WO2020133014A1 - Crystalline form c of cypyrafluone monoisopropylamine salt, and preparation method therefor and use thereof - Google Patents

Abstract

A crystalline form C of cypyrafluone monoisopropylamine salt, and a preparation method therefor and use thereof. The X-ray powder diffraction pattern of the crystalline form C of cypyrafluone monoisopropylamine salt has characteristic peaks at diffraction angles 2θ of 6.9°, 7.4°, 8.3°, 10.2°, 11.3°, 12.5°, 14.0°, 15.1°, 16.3°, 17.0°, 18.0°, 18.7°, 19.2°, 20.0°, 20.6°, 21.2°, 21.7°, 22.3°, 23.0°, 24.8°, 25.9°, 26.2°, 27.5°, 28.1°, 28.4°, 29.4°, 30.3°, 30.8°, 31.3°, 31.8°, 33.4°, 34.0°, 34.7°, 35.8°, 37.0°, 37.7°, 38.2°, 38.8°, 40.1°, 40.7°, 42.6°, and 44.0°, wherein the error range of the 2θ is within ±0.2°. The crystalline form C of cypyrafluone monoisopropylamine salt has good physicochemical stability, great solubility, and high biological activity, and can be used for preventing and removing weeds.

Description

Cyproterone-isopropylamine salt C crystal form and its preparation method and use Technical field

The invention belongs to the technical field of herbicide crystallization technology, and particularly relates to a crystalline form of ciprofloxacin-isopropylamine salt, and a preparation method and application thereof.

Background technique

Ciprofloxacin (structural formula:

) Is a newly developed HPPD inhibitor herbicide for post-emergence stem and leaf treatment of wheat fields, which has excellent biological activity and can effectively control a variety of malignant grass weeds in wheat fields. The compound patent has been authorized, authorization announcement number: CN 105218449 B.

Polymorphism refers to the phenomenon in which solid substances form solid states with different physical and chemical properties in two or more different spatial arrangements. Different crystal forms have different colors, melting points, dissolution, dissolution properties, chemical stability, reactivity, mechanical stability, etc. These physical and chemical properties or processability sometimes directly affect the safety and effective performance of drugs. Therefore, crystal form research and control has become an important research content in the process of drug development.

Summary of the invention

The present invention provides a new herbicide ciprofloxacin-isopropylamine salt C crystal form and its preparation method and use. The crystal form has good physical and chemical stability, high solubility and high biological activity, and can be used for controlling common weeds in crop fields.

The technical scheme adopted by the present invention is as follows:

A crystalline form of ciprofloxacin-isopropylamine salt, X-ray powder diffraction spectrum at diffraction angles 2θ of 6.9°, 7.4°, 8.3°, 10.2°, 11.3°, 12.5°, 14.0°, 15.1° , 16.3°, 17.0°, 18.0°, 18.7°, 19.2°, 20.0°, 20.6°, 21.2°, 21.7°, 22.3°, 23.0°, 24.8°, 25.9°, 26.2°, 27.5°, 28.1°, 28.4 °, 29.4°, 30.3°, 30.8°, 31.3°, 31.8°, 33.4°, 34.0°, 34.7°, 35.8°, 37.0°, 37.7°, 38.2°, 38.8°, 40.1°, 40.7°, 42.6°, There is a characteristic peak at 44.0°, where the 2θ error range is within ±0.2°.

Preferably, the corresponding I/I ₀ is 3.5, 53.5, 8.9, 80.6, 12.7, 2.8, 100.0, 46.5, 19.3, 3.9, 12.8, 11.6, 18.9, 51.8, 10.3, 5.1, 12.9, 5.7, 26.1, 23.5 , 25.8, 41.3, 12.9, 8.5, 9.4, 3.6, 14.3, 9.7, 4.7, 4.5, 3.2, 5.7, 27.9, 3.7, 5.0, 1.4, 2.7, 5.3, 2.1, 3.5, 3.0, 2.0.

More preferably, its X-ray powder diffraction pattern is substantially as shown in FIG. 1.

The preparation method of the crystalline form C of ciprofloxacin-isopropylamine salt includes the following steps: dissolve the ciprofloxacin-isopropylamine salt in methanol, stir until completely dissolved, and then add 1-10 times the volume of Methyl tert-butyl ether causes a large amount of solid crystals to precipitate out of the solution, and the resulting solid crystals are dried to obtain crystalline form C of flupiroxone-isopropylamine salt.

A herbicidal compound composition, comprising (i) the crystalline form of cyclofluxonone isopropylamine salt; preferably, it also includes (ii) one or more other active ingredients and/or safeners; Preferably, (iii) agrochemically acceptable formulation aids are also included.

