St?
`
`r: C6
`7' United States Patent 0
`
`3,093,659
`Patented June 11, 1963
`
`1
`
`3,093,659
`ANTIFUNGAL AND INSECTICIDAL HALOKOJIC
`ACID METAL COMPLEXES
`William E. Bell, Bayside, N.Y., and Jay S. Buckley,
`Groton, and Philip N. Gordon, Old Lyme, Conm, as
`signors to Chas. P?zer & Co., Inc., New York, N.Y.,
`a corporation of Delaware
`No Drawing. Filed June 20, 1956', Ser. No. 592,474
`4 Claims. (Cl. 260-3453)
`
`This invention relates to a group of organo-metallic
`compounds possessing useful fungicidal properties. More
`particularly it relates to a group of metal chelates or com
`plexes of the halokojic acids.
`Various materials have been proposed in the past for
`use as fungicides in agriculture and ‘for various industrial
`applications. These include Bordeaux mixture which is
`a mixture of copper sulfate, lime and water; various sul
`fur compounds, as well as sulfur itself; and certain cyclic
`nitrogen compounds. All of these materials suffer from
`certain disadvantages. For example, suspending dif?cul
`ties are sometimes encountered with commercial prepara
`tions of Bordeaux mixture which result in clogging of
`the spray nozzles employed in their application. Further
`more, di?‘iculty is sometimes encountered due to the
`excessive release of copper from the mixture which has
`a toxic reaction on the plant. Toxic reactions are simi
`larly noted in‘ many instances with the various sulfur and
`nitrogen compounds that ‘have been suggested for use as
`fungicides.
`The halokojic acids have the following structure
`0
`
`HO 1
`
`l
`0/ CHsX
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`2
`serious disadvantage of the halokojic acids is the di?iculty
`encountered in formulating them into suitable composi
`tions for use in agriculture. They are very light and
`?nely [divided powders which have a tendency to ?oat on
`water when it is attempted to prepare suspensions of
`them. This disadvantage coupled with their phytotoxicity
`and irritating properties militates against their use in
`agriculture as fungicides.
`The above disadvantages have been overcome by the
`valuable metal chelates of the present invention. These
`materials by and large are dense, insoluble solids which
`{are readily formulated into either solid or liquid fungi~
`cidal compositions, and they are non-irritating to humans
`either on exposure to the dust by breating or on contact
`with the skin. In addition some of them possess toxicity
`for the larvae of certain insects. Copper chlorokojic,
`for example, has been found to possess larvacidal activity
`for mosquito larvae.
`The precise structure of the valuable chelates of this
`invention is not known, but it is thought that, for example,
`with a divalent metal having a coordination number of
`4 such as copper, that salt formation occurs at the acidic
`S-hydroxyl group between the metal and two molecules
`of the halokojic acid. Further bonding of the metal oc~
`curs at the carbonyl oxygen atom in the 4-position of the
`halomethylkojic acid producing a bicyclic structure about
`the metal containing both coordinate and covalent bonds.
`Tri and quadrivalent metals having coordination num
`bers of 6 and 8 form chelates with respectively three and
`four molecules of the halokojic acid. In these instances
`tri and tetracyclic structures about the metal are thought
`to exist. While these structural formulations are conjec
`tural, it is a fact that the metal chelates of this invention
`are distinct chemical compounds of uniform and repro
`ducible composition.
`It has been found that the metal chelates of the above
`types and particularly those derived from chlorokojic
`acid, bromokojic acid, and iodokojic acid containing
`metals having atomic numbers in the range 12 to 82
`inclusive which includes such metals as aluminum, iron,
`copper, cobalt, zinc, mercury, magnesium, calcium, and
`barium have valuable fungicidal properties. Those metals
`having coordination numbers of 4 to 8 are preferred. By
`virtue of this activity these materials are useful in both
`agricultural and industrial applications. While the rare
`earth elements, whose atomic numbers fall within the
`above atomic number range, also have fungicidal activity,
`for practical reasons they are of less interest due to their
`limited availability. The rare earth elements have atomic
`numbers from 57 to 71. The preferred chelates, then,
`are those of chloro-, bromo-, and iodokojic acid contain
`ing metals whose atomic numbers are from 12 to 5 6 and
`72 to 82.
