U.S. patent application number 09/789142 was filed with the patent office on 2001-09-06 for methods of blocking an ethylene response in plants using cyclopropene derivatives.
Invention is credited to Sisler, Edward C..
Application Number | 20010019995 09/789142 |
Document ID | / |
Family ID | 26888772 |
Filed Date | 2001-09-06 |
United States Patent
Application |
20010019995 |
Kind Code |
A1 |
Sisler, Edward C. |
September 6, 2001 |
Methods of blocking an ethylene response in plants using
cyclopropene derivatives
Abstract
Methods of applying cyclopropene derivatives and compositions
thereof to block ethylene receptors in plants are disclosed. One
such method comprises applying to the plant an effective ethylene
response-inhibiting amount of cyclopropene derivatives or
compositions thereof. Also disclosed are methods of inhibiting
abscission in plants, methods of prolonging the life of cut
flowers, methods of inhibiting ripening of picked fruits, and
methods of inhibiting ripening of picked vegetables.
Inventors: |
Sisler, Edward C.; (Raleigh,
NC) |
Correspondence
Address: |
MYERS BIGEL SIBLEY & SAJOVEC
PO BOX 37428
RALEIGH
NC
27627
US
|
Family ID: |
26888772 |
Appl. No.: |
09/789142 |
Filed: |
February 20, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09789142 |
Feb 20, 2001 |
|
|
|
09448523 |
Nov 23, 1999 |
|
|
|
6194350 |
|
|
|
|
60193202 |
Mar 30, 2000 |
|
|
|
Current U.S.
Class: |
504/114 |
Current CPC
Class: |
A01N 33/04 20130101;
A01N 37/02 20130101; A01N 37/06 20130101; A01N 33/12 20130101; A01N
31/04 20130101; A01N 35/10 20130101; A01N 3/02 20130101; A01N 37/34
20130101; A01N 27/00 20130101; A01N 35/02 20130101 |
Class at
Publication: |
504/114 |
International
Class: |
A01N 003/02 |
Goverment Interests
[0002] This invention was made with government support under Grant
No. US-2786-96R awarded by the U.S. Department of Agriculture. The
government has certain rights in the invention.
Claims
That which is claimed is:
1. A method of inhibiting an ethylene response in a plant,
comprising applying to the plant an effective ethylene
response-inhibiting amount of a compound of Formula I: 15wherein: n
is a number from 1 to 4; and each R is independently a saturated or
unsaturated, linear or branched-chain, unsubstituted or
substituted, C.sub.5-C.sub.20 alkyl, alkenyl, or alkynyl, wherein
at least one R is a saturated or unsaturated, linear or
branched-chain, unsubstituted or substituted C.sub.5 alkyl,
alkenyl, or alkynyl.
2. The method according to claim 1, wherein n is 1 or 2.
3. The method according to claim 1, wherein n is 1.
4. The method according to claim 1, wherein said applying step is
carried out by contacting said plant to a composition comprising
said compound and an inert carrier.
5. The method according to claim 1, wherein said applying step is
carried out by contacting said plant to a gas of said compound.
6. The method according to claim 1, wherein said applying step is
carried out by spraying said plant with a solution comprising said
compound.
7. The method according to claim 1, wherein said applying step is
carried out by contacting said plant to a solid comprising said
compound.
8. The method according to claim 1, wherein said ethylene response
is fruit ripening.
9. The method according to claim 1, wherein said ethylene response
is vegetable ripening.
10. The method according to claim 1, wherein said ethylene response
is flower senescence.
11. The method according to claim 1, wherein said ethylene response
is abscission.
12. The method according to claim 1, wherein said plant is a
harvested fruit.
13. The method according to claim 1, wherein said plant is a
harvested vegetable.
14. The method according to claim 1, wherein at least one R is an
alkyl, alkenyl, or alkynyl substituted with at least one
substituent selected from the group consisting of halogen, amino,
alkoxy, carboxy, alkoxycarbonyl, oxycarbonylalkyl and hydroxy.
15. The method according to claim 1, wherein at least one of the
carbon atoms in at least one R group is replaced by at least one
constituent selected from the group consisting of ester groups,
nitriles, amines, amine salts, acids, acid salts, esters of acids,
hydroxyl groups, halogen groups, and heteroatoms selected from the
group consisting of oxygen and nitrogen.
16. The method according to claim 1, wherein the compound is
selected from the group consisting of 3,3-dipentyl-cyclopropene,
1-pent-2-enyl-2-pentyl-cyclopropene,
1-pent-2-enyl-3,3-dipentyl-cycloprop- ene,
4-(1-cyclopropenyl)-2-methylbutan-2-ol, 1-(n-amyl) -cyclopropene,
1-(5,5, 5-trifluoropentyl)-cyclopropene, and
1,2-dipentyl-cyclopropene.
17. A method of prolonging the life of a cut flower, comprising
applying to the cut flower an effective life-prolonging amount of a
compound of Formula I: 16wherein: n is a number from 1 to 4; and
each R is independently a saturated or unsaturated, linear or
branched-chain, unsubstituted or substituted, C.sub.5-C.sub.20
alkyl, alkenyl, or alkynyl, wherein at least one R is a saturated
or unsaturated, linear or branched-chain, unsubstituted or
substituted C.sub.5 alkyl, alkenyl, or alkynyl.
18. The method according to claim 17, wherein n is 1 or 2.
19. The method according to claim 17, wherein n is 1.
20. The method according to claim 17, wherein said applying step is
carried out by contacting said plant to a composition comprising
said compound and an inert carrier.
21. The method according to claim 17, wherein said applying step is
carried out by contacting said plant to a gas of said compound.
22. The method according to claim 17, wherein said applying step is
carried out by spraying said plant with a solution comprising said
compound.
23. The method according to claim 17, wherein said applying step is
carried out by contacting said plant to a solid comprising said
compound.
24. The method according to claim 17, wherein at least one R is an
alkyl, alkenyl, or alkynyl substituted with at least one
substituent selected from the group consisting of halogen, amino,
alkoxy, carboxy, alkoxycarbonyl, oxycarbonylalkyl, and hydroxy.
25. The method according to claim 17, wherein at least one of the
carbon atoms in at least one R group is replaced by at least one
constituent selected from the group consisting of ester groups,
nitrites, amines, amine salts, acids, acid salts, esters of acids,
hydroxyl groups, halogen groups, and heteroatoms selected from the
group consisting of oxygen and nitrogen.
26. The method according to claim 17, wherein the compound is
selected from the group consisting of 3,3-dipentyl-cyclopropene,
1-pent-2-enyl-2-pentyl-cyclopropene,
1-pent-2-enyl-3,3-dipentyl-cycloprop- ene,
4-(1-cyclopropenyl)-2-methylbutan-2-ol, 1-(n-amyl) -cyclopropene,
1-(5,5,5-trifluoropentyl)-cyclopropene, and
1,2-dipentyl-cyclopropene.
27. A method of inhibiting an ethylene response in a plant,
comprising applying to the plant an effective ethylene
response-inhibiting amount of a compound of Formula I: 17wherein: n
is a number from 1 to 4; each R is independently a saturated or
unsaturated, linear or branched-chain, unsubstituted or
substituted, C.sub.6-C.sub.20 alkyl, alkenyl, or alkynyl; and
wherein said compound is selected from the group consisting of
1-(7-methoxyheptyl) -cyclopropene,
1-(7-hydroxymethyl)-cyclopropene, 1-(7-acetoxyheptyl)-cyclopropene,
7-cycloprop-1-enyl-heptanoic acid, 7-cycloprop-1-enyl-heptanoic
acid isopropylamine salt, 7-cycloprop-1-enyl-heptanoic acid ethyl
ester, 1-(7-cyanoheptyl)-cyclopro- pene,
1-(7-N,N-diethylaminoheptyl)-cyclopropene,
1-(7-N,N-diethylammoniumh- eptyl)-cyclopropene acetate,
1-(7-N,N-diethylmethylammonium-heptyl)-cyclop- ropene iodide,
1-hexyloxymethyl-cyclopropene, 1-pentyloxyethyl-cyclopropen- e,
methyl sterculate, 1-(n-nonyl)-cyclopropene,
1-(n-decyl)-cyclopropene, 1-(n-heptyl)-cyclopropene,
1-(undecyl)-cyclopropene, 1-(3-ethylheptyl)-cyclopropene,
1-(tridecyl)-cyclopropene,
1-(2-(2-methoxy-ethoxy)-ethoxymethyl)-cyclopropene,
1-(2-methylheptyl)-cyclopropene,
1-(2-propionyloxyethyl)-cyclopropene,
1-(6-methylheptyl)-cyclopropene,
1-(3,5,5-trimethylhexyl)-cyclopropene, 1-pentadecyl-cyclopropene,
1-(4, 8-nonyl)-cyclopropene, 1-dodecyl-cyclopropene,
1-(di-n-butylaminomethyl)-cyclopropene, 1-tetradecyl-cyclopropene,
1-(3,3-dimethylbutyl)-cyclopropene, 1,3 -dihexyl-cyclopropene,
8-cycloprop-1-enyl-octan-2-one, 8-cycloprop-1-enyl-octan-2-one
O-methyl-oxime, 7-cycloprop-1-enyl-heptano- ic acid diethylamide,
1-(oct-7-enyl)-cyclopropene, 1-(7-octenyl)-cycloprop- ene,
1-(undec-5-ynl)-cyclopropene, and
hex-5-yne-2-octylcycloprop-2-ene-1-- carboxylate.
28. The method according to claim 27, wherein said applying step is
carried out by contacting said plant to a composition comprising
said compound and an inert carrier.
29. A method of prolonging the life of a cut flower, comprising
applying to the cut flower an effective life-prolonging amount of a
compound of Formula I: 18wherein: n is a number from 1 to 4; and
each R is independently a saturated or unsaturated, linear or
branched-chain, unsubstituted or substituted, C.sub.6-C.sub.20
alkyl, alkenyl, or alkynyl; and wherein said compound is selected
from the group consisting of 1-(7-methoxy-heptyl)-cyclopropene,
1-(7-hydroxymethyl)-cyclopropene, 1-(7-acetoxyheptyl)-cyclopropene,
7-cycloprop-1-enyl-heptanoic acid, 7-cycloprop-1-enyl-heptanoic
acid isopropylamine salt, 7-cycloprop-1-enyl-heptanoic acid ethyl
ester, 1-(7-cyanoheptyl) -cyclopropene,
1-(7-N,N-diethylaminoheptyl)-cyclopropene,
1-(7-N,N-diethylammoniumheptyl)-cyclopropene acetate,
1-(7-N,N-diethylmethylammonium-heptyl)-cyclopropene iodide, 1-
hexyloxymethyl-cyclopropene, 1-pentyloxyethyl-cyclopropene, methyl
sterculate, 1-(n-nonyl)-cyclopropene, 1-(n-decyl)-cyclopropene,
1-(n-heptyl)-cyclopropene, 1-(undecyl)-cyclopropene,
1-(3-ethylheptyl)-cyclopropene, 1-(tridecyl)-cyclopropene,
1-(2-(2-methoxy-ethoxy)-ethoxymethyl)-cyclopropene,
1-(2-methylheptyl)-cyclopropene,
1-(2-propionyloxy-ethyl)-cyclopropene,
1-(6-methylheptyl)-cyclopropene,
1-(3,5,5-trimethylhexyl)-cyclopropene, 1-pentadecyl-cyclopropene,
1-(4,8-nonyl)-cyclopropene, 1-dodecyl-cyclopropene,
1-(di-n-butylaminomethyl)-cyclopropene, 1-tetradecyl-cyclopropene,
1-(3,3-dimethylbutyl)-cyclopropene, 1,3 -dihexyl-cyclopropene,
8-cycloprop-1-enyl-octan-2-one, 8-cycloprop-1-enyl-octan-2-one
O-methyl-oxime, 7-cycloprop-1-enyl-heptano- ic acid diethylamide,
1-(oct-7-enyl)-cyclopropene, 1-(7-octenyl)-cycloprop- ene,
1-(undec-5-ynl)-cyclopropene, and
hex-5-yne-2-octylcycloprop-2-ene-1-- carboxylate.
