the present invention wherein the catalyst used in step (i) is selected
from silica supported sulphonic acid, heteropoly acids and supported inorganic acids
In another embodiment of the present invention, wherein the organic solvents used in the
reaction is selected from methanol, ethanol, 1,4-dioxane, tetrahydrofuran, acetonitrile,
toluene, hexane, chloroform and dichloromethane.
In yet another embodiment of the present invention, wherein the catalyst used in. step (i)
has various loadings ranging from 0.1 to 2 wt%.
In yet another embodirncnt of the presefit invention, wherein the source of the Pd in the
catalyst is selected from 5% Pd-C, 10% Pd-C, Ruthenium chloride with 5% Pd-C and
Ruthenium chloride with 10% Pd-C.
In yet another'embodiment of the present invention, wherein the organic solvent for the
hydrogenation and hydrogenolysis process is selected from isopropyl alcohol, acetonitrile,
methanol, 1,4-dioxan, toluene and ethanol.
In yet another embodiment of the present invention, wherein the stirring speed of the
autoclave reactor is in the range of 300-2000rpm.
. .
In yet another embodiment of the present invention, wherein the loading of Pd-C catalyst
in step (iii) is in the range of 0.2 to 4 wt%.
An efficient process has been developed for the preparation of perhme based compound .
Mefrosol. The present invention involves the preparation of arylpentanol derived from the easily
available starting materials. The present process comprises of two step synthetic methodologies
for the preparation.of Mefrosol. First step involves the treatment of aldehyde with the isoprenol in
presence of silica supported acid based catalyst and toluene as a solvent. The catalyst is prepared .
by adding chlorosulphonic acid dropwise to the silica dispersed chloroform. Though this catalyst
was found to be highly active and efficient for the preparation of Rosyrane, but the catalyst was
sensitive and the large scale preparation of the catalyst is tedious that makes the protocol
lethargic. Further, in the quest of searching the acid based c.atalyst for the preparation of
Rosyrane, attempts were made with heteropoly acids, supported inorganic acids and resin based
acid catalysts. 1t was found that the resin based acid catalysts was the better choice of catalysts
for the reaction of aldehyde and isoprenol to give the desired dihydropyran compound, Rosyrane.
Moreover, various types of resin based acid catalysts was screened for this organic
transformation. The optimized resin based acid catalysts was' found to be effective to catalyse the
condensation reaction followed by cyclization step and results in the formation of dihydropyran
type compound, Rosyrane with good yield and selectivity. To our delight, the catalyst is
regioselective and resulted in the formation of one major isomer among the three isomers of
Rosyrane. Thus the obtained crude product Rosryane was used as such without any further
purification for the next step. In the second step, the Rosyrane was treated with simple PdIC
catalyst in presence of isopropanol as a solvent. It initially undergoes the hydrogenation of double
bond in the oxacycle (pyran) at ambient reaction condition followed by the hydrogenolysis of
. ., .
cyclic ether to. give the 5-arylpentanol ie., 3-methyl-5-phenylpentanol at higher temperature and
pressure.This worlc contains the development of new process for the selective synthesis of 4-
methyl-2-phenyl-3,6-dihydro-2H-pyran, ' Rosyrane with 80-99% conversion and 75-95% .
.selectivity under the optirnizcd condition. The present process represents an environment friendly
alternative to the traditional method.
In an embodiment of the present invention, resin based acid catalyst loading in first step may be
. . from 0.1-2 wt%. I,
In an another embodiment of the present invention of the first step, organic solvents used may be
methanol, ethanol, 1,4-dioxane, tetrahydrofuran, dichlormethane, chloroform', benzene, xylene, .
toluene.
In another embodiment of the first step, reaction affected in the temperature range 50-200°C.
In another embodiment of this invention in the second step, catalyst loading may be 0.04-0.2
. . . wt%.
In an embodiment of the second step in the present invention organic solvents may be used
isopropanol, methanol, ethanol, tetrahydrofuran.
In still atiolher embodiment of the present invention in the second step hydrogenation and
. . hydrogenolysis is affected in temperature range 40-200°C.
In still another embodiment of the present invention hydrogen pressure for the second step may
be 200-800psi.
DESCRIPTION OF THE INVENTION
To synthesize the dihyropyran compound, generally isoprene is used, which is not industrially
acceptable because of its toxicity. Moreover, along with the Lewis acid catalyst it requires some
co-catalyst to improve the yield; it leads to the generation of by-products. The reported catalysts
are expensive and industrially unfavourable. The present invention describes the synthesis of
Mefrosol by two steps .directly from benzaldehyde and isoprenol using a simple recyclable resin
based acid catalyst in the first step and Pd/C as a hydrogenation catalyst in the second step
without any external additives.
The present invention overcomes the problem associated with the reported literatures for the
preparation of Rosyrane and Mefrosol. The drawbacks of the reported systems include the lower
yield and selectivity of the dihydropyran compound, Rosyrane and also in the 5-arylpentanol,
Mefrosol.
