|Title of Invention||
"A NOVEL COMPOUND 4-(P-METHOXYPHENYL)-2-AMINOBUTANE EXHIBITING GROWTH INHIBITION AND ANTIFEEDANT AVTIVITY AGAINST LARVAE"
|Abstract||The invention provides a novel compound 4-(p-methoxy-phenyl)-2-aminobutane exhibiting growth inhibition and antifeedant activity and represented by the structural formula. and an insecticidal composition comprising an effective amount of the novel compound and appropriate adjuvant.|
The invention provides novel biologically acme synthetic molecule 4-(pmethoxy
phenyl)-2-amino-butane The invention also provides a process for
preparation of said molecule from a naturally occurring compound 4-(phydroxyphenyl)
butan-2-ol. The molecule of the invention is a colorless crystalline
solid, represented by molecular formula. C H17ON. and structural formula (1) as
shown herein below :
= 4 - (p-methoxy phenyl)-2-arnino butane
The spectral characteristics of the molecule are as follows:
The EI mass spectrum of the compound showed its Mt at M/Z 179, thus
confirming its molecular formula as C11H17 ON, and other diagnostic fragment
peaks at M/Z 162, 147, 121 and 91; IRu max (KBr) 3360, 2940, 1610, 1515, 14501,
1030 and 850 cm-1
Further, the invention provides an insecticidal composition comprising the said
molecule 4-(p-methoxyphenyl)-2-amtno butane in an effective amount and an
The product is a new molecule which has been prepared from a redly available
starting material l-(,p-hydroxyphenyl)-butan-2-ol represented In formula (2) as
shown herein below isolated from the plant faxus wallichiana
C10H14O2 = (4 - (p-hydroxy phenyl)-butan-2-ol
Background and Prior Art.
The plant Taxus wallichiana. which also known as Himalayan yew is now
considered to be one of the most needed plants for commercial exploitation as it
contains the anticancer drug Taxol. Taxol, a highly oxygenated diterpenoid
molecule and potent anticancer drug was first isolated from the stem bark of Taxus
brevifolia. Thereafter, it has also been isolated from other Taxus plants including
the Himalayan yew Taxus wallichiana.
The applicants have been 'working on different parts of Taxus wallichiana
collected from different parts of India for the isolation of taxol, its important
analogues and precursor 10-deacetyl baccatin HI (DAB). During the course of
investigation, the applicants have isolated a major compound from tfie leaves of
Taxus wallichiana, identified as 4-(p-hydroxyphenyl)-butan-2-ol having structural
formula (2). This compound can be obtained with a yield of 0.2% from the leaves
of Taxus wallichiana. Accordingly, the applicants have developed a simple and
cost effective processing technology for isolation of this compound from the
leaves of Taxis wallichiana. The process of isolation of the compound comprises
the steps of defatting air dried pulverised Taxus leaves with aliphatic hydrocarbon
solvents, extracting the defatted leaves with chlorinated solvents and polar
solvents successively, concentrating the chlorinated solvent soluble fraction to a
residue and treating the residue with aqueous solution of alkali and isolating the
compound from the a l k a l i soluble fraction by acidifying it and extracting u
ethyl acetate. to obtain the compound having structural formula (2).
The compound (2) was not found to be active in bioassay studies for evaluation
of growth inhibition and aiUifeedam activity. The compound of formula (2) was
obtained with high yield (0 2°b). its conversion into other structural analogues
through a series of chemical reactions. In the course of this investigation, the
applicants prepared a new molecule represented by formula ( 1 ) from the
compound represented by formula (2) The compound having structural formula
(1) shows significant activity as a growth inhibitor and antifeedant.
The compound having formula(l) was evaluated as feeding deterrent and growth
inhibitor against 4th instar larvae of Spilarctia Obliqua. This insect attacks more
than twenty cash crops including urd, mong, arhar, mint and coleus etc.
Compound having formula (1) is non hazardous in nature and thus is ecologically
safe and environmentally sound for its use as an agrochemical.
The main object of this invention is to provide a new molecule, 4-(pmethoxyphenyl)-
2-amino butane, represented by structural formula (I) and
represented by molecular formula CnHpON.
