WO1991000009A1 - Novel glyoxylates and herbicidal and plant growth regulant activity of glyoxylates - Google Patents

Novel glyoxylates and herbicidal and plant growth regulant activity of glyoxylates Download PDF

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Publication number
WO1991000009A1
WO1991000009A1 PCT/US1990/003672 US9003672W WO9100009A1 WO 1991000009 A1 WO1991000009 A1 WO 1991000009A1 US 9003672 W US9003672 W US 9003672W WO 9100009 A1 WO9100009 A1 WO 9100009A1
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Prior art keywords
alkyl
lower alkyl
coor
mol
cycloalkyl
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PCT/US1990/003672
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French (fr)
Inventor
Keith D. Barnes
Frederick W. Hotzman
Lawrence E. Limpel
Thomas A. Magee
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Fermenta Asc Corporation
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Filing date
Publication date
Priority claimed from US07/373,210 external-priority patent/US4976770A/en
Application filed by Fermenta Asc Corporation filed Critical Fermenta Asc Corporation
Priority to AU59509/90A priority Critical patent/AU647401B2/en
Priority to CA002035024A priority patent/CA2035024C/en
Priority to BR909006844A priority patent/BR9006844A/en
Publication of WO1991000009A1 publication Critical patent/WO1991000009A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms

Definitions

  • the invention relates broadly to
  • Glyoxylates 12H-dibenzo[d,g] [1,3]dioxocin-6-carboxylic acid and certain derivatives thereof, generally referred to herein as "glyoxylates", and their use as plant growth regulant and/or herbicidal agents and more particularly to their use, usually in combination with appropriate carriers and surfactants, in influencing the growth and development of crops, ornamentals and turf grasses.
  • X and Y are hydrogen or a halogen and R is hydrogen or lower alkyl are disclosed to have utility as hypolipidemic agents for warm blooded animals.
  • pharmaceutically acceptable salts of such acids are disclosed.
  • An improved class of hypolipidemic agents are disclosed by the same inventors in U.S. Patent No. 3,941,173 wherein carboxamides are also contemplated.
  • no utility in the agricultural field is suggested, and on tests of the specific compounds disclosed in U.S. Patent No. 3,553,234 and U.S. Patent No. 3,941,173 no herbicidal activity was found.
  • the present invention is based upon the discovery that a selected group of such compounds possesses unexpected activity when employed as plant growth regulant and/or herbicidal agents at controlled dosages, while other closely related compounds within the genus of U.S. Patent 3,553,234 display no significant agrochemical activity.
  • plant growth regulant means a compound or composition which affects the maturation and metabolism of plants.
  • a plant growth regulant has many effects on plant growth.
  • plant growth regulant active compounds affect plants the same way. For example, they could affect vegetative growth by retarding or stimulating terminal growth, and/or stimulating side branching and could inhibit new growth such as the development of new sprouts of woody plants, the sprouting of tubers and rhizomes and the development of sucker growth.
  • Such regulants could affect flowering plants by eliminating early flowering, by thinning of blossoms or by increasing the number of flowers.
  • Fruit-bearing trees and bushes could be affected by increases in the number, size and quality of the fruit, by producing seedless fruit, by accelerating senescence and fruit ripening. Both flowering and fruit plants could be affected by accelerating plant dormancy and maintaining bud dormancy.
  • a "plant growth regulant" could cause selective postemergent control of weeds by reducing their vigor and competitiveness, and thus prevent their spread and stop normal seeding.
  • plant growth regulants Some specific applications of plant growth regulants include:
  • Plant growth regulant also means the retardation of terminal (i.e. vertical) growth of plants. In grasses and weeds, this regulant activity will retard the grass height and, hence, grass growth. In bushy plants, on the other hand, the resultant retardation of terminal growth by the regulant activity often results in enhancement of lateral growth, an effect desired, e.g. in tomato plants.
  • R is H, Na, K, di(C 1 - C 4 )alkylammonium, diethanolammonium, N(3-amino-propyl)N-oleylammonium, C 1 - C 8 alkyl, aryl, heteroaryl, C 2 - C 8 alkoxyalkyl, C 2 C 4 hydroxyalkyl, (alkoxycarbonyl) alkyl, dialkylaminoalkyl, cycloalkyl, tetrahydrofurfuryl or dimethydioxolanylmethyl;
  • R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N- (lower alkyl)-piperazino;
  • Z is H, CH 3 , CH 3 S, CH 3 S(O), COOR;
  • Y is H, C 1 - C 4 alkyl or alkoxy, CF 3 or X;
  • X is F, Cl or Br
  • a method of controlling the growth of undesired vegetation comprises applying to the vegetation locus, especially by postemergent application, a herbicidally effective amount of a compound having the same formula as above.
  • composition of matter useful in the regulation of plant growth and development which composition comprises a compound having the same formula as above, an inert carrier and a surfactant.
  • Y, B and Z are all H, resulting in a compound having the formula
  • B and Z are all H, resulting in a compound having the formula
  • the invention also encompasses certain novel compounds having herbicidal and/or plant growth regulating activity having the formula
  • R is C 2 - C 8 alkoxyalkyl, cycloalkyl. C 2 - C 4 hydroxyalkyl, (alkoxycarbonyl) alkyl, dialkylaminoalkyl, tetrahydrofurfuryl and dimethyldioxolanylmethyl; R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N-(lower alkyl)-piperazino;
  • Z is H, CH 3 , CH 3 S, CH 3 S(O) or COOR;
  • Y is H, C 1 - C 4 alkyl or alkoxy, CF 3 or X; and X is F, Cl or Br;
  • Y is other than H on either ring they must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or 11 positions on the rings, no more than one of Y is other than H. In other embodiments, no more than one of Y is other than H on either ring.
  • R is H, Na, K, di(C 1 - C 4 )alkylammonium, N(3-amino-propyl)N-oleylammonium, C 1 - C 8 alkyl, aryl, heteroaryl, C 2 - C 8 alkoxyalkyl, C 2 - C 4 hydroxyalkyl,
  • R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N- (lower alkyl)-piperazino;
  • Z is H, CH 3 , CH 3 S, CH 3 S(O), COOR;
  • Y and W are C 1 - C 4 alkyl or alkoxy or CF 3 ; m and n are 0-2 and the sum of m plus n is 1-4.
  • moieties suitable for use as A, Z, B and Y in the compositions of the present invention are moieties suitable for use as A, Z, B and Y in the compositions of the present invention.
  • moieties suitable for use as A mention may be made of a carboxyl group (-COOH) , simple esters such as:
  • Z may be:
  • B may be:
  • Y may be:
  • a nitrogen ring structure such as pyridine derivatives.
  • plant growth regulant or “plant growth regulating effect” refer to the ability of a glyoxylate, when applied to a plant locus, to influence the growth and development of useful crops, ornamentals and turf as for example described by illustration hereinbefore. A variety of effects may be obtained depending upon, among other considerations, the plant in question, the glyoxylate selected and the manner, amount and timing of application.
  • the result obtained by application of a glyoxylate is the desirable promotion, inhibition and/or alteration of a plant's physiological or morphological processes, such as accelerating or retarding leaf, shoot and root growth, reduction in stature, increased branching, tillering, terminal inhibition, inhibition of regrowth after pruning thereby reducing the need for follow-up pruning, increased root growth, delayed budding, increased bud count, yield increases, etc.
  • the glyoxylates of the present invention have been found to be effective growth retardants when applied to turf grasses such as, perennial rye, red and tall fescue and Kentucky bluegrass.
  • a further example of a plant growth regulating effect is the ability of a glyoxylate compound, when timely applied (preferably in the second or third growth stage) to act as a straw shortening agent on wheat, an especially useful effect where high nutrient levels are employed to increase grain yield.
  • herbicide or "herbicidal effect” refers to the application of a glyoxylate compound to kill, or at least substantially inhibit the growth of, an undesired plant.
  • a glyoxylate compound to kill, or at least substantially inhibit the growth of, an undesired plant.
  • one of the glyoxylates to control the growth of weeds, including grassy weeds, in wheat and reduce flowering in bolting weed beets.
  • the glyoxylates have been found to be particularly useful in controlling the growth of the generally hard to control sedges, especially yellow nut sedge, when applied to the soil in which the nut sedge tubers are beginning to germinate.
  • Each of the defined glyoxylate compounds has been found to have a herbicidal and/or plant growth regulating effect.
  • a particular ester or salt form of a glyoxylate will often be chosen for its convenience of handling and application, an example being the choice of the n-butyl ester, which has reduced volatility, over the methyl ester form.
  • volatility is desirable, e.g., for application by fumigation (smoke bombs) in a greenhouse to induce branching of ornamentals
  • compounds such as the nitrile and lower esters (e.g., methyl, ethyl and propyl) which are more volatile, may be preferred.
  • substitution opportunities are particularly limited when placed in the 1, 2, 10 and 11 positions according to the following number system:
  • the glyoxylates will be applied to the plant locus as the active ingredient in a composition also comprising a carrier and a surfactant, that is, a dispersing, emulsifying or wetting agent, although diluents, extenders and other active ingredients having a differing or complementary utility may be present.
  • a surfactant that is, a dispersing, emulsifying or wetting agent, although diluents, extenders and other active ingredients having a differing or complementary utility may be present.
  • the compositions may thus be in the form of finely divided particulate solids, granules, wettable powders, solutions and dispersions.
  • the inert carrier may be solid (e.g., clays, natural or synthetic silicates, talcs) or liquid (e.g., water, alcohols, esters, aromatic hydrocarbons, petroleum fractions).
  • the surface active agents may be anionic, cationic or non-ionic (e.g., salts of lignosulfonic acids, alkyl-aryl sulfonic acids, acetates of alkylamines and condensates of ethylene oxide with fatty alcohols or acids).
  • the compositions may contain thickeners, adhesives, stabilizers, preservatives and other adjuvants known to the art.
  • the glyoxylates may be applied by conventional techniques (e.g., spreading, dusting or spraying or via fumigation smoke bombs in confined areas such as greenhouses) in a variety of forms (e.g., solutions, suspensions, wettable powders or granules).
  • conventional techniques e.g., spreading, dusting or spraying or via fumigation smoke bombs in confined areas such as greenhouses
  • forms e.g., solutions, suspensions, wettable powders or granules.
  • compositions of the present invention generally will contain from 5 to 95 percent by weight of the active glyoxylate compound and will be applied at a rate of from 0.5 to 4 kilograms per hectare, when used as herbicides. While in a plant growth regulating composition the amount of active ingredient may be comparable, the amount employed will vary greatly depending upon the particular glyoxylate chosen and the effect in question, generally ranging from 0.01 gram to 4 kg per hectare. Conveniently, such applications are obtained by spraying a solution containing from 0.1 to 500 ppm active ingredient to run-off, depending on the plant species to be treated.
  • reaction mixture After 24 hours, the reaction mixture is cooled to room temperature and an additional 82.5 ml (1.0 mol) of dichloroacetic acid is added. Again, some effervescence is observed. The reaction mixture is then heated at reflux for an additional 72 hours. Total reflux time is 96 hours. After 48 hours of total reflux time, the reaction mixture thickens and vigorous stirring is maintained.
  • the condenser is replaced with a distillation head and 200 ml of isopropyl alcohol is distilled off at atmospheric pressure and replaced with 200 ml of H 2 O. This is repeated until the distillation temperature reaches 95-100oC.
  • the reaction mixture becomes much more fluid and eventually a reddish brown homogenous solution is obtained.
  • the reaction mixture is cooled to room temperature. Upon cooling, solids form, therefore it is important to maintain vigorous stirring.
  • the reaction mixture is then made strongly acidic by the careful addition of concentrated HCl (800 ml) over a period of 1-2 hours.
  • This evaporation with toluene facilitates the removal of n-butanol.
  • the residue obtained is taken up into 300 ml of 2:1 toluene:ether and washed with 200 ml of 5 percent NaOH.
  • Brine, 50 ml is added to break up the emulsion that forms with the 5 percent NaOH wash.
  • the organic solution is then washed with 200 ml of brine, dried over MgSO 4 and concentrated under reduced pressure to afford a thick light reddish-yellow liquid (130 grams).
  • This liquid is then subjected to vacuum distillation, using a Claisen adapter as the distillation head and an oil bath for heating. Care is taken during the course of the distillation to avoid solidification of the product in the distillation condenser.
  • a forerun (11 grams) is collected having a b.p. 70oC to 170oC at 0.25 mm. Pure n-butyl ester, 84.3 grams (62 percent), is then collected from 171oC to 180oC at 0.25 mm as a thick clear liquid which readily solidifies on cooling to afford a white solid: mp 63-66°C (softening at 60oC); greater than 99 percent purity as determined by L.C.
  • This material is then converted to the methyl ester by refluxing in a methanol solution (100 ml) in the presence of cone. H 2 SO 4 (0.6 ml) for 2 hours.
  • the solution is cooled, 50 ml of CH 2 Cl 2 is added and the mixture neutralized by the addition of solid Na 2 CO 3 .
  • the inorganic salts are removed by filtration and the filtrate concentrated and taken up into CH 2 Cl 2 , washed with brine, dried over MgSO 4 and concentrated to afford 11.5 grams of a dark semi-solid.
  • a mixture of crude 6-methyl 2,2'-methylene bisphenol (7.0 g, 0.0327 mol), potassium hydroxide (5.5 g, 0.098 mol) and dichloroacetic acid (2.7 ml, 0.0327 mol) in 130 ml of isopropyl alcohol is heated at reflux for 23 hours, following which an additional 5.5 g of potassium hydroxide (0.098 mol) and then 2.7 ml of dichloroacetic acid (0.0327 mol) are added and the reaction mixture is again heated at reflux for an additional 3 hours.
  • AR 2 CH 2 ) , 4 . 39 (q, 2 , CH 2 CH 3 ) , 5. 05 (s, 1 CH) , 7 . 0-7.4 (m, 7 , Ar-H) ; mass spectrum, m/e (M+) 340 , (M+ - CH 3 ) 323 ,
  • reaction is then heated at reflux for 20 hours, cooled to room temperature, poured into 300 ml of H 2 O, acidified by the addition of concentrated HCl, and extracted with ethyl acetate (2 ⁇ 200 ml). The ethyl acetate extract is washed with brine, dried over MgSO 4 and concentrated to afford an oily residue which is further washed with petroleum ether to give 4.6 g of an orange-yellow semi-solid. A solution of this material and p-toluene sulfonic acid (0.07 g) in 30 ml of 10:1 CHCl 3 -ethanol is heated at reflux for 1 hour with azetropic removal of water.
  • the herbicide screening test is designed to identify compounds that exhibit pre-emergence (Pre) and/or post-emergence (Post) herbicidal activity. Plantings of the indicated test species are seeded in separate fiber pans (8" X 10" X 3" deep) containing pasteurized soil. The Post pans are seeded two weeks prior to treatment. The Pre pans are seeded one day prior to application of the test compounds. One Pre and one Post pan is employed for each compound, unless otherwise indicated. Prior to application of the test formulation, the Pre pans are mist watered to stabilize the soil surface.
  • the standard laboratory formulation at the 8 kg/ha treatment rate is prepared by weighing 73.6 mg of the test compound into a 125 ml flask to which is then added 40 ml of acetone followed by 40 ml of 0.1% Ortho X-77 surfactant. If the test compound appears insoluble in the formulation, it is treated for 1-2 minutes with an ultrasonic probe. If still insoluble, the particle size is reduced by grinding to a size sufficient to allow it to pass through the spray nozzle. Following preparation of the test formulations, each is then sprayed equally and completely on the Pre and Post pans employing a handheld spray gun with an air atomizing nozzle. Acetone is employed to rinse the spray gun between application of each formulation.
  • the treated pans are then moved to a growth room, or greenhouse, where they are maintained and appropriately watered for 13 days following treatment. At this time, the pans are then evaluated to determine the percent kill/inhibition/suppression relative to an untreated control.
  • the rating numbers range from 0, indicating no injury, to 100, indicating complete kill or control. Compounds that show 80% control Post and 50% control Pre against any 3 species are considered for further testing. Results are shown in the following Table.