The present invention describes the better route to prepare dihydropyran compound as well as
important fragrance compound Mefrosol which gives high yield of product and selectivity.
In this typical process for synthesis of dihydropyran with high yield, initially silica sulphonic acid
as a heterogeneous and recyclable catalyst is prepared by the known procedure. Due to the
1 . . A . moisture sensitive nature and difficulty in the storage, we then switch over to the stable resin
based acid catalyst for the preparation of dihydropyran compound.
This present invention avoids the use of external corrosive acid additives for the preparation of
dihydropyran compound and also in the subsequent hydrogenation step.
STEP 1
Preparation of 4-methyl-2-phenyl-3,6-dihydro-2H-pyrawni th silica-sulphonic acid.
. - . In an oven dried two necked round bottom flask silica gel (without binder) was added and
dispersed in chloroform, then the chlorosulphonic acid was added dropwise to the silica dispersed
solution. After the completion of addition it was allowed to stir for 4-6 h to remove the generated
HCI from the reaction mixture. Then the solvent was evaporated using rota- vapour to give the
pale grey coloured silicasulphonic acid, which is then activated at 90 OC for the overnight Scheme
3..
1 In a typical process for the preparation of recyclable heterogeneous catalyst describe in following :-
steps.
EXAMPLE 1
In a two necked round bottom flask non binder silica gel (6grn) was mixed with
chloroform(l5ml) and stirred for 20min, then chlorosulphonic acid(l.5ml) was added slowly in
40min. after the conlplete addition of acid the reaction mixture was stirring for further 4hr, then
the solvent was removed by solvent evaporater and the crude was kept in oven at 90Oc for drying.
EXAMPLE 2'
In a two necked round bottom flask nun binder silica gel (6gm) was mixed with
chloroform(l5m1) and 'stirred for 20min, then chlorosulphonic acid(3ml) was added slowly in
40min. after the complete addition of acid the reaction mixture was stirring for further 4hr, then
. . the solvent was removed by solvent evaporater and the crude was kept in oven at 90Oc for drying.
EXAMPLE 3
In a two necked round bottom flask ncin binder silica gel (6gm) was mixed with
chloroform(l5ml) and stirred for 20min, then chlorosulphonic acid(3.5ml) was added slowly in
40min. after the complete addition of acid the reaction mixture was stirring for further 4hr, then
the solvent was removed by solvent evaporater and the crude was kept in oven at 90°c for drying.
EXAMPLE 4
In a two necked round bottom flask non binder silica gel (6gm) was mixed with
chlorofor1n(l5ml) and stirred for 20min, then chlorosulphonic acid(4ml) was added. slowly in
60min. afeer the complete addition of acid the reaction mixture was stirring for further 4hr, then
the.solvent was removed by solvent evaporater and the crude was kept in oven at 90°c for drying.
EXAMPLE 5
In a two necked round bottom flask non binder silica gel (6gm) was mixed with
, - .
chlorofonn(l5ml) and stirred for 20min, then chlorosulphonic acid(6ml) was added slowly in
60min. after the complete addition of acid the reaction mixture was stirring for further 4hr, then
the solvent was removed by solvent e.vaporater and the crude was kept in oven at 90Oc for drying.. . .
EXAMPLE 6
'In a two necked round bottom flask non binder silica gel (6gm) was mixed with
chloroform(l5ml) and stirred for 20min, thcn chl~rosul~honaicci d(8ml) was added slowly in
. . 60min. after the complete addition of acid the reaction mixture was stirring for further 4hr, then
the solvent was removed by solvent evaporater, but this catalyst was not stable due to large
amount of acid(8ml) that absorbs plenty of moisture.
Preparation of 4-methyl-2-phenyl-3,6-dihydro-2H-pyrabny heterogeneous silica based sulphonic
acid catalyst. I
I
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 36%
EXAMPLE 9
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
50mg(0.32mmol) of silicasulphonic acid (example 1) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45.-60°c.~ftetrh at mixture of 1 lml(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 3hr by addition funnel, after complete '
I
I ,' . ,addition the reaction mass was continue stirred for 4hr. Then the hcterogei~eous catalyst was
EXAMPLE 7
To a three neck round bottom flask equipped with dean-stark and condenser, 20mg (0.13mmol)
of silicasulphonic acid (example 1) and 6ml of dry toluene was added and stirred at 45-60 OC. To
the hot solution add the mixture of benzaldehyde and isoprenol(1 Iml) was added dropwise in 2hr .
by addition funnel, after the completion of addition the reaction mixture was further stirred for 4h
at the 45-60 OC. The reaction was monitorcd for the completion of reaction using GC. After the
completion of the reaction, the catalyst was separated by centrifuge and the solvent was
. . evaporated under reduced pressure, then the yield of'the desired product was calculated by Gas
chromatography. Yield- 29%
I separated simply by centrifuge and then solvent was evaporated under reduced pressure, 'then the
EXAMPLE 8
In a three neck round bottom flask which was well' equipped with dean-stark and condenser,
30mg(0.19mmol) of silicasulphonic acid (example 1) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.~ftetrh at mixture of 1l ml(53.7mmol)
. . - benzaldehyde and isoprenol was added dropwise in 2hr by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
I yield was calculated by Gas chromatography. Yield- 42%
EXAMPLE 10
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
~.
