DK146534B - PROCEDURE FOR PREPARING PURE SUBSTITUTED N-METHYL-PYRAZOL-ACETANILIDES - Google Patents
PROCEDURE FOR PREPARING PURE SUBSTITUTED N-METHYL-PYRAZOL-ACETANILIDES Download PDFInfo
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- DK146534B DK146534B DK481279AA DK481279A DK146534B DK 146534 B DK146534 B DK 146534B DK 481279A A DK481279A A DK 481279AA DK 481279 A DK481279 A DK 481279A DK 146534 B DK146534 B DK 146534B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Description
i 146534 opfindelsen angår en fremgangsmåde til fremstilling af i vidt omfang rene, substituerede N-methyl-pyrazol-acetanilider, af den i indledningen til kravet angivne art. De tilsvarende råprodukter kan f.eks. foreligge i den form, der svarer til 5 den tekniske fremstilling af pyrazolforbindelserne, eller i form af forurenede fremstillingscharger af pyrazolforbindelserne, hvis fremstillingsmetoden ikke skulle være forløbet efter forskrifterne, eller som de forekommer ved en forsimplet metode til fremstilling af pyrazolforbindelserne uden rensning 10 af mellemprodukterne, og fremgangsmåden er ejendommelig ved, at man behandler råprodukterne med koncentrerede, vandige opløsninger af uorganiske, stærke syrer, at man derpå separerer den vandige opløsning, og at man fortynder denne med vand og derefter separerer det udfældede, rene produkt fra den vandige 15 væske.The invention relates to a process for the preparation of substantially pure, substituted N-methyl-pyrazole-acetanilides of the kind set forth in the preamble to the claim. The corresponding raw products may e.g. available in the form corresponding to the technical preparation of the pyrazole compounds, or in the form of contaminated production batches of the pyrazole compounds, if the method of manufacture was not to be carried out according to the regulations or as they appear by a simplified method of preparing the pyrazole compounds without purification of the intermediates. and the process is characterized by treating the crude products with concentrated aqueous solutions of inorganic strong acids, then separating the aqueous solution and diluting it with water and then separating the precipitated pure product from the aqueous liquid .
Fremstillingen af disse pyrazolforbindelser er også kendt fra DE offentliggørelsesskrift nr. 26 48 008 og DE offentliggørelsesskrift nr. 27 04 281. I henhold til de der beskrevne metoder foreligger produkterne i et organisk opløsningsmiddel, 20 f.eks. chloroform, toluen, petrolether, eddikeester, benzin, opløst eller suspenderet, og må derpå separeres fra dette opløsningsmiddel, f.eks. ved afdampning af opløsningsmidlet eller filtrering. Disse metoder kan anvendes udmærket i laborato-riemålestok og giver også anledning til dannelsen af meget re- 25 ne produkter.The preparation of these pyrazole compounds is also known from DE Publication No. 26 48 008 and DE Publication No. 27 04 281. According to the methods described, the products are present in an organic solvent, e.g. chloroform, toluene, petroleum ether, vinegar ester, gasoline, dissolved or suspended, and must then be separated from this solvent, e.g. by evaporation of the solvent or filtration. These methods can be used very well on a laboratory scale and also give rise to the formation of very pure products.
Hvis man vil overføre disse laboratoriemetoder i større målestok, f.eks. pilot plant målestok eller produktionsmålestok, optræder der uventede vanskeligheder, hvoraf der i det følgende skal anføres nogle: 30 Hvis produktet foreligger i organisk opløsning, må opløsningsmidlet afdampes, eventuelt under formindsket tryk. Derved krystalliserer produktet fortrinsvis på væggene af den anvendte indampningsbeholder, f.eks. en kedel, eller bager fast der.If you want to transfer these laboratory methods on a larger scale, e.g. pilot plant scale or production scale, unexpected difficulties occur, some of which must be stated below: 30 If the product is in organic solution, the solvent must be evaporated, possibly under reduced pressure. Thereby, the product preferably crystallizes on the walls of the evaporating container used, e.g. a kettle, or baked there.