Preferably, the auxiliary agent is selected from one or more of solvents, solid diluents, emulsifiers, wetting agents, dispersants, antifreeze agents, defoamers and thickeners.

Selected solvents include but are not limited to polar solvents: water, N,N-dimethylamide, dimethyl sulfoxide, N-alkylpyrrolidone, methanol, ethanol, ethylene glycol, isopropanol, ethylene glycol Butyl ether, propylene glycol methyl ether, etc.; aromatic hydrocarbon solvent oil series: toluene, xylene, No. 100 solvent oil, No. 150 solvent oil, No. 180 solvent oil, No. 200 solvent oil, etc.; vegetable oils: castor oil, linseed oil, sesame oil , Corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and their corresponding methylated vegetable oils, etc.; ketones: cyclopentanone, cyclohexanone, cyclooctanone, 2-heptanone, isophorone and 4-Hydroxy-4-methyl-2-pentanone, etc.; Acetates: methyl acetate, ethyl acetate, propyl acetate, sec-butyl acetate, isoamyl acetate, hexyl acetate, heptyl acetate and acetic acid Octyl esters, etc.; other categories such as: decanamide, cyclohexanol, decanol, benzyl alcohol, and tetrahydrofurfuryl alcohol.

The selected solid diluent may be water-soluble or water-insoluble. Water-soluble solid diluents include, but are not limited to: salts, such as alkali metal phosphates (sodium dihydrogen phosphate), alkaline earth metal phosphates, sodium, potassium, magnesium and zinc sulfates, sodium chloride and potassium chloride, sodium acetate , Sodium carbonate and sodium benzoate, as well as sugar and sugar derivatives, such as sorbitol, lactose, sucrose and mannitol, corn starch, etc. Examples of non-water soluble solid diluents include, but are not limited to: clay, calcium carbonate, diatomaceous earth, white carbon, calcium silicate, bentonite, magnesium aluminum silicate, kaolin and the like.

Wetting agents include, but are not limited to: alkyl sulfosuccinates, laurates, alkyl sulfates, phosphates, ethoxylated fluorinated alcohols, ethoxylated silicones, alkylphenol ethoxylates , Benzene sulfonate, alkyl substituted benzene sulfonate, alkyl α-olefin sulfonate, naphthalene sulfonate, alkyl substituted naphthalene sulfonate alkali metal salt, naphthalene sulfonate alkali metal salt and alkyl substitution Condensate of naphthalene sulfonate and formaldehyde, alcohol ethoxylate.

Dispersants include, but are not limited to: sodium, calcium and ammonium salts of lignin sulfonic acid; sodium and ammonium salts of maleic anhydride copolymer; sodium salts of condensed phenolsulfonic acid; naphthalenesulfonate-formaldehyde condensate ; Phosphate ester dispersant, polycarboxylate dispersant, etc.

Thickeners include, but are not limited to: guar gum, pectin, xanthan gum, alginate, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, magnesium aluminum silicate, and the like. Synthetic thickeners include derivatives of the foregoing types, and also include polyvinyl alcohol, polyacrylamide, polyvinylpyrrolidone, various polyethers and their copolymers, and polyacrylic acid and their salts.

Other formulation ingredients such as dyes, defoamers, desiccants, etc. can be used in the present invention. These ingredients are well known to those skilled in the art.