20mg(O.l31nmol) of silicasulphonic acid (example 2) and 6ml of dry toluene was taken and I
I
! stirred and also temperature increases slowly upto 45-60°c.~ftert,h at mixture of 1 lml(53.7mmol)
I
I benzaldehyde and isoprenol was added dropwise in 2hr by addition funnel, after complete
addition .the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
. - . yield was calculated by Gas chromatography. Yield-34%
EXAMPLE 1 1
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
35mg(0.22mmol) of silicasulphonic acid (example 2) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.~fterth at mixture of 1 lm1(53.7mmol)
benzaldehyde and. isoprenol was added dropwise in 2hr by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 52%
,EXAMPLE 12
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
60mg(0.38mmol) of silicasulphonic acid (example 2) and 6ml of dry toluene was talten and
stirred and also temperathe increases slowly $to 45-60°c.After that mixture of 1 lml(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 3hr by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 64%
EXAMPLE 13
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
30mg(0.191-11mol) of silicasulphoiiic acid (example 3) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.After that mixture of 1 lml(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 60%
EXAMPLE 14
In a three neck round' bottom flask which was well equipped with dean-stark and condenser,
40mg(0.25mmol) of silicasulphonic acid (example 3) and 6ml of dry toluene was taken and ,,
stirred and also temperature increases slowly upto 45-60°c.After that mixture of 1 lml(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 61%
EXAMPLE 15
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
. . 50mg(0.32mmol) of silicasulphonic acid (example 3) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.After that mixture of 1 lml(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 65%
EXAMPLE 16
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
20mg(O.l3mmol) of silicasulphonic acid (example 4) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.~ftetrh at mixture of 1l ml(53.7mmol)~
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 88-92%
EXAMPLE 17
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
30mg(0.19mmol) of silicasulphonic acid (example 4) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.~ftetrh at mixture of 1 lm1(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 72%
EXAMPLE 18
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
35mg(0.22mmol) of silicasulphonic acid (example 4) and 6inl of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.~ftetrh at mixture of 1l m1(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 63%
EXAMPLE 19
: In a three neck round bottom flask which was well equipped with'dean-stark and condenser,
40mg(0.25mmol) of silicasulphonic acid (example 4) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.~ftetrh at mixture of 1l ml(53.7mmol)
benzaldehyde and isoprenbl was added dropwise in 2hr 30min by addition funnel, after complete
. ,
addition the' reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 65% -
EXAMPLE 20
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
30mg(0.l9mmol) of silicasulphonic acid (example 5) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.After that mixture of 1 lml(53.7mmoI)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reactibn mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield-46%
EXAMPLE 2 1
In a three necl; round bottom flask which was will equipped with dean-stark and condenser,
35mg(0.22mmol) of silicasulphonic acid (example 5) and 6ml of dry toluene was taken and , .
stirred and also temperature increases slowly upto 45-60°c.After that mixture of 1 lml(53.7mmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 49%
EXAMPLE 22
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
40mg(0.25mmol) of silicasulphonic acid (example 5) and 6ml of dry toluene was taken and
stirred and also temperature increases slowly upto 45-60°c.After that mixture of 1 lrnl(53.7mmol)
benialdehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by'centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 57%
Preparation of 4-methyl-2-phenyl-3,6-dihydro-2H-pyrawni th heterogeneous acid based resin.
Acid based heterogeneous resins are stable, industrially available and produces dihydropyran
compound very easily.
EXAMPLE 23
. . .- In a three neck round bottom flask which was well equipped with dean-stark and condenser,
10mg(O.O83wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-60°c.After that mixture of^ 12m1(58.lmmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the ,
yield was calculated by Gas chromatography. Yield- 15-1 9%
EXAMPLE 24
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
25mg(0.20wt%) of heterogeneous acid based resin and 6mi of dry toluene was taken and stirred
and also temperature increases slowly upto 45-60°c.After that mixlre of 12m1(58.lmmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
, separated simply hy centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 31%
EXAMPLE 25
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
.35mg(0.29wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
-. . and also temperature increases slowly upto 45-60°c.After that mixture of 12m1(58.lmmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was .