Det er kendt, at det er overordentligt vanskeligt fra en reak- 1A 6 5 3 Λ 2 tionskedel at udtage et fast, især et fastbagt produkt, med de sædvanlige små til- og af løbsåbninger. Til dette formål må det anvendte apparat nemlig demonteres af sagkyndige arbejdere, hvilket betyder et stort tid- og personaleopbud. Det fagperso-5 nåle, der anvendes til dette formål (klejnsmede) er dog normalt ikke vant til at arbejde med kemikalier eller skolet hvad angår kemiske sikkerhedsforanstaltninger og ville derfor ved indånding af eller ved kontakt med adhærerende, residuale opløsningsmiddelmængder eller produktstøv udsættes for skader.It is known that it is extremely difficult from a reaction boiler to take out a solid, especially a solid-baked product, with the usual small inlet and outlet openings. For this purpose, the apparatus used must be dismantled by skilled workers, which means a large time and staff supply. However, the professional needle used for this purpose (adhesives) is not usually used to work with chemicals or the school regarding chemical safety precautions and therefore, upon inhalation or contact with adherent residual solvent quantities or product dust, will be exposed to damage.
10 Hvis det lykkes at holde produktet i et organisk opløsningsmiddel i suspenderet form, må man fjerne dette sidste ved filtrering. I afhængighed af giftighed og e jplosionsevne af opløsningsmidlet må man derved træffe mere eller mindre omsteendelige sikkerhedsforanstaltninger, der igen betyder et stort 15 tids- og omkostningsopbud. Hyppigt går der også betydelige produktmængder tabt med filtratet.10 If the product can be kept in an organic solvent in suspended form, the latter must be removed by filtration. Thus, depending on the toxicity and explosiveness of the solvent, more or less cumbersome safety measures must be taken, which in turn means a large increase in time and cost. Often, significant amounts of product are lost with the filtrate.
Man kan således f.eks. udfælde det i et organisk opløsningsmiddel opløste produkt ved tilsætning af et andet opløsningsmiddel, som er blandbart med det første opløsningsmiddel, men 20 hvori produktet er tungtopløseligt. I afhængighed af mængden af fældningsopløsningsmidlet fælder der dog mere eller mindre produkt ud, hvorved renheden deraf igen afhænger af mængden af fældningsmidlet.Thus, for example, precipitate the product dissolved in an organic solvent by the addition of a second solvent which is miscible with the first solvent but in which the product is heavily soluble. However, depending on the amount of the precipitating solvent, more or less product precipitates, the purity thereof again depending on the amount of the precipitant.
Man kan også isolere produkterne på kendt måde, idet man i 25 form af salte udfælder dem fra deres opløsning i et vandfrit opløsningsmiddel, hvori deres salte er uopløselige, ved tilsætning af overskydende, vandfri syre, f.eks. ved indføring af gasformig chlorbrinte.It is also possible to isolate the products in a known manner, by precipitating them from their solution in an anhydrous solvent in which their salts are insoluble, by the addition of excess anhydrous acid, e.g. by introducing gaseous chlorine hydrogen.