30. The method according to claim 29, wherein said applying step is
carried out by contacting said plant to a composition comprising
said compound and an inert carrier.
Description
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of commonly
owned, copending application Ser. No. 09/448,523 of Edward C.
Sisler, filed Nov. 23, 1999, the disclosure of which is
incorporated by reference herein in its entirety. This application
also claims priority from Edward C. Sisler, U.S. Provisional
Application No. 60/193,202, filed Mar. 30, 2000, the disclosure of
which is incorporated by reference herein in its entirety.
FIELD OF THE INVENTION
[0003] The present invention generally relates to methods of
blocking ethylene responses in plants and plant materials, and
particularly relates to methods of inhibiting various ethylene
responses including plant maturation and degradation by applying
cyclopropene derivatives and compositions thereof to plants.
BACKGROUND OF THE INVENTION
[0004] Ethylene is known to mediate a variety of growth phenomena
in plants. See generally Fritz et al. U.S. Pat. No. 3,879,188. This
activity is understood to be achieved through a specific ethylene
receptor in plants. Many compounds other than ethylene interact
with this receptor: some mimic the action of ethylene; others
prevent ethylene from binding and thereby counteract its
action.
[0005] Many compounds that block the action of ethylene do so by
binding to the ethylene binding site. Unfortunately, they often
diffuse from the binding site over a period of several hours. See
E. Sisler and C. Wood, Plant Growth Reg. 7, 181-191 (1988). These
compounds may be used to counteract ethylene action. A problem with
such compounds, however, is that exposure must be continuous if the
effect is to last for more than a few hours.
[0006] Photoaffinity labeling has been used in biological studies
to label binding sites in a permanent manner: usually by generating
a carbene or nitrene intermediate. Such intermediates are very
reactive and react rapidly and indiscriminately with many things. A
compound already bound, however, would react mostly with the
binding site. In a preliminary study, it was shown that
transcyclooctene was an effective blocking agent for ethylene
binding. See E. Sisler et al., Plant Growth Reg. 9, 157-164 (1990).
Methods of combating the ethylene response in plants with
diazocyclopentadiene and derivatives thereof are disclosed in U.S.
Pat. No. 5,100,462 to Sisler et al. U.S. Pat. No. 5,518,988 to
Sisler et al. describes the use of cyclopropenes having a C.sub.1
to C.sub.4 alkyl group to block the action of ethylene.
[0007] Notwithstanding these efforts, there remains a need in the
art for improved plant maturation and degradation regulation.
SUMMARY OF THE INVENTION
[0008] Methods of inhibiting an ethylene response in a plant are
disclosed herein. According to the present invention, one such
method comprises applying to the plant an effective ethylene
response-inhibiting amount of a cyclopropene derivative or a
composition thereof described further in detail herein. Long-chain
cyclopropene derivatives are particularly preferred as described
below.
[0009] Another aspect of the present invention is a method of
blocking ethylene receptors in plants by applying to the plants an
effective ethylene receptor-blocking amount of a cyclopropene
derivative or a composition thereof.
[0010] Also disclosed is a method of inhibiting abscission in a
plant, comprising applying to the plant an effective
abscission-inhibiting amount of a cyclopropene derivative or a
composition thereof.
[0011] Also disclosed is a method of prolonging the life of a cut
flower, comprising applying to the cut flower an effective
life-prolonging amount of a cyclopropene derivative or a
composition thereof.
[0012] Also disclosed is a method of inhibiting the ripening of a
harvested fruit, comprising applying to the harvested fruit an
effective inhibiting amount of a cyclopropene derivative or a
composition thereof.
[0013] Also disclosed is a method of inhibiting the ripening of a
harvested vegetable, comprising applying to the harvested vegetable
an effective inhibiting amount of a cyclopropene derivative or a
composition thereof.
[0014] The methods described herein may be carried out in a number
of suitable manners, such as by contacting the plant with a
cyclopropene derivative or a composition thereof, whether in solid,
liquid, or gaseous form, or by introducing the plant, cut flower,
picked fruit or picked vegetable into an atmosphere infused with
the cyclopropene derivative or a composition thereof. These and
other suitable methods of application are discussed in detail
below.
[0015] Also disclosed is the use of a cyclopropene derivative as
described herein for the preparation of an agricultural composition
for carrying out any of the methods described above.
DETAILED DESCRIPTION OF THE INVENTION
[0016] Cyclopropene derivatives which may be used to carry out the
present invention are defined by Formula I: 1
[0017] wherein:
[0018] n is a number from 1 to 4. Preferably n is 1 or 2, and most
preferably n is 1.
[0019] R is a saturated or unsaturated, linear or branched-chain,
unsubstituted or substituted, C.sub.5 to C.sub.20 alkyl, alkenyl,
or alkynyl.
[0020] The terms "alkyl", "alkenyl", and "alkynyl", as used herein,
refer to linear or branched alkyl, alkenyl or alkynyl substituents.
The terms should be interpreted broadly and may include compounds
in which one or more of the carbons in one or more of the R groups
is replaced by a group such as ester groups, nitriles, amines,
amine salts, acids, acid salts, esters of acids, hydroxyl groups,
halogen groups, and heteroatoms selected from the group consisting
of oxygen and nitrogen or where such chains include halogen, amino,
alkoxy, carboxy, alkoxycarbonyl, oxycarbonylalkyl, or hydroxy
substituents. Thus, the resulting R groups can contain, for
example, hydroxyl, ether, ketone, aldehyde, ester, acid, acid salt,
amine, amine salt, amide, oxime, nitrile, and halogen groups.
[0021] Cyclopropene derivatives which may be used to carry out the
present invention may be prepared by various methods known to those
skilled in the art. For example, the reaction of a bromo-olefin
with dibromocarbene gives a tribromocyclopropane, which can be
converted to the cyclopropene with methyllithium or other
organolithium compounds as shown. (see Baird, M. S.; Hussain, H.
H.; Nethercott, W; J. Chem. Soc. Perkin Trans. 1, 1986,1845-1854
and Baird, M. S.; Fitton, H. L.; Clegg, W; McCamley, A.; J. Chem.
Soc. Perkin Trans. 1, 1993, 321-326). 2
[0022] The bromo-olefins can be prepared by standard methods.
[0023] Additionally, 3,3-disubstituted cyclopropenes can be
prepared using methods described by N. I. Yakushkina and I. G.
Bolesov in Dehydrohalogenation of Monohalogenocyclopropanes as a
Method for the Synthesis of Sterically Screened Cyclopropenes,
RUSSIAN J. OF ORGANIC CHEM. 15:853-59 (1979). Furthermore, a
1,1-disubstituted olefin can also react with dibromocarbene to give
a dibrominated intermediate. This can be reduced with zinc to the
mono-brominated cyclopropane. Elimination of the bromide with base
gives the cyclopropene (see Binger, P.; Synthesis 1974, 190). 3
[0024] Cyclopropene can be deprotonated with a strong base such as
sodium amide in liquid ammonia and alkylated with an alkyl halide
or other alkylating agent to give a substituted cyclopropene
(reference: Schipperijn, A. J.; Smael, P.; Recl. Trav. Chim.
Pays-Bas, 1973, 92, 1159). The lithium salt of substituted
cyclopropenes, generated from the cyclopropene or by reaction of
the tribromocyclopropane with an alkyllithium, can be alkylated to
give new cyclopropene derivatives. 4
[0025] Compounds according to the present invention can also be
obtained from a malonate derivative as shown. 5
[0026] Methyl sterculate was formed by the procedure of Gensler et.
al. (Gensler, W. J.; Floyd, M. B.; Yanase, R.; Pober, K. W. J. Am.
Chem. Soc., 1970, 92, 2472). 6
[0027] The addition of a diazo compound to an acetylene is another
method that can be used for the synthesis of cyclopropenes
(Mueller, P.; Cranisher, C; Helv. Chim. Acta 1993, 76, 521).
Alternatively, the commercially available ethyl diazo acetate can
be added to the acetylene to give the compound: 7
[0028] with R'" being ethyl. This compound can be hydrolyzed to the
carboxylic acid, and reacted with oxalyl chloride to give the acid
chloride. The acid chloride can then be reacted with an alcohol to
give the ester. In the foregoing synthesis routes, R.sup.1-R.sup.4
are as described above for R.
[0029] Agricultural compositions comprising the compounds defined
by Formula (I) described above are also encompassed by the
invention. Preferably the compositions comprise between a lower
limit of 0.005, 5, 10, 20 or 30% and an upper limit of 70, 80, 90,
95 or 99% by weight of the active compounds of the present
invention. These compositions may optionally include various
additives typically found in agricultural compositions including,
but not limited to, carriers, adjuvants, wetting agents and the
like.
[0030] Numerous organic solvents may be used as carriers for the
active compounds of the present invention, e.g., hydrocarbons such
as hexane, benzene, toluene, xylene, kerosene, diesel oil, fuel oil
and petroleum naphtha, ketones such as acetone, methyl ethyl ketone
and cyclohexanone, chlorinated hydrocarbons such as carbon
tetrachloride, esters such as ethyl acetate, amyl acetate and butyl
acetate, ethers, e.g., ethylene glycol monomethyl ether and
diethylene glycol monomethyl ether, alcohols, e.g., ethanol,
methanol, isopropanol, amyl alcohol, ethylene glycol, propylene
glycol, butyl carbitol acetate and glycerine.
[0031] Mixtures of water and organic solvents, either as solutions
or emulsions, can also be employed as inert carriers for the active
compounds.
[0032] The active compounds of the present invention may also
include adjuvants or carriers such as talc, pyrophyllite, synthetic
fine silica, attapulgus clay (attaclay), kieselguhr, chalk,
diatomaceous earth, lime, calcium carbonate, bentonite, fuller's
earth, cottonseed hulls, wheat flour, soybean flour pumice,
tripoli, wood flour, walnut shell flour, redwood flour and
lignin.
[0033] It may be desirable to incorporate a wetting agent in the
compositions of the present invention. Such wetting agents may be
employed in both the solid and liquid compositions. The wetting
agent can be anionic, cationic or nonionic in character.