Suitable active ingredients that can be mixed with the crystalline form C of ciprofloxone-isopropylamine salt of the present invention are, for example, "World Pesticide New Variety Technology Encyclopedia", China Agricultural Science and Technology Press, 2010.9 and the documents cited here Known substances. For example, the various substances mentioned below (note: the name of the compound, or the common name according to the International Organization for Standardization (ISO), or the chemical name, where appropriate, code): acetochlor, butachlor, alachlor Amine, propachlor, metolachlor, mesochlor, alachlor, alachlor, alachlor, naproxen, R-levonapropion, dipropanil, benzene Alafenamide, difenacetamide, flufenacetamide, chlorfenapyr, flufenacetamide, bromobutyramide, dimethoxamide, high-efficiency dimethoxamide, ethoxybenzamide Amine, flufenazone, alafenamide, metazachlor, clomazone, high-efficiency dicofol, high-efficiency propylpropanil, dipropoxyfen, dimethoprim, butachlor, cyprofen Glufosinate, fluoxanilam, heptochlor, isobutachlor, alachlor, terbutazone, xylolachlor, dimethylchlor, alachlor, trimechlor, chloroformyl Oxachlor, cyproteron, valerox, chloramphenicol, hexamethylene chloride, tricyclachlor, butachlor, butachlor, benzalkonium, quinamphetamine, fenfluramide, naphthalene Propylamine, acetochlor, naphthalene, alachlor, chlorfenapyr, cyproteron, beclomethoxazole, triclopyr, chlorophthalimide, butamidamide, fluroxypyr, atrazine, sima Jin, Fucaojing, cyanochlor, xicaojing, atrazine, promethazine, isopropyl, fluoxazin, terbutaline, terbutin, triazfluflur, cipromazine, gampizin , Kudazin, Promethazine, Cimaton, Azidene, Diquat, Isopentenyl, Ciprochlor, Ciprozine, Another Dingjin, Zhongdingtong, Tedintong, Methoxypropyl, Cyanochlor, acetochlor, clonazine, atrazine, trimethoprim, glycyrrhizin, cyanuric acid, Indaziflam, chlorsulfuron, metsulfuron, bensulfuron-methyl, chlorimuron-methyl, bensulfuron-methyl, Thisulfuron, pyrimsulfuron, methyldisulfuron, methyl iodosulfuron-methyl sodium salt, formamidosulfuron-methyl, ethersulfuron, ether besulfuron, methylsulfuron, nicosulfuron, amine Bensulfuron-methyl, acrimsulfuron, ethoxasulfuron-methyl, cyprosulfuron-methyl, sulfasulfuron-methyl, tetrazosulfuron-methyl, pyrasulfuron-methyl, monosulfuron-methyl, monosulfuron-methyl, fluorosulfuron Ketosulfuron, fluoropyrsulfuron-methyl, fluoropyrsulfuron-methyl, oxasulfuron-methyl, oxasulfuron-methyl, fluoropyrsulfuron-methyl, profensulfuron-methyl, trifluorosulfuron-sulfuron-sulfuron, trisulfuron-methyl Sulsulfuron, Flusulfuron, Trifamsulfuron, Metsulfuron-methyl sodium salt, Flufensulfuron, Metsulfuron-methyl, Pyrisulfuron-methyl, Propyrisulfuron (Promethisulfuron), azirsulfuron-methyl , Triflufenacil, fomesafen, milfluralin, acetoflufen, acetoflufen, ethoxyfop-methyl, gluconate, phenoxyfen, ethyl chloroflufenate, mecarben, Triflufenicol, methoxypyridin, triflufenicol, fluorinated herbicidal ether, flufenacetin, herbicidal ether, acetochlor, dimethoxin, fluoxifen, oxaflufen, fluroxypyr, Halosafen, chlormeron, isoproturon, rifauron, diuron, sapron, flusulfuron, phendiuron, metsulfuron, bensulfuron, sulfathion, isoxuron, terdin Thifensulfuron, oxasulfuron, chlorbromon, methylsulfuron, acesulfuron, methoxacarb, bromulon, methoxysulfuron, chlordiazepam, mefenuron, cyprosulfuron, non-grass Long, Flusulfuron, Cabulong, Caesalon, Caolonglong, Isomalon, cyclosulfuron, teflon, thidiazuron, atulon, p-fluorofuran, methamizon, sulfamethoxazole, trimethylisourea, oxazolon, Monisouron, Anisuron, Methiuron, Chloreturon, tetrafluoro Long, betanin, betanin-ethyl ester, beetroot, sulfachlor, terachlor, oat ling, anilin, chlorpheniramine, diclofenac, chlorpyrifos, chlorpyral, carboxazole, Chlorprocarb, Fenasulam, BCPC, CPPC, Carbasulam, butachlor, cyproteron, cyproteron, cyproteron, dicamba, piperazine, cypermethrin, barnyardgrass, cyprodione, oats dichloride, chlordiazepam, Acesulfame, pingcaodan, kecameng, benzalkonium, chlorpyrifos, thiodimethalin, chlorpyrifos, Isopolinate, Methiobencarb, 2,4-D butyl ester, 2 methyl 4 sodium chloride, 2, 4-Dip Isooctyl Ester, 2M 4 Chloro Isooctyl Ester, 2,4-D Sodium Salt, 2,4-D Monoisopropylamine Salt, 2M 4 Chloroethane Thioester, 2M 4 Chlorothioate, 2,4 -Dipropionic acid, high 2,4-D propionate, 2,4-D butyric acid, 2 methyl 4 chloropropionic acid, 2 methyl 4 chloropropionic acid, 2 methyl 4 chlorobutyric acid, 2,4,5 -Aldi, 2,4,5-aldipropionic acid, 2,4,5-dibutyric acid, 2 methyl 4 chloramine salt, dicamba, pymetrozine, valerazine, cyperson, triclosan, ammonia Diclofenac, trimethoprim-acid, triclopyr, diflufenicol, diflufenicol, diflufenicol, flupyralin, high-efficiency diflufenarin, quizalofop, quizalofop , Oxachlor, oxamethoxazole, oxamethoxam, cyflufenazone, oxachlor, cyproxon, thiazolachlor, cyproxon, oxypentalin, triflufopram Oxaloxime, clomazone, paraquat, diquat, sulfamethoxazole, ebuprofen, isoprofen, mesosulfuron, ciprofloxacin, aminopropion, eprofen, Chloroflufen, Aminofluorine, Difluralin, Chlorodifloxacin, Methalpropalin, Propofol, Glyphosate, Sarcofosine, Glufosinate, Glufosinate, Methamidophos, Grass Thiophosphorus, piperfosin, dipropylphosphinate, diphosphazene, glufosinate, glufosinate, valerian phosphorus, bismethamine, glufosinate, imidazole nicotinic acid, imidazole nicotinic acid, imidazoquinoline acid, methoxymethoxine Imazamox, imimethapyr ammonium salt, imicarbazole nicotinic acid, imazapyr, clofloxacin, isooctyl clofloxacin, diclofenac, amiloride, triclofenac Acetic acid, fluroxypyr, fipronil, triclofenol, thiacloprid, fluroxypyr, clopyralid, fluroxypyr, butoxyethyl triclofenac, Cliodinate, dimethoate Cyproterone, clethodim, thiacopyr, chlorfenapyr, ciclofenone, bufofenone, oxadiazon, pyranone, Buthidazole, chlorfenapyr, cycloazinone, phenazin, ethazine Oxaphenone, Ametridione, Amibuzin, bromoxynil, octanoyl bromoxynil, octanoyl iodile nitrile, iodobenzonitrile, diquat, diphenylacetonitrile, bisacrylonitrile, hydroxyditrile, Iodobonil, herbicide bromide, Oxachlor , Fomesulam, penoxsulam, sulfoxazosin, chlorfenazone, chlorfenapyr, chlorfenapyr, chlorfenapyr, fluroxypyr, chlorfenapyr, pymetrozine, pyrimethanil, cyclic esters Glufosinate, chlorfenuron, chlorfenapyr, bicyclosulone, mesotrione, sulcotrione, Tembotrione, Tefuryltrione, Bicyclopyrone, Ketodpiradox, isoxaflutole, clomazone, Fenoxasulfone, Methiozolin, Isoprofen, mepyroxyfen, pyrazolate, pyraclopyr, benzimidazole, pyraclostrobin, pyroxachlor, Pyrasulfotole, oxachlor, Pyroxasulfone, pyrachlor, fluoxazone, trimethoprim Chlortetracyclone, chlorpyrifosin, chlorpyrifosin, fluoxazone, mesotrione, Bencarbazone, diflufenazone, fluoxaprofen, herbicin, clomazone, cyproteron, special grass Ding, Flupropacil, indoxachlor, flufenoxalic acid, propynyl oxachlor, ethoxychlor, benzalkonium ether, Flumezin, pentachlorophenol (sodium), tetrol, teraphenol, teramate, pentol Nitrophenol, Dinitrophenol, Chloronitrate, Dextrol, Dilox, Propyraxazone, Oxadiazone, Cyclopentoxazone, Fluoxazone, Methyloxamate, Tetraxazone , Flupyrazine, chlorfenapyr, bromachlor, dicarpyrazine, pyraclostrobin, pyridoxazone, tripyridamole, pyrrazine, Pyridafol, quinclorac, chloroquinolinic acid, Bendazon, dapyrazine, oxadiazon, chlorpyrifos, clomazone, cyprofen, isopropyl chlorfen, propyl fenpyr, indoxazone, sodium chlorate, thatch Chloroacetic acid, monochloroacetic acid, hexachloroacetone, tetrafluoropropionic acid, carbendazole, forage fast, bromophenol oxime, triazolasulfon, mefenazole, furazone, furasulfon, acetofuran, pyrimex Amine, chlorophthalic acid, fluroxypyr, barnyard grass dilute, acrolein, benzeben, chlorfenapyr, oat ester, thiadiazolamide, trimethoprim, hypromone, amilofenone, methoxymethoxine Benzophenone, alafenamide, chlorfenapyr, trichloropropionic acid, Alorac, Diethamquat, Etnipromid, Iprymidam, Ipfencarbazone, Thiencarbazone-methyl, Pyrimisulfan, Chlorflurazole, Tripropindan, Sulglycapin, metsulfuron, Cambendichlor, cyprofen Pyrimidine acid, thiocyananilide, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, acetonitrile, oxalane, oxachlor, acetonitrile, oxamethrin, pyrazolamate, Furoxanazole, oxamethoxam, bisoxazolic acid, dichloropropenylamine, fluorochloropyridine ester, DOW848, UBH-509, D489, LS 82-556, KPP-300, NC-324, NC-330, KH-218, DPX-N8189, SC-0744, DOWCO535, DK-8910, V-53482, PP-600 , MBH-001, KIH-9201, ET-751, KIH-6127 and KIH-2023. Furthermore, it has been experimentally verified that the crystalline form C of ciprofloxacin-isopropylamine salt and one or more of the herbicides listed above have obvious synergistic and synergistic effects.