Men også i dette tilfælde må man frasuge det syreholdige, or-30 ganiske opløsningsmiddel fra saltet, hvorved det som et yderligere vanskeliggørende moment kommer til, at den overskydende syre både kan adhærere til produktet og kan virke miljøbelastende og korroderende, og desuden også foreligger i filtratet 1Λ 6 5 3 Λ 3 og frembyder vanskeligheder ved oparbejdningen eller tilintetgørelsen af opløsningsmidlet. Hyppigt forekommer der ved blandingen af organiske opløsningsmidler med koncentrerede, vandfrie syrer, f.eks. chlorbrinte, svovlsyre eller salpetersyre, 5 også uønskede eller ligefrem farlige bireaktioner. Ved den kendte udfældning af produkterne med syre optræder der yderligere den ulempe, at ikke blot selve det ønskede produkt, men også samtlige andre biprodukter, der er i'stand til at danne salte, samtidigt udfældes. Desuden må man tage i betragtning, 10 at de som salte fældede produkter i en yderligere arbejdsgang igen må omdannes til de tilsvarende, frie baser. Dette er u-betinget nødvendigt, fordi saltene hydrolyserer i fugtigt milieu, f.eks. i luften, og derved frigiver ætsende og korroderende syre.But in this case, too, the acid-containing organic solvent must be aspirated from the salt, which, as a further difficult step, causes the excess acid to both adhere to the product and to act environmentally and corrosively, and also in the filtrate 1Λ 6 5 3 Λ 3 and presents difficulties in working up or destroying the solvent. Frequently, the mixture of organic solvents with concentrated anhydrous acids, e.g. hydrochloric, sulfuric or nitric, also undesirable or downright dangerous side reactions. In the known precipitation of the products with acid, there is further the disadvantage that not only the desired product itself but also all other by-products capable of forming salts are precipitated simultaneously. In addition, it must be borne in mind that 10, in a further operation, the salt precipitated products must again be converted to the corresponding free bases. This is unconditionally necessary because the salts hydrolyze in a humid environment, e.g. in the air, releasing corrosive and corrosive acid.
15 En yderligere forhindring ved overføringen af den kendte og i og for sig udmærkede laboratoriemetode til pilot plant målestok eller produktionsmålestok består i, at man til arbejder i stor målestok hyppigt ikke har så rene reagenser og opløsningsmidler og ej heller et personale, der er så godt skolet 20 i kemisk henseende som i laboratoriet. Dette er grunden til, at de fremkomne produkter for det meste er forurenet med biprodukter. Fjernelsen af disse biprodukter er næsten altid meget omstændelig og lykkes kun sjældent fuldstændigt. F.eks. kan man omkrystallisere nogle af de kendte produkter af cyclo-25 hexan. Derved kan man dog lom ufuldkomment fjerne de hyppigste forureninger, nemlig forbindelser med den almene formel ,4k-«¥15 A further obstacle to the transfer of the known and perceptible laboratory method to the pilot plant scale or production scale consists in the fact that for large scale workers often do not have as clean reagents and solvents, nor a staff that is as good schooled 20 in chemical terms as in the laboratory. This is why the resulting products are mostly contaminated with by-products. The removal of these by-products is almost always very cumbersome and only rarely succeeds completely. Eg. For example, some of the known products of cyclohexane can be recrystallized. In this way, however, one can imperfectly remove the most frequent contaminants, namely compounds of the general formula, 4k- «¥
R1 OR1 O
PP
hvori R, R , R og X har den ovenfor angivne betydning, fra pyrazolforbindelserne, fordi de ligeledes er tungtopløselige i kold cyclohexan. Desuden går store mængder af pyrazolforbin- 146534 4 delserne tabt ved omkrystallisationen. Ved isolationen af de omkrystalliserede stoffer fra organiske opløsningsmidler i stor målestok optræder de før beskrevne problemer også igen.wherein R, R, R and X are as defined above from the pyrazole compounds because they are also soluble in cold cyclohexane. In addition, large amounts of the pyrazole compounds are lost upon recrystallization. When isolating the recrystallized substances from large scale organic solvents, the problems described above also occur again.
Man har derfor søgt en fremgangsmåde, ved hvis hjælp det på 5 simpel måde Tykkes at isolere pyrazolforbindelsen i høj renhed, selv fra meget store pilot plant mængder og produktionsmængder, og ved hvis hjælp man også let kan rense forurenede charger af pyrazolforbindelsen.Therefore, a process has been sought by which it seems simple to isolate the pyrazole compound in high purity, even from very large pilot plant quantities and production volumes, and by which it is also possible to easily clean contaminated batches of the pyrazole compound.