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
I yield was calculated by Gas chromatography. Yield- 33%
EXAMPLE26
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
40mg(0.33wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-60°c.After that mixture of 12m1(58.lmmol)
benzaldehyde and isoprenol was added dropwise in 2hr 30min by addition funnel, after complete
, addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
. . yield was calculated by Gas chromatography. Yield- 35%
EXAMPLE 27
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
50mg(0.42wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-8o0;.~fter that mixture of 12m1(58.lmmol)
benzaldehyde and isoprenol was added dropwise in 3hr by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield- 35%
EXAMPLE 28 . t
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
60mg(0.5wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-80'c.~ftel. that mixture of 12m1(58.lmmol)
benzaldehyde and isoprenol was added dropwise in 3hr by addition funnel, after complete
addition the reaction mass was continue stirred for 4hr. Then the heterogeneous catalyst was
I' separated simply by centrifuge and then solvent was evaporated under reduced pressure, thcri the
I yield was calculated by Gas chromatography. Yield- 39%
EXAMPLE 29
.
. .. In a three neck round bottom flask which was well equipped with dean-stark and condenser,
I 60mg(0.5wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
and also temperature increases slowly upto'45-85'c.~fter that mixture of 5m1(49.lmmol)
benzaldehyde and 7m1(59.42) isoprenol was added dropwise in4hr by separate addition funnel,
I after complete addition the reaction mass was continue stirred for 4hr. Then the heterogeneous
I . catalyst was separated simply by centrifuge and then solvent was evaporated under reduced
pressure, then the yield was calculated by Gas chromatography. Yield- 38%
EXAMPLE 30
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
70mg(0.58wt%) of heterogeneous acid based resin and 6ml of dry toluene was talcen and stirred
and also temperature increases slowly upto 45-85'c.~fter that mixture of 5m1(49.lmmol)
benzaldehyde and 7m1(59.42) isoprenol was added dropwise in 4hr by separate addition funnel,
, after complete addition the reaction mass was continue stirred for 4hr. Then the heterogeneous
.. .
catalyst was separated simply by centrifuge and then solvent was evaporated under reduced
pressure, then the yield was calculated by Gas chromatography. Yield- 39%
I . EXAMPLE 3 1
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
80mg(0.67wt%) of heterogeneous acid based resin and 6ml of dry. toluene was taken andstirred
and also temperature increases slowly upto 45-85'c.After that mixture of 5m1(49.lmmol)
... . . ... benzaldehyde and 7m1(59.42) isoprenol was added dropwise in 4hr by separate addition funnel,
after complete addition the reaction mass was continue stirred for 4hr. Then the heterogeneous
catalyst was separated simply by centrifuge and then solvent was evaporated under reduced
pressure, then the yield was calculated by Gas chromatography. Yield- 46%
' EXAMPLE 32
In a three neck round bottom flask.which was well equipped with dean-stark and condenser,
.. ..- 80mg(0.67wt%) of heterogeneous acid based resin and 6ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.After that mixture of 5m1(49. Immol)
-- -- - - -
. . 1
benzaldehyde and 7m1(59.42) isoprenol was added dropwise in 2hr by separate addition funnel,
after complete addition the reaction mass was continue stirred for 4hr. Then the heterogeneous
catalyst was separated simply by centrifuge and then solvent was evaporated under reduced
pressure, then the yield was calculated by Gas chromatography. Yield- 39%
EXAMPLE 33
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
80mg(0.67wt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred .
and also temperature increases slowly upto 45-85'c.After that mixture of
5ml(49.lmmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added .
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 45%
EXAMPLE 34
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
80mg(0.67wt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.After that mixture of
5ml(49. l mmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 6hr by separate addition funnel, after con~pletea ddition the reaction mass was
continue stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 47%
EXAMPLE 35
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
80mg(0.67wt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
1
and also temperature increases slowly upto 45-85'c.After that mixture of
5m1(49.1 mmo1)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 8hr. Then the heterogeneous .catalyst was separated simply by centrifuge and
. . ...-
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 45%.
EXAMPLE 36'
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
100mg(0.83wt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.After that mixture of
-r -r t 2 DEFMx 18-t35-201E 17
5ml(49.lmmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by sparate addition funnel, aftcr complete addition the reaction mass was
continue'stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 50%.
..' EXAMPLE 37
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
105mg(0.875wt%)'~hfe terogeneous acid based resin and 4ml of dry .t o* luene was taken and
stirred and also temperature increases slowi; upto 45-85Oc.After that mixture of
5m1(49.1mmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrihge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 5 1 %
EXAMPLE 3 8
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
110mg(0.92wt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.~fter that mixture of
5ml(49.lmmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
I then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
I
I chromatography. Yield- 53%
EXAMPLE 39
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
120mg(O.lwt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly upto 45-85Oc.After that mixture of
5m1(49.1mmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was ev'aporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield-69%.
EXAMPLE 40
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
120mg(O.lwt%) of lietcrogeneous acid based resin and 2ml of' dry toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.~fter that mixture of
5m1(49.1mmol)benzaldehyde +4m1 toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by. separate addition funnel, after complete addition the reaction mass was
continue stirred for 6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 58%
EXAMPLE 4!