It is also an object of the invention to provide a process for the preparation of a
biologically active compound represented by structural formula ( I ) with higher
yields, from a readily available starting material isolated from the plant Taxu.s
Yel another object of (he invention is to provide an insecticidal composition
comprising an effective amount of the new molecule 4-(p-methoxy phenyl-2-
amino butane and an adjuvant.
Detailed description of the invention
Accordingly, the present invention provides novel molecule 4-(p-methoxyphen\0-
2-amino butane.C|iHi?ON. represented by the structural formula (1) as slumn
= 4-(p-methoxyphenyl)-2-amino butane
The compound exhibits growth inhibitory and antifeedant activity. The process for
the isolation of the novel compound comprises the steps of:
a) isolating a phenolic molecule represented by structural formula (2) from the
leaves of Taxus wallichiana by known methods,
b) treating the compound having formula (2) in aqueous mineral acid at 25-
100°C for 2-10 hours to obtain a phenolic halide derivative,
c) converting the phenolic halide derivative into its methyl ether by treating it
with a methylating agent to obtain a methyl ether halide,
d) reacting the methyl ether formed with azide to obtain an azido derivative,
e) hydrogenating the azido compound thus formed by catalytic hydrogenation
in the presence of a catalyst in lower aliphatic alcohol to obtain a
compound having structural formula (1 ).
The aqueous mineral acid used in step (b) may be selected from the group
consisting of hydrochloric acid, hydrobromic acid and hydroiodic acid. The
methylating agent used in step (c) may be selected from methyl iodide or dimethyl
The a/.ide, used in step (d) is sodium n/idc or trimcthyl silyi a?.ide.
The catalyst used in the hydrogennlion process is selected from palladium charcoal
and platinum oxide. The lower alcohol used as medium to dissolve the a/ide
derivative in the hydrogenation process may be methyl alcohol, ethyl alcohol.
As mentioned earlier, the compound 4-(p-methoxy pheny!)-2-amino butane
exhibits antifeedant and growth inhibiting activity against certain insects,
especially the larvae of Spilarctia Obliqua.
Hence, the compound has potential use as an insecticide, and would have wide
spread applications in insecticidal compositions. Without wishing to be bound by
any theory, the Applicants state that an insecticidal composition comprising an
effective amount of the compound 4-(p-methoxy phenyl)-2-amino butane and an
adjuvant in an amount sufficient to enhance the activity of the composition may
be prepared. In practice, it is found that the novel compound 4-(pmethoxyphenyl)-
2-amino butane per se may also be used to control insects in
fields, though it is recommended that the compound be mixed with augmenting
adjuvants such as distilled water, acetone or such other solvents before use. The
insecticidal compositions may be sprayed or applied in the soil for control of pests.
Further, the said insecticidal composition may be effectively used for the control
of insects/their larvae such as Spilarctia Obliqua. In practice, the compound is
found to be very useful 'in controlling phytopathogenic insects and mites.
The invention, its embodiments and applications are described in detail in the
examples given below which are provided to illustrate the invention and therefore
should not be construed to limit the scope of this invention.
The products of the reactions as described in the steps hereinbelow is represented
The products of the reactions as described in the sicps hcreinbelmv is represented
Stgp__ 1 - preparation of 4-(p-hydroxyphcnyl;-2 jrompbutane ltonmila ...D::
h a 50ml conical flask was charged with compound of formula (2) ( I g m ) and to it
was added HBr (44%) (5ml) dropwise and the reaction mixture was refluxed for 6
hours at 80°C with constant stirring. The reaction mixture was diluted with excess
water and extracted with ethyl acetate (25ml x 3); The ethyl acetate was dried over
anhydrous sodium sulphate and concentrated. The oily residue thus obtained
above was subjected to column chromatography over silica gel to get pure
compound having formula (3) (1 gm).
Step 2 Preparation of 4-(p-methoxyphenvn-2-bromobutane.
The compound having formula (3) (Ig) was dissolved in acetone (10 ml) and to it
were added anhydrous potassium carbonate (lOg) and dimethyl sulphate (3ml) and
refluxed with stirring for 4 hours. Water was added to the reaction flask and stirred
for 3 hours. It was then extracted with water CHCl^ (25ml x 3) and washed with
water (25ml x 2). The organic layer was dried over anhydrous sodium sulphate
and concentrated in vaccuo to get oily material (4) (l.Og).