Ved pyrazolforbindelseme drejer det sig om såkaldte aminaler, 10 fordi de indeholder to nitrogenatomer bundet til en methylen-gruppe. Det har blandt sagkyndige været kendt i lang tid, at en aminal med stærk syre i vandig opløsning lader sig spalte i en carbonylforbindelse og to nitrogenforbindelser (P.A.S. Smith, Open-Chain Nitrogen Compounds, W.A. Benjamin, Inc., 15 New York, Amsterdam 1965» bind I, S. 322).The pyrazole compounds are so-called amines, because they contain two nitrogen atoms attached to a methylene group. It has been known to those skilled in the art for a long time that an amine of strong acid in aqueous solution can be cleaved into a carbonyl compound and two nitrogen compounds (PAS Smith, Open-Chain Nitrogen Compounds, WA Benjamin, Inc., New York, Amsterdam 1965 »Volume I, p. 322).
Det har overraskende vist sig, at pyrazolforbindelseme er stabile overfor stærke, vandige syrer, selvom de udviser aminal- struktur, og at de i koncentrerede vandige syrer endog opløser sig i form af deres salte i ikke scnderdelt tilstand. Da 20 pyrazolforbindelseme imidlertid kun er meget svage baser, forbliver de uopløst i fortyndede , vandige syrer.Surprisingly, it has been found that the pyrazole compounds are stable to strong aqueous acids, even though they exhibit aminal structure, and that in concentrated aqueous acids they even dissolve in the form of their salts in unshared state. However, since the 20 pyrazole compounds are only very weak bases, they remain undissolved in dilute aqueous acids.
Fremgangsmåden ifølge opfindelsen består følgeligt deri, at man behandler råprodukterne med koncentrerede, vandige opløsninger af stærke syrer, at man derpå separerer den vandige op-25 løsning, fortynder med vand og separerer det derved udfældende, rene produkt fra den vandige væske. F.eks. blander man grundigt opløsningen af råproduktet i et med vand ikke eller kun lidet blandbart, organisk opløsningsmiddel med en koncentreret vandig opløsning af en stærk, uorganisk syre, sepa-30 rerer den vandige fase og derpå fortynder med vand, hvor ved produktet udfælder i ren form og.fra den vandige suspension let kan frafiltreres og tørres.Accordingly, the process of the invention consists in treating the crude products with concentrated aqueous solutions of strong acids, then separating the aqueous solution, diluting with water and separating the precipitated pure product from the aqueous liquid. Eg. thoroughly dissolve the solution of the crude product in a water-immiscible or only immiscible organic solvent with a concentrated aqueous solution of a strong inorganic acid, separate the aqueous phase and then dilute with water where the product precipitates in pure form and from the aqueous suspension can be easily filtered and dried.
146534 5146534 5
Men man kan f.eks. også grundigt blande krystalliseret råprodukt eller forurenet råprodukt i fast, findelt form med en koncentreret, vandig syre, filtrere og fortynde filtratet med vand og frasuge det derved udfældede, rene produkt. Tørringen 5 af de vandfugtige, rene produkter frembringer ingen tekniske problemer eller sikkerhedsproblemer.But one can, for example. also thoroughly mixing crystallized crude product or contaminated crude product in solid, finely divided form with a concentrated aqueous acid, filtering and diluting the filtrate with water, and suctioning the precipitated pure product. The drying 5 of the water-moist, clean products produces no technical or safety problems.