.. - In a three neck round bottom flask which was well equipped with dean-stark and condenser,
120mg(O.lwt%) of heterogeneous acid based resin and 6ml of diy toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.After that mixture of
5ml(49.lmmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dripwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 6hr. d hen the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatogr~pl~Yy.i eld-63%
EXAMPLE 42
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
120mg(0. I wt%) of heterogeneous acid based resin and 6m1 of dry toluene was taken and stirred
and also temperature increases slowly upto 45-85'c.After that mixture of
5ml(49.lmmol)benzaldehyde +61nl toluene and 7m1(59.42) isoprenol+6ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for'6hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 57%
EXAM.PT.E 43
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
'120mg(0.75wt%) of heterogeneous acid based resin and 6ml of dry xylene was taken and stirred
and also temperature increases slowly upto 45-85'c.After that 5ml(49.lmmol)benzaldehyde and
7m1(59.42) isoprenol was added dropwise in 5hr by separate addition funnel, after complete
addition the reaction mass was continue stirred for 6hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated'by Gas chromatography. Yield- 46%
. .. .
EXAMPLE 44
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
120mg(O.lwt%) of heterogeneous acid based resin and 6ml of dry melhanol was taken a~ldst irred .
and also temperature increases slowly upto 45-85'c.After that 5m1(49.1mmol)benzaldehyde and
7m1(59.42) isoprenol was .added dropwise in 5hr by separate addition funnel, after complete
addition the reaction mass was continue stirred for 6hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield-43%
EXAMPLE 45
In a three neclc round bottom flask which was well equipped with dean-stark and condenser,
120mg(0.lwt%) of heterogeneous acid based resin and 6ml of dry THF was taken and stirred and
also temperature increases slowly upto 45-85'c.~fter that 5ml(49.lmmol)benzaldehyde and
7m1(59.42) isoprenol was added dropwise in 5hr by separate addition funnel, after complete
addition the reaction mass was continue stirred for 6hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calculated by Gas chromatography. Yield-41%
EXAMPLE 46
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
-. -
120mg(O.lwt%) of heterogeneous acid based resin and 6ml of dry dioxan was taken and stirred
and also temperature increases slowly upto 45-85'c.After that 5ml(49.lmmol)benzaldehyde and
7m1(59.42) isoprenol was added dropwise in 5hr by separate addition funnel, after complete
addition the reaction mass was continue stirred for 6hr. Then the heterogeneous catalyst was
separated simply by centrifuge and then solvent was evaporated under reduced pressure, then the
yield was calci~latedb y Gas chromatography. Yield-43%.
EXAMPLE 47
In a three neck round bottom flask which was well equipped with dean-stark and condenser, ,
120mg(O.lwt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly upto 90'c. After that mixture of
5ml(4'9.1mmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction.mass was
- - continue stirred for 4hr. Then the heterogeneous catalyst was separated simply by centrifuge and
then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. yield- 64-67%
EXAMPLE 48
In a three neclc round bottom flask which was well equipped with dean-stark and condenser,
i20mg(O.l wt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly to 100'~. After that mixture of
5m1(49..1mmol)benzaldehyde +4ml toluene and 7m1(59:42) isoprenol+4ml toluene was added
BRA
~r r- 62
dropwise in 5hr by' separate addition funnel, after complete addition the reaction mass was
continue stirred for 1 -4hr. Then the heterogeneous catalyst was separated simply by centrifuge
and then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 70-73%
EXAMPLE 49
In a three neck round bottom flask which was well equipped with dean-, stark and condenser,
120mg(O.lwt%) of heterogeneous acid based resin and 4ml o q r y toluene was taken and stirred
and also temperature increases slowly upto 120°c. After that mixture of
5ml(49.lmmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
- continue stirred for 1-4hr. Then the heterogeneous catalyst was sepai-ated simply by centrifuge
and then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 87% I ..,
EXAMPLE 50
In a three neck round bottom flask which was well equipped with dean-stark and condenser,
120mg(O,lwt%) of heterogeneous acid based resin and 4ml of dry toluene was taken and stirred
and also temperature increases slowly upto 125'~. After that mixture of
5m1(49.1mmol)benzaldehyde +4ml toluene and 7m1(59.42) isoprenol+4ml toluene was added
dropwise in 5hr by separate addition funnel, after complete addition the reaction mass was
continue stirred for 1.-4hr. Then the heterogeneous catalyst was separated simply by centrifuge
and then solvent was evaporated under reduced pressure, then the yield was calculated by Gas
chromatography. Yield- 92-95%
STEP 2
Hydrogenation of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran
The second step contains'the one pot reaction of hydrogenation and hydrogenolysis of
I ~ dihydropyran com$ound to give the perfume based compound 3-methyl-5-phenylpentanol in
good conversion and selectivity.using Pd/C as a catalyst and isoproponal as a solvent.