Preferably, the other active ingredients include, but are not limited to: pyrachlor (CAS No.: 83164-33-4), isoxaflutole (CAS No.: 141112-29-0), cypromethrin (CAS No.: 105512-06-9), oxazolin (CAS No.: 243973-20-8), isoproturon (CAS No.: 34123-59-6), chlormeron (CAS No.: 15545-48-9 ), octanoyl bromoxynil (CAS number: 1689-99-2), azoxystrobin (CAS number: 21087-64-9), dapyridine (CAS number: 55512-33-9), azaprofen (CAS number: 129909-90-6), 2 methyl 4 chlorine (CAS number: 94-74-6), chlorofluoropyroxyacetic acid (CAS number: 69377-81-7), fluorochloropyridine ester (CAS number: 943831-98-9), dicamba (CAS number: 1918-00-9), alafenamide (CAS number: 372137-35-4), flufenazone (CAS number: 142459-58-3) , Refined metolachlor (CAS number: 178961-20-1), sulfamethoxazole (CAS number: 447399-55-5), pendimethalin (CAS number: 40487-42-1), methyl Disulfuron (CAS No.: 208465-21-8), fluoxuron (CAS No.: 181274-17-9), sulfamethoxam (CAS No.: 422556-08-9), benzedan (CAS No. : 52888-80-9) and one or more of its derivatives.