  • Post 8 100 100 100 0 20 30 20 100 30 40
  • Post 8 50 100 100 30 50 60 30 70 20 60
  • Post 8 90 100 100 20 30 10 30 100 70 0 4 20 70 100 20 30 20 30 100 20 2 50 80 10 20 10 20 80 20 0 1 50 70 70 10 20 10 10 80 0 10
  • the acid form of the glyoxylate prepared in Example 1 was evaluated as a turf growth retardant on four grass species at varying rates as indicated in Table 2.
  • Turf species were planted in 8 by 8 cm fiber pots using steam pasteurized soil, and allowed to grow until well established, i.e., roots extended to the bottom of the fiber pot.
  • the turf was clipped periodically to keep the thatch at a manageable level and fertilizer was applied on a regular basis. Prior to application of the compound to the turf, the grass was cut to one cm.
  • the compound was formulated in 15 X 125 mm disposable test tubes and foliar applications were made in a hood using a DeVilbliss Model EGA-502 hand held sprayer.
  • Example 99 Using the turf species set forth and grown as in Example 99, the effect of the method of application of the compounds of Examples 16 and 2 is evaluated, with results set forth in Table 3. Weight measurements are taken by cutting each turf pot, after two weeks, to a uniform height, combining the clippings from all species and oven drying prior to weighing.
  • Granular application is found to result in the lowest degree of phytotoxicity to the grass species.
  • Wheat testing is done in 13 cm round plastic pots.
  • the wheat is planted in a mixture of 75 percent soil and 25 percent sand which has been steam pasteurized to control indigenous weed seed and pathogens. Seeds are planted and then covered with approximately 1 cm soil/sand mix and placed on fiber matting in the greenhouse. The pots are both mist watered and bottom watered until seedlings emerged. After emergence, only bottom watering is done.
  • the growth stage is recorded, and pots are removed to a spray hood for treatment.
  • the compound to be applied is placed in a 15 by 125 mm test tube and dissolved in 12 ml of acetone and water. The compound is sprayed onto the foliage using a hand held Devilbiss spray gun (Model EGA-502). This sprayer emits an extremely fine spray particle and results in maximum coverage of the foliage. Operating air pressure is 840 gm/cm 2 .
  • Applications are made at four different rates at each of six growth stages. The growth stages are as follows:
  • Acer palmatum Japanese cutleaf maple
  • ATRINALTM a commercial formulation by MAAG of dikegulac
  • Rooted single-stem cuttings of azaleas (Rhododendron sp., cv 'Elsi Lee') are transplanted to artificial potting medium in 4 inch round plastic pots. These cuttings are pinched as they were moved. After growth resumes, these plants are sprayed to run-off using a hand held spray unit. Treatments employ the K salt of Example 15 and dikegulac, a commercial plant growth regulator which is used to induce branching and to prevent regrowth after pruning. Treatments, based on five replicates of each are listed in Table 9.
  • Non-sprayed control plants in which the terminal bud was pinched grew 18.3 cm while non-sprayed non-pinched plants grew 11 cm.
  • pinched control plants sprayed with the solvent increased in height 15 cm and non-pinched, non-sprayed plants grew 8.5 cm.
  • all compounds tested essentially eliminated terminal bud elongation, regardless of concentration of the applied solution. Thus, these compounds appear to have excellent utility when used to reduce vertical growth of this tree species.

Abstract

12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid and certain derivatives thereof (glyoxylates) exhibit plant growth regulant and herbicidal activity when applied to a plant locus.

Description

NOVEL GLYOXYLATES AND HERBICIDAL AND PLANT GROWTH REGULANT ACTIVITY OF GLYOXYLATES
RELATED APPLICATION
This is a continuation-in-part of application Serial No. 373,210, filed June 29, 1989.
BACKGROUND OF THE INVENTION
The invention relates broadly to
12H-dibenzo[d,g] [1,3]dioxocin-6-carboxylic acid and certain derivatives thereof, generally referred to herein as "glyoxylates", and their use as plant growth regulant and/or herbicidal agents and more particularly to their use, usually in combination with appropriate carriers and surfactants, in influencing the growth and development of crops, ornamentals and turf grasses.
Some of the compounds which find utility in the present invention are known generically, and specifically in the case of the methyl ester, from U.S. Patent 3,553,234. Therein, a class of compounds described as 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acids and their esters and having the formula
Figure imgf000003_0001
wherein X and Y are hydrogen or a halogen and R is hydrogen or lower alkyl are disclosed to have utility as hypolipidemic agents for warm blooded animals. Also mentioned are the pharmaceutically acceptable salts of such acids. An improved class of hypolipidemic agents are disclosed by the same inventors in U.S. Patent No. 3,941,173 wherein carboxamides are also contemplated. However, no utility in the agricultural field is suggested, and on tests of the specific compounds disclosed in U.S. Patent No. 3,553,234 and U.S. Patent No. 3,941,173 no herbicidal activity was found.
The present invention is based upon the discovery that a selected group of such compounds possesses unexpected activity when employed as plant growth regulant and/or herbicidal agents at controlled dosages, while other closely related compounds within the genus of U.S. Patent 3,553,234 display no significant agrochemical activity.
As used herein, "plant growth regulant" means a compound or composition which affects the maturation and metabolism of plants. Hence, a "plant growth regulant" has many effects on plant growth. However, not all plant growth regulant active compounds affect plants the same way. For example, they could affect vegetative growth by retarding or stimulating terminal growth, and/or stimulating side branching and could inhibit new growth such as the development of new sprouts of woody plants, the sprouting of tubers and rhizomes and the development of sucker growth. Such regulants could affect flowering plants by eliminating early flowering, by thinning of blossoms or by increasing the number of flowers. Fruit-bearing trees and bushes could be affected by increases in the number, size and quality of the fruit, by producing seedless fruit, by accelerating senescence and fruit ripening. Both flowering and fruit plants could be affected by accelerating plant dormancy and maintaining bud dormancy. A "plant growth regulant" could cause selective postemergent control of weeds by reducing their vigor and competitiveness, and thus prevent their spread and stop normal seeding.
Some specific applications of plant growth regulants include:
preventing lodging of cereals;
increasing production of harvestable tea leaves by promoting side branching;
inhibiting sprouting of potatoes and onions in storage;
suppressing growth of grass, trees, shrubs, and other vegetation in decorative lawn areas, parks, golf courses and along highways and other rights-of-way;
accelerating fruit ripening and thus, aiding mechanical harvesting by a single or reduced number of pickings;
defoliating cotton to permit mechanical harvest;
inhibiting new growth of defoliated cotton and, thus, reducing staining of fiber during mechanical harvesting;
increasing the quality of the harvested crop, e.g., sugar content of sugar cane, sugarbeets, grapefruit, grapes, and other fruits;
aiding mechanical harvesting of nut crops by accelerating ripening, stimulating husk cracking and promoting abscission;
protecting crops from drought; protecting fruit crops from frost by stimulating early dormancy and/or preventing premature breaking of dormancy;
increasing latex flow of rubber;
increasing frost resistance of winter cereals; reducing the flowering or bolting of lettuce, sugar beets and tobacco;
controlling tobacco suckering;
stimulating increased fruit set of soybeans, peanuts, cotton, tomatoes, melons, and other fruits and enhancing fruit color and quality; stimulating branching of pot plants; e.g. heather, azalea, chrysanthemum and geranium;
growth retardation in pot plants, e.g. poinsetta, petunia, chrysanthemum and azaleas;
stimulating branching of young fruit trees, e.g. apple and pear.
"Plant growth regulant" also means the retardation of terminal (i.e. vertical) growth of plants. In grasses and weeds, this regulant activity will retard the grass height and, hence, grass growth. In bushy plants, on the other hand, the resultant retardation of terminal growth by the regulant activity often results in enhancement of lateral growth, an effect desired, e.g. in tomato plants.
SUMMARY OF THE INVENTION
There has now been discovered a method of modifying the natural growth and development of a plant, which method comprises applying to the plant locus an effective, nonlethal, plant regulating amount of a compound having the formula wherein:
Figure imgf000007_0001
A is COOR, COSR, CONR'R", CSNH2, CN or, together with one of B, -C(=O)O-
R is H, Na, K, di(C1 - C4)alkylammonium, diethanolammonium, N(3-amino-propyl)N-oleylammonium, C1 - C8 alkyl, aryl, heteroaryl, C2 - C8 alkoxyalkyl, C2 C4 hydroxyalkyl, (alkoxycarbonyl) alkyl, dialkylaminoalkyl, cycloalkyl, tetrahydrofurfuryl or dimethydioxolanylmethyl;
R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N- (lower alkyl)-piperazino;
Z is H, CH3, CH3S, CH3S(O), COOR;
B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y is H, C1 - C4 alkyl or alkoxy, CF3 or X; and
X is F, Cl or Br,
provided that where more than one of Y is other than H on either ring they must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or 11 positions on the rings, no more than one of Y is other than H. In other embodiments, no more than one of Y is other than H on either ring. There has further been found a method of controlling the growth of undesired vegetation, which method comprises applying to the vegetation locus, especially by postemergent application, a herbicidally effective amount of a compound having the same formula as above.
There has still further been found a composition of matter useful in the regulation of plant growth and development, which composition comprises a compound having the same formula as above, an inert carrier and a surfactant.
In one preferred embodiment of the foregoing methods and composition of the present invention, Y, B and Z are all H, resulting in a compound having the formula
Figure imgf000008_0001
In a further embodiment of the foregoing methods and composition of the present invention, B and Z are all H, resulting in a compound having the formula
Figure imgf000008_0002
In yet another embodiment of the foregoing methods and compositions, Y and Z are all H, resulting in a compound having the formula
Figure imgf000009_0001
The invention also encompasses certain novel compounds having herbicidal and/or plant growth regulating activity having the formula
Figure imgf000009_0002
wherein:
A is COOR, COSR, CONR'R'' CSNH 2, CN or, together with one of B, -C(=O)O-;
R is C2 - C8 alkoxyalkyl, cycloalkyl. C2 - C4 hydroxyalkyl, (alkoxycarbonyl) alkyl, dialkylaminoalkyl, tetrahydrofurfuryl and dimethyldioxolanylmethyl; R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N-(lower alkyl)-piperazino;
Z is H, CH3, CH3S, CH3S(O) or COOR;
B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y is H, C1 - C4 alkyl or alkoxy, CF3 or X; and X is F, Cl or Br;
provided that where more than one of Y is other than H on either ring they must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or 11 positions on the rings, no more than one of Y is other than H. In other embodiments, no more than one of Y is other than H on either ring.
Another group of novel compounds within the scope of the invention has the formula
Figure imgf000010_0001
wherein: A is COOR, COSR, CONR'R", CSNH2, CN or, together with one of B, -C(=O)O-;
R is H, Na, K, di(C1 - C4)alkylammonium, N(3-amino-propyl)N-oleylammonium, C1 - C8 alkyl, aryl, heteroaryl, C2 - C8 alkoxyalkyl, C2 - C4 hydroxyalkyl,
(alkoxycarbonyl) alkyl, dialkylaminoalkyl, cycloalkyl, tetrahydrofurfuryl or dimethydioxolanylmethyl;
R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N- (lower alkyl)-piperazino;
Z is H, CH3, CH3S, CH3S(O), COOR;
B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y and W are C1 - C4 alkyl or alkoxy or CF3; m and n are 0-2 and the sum of m plus n is 1-4. By way of illustration, and not by way of limitation, the following are moieties suitable for use as A, Z, B and Y in the compositions of the present invention.
As examples of moieties suitable for use as A mention may be made of a carboxyl group (-COOH) , simple esters such as:
COOCH3
COOCH2CH3
COOCH2CH2CH3
COOCH (CH3) 2
COOCH2CH2CH2CH3
COOC (CH3)3 COOCH2(CH2)6CH3
COOCH2CH (CH2CH3) CH2CH2CH2CH3 COOC6H11
COOC6H5
substituted esters such as:
COOCH2CH2OCH3
COOCH2CH2OCH2CH2CH2CH3
COOCH2CH (OH) CH2OH
O O COOCH2CH-CH2
COOCH2
Figure imgf000012_0001
COOCH (CH3) COOCH2CH3
COOCH2CH2N(CH3)2
COOCH2CH2N(CH3)2.HCl
amides such as:
CONH2
CONHCH3
COHNC6H5
CON(CH3)2
salts such as:
COONa
COOK
COOH. (CH3)2NH
COOH.(HOCH2CH2)2NH
COOH.CH3(CH2)7CH=CH(CH2)8NHCH2CH2CH2NH2 and other moieties such as:
CH2OH
CH2OSO2C6H6-CH3-4
CH(OH)CN
CH=CHCOOCH2CH3 CN
C(=S)NH2
C(=O)SCH2CH3 C(=O)NHNH2. Z may be:
H
CH3
CH3S
CH3S (O)
C(=O)OCH2CH3;
B may be:
H
CH3
(CH3)2
CH2=
CH3CH2
(CH3)2CH-
CF3
HO-
CH3O-
C6H5-CH2O-
CH3C(=O)O-
=O
Figure imgf000013_0001
(CH3)2CHCOC(=O)- lactone (B + A); and
Y may be:
H CH3 (CH3)3C
F
Cl
HO CH3O
C6H5CH2O
CH3C(=O)O
NO2
a nitrogen ring structure such as pyridine derivatives.
These and other aspects of the invention will become clear to one skilled in the art from the specification and claims that follow.
DETAILED DESCRIPTION
When used in the present invention, the terms
"plant growth regulant" or "plant growth regulating effect" refer to the ability of a glyoxylate, when applied to a plant locus, to influence the growth and development of useful crops, ornamentals and turf as for example described by illustration hereinbefore. A variety of effects may be obtained depending upon, among other considerations, the plant in question, the glyoxylate selected and the manner, amount and timing of application. Generally the result obtained by application of a glyoxylate is the desirable promotion, inhibition and/or alteration of a plant's physiological or morphological processes, such as accelerating or retarding leaf, shoot and root growth, reduction in stature, increased branching, tillering, terminal inhibition, inhibition of regrowth after pruning thereby reducing the need for follow-up pruning, increased root growth, delayed budding, increased bud count, yield increases, etc. In particular, the glyoxylates of the present invention have been found to be effective growth retardants when applied to turf grasses such as, perennial rye, red and tall fescue and Kentucky bluegrass. A further example of a plant growth regulating effect is the ability of a glyoxylate compound, when timely applied (preferably in the second or third growth stage) to act as a straw shortening agent on wheat, an especially useful effect where high nutrient levels are employed to increase grain yield.
The use of the terms "herbicide" or "herbicidal effect" refers to the application of a glyoxylate compound to kill, or at least substantially inhibit the growth of, an undesired plant. Especially significant examples are the use of one of the glyoxylates to control the growth of weeds, including grassy weeds, in wheat and reduce flowering in bolting weed beets. The glyoxylates have been found to be particularly useful in controlling the growth of the generally hard to control sedges, especially yellow nut sedge, when applied to the soil in which the nut sedge tubers are beginning to germinate.
The compounds useful herein are those having the formula
Figure imgf000015_0001
Each of the defined glyoxylate compounds has been found to have a herbicidal and/or plant growth regulating effect. In addition to activity and selectivity considerations, a particular ester or salt form of a glyoxylate will often be chosen for its convenience of handling and application, an example being the choice of the n-butyl ester, which has reduced volatility, over the methyl ester form. On the other hand, where volatility is desirable, e.g., for application by fumigation (smoke bombs) in a greenhouse to induce branching of ornamentals, compounds such as the nitrile and lower esters (e.g., methyl, ethyl and propyl) which are more volatile, may be preferred.