(a) In the hydrogenation experiment, amount of Pd-C (5%) required as a catalyst 0.2-4wt%,
substrate 4-methyl-2-phenyl-3,6-dihydro-2H-pyra(nR osyrane) 1O gm, solvent 2- 15m1, were
charged into a stainless steel autoclave 100. mL reactor.
(b) The stirring rate was adjusted to 300-2000 rpm:
(c) The rdactor wasthen flushed thrice with hydrogen gas at room temperature (27 OC ;t 3,OC) and
then pressurized with hydrogen gas at a desired pressure (50-800 psi).
I (d) The pressurized reaction mixture was stirred at 300-2000 rpm at (27 OC k 3°C) for 10-30min,
at 60-80Oc for 1-4hr and at 100-150°c for 2-8hr. Then the stirring was stopped and the reactor was
allowed to attain room temperature (27 "C * 3°C).
I (e) The reactor was depressurized, opened, and the supernatant was decanted from the reaction
I mixture leaving behind the settled catalyst inside the reactor, .which was reused with purification
I for the next hydrugenation run.
I (f)The solvent is removed from the supernatant obtained from step (e) by solvent evaporator, and
this product was further purified by distillation to get the highly pure product Mefrosol.
The process will b.e here in after described more in detail by way of the following examples
which are not intended to restrict the invention.
EXAMPLE 5 1
In an 100ml autoclave reactor, 6gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran3,0 mg of 5%
Pd-C and 121111 of IPA were charged. After pressurizing to 100psi with hydrogen gas, the mixture
was stirred at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c for 4hr.
After the colnpletion of the reaction, the catalyst was separated by centrifuge and the solvent was
evaporated under reduced pressure, then the yield of the desired product was calculated by Gas
chromatography. Yield- NIL
EXAMPLE 52
In an 1001nl a~~toclavreea ctor, 6gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran4,0 mg of 5%
Pd-C and 121111 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min; at60°c for 2hr and at 100'c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-5%
EXAMPLE 53
In an 10011,l autoclave reactor, 6gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra4n,0 mg of 5%
Pd-C and 15mI of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm (27 "C k 3OC) for.10-30min, at 60°c for 2hr and at 100'~ for
4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the solvent
was evaporated under reduced pressure, then the yield of the desired product was calculated by
Gas chromatography. Yield-NIL-
. . EXAMPLE 54
In an 100ml autoclave reactor, 6grn of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra5n0,m g of 5%
Pd-C and 121n1 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 OC * 3°C) for 10-30min, at 60'c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yicld of the desired,product was
calculated by Gas chromatography. Yield-5%
EXAMPLE 55 . '
In an 100ml autoclave reactor, 1Ogm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra3n,5 mg of 5%
. .
Pd-C and 5ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at'(27 "C i 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was:separated by centrifuge and the
solvent was evaporated under reduCed pressure, then the yield of the desired product was
'
calculated by Gas chromatography. Yield-1 0%
1 EXAMPLE 56
I In an lOOml autoclave reactor, lOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran4, h go f 5%
Pd-C and 51nl of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C h 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-25%
EXAMPLE 57
In an 1001nl autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran4,0 mg of 5%
Pd-C and 101111 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C i 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield- 10%
EXAMPLE 58
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra5n0,m g of 5%
Pd-C.and 10ml of IPA were charged. After pressurizing to 6OOpsi with hydrogen gas, the mixture
. .
, was allowed to stir at 300,-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculatec! by Gas chromatography. Yield-30%
EXAMPLE 59
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2~-pyr6a0nm,g of 5%
. -
Pd-C and 101111 of IPA were charged. After pressurizing-to 600psi with hydrogen gas, the mixture
,was allowed to stir at 300-2000 rpm at (27 OC k 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield- 40%
EXAMPLE 60
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2~-pyr7a0nm,g of 5%
Pd-C and 8ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at (27 "C * 3°C) for 10-30min, at 60-80°c for 2hr and at 100-140°c for 4hr.
After the completion of the reaction, the catalyst was separated by centrifuge and the solvent was
evaporated under reduced pressure, then the yield of the desired product was calculated by Gas
chromatograpliy. Yield-49%
EXAMPLE 6 1
In an 100ml autoclave'reactor, 1Ogm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran, 1 OOmg of 5%
Pd-C and 6ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
'
was allowed to stir at 300-2000 rpm at (27 OC & 3OC) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure,,then the yield of the desired product was
calculated by Gas chromatography. Yield-55%
EXAMPLE 62
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra1n I,5 mg of 5%
Pd-C and 6ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 OC k 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield- 69%
EXAMPLE 63
In an 1O Oml autoclave reactor, 1O gm of 4-methyl-2-phenyl-3,6-dihydro-2H~pyra1n3,5 mg of 5%
. .