In the context of this specification, if the abbreviated form of the common name of the active compound is used, then in each case all conventional derivatives, such as esters and salts, as well as isomers, especially optical isomers, especially One or more commercially available forms. If the generic name indicates an ester or salt, then in each case all other conventional derivatives are also included, such as other esters and salts, free acids and neutral compounds, as well as isomers, especially optical isomers, especially Is one or more forms of market. The chemical names of the compounds given represent at least one compound covered by the common name and are generally preferred compounds. In the case of sulfonamides such as sulfonylurea, salts also include salts formed by the exchange of cations with hydrogen atoms in the sulfonamide group. For example, 2M 4 Chlorine derivatives include but are not limited to: 2M 4 Chlorine sodium salt, potassium salt, dimethyl ammonium salt, isopropylamine salt, etc., as well as 2M 4 Chlorine methyl ester, ethyl ester, isooctyl ester, ethyl sulfide Ester etc.

In the context of the present invention, the salt of the compound is preferably in the form of a respective alkali metal salt, alkaline earth metal salt or ammonium salt, preferably in the form of a respective alkali metal salt, more preferably in the form of a respective sodium or potassium salt, Most preferred is the form of the respective sodium salt.

The total mass percentage of active ingredients in the composition accounts for 1-95% of the total.

The safener is preferably bisoxazolic acid (CAS: 163520-33-0), cyprosulfamide (CAS: 221667-31-8), pyrazolinate (CAS: 135590-91-9), detoxified quinoline (CAS : 99607-70-2), gibberellic acid (CAS: 7-06-5), furilazole (CAS: 121776-33-8), one or more of metcamifen (CAS: 129531-12-0).

The dosage form of the composition is water suspension (SC), dispersible oil suspension (OD), emulsifiable concentrate (EC), microemulsion (ME), granule (GR), suspension emulsion (SE) or water dispersible granule (WDG).

The invention also provides a method for controlling weeds in crops, which comprises using a herbicidally effective amount of the crystalline form C of ciprofloxacin-isopropylamine salt or the herbicidal compound composition on crops or Weed area.

The present invention also provides the use of the ciprofloxone-isopropylamine salt crystal form C or the herbicidal compound composition in controlling weeds; preferably, it is used to control impurities in useful crops Grass, the useful crops are genetically modified crops or crops processed by genome editing technology.

Preferably, the crop is wheat, and the weeds are gramineous weeds, such as maidenhair, Japanese maidenhair, etc.

The ciprofloxone-isopropylamine salt C crystal form of the present invention has been tested and has good physical and chemical stability, good water solubility, and the solubility in water is increased more than ten times compared to ciprofloxacin, compared to ciprofloxacin The sodium salt of ketone increases nearly six times, and the crystalline form C or the compound composition with other active ingredients has a good control effect on wheat field grasses weeds, and the effect is significantly better than ciprofloxacin and its Sodium salt.

BRIEF DESCRIPTION

FIG. 1 is an XRPD pattern of the crystalline form C of flufenazone-isopropylamine salt of Example 2 in the present invention.

detailed description

The above contents of the present invention will be further described in detail through the following embodiments, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following embodiments, and all technologies implemented based on the above contents of the present invention belong to the scope of the present invention.

