U.S. patent application number 09/574543 was filed with the patent office on 2002-04-25 for synthetic precursors to 4-(p-methoxyphenyl)-2-amino-butane.
Invention is credited to Chattopadhyay, Sunil Kumar, Kumar, Sushil, Prajapati, Veena, Sashidhara, Koneni Venkata, Tripathi, Arun Kumar, Tripathi, Vinayak.
Application Number | 20020049353 09/574543 |
Document ID | / |
Family ID | 24296591 |
Filed Date | 2002-04-25 |
United States Patent
Application |
20020049353 |
Kind Code |
A1 |
Chattopadhyay, Sunil Kumar ;
et al. |
April 25, 2002 |
Synthetic precursors to 4-(P-methoxyphenyl)-2-amino-butane
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. 1
C.sub.11H.sub.17ON=4-(p-methoxy phenyl)-2-amino butane and an
insecticidal composition comprising an effective amount of the
novel compound and appropriate adjuvant.
Inventors: |
Chattopadhyay, Sunil Kumar;
(Lucknow, IN) ; Sashidhara, Koneni Venkata;
(Lucknow, IN) ; Tripathi, Vinayak; (Licknow,
IN) ; Tripathi, Arun Kumar; (Lucknow, IN) ;
Prajapati, Veena; (Lucknow, IN) ; Kumar, Sushil;
(Lucknow, IN) |
Correspondence
Address: |
Allan Ratner
Ratner & Prestia
Suite 301 One Westlakes Berwyn
PO Box 980
Valley Forge
PA
19482-0980
US
|
Family ID: |
24296591 |
Appl. No.: |
09/574543 |
Filed: |
May 19, 2000 |
Current U.S.
Class: |
564/336 ;
504/326; 504/351; 568/626 |
Current CPC
Class: |
A01N 33/10 20130101;
C07C 217/62 20130101 |
Class at
Publication: |
564/336 ;
568/626; 504/351; 504/326 |
International
Class: |
C07C 259/00 |
Claims
1. Novel compound 4-(p-methoxyphenyl)-2-aminobutane exhibiting
growth inhibition and antifeedant activity against larvae and
represented by the structural formula. 6
2. An insecticidal composition comprising an effective amount of
4-(p-methoxyphenyl)-2-aminobutane represented by structural formula
(1) and an adjuvant in an amount sufficient enhance the activity of
the insecticidal composition.
3. A composition as claimed in claim 2 wherein the adjuvants are
selected from distilled water, acetone and organic solvents.
Description
FIELD
[0001] The invention provides novel biologically active synthetic
molecule 4-p-methoxyphenyl)-2-amino-butane. The invention also
provides a process for preparation of said molecule from a
naturally occurring compound 4-(p-hydroxyphenyl)butan-2-ol. The
molecule of the invention is a colorless crystalline solid,
represented by molecular formula, C.sub.11H.sub.17ON, and
structural formula (1) as shown herein below: 2
[0002] The spectral characteristics of the molecule are as
follows:
[0003] The EI mass spectrum of the compound showed its M.sup.t at
M/Z 179, thus confirming its molecular formula as
C.sub.11H.sub.17ON, and other diagnostic fragment peaks at M/Z 162,
147, 121 and 91; IR.nu..sub.max (KBr) 3360, 2940, 1610, 1515,
14501, 1030 and 850 cm.sup.-1
[0004] Further, the invention provides an insecticidal composition
comprising the said molecule 4-(p-methoxyphenyl)-2-amino butane in
an effective amount and an adjuvant.
[0005] The product is a new molecule which has been prepared from a
readily available starting material 4-(p-hydroxyphenyl)-butan-2-ol
represented by formula (2) as shown herein below isolated from the
plant Taxus wallichiana. 3
BACKGROUND AND PRIOR ART
[0006] 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.
[0007] 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 III (DAB). During the course of investigation,
the applicants have isolated a major compound from the 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 alkali
soluble fraction by acidifying it and extracting it with ethyl
acetate, to obtain the compound having structural formula (2).
[0008] The compound (2) was not found to be active in bioassay
studies for evaluation of growth inhibition and antifeedant
activity. The compound of formula (2) was obtained with high yield
(0.2%), 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.