[0034] Typical classes of wetting agents include alkyl sulfonate
salts, alkylaryl sulfonate salts, alkyl sulfate salts, alkylamide
sulfonate salts, alkylaryl polyether alcohols, fatty acid esters of
polyhydric alcohols and the alkylene oxide addition products of
such esters, and addition products of long chain mercaptans and
alkylene oxides. Typical examples of such wetting agents include
the sodium alkylbenzene sulfonates having 10 to 18 carbon atoms in
the alkyl group, alkylphenol ethylene oxide condensation products,
e.g., p-isooctylphenol condensed with 10 ethylene oxide units,
soaps, e.g., sodium stearate and potassium oleate, sodium salt of
propylnaphthalene sulfonic acid (di-2-ethylhexyl), ester of sodium
sulfosuccinic acid, sodium lauryl sulfate, sodium stearate and
potassium oleate, sodium salt of the sulfonated monoglyceride of
coconut fatty acids, sorbitan, sesquioleate, lauryl trimethyl
ammonium chloride, octadecyl trimethyl ammonium chloride,
polyethylene glycol lauryl ether, polyethylene esters of fatty
acids and rosin acids (e.g., Ethofat.RTM. 7 and 13, commercially
available from Akzo Nobel Chemicals, Inc. of Chicago, Ill.), sodium
N-methyl-N-oleyltaurate, Turkey Red oil, sodium dibutyinaphthalene
sulfonate, sodium lignin sulfonate (Maraspers.RTM. N, commercially
available from LignoTech USA of Rothschild, Wis.), polyethylene
glycol stearate, sodium dodecylbenzene sulfonate, tertiary dodecyl
polyethylene glycol thioether, long chain ethylene oxide-propylene
oxide condensation products (e.g., Pluronic.RTM. 61 (molecular
weight 1,000) commercially available from BASF of Mount Olive,
N.J.), sorbitan sesquioleate, polyethylene glycol ester of tall oil
acids, sodium octyl phenoxyethoxyethyl sulfate, polyoxyethylene
(20) sorbitan monolaurate (Tween.RTM. 20, commercially available
from ICI Americas Inc. of Wilmington, Del.) tris (polyoxyethylene)
sorbitan monostearate (Tween.RTM. 60, commercially available from
ICI Americas Inc. of Wilmington, Del.), and sodium dihexyl
sulfosuccinate.
[0035] The solid, liquid, and gaseous formulations can be prepared
by various conventional procedures. Thus, the active ingredient, in
finely divided form if a solid, may be tumbled together with finely
divided solid carrier. Alternatively, the active ingredient in
liquid form, including mixtures, solutions, dispersions, emulsions
and suspensions thereof, may be admixed with the solid carrier in
finely divided form. Furthermore, the active ingredient in solid
form may be admixed with a liquid carrier to form a mixture,
solution, dispersion, emulsion, suspension or the like.
[0036] The active compounds of the present invention can be applied
to plants by various suitable means. For example, an active
compound may be applied alone in gaseous, liquid, or solid form by
contacting the compound with the plant to be treated. Additionally
the active compound may be converted to the salt form, and then
applied to the plants. Alternatively, compositions containing one
or more active compounds of the present invention may be formed.
The compositions may be applied in gaseous, liquid, or solid form
by contacting the composition with the plant to be treated. Such
compositions may include an inert carrier. Suitable solid carriers
include dusts. Similarly, when in gaseous form, the compound may be
dispersed in an inert gaseous carrier to provide a gaseous
solution. The active compound may also be suspended in a liquid
solution such as an organic solvent or an aqueous solution that may
serve as the inert carrier. Solutions containing the active
compound may be heterogeneous or homogeneous and may be of various
forms including mixtures, dispersions, emulsions, suspensions and
the like.
[0037] The active compounds and compositions thereof can also be
applied as aerosols, e.g., by dispersing them in air using a
compressed gas such as dichlorodifluoromethane,
trichlorofluoromethane, and other Freons, for example.
[0038] The term "plant" is used in a generic sense herein, and
includes woody-stemmed plants such as trees and shrubs. Plants to
be treated by the methods described herein include whole plants and
any portions thereof, such as field crops, potted plants, cut
flowers (stems and flowers), and harvested fruits and
vegetables.
[0039] Plants treated with the compounds and by the methods of the
present invention are preferably treated with a non-phytotoxic
amount of the active compound.
[0040] The present invention can be employed to modify a variety of
different ethylene responses. Ethylene responses may be initiated
by either exogenous or endogenous sources of ethylene. Ethylene
responses include, for example, the ripening and/or senescence of
flowers, fruits and vegetables, abscission of foliage, flowers and
fruit, the shortening of life of ornamentals such as potted plants,
cut flowers, shrubbery, seeds, and dormant seedlings, in some
plants (e.g., pea) the inhibition of growth, and in other plants
(e.g., rice) the stimulation of growth. Additional ethylene
responses or ethylene-type responses that may be inhibited by
active compounds of the present invention include, but are not
limited to, auxin activity, inhibition of terminal growth, control
of apical dominance, increase in branching, increase in tillering,
changing biochemical compositions of plants (such as increasing
leaf area relative to stem area), abortion or inhibition of
flowering and seed development, lodging effects, stimulation of
seed germination and breaking of dormancy, and hormone or epinasty
effects.
[0041] Methods according to embodiments of the present invention
inhibit the ripening and/or senescence of vegetables. As used
herein, "vegetable ripening" includes the ripening of the vegetable
while still on the vegetable-bearing plant and the ripening of the
vegetable after having been harvested from the vegetable-bearing
plant. Vegetables which may be treated by the method of the present
invention to inhibit ripening and/or senescence include leafy green
vegetables such as lettuce (e.g., Lactuea sativa), spinach (Spinaca
oleracea), and cabbage (Brassica oleracea), various roots, such as
potatoes (Solanum tuberosum) and carrots (Daucus), bulbs, such as
onions (Allium sp.), herbs, such as basil (Ocimum basilicum),
oregano (Origanum vulgare), dill (Anethum graveolens), as well as
soybean (Glycine max), lima beans (Phaseolus limensis), peas
(Lathyrus spp.), corn (Zea mays), broccoli (Brassica oleracea
italica), cauliflower (Brassica oleracea botrytis), and asparagus
(Asparagus officinalis).
[0042] Methods according to embodiments of the present invention
inhibit the ripening of fruits. As used herein, "fruit ripening"
includes the ripening of fruit while still on the fruit-bearing
plant as well as the ripening of fruit after having been harvested
from the fruit-bearing plant. Fruits which may be treated by the
method of the present invention to inhibit ripening include
tomatoes (Lycopersicon esculentum), apples (Malus domestics),
bananas (Musa sapientum), pears (Pyrus communis), papaya (Carica
papaya), mangoes (Mangifera indica), peaches (Prunus persica),
apricots (Prunus armeniaca), nectarines (Prunus persica nectarina),
oranges (Citrus sp.), lemons (Citrus limonia), limes (Citrus
aurantifolia), grapefruit (Citrus paradisi), tangerines (Citrus
nobilis deliciosa), kiwi (Actinidia chinenus), melons such as
cantaloupe (C. cantalupensis) and musk melon (C. melo), pineapple
(Aranas comosus), persimmon (Diospyros sp.), various small fruits
including berries such as strawberries (Fragaria), blueberries
(Vaccinium sp.) and raspberries (e.g., Rubus ursinus), green beans
(Phaseolus vulgaris), members of the genus Cucumis such as cucumber
(C. sativus), and avocados (Persea americana).
[0043] Ornamental plants which may be treated by the method of the
present invention to inhibit senescence and/or to prolong flower
life and appearance (e.g., delay wilting), include potted
ornamentals, and cut flowers. Potted ornamentals and cut flowers
which may be treated with the present invention include azalea
(Rhododendron spp.), hydrangea (Macrophylla hydrangea), hybiscus
(Hibiscus rosasanensis), snapdragons (Antirrhinum sp.), poinsettia
(Euphorbia pulcherima), cactus (e.g. Cactaceae schlumbergera
truncata), begonias (Begonia sp.), roses (Rosa spp.), tulips
(Tulipa sp.), daffodils (Narcissus spp.), petunias (Petunia
hybrida), carnation (Dianthus caryophyllus), lily (e.g., Lilium
sp.), gladiolus (Gladiolus sp.), alstroemeria (Alstoemeria
brasiliensis), anemone (e.g., Anemone blanda), columbine (Aquilegia
sp.), aralia (e.g., Aralia chinensis), aster (e.g., Aster
carolinianus), bougainvillea (Bougainvillea sp.), camellia
(Camellia sp.), bellflower (Campanula sp.), cockscomb (celosia
sp.), falsecypress (Chamaecyparis sp.), chrysanthemum
(Chrysanthemum sp.), clematis (Clematis sp.), cyclamen (Cyclamen
sp.), freesia (e.g., Freesia refracta), and orchids of the family
Orchidaceae.
[0044] Plants which may be treated by the method of the present
invention to inhibit abscission of foliage, flowers and fruit
include cotton (Gossypium spp.), apples, pears, cherries (Prunus
avium), pecans (Carva illinoensis), grapes (Vitis vinifera), olives
(e.g. Vitis vinifera and Olea europaea), coffee (Coffea arabica),
snapbeans (Phaseolus vulgaris), and weeping fig (ficus benjamina),
as well as dormant seedlings such as various fruit trees including
apple, ornamental plants, shrubbery, and tree seedlings. In
addition, shrubbery which may be treated according to the present
invention to inhibit abscission of foliage include privet
(Ligustrum sp.), photinea (Photinia sp.), holly (Ilex sp.), ferns
of the family Polypodiaceae, schefflera (Schefflera sp.), aglaonema
(Aglaonema sp.), cotoneaster (Cotoneaster sp.), barberry (Berberis
sp.), waxmyrtle (Myrica sp.), abelia (Abelia sp.), acacia (Acacia
sp.) and bromeliades of the family Bromeliaceae.
[0045] Active compounds of the present invention have proven to be
unexpectedly potent inhibitors of ethylene action on plants, fruits
and vegetables, even when applied at low concentrations. Among
other things, compounds of the present invention may result in a
longer period of insensitivity to ethylene than compounds found in
the prior art. This longer period of insensitivity may occur even
when compounds of the present invention are applied at a lower
concentration than previous compounds.
[0046] The present invention is explained in greater detail in the
following non-limiting Examples. In these examples, .mu.l means
microliters; ml means milliliters; nl means nanoliters; l means
liters; cm means centimeters; and temperatures are given in degrees
Celsius.
COMPARATIVE EXAMPLE A
[0047] Activity of Short-Chain Cyclopropene Derivatives
[0048] To obtain the minimum concentration that protected bananas
from 333 .mu.l/l of ethylene, compounds described in U.S. Pat. No.
5,518,988 to Sisler et al. were applied to bananas according to the
methods setforth herein. A known amount of an active compound was
injected as a gas into a 3-liter jar containing a banana. The jar
was sealed and the banana was removed after 24 hours. At the end of
exposure, the banana was treated with 333 .mu.l/l of ethylene in a
3-liter jar for 12-15 hours. It was then observed for ripening. The
minimum concentration is the minimum concentration that protected
the banana from 333 .mu.l/l of ethylene. Ten microliters/liter of
ethylene is usually considered to be a saturating amount.
[0049] To obtain the time of protection, bananas were exposed to a
saturating amount of the compound for 24 hours (this was done as
above and at least 10 times the minimum protection amount was
used). After exposure, bananas were removed from the jars and each
day individual bananas were exposed to 333 .mu.l/l of ethylene for
12-15 hours. The day the bananas responded to ethylene was recorded
as the protection time. The results are shown in Table A.