The choice of substituents to be placed on the benzene rings, on the other hand, seems to affect the nature and extent of plant growth regulating effect to be obtained and such substitution is limited with respect to (1) the identity of the substituent, (2) location on the ring or rings and (3) number of substitutions that may be accommodated. Substitution opportunities are particularly limited when placed in the 1, 2, 10 and 11 positions according to the following number system:
Figure imgf000016_0001
In such cases, substitution of a methyl group at no more than one position has been found possible without a significant loss of herbicidal activity. Substituent possibilities at the remaining benzene ring positions (3, 4, 8 and 9), in order to vary the growth regulating and/or herbicidal effect obtained without significant overall loss of activity, are more numerous. While it is preferred that not more than one position on either ring be substituted, the choice of substituents may be increased as defined above.
Generally the glyoxylates will be applied to the plant locus as the active ingredient in a composition also comprising a carrier and a surfactant, that is, a dispersing, emulsifying or wetting agent, although diluents, extenders and other active ingredients having a differing or complementary utility may be present. The compositions may thus be in the form of finely divided particulate solids, granules, wettable powders, solutions and dispersions.
The inert carrier may be solid (e.g., clays, natural or synthetic silicates, talcs) or liquid (e.g., water, alcohols, esters, aromatic hydrocarbons, petroleum fractions). The surface active agents may be anionic, cationic or non-ionic (e.g., salts of lignosulfonic acids, alkyl-aryl sulfonic acids, acetates of alkylamines and condensates of ethylene oxide with fatty alcohols or acids). In addition, the compositions may contain thickeners, adhesives, stabilizers, preservatives and other adjuvants known to the art.
The glyoxylates may be applied by conventional techniques (e.g., spreading, dusting or spraying or via fumigation smoke bombs in confined areas such as greenhouses) in a variety of forms (e.g., solutions, suspensions, wettable powders or granules).
The compositions of the present invention generally will contain from 5 to 95 percent by weight of the active glyoxylate compound and will be applied at a rate of from 0.5 to 4 kilograms per hectare, when used as herbicides. While in a plant growth regulating composition the amount of active ingredient may be comparable, the amount employed will vary greatly depending upon the particular glyoxylate chosen and the effect in question, generally ranging from 0.01 gram to 4 kg per hectare. Conveniently, such applications are obtained by spraying a solution containing from 0.1 to 500 ppm active ingredient to run-off, depending on the plant species to be treated.
Some of the compounds which are the subject of the present invention are derived from the acid form which may be prepared by methods known to the art, for example, according to the teachings of U.S. Patent 3,836,543 incorporated herein by reference. Modifications and variations of these procedures where benzene ring substituents are other than those described in the '543 patent and where substitution is desired at the 12 position, are shown in the examples below. Thereafter, they may be converted to the final form generally according to methods also known in the art, for example, conventional esterification when preparing a lower alkyl ester.
In order that those skilled in the art may more readily understand the present invention and certain preferred embodiments by which it may be carried into effect, the following specific examples are afforded.
PREPARATIONS
EXAMPLE 1 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylic acid
Into a 12 liter 3-neck flask fitted with an air-driven overhead stirrer and a condenser are placed 2,2'-methylene bisphenol (200.24 gram, 1.0 mol), 4 liter of isopropyl alcohol and then potassium carbonate (552.84 gram, 4.0 mol), while stirring. Dichloroacetic acid, (82.5 ml, 1.0 mol) is added over a period of 2 minutes. During the addition of the dichloroacetic acid some effervescence is observed. The reaction mixture, which is a white, easily stirred, heterogenous mixture, is heated at reflux and stirred vigorously. After 24 hours, the reaction mixture is cooled to room temperature and an additional 82.5 ml (1.0 mol) of dichloroacetic acid is added. Again, some effervescence is observed. The reaction mixture is then heated at reflux for an additional 72 hours. Total reflux time is 96 hours. After 48 hours of total reflux time, the reaction mixture thickens and vigorous stirring is maintained.
Once the 96 hour reflux period is complete, the condenser is replaced with a distillation head and 200 ml of isopropyl alcohol is distilled off at atmospheric pressure and replaced with 200 ml of H2O. This is repeated until the distillation temperature reaches 95-100ºC. During the distillation procedure, once H2O is added, the reaction mixture becomes much more fluid and eventually a reddish brown homogenous solution is obtained. After the distillation temperature reaches 95-100ºC, the reaction mixture is cooled to room temperature. Upon cooling, solids form, therefore it is important to maintain vigorous stirring. The reaction mixture is then made strongly acidic by the careful addition of concentrated HCl (800 ml) over a period of 1-2 hours. Extreme caution must be taken during the addition of the HCl because of effervescence. The effervescence is particularly vigorous during the latter stage of HCl addition. Once the HCl has been added, the reaction is stirred an additional 2 hours at room temperature. The solids are collected by filtration and washed well with H2O.
These solids are then placed in a separatory funnel with 2 liters of ethyl acetate and 2 liters of IN HCl and shaken vigorously. The organic layer is separated, washed with brine, dried over MgSO4 and concentrated. The solids obtained are then dried in a vacuum oven to afford 239 grams (93 percent) of crude product as a brown-tan solid, which are then placed in a Soxhlet extraction apparatus and exhaustively extracted with refluxing cyclohexane (2 liters). Periodically the cyclohexane solution is cooled and the precipitated product collected by filtration. The rate of the extraction depends on how vigorously the cyclohexane refluxes and recycles. There is obtained 147 grams of 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid as a white solid: mp 153-157ºC; IR (KBr) 5.78, 6.76, 6.93, 8.12, 10.1, 13.1 cm-1; 1H NMR (60 MHz, DMSO-d6) 3.64 and 4.38 (2d, 2, CH2), 5.09 (s, 1, CH), 6.9-7.6 (m, 8, Ar-H); greater than 99 percent purity as determined by liquid chromatography.
EXAMPLE 2 n-Butyl 12H-Dibenzo[d,g] [1,3.dioxocin-6-carboxylate Into a 500 ml round bottom flask fitted with a stir bar and a Dean-Stark apparatus is placed 111.4 grams of crude (87 percent) 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid in 300 ml of 2:1 n-butanol:toluene. The mixture is stirred at room temperature for 15 minutes to effect the complete dissolution of the acid. Concentrated sulfuric acid (4.0 ml) is then added and the reaction mixture is heated to reflux. Immediately upon attaining reflux, an aqueous layer begins to separate out in the Dean-Stark apparatus. After 2 hours at reflux, no additional water formation is observed and the reaction is cooled to room temperature with a cold water bath. A total of 10 ml of water is collected, the majority of this water being formed in the initial 30 minutes of reflux. The cooled reddish-yellow reaction solution is diluted with 200 ml of toluene, washed with 300 ml of water, 300 ml of saturated aqueous NaHCO3, 300 ml of brine and then concentrated under reduced pressure on a rota-vap. Toluene (200 ml) is added to the residue and the solution again is concentrated under reduced pressure. This evaporation with toluene facilitates the removal of n-butanol. The residue obtained is taken up into 300 ml of 2:1 toluene:ether and washed with 200 ml of 5 percent NaOH. Brine, 50 ml, is added to break up the emulsion that forms with the 5 percent NaOH wash. The organic solution is then washed with 200 ml of brine, dried over MgSO4 and concentrated under reduced pressure to afford a thick light reddish-yellow liquid (130 grams). This liquid is then subjected to vacuum distillation, using a Claisen adapter as the distillation head and an oil bath for heating. Care is taken during the course of the distillation to avoid solidification of the product in the distillation condenser. A forerun (11 grams) is collected having a b.p. 70ºC to 170ºC at 0.25 mm. Pure n-butyl ester, 84.3 grams (62 percent), is then collected from 171ºC to 180ºC at 0.25 mm as a thick clear liquid which readily solidifies on cooling to afford a white solid: mp 63-66°C (softening at 60ºC); greater than 99 percent purity as determined by L.C. bp 189-195ºC/0.4mm; IR (neat) 3.45, 5.75, 6.95, 8.35, 10.4 cm-1; H NRM (60 MHz, CDCl3) 0.9-1.9 (m, 7, OCH2CH2CH2CH3), 3.42 and 4.6 (2d, 2, CH2), 4.35, (t, 2, OCH2CH2CH2CH3), 5.05 (s, 1, CH), 7.0-7.4 (m, 8, Ar-H)).
Anal. Calcd. for C19H20O4: C, 73.06; H, 6.45
Found: C, 73.0; H, 6.7
EXAMPLE 3
Ethyl 12H-Dibenzo[d,g][1,31dioxocin-6-carboxylate
A solution of 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid (31.8 grams, 0.124 mol) and cone. H2SO4 (1.6 ml) in 215 ml of ethanol is heated at reflux, allowing the condensate to pass through 4A molecular sieves. After 2 hours, the reaction is cooled to room temperature and 100 ml of methylene chloride is added and then neutralized by the addition of solid Na2CO3. The salts are removed by filtration and the filtrate concentrated. The residue is taken up into CH2Cl2, washed with water, 5 percent aq. NaOH and brine, dried over MgSO4 and concentrated to afford 31.1 grams (88 percent) of product as a white solid: mp 86.5-88.5°C; IR (KBr) 5.63, 6.7, 6.88, 7.2, 8.12, 8.98, 9.25, 10.1 cm-1; 1H NMR (60 MHz, CDCl3) 1.4 (t, 3, CH3) , 3.43 and 4.6 (2d, 2, CH2) , 4.42 (q, 2, CH2CH3), 5.1 (s, 1, CH), 7.0-7.4 (m, 8, Ar-H).
Anal. Calcd. for C17H16O4: C, 71.82; H, 5.67
Found: C, 71.7; H, 5.8 EXAMPLE 4
Methyl 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
Preparation proceeds as described in Example 3, only substituting methanol for ethanol. Obtained is a white solid: mp 107-110ºC; IR (KBr) 5.69, 6.77, 8.2, 9.3, 10.05 cm-1; 1H NMR (60 MHz, CDCl3) 3.5 and 4.62
(2d, 2, CH2), 3.98 (s, 3, CH3), 5.1 (s, 1, CH), 7.0-7.5
(m, 8, Ar-H).
Anal . Calcd. for C16H14O4 : C, 71. 10 ; H, 5.22
Found: C, 71. 0 ; H, 5. 1
EXAMPLE 5 n-Propyl 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
Preparation proceeds as in Example 3, only substituting a like quantity of n-propanol for the ethanol, to obtain a white solid: mp 82-85°C; IR (KBr)
5.7, 8.35, 9.4, 10.15 cm-1; 1H NMR (60 MHz, CDCl3) 1.05
(t, 3, CH3), 1.95 (m, 2, CH2CH2CH3), 3.47 and 4.65 (2d, 2, CH2), 4.33 (t, CH2CH2CH3), 5.1 (s, 1, CH), 6.9-7.5 (m, 8, Ar-H). Anal. Calcd. for C18H18O4: C, 72.47; H, 6.08
Found: C, 72.7; H, 6.0
EXAMPLE 6 iso-Propyl 12H-Dibenzo[d,g][1.3]dioxocin-6-carboxylate
The subject product is prepared as described in Example 3, only substituting iso-propanol for ethanol, yielding a white solid: mp 94-97ºC; IR (KBr) 5.73, 6.78, 8.25, 9.05, 9.4, 10.1 cm-1; 1H NMR (60 MHz, CDCl3) 1.4
(d, 6, CH-(CH3)2), 3.46 and 4.6 (2d, 2, CH2) , 5.03 (s, 1, O-CH-O), 5.25 (m, 1, CH(CH3)2), 6.9-7.5 (m, 8, Ar-H). Anal. Calcd. for C18H18O4: C, 72.47; H, 6.08
Found: C, 72.4; H, 5.9 EXAMPLE 7 t-Butyl 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
A solution of 12H-dibenzo[d,g] [1,3]dioxocin-6-carboxylic acid (3.0 g, 0.0117 mol) in 45 ml of thionyl chloride is heated at reflux. After 4 hours at reflux, the excess thionyl chloride is distilled off at atmospheric pressure and then under vacuum to remove traces of thionyl chloride. The acid chloride obtained is dissolved in 35 ml of toluene and added dropwise over a period of 20 minutes to a solution of t-butyl alcohol (15 ml) containing N,N-dimethylaniline (1.8 ml, 0.01405 mol). After stirring 23 hours at room temperature, the reaction mixture is concentrated under reduced pressure and the residue obtained is taken up into ethyl acetate, washed with water and brine, dried over MgSO4 and concentrated to yield 3.4 g of a syrupy residue. Dry column chromatography (elution with 1:4 ethyl acetate-hexanes) afforded 1.57 g (43 percent) of product as a white solid: mp 94-97ºC; IR (KBr) 5.75, 8.22, 8.7, 9.43, 10.22, 13.21 cm-1; 1H NMR (60 MHz, CDCl3) 1.6 (s, 9, C(CH3)3), 3.45 and 4.6 (2d, 2, CH2), 4.93 (s, 1, CH) 6.95-7.4 (m, 8, Ar-H).
Anal. Calcd. for C19H20O4: C, 73.06; H, 6.45
Found: C, 73.0; H, 6.3
EXAMPLE 8 n-Octyl 12H-Dibenzo[d,g][1-3]dioxocin-6-carboxylate
12H-Dibenzo[d,g] [1,3]dioxocin-6-carboxylic acid (4.0 g, 0.0156 mol) and 45 ml of thionyl chloride are refluxed/distilled as in Example 7. The acid chloride is then dissolved in 50 ml of toluene and added dropwise over a period of 10 minutes to a solution of n-octyl alcohol (20 ml) containing triethylamine (2.0 ml, 0.0187 mol). After stirring 20 hours at room temperature, the insolubles that form are filtered off and the filtrate concentrated under reduced pressure. The residue obtained is taken up into CHCl3, washed with H2O then brine, dried over MgSO4 and concentrated. The residue obtained is purified by dry column chromatography (elution with 1:10 ether-petroleum ether) to afford 4.18 g (73 percent) of product as a clear syrup; IR (neat) 3.42, 5.63, 6.71, 6.87, 8.95, 10.1 cm-1; 1H NMR (60 MHz, CDCl3) 0.9-2.0 (m, 15, OCH2 (CH2)6(CH3)), 3.48 and 4.62 (2d, 2, CH2), 4.35 (t, 3, OCH2 (CH2)6CH3)), 5.07 (s, 1, CH), 7.0-7.5 (m, 8, Ar-H).
Anal. Calcd. for C23H28O4 C, 74.97; H, 7.66
Found: C, 74.6; H, 8.2
EXAMPLE 9 n-Butoxyethyl 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
Crude12H-dibenzo[d,g] [1,3]dioxocin-6-carbonyl chloride (4.8 g, 17.5 mmol) is dissolved in toluene and treated with a solution of 2-butoxyethanol (2.77 ml, 21 mmol) and 5 ml of triethylamine in toluene at 0ºC under argon. The mixture is heated at reflux for 2 hours and then cooled to room temperature. The mixture is poured into 150 ml of water and extracted with 4 × 100 ml of ethyl acetate. The organic solution is washed with 5 percent hydrochloric acid, 5 percent sodium hydroxide and then brine, dried with magnesium sulfate and filtered. The solvent is removed to leave a yellow liquid which is chromatographed on dry column silica gel, using ethyl ether/hexane (1:2) as the solvent, to give a yellowish oil (4.3 g, 69 percent). An analytically pure material is obtained by using prep thin layer chromatography. IR (neat) 1770, 1582 cm-1. 1H NMR (CDCl3) 0.75-1.3 (m, 3H, CH3), 1.2-2.0 (m, 4H, CH2) , 3.3-4.0 (m, 5H, OCH2 and benzylic), 4.4-4.9 (m, 3H, OCOCH2 and benzylic), 5.6 (s, 1H, CH), 6.9-7.5 (m, 8H, aromatic).