`The term fungicide is meant to include not only the
`property of destroying fungi but also the property of
`inhibiting the germination of the spores or the sporulation
`of the fungi, a property sometimes referred to as fungi
`static or fungitoxic. As pointed out above the valuable
`fungicidal metal chelates of the halokojic acids have im
`portant applications in agriculture against certain fungus
`diseases of plants. In particular, these agents have been
`found to be effective against early blight of tomatoes
`(Alternaria solani), bean mildew (Erysiphe polygoin),
`and bean rust (Uromyces appendiculatus). Further ap
`plications of these valuable metal chelates include various
`industrial uses where mildew or mold attack is a problem.
`They are useful in the textile, paint, paper, glue and
`adhesive, and plastic industry. For example, the incorpo
`ration of the metal chelates of this invention such as zinc
`iodokojate or .cgppgr Higdokojateiptopaint‘affords protec
`tion of the dried painted surface against mildew (Palla
`
`wherein X is a halogen atom i.e., a ?uorine, a chlorine,
`a bromine, or an iodine atom. The halokojic acids are
`structurally related to kojic acid which has the above
`formula wherein X is the hydroxyl group and the syste
`matic name 5-hydroxy-2Ahydroxymethylpyran»4-one.
`Chlorokojic acid, S-hydroxy - 2 - chloromethylpyran-4
`one, and iodokojic acid, 5-hydroxy-2-iodomethylpyran-4
`one, are known in the art. The bromo compound is a
`new compound whose preparation is described in copend
`ing application Serial No. 592,473, now abandoned, ?led
`herewith. The systematic name for bromokojic acid is
`5-hydroxy-2-bromomethylpyran-4-one. One method that
`has been used for preparing chlorokojic acid, involves
`treatment of kojic acid with thionyl chloride. Iodokojic
`acid has been prepared from chlorokojic acid by treat
`ment with potassium iodide in acetone. Fluorokojic acid
`may be prepared from one of the other halokojic acids by
`treatment according to well known techniques with vari—
`ous metal ?uorides such as mercuric ?uoride, silver ?uo
`ride, and antimony tri?uoride.
`Of the halokojic acids chlorokojic has been reported to
`have a degree of fungicidal activity against certain organ
`isms. However, it too has certain serious shortcomings.
`For example, it is an irritating compound being a highly
`active sternutator. Chlorokojic acid is hazardous to han
`dle for this reason. From this point of view, the other
`halokojic acids also lack properties necessary to make
`them desirable fungicides. Iodokojic acid is particularly
`disadvantageous since iodine is released from it on warm
`ing or prolonged standing. It has been observed to have
`a defolient action on green plants. Chlorokojic acid,
`while more stable than the iodo compound also suffers
`from a stability problem and indeed has been observed
`to have a herbitstatic action on green plants. A further
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`70
`
`CFAD Exhibit 1021
`
`

`
`3,093,659
`
`laria pulltzlons). Similarly, these materials are effective
`in protecting so-called emulsion type paints such as casein
`paints during storage. When stored in the container at
`ambient temperature, such paints are subject to fungicidal
`attack resulting in a breaking of the emulsion rendering
`the paint generally un?t for use and sometimes producing
`undesirable odoriferous degradation products. Other ex
`amples of applications of the metal complexes of this
`invention include fabric mildew proo?ng, protection of
`plastics, preservatives for paper to prevent slime mold
`formation and in particular for cardboard containers sub~
`jected to high temperature and humidity conditions, and
`as preservatives for leather. They have also been found
`to possess activity against certain human pathogens such
`as Candida albicans and Trichophyton rubrum. In all of
`these uses, the unexpected stability of these materials and
`the lack of irritating e?'ects are unique and important
`advantages.
`The metal chelates of this invention are very readily
`
`4
`The antifungal activity of these valuable products was
`demonstrated by a number of methods. In one series of
`tests the agar incorporation method was used. According
`to this method a nutrient medium was prepared and cast
`into agar plates. Before adding the agar and pouring into
`the plates, the medium was inoculated with spores of the
`particular organism under consideration and the test com
`pound added at a predetermined test concentration. In
`most instances a concentration of 100 parts per million
`of the test compound was employed although with some,
`tests at lower concentrations were carried out. The results
`of these tests are given in Table vI. In this table the values
`obtained when chlorokojic acid, bromokojic acid and
`iodokojic acid were used are given for comparison. It can
`be seen from this table that a change in the antifungal
`spectrum of these valuable chelates is obtained. This is
`particularly noticeable with the industrial contaminants,
`Aspergillus niger and Penicillum funiculosum.