1TABLE A Minimum Concentration and Time of Insensitivity for
1-Cyclopropenes Described in U.S. Pat. No. 5,518,988 to Sisler et
al. Con- centration Time Compound Structure (nl/l) (days)
cyclopropene (CP) 8 0.7 12 1-methylcyclopropene (1-MCP) 9 0.7 12
1-ethylcyclopropene (1-ECP) 10 4 12 1-propylcyclopropene (1-PCP) 11
6 12 1-butylcyclopropene (1-BCP) 12 3 12
EXAMPLE 1
[0050] Compounds of the Present Invention: Minimum Concentration
for Protection
[0051] To obtain the minimum concentration that protected bananas
from 333 .mu.l/l of ethylene, compounds according to the present
invention were applied to bananas according to the method described
herein. A known amount of the active compound was placed on filter
paper in a 3-liter jar to facilitate evaporation into the vapor
state. The compounds were applied in an ethyl ether solution
because the amount used was potentially too small to apply unless
they were in solution. The amount of ether (about 10 .mu.l in 3 l)
was without effect when applied alone on a banana contained in a
3-liter jar. The jar was sealed and the banana was removed after 4
hours of exposure. At the end of exposure, the banana was treated
with 333 .mu.l/l of ethylene in a 3-liter jar for 12-15 hours. It
was then observed for ripening. The minimum concentration is the
concentration that protected the bananas from 333 .mu.l/l of
ethylene. Ten microliters/liter of ethylene is usually considered
to be a saturating amount. This procedure was repeated for 8-, 24-
and 48-hour treatment times to determine the minimum concentration
of active compounds of the present invention needed to provide
protection from 333 .mu.l/l of ethylene for a given treatment time.
The results are shown in Table 1.
2TABLE 1 Treatment Time and Minimum Concentration of
1-Cyclopropenes of the Present Invention on Banana Fruit Treatment
Time Minimum Concentration Active Compound (hours) (nl/l)
1-hexylcyclopropene 4 12.0 8 0.8 24 0.4 48 0.3 1-octylcyclopropene
4 0.8 8 0.45 24 0.3 48 0.25
EXAMPLE 2
[0052] Compounds of the Present Invention: Time of Protection
[0053] To obtain the time of protection, bananas were exposed to a
saturating amount of the compound for 24 hours (this was done as
described in Example 1 above and at least 10 times the minimum
protection amount was used). After exposure, bananas were removed
from the jars and each day individual bananas were exposed to 333
.mu.l/l of ethylene for 12-15 hours. The day the bananas responded
to ethylene was recorded as the protection time. The results are
shown in Table 2.
3TABLE 2 Minimum Concentration and Time of Insensitivity for
1-Cyclopropenes Provided by the Present Invention Con- centration
Time Active Compound Structure (nl/l) (days) 1-hexylcyclopropene
(1-HCP) 13 0.4 20 1-octylcyclopropene (1-OCP) 14 0.3 25
EXAMPLES 3 THROUGH 29
[0054] In general, all cyclopropenes are stored at -80.degree. C.
All reactions were carried out under an atmosphere of nitrogen.
Flash chromatography of cyclopropenes was carried out under an
atmosphere of nitrogen. All target compounds were 80% or greater
purity unless otherwise noted.
EXAMPLE 3
[0055] Preparation of N,
N'-dibenzyl-N,N,N',N'-tetramethylethylenediammoni- um dibromide and
N,N'-dibenzyl-N,N,N',N'-tetraethylethylenediammonium dibromide
[0056] To a stirred solution of 16.5 g (142 mmol) of
N,N,N',N'-tetramethylethylenediamine in 60 g of acetonitrile was
added 50.1 g (292 mmol) of benzyl bromide. The mixture self warmed
and was allowed to stir for 2.5 hours whereon a heavy precipitate
was observed. The slurry was diluted with diethyl ether, filtered,
washed with diethyl ether and dried yielding 61.8 g of the desired
N,N'-dibenzyl-N,N,N',N'-te- tramethylethylenediammonium dibromide,
a white solid mp 230-232.degree. C.
[0057] In an analogous way, using
N,N,N',N'-tetraethylethylenediamine one obtains
N,N'-dibenzyl-N,N,N',N'-tetraethylethylenediammonium dibromide, a
white solid mp 190-193.degree. C., decomposes.
EXAMPLE 4
[0058] Preparation of 1-Hexyl-cyclopropene (Compound 1)
[0059] a. 2-Bromo-oct-1-ene
[0060] A solution of 9.42 ml (0.0728 mol) of 2,3-dibromopropene in
70 ml diethylether was placed under a nitrogen atmosphere by use of
a Firestone valve. While cooling in an ice water bath, a solution
of 0.091 mol of pentylmagnesium bromide in 70 ml diethyl ether was
added slowly via addition funnel. After stirring for 2 hours while
warming to room temperature, there was then added via syringe 50 ml
of 1 N hydrochloric acid to the reaction cooling in an ice water
bath. The resulting mixture was transferred to a separatory funnel
and the phases were separated. The organic layer was dried over
MgSO.sub.4 and filtered. The solvent was removed from the filtrate
in vacuo to yield 15.0 g (85.7% of theory) of 81 % pure
2-bromo-oct-1-ene as an oil.
[0061] b. 1,1,2-Tribromo-2-hexyl-cyclopropane
[0062] To 5.42 g (0.0284 mol) of 2-bromo-oct-1-ene in 7.42 ml
(0.0851 mol) of bromoform and 48.8 ml of methylene chloride, were
added 1.30 g (0.00284 mol) of
N,N'-dibenzyl-N,N,N',N'-tetramethylethylenediammonium dibromide and
12.1 ml (0.142 mol) of 45% aqueous potassium hydroxide. The mixture
was left at room temperature for 5 days. There was then added
hexanes and water. This mixture was gravity filtered through
qualitative fluted filter paper. The resulting mixture was
transferred to a separatory funnel and the phases were separated.
The organic layer was dried over MgSO.sub.4 and filtered. The
solvent was removed from the filtrate in vacuo to yield 5.25 g
(51.0% of theoretical) of 1,1,2-tribromo-2-hexyl-cyclopropane as an
oil.
[0063] c. 1 -Hexyl-cyclopropene
[0064] A solution of 1.01 g (0.00278 mol) of
1,1,2-tribromo-2-hexyl-cyclop- ropane in 4 ml of diethyl ether was
placed under a nitrogen atmosphere via use of a Firestone valve.
While cooling in an ice water bath, 6.3 ml (0.00835 mol) of 1.4M
methyl lithium in diethyl ether was added slowly by syringe. After
15 minutes, 2 ml of water was added via syringe. The resulting
mixture was transferred to a separatory funnel and the phases were
separated. The organic layer was dried over MgSO.sub.4 and
filtered. The solvent was removed from the filtrate in vacuo with a
bath temperature under 20.degree. C. to yield 0.300 g (87% of
theoretical) of 1-hexyl-cyclopropene pure as an oil.
EXAMPLE 5
[0065] Preparation of 3-Octylcyclopropene (Compound 2)
[0066] 1-Bromo-dec-1-ene was prepared by the method of Millar et al
(Millar, J. G.; Underhill, E. W.; J. Org. Chem. 1986, 51, 4726).
This olefin was converted to 3-octylcyclopropene in a similar
manner to the preparation of 70% pure 1-hexylcyclopropene.
EXAMPLE 6
[0067] Preparation of 1-(7-Methoxyheptyl)-cyclopropene (Compound
3)
[0068] 6-Bromohexyl methyl ether was prepared from
1,6-dibromohexane. To 48.8 g (200 mmol) of 1,6-dibromohexane at
60.degree. C. was added 44 g (200 mmol) of a 25% solution of sodium
methoxide in methanol. The reaction mixture was held 0.5 hours,
then an additional 4 g of sodium methoxide solution was added, and
the reaction mixture was held an additional hour. Hexane and water
were added, the organic phase was washed with brine and dried with
magnesium sulfate, filtered and stripped. Fractional distillation
under vacuum gave 93% pure 6-bromohexyl methyl ether. This bromide
was converted to the Grignard reagent, which was converted to
1-(7-methoxyheptyl)-cyclopropene in the same manner that
pentylmagnesium bromide was converted to 1-hexylcyclopropene.
EXAMPLE 7
[0069] Preparation of 1-(Undec-5-ynl)-cyclopropene (Compound 4)
[0070] 1-Bromodec-4-yne was prepared from 1-chlorodec-4-yne. The
1-chlorodec-4-yne (10.6 g, 61 mmol) and 25 g of lithium bromide
were refluxed in 80 ml of THF for 21 hours. The conversion was 74%.
Ether was added, the reaction mixture was washed with water
(2.times.) and brine, dried over magnesium sulfate and stripped.
The product was dissolved in 70 ml of THF and refluxed for 8 hours
with an additional 25 g of lithium bromide. This gave 95%
conversion of the chloride to the bromide. The same workup provided
11.36 g of 1-bromodec-4-yne.
[0071] The 1-bromodec-4-yne was converted to the Grignard reagent
in THF. The Grignard reagent was converted to
1-(undec-5-ynl)-cyclopropene in the same manner that
pentylmagnesium bromide was converted to 1-hexylcyclopropene.
EXAMPLE 8
[0072] Preparation of 1-(7-Hydroxyheptyl)-cyclopropene (Compound
5)
[0073] a. 1 -(1 -Ethoxyethoxy)-6-bromohexane
[0074] To a cooled solution of 80 mg of toluenesulfonic acid in 40
ml of ether was fed 20 g (110 mmol) of 6-bromohexanol and 40 ml of
ethyl vinyl ether simultaneously by separate additional funnels.
The temperature of the reaction mixture was kept at 7.degree. C. or
lower during the feeds, which took 1 hour. The reaction mixture was
stirred 20 minutes longer, then roughly 1 ml of triethylamine was
added. The reaction mixture was washed with water and brine, dried
over potassium carbonate, filtered and stripped to give 25.7 g of a
pale yellow liquid, which was used without further
purification.
[0075] b. 9-(1-Ethoxyethoxy)-2-bromonon-1-ene
[0076] A slurry of 5.6 g of magnesium turnings (230 mmol) in 100 ml
of THF was treated with a small amount of 1,2-dibromoethane.
1-(1-Ethoxyethoxy)-6-bromohexane (38.5 g, 152 mmol) was fed slowly
to the reaction mixture, maintaining the temperature at
40-50.degree. C. At the end of the addition the reaction mixture
was held 20 minutes, then transferred by cannula to solution of
33.4 g (167 mmol) of 1,2-dibromoprop-2-ene in 25 ml of THF at
0.degree. C. The reaction mixture was stirred at 0.degree. C. for
15 minutes, then stirred at room temperature for 15 minutes, then
quenched with water. The reaction mixture was transferred into a
separatory funnel. A small amount of 1 N HCl was added, the phases
were separated, the ether phase was washed with water and brine,
then dried over magnesium sulfate, filtered, and stripped to give
33.63 g of a yellow liquid which was used without further
purification.
[0077] c. 1,1,2-Tribromo-2-(7-hydroxyheptyl)cyclopropane
[0078] A mixture of 9-(1-ethoxyethoxy)-2-bromonon-1-ene (33.63g,
115 mmol), 4.1 g of
N,N'-dibenzyl-N,N,N',N'-tetraethylethylenediammonium dibromide, 42
g of 45% potassium hydroxide (337 mmol), 93 g of bromoform (368
mmol) and 280 g of methylene chloride were rapidly stirred at room
temperature for two days. When the reaction stalled, the reaction
mixture was transferred to a separatory funnel and washed with
water. The methylene chloride phase was transferred to a flask and
treated with the same amount of the phase transfer catalyst and 45%
potassium hydroxide, then stirred at room temperature for an
additional 3 days. The reaction mixture was washed with water, the
methylene chloride phase was dried with magnesium sulfate, and then
stripped. The product was treated with 320 ml of methanol and 40 ml
of 1 N HCl for 1 hour at room temperature. The methanol was
stripped, ethyl acetate was added. The organic phase was washed
with water and brine, then treated with 200 ml of silica gel.
Filtration followed by a strip gave 38 g of black product. This was
chromatographed on silica gel to give 19.0 g of
1,1,2-tribromo-2-(7-hydro- xyheptyl)cyclopropane as a pale yellow
liquid.