Anal. Calcd. for C21H24O5: C, 70.7; H, 6.79
Found: C, 70.4; H, 6.9
EXAMPLE 10
Cvclohexyl 12H-Dibenzo[d,g][1.3]dioxocin-6-carboxylate
Crude12H-dibenzo[d,g] [1,3]dioxocin-6-carbonyl chloride (4 g, 14.5 mmol) is dissolved in 45 ml of toluene and treated with cyclohexanol (1.75 g, 17.5 mmol) and 3 ml of triethylamine at 0ºC under argon. The mixture is heated at reflux for 2 hours, cooled, washed with 5 percent sodium hydroxide then brine, dried with magnesium sulfate and filtered. The solvent is removed to leave a brown liquid which is chromatographed on dry column silica gel, using ethyl ether/hexane as solvent, to isolate a yellow solid. This solid is decolorized with charcoal to give a off-white solid (4.32 g, 87.7 percent), mp 120-125ºC: IR (KBr) 1755, 1580 cm-1. 1H NMR (CDCl3) 1.0-2.4 (m, 11H, cyclohexyl), 3.37, 3.6, 4.51 and 4.73 (q, 2H, CH2), 5.05 (s, 1H, OCH) 6.9-7.45 (m, 8H, aromatic).
Anal. Calcd. for C21H22O4: C, 74.54; H, 6.55
Found: C, 74.3; H, 6.6
EXAMPLE 11
Tetrahydrofurfuryl 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
To a solution of crude 12H-dibenzo[d,g][1,3] dioxocin-6-carbonyl chloride (4.25 g, 15 mmol) in toluene is slowly added a solution of tetrahydrofurfuryl alcohol (1.8 ml, 18 mmol) and 3 ml of triethylamine in toluene at 0ºC under nitrogen. The mixture is heated at reflux for 1 hour, cooled and treated with water and ethyl acetate. The organic layer is washed with 10 percent sodium hydroxide then brine, dried with magnesium sulfate and filtered. The solvent is removed leaving a yellowish oil which is chromatographed on dry column silica gel using ethyl acetate/hexane as the solvent. The resultant (still yellow) oil is decolorized with charcoal and solidified to yield a white solid (4.12 g, 78 percent) mp 83-85ºC: IR (KBr) 1760, 1580, cm-1, 1H NMR (CDCl3) 1.6-2.4 (m, 4H, CH2), 3.35, 3.57, 4.5 and 4.71 (q, 2H, CH2), 3.7-4.1 (m, 2H, CH2O), 4.1-4.5 (m, 3H, OCH2CHO), 5.1 (S, 1H, CH) 6.95-7.5 (m, 8H, aromatic). Anal. Calcd. for C20H20O5: C, 70.58; H, 5.92
Found: C, 70.8; H, 5.9
EXAMPLE 12
Ethyl 12H-Dibenzo[d,g][1,3]dioxocin-6-thiocarboxylate
To a solution of 12H-dibenzo[d,g][1,3]dioxocin -6-carboxylic acid (1 gram, 3.9 mmol) and ethanethiol (0.8 ml, 5.9 mmol) in 10 ml of dry tetrahydrofuran at -25ºC, is added dicyclohexyl carboximide (DCC, 2 grams, 9.8 mmol) under argon. The mixture is stirred at -20ºC for 2 hours and then kept in the refrigerator overnight. The mixture is warmed to room temperature and to it is added an aqueous solution of oxalic acid to destroy the excess DCC. The mixture is diluted with ethyl ether and filtered. The solid is washed with ethylacetate and the filtrate separated. The organic layer is washed with 10 percent sodium hydroxide and then with water twice and brine once. The organic solution is next dried over magnesium sulfate and filtered. The solvent is removed to give a yellowish viscous oil which was chromatographed on dry column silica gel using ethyl acetate/hexane (1:2) as the solvent to give a yellowish viscous oil (890 mg). This oil was solidified in petroleum ether to give a white solid, mp 77.5-79°C: IR (KBr) 1690, 1000, 7580 cm-1; 1H NMR (CDCl3) 1.2-1.6 (t, 3H, CH3) , 2.82-3.28 (q, 2H, SCH2), 3.37, 3.58, 4.49 and 4.69 (q, 2H, CH2), 4.99 (s, 1H, CHO), 7.02-7.45 (m, 8H, aromatic).
Anal. Calcd. for C17H16O3S: C, 67.98; H, 5.37
Found: C, 67.8; H, 5.5
EXAMPLE 12A
12H-Dibenzo[d,g][1.3]dioxocin-6-thiocarboxamide
A stirred solution of 12H-dibenzo[d,g][1,3] dioxocin-6-carboxamide (3.88 grams, 0.0152 mol) and Lawesson's reagent (3.69 grams, 0.00912 mol) in 40 ml of toluene is heated at reflux. After 2.5 hours, the reaction is cooled to room temperature and concentrated under reduced pressure to afford a dark gummy residue. Flash chromatography of this material (elution with CH2Cl2) affords 1.6 grams of product as a tan solid. Recrystallization from hexanes results in 1.1 grams of product as an off white solid: mp. 165-169ºC; IR (KBr) 3380 , 3140 , 1615 , 1440 , 1220 , 975 cm-1; 1H NMR (DMSO-d6) 3 . 65 and 4 .41 (2d, 2 , 12a and 12b) , 5. 17 (s , 1 , H6) , 7 . 0-7. 6 (m, 8 , Ar-H) .
Anal . Calcd. for C15H13NO2S : C, 66.4 ; H, 4 .8 ; N, 5.2
Found: C, 66.5; H, 4.9; N, 5.1
EXAMPLE 13
12H-Dibenzo[d,g][1,3]dioxocin-6-nitrile
To a stirred solution of 12H-dibenzo[d,g][1,3] dioxocin-6-carboxamide (8.24 grams, 0.0323 mol) and pyridine (5.74 ml, 0.071 mol) in 80 ml of 1,4-dioxane at 0°C, is added trifluoroacetic anhydride (5.0 ml, 0.0355 mol). After stirring for 5 minutes at 0°C, the reaction is warmed to room temperature and stirred for 3 hours. The volatiles are removed under reduced pressure, the residue taken up into ethyl acetate, washed with IN HCl, H2O, saturated aqueous NaHCO3, brine, dried over MgSO4 and concentrated to afford 6.8 grams of a white solid. Recrystallization from cyclohexane affords 5.46 grams (71 percent) of product as a white solid; mp 127-130ºC; IR (KBr) 6.28, 6.71, 6.85, 7.44, 8.1, 8.45, 8.96, 13.1 cm-1; 1H NMR (60 MHz, CDCl3) 3.83 and 4.29 (2d, 2, CH2) , 5.84 (S, 1, CH), 7.2-7.0 (m, 8, Ar-H).
Anal. Calcd. for C15H1NO2: C, 75.94; H, 4.07; N, 5.90
Found: C, 75.8; H, 4.0; N, 5.9 EXAMPLE 14
Sodium 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
A solution of 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid (1.3 grams, 0.00507 mol) and NaOH (0.41 grams, 0.0101 mol) in 50 ml of methanol is refluxed for 30 minutes. The reaction mixture is then concentrated under reduced pressure and the residue recrystallized from ethanol-water to afford 0.65 grams (45 percent) of product as a white solid: mp greater than 320ºC; IR (KBr) 3.0, 6.2, 7.0, 8.25, 8.35, 10.45, 13.3 cm-1; 1H NMR (60 MHz, D2O) 3.3 and 4.4 (2d, 2, CH2) , 4.8 (s, 1, CH), 6.8-7.4 (M, 8, Ar-H).
Anal. Calcd. for C15H11O4Na 1/2 H2O: C, 62.7; H, 4.2
Found: C, 63.0; H, 3.9 EXAMPLE 15
Potassium 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
A mixture of 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid (5.0 g, 0.0195 mol) and potassium carbonate (1.95 g, 0.0195 mol) in 100 ml of water is stirred at room temperature for 4 hours then at 45ºC for 2 hours. The reaction mixture is then cooled to room temperature, treated with charcoal and concentrated to afford a wet off-white solid. This material is recrystallized from ethanol to give 2.27 g (39.5 percent) of product as a white-gray solid: mp 275-290ºC; IR (KBr) 2730-3600, 1610, 980, 760 cm-1; % NMR (CDCl3) 3.5 and 4.35 (2d, 2, CH2), 4.5 (S, 1, H6), 6.8-7.5 (m, 8, Ar-H).
Anal. Calcd. for Cl5H11O4K·1/2 H2O: C, 59.4; H, 3.99
Found: C, 59.2; H, 4.5
EXAMPLE 16
Diethanolamine Salt of 12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylic Acid
To a stirred solution of 12H-dibenzo[d,g][1,3] diox[cin-6-carboxylic acid (4.0 grams, 0.0156 mol) in 40 ml of tetrahydrofuran is added diethanolamine (1.64 grams, 0.0156 mol). After 2 hours at room temperature, the solids that formed are collected by filtration, washed with ether and dried to afford 5.04 grams (89 percent) of product as a white solid: mp 114-116ºC; IR (KBr) 3.0-4.0, 6.25, 6.79, 7.05, 8.1, 10.35 cm-1; 'H NMR (60 MHz, DMSO-d6) 3.05 (m, 4, (CH2CH2OH)2), 3.55 and 4.37 (2d, 2, CH2), 3.75 (m, 4, (CH2CH2OH)2), 4.69 (s, 1,CH), 6.4-7.5 (m, 12, Ar-H and 4 exchangeable).
Anal. Calcd. for C19H23O6: C, 63.15; H, 6.41; N, 3.88
Found: C, 63.2; H, 6.4; N, 4.0
EXAMPLE 17
12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylic acid dimethyl amine salt
To a solution of 12H-dibenzo[d,g] [1, 3]dioxocin -6-carboxylic acid (5 g, 19.5 mmol) in ethyl acetate/benzene is added excess liquid dimethylamine at 0"C under nitrogen. The mixture is stirred overnight at room temperature under nitrogen. The resultant solid is filtered and dried to yield 5.5 g of white solid, mp 164-172° C: IR (KBr) 1640 cm-1; 1H NMR (CDCl3) 2.51 (S, 6H, NCH3) , 3.47, 3.6, 4.25, and 4.4 (q, 2H, CH2), 4.55 (s, 1H, CHCO2) 6.8-7.5 (m, 8H, aromatic).
Anal. Calcd, for C17H19O4N: C, 67.76; H, 6.36; N, 4.65
Found: C, 67.7; H, 6.5; N, 5.0
EXAMPLE 18
4(2,2-Dimethyl-1,3-dioxolanyl)methyl 12H-dibenzo[d,g][1.3] dioxocin-6-carboxylate
12H-Dibenzo [d, g] [1,3] dioxocin-6-carbonyl chloride (10 g, 39 mmol) is dissolved in toluene and added to a solution of glycerolketal (5.6 ml, 45 mmol) and 10 ml of triethylamine in toluene at 0-10ºC under argon. The mixture is heated at reflux for 5 hours, cooled to room temperature, poured into 150 ml of water and extracted with 4 × 150 ml of ethyl acetate. The organic solution is washed with 5 percent HCl, 5 percent NaOH and then brine, dried with magnesium sulfate and filtered. The solvent is removed and the residue chromatographed on dry column silica gel using ethyl ether/hexane (1:1) as the solvent to give a yellowish liquid which is crystallized in petroleum ether. The solid is filtered and washed with petroleum ether to give a white solid, mp 109-111ºC: IR (KBr) 1780, 1581 cm-1, 1H NMR (CDCl3) 1.4 and 1.47 (2S, 6H, CH3) , 3.36, 3.58, 4.49 and 4.7 (q, 2H, CH2), 3.7-4.4 (m, 3H, CHO and CH2O) , 4.4-4.6 (m, 2H, OCH2), 5.1 (s, 1H, OCHO) , 6.95-7.45 (m, 8H, aromatic).
Anal. Calcd. for C21H22O6: C, 68.10; H, 5.99
Found: C, 68.3; H, 6.0
EXAMPLE 19 Methyl-6-Methyl-12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
To a stirred solution of isopropyl cyclohexyl amine (2.92 ml, 0.0178 mol) in 15 ml of dry tetrahydrofuran (THF) under N2 at 0ºC is added n-BuLi (11.84 ml of 1.5 M in hexane). After stirring 15 minutes at 0°C, the solution is cooled to -65ºC and a solution of methyl 12H-dibenzo[d,g] [1,3]dioxocin-6-carboxylate (4.0 g, 0.0148 mol) in 10 ml of THF is added dropwise over a period of 5 minutes. The solution is stirred at -65ºC for an additional 10 minutes and then added via syringe over a period of 2 minutes to a solution of methyl iodide (1.84 ml, 0.0246 mol) in 25 ml of dry dimethyl sulfoxide at room temperature. After stirring for 30 minutes, the reaction mixture is diluted with 300 ml of CH2Cl2, washed with H2O, IN HCl and then brine, dried over MgSO4 and concentrated. The residue obtained is purified by dry column chromatography (elution with 1:4 ethyl acetate-hexanes) to afford 2 g of a yellow syrup. This material was subjected to HPLC purification (Waters 500, 2 columns, 4 cycles, elution with 1:7 ethylacetate- hexanes) to afford 1.1 g (26 percent) of product as a clear syrup: IR (neat) 5.65, 6.3, 6.7, 6.85, 7.25 cm-1; 1H NMR (60 MHZ, CDCl3) 1.36 (s, 3, CH3), 3.71 and 4.32 (2d, 2, CH2) 3.9 (s, 3, OCH3), 6.95-7.4 (m, 8, Ar-H).
Anal. Calcd. for C17H16O4: C, 71.82; H, 5.67
Found: C, 71.8; H, 5.7
EXAMPLE 20
(cis and trans) Methyl-12-Methyl-12H-Dibenzo[d,g][1,3] dioxocin-6-ccrboxylate
A mixture of 2,2'ethylidenebisphenol (10.0 grams, 0.0467 mol), dichloroacetic acid (3.85 ml, 0.0467 mol) and potassium carbonate (25.8 grams, 0.187 mol) in 200 ml of isopropyl alcohol is heated at reflux for 24 hours with vigorous stirring, after which an additional 3.85 ml of dichloroacetic acid is added and the mixture refluxed with stirring for 70 hours. The isopropyl alcohol is removed by distillation at atmospheric pressure and replaced gradually with H2O. The reaction mixture is cooled, acidified by addition of concentrated HCl and extracted into chloroform. The chloroform extract is washed with brine, treated with charcoal, dried over MgSO4 and concentrated to afford a quantitative yield of crude acid. This material is then converted to the methyl ester by refluxing in a methanol solution (100 ml) in the presence of cone. H2SO4 (0.6 ml) for 2 hours. The solution is cooled, 50 ml of CH2Cl2 is added and the mixture neutralized by the addition of solid Na2CO3. The inorganic salts are removed by filtration and the filtrate concentrated and taken up into CH2Cl2, washed with brine, dried over MgSO4 and concentrated to afford 11.5 grams of a dark semi-solid. Dry column chromatography (elution with 1:4 EtOAc-hexane) yields 5.0 grams (38 percent) of product as a white solid consisting of a 1:1 mixture of cis and trans isomers: mp 95-120°C; IR (thin film) 5.62, 6.7, 6.9, 8.2, 9.25, 10.05, 13.05 cm-1; 1H NMR (60 MHz, CDCl3) 1.66 and 1.89 (2d, 2, CH3), 3.88 and 3.95 (2s, 3, OCH3), 3.95 and 5.1 (2q, 2, CH), 5.0 and 5.36 (2s, 1, CH), 7.0-7.5 (m, 8, Ar-H).