`TABLE I
`Comparative Antifungal Activity of the Halokojic Acids
`and Chelates Thereof at 100 p.p.m. by the Agar
`Incorporation Method
`
`Halokojie acid
`
`Metal
`chelate
`
`Candida
`albzcans
`No. 8
`
`Tricho-
`phyton
`rabram
`
`Alte_r-
`narzd
`solam
`
`Rhinoc-
`tam'd
`solam
`
`Asper-
`gillus
`niger
`
`Pent.
`cillium
`ftmicu-
`Zoram
`
`clad‘).
`sporium
`dado.
`sporoidea
`
`Chlorokojlo acid.--" Free acid_.._
`Gil" ----- --
`
`Bromokojic acid-.-“
`
`011“
`
`Iodokojie acid _____ __ Free acid____
`
`Z1111 _______ __
`
`+
`+
`—
`
`><
`
`+
`
`+
`
`-
`
`+
`
`C111! _______ __
`
`_
`
`-
`—
`—
`
`-
`
`-—
`
`_.
`
`—
`
`._
`
`_.
`
`-
`+
`—
`
`——
`
`-—
`
`--
`
`—
`
`_1
`
`._l
`
`X
`+
`—
`
`X
`
`-
`
`_-
`
`-
`
`,_
`
`__
`
`+
`--
`-
`
`x
`
`-
`
`._
`
`X
`
`_
`
`_
`
`+
`—
`__
`
`X
`
`_
`
`_
`
`_
`
`__
`
`_
`
`x
`x
`__
`
`x
`
`_
`
`.
`
`__
`
`__
`
`_
`
`45
`
`50
`
`55
`
`TABLE II
`
`Antifungal Activity of Representative Metal Chelates at
`100 p.p.m.
`
`Oupric
`iodoko
`jate
`
`Zinc
`lodoko
`jate
`
`Cobalt
`chloroko
`jate
`
`Mercury
`chloroko
`jate
`
`3 Complete inhibition at 10 p.p.m. or less.
`Norr:.-— +=Growth; —=No growth; X=Reduced growth.
`prepared by simply bringing together in solution the de
`Zinc iodokojate, copper iodokojate, cobalt chlorokojate,
`sired halokojic acid and a source of the appropriate metal.
`and mercury chlorokojate were tested further by the agar
`Both aqueous and non-aqueous solvents have been em
`incorporation method against an additional group of
`ployed. For operation in aqueous solution, it is necessary
`organisms. Concentrations of the test compounds of 100,
`to employ a soluble salt of the halokojic acid since the
`10 and 1 part per million were used. The results of this
`acids are insoluble in water. One convenient method is
`test are arranged in Table II. Of 64 species tested, copper
`to suspend the halokojic acid in water and then to bring
`iodokojate inhibited the growth of 52, and zinc iodokojate
`it into solution by the addition of ‘an alkali for example,
`inhibited 45. Of the 61 species tested against cobalt chlo
`sodium hydroxide. Buifer solutions may also be used.
`rokojate and mercury chlorokojate, the growth of 12 was
`The metal salt is then dissolved in water and the two solu
`inhibited by the former and 49 by the latter. In addition,
`tions are mixed. This type of process is ordinarily carried
`mercury chlorokojate demonstrated remarkable activity
`out at room temperature since the halokojic acids are sub
`at the lower levels. Ferric chlorokojate was similarly
`ject to hydrolysis in alkaline solution at elevated tempera
`tested and found to inhibit Histoplasma capsulatum at
`tures. Temperatures up to about 40° C. are satisfactory.
`100 ppm.
`A more convenient method of operation involves the use
`of organic solvents such as the lower alkanols when the
`inorganic salt is soluble in such a solvent. Other organic
`solvents may of course be used. When non-aqueous sol
`vents are used, elevated temperatures up to about 100° C.