[0079] d. 1-(7-Hydroxyheptyl)-cyclopropene
[0080] A solution of 1.0 g
1,1,2-tribromo-2-(7-hydroxyheptyl)cyclopropane (2.5 mmol) in 25 ml
of ether was treated at -78.degree. C. with 7.2 ml of methyllithium
(1.4 M, 10 mmol). After 5 minutes, the reaction mixture was warmed
to 0.degree. C. and held at this temperature. The reaction was
quenched with saturated ammonium chloride. The reaction mixture was
washed with water and brine, dried over magnesium sulfate, filtered
and stripped to give 240 mg of 1-(7-hydroxyheptyl)-cyclopropene
(90% purity).
EXAMPLE 9
[0081] Preparation of 1-(7-Acetoxyheptyl)-cyclopropene (Compound
6)
[0082] A solution of 2.5 mmol of 1-(7-hydroxyheptyl)-cyclopropene
in 5 ml of ether was cooled in an ice bath. Triethylamine (0.44 ml)
and 0.21 g (2.7 mmol) of acetyl chloride were added, and the
reaction mixture was stirred 1 hour at 5.degree. C. Additional
acetyl chloride (0.11 g), ether and triethylamine were added, and
the reaction was stirred at 5.degree. C. until GC analysis
indicated 95% conversion. The reaction was worked up by adding more
ether and washing the organic phase with water, dilute HCl solution
(diluted 1M aqueous HCl), potassium carbonate solution (2.times.),
water and brine. The ether phase was dried over magnesium sulfate
and stripped. Hexane was added and the reaction was stripped again
to give 1-(7-acetoxyheptyl)-cyclopropene.
EXAMPLE 10
[0083] Preparation of 7-Cycloprop-1-enyl-heptanoic acid (Compound
7)
[0084] a. 7-(1,1,2-Tribromo-cyclopropyl)-heptanoic acid:
[0085] 1,1,2-Tribromo-2-(7-hydroxyheptyl)cyclopropane (0.90 g, 2.3
mmol) was dissolved in 60 ml of glacial acetic acid. A solution of
1.0 g (10 mmol) of chromium trioxide dissolved in 14 ml of 90%
aqueous acetic acid was added and the reaction mixture was stirred
at room temperature for 24 hours. Water (300 ml)was added. The
solution was extracted with ether. The ether phase was extracted
three times with 1N NaOH solution. A little sodium bisulfite was
added. The aqueous extracts were acidified with 6N HCl, and
extracted with ether twice. The ether extracts were washed with
brine, dried over magnesium sulfate and stripped to give 0.56 g
7-(1,1,2-tribromo-cyclopropyl)-heptanoic acid.
[0086] b. 7-Cycloprop-1-enyl-heptanoic acid:
[0087] 1,1,2-Tribromo-2-(7-carboxyheptyl)-cyclopropane (1.28 g, 3.1
mmol) was dissolved in 60 ml of ether and cooled to -78.degree. C.
Methyllithium (9.0 ml, 12.6 mmol) was added and the reaction was
stirred at -78.degree. C. for two hours. The reaction mixture was
put in an ice bath for 5 minutes, then recooled to -78.degree. C.
until workup. Water was added to the reaction mixture, which was
warmed to room temperature. The aqueous phase was separated, and
the ether phase was extracted with three times with 1N NaOH
solution. The combined aqueous extracts were acidified with aqueous
HCl, and extracted with ether three times. The ether extracts were
washed with brine, dried over magnesium sulfate and stripped to
give 300 mg of 7-cycloprop-1-enyl-heptanoic acid.
EXAMPLE 11
[0088] Preparation of 7-Cycloprop-1-enyl-heptanoic acid
isopropylamine salt (Compound 8)
[0089] A solution of 7-cycloprop-1-enyl-heptanoic acid ethyl ester
in 5 ml of ether was treated with 0.1 g of isopropyl amine at room
temperature. The solvent was stripped to give 40 mg of
7-cycloprop-1-enyl-heptanoic acid isopropylamine salt.
EXAMPLE 12
[0090] Preparation of 7-Cycloprop-1-enyl-heptanoic acid ethyl ester
(Compound 9)
[0091] A solution of 220 mg (1.3 mmol) of
1-(7-carboxyheptyl)-cyclopropene in ether was cooled to 0.degree.
C. Triethylamine (0.20 g, 2 mmol) was added, then 0.12 g (1.3 mmol)
of methylchloroformate was added. After 2 hours at 0.degree. C.,
the reaction mixture was transferred to a separatory funnel. The
ether phase was washed with water (2.times.) and brine, dried over
magnesium sulfate, filtered and stripped. The product was dissolved
in ethanol, cooled in an ice bath and treated with 1 ml of a 21%
sodium ethoxide in ethanol solution. The reaction mixture was
stirred 1/2 hour, then water and ether were added. The ether phase
was washed with 1N sodium hydroxide solution, water, and brine,
dried over magnesium sulfate, filtered and stripped to give 10 mg
of 75% pure 7-cycloprop-1-enyl-heptanoic acid ethyl ester.
EXAMPLE 13
[0092] Preparation of 1-(7-Cyanoheptyl)-cyclopropene (Compound
10)
[0093] a. 1-(7-Methanesulfonyloxyheptyl)-cyclopropene
[0094] A solution of 3.8 mmol of 1-(7-hydroxyheptyl)-cyclopropene
in 50 ml of ether was cooled in an ice bath. Triethylamine (1 ml)
and 0.48 g of methanesulfonyl chloride (4.2 mmol) were added and
the reaction mixture was stirred for 21/2 hours at 0.degree. C. The
reaction mixture was washed with water and brine, dried over
magnesium sulfate, filtered and stripped to give
1-(7-methanesulfonyloxyheptyl)-cyclopropene which was used without
further purification.
[0095] b. 1-(7-Cyanoheptyl)-cyclopropene
[0096] The crude product from the above reaction was dissolved in 5
ml of DMSO, and treated with 0.99 g (15 mmol) of potassium cyanide.
After 6.5 hours at room temperature, the reaction was 72% complete.
Ether and water were added. The aqueous phase was washed with more
ether. The combined organic phases were washed with water
(2.times.) and brine, dried over magnesium sulfate, filtered and
stripped. The product was rapidly chromatographed on silica gel to
give 190 mg of 1-(7-cyanoheptyl)-cyclopr- opene as a colorless
liquid, >95% purity.
EXAMPLE 14
[0097] Preparation of 1-(7-N,N-Diethylaminoheptyl)-cyclopropene
(Compound 1 1)
[0098] a.
1,1,2-Tribromo-2-(7-N,N-diethylaminoheptyl)-cyclopropane
[0099] A solution of 1.5 g of
1,1,2-Tribromo-2-(7-hydroxyheptyl)cyclopropa- ne (3.8 mmol) in 10
ml of ether was cooled in an ice bath and treated with 0.77 g (6
mmol) of diisopropylethyl amine. Triflic anhydride (1.18 g, 4.2
mmol) was added dropwise, and the reaction was stirred at 0.degree.
C. for 1/2 hour. Excess diethylamine (roughly 4 ml) was added and
the reaction was stirred overnight. The reaction mixture was
quenched with water and transferred to a separatory funnel. A small
amount of 1N NaOH was added. The aqueous phase was separated, the
organic phase was washed twice more with water, then extracted
three times with 1N HCl. The acidic washes were treated made basic
with aqueous sodium hydroxide solution and extracted three times
with ether. The ether was washed with brine, dried over potassium
carbonate and stripped. The product was chromatographed through
Florisil to give 1,1 ,2-tribromo-2-(7-N,N-diethylaminoheptyl)-cyc-
lopropane.
[0100] b. 1-(7-N,N-Diethylaminoheptyl)-cyclopropene
[0101] To a solution of 1.0 g (2.4 mmol) of
1,1,2-tribromo-2-(7-N,N-diethy- laminoheptyl)-cyclopropane in 25 ml
of THF at -78.degree. C. was added 4.55 ml (1.6 M, 7.3 mmol) of
n-BuLi. The reaction mixture was stirred 1/2 hour, then quenched
with methanol. The reaction mixture was warmed to room temperature.
Ether was added, the organic phase was washed with water (3.times.)
and brine, dried over magnesium sulfate, and filtered. The solution
was stripped on a rotary evaporator with no heat added. A few
pipetfuls of toluene were added, and the sample was stripped again
to give 1-(7-N,N-diethylaminoheptyl)-cyclopropene.
EXAMPLE 15
[0102] Preparation of 1-(7-N,N,-Diethylammoniumheptyl)-cyclopropene
acetate (Compound 12)
[0103] A solution of 1-(7-N,N,-diethylamminoheptyl)-cyclopropene in
ether was treated with acetic acid. The solvent was removed to give
the salt.
EXAMPLE 16
[0104] Preparation of
1-(7-N,N,N-Diethylmethylammoniumheptyl)-cyclopropene iodide
(Compound 13)
[0105] A mixture of roughly 1.6 mmol of
1-(7-N,N-diethylaminoheptyl)-cyclo- propene and excess iodomethane
(roughly 1/2 ml in 5 ml of acetonitrile were stirred at room
temperature for two hours. The reaction mixture was stripped to
give 300 mg of 1-(7-N,N, N-diethylmethylammoniumheptyl)-cyclo-
propene iodide.
EXAMPLE 17
[0106] Preparation of 1-Hexyloxymethyl-cyclopropene (Compound
14)
[0107] a. Preparation of 2-Bromo-3-hexyloxypropene
[0108] To a three neck round bottom flask equipped with an addition
funnel and an overhead stirrer was added 35 ml of hexane, 42 g of
50% sodium hydroxide and 0.50 g of tetra-n-butylammonium bromide. A
mixture of 6.74 g of hexanol (66 mmol) and 20 g (100 mmol) of
2,3-dibromopropene were fed to the well-stirred reaction mixture
over a 20 minute period. The reaction was stirred an additional 1
hour, then water was added, and the phases were separated. The
organic phase was washed with water and brine, dried over magnesium
sulfate, filtered and stripped. The product was fractionally
distilled under reduced pressure to give 6.1 g of 95% pure
2-bromo-3-hexyloxypropene.
[0109] b. 1,1,2-Tribromo-2-(hexyloxymethyl)cyclopropane
[0110] A mixture of 5.9 g of 2-bromo-3-hexyloxypropene(26.7 mmol),
2.05 g of N,N'-dibenzyl-ethane-1,2-bis-(diethylammonium bromide),
10.5 g of 45% potassium hydroxide (84 mmol), 23.3 g of bromoform
(92 mmol) and 70 g of methylene chloride were rapidly stirred at
room temperature for two days. When the reaction stalled, the
reaction mixture was transferred to a separatory funnel and washed
with water. The methylene chloride phase was transferred to a flask
and treated with the same amount of the phase transfer catalyst and
45% potassium hydroxide, then stirred at room temperature for an
additional 3 days. The workup-recharge sequence was repeated once
more, and the reaction was stirred one more day at room
temperature. The reaction mixture was washed with water, the
methylene chloride phase was dried with magnesium sulfate, and then
stripped. The product was chromatographed on silica gel with 20%
ethyl acetate 80% hexane to give 1.35 g of 87% pure
1,1,2-tribromo-2-(hexyloxymethyl)cyclop- ropane.
[0111] c. 1-Hexyloxymethyl-cyclopropene
[0112] A solution of 1.15 g of
1,1,2-tribromo-2-(hexyloxymethyl)cyclopropa- ne (2.9 mmol) in 6 ml
of ether was treated at -78.degree. C. with 1.4 ml of methyllithium
(1.4 M, 8.8 mmol). After 5 minutes, the reaction mixture was warmed
to 0.degree. C. and held at this temperature. The reaction was
quenched with saturated ammonium chloride. The reaction mixture was
washed with water and brine, dried over magnesium sulfate, filtered
and stripped to give 320 mg of 1-hexyloxymethyl-cyclopropene, as a
dark yellow liquid.