Anal . Calcd. for C17H16O4: C, 71.82 ; H, 5. 67
Found: C, 71.6; H, 5.7
EXAMPLE 21 Ethyl 12,12-Dimethyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
A mixture of 2,2'-isopropylidene bisphenol (3.65 g, 0.01594 mol), potassium hydroxide (2.68 g of 85 percent, 0.0478 mol) and dichloroacetic acid (1.31 ml, 0.01594 mol) in 65 ml of isopropyl alcohol is heated at reflux. After 20 hours at reflux, an additional 1.79 g of 85 percent KOH and 1.31 ml of dichloroacetic acid are added and the reaction mixture is heated at reflux for 2 days. The reaction mixture is then diluted with 200 ml of H2O, acidified by the addition of concentrated HCl (10 ml) and extracted into ethyl acetate. The ethyl acetate solution is washed with brine, dried over MgSO4 and concentrated. The residue is washed with petroleum ether to afford 3.7 g of crude product as a red-brown syrup. This material is then purified by an esterification-saponification-esterification procedure (esterification agent methanol, H2SO4). Dry column chromatography yields 0.97 g of crude product, which is saponified (NaOH, MeOH-H2O), and purified by dry column chromatography to afford 0.60 g of a white solid. Esterification of this material (EtOH, H2SO4) and purification by preparative thin layer chromatography (elution with 1:4 ethyl acetate-hexanes) yields 0.25 g of product as a clear syrup: IR (neat) 3.34, 5.65, 6.95, 8.2, 13.2 cm-1; 1H NMR (CDCl3) 1.28 (t, 3, CH2CH3), 1.75 and 1.9 (2s, 6, (CH3)2C), 4.24 (q, 2, CH2CH3), (s, 1, CH), 6.9-7.6 (m, 8, Ar-H); m/e 312. Anal. Calcd. for C19H20O4: C, 73.06; H, 6.45
Found: C, 72.4; H, 5.7
EXAMPLE 22
12H-Dibenzo[d,g][1,3]dioxocin-12-hydroxy-6-carboxylic acid Lactone
To a stirred solution of 12H-dibenzo[d,g] [1,3] dioxocin-12-keto-6-carboxylic acid (10.0 g, 0.0370 mol) and sodium hydroxide (1.63 g, 0.0407 mol) in 200 ml of 5:3 ethanol-water is added sodium borohydride (1.40 g, 0.0370 mol) and the reaction is heated to 55ºC. After 16 hours at 55ºC, the reaction is cooled to room temperature and poured cautiously onto 1 HCl (500 ml), then extracted with ethyl acetate. The ethyl acetate solution is washed with brine, dried over MgSO4 and concentrated to afford a quantitative yield of a mixture of alcohols and lactone. This mixture and p-toluenesulfonic acid (0.05 g) in 250 ml of benzene is heated at reflux. After 2 hours, the reaction is cooled to room temperature, diluted with ethyl acetate and filtered to remove insoluble polymeric material. The filtrate is washed with saturated aqueous NaHCO3, then brine, dried over MgSO4 and concentrated to afford 6.1 g (64 percent) of a white solid (approximately 95 percent pure). Analytically pure material is obtained by dry column chromatography (elution with 1:2 EtOAc-hexanes), followed by recrystallization from benzene-hexanes: mp 147-149ºC; IR (KBr) 5.73 , 6.74 , 7.76 , 8.41 , 9 . 74 , 13 . 36 cm-1, 1H NMR
( 60 MHZ , CDCl3) 5.97 (s , 1 , CHCO2-) , 6. 39 (s , 1 ,
Ar2CH-O) , 6. 8-7 . 4 (m, 8 , Ar-H) .
Anal . Calcd. for C15H10O4: C, 70.86 ; H, 3 .96
Found: C, 71.2 ; H, 4 .0 EXAMPLE 23
Ethyl 1-Methyl 12H-dibenzo[d,g][1,3]dioxocin-6- carboxylate
A mixture of 6-methyl-2,2'-methylene bisphenol (3.1 g, 0.0145 mole), potassium hydroxide (2.87 g of 85 percent, 0.0434 mol) and dichloroacetic acid (1.2 ml, 0.0145 mol) in 55 ml of isopropyl alcohol is heated at reflux. After 22 hours at reflux, an additional 1.91 g of 85 percent KOH and 1.2 ml of dichloroacetic acid are added and the reaction mixture is refluxed for 4 hours. The reaction mixture is then cooled, diluted with 150 ml of H2O, acidified by the addition of concentrated HCl and extracted into ethyl acetate. The ethyl acetate solution is washed with brine, dried over MgSO4 and concentrated to afford the crude acid as a gummy yellow-tan solid. A solution of the crude acid and concentrated H2SO4 (0.2 ml) in 25 ml of ethanol is heated at reflux. After 2 hours, the solution is cooled to room temperature, diluted with CH2Cl2 (15 ml) and neutralized by the addition of solid Na2CO3. The inorganics are removed by filtration and the filtrate is concentrated under reduced pressure. The residue obtained is taken up into ethyl acetate, washed with H2O, then brine, dried over MgSO4 and concentrated to afford 3.9 g of an amber syrup. Dry column chromatography (elution with 1:4 ethyl acetate-hexanes) followed by recrystallization from cyclohexane yields 1.0 g of product as a white solid: mp 78-83'C; IR (KBr) 1759, 1205, 1065, 980 cm-1; 1H NMR (CDCl3) 1.41 (t, 3, CH2CH3) , 2.52 (s, 3, CH3), 3.69 and 4.45 (2d, 2, (AR)2-CH2), 4.4 (q, 2, CH2CH3) , 5.05 (s, 1, CH), 6.85-7.5 (m, 7, Ar-H); mass spectrum, m/e (M+) 298.
EXAMPLE 24
Methyl 2-Methyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
Into a 3-neck round bottom flask fitted with a mechanical stirrer and a condenser, is placed 4-methyl bis (1-hydroxy-2-phenyl)-methane (10.2 g, 48 mmol) and potassium carbonate (26.33 g, 190 mmol) in 200 ml of isopropanol. Dichloroacetic acid (3.93 ml, 48 mmol) is then added and the mixture is heated at reflux for 1 day. More dichloroacetic acid (3.93 ml, 48 mmol) is added and reflux is resumed for 3 more days. 400 ml of water is then added and the mixture is acidified with hydrochloric acid. After stirring the mixture for 2 hours at room temperature and extracting with 200 ml of ethyl acetate twice, the combined organic layer is next washed with 200 ml of IM HCl and 150 ml of brine, dried with magnesium sulfate and filtered. The solvent is removed, yielding about 17 g of brown oil. This oil is used directly for esterification. It is dissolved in 150 ml of methanol and 0.3 ml of concentrated sulfuric acid is added. The mixture is heated to reflux for 2 hours and then cooled to room temperature. Sodium carbonate is added and the mixture is stirred for ½ hour. Following filtration of the mixture, the solvent is removed and the crude solids dissolved in methylene chloride, washed with 100 ml of 5 percent sodium hydroxide and 150 ml of brine, dried with MgSO4 and filtered. The solvent is then removed to yield about 7 g of brown solid, which is chromatographed on dry column silica gel using ethyl ether/hexane as the solvent to give about 5.5 g of white solid. This solid was re-crystallized in ethyl ether/hexane to give 4.51 g of white solid. mp 106-108.5ºC. IR (KBr): 1761, 1748 cm-1. 1H NMR (CDCl3): 2.27 (s, 3H, CH3), 3.3, 3.5, 4.46 and 4.67 (q, 2H, CH), 3.92 (s, 3H, OCH3), 5.02 (s, 1H, CHO) , 6.85-7.5 (m, 7H aromatic H).
Anal. Calcd. for C17H16H4: C, 71.82, H, 5.67
Found: C, 71.5; H, 5.7
EXAMPLE 25
3-Methyl-12-H-dibenzo[d.q][1,3]dioxocin-6-carboxylic acid
To a suspension of sodium hydride (5.7 g of a 50 percent dispersion in oil, washed with petroleum ether; 0.1193 mol) and 18-crown-6 (0.45 g) in 65 ml of 1,4-dioxane is added slowly, dropwise, a solution of dichloroacetic acid (4.0 ml, 0.049 mol) in 65 ml of 1,4-dioxane over a period of 15 minutes, followed by the dropwise addition of 5-methyl-2,2'methylenebisphenol (6.36 g, 0.0297 mol) in 85 ml of 1,4-dioxane over a period of 45 minutes. The reaction mix is then heated at about 90ºC for 18 hours and then at reflux for 4 hours. Next, it is cooled to room temperature, poured onto 600 ml of H2O, acidified by the addition of concentrated
HCl and extracted with ethyl acetate (2 × 500 ml). The ethyl acetate extract, is washed with brine, dried over
MgSO4 and concentrated to afford 9.9 g of crude product as a semi-solid. Purification via extraction with cyclohexane in a Soxhlet apparatus yields 5.0 g (62.3 percent) of product as a white solid: mp 149-152ºC; IR
(KBr) 1730, 1245, 1220, 1015 cm-1; 1H NMR (DMSO-d6) 2.2
(s, 3, CH3) , 3.54 and 4.3 (2d, 2, h12a + H12b) , 5.01 (s, 1, H6) , 6.8-7.5 (m, 7, Ar-H).
Anal. Calcd. for C16H14O4: C, 70.7; H, 5.3
Found: C, 71.1; H, 5.22
EXAMPLE 26
Methyl 4-methyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
A mixture of crude 6-methyl 2,2'-methylene bisphenol (7.0 g, 0.0327 mol), potassium hydroxide (5.5 g, 0.098 mol) and dichloroacetic acid (2.7 ml, 0.0327 mol) in 130 ml of isopropyl alcohol is heated at reflux for 23 hours, following which an additional 5.5 g of potassium hydroxide (0.098 mol) and then 2.7 ml of dichloroacetic acid (0.0327 mol) are added and the reaction mixture is again heated at reflux for an additional 3 hours. The mixture is then cooled to room temperature, diluted with 400 ml of water, acidified by the addition of concentrated HCl (15 ml), extracted with ethyl acetate (200 ml) and the resultant organic solution is washed with brine, dried over MgSO4 and concentrated. The residue is then co-evaporated with toluene to afford 10 g of crude acid as a tan solid. A solution of the crude acid and concentrated H2SO4 (0.6 ml) in 100 ml of methanol is heated at reflux for 2 hours, after which the reaction mixture is cooled to room temperature, diluted with 25 ml of CH2Cl and neutralized by the addition of solid Na2CO3. The inorganic salts are removed by filtration and the filtrate concentrated under reduced pressure. The residue is taken up into a mixture of EtOAc-ether, washed with water, 5 percent aqueous NaOH, then brine, dried over MgSO4 and concentrated to afford 7.0 g of a yellow syrup. Dry column chromatography (elution with 1:4 EtOAc-hexanes) afforded 4.1 g (44 percent) of product as a white solid; greater than 95 percent purity. Recrystallization from cyclohexane afforded 2.1 g (23 percent) of pure product: mp 107-109?; IR (KBr) 5.74, 6.97, 8.3, 9.5, 10.2, 13.5 cm-1; 1H NMR (90 MHz, CDCl3), 2.23 (s, 3, CH3), 3.41 (d, 1, H-CH), 3.95 (s, 3, OCH3), 4.62 (d, 1, H C-H), 5.04 (s, 1, OCHO), 6.9-7.4 (m, 7, Ar-H).
Anal . Calcd. for C17H16O4: C, 71.82 ; H, 5.67
Found: C, 71.8 ; H, 5. 6
EXAMPLE 27 2-Methoxyethyl 12H-Dibenzo [d,g] [1 , 3 ]dioxocin-6-carboxylate
12H-Dibenzo [ d , g ] [ 1 , 3 ] dioxocin-6-carbonyl chloride (5.33 g, 19.5 mmol) is dissolved in toluene and added to a solution of 2-methoxyethanol (2.2 ml, 27.6 mmol) and 7 ml of triethylamine in toluene at 0°-10ºC under argon. The mixture is heated at reflux for 3 hours, cooled to room temperature, poured into 150 ml of water and extracted with 4 × 100 ml of ethyl acetate. The resultant organic solution is washed with 5 percent hydrochloric acid, 5 percent sodium hydroxide and brine, dried with magnesium sulfate and filtered. The solvent is removed to give a brownish solid which is chromatographed on dry column silica gel, using ethyl ether/hexane (1:1) as the solvent, to give a yellowish oil. This oil is solidified, the solid is filtered and washed with ethyl ether/hexane to yield a white solid: mp 74-76ºC: IR (KBr) 1779, 1581 cm-1; 1H NMR (CDCl3) 3.42 (s, 3H, CH3), 3.3-4.0 (m, 3H, CH and OCH2), 4.35-4.8 (m, 3H, CH and OCH2), 5.1 (s, 1H, OCHO), 6.9-7.45 (m, 8H, aromatic).
Anal. Calcd. for C18H18O5: C, 68.78; H, 5.77
Found: C, 69.1; H, 5.9 EXAMPLE 28
2-Ethylhexyl12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylate
To a stirred solution of 12H-dibenzo[d,g] dioxocin-6-carbonyl chloride (4 g, 0.015 mol) in 45 ml of toluene is added a solution of 2-ethylhexanol (2.28 g, 0.017 mol) and 4 ml of triethylamine in toluene at 0ºC under argon. The mixture is heated at reflux for 2 hours, cooled, washed with 5 percent NaOH and then brine, dried with magnesium sulfate and filtered. The solvent is removed to give a brown liquid which is chromatographed on dry column silica gel using ethyl ether/hexane as the solvent to yield a yellowish oil (4.5 g): IR (neat) 1770, 1580 cm-1. 1H NMR (CDCl3) 0.5-2.0 (m, 15H, CH2 and CH3) , 3.33, 3.53, 4.48, and 4.68 (q, 2H, CH2), 4.15-4.35 (d, 2H, OCH2), 5.2 (s, 1H, CH), 6.9-7.4 (m, 8H, aromatic).
Anal. Calcd. for C23H28O4: C, 74.97; H, 7.66
Found: C, 75.1, H, 7.9 EXAMPLE 29
Ethyl 3-t-Butyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
Amixture of 4-t-butyl-2,2'-methylene bisphenol (3.67 g, 0.0143 mol), potassium hydroxide (2.84 g of 85 percent, 0.0429 mol) and dichloroacetic acid (1.18 ml, 0.0143 mol) in 55 ml of isopropyl alcohol is heated at reflux. After 17 hours at reflux, an additional 1.90 g of 85 percent KOH and 1.18 ml of dichloroacetic acid is added and reflux is continued for 4 hours. Thereafter, the reaction mixture is cooled to room temperature, diluted with 150 ml of H2O, acidified by the addition of concentrated HCl and extracted into ethyl acetate. The ethyl acetate solution is washed with brine, dried over MgSO4 and concentrated to afford crude acid as a yellow-brown syrup. A solution of the crude acid and p-toluene sulfonic acid (0.07 g) in 25 ml of 10:1 CHCl3-ethanol is heated at reflux for 1.5 hours with azetropic removal of water. The solution is then cooled to room temperature, diluted with 50 ml of CHCl3, washed with H2O, 5 percent aqueous NaOH and then brine, dried over MgSO4, and concentrated to afford 3.93 g of a yellow-brown syrup. Dry column chromatography (elution with 1:4 EtOAc-hexanes) yields 2.4 g (49 percent) of product as a cloudy syrup: IR (neat) 2975, 1770, 1755,
1485, 1410, 1260, 76 cm-1; 1H NMR (CDCl3) 1.24 (s, 9,
C(CH3)3), 1.43 (t, 3, CH2CH3), 3.43 and 4.51 (2d, 2
AR2CH2) , 4 . 39 (q, 2 , CH2CH3) , 5. 05 (s, 1 CH) , 7 . 0-7.4 (m, 7 , Ar-H) ; mass spectrum, m/e (M+) 340 , (M+ - CH3) 323 ,
(M+ - CH3CH2OH) 294 , (M+ - C4H9) 283 , (M+ - CO2Et) 267.