`may be used since there is no danger of hydrolysis. The
`use of an elevated temperature has the advantage of per
`mitting the use of smaller solvent volumes and better 60
`control of the crystallization rate thus permitting control
`of the particle size of the precipitate. In any case, the
`halokojic acid metal chelate precipitates from the reaction
`mixture and is collected by some suitable means such as
`?ltration or centrifugation, washed and dried. The com
`position of the product so obtained generally corresponds
`to the calculated value based on the above structural pre—
`sentation. Further puri?cation is ordinarily unnecessary.
`In most instances these chelate products are highly colored.
`The colors vary from ‘deep red to tan, yellow, and green
`depending primarily upon the metal contained in the
`chelate. Variations in shade do occur resulting probably
`from differences in particle size, etc. Speci?c examples
`for the preparation of a number of these materials are
`given hereinafter.
`
`ORGANISM
`
`_
`
`Histoplasma capsulaiam ____ ._
`Blastomyces brasiliensis _____ ._
`Blastomyces dermatitidis ____ _
`Trichophyton suljureum
`Trichophyton violaceum._
`Sporoirichum scheduled"..
`Hormodendrum campactum
`Cryptacoccus neoformans
`_
`Phialophora verrucosa _______ ..
`Candida albicans N0. 8 _____ .
`Candida albicans No. 9 _____ _
`Candida albicans No. 11.
`Candida albicans N0. 15
`Candida albictms “e”-_
`Epidermophyton?occos
`
`70
`
`75
`
`Microsproum audovini _ _ _
`_ __
`Trichlphz/ton rubmm ....... _
`
`
`
`I LL+++| | |++++ L++L
`
`1><|+++|+1++++1++L
`
`I
`
`l
`
`+| 1+
`
`+1++
`
`2
`
`

`
`3,098,659
`
`TABLE II-—Continued
`
`Cu prlc
`iodoko
`te
`
`Zinc
`lodoko
`jate
`
`Cobalt
`ehloroko
`
`Mercury
`chloroko
`late
`
`PHYTOPATHOGENS
`
`Altemun'a salam'n
`Botrytis alli-- -_
`Septoria noderu'm.
`Endothz‘a parasiticu
`Neocosmospora vasinjecta.
`Fusarium ozyspon‘um--_- .
`N ematospora coryli _________ -
`Cemtostomellu ul'mi (Ophlo
`
`stom ................... -.
`Sclerotinia ructicola ______ __
`Collectotric um circinana.
`.
`Verticilliu'm albo-atrum
`Physalospora 'mulorum.
`Helminthosporium victo
`Hormondendmm resim'ae.
`Glomerella cingulata--.
`.Phoma batae ............... -.
`Fusariu'm lucopersz‘ci var.
`
`Penicillium citrinum- _ _ __
`
`bulbigenwm ............... -.
`Rhizoctonia solam'-..
`-_
`Pthium debaryanum ........ -.
`Hel'minthospon'um terricum -
`Mycogene pe'nm'ciosa ....... .
`Peirlricilillum sp. marathon
`o ____________________ __
`Rhizopus niaricans- -
`-
`Penicillium steckii.--
`-
`Aspergillus niger ......... -_
`Penicilliu'm jreguentans"
`Penicilliumfuniwlosum.
`Aspergillua nidulous.
`Penicillium soppi.
`Aspergill'us terreus--.
`Aspergz'llus fumigatus
`_--.
`Faecilomyces variotL-
`Hormondendron sp. (Wehy
`mer) _____________________ ..
`Mucor mucedo .... -.
`Penicillium oxalicum.--.- .
`Saccharomuces ceresisiue. .. _..
`Schizosaccharomvces ocloapo
`ms
`Pullulan'a pullulo'n
`Byssochlamya fulva._
`Uladospon‘um herbarum
`-
`C'Zadosporium (Hormonden
`drum) cladospprozdes ..... _.
`Endomyces ?buhaer ______ __
`Margarinomyces bubaki...
`
`_
`Oospora lactis _________ -_
`Penicillium dipitatum ....... -.
`
`+llXlll
`
`-
`—1
`
`Li I | |
`
`llXl++llllll
`
`| l | L
`
`><L|||
`
`l+++++l l lXXl
`
`LHL
`+L++|
`
`
`
`
`
`3 |++|+ ++l |+++++ +++ei++
`
`+++++++++++
`
`
`
`
`
`+++++ ++++ +++|
`
`1Complete inhibition at 10 p.p.m. or less.
`tested.
`growth ;
`Norn.—- + :Growth; — :No
`X :Reduced
`growth.