EXAMPLE 18
[0113] Preparation of 1-Pentyloxyethyl-cyclopropene (Compound
15)
[0114] a. Preparation of 2-Bromo-4-pentyloxybutene
[0115] To a three neck round bottom flask equipped with an addition
funnel and an overhead stirrer was added 35 ml of hexane, 42 g of
50% sodium hydroxide and 0.50 g of tetra-n-butylammonium bromide. A
mixture of 10 g of 2-bromobuten-4-ol (66 mmol) and 15 g (100 mmol)
of 2,3-dibromopropene were fed to the well-stirred reaction
mixture. When the addition was complete, the reaction mixture was
warmed to for 1 hour, then water was added, and the phases were
separated. The organic phase was washed with water and brine, dried
over magnesium sulfate, filtered and stripped. A column was run
(silica gel, 20% ethyl acetate/80% hexane) to give product that was
70% pure. The more volatile material was removed by distillation
under reduced pressure; the material left in the pot was 1.63 g of
99% pure 2-bromo-4-pentyloxybutene.
[0116] This olefin was converted to 1-pentyloxyethyl-cyclopropene
in the same manner that 2-bromo-3-hexyloxypropene was converted to
1-hexyloxymethyl-cyclopropene.
EXAMPLE 19
[0117] Preparation of 3,3-Dipentyl-cyclopropene (Compound 16)
[0118] a. 2-Pentyl-hept-1-ene
[0119] To a 500 ml, 3 necked, round bottom flask, which was
previously placed under a nitrogen atmosphere via use of a
Firestone valve, was added 8.50 g (0.0759 mol) of potassium
t-butoxide and 27.2 g (0.0762 mol) of methyl triphenylphosphonium
bromide and 200 ml tetrahydrofuran. After stirring at room
temperature for 4 hours, 12.0 ml (0.0849 mol) of 6-undecanone was
added. After 3 days, the reaction mixture was poured onto 200 ml
10% w/v aqueous ammonium chloride. The resulting mixture was
transferred to a separatory funnel, extracted twice with hexanes
and the phases were separated. The combined organic layers were
dried over MgSO.sub.4 and filtered. The solvent was removed from
the filtrate in vacuo to yield 18.5 g orange solid. This was
slurried in 125 ml diethyl ether and gravity filtered through
qualitative fluted filter paper rinsing with an additional 125 ml
diethyl ether. The solvent was removed from the filtrate in vacuo
to yield 12.7 g orange oil. This residue was purified by column
chromatography with hexanes to give 6.79 g (47.5% of theoretical)
of 2-pentyl-hept-1-ene as an oil.
[0120] b. 2,2-Dibromo-1,1-dipentyl-cyclopropane
[0121] To a solution of 4.16 g (0.0247 mol) of 2-pentyl-hept-1-ene
in 31 ml of pentanes, was added 4.95 g (0.0441 mol) of potassium
t-butoxide. While cooling the resulting mixture to an internal
temperature of 5.degree. C., 4.01 ml ( 0.0459 mol) of bromoform was
added slowly via addition funnel. The reaction mixture was allowed
to warm naturally to room temperature and left overnight. To the
reaction mixture was added 25 ml of water then 36 ml of 1N
hydrochloric acid. The resulting mixture was transferred to a
separatory funnel and the phases were separated. The organic layer
was dried over MgSO.sub.4 and filtered. The solvent was removed
from the filtrate in vacuo to yield 7.00 g (83.4 % of theory) of
2,2-dibromo-1,1-dipentyl-cyclopropane as an oil.
[0122] c. 2-Bromo-1,1-dipentyl-cyclopropane
[0123] To a solution of 4.00 g (0.0118 mol) of
2,2-dibromo-1,1-dipentyl-cy- clopropane in 11 ml of methanol was
added 0.744 ml ( 0.0129 mol) of glacial acetic acid and 0.766 g
(0.0118 mol) of zinc dust. After 2 hours 0.744 ml of glacial acetic
acid and 0.766 g of zinc dust were added to the mixture. After 2
further hours, the solvent was removed from the reaction mixture in
vacuo. The resulting residue was extracted with hexanes and then
diethyl ether from water. The combined organic layers were dried
over MgSO.sub.4 and filtered. The solvent was removed from the
filtrate in vacuo to yield 2.1 g (68.2% of theory) of an equal
mixture of 2-bromo-1,1-dipentyl-cyclopropane and
1,1-dipentyl-cyclopropane as an oil.
[0124] d. 3,3-Dipentyl-cyclopropene
[0125] To a solution of 1.90 g of an equal mixture of
2-bromo-1,1-dipentyl-cyclopropane and 1,1-dipentyl-cyclopropane in
10 ml dimethylsulfoxide was added 0.818 g (0.00308 mol) of
potassium t-butoxide. The resulting mixture was heated to
85.degree. C. for 5 hours and then stirred at room temperature for
16 hours. To this was added 0.100 g of potassium t-butoxide. The
resulting mixture was heated to 85.degree. C. for 2 hours then
cooled to room temperature. The reaction mixture was poured onto
water and then extracted with diethyl ether. The resulting mixture
was transferred to a separatory funnel and the phases were
separated. The organic layer was dried over MgSO.sub.4 and
filtered. The solvent was removed from the filtrate in vacuo to
yield 1.90 g of 3,3-dipentyl-cyclopropene mixed in equal parts with
1,1-dipentyl-cyclopropane as an oil.
EXAMPLE 20
[0126] Preparation of 1-Pent-2-enyl-2-pentyl-cyclopropene (Compound
17)
[0127] A solution of 1.00 g (0.00287 mol) of
1,1,2-tribromo-2-pentyl-cyclo- propane in 4 ml of tetrahydrofuran
was placed under an inert atmosphere of nitrogen via a Firestone
valve. To this mixture, cooling in an ice water bath, was added via
syringe 3.58 ml (0.00861 mol) of 1.6M n-butyllithium in hexanes.
After 30 minutes, 0.432 ml (0.00287 mol) of tetramethylethylene
diamine and 0.339 ml (0.00287 mol) of 1-bromo-2-pentene were added
by syringe. The reaction stirred for one hour while warming to room
temperature, then for three hours at room temperature. To the
resulting mixture was added 2 ml of water. This residue was
extracted with diethyl ether. The resulting mixture was transferred
to a separatory funnel and the phases were separated. The organic
layer was dried over MgSO.sub.4 and filtered. The solvent was
removed from the filtrate in vacuo to yield 0.200 g (39.1% of
theory) of 1-pent-2-enyl-2-pentyl-cyclopropene as an oil.
EXAMPLE 21
[0128] Preparation of 1-Pent-2-enyl-3,3-dipentyl-cyclopropene
(Compound 18)
[0129] A solution of 0.450 g of a 1:1 mixture of
3,3-dipentyl-cyclopropene and 1,1-dipentyl-cyclopropane in 2 ml of
tetrahydrofuran with 0.070 (0.000500 mol) ml of diisopropylamine
was placed under an inert atmosphere of nitrogen via a Firestone
valve. To this mixture, cooling in an ice water bath, was added via
syringe 1.72 ml (0.00275 mol) of 1.6M N-butyllithium in hexanes.
After 1 hour, 0.478 ml hexamethylphosphoramide and 0.325 ml of
1-bromo-2-pentene were added separately via syringe. The reaction
mixture was allowed to warm to room temperature and stirred for 2
days. The reaction was quenched by the addition of 2 ml of water by
syringe. This residue was extracted with diethyl ether. The
resulting mixture was transferred to a separatory funnel and the
phases were separated. The organic layer was dried over MgSO.sub.4
and filtered. The solvent was removed from the filtrate in vacuo to
yield 0.280 g of 1:1 mixture of
1-pent-2-enyl-3,3-dipentyl-cyclopropene and
1,1-dipentyl-cyclopropane as an oil.
EXAMPLE 22
[0130] Preparation of 1-(Oct-7-enyl)-cyclopropene (Compound 19)
[0131] Cyclopropene was prepared according to the following
reference: Binger, P.; Wedemann, P.; Goddard, R.; Brinker, U.; J.
Org. Chem., 1996, 61, 6462.
[0132] 8-Iodooct-1-ene was prepared by refluxing 5 g of
8-bromooct-1-ene (26 mmol) and 10 g of sodium iodide in 50 ml of
acetone for 1 hour. The acetone was stripped and the residue was
partitioned between water and ether. The aqueous phase was washed
with brine, dried over magnesium sulfate and stripped to give 5.66
g of 8-iodooct-1-ene.
[0133] A mixture of 0.43 g (11 mmol) of sodium amide in roughly 15
ml of ammonia was cooled to -78.degree. C. A chilled solution of
cyclopropene in ammonia (1:1, 0.85 g, 10 mmol) was poured into the
reaction mixture. The reaction mixture was stirred at -78.degree.
C. for 1/2 hour, warmed briefly to the ammonia boiling point, then
recooled to -78.degree. C. 8-Iodooct-1-ene (1.2 g, 5 mmol) was
added by syringe, and the reaction mixture was warmed to reflux for
1/2 hour. A few ml of ethanol were added. Ether (25 ml) was slowly
added while the ammonia was allowed to distill out of the reaction
mixture. The reaction mixture was washed with water, 0.5M HCl
(2.times.), water and brine. It was dried over MgSO.sub.4, filtered
and stripped. The product was purified by chromatography on silica
gel using hexane as the eluent. A 10 mg sample of 67% pure
1-(oct-7-enyl)-cyclopropene was obtained.
EXAMPLE 23
[0134] Preparation of 4-(1-Cyclopropenyl)-2-methylbutan-2-ol
(Compound 20)
[0135] a. 4-Bromo-pent-4-enoic acid ethyl ester
[0136] This ester was prepared by the method of Mori, JOC, 1983 48,
4062
[0137] b. 3-(1,2,2-Tribromo-cyclopropyl)-propionic acid ethyl
ester
[0138] To a solution made of 12.12 g (58 mmol) of
4-bromo-pent-4-enoic acid ethyl ester and 51 g (202 mmol) of
bromoform and 100 g of methylene chloride was added 2.0 g of
N,N'-dibenzyl-N,N,N',N'-tetramethylethylenedi- ammonium dibromide
and 27.1 g (218 mmol) of 45% aqueous potassium hydroxide. The
reaction mixture was stirred rapidly for 4 days. The resulting
mixture was transferred to a separatory funnel and the phases were
separated. The solvent was removed from the isolated organic layer
in vacuo. This residue was extracted with hexanes from water. The
resulting mixture was transferred to a separatory funnel and the
phases were separated. The organic layer was dried over MgSO.sub.4
and filtered. The solvent was removed from the filtrate in vacuo.
This residue was purified by column chromatography with 10% diethyl
ether/hexanes to yield 14.6 g (66.3% of theory) of
3-(1,2,2-tribromo-cyclopropyl)-propionic acid ethyl ester.