EXAMPLE 30
Ethyl3-Trifluoromethyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate To a suspension of sodium hydride (2.55 g of a
50 percent dispersion in oil, washed with petroleum ether, 0.0531 mol) and 18-crown-6 (0.2 g) in 30 ml of 1,4-dioxane is slowly added dropwise, a solution of dichloroacetic acid (1.81 Ml, 0.0219 mol) in 30 ml of 1,4-dioxane over a period of 15 minutes, followed by the dropwise addition of 5-trifluoromethy1-2, 2'-methylene bisphenol (3.56 g, 0.0133 mol) in 40 ml of 1,4-dioxane over a period of 45 minutes. The reaction is then heated at reflux for 20 hours, cooled to room temperature, poured into 300 ml of H2O, acidified by the addition of concentrated HCl, and extracted with ethyl acetate (2 × 200 ml). The ethyl acetate extract is washed with brine, dried over MgSO4 and concentrated to afford an oily residue which is further washed with petroleum ether to give 4.6 g of an orange-yellow semi-solid. A solution of this material and p-toluene sulfonic acid (0.07 g) in 30 ml of 10:1 CHCl3-ethanol is heated at reflux for 1 hour with azetropic removal of water. The solution is then cooled to room temperature, diluted with 50 ml of CHCl3, washed with H2O, 5 percent aqueous NaOH, and then brine, dried over MgSO4, and concentrated to afford 3.75 g of a dark residue. Flash chromatography of this material (elution with 1:6 ethyl acetate-hexanes) affords
1.91 g (41 percent) of product as a white solid: mp 78-81ºC; IR (KBr) 1765, 1325, 1115, 990 cm-1; 1H NMR
(CDCl3) 1.41 (t, 3, CH2CH3), 3.52 and 4.51 (2 d, 2,
H12a, H12b) , 4 . 41 (q, 2 , CH2CH3) , 5. 09 (s , 1 , H6) , 7 . 0-7 . 5 (m, 7 , Ar-H) .
Anal . Calcd. for C18H15F3O4 : C, 61. 37 ; H, 4 .29
Found: C, 61.4; H, 4.2
EXAMPLE 31
Methyl 4,8-Dimethyl 12H-dibenzo[d,g][1,3]dioxocin-6- carboxylate
A mixture of 2,2'-methylene bis-6-methyl phenol (4.0 g, 0.0175 mol), dichloroacetic acid (1.45 ml, 0.0175 mol) and potassium carbonate (9.7 g, 0.070 mol) in 100 ml of isopropyl alcohol is heated at reflux for 24 hours with vigorous stirring after which an additional 1.45 ml of dichloroacetic acid is added and the mixture refluxed with stirring for 70 hours. The isopropyl alcohol is removed by distillation at atmospheric pressure and replaced gradually with H2O. The mixture is cooled to 0ºC and the solids collected by filtration.
Water (75 m) is added to the solids and the mixture made strongly acidic with concentrated HCl. The mixture is extracted into CH2Cl2, washed with brine, dried over
MgSO4 and concentrated to afford 3.0 g (73 percent) of the carboxylic acid. Esterification (methanol, H2SO4, reflux) followed by dry column chromatography (elution with 1:4 ethyl acetate- hexanes), affords 1.9 g (50 percent) of product as a white solid: mp 134-135ºC; IR
(KBr) 5.65, 6.72, 8.2, 13.1 cm-1; 1H NMR (60 MHz,
CDCl3) 2.21 (s, 6, 2 CH3) , 3.38 and 4.62 (2d, 2, CH2) ,
4.0 (s, 3, CH3), 4.99 (s, 1, CH), 6.9-7.3 (m, 6, Ar-H).
Anal. Calcd. for C18H18O4.1/4 H2O: C, 71.4; H, 6.16
Found: C, 71.2; H, 6.1
EXAMPLE 32
Methyl 4,8-Dichloro 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
A mixture of 2,2'-methylene bis-6-chlorophenol (10.0 g, 0.0372 mol), dichloroacetic acid (3.07 ml, 0.0372 mol) and potassium carbonate (20.6 g, 0.149 mol) in 150 ml of isopropyl alcohol is heated at reflux for 24 hours with vigorous stirring after which an additional 3.07 ml of dichloroacetic acid is added and the mixture refluxed with stirring for 67 hours. The isopropyl alcohol is removed by distillation at atmospheric pressure and replaced with water, gradually. The reaction mixture is cooled, acidified by addition of concentrated HCl and extracted with CHCl3. The chloroform extract is washed with brine, treated with charcoal, dried over MgSO4 and concentrated to afford 12.3g of crude carboxylic acid. Esterification (methanol, H2SO4, reflux) followed by dry column chromatography (elution with 1:4 ethyl acetate-hexanes) affords 5.29 g of product as a white solid: mp 114-116ºC; IR (KBr) 5.65, 6.95, 8.29, 9.47, 10.3 cm-1; 1H NMR (60 MHz, CDCl3) 3.47 and 4.67 (2d, 2, CH2), 3.99 (s, 3, CH3), 5.04 (S, l, CH), 6.9-7.3 (8, m, Ar-H).
Anal. Calcd. for C16H12Cl2O4: C, 56.66; H, 3.57
Found: C, 56.7; H, 3.5
EXAMPLE 33
3,9-Dimethyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid
A mixture of 2,2'-methylenebis (5-methylphenol) (8.3 g, 0.0364 mol), dichloroacetic acid (3.0 ml, 0.0364 mol) and potassium carbonate (20.1 g, 0.145 mol) in 220 ml of isopropyl alcohol is heated at reflux for 24 hours with vigorous stirring after which an additional 3.0 ml (0.0364 mol) of dichloroacetic acid is added and the mixture is refluxed for an additional 72 hours. The isopropyl alcohol is distilled off and replaced with water. The reaction mixture is then cooled to room temperature and acidified by the addition of concentrated HCl (35 ml). The solids that form are collected by filtration, taken up into ethyl acetate and the ethyl acetate solution is washed with IN HCl, then brine, dried over MgSO4 and concentrated to afford a quantitative yield of crude product as a tan solid. Extraction of the crude product with hot cyclohexane in a Soxhlet extraction apparatus results in 4.55 g (44 percent) of product as a white solid from the cooled cyclohexane solution. Recrystallization from benzene-hexanes yields an analytically pure material: mp 172-174ºC; IR (KBr)
3.4, 5.8, 8.0, 8.9 cm-1; 1H NMR (60 MHz, DMSO-d6) 2.21
(S, 6, 2 CH3), 3.52 (d, 1, H-C-H) 4.23 (d, 1, H-C-H), 6.8-7.4 (6, m, Ar-H).
Anal. Calcd. for C17H10O4: C, 71.82; H, 5.67
Found: C, 72.1; H, 5.7
EXAMPLE 34
Methyl 3,9-Dimethoxy-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
To a solution of potassium hydroxide (1.29 g, 23 mmol) in 100 ml of isopropanol is added 1,1'-methylene bis(4-methoxy-2-phenol) (1.8 g, 6.9 mmol) and then, 0.6 ml of dichloroacetic acid (7.2 mmol). The mixture is heated at reflux overnight. The mixture is then cooled to room temperature and potassium hydroxide (1.29 g, 23 mmol) and dichloroacetic acid (0.6 ml, 7.2 mmol) are added. The mixture is again refluxed overnight. The solvent is removed on a rotavap and water is added. The mixture is then acidified with concentrated hydrochloric acid and extracted with ethyl acetate three times. The organic layer is washed with brine, dried with magnesium sulfate and filtered. The solvent is removed, leaving a yellow oil. This oil is dissolved in 30 ml of methanol and 1 ml of boron trifluoride etherate is added. The mixture is next stirred at room temperature for 4 hours, poured into saturated aqueous sodium chloride (50 ml) and extracted with ethyl acetate three times. The resulting organic solution is washed with 5 percent sodium hydroxide (50 ml) and brine, dried with magnesium sulfate and filtered. The solvent is removed to leave a yellow oil which is chromatographed on a dry column silica gel using ethyl acetate/hexane (2:1) as the solvent to give a white solid (1.16 g), mp 102-106ºC: IR (KBr) 1750, 1620, 1505 cm -1. 1Η NMR (CDCl3) 3.25, 3.4, 4.31 and 4.45 (q, 2H, CH2), 367 (s, 6H, OCH3), 3.92 (s, 3H, OCH3), 5.06 (s, 2H, OCH) , 6.5-7.25 (m, 6H, aromatic).
Anal . Calcd. for C18H18O6: C, 65.45 ; H, 5.49
Found: C, 65.2; H, 5.5
EXAMPLE 35
Methyl 4-t-Butyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate
To a suspension of sodium hydride (1.65 g of a 50 percent dispersion in oil, washed with petroleum ether, 0.0343 mol) and 18-crown-6 (0.13 g) in 16 ml of 1,4-dioxane is added slowly, dropwise, a solution of dichloroacetic acid (1.17 ml, 0.0142 mol) in 18 ml of 1,4-dioxane over a period of 15 minutes followed by the dropwise addition of 6-t-butyl-2,2'-methylene bisphenol (2.2g, 0.00858 mol) in 21 ml of 1,4-dioxane over a period of 25 minutes. The reaction mixture is then heated at reflux. After 24 hours at reflux, the reaction mixture is cooled to room temperature, poured into 150 ml of H2O, acidified by the addition of concentrated HCl (10 ml) and extracted with ethyl acetate (2 × 100 ml). The extract is washed with brine, dried over MgSO4 and concentrated to afford crude carboxylic acid as a yellow-brown syrupy residue. This material is taken up into ether (15 ml) and treated with excess ethereal diazomethane (about 0.6 g in 30 ml of ether). After standing overnight at room temperature, the reaction mixture is evaporated and the residue purified by dry column chromatography (elution with 1:4 EtOAC-hexanes) to afford 0.66 g of slightly impure product. Preparative TLC (elution with 1:10 ether: petroleum ether) yields 0.44 g (16 percent) of pure product as an off white solid: mp 113-117ºC; IR (KBr) 2950, 1760, 1205, 970 cm-1; 1H NMR (CDCl3) 1.3 (s, 9, (CH3)3C), 3.42 and 4.6 (2d, 2, CH2), 3.94 (s, 3, COOCH3) , 5.05 (s, 1, CH), 6.97-7.4 (m, 7, Ar-H).
Anal . Calcd. for C20H22O4: C, 73.6 ; H, 6.79
Found: C, 73.5; H, 7.0
EXAMPLE 36
4-Methyl-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid, diethanolamine salt
A solution of 4-methyl-12H-dibenzo[d,g][1,3] dioxocin-6-carboxylic acid (0.64 g, 0.00237 mol) and diethanolamine (0.25 g, 0.00237 mol) in 6.4 ml of THF is stirred at room temperature. After 18 hours, the clear solution is concentrated under reduced pressure and the residue stirred for 1 hour with 15 ml of ether. The ether is then decanted away, leaving a clear syrup which is dried under vacuum to afford 0.88 g (99 percent) of a white hygroscopic crystalline foam: IR (thin film) 3.0, 6.15, 8.12, 10.32; 1H NMR (CDCl3) 2.21 (s, 3, CH3), 3.1-3.5 (m, 5, 2 CH2 and (Ar)2-C-H), 3.8-4.2 (m, 4, 2 CH2), 4.45 (d, 1, (Ar)2-C-H), 4.8 (s, 1, CH), 6.8-7.4 (m, 7, Ar-H).
EXAMPLE 37
N-Phenyl-12H-dibenzo[d.g][1.3]dioxocin-6-carboxamide
To a stirred solution of crude 12H-dibenzo[d,g] [1,3]dioxocin-6-carboxylicacidchloride (4.3 g, 0.016 mol) and triethylamine (3.3 ml, 0.24 mol) in 40 ml of toluene was added dropwise a solution of aniline
(1.6 ml, 0.017 mol) in 10 ml of toluene over a period of
5 minutes. After being stirred 4.5 h at RT, the reaction was filtered to remove the insolubles that formed, the filtrate was concentrated under reduced pressure. The residue obtained was purified by dry column chromatography (elution with 1:2 ethyl acetat-hexanes) to afford 3.2 g of product. Recrystallization from ethyl acetate-hexanes gave 1.8 g (35%) of product as a white solid: mp 164-165:C; IR (KBr) 6.0, 6.79, 6.97, 8.28,
10.35, 13.27m; 1H NMR (60 MHz, CDCl3) 3.45 and 4.55 (2d,
2, CH2), 5.07 (s, 1, CH), 7.0-8.8 (m, 8, Ar-H), 8.6 (b,
1, NH). Anal . Calcd. for C21H17O3N: C , 76. 1 ; H, 5. 2 ; N, 4 . 2 .
C, 76. 0 ; H, 5. 3 ; N, 4 . 3
EXAMPLE 38
1-Aza-12H-Dibenzo[d.q][1.3]dioxocin-6-carboxylic acid To a suspension of sodium hydride (4.93 g of a
50% dispersion in oil which was washed with petroleum ether, 0.1 mol) and 18-crown-6 (0.39 g) in 55 ml of 1,4-dioxane was added dropwise a solution of dichloroacetic acid (3.5 ml, 0.04 mol) in 55 ml of 1,4-dioxane of a period of 15 min. followed by the dropwise addition of 3-hydrosy-2-(2'-hydroxybenzyl)pyridine (5.17 g, 0.026 mol) in 75 ml of 1,4-dioxane of a period of 40 minutes. The reaction was then heated at reflux. After 24 h at reflux the reaction was cooled to room temperature, poured onto 500 ml of H2O, cautiously neutralized by the addition of 1H HCl and extracted with ethyl acetate (3 × 500 ml). The ehtyl acetate extract was washed with brine, dried over MqSO4 and concentrated to afford the crude carboxylic acid as a yellow-brown solid. Recrystallization from methanol gave 1.5 g (23%) of pure product as an off white solid; mp 224-227:C (d); IR (KBr) 1748, 1440, 1225, 975 cm-1; 1H NMR (DMSO-d6) D=d3.8 and 4.55 (2d, 2, H12a and H12b) , 5.2 (s, 1, H6), 7.0-7.5 (m, 6, H3, H4, H8, H9, H10, H11), 8.2 (m, 1, H2). Anal. Calcd. for C14H11NO4.½ H2O: C, 63.15, H, 4.5; H, 5.3
C, 63.0; H, 4.2; H, 5.0 EXAMPLES 39 THROUGH 97
Additional examples of compounds that fall within the scope of the present invention are described in Table A. These were prepared by procedures analogous to those given in the preceding examples.
Figure imgf000057_0001
Figure imgf000058_0001
h
Figure imgf000059_0001
EXAMPLE 98
Pre and Post Emergent Herbicidal Activity
The herbicide screening test is designed to identify compounds that exhibit pre-emergence (Pre) and/or post-emergence (Post) herbicidal activity. Plantings of the indicated test species are seeded in separate fiber pans (8" X 10" X 3" deep) containing pasteurized soil. The Post pans are seeded two weeks prior to treatment. The Pre pans are seeded one day prior to application of the test compounds. One Pre and one Post pan is employed for each compound, unless otherwise indicated. Prior to application of the test formulation, the Pre pans are mist watered to stabilize the soil surface. The standard laboratory formulation at the 8 kg/ha treatment rate is prepared by weighing 73.6 mg of the test compound into a 125 ml flask to which is then added 40 ml of acetone followed by 40 ml of 0.1% Ortho X-77 surfactant. If the test compound appears insoluble in the formulation, it is treated for 1-2 minutes with an ultrasonic probe. If still insoluble, the particle size is reduced by grinding to a size sufficient to allow it to pass through the spray nozzle. Following preparation of the test formulations, each is then sprayed equally and completely on the Pre and Post pans employing a handheld spray gun with an air atomizing nozzle. Acetone is employed to rinse the spray gun between application of each formulation. The treated pans are then moved to a growth room, or greenhouse, where they are maintained and appropriately watered for 13 days following treatment. At this time, the pans are then evaluated to determine the percent kill/inhibition/suppression relative to an untreated control. The rating numbers range from 0, indicating no injury, to 100, indicating complete kill or control. Compounds that show 80% control Post and 50% control Pre against any 3 species are considered for further testing. Results are shown in the following Table.