`Some of the valuable halokojic metal chelates of this
`invention were evaluated in a contact test. In this test
`small plugs were cut from agar plates covered with a mat
`of fully sporulated test fungus which served as the in
`oculant. Aqueous solutions having a concentration of 1%
`of the test compound were prepared. Suitable organic
`solvents were employed with the compounds insoluble in
`water to the extent of 1%. The agar plugs containing the
`fully sporulated test fungus were then exposed to this
`solution for 15 minutes. After exposure, the plugs were
`removed from the test solution and washed with sterile
`broth to remove residual test solution. The plugs were
`then placed on agar plates and incubated. The test com
`
`-‘
`
`10
`
`15
`
`pound was considered to be active if the fungus failed
`to grow after incubation in this fashion and inactive if
`the fungus grew. A variety of different species of fungi
`were selected for this test. In all, seven species were used.
`Two of these were human pathogens causing such diseases
`as ringworm and athlete’s foot; two were plant pathogens,
`one causing early blight of tomatoes and the other damp
`ing off; and three were common contaminants of industrial
`importance of concern to the textile fabric industry and
`the meat industry. The results of the test are arranged
`in Table III. This table shows that zinc chlorokojate has
`a rather wide range of activity in preventing the growth
`of four and seven species when employed in this contact
`method of disinfecting an agar plug of the fungus. Alumi—
`num chlorokojate is somewhat more restricted in its range
`of activity preventing the growth of two of seven species.
`The halokojic acid metal chelates of this invention have
`low water solubilities. They are therefore well suited as
`fungicides for topical application since they are not read
`ily washed from the plant or fabric to which they are
`applied. One convenient method for applying them is
`as an aqueous spray. Aqueous suspensions or emulsions
`are readily prepared by incorporating the chelate with
`suitable wetting or emulsifying agents such as the poly
`sorbates, sodium stearate, and salts of abietic acid or the
`like. In such event, concentrates of the metal chelates
`may be prepared for subsequent dilution prior to use.
`For their ultimate application it is preferred to use sus
`pensions having concentrations of the chelate in the range
`of 0.001% to about 10%. However, suspensions having
`higher concentrations may be prepared for subsequent
`dilution as indicated above. The chelates may also be
`applied as dusts. For this purpose, it is convenient to
`mix them or to coat them with a suitable carrier, such as
`clay, magnesium carbonate, talc, tricalcium phosphate,
`etc. For use in fabrics, paper, etc., they are incorporated
`directly into the composition which it is desired to protect.
`This can be conveniently accomplished by treatment of
`the material with an aqueous suspension such as the type
`referred to above. Suspensions in volatile organic sol
`vents may also be used. These valuable fungicides may
`be used with other active ingredients such as antibacterial
`agents, insecticides, and even in combination with other
`fungicides. For topical application to animals including
`humans, the metal chelates are associated with suitable
`pharmaceutical carriers which can be in the form of oint
`ments, lotions, suppositories or powders suitable for use
`as dusting powders or insu?lation powders. For this use
`concentrations of about 0.001% to 1% are preferred.
`In addition to the above tests a number of these metal
`chelates were employed in tests on plants a?licted with
`various fungus infections. Control groups of plants were
`maintained in each experiment for comparison purposes
`to indicate the virulence of the infecting organism. In
`such a test against early blight of tomatoes, copper chlo- '
`rokojate, zinc chlorokojate, copper iodokojate, and zinc
`iodokojate were found to eradicate the disease in 90%
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`TABLE III
`
`Contact Time Amifungal Activity of Zinc and Aluminum
`Chlorokojate
`[15 minute exposure to a 1% solution]
`
`Oompound
`
`Tricho- i Alter-
`Candida phyton
`naria
`alblcam sul/ureu'm sola'ni
`
`Fe.
`3!
`Pythium Asper-
`debar-
`aillus
`uam'um
`nicer
`
`Olada
`Penicil-
`Hum sporium
`junicu- cladospo
`lormn
`roides
`
`Zine chlorokojatn
`Aluminum chlorokojate
`
`+
`+
`
`—
`-
`
`-
`+
`
`—
`+
`
`+
`+
`
`+
`+
`
`—
`—
`
`NO'l‘Er- +=Growth; -=No growth.