[0139] c. 4-(1-Cyclopropenyl)-2-methylbutan-2-ol
[0140] A solution of 1.08 g (0.00285 mol) of
3-(1,2,2-tribromo-cyclopropyl- )-propionic acid ethyl ester in 4 ml
of diethyl ether was placed under a nitrogen atmosphere by use of a
Firestone valve. While cooling in an ice water bath, 10.2 ml
(0.0142 mol) of 1.4 M methyl lithium in diethyl ether was added
slowly via syringe. After 15 minutes, 2 ml of water was added via
syringe. The resulting mixture was transferred to a separatory
funnel and the phases were separated. The organic layer was dried
over MgSO.sub.4 and filtered. The solvent was removed from the
filtrate in vacuo with a bath temperature under 20.degree. C. to
yield 0.380 g of 75% pure with remainder being diethyl ether (79%
of theoretical yield corrected for ether) of
4-cycloprop-1-enyl-2-methyl-butan-2-ol as an oil. Product is stored
at -80.degree. C.
EXAMPLE 24
[0141] Preparation of Methyl sterculate (Compound 21)
[0142] Methyl sterculate (40% purity) was formed by the procedure
of Gensler et. al. (Gensler, W. J.; Floyd, M. B.; Yanase, R.;
Pober, K. W. J. Am. Chem. Soc., 1970, 92, 2472).
EXAMPLE 25
[0143] Preparation of Hex-5-yne
2-octylcycloprop-2-ene-1-carboxylate (Compound 22)
[0144] a. Ethyl 2-octylcycloprop-2-ene-1-carboxylate
[0145] Ethyl 2-octylcycloprop-2-ene-1-carboxylate was prepared from
1-decyne and ethyl diazoacetate by the method of Mueller, P.;
Pautex, N.; Helv. Chim Acta 1990, 73, 1233.
[0146] b. 2-Octylcycloprop-2-ene-1-carboxylic acid
[0147] Ethyl 2-octylcycloprop-2-ene-1-carboxylate (1.12 g, 5 mmol)
and 100 ml of 0.2 N potassium hydroxide were stirred at room
temperature for one week. Ether was added and the phases were
separated. The aqueous phase was acidified and extracted with
methylene chloride. The organic phase was dried over magnesium
sulfate and stripped to give 0.8 g of
2-octylcycloprop-2-ene-1-carboxylic acid.
[0148] c. 2-Octylcycloprop-2-ene-1-carbonyl chloride
[0149] A solution of 2-octylcycloprop-2-ene-1-carboxylic acid (350
mg, 1.8 mmol) in ether was treated with 0.45 g (3.5 mmol) of oxalyl
chloride at room temperature. The reaction mixture was stirred for
one hour then stripped to give 330 mg of
2-octylcycloprop-2-ene-1-carbonyl chloride.
[0150] d. Hex-5-yne 2-octylcycloprop-2-ene-1-carboxylate
[0151] To a solution of 2-octylcycloprop-2-ene-1-carbonyl chloride
(330 mg, 1.5 mmol) in 5 ml of ether is added 1.5 ml of
triethylamine. 5-Hexyn-1-ol (0.18g, 1.8 mmol) was added to the
reaction mixture, which was stirred at room temperature over the
weekend. Water and additional ether were added, and the resulting
mixture was transferred to a separatory funnel and the phases were
separated. The organic layer was washed with water and brine, dried
over MgSO.sub.4, filtered and stripped. The product was
chromatographed on silica gel to give 40 mg of 60% pure hex-5-yne
2-octylcycloprop-2-ene-1-carboxylate containing roughly 40%
2-octylcycloprop-2-ene-1-carboxylic acid.
EXAMPLE 26
[0152] Preparation of 7-Cycloprop-1-enyl-heptanoic acid (Compound
7) and 8-Cycloprop-1-enyl-octan-2-one (Compound 46)
[0153] a. 7-(1,1,2-Tribromo-cyclopropyl)-heptanoic acid:
[0154] 1,1,2-Tribromo-2-(7-hydroxyheptyl)cyclopropane (0.90 g, 2.3
mmol) was dissolved in 60 ml of glacial acetic acid. A solution of
1.0 g (10 mmol) of chromium trioxide dissolved in 14 ml of 90%
aqueous acetic acid was added and the reaction mixture was stirred
at room temperature for 24 hours. Water (300 ml)was added. The
solution was extracted with ether. The ether phase was extracted
three times with 1N NaOH solution. A little sodium bisulfite was
added. The aqueous extracts were acidified with 6N HCl, and
extracted with ether twice. The ether extracts were washed with
brine, dried over magnesium sulfate and stripped to give 0.56 g
7-(1,1,2-tribromo-cyclopropyl)-heptanoic acid.
[0155] b. 7-Cycloprop-1-enyl-heptanoic acid and
8-Cycloprop-1-enyl-octan-2- -one:
[0156] 1,1,2-Tribromo-2-(7-carboxyheptyl)-cyclopropane (1.28 g, 3.1
mmol) was dissolved in 60 ml of ether and cooled to -78.degree. C.
Methyllithium (9.0 ml, 12.6 mmol) was added and the reaction was
stirred at -78.degree. C. for two hours. The reaction mixture was
put in an ice bath for 5 minutes, then recooled to -78.degree. C.
until workup. Water was added to the reaction mixture, which was
warmed to room temperature. The aqueous phase was separated, and
the ether phase was extracted with three times with 1N NaOH
solution. The ether phase contained 8-cycloprop-1-enyl-octan-2-one
and the combined aqueous extracts contained
7-cycloprop-1-enyl-heptanoic acid.
[0157] The ether phase from above was washed with brine, dried over
magnesium sulfate and stripped to give 200 mg of
8-cycloprop-1-enyl-octan- -2-one, Compound 46.
[0158] The combined aqueous extracts containing
7-cycloprop-1-enyl-heptano- ic acid were acidified with aqueous
HCl, and extracted with ether three times. The ether extracts were
washed with brine, dried over magnesium sulfate and stripped to
give 300 mg of 7-cycloprop-1-enyl-heptanoic acid, Compound 7.
EXAMPLE 27
[0159] Preparation of 8-Cycloprop-1-enyl-octan-2-one 0-methyl oxime
(Compound 47)
[0160] To a solution of 0.15 g (0.9 mmol) of
8-cycloprop-1-enyl-octan-2-on- e in 10 mL of methanol cooled in an
ice bath was added 0.30 g (3 mmol) of triethylamine and 0.83 g of a
30-35% aqueous solution of methoxylamine hydrochloride (3 mmol).
The ice bath was removed, and the reaction mixture was stirred at
room temperature for 1.5 hours. Water and ether were added. The
phases were separated and the aqueous phase was washed with ether.
The combined ether phases were washed with dilute aqueous
hydrochloride acid, water (2.times.), and brine, then dried over
magnesium sulfate, filtered and stripped. Column chromatography
gave 50 mg of 8-cycloprop-1-enyl-octan-2-one 0-methyl oxime
(Compound 47) as a 30% solution in ether. The ratio of oxime
isomers was 3:1.
EXAMPLE 28
[0161] Preparation of 7-Cycloprop-1-enyl-heptanoic acid
diethylamide (Compound 48)
[0162] A solution of 7-cycloprop-1-enyl-heptanoic acid (0.25 g, 1.5
mmol) in 10 ml of ether was cooled in an ice bath and treated with
0.3 mL of triethyl amine. Methyl chloroformate (0.16 g, 17 mmol)
was added, and the reaction was stirred for 1.5 hours. Excess
diethylamine was added while the reaction was still cooled in an
ice bath, and the reaction was stirred for one half hour.
Additional ether and water were added, and the aqueous phase was
acidified to pH 1 with aqueous HCl. The phases were separated, and
the organic phase was washed with water, 1N sodium hydroxide, water
and brine. The organic phase was dried over magnesium sulfate,
filtered and stripped. Column chromatography gave 70 mg of
colorless liquid 7-cycloprop-1-enyl-heptanoic acid diethylamide
(Compound 48) in 74% purity.
EXAMPLE 29
[0163] In a manner similar to those described above, the following
compounds were made:
4TABLE 3 Additional compounds Compound R1 R2 R3 R4 Comments 23
Octyl H H H 24 n-Nonyl H H H 1:1 mixture with 1- bromo-2-
nonylcyclopropene 25 n-Decyl H H H 26 n-Heptyl H H H 27 Undecyl H H
H 70% purity 28 3-Ethylheptyl H H H 29 Tridecyl H H H 30
2-(2-methoxy-ethoxy)- H H H ethoxymethyl 31 n-Amyl H H H 32
2-Methylheptyl H H H 33 2-propionyloxyethane H H H 75% purity 34
6-Methylheptyl H H H 35 3,5,5-Trimethylhexyl H H H 36 7-Octenyl H H
H 37 5,5,5-Trifluoropentyl H H H Tested as a 51% solution in ether
38 Pentadecyl H H H 39 4,8-Nonyl H H H 40 Dodecyl H H H 41 Di-n- H
H H 1:4 mixture with 2- butylaminomethyl bromo-3-(di-N-
butylamino)prop-1- ene 42 Tetradecyl H H H 43 3,3-Dimethylbutyl H H
H 44 Hexyl H Hexyl H 70% purity 45 Pentyl Pentyl H H
EXAMPLE 30
[0164] The compounds described above were characterized using a
variety of spectroscopic techniques. The NMR data for compounds
1-45 is given in Table 4. For compounds containing impurities, the
chemical shifts of the impurities are not reported, and the
integrals are adjusted to reflect only the contribution of the
target compound.