XRPD measurement method

Instrument model: Bruker D8 advance, target: Cu Kα (40kV, 40mA), sample-to-detector distance: 30cm, scanning range: 3 ⁰ -45 ⁰ (2θ value), scanning step size: 0.05s.

Example 1

According to CN method 105218449, preparation of ciprofloxacin original drug, then 1 kg of ciprofloxacin and 0.3 kg of 30% sodium hydroxide aqueous solution were reacted, and a large amount of solid crystals were obtained by reaction, the solid was filtered and dried to obtain ciprofloxacin Oxalate sodium salt powder.

Example 2

1 kg of cyclofluxonone obtained in Example 1 was reacted with 0.27 kg of 50% aqueous solution of monoisopropylamine to obtain a large amount of solid crystals. The solid was filtered and dried to obtain powder of cyclofluxonone-isopropylamine salt.

Place 1000 g of cycloflufenone-isopropylamine salt in a 10 L flask, add 2 L of methanol, heat and stir until the raw materials are completely dissolved, then add 7 liters of methyl tert-butyl ether to precipitate a large amount of crystals, filter the solid and Drying to obtain ciprofloxone-isopropylamine salt C crystalline powder.

Physical and chemical stability experiment

The three powders of ciprofloxacin and its sodium salt obtained in Example 1 and the crystalline form of ciprofloxacin-isopropylamine obtained in Example 2 were measured by HPLC. The content of ciprofloxacin was 97.2%. The content of fluroxypyr sodium salt is 98.0%, and the content of cyclofipronone-isopropylamine C crystal form is 98.0%. After that, the three original drug powders are placed at 25 ℃, 40 ℃, 55 ℃ and 70 Place in the oven at ℃ for 2 months to conduct the heat storage experiment, and then test the purity.

Table 1 Investigation of the stability of different samples

sample	Ciprofloxacin	Ciprofloxan sodium salt	Ciprofloxacin-isopropylamine salt form C
25℃	97.2%	98.0%	98.0%
40℃	96.6%	97.8%	97.9%
55℃	96.1%	97.3%	97.7%
70℃	95.5%	96.5%	97.3%

It can be seen from Table 1 that ciprofloxone and its sodium salt and ciprofloxone-isopropylamine salt C crystal form have good stability under different temperature conditions, especially at 55 ℃ and 70 ℃ At temperature, the crystalline form C still maintains good physical and chemical stability, and the purity detection is comparable or slightly better than ciprofloxacin and its sodium salt, and has good application prospects.

Determination of solubility in water

The two powders of ciprofloxanone and its sodium salt obtained in Example 1 and the crystalline form of ciprofloxone-isopropylamine salt obtained in Example 2 were dissolved in pure water and shaken at 25°C for 24h , To make it fully dissolved, then centrifuged and filtered, the filtrate was passed through a 0.22μm filter membrane, and the solubility in water was determined by HPLC. The results are shown in Table 2 below:

Table 2 Results of water solubility test of different samples

sample	Solubility in pure water (g/L)
Ciprofloxacin	0.526
Ciprofloxan sodium salt	1.194
Ciprofloxacin-isopropylamine salt form C	6.375

From the results in Table 2, it can be seen that the crystalline form C of ciprofloxone-isopropylamine salt has a significantly increased solubility compared to ciprofloxone and its sodium salt.

Example 1 and Example 2 formulation processing and field efficacy experiment

The ciprofloxanone and its sodium salt obtained in Example 1 and the crystalline form of ciprofloxone-isopropylamine salt C obtained in Example 2 were processed into the following formulations according to the same formula. The specific formula is as follows, which is effective Component A represents the crystalline form of ciprofloxacin, ciprofloxacin sodium salt and ciprofloxacin-isopropylamine salt.

6% A OD

6% A+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.5% fumed silica+5%150# Solvent oil + methyl oleate make up

14% A·Pyfluramide OD

6%A+8%pyramethoprim+5% calcium dodecylbenzenesulfonate+8% fatty alcohol polyoxyethylene ether+4% castor oil polyoxyethylene ether+2.0% organic bentonite+1.0% gas phase method White carbon black + 10% 150# solvent oil + methyl oleate make up

9% A · Isoxaflutole SC

6%A+3%isoxachlor+5% phenethylphenol polyoxyethylene ether phosphate monoisopropylamine salt+1.5% fatty alcohol polyoxyethylene ether+0.2% xanthan gum+2.2% magnesium aluminum silicate +0.1% defoamer +4% ethylene glycol + water to make up

7.5% A · ethinyl OD

6% A + 1.5% ethinyl oxalate + 5% calcium dodecylbenzene sulfonate + 5% fatty alcohol polyoxyethylene ether + 6% castor oil polyoxyethylene ether + 2.0% organic bentonite + 2.0% fumed white carbon Black + 10% 150# solvent oil + methyl oleate make up