TABLE 1
TEST DOSE PIGVEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 1 1 Pre 8 95 40 95 10 25 60 60 60 45 25
4 40 60 100 10 20 80 40 70 40 30
2 40 60 100 10 30 60 20 40 30 20
1 40 30 100 0 0 30 10 30 20 20
Post 8 35 95 100 10 30 35 20 85 70 10
4 90 25 90 10 10 20 10 100 20 10
2 70 10 80 0 0 20 10 80 0 0
1 40 0 70 0 0 10 0 40 0 0
2 Pre 4 70 50 90 20 60 20 60 40 0 0
4 100 50 100 20 70 50 70 70 50 50
2 70 0 80 20 60 20 20 20 0 60
2 100 20 100 0 50 10 40 30 10 50
1 50 50 80 10 30 10 0 0 0 20
1 100 0 90 0 20 10 20 0 0 0 Post 4 50 100 100 20 50 20 30 100 0 20
4 100 100 100 30 60 60 70 100 20 60
2 50 60 90 10 30 10 20 90 0 20
2 90 50 100 20 60 30 60 100 10 30
1 50 60 80 10 20 10 10 80 0 20
1 60 20 80 30 50 30 60 80 10 60
TABLE 1
TEST DOSE PIGVEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 2 Pre 8 50 30 90 10 20 20 10 20 0 20
4 10 10 50 10 20 20 10 0 0 0
2 0 0 50 0 20 30 10 0 0 0
1 0 0 50 0 0 20 0 0 0 0
Post 8 100 100 100 0 20 30 20 100 30 40
4 70 100 100 10 30 20 30 100 0 30
2 40 90 80 0 20 20 0 40 0 20
1 30 60 40 0 10 10 0 40 0 20
Pre 4 90 50 100 0 60 80 70 50 30 50
2 90 10 100 0 50 60 50 50 0 50
1 90 0 90 0 20 30 30 30 0 0
Post 4 80 100 90 10 50 50 60 100 10 60
2 20 50 50 10 10 50 20 60 0 20
1 50 30 50 0 0 50 10 30 0 20
Exp. 3 Pre 8 50 40 100 20 70 70 50 30 20 20
4 30 10 100 0 40 30 10 0 0 10
4 50 90 100 10 70 10 70 20 20 0
2 20 0 50 0 20 20 10 0 0 0
2 50 0 80 0 50 10 70 20 0 0
1 0 10 30 0 10 20 0 0 0 0
1 30 0 80 0 20 0 40 0 0 30
Post 8 95 100 100 10 10 30 10 100 20 20
4 60 100 90 20 10 10 10 100 30 10
4 100 100 100 50 60 60 70 100 40 60
2 60 50 90 10 10 0 10 80 30 10
2 100 100 100 20 60 40 60 100 20 30
1 50 40 90 10 10 20 0 70 0 0
1 50 90 80 0 30 0 20 100 10 20
TABLE 1
TEST DOSE PIG- VEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 4 Pre 8 100 95 100 35 70 90 100 60 80 - - -
4 95 45 100 50 55 70 70 60 50 - - -
2 90 15 95 35 20 80 50 20 50 - - -
1 90 0 90 30 35 50 50 20 20 - - -
Post 8 - - - 100 100 25 45 80 95 100 75 - - -
4 80 90 90 55 70 80 65 95 65 - - -
2 75 80 80 35 50 60 55 80 50 - - -
1 50 40 80 15 20 45 20 75 0 - - -
Pre 8 100 40 100 0 20 70 45 60 25 30
4 85 30 100 0 10 65 40 45 20 25
2 75 10 90 0 0 45 40 35 20 20
1 75 10 90 0 0 40 30 30 20 20
Post 8 70 100 100 10 10 25 25 95 0 10
4 95 100 100 0 0 20 25 95 0 0
2 90 90 95 0 0 10 10 85 0 0
1 90 90 95 0 0 10 10 85 0 0
Exp. 5 Pre 8 20 20 70 0 20 60 20 10 0 20
4 20 10 50 0 20 20 30 10 0 0
2 20 0 40 0 10 20 0 0 0 0
1 10 0 30 0 0 20 0 0 0 0
Post 8 70 90 90 10 20 30 20 100 20 20
4 90 90 100 20 20 20 30 100 30 20
2 100 100 100 10 20 20 30 100 0 10
1 30 40 100 0 0 0 0 80 0 10
TABLE 1
TEST DOSE PIGVEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 6 Pre 8 50 40 90 0 50 60 50 20 20 20
4 20 10 50 0 30 30 10 0 0 0
2 10 0 50 0 30 20 0 20 0 0
1 0 0 40 0 20 20 0 0 0 0
Post 8 70 100 80 20 20 20 20 90 30 20
4 80 100 100 10 10 10 0 70 0 0
2 70 100 40 0 10 10 0 70 0 0
1 20 0 20 0 0 10 0 20 0 0
Exp. 7 Pre 8 50 30 60 0 80 40 20 0 0 10
4 40 20 20 0 50 40 40 0 0 20
2 20 0 0 0 50 30 20 0 0 10
1 20 0 0 0 40 30 20 0 0 10
Post 8 40 80 80 20 20 30 30 90 20 0
4 100 100 90 0 30 40 20 80 20 0
2 90 100 80 0 20 20 20 50 0 0
1 40 60 40 0 10 10 10 40 0 0
Exp. 8 Pre 8 30 10 95 0 0 80 85 45 35 50
4 40 0 100 0 0 40 80 30 0 40
2 0 0 90 0 0 35 40 25 0 10
1 0 0 80 0 0 10 10 0 0 0
Post 8 75 80 99 0 0 50 50 95 50 45
4 95 85 100 10 10 45 80 95 40 40
2 45 80 95 0 0 45 15 90 30 25
1 45 30 70 0 0 40 15 25 10 20
Exp. 9 Pre 4 100 20 90 20 40 30 30 80 80 20
2 75 0 95 20 30 10 0 40 40 20
1 50 0 60 0 0 0 20 30 20 0 Post 4 90 70 70 10 20 20 10 60 70 30
TABLE 1
TEST DOSE PIG- VEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 10 1 Pre 4 20 0 40 0 0 0 20 30 0 20
1 Post 4 40 100 85 0 30 30 40 100 40 40
2 50 0 40 0 0 20 0 40 20 0
Exp. 11 1 Pre 4 80 0 60 0 0 0 20 50 30 20
2 40 0 70 0 20 0 30 40 40 10 1 40 0 70 0 20 0 30 30 20 10
1 Post 4 80 100 100 0 30 30 40 100 80 30
2 50 0 80 0 0 10 0 40 0 0 1 0 0 40 0 0 0 0 20 0 0
Exp. 12 1 Pre 8 80 70 90 20 80 70 70 70 30 70
4 40 20 80 0 70 80 40 60 30 40 2 40 10 90 0 60 0 30 70 30 10 1 30 0 60 0 30 0 10 70 30 10
Post 8 20 100 100 20 30 30 40 90 70 50
4 30 100 80 0 30 0 40 100 20 10 2 20 100 70 0 0 0 30 100 20 0 1 40 40 40 0 0 0 10 70 0 0
Exp. 12A 1 Pre 4 80 40 80 0 40 40 20 50 10 0
1 20 0 60 0 0 0 0 0 0 0 .25 0 0 40 0 0 0 0 0 0 0
Post 4 90 90 100 0 40 40 40 100 80 40
1 60 2 90 0 20 40 0 80 40 40
.25 20 10 60 0 0 10 0 70 10 10
TABLE 1
TEST DOSE PIGVEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 13 1 Pre 8 90 80 100 50 70 80 60 60 50 60
4 100 60 100 60 50 90 80 50 70 60
2 70 20 80 50 60 60 60 20 10 20
1 50 0 70 10 50 50 60 10 10 0
Post 8 50 100 100 30 50 60 30 70 20 60
4 60 70 90 50 60 60 40 100 40 50
2 50 60 80 10 20 30 40 50 20 20
1 50 40 80 0 10 10 30 50 0 10
Exp. 14 1 Pre 8 95 30 95 0 10 70 50 60 35 25
4 90 70 100 10 20 70 90 90 60 20
2 90 50 100 0 0 60 60 80 40 20
1 90 0 100 0 0 40 30 50 40 10
Post 8 60 90 45 25 25 20 35 100 0 10
4 40 10 90 0 10 20 0 70 0 0
2 30 0 60 0 0 20 0 30 0 0
1 10 0 60 0 0 10 0 30 0 0
Exp. 15
Exp. 16 1 Pre 8 70 25 90 0 20 45 25 40 40 20
4 90 20 90 0 0 70 20 45 20 20 2 25 0 70 0 0 40 20 45 20 10 1 25 0 70 0 0 20 10 30 0 0
Post 8 100 70 85 10 10 25 20 45 20 20
4 100 20 70 0 0 0 0 80 20 0 2 40 0 45 0 0 0 0 40 10 0 1 40 0 40 0 0 0 0 40 0 0 Exp. 17 1 Pre 4 80 0 70 0 0 0 20 20 0 0
1 Post 4 40 50 100 0 20 0 30 100 20 40 TABLE 1
TEST DOSE PIGVEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 18 1 Pre 4 70 0 80 0 0 0 10 30 2 0 0
2 30 0 30 0 0 0 0 0 0 0
1 30 0 40 0 0 0 0 30 0 0
Post 4 80 95 90 0 40 10 40 95 60 40
2 20 75 100 0 0 0 20 100 30 20
1 0 60 90 0 0 0 20 95 20 20
Exp. 19 1 Pre 8 90 0 90 0 0 0 0 0 0 0
1 Post 8 90 70 100 0 10 0 20 100 0 0
Exp. 20 1 Pre 8 100 80 100 80 90 90 90 80 80 80
4 100 50 100 50 60 50 80 70 20 60
2 100 20 100 0 50 60 70 50 0 30
1 90 0 90 0 20 20 30 0 0 10
Post 8 90 70 100 50 60 50 80 100 70 50
4 100 60 100 30 50 40 60 100 50 60
2 100 20 100 10 50 60 60 90 20 50
1 70 10 70 10 30 50 40 80 30 30
Exp. 21 1 Pre 4 90 70 80 0 0 0 30 80 2 0 0
2 90 40 90 0 20 0 40 50 4 0 0
1 60 20 20 0 0 0 20 50 2 0 0
1 Post 4 100 90 95 0 20 20 50 100 80 30
2 0 50 70 0 10 30 0 90 30 10
1 0 50 70 0 0 20 80 30 0 0
TABLE 1
TEST DOSE PIGVEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 22 1 Pre 8 70 0 90 0 50 0 0 0 0 0
4 0 0 90 50 60 50 40 0 0 50
2 0 0 70 40 60 40 20 0 0 30
1 0 0 50 20 30 20 0 0 0 0
Post 8 0 30 60 10 30 20 20 10 3 0 0
Exp. 23 1 Pre 4 0 0 30 0 0 0 0 0 0 0
Post 4 50 20 100 0 0 0 0 80 0 0
Exp. 24 1 Pre 8 50 40 80 70 70 70 0 70 0 0
4 60 20 50 20 20 10 0 70 0 30 2 30 0 40 0 0 0 0 50 0 0 1 0 0 0 0 0 0 0 0 0 0 1 Post 8 70 30 100 50 60 50 0 80 0 0
4 0 30 60 10 20 20 0 70 0 0 2 0 0 60 0 0 0 0 50 0 0 1 0 0 0 0 0 0 0 0 0 0
Exp. 25 1 Post 2 90 60 90 0 0 0 0 100 8 0 0
1 80 70 95 0 0 0 0 90 7 0 0
.50 60 40 90 0 0 0 0 80 4 0 0
Exp. 26 1 Pre 8 70 40 70 20 70 20 50 20 20 40
4 40 60 70 10 20 60 40 70 40 40 2 50 40 60 0 30 0 40 30 40 30 1 40 40 40 0 20 0 30 40 3 0 0 1 Post 8 10 70 80 10 40 10 40 100 20 20
4 70 100 100 0 30 10 80 100 80 30 2 40 100 70 0 0 0 40 100 30 20 1 70 100 70 0 0 0 30 90 20 30
TABLE 1
TEST DOSE PIG- VEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 27 1 Pre 4 20 30 80 0 10 0 30 60 40 10
2 50 0 80 0 20 0 40 0 0 10 1 10 0 60 0 0 0 0 0 0 0
1 Post 4 100 100 100 0 70 40 50 100 85 60
2 20 70 80 0 0 20 0 40 20 0 1 0 0 70 0 0 20 0 50 0 0
Exp. 28 1 Pre 4 30 0 40 0 0 0 30 50 20 0
1 Post 4 30 50 95 0 40 40 40 100 40 30
Exp. 29 1 Pre 4 0 50 0 0 0 0 0 20 0 0
1 Post 4 0 20 90 0 0 0 0 40 40 0
Exp. 30 1 Pre 40 20 70
1 Post 4 90 80 90 0 20 40 50 70 60 40
2 80 80 95 0 0 40 70 80 70 60
1 70 40 90 0 0 40 60 80 70 40
.50 20 20 80 0 0 20 20 80 70 20
Exp . 31 1 Pre 8 70 60 100 0 0 0 0 50 0 0
4 80 0 100 0 0 0 0 0 0 0
2 70 0 90 0 0 0 0 0 0 0
1 70 0 90 0 0 0 0 0 0 0 1 Post 8 50 60 90 0 0 0 0 70 10 10
TABLE 1
TEST DOSE PIG- VEL. MUSRED FOX B.Y. JOHN HEMP MORN WILD
COMPOUND BATCH TYPE KG/HA WEED LEAF TARD MIL. TAIL GRSS SON SESB GLRY OATS
Exp. 32 1 Pre 8 80 0 80 0 0 0 0 0 0 0
1 Post 8 80 40 90 20 20 10 30 100 30 30
4 100 70 100 10 10 10 10 100 0 50 2 80 50 100 0 0 0 0 100 0 50 1 70 50 100 0 0 0 0 70 0 0
Exp. 33 1 Pre 8 100 100 100 50 50 20 20 80 70 0
4 10 20 70 0 20 0 0 0 0 0 2 30 20 60 0 0 0 0 20 0 0 1 0 70 20 0 0 0 0 0 0 0
Post 8 90 100 100 20 30 10 30 100 70 0 4 20 70 100 20 30 20 30 100 20 20 2 50 80 80 10 20 10 20 80 20 0 1 50 70 70 10 20 10 10 80 0 10
Exp. 34 1 Pre 4 0 0 10 0 0 0 0 0 10 0
1 Post 4 40 80 90 0 0 0 0 90 30 0
2 0 10 50 0 20 20 0 20 0 10 1 0 0 60 0 0 0 0 10 0 0
Exp. 35 1 Pre 4 0 0 40 0 0 0 0 0 0 0
1 Post 4 0 70 80 0 0 0 0 60 20 60
Exp. 36 1 Pre 4 60 0 70 0 10 10 30 50 20 10
2 30 30 100 0 20 0 60 50 20 30 1 50 10 70 0 20 0 30 20 0 0 1 Post 4 20 40 90 0 0 0 20 90 40 20
The following examples and tables illustrate some of the plant growth regulation activities of the glyoxylate compositions of the present invention.
EXAMPLE 99 Effect on Turf Growth
The acid form of the glyoxylate prepared in Example 1 was evaluated as a turf growth retardant on four grass species at varying rates as indicated in Table 2.
Turf species were planted in 8 by 8 cm fiber pots using steam pasteurized soil, and allowed to grow until well established, i.e., roots extended to the bottom of the fiber pot. The turf was clipped periodically to keep the thatch at a manageable level and fertilizer was applied on a regular basis. Prior to application of the compound to the turf, the grass was cut to one cm. The compound was formulated in 15 X 125 mm disposable test tubes and foliar applications were made in a hood using a DeVilbliss Model EGA-502 hand held sprayer.
Height measurements were taken two weeks after application of the compound, with the results set forth in Table 2.
Figure imgf000073_0001
Despite some phytotoxicity observed with this method of application, good retardant effect, especially on Kentucky Bluegrass, was demonstrated.
EXAMPLE 100
Effect of Application Method on Turf Retardancy
Using the turf species set forth and grown as in Example 99, the effect of the method of application of the compounds of Examples 16 and 2 is evaluated, with results set forth in Table 3. Weight measurements are taken by cutting each turf pot, after two weeks, to a uniform height, combining the clippings from all species and oven drying prior to weighing.
Figure imgf000074_0001
Granular application is found to result in the lowest degree of phytotoxicity to the grass species.