5TABLE 4 NMR Data Compound NMR data 1 (CDCl3): 0.9(m,5H),
1.3(m,6H), 1.5(m,2H), 2.5(t,2H), 6.4(t,1H). 2 (CDCl3): 0.88(t,3H),
1.15-1.35(m,14H), 1.5(m,1H), 7.3(s,2H). 3 (CDCl3): 0.88 (d, 2H),
1.2-1.45 (m, 6H), 1.5-1.7 (m, 4H), 2.45 (dt, 2H), 3.33 (s, 3H),
3.37 (t, 2H), 6.45 (t, 1H). 4 (CDCl3): 0.89 (t and d, 5H), 1.2-1.45
(m, 4H), 1.45-1.6 (m, 4H), 1.6-1.75 (m, 2H), 2.05-2.2 (m, 4H), 2.48
(dt, 2H), 6.45 (s, 1H). 5 (CDCl3): 0.88 (d, 2H), 1.2-1.45 (m, 6H),
1.5-1.7 (m, 4H), 1.8 (bs, 1H), 2.47 (dt, 2H), 3.63 (t, 2H), 6.4 (s,
1H). 6 (CDCl3): 0.88 (d, 2H), 1.25-1.45 (m, 6H), 1.5-1.75 (m, 4H),
2.05 (s, 3H), 2.5 (dt, 2H), 4.05 (t, 2H), 6.45 (s, 1H). 7 (CDCl3):
0.88 (d, 2H), 1.25-1.45 (m, 4H), 1.5-1.8 (m, 4H), 2.36 (t, 2H),
2.48 (dt, 2H), 6.44 (t, 1H). 8 (CDCl3): 0.88 (d, 2H), 1.22 (d, 6H),
1.3-1.45 (m, 4H), 1.5-1.7 (m, 4H), 2.24 (t, 2H), 2.47 (dt, 2H), 3.2
(m, 1H),3.4-3.9 (bs, 2H and water), 6.45 (t, 1H). 9 (CDCl3): 0.88
(d, 2H), 1.2 (t, 3H),1.25-1.45 (m, 4H), 1.5-1.8 (m, 4H), 2.28 (t,
2H), 2.45 (dt, 2H), 4.13 (q, 2H), 6.45 (s, 1H). 10 (CDCl3): 0.88
(d, 2H), 1.4-1.55 (m, 6H), 1.55-1.75 (m, 4H), 2.34 (t, 2H), 2.48
(dt, 2H), 6.44 (t, 1H). 11 (CDCl3): 0.88 (d, 2H), 1.04 (t,
6H),1.2-1.4 (m, 6H), 1.4-1.55 (m, 2H), 1.55-1.65 (m, 2H), 2.4-2.5
(m, 4H), 2.55 (q, 4H), 6.44 (s, 1H). 12 (CDCl3): 0.88 (d, 2H), 1.25
(t, 6H),1.3-1.4 (m, 6H), 1.5-1.7 (m, 4H), 2.02 (s, 3H), 2.45 (t,
2H), 2.85-2.95 (m, 2H), 3.05 (q, 4H), 6.45 (s, 1H). 13 (CDCl3):
0.88 (d, 2H), 1.3-1.45 (t and m, 12H), 1.6 (quintet, 2H), 1.75 (m,
2H), 2.45 (dt, 2H), 3.27 (s, 3H), 3.35-3.5 (m, 2H), 3.61 (q, 4H),
6.45 (s, 1H). 14 (CDCl3): 0.89 (t, 3H), 1.06 (d, 2H), 1.2-1.45 (m,
6H), 1.5-1.7 (m, 2H), 3.5 (t, 2H), 4.51 (d, 2H), 6.74 (t, 1H). 15
(CDCl3): 0.90 (m, 5H), 1.2-1.45 (m, 4H), 1.5-1.7 (m, 2H), 2.76 (dt,
2H), 3.45 (t, 2H), 3.65 (t, 2H), 6.55 (t, 1H). 16 (Acetone-d6):
0.7(m,6H), 1.05-1.3(m,12H), 1.85(m,4H), 7.25(s,2H). 17 (CDCl3):
0.85-1.05(m,8H), 1.15-1.35(m,4H), 1.45-1.65(m,2H), 2- 2.1 (m,2H),
2.4(m,2H), 3.15(m,2H), 5.4-5.6(m,2H). 18 (Acetone-d6): 0.9(m,6H),
1.0(m,3H), 1.05-1.55(m,18H), 2.86(d,2H), 5,4-5.75(m,2H),
6.85(s,1H). 19 (CDCl3): 0.88 (d, 2H), 1.25-1.5 (m, 6H), 1.5-1.7 (m,
2H), 1.95- 2.15 (m, 2H), 2.47 (dt, 2H), 4.92 (dd, 1H), 4..98 (dd,
1H), 5.8 (m, 1H), 6.44 (t, 1H). 20 (CDCl3): 0.9(d,2H), 1.25(s,6H),
1.35(m,2H), 1.65(s,1H), 1.8(t,2H), 6.45(t, 1H). 21 (CDCl3): 0.76
(s, 2H), 0.88 (t, 3H), 1.15-1.4 (m, 18H), 1.45-1.7(m, 4H), 2.1 (m,
2H), 2.3 (t, 2H), 2.4 (t, 3H), 3.67 (s, 3H) 22 (CDCl3): 0.88 (t,
3H), 1.2-1.45 (m, 10H), 1.5-1.7 (m, 4H), 1.75 (m, 2H), 1.95 (t,
1H), 2.18 (s, 1H), 2.23 (dt, 2H), 2.4-2.55 (m, 2H), 4.05-4.15 (m,
2H), 6.32 (s, 1H). 23 (CDCl3): 0.9 (t and s, 5H), 1.2-1.5 (m, 10H),
1.6 (m, 2H), 2.5 (t, 2H), 6.42 (s, 1H). 24 (CDCl3): 0.9 (t and s,
5H), 1.2-1.5 (m, 12H), 1.7 (m, 2H), 2.4 (t, 2H), 6.45 (s, 1H). 25
(CDCl3): 0.88 (t and s, 5H), 1.2-1.5 (m, 14H), 1.7 (m, 2H), 2.5 (t,
2H), 6.45 (s, 1H). 26 (CDCl3): 0.88 (t and d, 5H), 1.2-1.5 (m, 8H),
1.7 (m, 2H), 2.5 (t, 2H), 6.42 (s, 1H). 27 (CDCl3): 0.88 (t and d,
5H), 1.2-1.5 (m, 16H), 1.7 (m, 2H), 2.4 (t, 2H), 6.4 (s, 1H). 28
(CDCl3): 0.8 (m, 8H), 1.1-1.4 (m, 10H), 1.7 (m, 2H), 2.4 (t, 2H),
6.42 (s, 1H). 29 (CDCl3): 0.9 (m, 5H), 1.2-1.5 (m, 20H), 1.6 (m,
2H), 2.4 (t, 2H), 6.4 (s, 1H). 30 (CDCl3): 1.06 (d, 2H), 3.39 (s,
3H), 3.5-3.8 (m, 8H), 4.59 (d, 2H), 6.75 (t, 1H). 31 (CDCl3):
0.9(m,5H), 1.3(m,4H), 1.6(m,2H), 2.5(t,2H), 6.4(s,1H). 32 (CDCl3):
0.85-0.95(m,8H), 1.1-1.4(m,8H), 1.8(m, 1H), 2.25- 2.6(2dd,2H),
6.45(s,1H). 33 (CDCl3): 0.93 (d, 2H), 1.12 (t, 3H), 2.32 (q, 2H),
2.82 (dt, 2H), 4.32 (t, 2H), 6.60 (s, 1H). 34 (CDCl3): 0.88(m,8H),
1.1-1.4(m,5H), 1.45-1.1.7(m,4H), 2.45(t,2H), 6.45(s,1H). 35
(CDCl3): 0.88(m,14H), 1-1.6(m,7H), 2.4(t,2H), 6.45(s,1H). 36
(CDCl3): 0.9(m,8H), 1-1.8(m,7H), 2.5(m,2H), 6.4(t,1H). 37 (CDCl3):
0.90 (d, 2H), 1.5-1.75 (m, 4H), 2.0-2.2 (m, 2H), 2.55 (dt, 2H),
4.92 (dd, 1H), 4..98 (dd, 1H), 5.8 (m, 1H), 6.5 (t, 1H). 38
(CDCl3): 0.88(m,5H), 1.15-1.3(m,24H), 1.55(m,2H), 2.45(t,2H),
6.45(s,1H). 39 (CDCl3): 0.9(d,11H), 1.05-1.7(m,12H), 2.45(t,2H),
6.45(s,1H). 40 (CDCl3): 0.88(m,5H), 1.15-1.45(m, 16H), 1.6(m,4H),
2.45(t,2H), 6.45(s,1H). 41 (CDCl3): 0.88(d, 2H), 1.05(t,6H),
1.3-1.55(m,8H), 2.4-2.65(m,4H), 3.65(s,2H), 6.6(t,1H). 42 (CDCl3):
0.88(m,5H), 1.25(s,24H), 2.45(t,2H), 6.45(s,1H). 43 (CDCl3): 0.9(m,
11H), 1.45-1.55(m,2H), 2.4-2.55(m,2H), 6.4(s,1 H). 44 (CDCl3):
0.9(m,6H), 1.25-1.4.5(m,17H), 1.5(m,2H), 2.45(t,2H), 6.65(s, 1H).
45 (CDCl3): 0.77(s,2H), 0.9(t,6H), 1.3(m,4H), 1.5(m,8H), 2.4(m,4H).
46 (CDCl3): 0.88 (d, 2H), 1.2-1.4 (m, 4H), 1.5-1.7 (m, 4H), 2.14
(s, 3H), 2.43 (t, 2H), 2.47 (dt, 2H), 6.45 (t, 1H). 47 (CDCl3):
0.88 (d, 2H), 1.2-1.45 (m, 4H), 1.5-1.7 (m, 4H), 1.82 (major
isomer), 1.85 (minor isomer) (2s, 3H), 2.15 (major isomer) 2.30
(minor isomer) (2 t, 2H), 2.47 (dt, 2H), 3.80 (minor isomer), 3.83
(major isomer) (2 s, 3H), 6.45 (t, 1H). 48 (CDCl3): 0.87 (d, 2H),
1.1,1.15 (2tx, 6H), 1.3-1.45 (m, 4H), 1.5- 1.75 (m, 4H), 2.29 (t,
2H), 2.47 (dt, 2H), 3.30 (q, 2H), 3.37 (q, 2H), 6.43 (t, 1H).
EXAMPLE 31
[0165] Biological Activity Tomato Epinasty Test Protocols
[0166] The test procedure is designed to determine the ability of
an compound according to the present invention to block the
epinastic growth response induced by ethylene in tomato plants when
the compound is administered either as a volatile gas or as a
component of a spray solution.
[0167] Treatment chambers are of an appropriate size for the test
plants and are airtight. Each is fitted with a reusable septum to
be used for injection of ethylene.
[0168] Test plants are Patio variety tomato seedlings planted two
plants per three inch square plastic pot.
[0169] Volatile gas treatment entails placing two pots of Patio
var. tomatoes into a polystyrene 4.8 L volume treatment chamber
along with one-half (upper or lower section) of a 50.times.9 mm
plastic Petri dish containing a Gelman filter pad. The appropriate
amount of experimental compound, dissolved in 1.0 ml acetone, is
pipetted onto the filter pad and the chamber immediately sealed.
Four hours later ethylene gas equal to 10 ppm v/v final
concentration is injected into the sealed chamber. Sixteen hours
later the chambers are opened in an exhaust hood, allowed to air
and the plants scored visually for the degree of protection against
ethylene-induced epinasty conferred by the experimental compound
when compared to ethylene treated and untreated controls on a scale
of 0 to 10. A rating of 10 means complete protection. A rating of 0
means no protection from the effects of ethylene.
[0170] Spray application treatment entails using a DeVilbiss
atomizer to completely cover all foliage and stems of two pots of
Patio var. tomato plants with the appropriate amount of
experimental compound dissolved in 10% acetone/90% water with 0.05%
Silwett L-77 surfactant. Plants are air-dried in a drying hood for
four hours then transferred to a 4.8 L polystyrene chamber which is
sealed.
[0171] Ethylene gas equal to 10 ppm v/v final concentration is
injected into the sealed chamber. Sixteen hours later the chambers
are opened in an exhaust hood, allowed to air and the plants scored
visually for the degree of protection against ethylene-induced
epinasty conferred by the experimental compound when compared to
ethylene treated and untreated controls on a scale of 0 to 10. A
rating of 10 means complete protection. A rating of 0 means no
protection from the effects of ethylene.
[0172] When applied as a spray in the tomato epinasty test,
1-pentylcyclobutene was superior to 1-butylcyclobutene. The pentyl
analog was rated 10 (complete protection), while the butyl analog
was rated 5.
[0173] The activity of the compounds of this invention in the
tomato epinasty test when applied as a gas is given in the
table.
6TABLE 5 Activity of compounds according to the present invention
in the tomato epinasty test Gas Gas Gas Gas Compound 1000 ppm 750
ppm 500 ppm 10 ppm 1 10 2 10 0 3 9.5 4 10 5 10 0 6 10 0 7 8 3 8 8 0
9 4 10 10 2 11 10 3 12 10 2 13 6 14 10 15 10 16 10 0 17 10 0 18 10
0 19 10 20 8 0 21 9 5 22 9 0 23 10 24 9.5 25 9 26 10 27 10 28 9 29
10 3.5 30 10 3 31 10 32 9.5 33 10 0 34 10 35 10 36 10 37 10 38 10
4.5 39 10 40 10 4 41 10 3 42 10 2 43 10 44 10 0 45 10 0 46 9 3 47
9.5 48 7 0
[0174] The foregoing embodiments and examples are illustrative of
the present invention and are not to be construed as limiting
thereof. The invention is defined by the following claims, with
equivalents of the claims to be included therein.
* * * * *