`
`3
`
`

`
`3,093,659
`
`8
`and 25 ml. of chloroform. An immediate precipitate
`formed. The mixture was allowed to cool to room tem
`perature and the solid collected, washed with ethanol,
`and air dried yielding 10 g. of product.
`Analytical data is tabulated in Table IV.
`EXAMPLE III
`Alkaline earth halokojates; magnesium brom0koiate.—
`This material was prepared substantially by procedure B
`as applied to cupric bromokojate. Bromokojic acid, 10.3
`g., was dissolved in hot ethanol, 200 ml. This solution
`was slowly added to a warm solution of 5.6 g. of mag
`nesium chloride hexahydrate in 50 ml. of ethanol. A
`precipitate formed which was collected after cooling,
`washed on the ?lter with ethanol and air dried.
`Calcium bromokojate was prepared by an analogous
`procedure.
`Barium chlorokoiate.—This material was prepared by
`procedure A substantially as described for ferric bromo
`kojate. Chlorokojic acid, 32 g., was suspended in 200
`ml. of water and a solution of 8 g. NaOH in 50 ml. of
`water was added. The solution was warmed to elfect
`solution. A solution of 13.9 g. of barium chloride in
`100 ml. of water was then added to the above solu
`tion. The solution was cooled to room temperature,
`and the precipitate collected and washed ?rst with water
`and then with alcohol. It was air dried.
`
`of the plants in the test group employing a spray contain
`ing 400 parts per million of the test compound. Copper
`chlorokojate, and copper bromokojate were similarly
`found active against bean mildew. Zinc iodokojate had
`therapeutic activity in bean plants infected with bean
`rust (Uromyces appendiculatus) when applied to the soil
`in which the bean plants were growing.
`‘The following examples are given to further illustrate
`this valuable invention but they are not considered to be
`limiting thereof in any way. Various changes and modi
`?cations may be made within the scope of the appended
`claims.
`
`EXAMPLE I
`
`Two different types of procedure were used in the prep
`aration of these compounds. In one water was used as
`the solvent and in the other an organic solvent. Method
`A using water as the solvent was used in those cases where
`the metal salt employed was insoluble in ethanol. Method
`B using ethanol-chloroform was used when the solubility
`of the metal salt permitted.
`(A) Use of water as the solvent; ferric br0mok0iate.-—
`Bromokojic acid, 4.10 g. (0.02 mole) was added to 500
`ml. of water containing 0.80 g. (0.02 mole) of sodium
`hydroxide. The mixture was heated gently yielding a
`clear reddish-brown solution. A solution of ferric chlo
`ride hexahydrate, 1.80 g. in 100 ml. of water, was pre
`pared and added to this solution. The solution turned
`red-brown on mixing and a dark red precipitate formed.
`The mixture was allowed to cool to room temperature,
`digested for several hours at room temperature and the
`crop collected. The dark red solid was washed on the
`?lter with ice water and then dried in vacuo.
`
`TABLE IV
`
`Preparation of the Halokojic Chelates
`
`Compound
`
`Procedure
`
`Metal anal.
`
`Color
`
`Calc’d
`
`Found '
`
`Felllchlorokojate ____ __ B
`Collchlorokojate _____ __ B
`Al chlorokojate-..
`A
`Zn chlorokojate
`A
`Hg ehlorokojate
`A
`Cull bromokojic- _
`B
`Zn brornokojic _ _ _ _ _ __ A
`Zn iodokojate ________ -_ B
`CuIliodokojate ______ __ B
`
`10.40
`15.6
`5.3
`14. 25
`29. 6
`(l)
`(1)
`(1)
`(2)
`
`10.32 Deep red.
`11.0
`Tan.
`5.1
`Yellow.
`14. 50 Lt. yellow.
`31. 2
`Lt. green.
`(1)
`Green.
`(2)
`White.
`(3)
`Lt. yellow.
`(4)
`Green.
`
`1Calcd. for (CoH40sB1')2Cl1I C, 30.56; H, 1.71; Br, 33.90;
`Cu, ‘13.46. Found: ,
`. '1; H, 2.05; Br, 34.12; Cu, 13.33.