Hvis råproduktet foreligger i form af en opløsning i et organisk opløsningsmiddel, hvori en del af forureningerne km er dårligt opløselige, f.eks. i et åbenkædet eller cyclisk 10 paraffincarbonhydrid , såsom hexan, heptan, octan, cyclohexan, petrolether, ligroin, benzin og lignende, kan det anbefales at filtrere blandingen med den vandige syre før faseadskillelsen for at kunne adskille faserne rent. Som opløsningsmiddel for råproduktet egner sig foruden de allerede angivne alle så-15 danne opløsningsmidler, der ikke eller km i ringe omfang er blandbare med vandige syrer, f.eks. aromatiske carbonhydrider, såsom benzen, toluen, xylen, chlorbenzen, dichlorbenzen, chlor-toluen, højere alkylbenzener; alifatiske chlorcarbbnhydrider, såsom dichlormethan, chloroform, dichlorethan, tetrachlorme-20 than; ethere, såsom diethylether, diisopropylether, og andre.If the crude product is in the form of a solution in an organic solvent in which some of the contaminants km are poorly soluble, e.g. in an open-chain or cyclic paraffin hydrocarbon such as hexane, heptane, octane, cyclohexane, petroleum ether, ligroin, gasoline and the like, it is recommended to filter the mixture with the aqueous acid before the phase separation in order to separate the phases purely. As the solvent for the crude product, besides the already stated solvents, which are not or km to a small extent miscible with aqueous acids, e.g. aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, higher alkylbenzenes; aliphatic chlorocarbons, such as dichloromethane, chloroform, dichloroethane, tetrachloromethane; ethers such as diethyl ether, diisopropyl ether, and others.
Man kan også anvende estere, amider, nitriler og lignende forbindelser som opløsningsmidler, hvis disse opløsningsmidler er tilstrækkeligt stabile mod vandige syrer eller hvis man arbejder hurtigt nok til at forhindre en nævneværdig hydrolyse af 25 opløsningsmidlerne. Basiske opløsningsmidler, der danner sålte med de anvendte syrer, kommer ikke i betragtning.Esters, amides, nitriles and similar compounds can also be used as solvents if these solvents are sufficiently stable against aqueous acids or if they work fast enough to prevent a significant hydrolysis of the solvents. Basic solvents formed with the acids used are not considered.
Som syrer kommer i det væsentlige alle stærke, uorganiske syrer i betragtning, f.eks. saltsyre, brombrintesyre, perchlor-syre, svovlsyre, salpetersyre og phosphorsyre. De anvendte, kon-3Q centrerede opløsninger af syrerne skal indeholde mellem 10 og 70 vægt-% vand, især mellem 20 og 65 %, f.eks. mellem 32 og 38% saltsyre eller 40 til 80 % svovlsyre. Højkoncentrerede syrer, f.eks. 96 % svovlsyre eller over 50 % salpetersyre, egner sig dårligt på grund af deres oxidationsvirkning.As acids, essentially all strong, inorganic acids are considered, e.g. hydrochloric, hydrochloric, perchloric, sulfuric, nitric and phosphoric. The concentrated solutions of the acids used should contain between 10 and 70% by weight of water, especially between 20 and 65%, e.g. between 32 and 38% hydrochloric acid or 40 to 80% sulfuric acid. Highly concentrated acids, e.g. 96% sulfuric acid, or more than 50% nitric acid, is poorly suited because of their oxidation effect.
146534 6 . Mængden af anvendt syre må være dimensioneret sådan, at samtlige af de basiske stoffer, der er opløst i det organiske opløsningsmiddel eller som befinder sig i den faste remanens, overføres til deres salt. Til dette formål er den syremængde 5 nødvendig, der er ækvivalent med den teoretisk beregnede mængde af pyrazolforbindelsen. Det må dog anbefales at anvende et syreoverskud, der kan ligge mellem 10 og 1000 %. Anvendelsen af et to- til femdobbelt molært overskud har vist sig at være særligt gunstigt. Hvis der på trods af anvendelsen af et sådant 10 overskud endnu bliver en del af det ønskede produkt tilbage i det organiske opløsningsmiddel eller i fast tilstand, kan man naturligvis også behandle råproduktet endnu en gang eller endog flere gange med koncentreret, vandig syre. Naturligvis kan man også kontinuerligt extrahere pyrazolforbindelseme fra 15 deres opløsning eller en fast remanens, hvori de foreligger, med syre.146534 6. The amount of acid used must be sized such that all of the basic substances dissolved in the organic solvent or contained in the solid residue are transferred to their salt. For this purpose, the amount of acid 5 needed is equivalent to the theoretically calculated amount of the pyrazole compound. However, it is recommended to use an acid surplus that can be between 10 and 1000%. The use of a two- to five-fold molar excess has proven to be particularly favorable. Of course, in spite of the use of such excess, a portion of the desired product remains in the organic solvent or solid state, of course, the crude product may also be treated once more or even several times with concentrated aqueous acid. Of course, one can also continuously extract the pyrazole compounds from their solution or a solid residue in which they are present with acid.