~ d - Can d 6ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was illowed to stir at 300-2000 rpm at (27 "C & 3OC) for 10-30min, at 60°c .for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield ofthe desired product was
calculated by Gas chromatography. Yield-73%
EXAMPLE 64
In an 100ml autoclave reactor, 1 Ogrn of.4-methyl-2-phenyl-3,6-dihydro-2H-pyran, 150mg of 5%
Pd-C:,and 61nl of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
. - was.allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-78%
EXAMPLE 65
In an 100ml autoclave reactor, IOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra1n5, 0mg of 5%
. .
Pd-C and 2m1 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir, at 300-2000 rpm at (27 OC * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and thi
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Y ield-42%
EXAMPLE 66
In an loom1 autoclave reactor, 1O gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra1n,5 0mg of 5%
Pd-C and 101nl of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 OC k 3OC) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was.
calculated by Gas chromatography. Yield-49%
EXAMPLE 67
In an 100n1l autoclave reactor, IOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran1,7 0mg of 5%
Pd-C and 6ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C k 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-82%
EXAMPLE 68
In an 1O Oml autoclave reactor, 1O gm of 4-methyl-2-phenyl-3,6-dihydro-2~-pyr1a9~0,m g of 5%
Pd-C and 611-11 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c ,
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-87%
EXAMPLE 69 . . . .
, In in 1O Oml autoclave reactor, 1O grn of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n0,0 mg of 5% .
Pd-C and 6ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2.000 rprn at (27 "C It 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-90-92%
EXAMPLE 70
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n0, 0mg of 5%
Pd-C and 8ml of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-77%
EXAMPLE 7 1
In an 100ml autoclave reactor, 1Ogm of 4-methyl-2-phenyl-3;6-dihydro-2H-pyran2,0 0mg of 5% '
Pd-C and 101nl of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 1 20°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-6 1 %
EXAMPLE 72
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n1, 0 mg of 5%
Pd-C and 61111 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir,at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the colnpletion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-73%
EXAMPLE 73
In'an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n2,0 mg of 5%
Pd-C and 61n1 of IPA were charged. After pressurizing to 600psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. 'After the completion of the reaction, the catalyst-was separated by centrifuge,and the
solvent was evaporated under reduced pressure; then, the yield of the desired product was
-calculated by Gas chromatography. Yield-%% i
EXAMPLE 74
In an 100ml autocla,ve reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran2,0 0mg of 5%
Pd-C and 8ml of methanol were charged. After pressurizing to 600psi with hydrogen gas, the
mixture was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at
'e9-!Fy.- u -K- FI .-L54R:eg- - -IF:3 35
120°c for 4hr. After the completion of the reaction, the.catalyst was separated by centrifuge and
the solvent was evaporated iinder reduced pressure,' then the yield of the desired product was
calculated by Gas chromatography. Yield-67%
EXAMPLE 75 . .
In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n0, 0mg of 5% . .
Pd-C and 8m1 of ethanol were charged. After pressurizing to 600psi with hydrogen gas, the
i
mixture was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at . .
120°c for 4hr. After the completion of the reaction, the catalyst wqs separated by centrifuge and
. - the solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-64%
EXAMPLE 76
In an 1001nI autoclave reactor, 1Ogm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n0,0 mg of 5%
'Pd-C and 81111 of dioxan were charged. After pressurizing to 600psi with hydrogen gas, the
.mixture was allowed to stir at 300-2000 rpm at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at
. . . 120°c for 4hr. After the completion of the reaction, the catalyst was separated by cent.rifuge and
the solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-47%
EXAMPLE 77
In an 1001111 autoclave reactor, l0gm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyra2n,0 0mg of 5%
Pd-C and 8ml of acetonitrile were charged. After pressurizing to 600psi with hydrogen gas, the
, mixture was allowed to stir at 300-2000 rpm at (27 "C -+ 3°C) for 10-30min, at 60°c'for 2hr and at
.
I 120°c for 4hr. Aftei the completion of the reaction, the catalyst.was separated by centrifuge and
I
I the solvent was evaporated under reduced pressure, then the yield of the desired product was .
cal~ilatedb y Gas chromatography. Yield- 48%
EXAMPLE 78'
In an 1O Oml autoclave reactor, 1O gm of 4-methyl-2-phenyl-3,6-dihydro-2~-pyr2a0n0,m g of 5%
Pd-C and 8ml of toluene were charged. After .pressurizing to 600psi with hydrogen gas, the
. . -
mixture was allowed to stir at 300-2000 rpm at (27 "C f3"C) for 10-30min, at 60°c for 2hr and at
120°c for 4lir. After the completion of the reaction, the catalyst was separated'by centrifuge and
the solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography.. Yield-NIL
EXAMPLE 79
. In an 100ml autoclave reactor, 10gm of 4-methyl-2-phenyl-3,6-dihydro-m-pyra1nO ,m g of 10%
Pd-C and 51111 of IPA were charged. After pressurizing to 300psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rprn at (27 "C * 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge.and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield- NIL
EXAMPLE 80
In an 100ml autoclave reactor, lOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran, 40mg of 10%
Pd-C and 5ml of IPA were charged. After pressurizing to 300psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 °C ± 3°C) for 10-30min, at 60°c for 2hr and at 120°c •.