`2Calcd. for (COHAOSBI')2ZH2 C, 30.44; H, 1.70; Br, 33.76,
`Zng 13.81. Found: C ‘20.41; H, 1.77; Br 34.15, Zn, ‘13.73
`Calcd. for (CaHiOabazn: C, ‘25.40; H 1.42; I, 44.74; Zn,
`11.52. Found: C, 26.04; H, 1.54; I, 44.83; Zn, 10.71.
`V 4-C‘alcd. for (CaH40sD2C1l: ‘C, 25.48; H 1.43; I, 44.88; Cu,
`11.24. Found: C, 27.01; H, 1.74; I 44.65, Cu, 11.32
`
`10
`
`15
`
`20
`
`25
`
`80
`
`85
`
`40
`
`50
`
`55
`
`(B) Use of ethanol-chloroform as the solvent; cupric
`bromokojate.—-Bromokojic acid, 10.3 g., was dissolved in
`hot ethanol, 200 ml. A clear solution resulted which was
`added to a hot solution of cupric acetate monohydrate,
`5 g. in 50 ml. of ethanol and 25 ml. of chloroform. A
`?nely divided green precipitate formed almost immedi
`ately. The mixture was cooled to room temperature and
`the crop collected. The product was washed on the ?lter
`with ethanol and air dried yielding 10.8 g. of a micro
`crystalline product.
`
`60
`
`EXAMPLE IV
`A suitable fungicidal ointment composition consists of
`G.
`900
`Stearic acid
`__ 800
`Glycerine
`80
`Anhydrous lanolin
`40
`2-amino-2-methyl-1-propanol ________________ __
`2100
`Distilled water
`40
`Copper iodokojate
`The stearic acid and lanolin were melted together at
`about 70° C. The glycerine, 2-amino-2-methyl-l-propa~
`1101, and water were mixed and heated to about 70° C.
`and the copper iodokojate added to this solution fol—
`lowed by the stearic acid-lanolin melt. The mass was
`thoroughly mixed and milled to avoid lumps and ?lled
`into two ounce jars. The composition contains about
`1% of the active fungicidal agent, copper iodokojate.
`EXAMPLE V
`A suitable fungicidal dusting powder consists of :
`Percent
`98
`(A) Talc USP
`2
`(B) Zinc iodokoiate
`The two ingredients were ground together to a powder
`which passes through a 200 mesh screen and the powder
`then ?lled into boxes.
`EXAMPLE V1
`A suspension was prepared by ?nely grinding copper
`chlorokojate and adding 100 g. of this material to 1 l. of
`water containing 1 g. of polysorbate 80. This mixture
`was vigorously ‘agitated to suspend the solid and was
`then further diluted to 250 l. with water to obtain a
`formulation suitable for application to plants. The re
`sulting dispersion contained 400 parts per million of
`the fungicide and was found eifective in the treatment
`of early blight of tomatoes.
`
`EXAMPLE VII
`Typical dust formulations of our fungicides were pre
`pared as follows: equal parts of the halokojate chclate,
`for example ferric bromokojate, and fuller’s earth were
`placed in a hammermill and milled for a period of one
`hour and then screened, collecting the fraction passing
`through a mesh screen. This 50% by weight formula
`tion was stable and could be stored and shipped as such.
`For use a further dilution was made by milling 2 parts
`
`EXAMPLE II
`
`Zinc iod0kojate.-—'I'his chelate was prepared essentially
`by procedure B. Iodokojic acid, 12.6 g., was dissolved
`in warm ethanol. To this solution was added a solution
`of 5.5 g. of zinc acetate dihydrate in 75 ml. of hot ethanol
`
`70
`
`75
`
`4
`
`

`
`3,093,659
`
`of 50% formulation with an additional 98 parts of ful-
`1.6!’5 ear-th. The resulting dust was suitable for use on
`pligt?ét is claimed is:
`1. A copper (II) complex of iodokojic acid.
`2. A copper (II) complex of bromokojioacid.
`3. A mercury (II) complex of chlorokopc 'acld.
`4. A zinc complex of bromokojic acid.
`
`10
`References Cited in the ?le of this patent
`UNITED STATES PATENTS
`O’Kgqe et a1 ___________ __ Ian. 25, 1949
`Metlvler ------------- -- June 26’ 1956
`OTHER REFERENCES
`Barham et ah: “Tram Kansas Acad_ Sci” 37, pages
`91413 (1934).
`
`2,460,188
`5 2,752,283
`
`5