Temperaturen spiller ingen stor rolle for extraktionen, når man ser bort fra, at der ved for høj temperatur kan indtræde dekompositioner og dårlige faseseparationer eller der kan over-20 gå for mange upolare biprodukter i vandfasen,og at både produkt og opløsningsmiddel og vand ved for lave temperaturer kan frembyde vanskeligheder ved udkrystallisation. Temperaturer mellem 0 og 50° C har vist sig som værende gunstige, især omgivelsernes temperatur. Mængden af det til fortynding anvendte vand 25 bør være sådan afpasset, at det ønskede produkt så vidt muligt udfældes kvantitativt. Man kan, beregnet på syremængden, anvende 2 til 100 gange så stor vandmængde, men af praktiske grunde har det dog vist sig mest hensigtsmæssigt at fortynde syreextrakten til det 5- til 10-dobbelte volumen. Temperaturen 30 ved fortyndingen spiller ingen væsentlig rolle, men dog bør man tage i betragtning, at nogle af de stoffer, der skal udfældes, har et lavt smeltepunkt og derfor vil kunne udfældes ved for høj temperatur som olier, der kan indeslutte eventuelle urenheder, og at modstandsevnen af pyrazolforbindelseme 35 overfor vandig syre ved forøgelse af temperaturen kan reduceres. Derfor fortynder man i almindelighed ved mellem 0 og 50° C, simplest ved omgivelsernes temperatur. Med henblik på fortyn-: 7 U6534 ding kan man tilsætte vandet til syre, med det viser sig i almindelighed at være det fordelagtigste at lade syren løbe til vandet under god omrøring. Derved udfældes kun den ønskede, rene pyrazolforbindelse, mens alle andre opløste stoffer for-5 bliver i opløsning.The temperature does not play a major role in the extraction, considering that at too high temperatures decompositions and poor phase separations can occur or too many unpolar by-products in the aqueous phase can occur, and that both product and solvent and water at low temperatures can present difficulties in crystallization. Temperatures between 0 and 50 ° C have been found to be favorable, especially ambient temperature. The amount of diluted water 25 should be adjusted so that the desired product is precipitated quantitatively as far as possible. Based on the amount of acid, 2 to 100 times the amount of water can be used, but for practical reasons it has proved most convenient to dilute the acid extract to the 5- to 10-fold volume. The temperature of 30 at the dilution plays no significant role, but it should be borne in mind that some of the substances to be precipitated have a low melting point and may therefore be precipitated at too high a temperature as oils which may contain any impurities, and that the resistance of the pyrazole compounds 35 to aqueous acid can be reduced by increasing the temperature. Therefore, it is generally diluted at between 0 and 50 ° C, simplest at ambient temperature. For the purpose of dilution, the water can be added to acid, but it generally turns out to be the most advantageous to allow the acid to flow to the water under good stirring. Thereby, only the desired pure pyrazole compound precipitates, while all other solutes remain in solution.
Det rene produkt kan derpå f.eks. frasuges over en stor filtertragt og vaskes med vand, og det bliver herved så lugtneutralt, at det endog manuelt kan skovles ud fra filtertragten og eventuelt kan fyldes ind i et tørreapparatur.The pure product can then e.g. is filtered off over a large filter funnel and washed with water, thereby becoming so odor neutral that it can even be manually purged from the filter funnel and possibly filled into a drying apparatus.