[0009] The compound having formula (1) was evaluated as feeding
deterrent and growth inhibitor against 4.sup.th instar larvae of
Spilarctia Obliqua. This insect attacks more than twenty cash crops
including urd, mong, arhar, mint and coleus etc.
[0010] Compound having formula (1) is non hazardous in nature and
thus is ecologically safe and environmentally sound for its use as
an agrochemical.
[0011] Objects
[0012] The main object of this invention is to provide a new
molecule, 4-(p-methoxyphenyl)-2-amino butane, represented by
structural formula (1) and represented by molecular formula
C.sub.11H.sub.17ON.
[0013] It is also an object of the invention to provide a process
for the preparation of a biologically active compound represented
by structural formula (1) with higher yields, from a readily
available starting material isolated from the plant Taxus
wallichiana.
[0014] Yet another object of the 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
[0015] Accordingly, the present invention provides novel molecule
4-(p-methoxyphenyl)-2-amino butane, C.sub.11H.sub.17ON, represented
by the structural formula (1) as shown herein below. 4
[0016] The compound exhibits growth inhibitory and antifeedant
activity. The process for the isolation of the novel compound
comprises the steps of:
[0017] a) isolating a phenolic molecule represented by structural
formula (2) from the leaves of Taxus wallichiana by known
methods,
[0018] b) treating the compound having formula (2) in aqueous
mineral acid at 25-100.degree. C. for 2-10 hours to obtain a
phenolic halide derivative,
[0019] c) converting the phenolic halide derivative into its methyl
ether by treating it with a methylating agent to obtain a methyl
ether halide,
[0020] d) reacting the methyl ether formed with azide to obtain an
azido derivative, and
[0021] 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).
[0022] 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 sulphate.
[0023] The azide, used in step (d) is sodium azide or trimethyl
silyl azide.
[0024] The catalyst used in the hydrogenation process is selected
from palladium charcoal and platinum oxide. The lower alcohol used
as medium to dissolve the azide derivative in the hydrogenation
process may be methyl alcohol, ethyl alcohol.
[0025] As mentioned earlier, the compound 4-(p-methoxy
phenyl)-2-amino butane exhibits antifeedant and growth inhibiting
activity against certain insects, especially the larvae of
Spilarctia Obliqua.
[0026] 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-(p-methoxyphenyl)-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.
[0027] 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.
[0028] The products of the reactions as described in the steps
hereinbelow is represented hereunder:
[0029] The products of the reactions as described in the steps
hereinbelow is represented hereunder: 5
EXAMPLE 1
[0030] Step 1--preparation of 4-(p-hydroxyphenyl)-2 bromobutane
(formula 3)--(C.sub.10H.sub.13OBr)
[0031] In a 50 ml conical flask was charged with compound of
formula (2) (1 gm) and to it was added HBr (44%) (5 ml) dropwise
and the reaction mixture was refluxed for 6 hours at 80.degree. C.
with constant stirring. The reaction mixture was diluted with
excess water and extracted with ethyl acetate (25 ml.times.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).
[0032] Step 2 Preparation of 4-(p-methoxyphenyl)-2-bromobutane
[0033] The compound having formula (3) (1 g) was dissolved in
acetone (10 ml) and to it were added anhydrous potassium carbonate
(10 g) and dimethyl sulphate (3 ml) 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.sub.3 (25 ml.times.3)
and washed with water (25 ml.times.2). The organic layer was dried
over anhydrous sodium sulphate and concentrated in vaccuo to get
oily material (4) (1.0 g).
[0034] Step 3 preparation of 4-(p-methoxyphenyl)-2-azido-butane
(C.sub.11H.sub.15ON.sub.3)
[0035] Compound having formula (4) (1.0 g) was dissolved in DMF (10
ml) and treated with sodium azide (2 g) and stirred at
20-80.degree. for 6 hours. The reaction mixture was poured in water
and extracted with benzene (50 ml.times.3); the organic layer was
washed with water (25 ml.times.2, dried over sodium sulphate and
concentrated to give Azide (5) (800 mg).
[0036] Step 4 preparation of 4-(p-methoxyphenyl)-2-amino-butane
(C.sub.11H.sub.17ON), having formula (1)
[0037] The azide (5) (300 mg) was dissolved in methanol (20 ml) and
to it was added palladium charcoal (30 mg) and stirred under
hydrogen for 6 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).