7.5% A·oxazolin OD

6%A+1.5%oxazolinate+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.0% organic bentonite+2.0% gas-phase method white Carbon black + 20% 150# solvent oil + methyl oleate make up

56% A·Ipromethon WDG

6% A+50% Isoprofen+5% Sodium Lauryl Sulfate+8% Polycarboxylate Dispersant+2% Polyethylene Glycol 4000+5.0% Precipitation Method White Carbon + Kaolin Supplement

66%A·Green McLong WDG

6%A+60% chlormeruron+5% sodium dodecyl sulfate+8% polycarboxylate dispersant+2% polyethylene glycol 4000+5.0% precipitation white carbon black + kaolin supplement

26%A·Octanoyl bromoxynil OD

6%A+20%octanoyl bromoxynil+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% gas phase method White carbon black + 10% 150# solvent oil + methyl oleate make up

12% A·pyrazine OD

6%A+6%azoxazone+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.5% fumed white carbon Black + 10% 150# solvent oil + methyl oleate make up

32.3% A·Dapote OD

2.3% A+30% dasapate+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.8% organic bentonite+2.5% fumed white carbon Black +20%150# solvent oil + methyl oleate to make up

13%A·Azoxystrobin OD

6% A+7% Amoxachlor+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.3% organic bentonite+2.0% gas phase white Carbon black + 20% 150# solvent oil + methyl oleate make up

26% A·2 A 4 Chlorine SL

6% A + 20% 2 methyl 4 chlorine + 6% monoisopropylamine + 40% ethanol + 10% fatty alcohol polyoxyethylene ether sodium sulfate + water to make up

11%A·chlorofluoropyridineacetic acid OD

6%A+5%chlorofluoropyroxyacetic acid+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.3% organic bentonite+2.0% gas phase method White carbon black +12%150# solvent oil + methyl oleate make up

6.5% A·fluorochloropyridine ester OD

6%A+0.5%fluorochloropyridinyl ester+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.3% organic bentonite+2.0% fumed white Carbon black + 10% 150# solvent oil + methyl oleate make up

18% A. dicamba SL

6% A + 12% dicamba + 7% monoisopropylamine + 40% ethanol + 10% fatty alcohol polyoxyethylene ether sodium sulfate + water to make up

8.5%A·Sulfentrazone OD

6%A+2.5%amphetrofen+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% gas phase method White carbon black + 10% 150# solvent oil + methyl oleate make up

18%A· Fluoxazone OD

6%A+12% fluoxazone+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.0% organic bentonite+2.0% fumed white Carbon black + 10% 150# solvent oil + methyl oleate make up

14% A·Promethorone OD

6% A + 8% refined metolachlor + 5% calcium dodecylbenzene sulfonate + 5% fatty alcohol polyoxyethylene ether + 6% castor oil polyoxyethylene ether + 2.5% organic bentonite + 2.0% gas phase French white carbon + 10% 150# solvent oil + methyl oleate

12% A·sulfoxamethoxazole OD

6%A+6%sulfoxamethoxazole+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% fumed white Carbon black + 10% 150# solvent oil + methyl oleate make up

22%A·Dimethalin OD

2%A+20% pendimethalin+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% fumed white Carbon black + 20% 150# solvent oil + methyl oleate make up

6.6% A·Methyldisulfuron OD

6%A+0.6%methyldisulfuron+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% gas phase method White carbon black + 10% 150# solvent oil + methyl oleate make up

8%A·Foxasulfuron OD

6%A+2% fluoxuron+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% fumed white Carbon black + 10% 150# solvent oil + methyl oleate make up

6.6% A·Sulfentrazone OD

6%A+0.6%Sulfentrazone+5%Calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5%organic bentonite+2.0% fumed white Carbon black + 10% 150# solvent oil + methyl oleate make up

43%A·benzyldan OD

3%A+40%benzyldan+5% calcium dodecylbenzenesulfonate+5% fatty alcohol polyoxyethylene ether+6% castor oil polyoxyethylene ether+2.5% organic bentonite+2.0% fumed white carbon Black + 10% 150# solvent oil + methyl oleate make up

Field effect test: after three leaves of wheat, look at the 3-4 leaf stage of Mai Niang, the 3-4 leaf stage of Mai Niang in Japan, the electric dynamic sprayer, the water amount is 30 kg/667m ² , the stem and leaf spray is evenly sprayed, and the area is 30 Square meters, the average plant control effect (visual observation) 45 days after each treatment was repeated 4 times after application, see Table 3 below.