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-7%
EXAMPLE 81
In an 100ml autoclave reactor, lOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran, lOOmgof 10%
Pd-C and 5ml of IPA were charged. After pressurizing to 300psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 °C ± 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-23%
EXAMPLE 82
In an 100ml autoclave reactor, lOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran, lOOmg of 10%
Pd-C and 5ml of IPA were charged. After pressurizing to 400psi with hydrogen gas, the mixture
was allowed to stir at 300-2000 rpm at (27 °C ± 3°C) for 10-30min, at 60°c for 2hr and at 120°c
for 4hr. After the completion of the reaction, the catalyst was separated by centrifuge and the
solvent was evaporated under reduced pressure, then the yield of the desired product was
calculated by Gas chromatography. Yield-32%
EXAMPLE 83
In an 100ml autoclave reactor, lOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran, 20mg of
ruthenium chloride, 50mg of 5% Pd-C and 5ml of IPA were charged. After pressurizing to 600psi
with hydrogen gas, the mixture was allowed to stir at 300-2000 rpm at (27 °C ± 3°C) for 10-
30min, at 60°c for 2hr and at 120°c for 4hr. After the completion of the reaction, the catalyst was
separated by centrifuge and the solvent was evaporated under reduced pressure, then the yield of
the desired product was calculated by Gas chromatography. Yield-15%
EXAMPLE 84
In an 100ml autoclave reactor, lOgm of 4-methyl-2-phenyl-3,6-dihydro-2H-pyran, lOmg of
ruthenium chloride, 30mg of 10% Pd-C and 5ml of IPA were charged. After pressurizing to
600psi with hydrogen gas, the mixture was allowed to stir at (27 °C ± 3°C) for 10-30min, at 60°c
for 2hr and at 120°c for 4hr. After the completion of the reaction, the catalyst was separated by
centrifuge and the solvent was evaporated under reduced pressure; then the yield of the desired
product was calculated by Gas chromatography. Yield-18-23%

WE CLAIM:
1. A process for the preparation of 3-methyl-5-phenylpentane-l-ol comprising the steps of:
i) adding benzaldehyde. and 3-methyl-3-butene'l-ol in the ratio of the vange of 1:1.2
to 1:1.4 in the presence of catalyst and organic solvent under stirring at a
temperature range between 40-200°C to obtain a reaction mixture;
ii) cooling the reaction mixture as obtained from is step (i) upto 25-30°C and
separating the catalyst from the reaction mixture by centrifuge followed by
decantation of solvent to obtain 4-methyI-6-phenyl-3,6-dihydro-2H-pyran;
iii) hydrogenolysing 4-methyl-6-phenyl-3,6-dihydro-2H-pyran as obtained from the
step (ii) in presence of palladium-carbon as catalyst and organic solvent followed
by stirring at a temperature range in between 40-250°C under hydrogen pressure of
15-800psi wherein the substrate to catalyst ratio is in the range of 10-200w/w to
obtain hydrogenolysed reaction mixture;
(iv) the hydrogenolysed reaction mixture as obtained from step (iii) is cooled to 25-30°C
and separating the catalyst from the reaction mixture by filtration and removing the
solvent by evaporation to obtain 3-methyl-5-phenylpentane-l-ol.
2. A process as claimed in claim 1, wherein the catalyst used in step (i) is selected from
silica supported sulphonic acid, heteropoly acids and supported inorganic acids
3. A process as claimed in claim 1, wherein the organic solvents used in the reaction is
selected from methanol, ethanol, 1,4-dioxane, tetrahydrofuran, acetonitrile, toluene,
hexane, chloroform and dichloromethane.
4. A process as claimed in claim 1, wherein the catalyst used in step (i) has various loadings
ranging from 0.1 to 2 wt%.
5. A process as claimed in claim 1, wherein the source of the Pd in the catalyst is selected
from 5% Pd-C, 10% Pd-C, Ruthenium chloride with 5% Pd-C and Ruthenium chloride
with 10% Pd-C.
6. A process as claimed in claim 1, wherein the organic solvent for the hydrogenation and
hydrogenolysis process is selected from isopropyl alcohol, acetonitrile, methanol, 1,4-
dioxan, toluene and ethanol.
7. A process as claimed in claim 1, wherein the stirring speed of the autoclave reactor is in
the range of 300-2000rpm.
8. A process as claimed in claim 1, wherein the loading of Pd-C catalyst in step (iii) is in the
range of 0.2 to 4 wt%.