EXAMPLE 2
[0038] Step 1 Preparation of (4-(p-hydroxyphenyl)-2-chlorobutane
(C.sub.10H.sub.13OCl)
[0039] In a 50 ml conical flask was charged with compound having
formula 2 (1 g) and to it added HCl 37% 5 ml dropwise and the
reaction mixture was refluxed for 6 hours at 80.degree. C. with
constant stirring. The reaction mixture was diluted with excess
water and extracted with ethyl acetate (25 ml.times.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) (1 g).
[0040] Step 2 preparation of (4-(p-methoxyphenyl)-2-chlorobutane
(C.sub.11H.sub.15OCl) represented by formula (4)
[0041] The compound (3) (1 g) was dissolved in acetone (10 ml) was
dissolved in acetone (10 ml) and to it were added anhydrous
potassium carbonate (10 g) and methyl iodide (3 ml) 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.sub.3 (25 ml.times.3) and washed with water (25 ml.times.2).
The organic layer was dried over anhydrous sodium sulphate and
concentrated in vaccuo to get oily material having formula (4) (1
g).
[0042] Step 3 preparation of 4-(p-methoxyphenyl)-2-azido-butane
(C.sub.11H.sub.15ON.sub.3) represented by the formula (5)
[0043] Compound (4) (1.0 g) was dissolved in DMF (10 ml) and
treated with trimethyl silyl azide (2 g) and stirred at
20-80.degree. C. for 6 hours. The reaction mixture was poured in
water and extracted with benzene (50 ml.times.3); The organic layer
was washed with water (25 ml.times.2); dried over anhydrous sodium
sulphate and concentrated to give 800 mg of azide of formula
(5).
[0044] Step 4 preparation of 4-(p-methoxyphenyl)-2-amino butane
(C.sub.11H.sub.17ON) having formula (1)
[0045] The azide (5) (300 mg) was dissolved in ethanol (20 ml) and
to it was added PtO.sub.2 (10 mg) 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 208 mg of compound of formula
(1).
[0046] The spectral characteristics of the molecule are as
follows:
[0047] The EI mass spectrum of the compound showed its M.sup.+ at
M/Z 179, thus confirming its molecular formula as
C.sub.11H.sub.17ON, and other diagnostic fragment peaks at M/Z 162,
147, 121, and 91 IR{square root}.sub.max (KBr) 3360, 2940, 1610,
1515, 14501, 1030 and 850 Cm.sup.-1.
[0048] The molecule has been prepared from a readily available
starting material 4-(p-hydroxyphenyl)-butan-2-ol having formula (2)
isolated from the plant Taxus wallichiana.
[0049] Evaluation of the Novel Molecule for Antifeedant
Activity
[0050] The compound having formula (1) was evaluated as feeding
deterrent and growth inhibitor against 4.sup.th in star larvae of
spilarctia obliqua (Bihar hairy caterpillar). This insect attacks
more than twenty cash crops like urd, moong, arhar, mint and coleus
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.
[0051] 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 .mu.g of the compound (1). 4.sup.th 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.
[0052] 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 1.
1 TABLE 1 Concentration % feeding % growth Compound (ppm)
deterrency inhibition Compound 1 1000 32.0 48.0 2000 40.0 59.0 3000
64.0 72.0 4000 82.0 100.0 5000 100.0 128.0 Azadirachtin 1000 100.0
-- Diflubenzuron 5 -- 100.0
[0053] 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:
[0054] (a) Compound 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.
[0055] 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 to date.
[0056] In terms of growth inhibitory properties, compound having
formula (1) is less active that the standard compound
diflubenzuron. However, many insects are developing resistance to
this particular compound and therefore higher doses are required to
kill the insects as compared to 5 ppm as mentioned in table 1.
Ultimately its effectiveness will be stopped.
[0057] Therefore, compound having formula (1) which is structurally
different from diflubenzuron will be useful against diflubenzuron
resistant insects.
[0058] Also, diflubenzuron contains fluorine 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 environmentally sound.
[0059] 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.
Advantages
[0060] 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 commercial production.
[0061] 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.
* * * * *