Table 3 Effect of different preparations on weed control in wheat direct seeding field (%)-control effect after 45 days of application

It can be seen from Table 3 that compared with the effect of different preparations of ciprofloxacin on weeds in wheat direct field, the control effect of crystalline form C of ciprofloxacin-isopropylamine salt is significantly higher than that of ciprofloxacin and its sodium salt preparation.

At the same time, after many tests, it has been found that the compounds and compositions of the present invention can control many key grass weeds and broad-leaved weeds. Tests on wheat, corn, rice, sugar cane, soybean, cotton, oil sunflower, potato, fruit tree, vegetable, etc. under different application methods also showed excellent selectivity and commercial value.

The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above-mentioned embodiments. The above-mentioned embodiments and the description only describe the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention will have various changes and improvements, and these changes and improvements fall within the scope of protection of the present invention.

Claims (10)

1. A crystalline form of ciprofloxacin-isopropylamine salt, characterized by: X-ray powder diffraction spectrum at a diffraction angle 2θ of 6.9°, 7.4°, 8.3°, 10.2°, 11.3°, 12.5°, 14.0 °, 15.1°, 16.3°, 17.0°, 18.0°, 18.7°, 19.2°, 20.0°, 20.6°, 21.2°, 21.7°, 22.3°, 23.0°, 24.8°, 25.9°, 26.2°, 27.5°, 28.1°, 28.4°, 29.4°, 30.3°, 30.8°, 31.3°, 31.8°, 33.4°, 34.0°, 34.7°, 35.8°, 37.0°, 37.7°, 38.2°, 38.8°, 40.1°, 40.7° , 42.6°, 44.0° have characteristic peaks, where the 2θ error range is within ±0.2°.
2. The crystalline form C of ciprofloxacin-isopropylamine salt according to claim 1, wherein the corresponding I/I0 is 3.5, 53.5, 8.9, 80.6, 12.7, 2.8, 100.0, 46.5, 19.3 , 3.9, 12.8, 11.6, 18.9, 51.8, 10.3, 5.1, 12.9, 5.7, 26.1, 23.5, 25.8, 41.3, 12.9, 8.5, 9.4, 3.6, 14.3, 9.7, 4.7, 4.5, 3.2, 5.7, 27.9, 3.7 , 5.0, 1.4, 2.7, 5.3, 2.1, 3.5, 3.0, 2.0.
3. The crystalline form C of ciprofloxacin-isopropylamine salt according to claim 1 or 2, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.
4. The preparation method of ciprofloxacin-isopropylamine salt C according to any one of claims 1 to 3, characterized in that it comprises the steps of: dissolving ciprofloxacin-isopropylamine salt in methanol and stirring to After complete dissolution, 1-10 volumes of methyl tert-butyl ether was added to precipitate a large amount of solid crystals in the solution, and the resulting solid crystals were dried to obtain crystalline form C of flupiroxone-isopropylamine salt.
5. A herbicidal compound composition, characterized by comprising (i) the crystalline form C of flupiroxone-isopropylamine salt according to any one of claims 1-3; preferably, (ii) one or A variety of other active ingredients and/or safeners; more preferably, (iii) agrochemically acceptable formulation aids.
6. The herbicidal compound composition according to claim 5, characterized in that the other active ingredients are selected from the group consisting of pyraclostrobin, isoxaflutole, ethinal, oxafen, isoprofen, green Myron, octanoyl bromoxynil, azoxystrobin, dapyridine, azaclofen, 2methyl-4chloro, chlorofluoropyroxyacetic acid, fluopyridin, dicamba, alafenamide, flufenazone One or more of amine, mesochlor, sulfamethoxazole, pendimethalin, methyldisulfuron, flusulfuron, sulfamethoxam, benomyd and their derivatives.
7. The herbicidal compound composition according to claim 6, characterized in that the total mass percentage of active ingredients in the composition accounts for 1-95% of the total.
8. The herbicidal compound composition according to any one of claims 5-7, characterized in that the dosage form of the composition is an aqueous suspending agent, a dispersible oil suspending agent, emulsifiable concentrate, microemulsion, granule, suspending emulsion or Water dispersible granules.
9. A method for controlling weeds in crops, characterized in that it comprises a herbicidally effective amount of ciprofloxacin-isopropylamine salt crystal form C according to any one of claims 1-3 or any one of claims 5-8 The herbicidal compound composition according to one item is used on crops or weed areas; preferably, the crop is wheat, and the weeds are gramineous weeds (for example, see maidenhair, Japanese see maidenhair).
10. The use of ciprofloxone-isopropylamine salt crystal form C according to any one of claims 1-3 or the herbicidal compound composition according to any one of claims 5-8 for controlling weeds, preferably It is used to control weeds in useful crops, which are genetically modified crops or crops treated by genome editing technology; preferably, the crops are wheat, and the weeds are grass weeds (such as See Mai Niang, Japan see Mai Niang).

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