Step 3 preparation of 4-(p-methoxvphenvn-2-a2ido-butane (CnH^ ONQ
Compound having formula (4) (l.Og) was dissolved in DMF (10 ml) and treated
with sodium azide (2g) and stirred at 20-80° for 6 hours. The reaction mixture
was poured in water and extracted with benzene (50 mlx3); the organic layer was
washed with water (25mlx2, dried over sodium sulphate and concentrated to give
Azide (5) (SOOmg).
Step 4 preparation of 4-(p-rncthoxvphenvl)-2-amino-butane ( C , i M | ? ON), having ..
(brnnila ( I ) .
The a/.ide (5) (300mg) was dissolved in methanol (20 ml) and to it was added
palladium charcoal (30 mg) and stirred under hydrogen for C> hrs at 55 Psi; catalyst
was then filtered off, the filtrate was concentrated to give a residue which
crystallized from acetone-hexane mixture as needles to give compound having
formula (1) (208 mg).
Ste 1 Prearation of (4-(p-hydroxvphenyl)-2-chlorobutane
In a 50 ml conical flask was charged with compound having formula 2 (Ig) and to
it added HC1 37% 5ml dropwise and the reaction mixture was refluxed for 6 hours
at 80°C with constant stirring. The reaction mixture was diluted with excess water
and extracted with ethyl acetate (25ml x 3). The ethyl acetate extract was dried
over anhydrous sodium sulphate and concentrated. The oily residue thus obtained
was subjected to flash chromatography over fluorosil to give pure compound
having formula (3) (Ig).
Step 2 preparation of (4-(p-methoxyphenvn-2-chlorobutane
represented by formula (4)
The compound (3) (Ig) was dissolved in acetone (10 ml) was dissolved in acetone
(10 ml) and to it were added anhydrous potassium carbonate (lOg) and methyl
iodide (3ml) and refluxed with stirring for 4 hours, water was added to the reaction
flask and was stirred for 3 hours. It was then extracted with water CHC} (25ml x
3) and washed with water (25ml x 2). The organic layer was dried over anhydrous
sodium sulphate and concentrated in vaccuo to get oily material having formula
Step 3 preparation of 4-(p-methoxyphenyl)-2-azido-butane
represented by the formula (5)
Compound (4) (l.Og) was dissolved in DMF (10ml) and treated with trimethyl
silyl azide (2g) and stirred at 20-80°C for 6 hours. The reaction mixture was
poured in water and extracted with benzene (50 ml x 3): The organic layer was
washed with water (25 ml x 2); dried over anhydrous sodium sulphate and
concentrated to give 800 mg of azide of formula (5).
Step 4 preparation of 4-(p-methoxvphenvn-2-amino butane (CijEn^ON) having
The azide (5) (300mg) was dissolved in ethanol (20ml) and to it was added Pt02
(lOmg) and stirred under hydrogen for 6 hours at 55 Psi; catalyst was then filtered
off, filtrate was concentrated to give a residue which crystallized from acetone
hexane mixture as needless to give 208mg of compound of formula (1).
The spectral characteristics of the molecule are as follows :
The El mass spectrum of the compound showed its M* at M/Z 179, thus
confirming its molecular formula as CnH]7ON, and other diagnostic fragment
peaks at M/Z 162, 147, 121, and 91 IRA/ max (KB r) 3360, 2940, 1610, 1515, 14501,
1 030 and 850 Cm'1.
The molecule "hals been prepared from a readily available starting material 4-(phydroxyphenyl)-
butan-2-ol having formula (2) isolated from the plant Taxus
of the Novel molecule for antifeedant activity
The compound having formula ( I ) was evaluated as feeding deterrent and growth
against 4'1' in star larvae of spilarctia obliqua i^'hai hairy caterpillar)
Tim insect attacks more than twenty cash crops like urd. moong. arhar, mint and
coicus etc Several synthetic insecticides like quinalphos. Phosphamidon and
synthetic pyrethroids are commercially used to manage this insect pest. But. the
insect is developing resistance towards some of these insecticides. Therefore, it
has now become imperative to search for new ecologically safe, environmentally
sound and non-toxic chemicals to manage this pest.