EXAMPLE 101
Growth Regulation of Wheat
Wheat testing is done in 13 cm round plastic pots. The wheat is planted in a mixture of 75 percent soil and 25 percent sand which has been steam pasteurized to control indigenous weed seed and pathogens. Seeds are planted and then covered with approximately 1 cm soil/sand mix and placed on fiber matting in the greenhouse. The pots are both mist watered and bottom watered until seedlings emerged. After emergence, only bottom watering is done. At the times of treatment, the growth stage is recorded, and pots are removed to a spray hood for treatment. The compound to be applied is placed in a 15 by 125 mm test tube and dissolved in 12 ml of acetone and water. The compound is sprayed onto the foliage using a hand held Devilbiss spray gun (Model EGA-502). This sprayer emits an extremely fine spray particle and results in maximum coverage of the foliage. Operating air pressure is 840 gm/cm2. Applications are made at four different rates at each of six growth stages. The growth stages are as follows:
I. one leaf
II. three to four leaf, some initial tillering
III. three to four leaf, distinct tillers with two to three leaves
IV. five to six leaf, with four to five tillers
V. flag leaf present, inflorescence within culm VI. boot stage, inflorescence emerging from culm
Results (being an average of all indicated readings) for the compounds of Examples 1 and 16 are set forth in Tables 4 and 5, respectively.
Figure imgf000076_0001
Figure imgf000076_0002
Figure imgf000076_0003
EXAMPLE 102
Effect on Wheat Tillering
Single soft red winter wheat (Triticum aestivum) seedlings growing in soil in 4 inch R plastic pots are treated with broadcast spray applications of the compound of Example 15. At the time of treatment, the plants are starting to tiller. Most seedlings have one tiller, while a few have two or no tillers. Treatments are replicated six times (except 5 times at 3 gm/ha). At various times during the course of the study, various parameters are determined: number of flag leaves, number of seed heads and yield measurements. These and other determinations are reported in Table 6. No commercial standard is included, because none is known. The yield increases are attributed to increased tillering (flag leaf counts) and therefore more seed heads per plant. The high dosage (1,000 gm/ha tends to delay tillering.
Figure imgf000077_0001
EXAMPLE 103
Effect on Weed Beets
In some areas where sugar beets (Beta vulgaris) are grown, many fields become infested with weed beets which do not form usable roots. These weed beets can also bolt any time during the season thus insuring continuing infestations. No herbicide is selective enough to control weed beets in sugar beets. A possible weed beet management approach would be to prevent seed production by early treatment of flower stalks with wipe-on or recirculating sprayer applications. To this end, three greenhouse studies are attempted and reported in Table 7. Test plants are grown in 5" R plastic pots. Treatments are applied as directed sprays onto developing flower stalks. Percent reduction is based on fresh weight of surviving floral growth. The compound from Example 1 is prepared as an acetone/water/ surfactant lab formulation. ROUNDUP™ (Monsanto) and A-REST™ (Eli Lilly) are commercial herbicide and plant growth regulant formulations, respectively.
Figure imgf000079_0001
EXAMPLE 104
Effect on Maple Seedlings
Actively growing seedlings of Acer palmatum (Japanese cutleaf maple) are sprayed to runoff with aqueous dilutions of the compound of Example 15 and ATRINAL™ (a commercial formulation by MAAG of dikegulac). Pinched as well as untreated controls are included. All treatments (4 replicates each, recorded 78 days after treatment) are listed in Table 8. Glyoxylate dosages bracket the range from no effect to an excessive effect at the dosages tested.
Figure imgf000080_0001
EXAMPLE 105
Effect on Azaleas
Rooted single-stem cuttings of azaleas (Rhododendron sp., cv 'Elsi Lee') are transplanted to artificial potting medium in 4 inch round plastic pots. These cuttings are pinched as they were moved. After growth resumes, these plants are sprayed to run-off using a hand held spray unit. Treatments employ the K salt of Example 15 and dikegulac, a commercial plant growth regulator which is used to induce branching and to prevent regrowth after pruning. Treatments, based on five replicates of each are listed in Table 9.
Flower bud counts are recorded 122 days after treatment. Glyoxylate treatments induced increases in flower bud numbers.
Figure imgf000081_0001
EXAMPLE 106
Effect on Branching of Beans
In order to determine their effect on branching patterns in plants, compounds were evaluated on Charlevoix climbing beans. Under normal conditions, these plants exhibit strong apical dominance with little or no branching. Plants were grown individually in 4" diameter pots in the greenhouse, and were treated when the 1st trifoliate leaf was expanded (plants approximately 10" tall). Two independent studies were conducted. In the first, compounds were applied at 25 ppm, while in the second the application rate was increased to 100 ppm. In both studies, compounds were sprayed on plants to runoff using a hand-held sprayer. Compounds were dissolved in a solvent system of 67% water and 33% acetone with 0.067% (v/v) Tween 20 added as a surfactant. For some compounds not soluble in this system, 100% acetone with Tween 20 was used. For each compound, three replicate plants were treated and evaluated. Plants were grown in the greenhouse for an additional 3 weeks before the compounds' activity was evaluated. Results are summarized in Table 10.
Figure imgf000083_0001
Figure imgf000084_0001
All of the compounds ellicited some degree of increased bud break and/or branching in climbing beans. For most compounds, activity tended to be greater at 100 ppm than at 25 ppm. In summary, these compounds are effective as branching enhancement agents in beans. EXAMPLE 107
Effect on Size Maintenance of Privet Hedge
Ten compounds were evaluated to determine their efficacy in size maintenance of privet hedge. Potted privet plants were overwintered in a protective cool greenhouse and transferred to a warm greenhouse in early March. Bud break and leaf development were allowed to continue for 1 month until plant height was approximately 30 cm. Because privet hedge plants are commonly trimmed to a desired shape, one-half of the plants were trimmed prior to chemical application. Plants were sprayed to runoff using a hand-held sprayer. Compounds were applied at a concentration of 20 ppm in a solvent system of 50% water, and 50% acetone containing 0.1% (v/v) Triton X-100 as a surfactant. For each treatment, 2 replicate trimmed plants and 2 replicate non-trimmed plants were treated. Plant height of each plant was recorded on the day of treatment and compared to the plant height at 29 days after treatment. Table 11 shows the net increase in plant height after treatment.
Figure imgf000086_0001
Trimmed and non-trimmed plants responded similarly to application of the compounds. Control plants (both non-sprayed and those sprayed with the solvent) grew from 7 to 8.5 cm. In contrast, plant height remained essentially the same in all plants treated with the compounds. Thus, these compounds were quite effective in maintaining plant size both in trimmed and non-trimmed privet hedge plants. EXAMPLE 108
Effect on Terminal Elongation of Green Ash
Ten compounds were applied to green ash seedlings to determine if they could control elongation of terminal buds. Potted green ash seedlings were overwintered in a cool greenhouse and transferred to a warm greenhouse in early March. Within 1 month terminal buds were released and began to grow. Plants were then sprayed to runoff using a hand-held sprayer. Compounds were applied at two concentrations, 20 ppm and 100 ppm, in a solvent system of 50% water, 50% acetone containing 0.1% (v/v) Triton X-100 as a surfactant. For each treatment, 4 replicate plants were treated. Plant height of each plant was recorded on the day of treatment and compared to the plant height at 28 days after treatment. Table 12 shows the net increase in plant height after treatment.
Figure imgf000088_0001
Non-sprayed control plants in which the terminal bud was pinched grew 18.3 cm while non-sprayed non-pinched plants grew 11 cm. Similarly, pinched control plants sprayed with the solvent increased in height 15 cm and non-pinched, non-sprayed plants grew 8.5 cm. In contrast, all compounds tested essentially eliminated terminal bud elongation, regardless of concentration of the applied solution. Thus, these compounds appear to have excellent utility when used to reduce vertical growth of this tree species.
EXAMPLE 109
Effect on Turfgrass Growth
Twenty-three compounds were tested for their utility as turfgrass retardants. Bluegrass, cv Baron and perennial ryegrass, cv Pennfine were planted in 3" sqaure pots in late February. Grass was allowed to grow for 6 weeks before treatment. Grass was cut and fertilized on a regular basis to provide a thick turf. Just prior to chemical treatment, the bluegrass and ryegrass were trimmed to heights of 20 mm and 15 mm, respectively.
Four replicate pots of each species were treated at two rates, 0.5 kg/ha and 2.0 kg/ha. Compounds were sprayed in 50% acetone, 50% water containing Triton X-100 at 0.1% (v/v) as a surfactant. Some compounds were sprayed in
100% acetone containing Triton X-100. Plant heights 2 weeks after treatment were recorded and are summarized in
Table 13.
Figure imgf000090_0001
Figure imgf000091_0001
Both bluegrass and ryegrass controls grew to a total height of approximately 130 mm (net growth of 115 mm) during the two week preiod after treatment. The commercial standards. Limit and Embark, reduced total plant height to approximately 30 to 50 mm, depending upon rate and species. Similar plant height reductions were observed in many of the compounds tested. Several compounds, however, showed little or no activity. In addition, responses also varied between the two species, with ryegrass growth appearing to be more susceptible to chemical retardation, particularly at low rates. In summary, turf retardant activity of this class of chemistry appears to be at least comparable to the currently available commercial standards.

Claims

WHAT IS CLAIMED IS:
1. A method of modifying the natural growth and development of a plant, which method comprises applying to the plant locus an effective, nonlethal, plant-regulating amount of a compound having the formula
Figure imgf000092_0001
wherein:
A is COOR, COSR, CONR'R", CSNH2, CN or, together with one of B, -C(=O)O-
R is H, Na, K, di(C1 - C4)alkylammonium, diethanolammonium, N(3-amino-propyl)N-oleylammonium, C1 - C8 alkyl, aryl, heteroaryl, C2 - C8 alkoxyalkyl, C2
C4 hydroxyalkyl, (alkoxycarbonyl)alkyl, dialkylaminoalkyl, cycloalkyl, tetrahydrofurfuryl or dimethydioxolanylmethyl;
R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N- (lower alkyl)-piperazino;
Z is H, CH3, CH3S, CH3S(O), COOR; B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y is H, C1 - C4 alkyl or alkoxy, CF3 or X; and X is F, Cl or Br,
provided that where more than one of Y is other than H on either ring they must be present in either the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or 11 positions on the rings, no more than one of Y is other than H and that one Y is CH3.
2. A method of inhibiting the growth of undesirable vegetation which comprises contacting said vegetation's locus with a herbicidally effective amount of a compound having the formula
Figure imgf000093_0001
wherein:
A is COOR, COSR, CSNH2, CN or, together with one of B, -C(=O)O-;
R is H, Na, K, di(C1 - C4)alkylammonium, diethanolammonium, C1 - C8 alkyl, C2 - C4 alkoxyalkyl, cyclohexyl , tetrahydrofurfuryl or dimethyldioxolanylmethyl;
Z is H or CH3;
B is H, CH3 or, together with A, -C(=O)O-; Y is H, C1 - C4 alkyl or alkoxy, CF3 or X; and X is F, Cl or Br,
provided that where more than one of Y is other than H on either ring they must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or 11 positions on the rings, no more than one of Y is other than H and that one Y is CH3.
3. A method as in Claim 1 or 2 wherein Y, B and Z are all H.
4. A method as in Claim 1 or 2 wherein B and Z are all H.
5. A method as in Claim 1 or 2 wherein Y and Z are all H.
6. A method as in Claim 1 or 2 wherein Y at the 1, 2, 10 and 11 positions, B and Z are all H.
7. A method as in Claim 1 or 2 wherein Y and Z are all H and B is CH3.
8. A composition of matter useful in the modification of plant growth, which composition comprises an agronomically acceptable inert carrier, a surfactant and a compound having the formula
Figure imgf000094_0001
wherein :
A is COOR, COSR, CONR'R", CSNH2, CN or, together with one of B, -C(=O)O- R is H, Na, K, di(C1 - C4)alkylammonium, diethanolammonium, N(3-amino-propyl)N-oleylammonium, C1 - C8 alkyl, aryl, heteroaryl, C2 - C8 alkoxyalkyl, C2 C4 hydroxyalkyl, (alkoxycarbonyl)alkyl, dialkylaminoalkyl, cycloalkyl, tetrahydrofurfuryl or dimethydioxolanylmethyl;
R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N- (lower alkyl)-piper-zino;
Z is H, CH3, CH3S, CH3S(O), COOR;
B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y is H, C1 - C4 alkyl or alkoxy, CF3 or X; and X is F, Cl or Br,
provided that where more than one of Y is other than H on either ring they must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or 11 positions on the rings, no more than one of Y is other than H and that one Y is CH3.
9. A method as in Claim 8 wherein Y, B and Z are all H.
10. A method as in Claim 8 wherein B and Z are all H.
11. A method as in Claim 8 wherein Y and Z are all H.
12. A method in Claim 8 wherein Y and Z are all H and B is CH3.
13. A method as in Claim 8 wherein Y at the 1, 2, 10 and 11 positions, B and Z are all H.
14. A compound having the formula
Figure imgf000096_0001
wherein:
A is COOR, COSR, CONR'R", CSNH2, CN or, together with one of B, -C(=O)O-;
R is C2 - C8 alkoxyalkyl, cycloalkyl, C2 - C4 hydroxyalkyl, (alkoxycarbonyl) alkyl, dialkylaminoalkyl, tetrahydrofurfuryl and dimethyldioxolanylmethyl;
R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N-(lower alkyl)-piperazino;
Z is H, CH3, CH3S, CH3S(O) or COOR;
B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y is H, C1 - C4 alkyl or alkoxy, CF3 or X; and X is F, Cl or Br.
15. A compound having the formula
Figure imgf000097_0001
wherein:
A is COOR, COSR, CONR'R", CSNH2, CN or, together with one of B, -C(=O)O-;
R is H, Na, K, di(C1 - C4)alkylammonium, N(3-amino-propyl)N-oleylammonium, C1 - C8 alkyl, aryl, heteroaryl, C2 - C8 alkoxyalkyl, C2 - C4 hydroxyalkyl, (alkoxycarbonyl) alkyl, dialkylaminoalkyl, cycloalkyl, tetrahydrofurfuryl or dimethydioxolanylmethyl;
R' and R" may be the same or different, and each is a member selected from the group consisting of H, lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl, or alkoxycarbonylalkyl; or NR'R" taken together represent a saturated monocylic heterocyclic group such as pyyrolidino, piperidino, morpholino, piperazino or N-(lower alkyl)-piperazino;
Z is H, CH3, CH3S, CH3S(O), COOR;
B is H, lower alkyl, lower alkoxy, hydroxy, benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y and W are C1 - C4 alkyl or alkoxy or CF3; m and n are 0-2 and the sum of m plus n is 1-4.
PCT/US1990/003672 1989-06-29 1990-06-27 Novel glyoxylates and herbicidal and plant growth regulant activity of glyoxylates WO1991000009A1 (en)

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AU59509/90A AU647401B2 (en) 1989-06-29 1990-06-27 Novel glyoxylates and herbicidal and plant growth regulant activity of glyoxylates
CA002035024A CA2035024C (en) 1989-06-29 1990-06-27 Novel glyoxylates and herbicidal and plant growth regulant activity of glyoxylates
BR909006844A BR9006844A (en) 1989-06-29 1990-06-27 NEW GLIOXYLATES AND HERBICIDE AND REGULATORY ACTIVITY FOR THE GROWTH OF GLIOXYLATE PLANTS

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US07/373,210 US4976770A (en) 1989-06-29 1989-06-29 Herbicidal and plant growth regulant activity of glyoxylates
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CN111108205A (en) * 2017-09-11 2020-05-05 奥驰亚客户服务有限公司 Compositions and methods for producing tobacco plants and articles with reduced or eliminated smoke branches
US11879130B2 (en) 2017-09-11 2024-01-23 Altria Client Services Llc Compositions and methods for producing tobacco plants and products having reduced or eliminated suckers

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EP0439607A1 (en) 1991-08-07
CA2035024A1 (en) 1990-12-30
CA2035024C (en) 2001-05-29
AU647401B2 (en) 1994-03-24
AU5950990A (en) 1991-01-17
AU5381394A (en) 1994-03-17

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