With compound having formula (1) insect feeding deterrency and growth
inhibition was tested by diet-mix method. In this method, 4-(p-methoxyphenyl)-2-
aminobutane the compound having formula (1) was dissolved in acetone to make
various concentrations ranging from 1000 to 5000 ppm. Test solution was mixed
in the artificial diet of the insect so that each gram of diet contained 60-300 j^g of
the compound (1). 4th in star larva (newly molted) starved four hours, was
weighed and released on treated artificial diet in thirty replications. In control,
only solvent acetone was mixed and azadirachtin at 1000 ppm concentration was
taken as standard for feeding bioassay. After 24 hours, number of fecal pellets
produced were counted, and the data were analyzed for % feeding deterrency.
Some experiments were continued for next 24 hours and weights of the larva were
taken daily. After 3 days, experiment was discontinued and weight gain or loss
was analyzed for % growth inhibition.
Diflubenzuron at 5 ppm was taken as a standard in case of growth inhibitory
assay. The test result of compound having formula (1) in terms of its feeding
deterrency and growth inhibition as compared to standards azadirachtin and
diflubenzuron are given in table I.
As it appears from the table 1. compound having formula (1) is less active as a
feeding deterrent agent as compared to azadirachtin. However, the new molecule
(1) has several other advantages over azadirachtin which include.
(a) Compound having formula (1) is a very small molecule (molecular weight
179), structurally as compared to azadirachtin which is a large molecule
with many chiral centres, molecular weight 720; therefore, the molecule (1)
can be synthesized easily as compared to azadirachtin, the synthesis of
which would never be commercially viable.
(b) Unlike azadirachtin which is photosensitive i.e., it decomposes on exposure
to sun light, compound having formula (1) is not sensitive to light (both UV
and sunlight). Therefore, compound (1) can be used under field condition
in contrast to azadirachtin which can not be used under field condition till
In terms of growth inhibitory properties, compound having formula (1J is
less active than the standard compound diflubenzuron. However, many
insects arc developing, resistance to this particular compound and ihcrctore
higher doses are required to k i l l the insects as compared to 5 ppm ;»s
mentioned in table I Ultimately i t s effectiveness w i l l be stopped
Therefore, compound having formula (1) which is structurally different
from diflubenzuron will be useful against diflubenzuron resistant insects
Also, diflubenzuron contains fluonne atoms in its molecule and therefore it
is prone to be carcinogenic and environmentally hardazous on microbial
activation. Due to its different structure as compared to diflubenzuron,
compound having formula (1) will be ecologically non hazardous and
From the foregoing, it will be clear that the compounds of the invention
have extremely high controlling effects against various types of
phytopathogenes insects, mites etc and thus are useful as active ingredients
of agricultural and horticultural insecticides, miticides etc.
1. The chemicals and reagents that are used to prepare the active compound
are not expensive and thus the process is cost effective and viable for
2. All the steps in the process are straight forward; no extreme reaction
conditions are necessary to be maintained for preparation of the active
compound and thus the process will be commercially viable.
Novel compound l-(P-met.hoss phenyl)-2-ammobutane exhibiting growth
inhibition and antifeedant activity against larvae and represented by the
- 4 - (p-methoxy phenyl)-2-anino butane
An insecticidal composition comprising an effective amount of 4-(pmethoxyphenyl)-
2-aminobutane represented by structural formula (I) and
an adjuvant in an amount sufficient enhance the activity of the insecticidal
A composition as claimed in claim 2 wherein the adjuvants arc selected
from distilled water, acctone and organic solvents.
A novel compound 4-(p-methoxyphenyl) -2- amino but one exhibiting growth inhibition and an insecticidal composition substantially as herein described with
Reference to examples.
|Indian Patent Application Number||376/DEL/2000|
|PG Journal Number||13/2008|
|Date of Filing||31-Mar-2000|
|Name of Patentee||COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH|
|Applicant Address||RAFI MARG, NEW DELHI-110001, INDIA.|
|PCT International Classification Number||C07C 217/62|
|PCT International Application Number||N/A|
|PCT International Filing date|