10 Hvis produktet imidlertid med henblik på videreforarbejdning skal opløses i et organisk opløsningsmiddel, kan man naturligvis extrahere det direkte efter udfældningen fra den sure, fortyndede, vandige opløsning med det ønskede opløsningsmiddel, hvis dette opløsningsmiddel ikke er blandbart med vand.However, if the product is to be dissolved in an organic solvent for further processing, it can of course be extracted directly after the precipitation from the acidic, diluted aqueous solution with the desired solvent if this solvent is not miscible with water.
15 Fremgangsmåden ifølge opfindelsen beror i kemisk henseende på, at de svagt basiske, overraskende syrestabile pyrazolforbindelser sammen med andre polære eller til saltdannelse velegnede forbindelser fra reaktionsblandingen i et primært rensningstrin opløses i den koncentrerede syre, mens de upolare stoffer en- 20 ten forbliver i det organiske opløsningsmiddel, eller - hvis man giver afkald på dette sidste - frafiltreres som fast remanens. Det sekundære, væsentlige kemiske grundlag for fremgangsmåden består i, at de stærkt sure, opløste syreadditionssalte af pyrazolforbindelseme i et sekundært rensningstrin 25 allerede i fortyndet syreopløsning igen sønderdeles til syre og pyrazolforbindelse, mens alle andre polare og saltagtige forbindelser.forbliver i den ved blandingen med vand opståede, fortyndede syre. Ved hjælp af denne dobbelte rensning kommer slutprodukternes høje renhedsgrad i stand.The process of the invention is chemical in that the weakly basic, surprisingly acid-stable pyrazole compounds, together with other polar or salt-forming compounds of the reaction mixture in a primary purification step, are dissolved in the concentrated acid while the unpolar substances remain in the organic solvent, or - if this is waived - is filtered off as a solid residue. The secondary essential chemical basis of the process is that the highly acidic, dissolved acid addition salts of the pyrazole compounds in a secondary purification step 25 are already decomposed into dilute acid solution again into acid and pyrazole compound, while all other polar and saline compounds remain in the mixture with water arose, dilute acid. By means of this double purification, the high purity of the final products is achieved.
30 Fremgangsmåden ifølge opfindelsen egner sig udmærket til isolation af pyrazolforbindelseme fra deres rå reaktionsopløsninger og lader sig også gennemføre i pilot plant målestok og produktionsmålestok. Fremgangsmåden ifølge opfindelsen lader 146534 8 sig også let anvende til rensning af store, forurenede mængder . af pyrazolforbindelser. Ved hjælp af fremgangsmåden kan man endog på basis af fejlcharger, i forbindelse med hvilke fremstillingsreaktionen for pyrazolforbindelseme ikke er forløbet 5 forskriftsmæssigt, på fejlfri måde isolere de hyppigt kun i ringe mængder foreliggende, værdifulde pyrazolforbindelser.The process of the invention is well suited for isolating the pyrazole compounds from their crude reaction solutions and is also practicable on pilot plant scale and production scale. The process of the invention is also readily applicable to the purification of large, contaminated quantities. of pyrazole compounds. By means of the method, even on the basis of error charges, in which the preparation reaction for the pyrazole compounds has not proceeded properly, they can isolate in error-free manner frequently only in small quantities of valuable pyrazole compounds.
Derudover lykkes det også at rense sådanne pyrazolforbindelser, som er fremstillet i henhold til en forsimplet fremgangsmåde. Det er kendt, at man kan fremstille pyrazolforbindelser 10 på den måde, at man omsætter forbindelser med den almene formelIn addition, it is also possible to purify such pyrazole compounds prepared according to a simplified process. It is known that pyrazole compounds 10 can be prepared by reacting compounds of the general formula
X /K2-XX / K2-X
2φ·\ noch-X / in* R1 0 1 2 hvor R, R , R og X har den ovenfor angivne betydning, eventuelt i nærværelse af et halogenbrintebindende middel og i nærværelse af et indifferent opløsningsmiddel, med en pyrazol 15 med den almene formel R3 fk- R“Wherein R, R, R and X have the meaning given above, optionally in the presence of a hydrogen peroxide binding agent and in the presence of an inert solvent, with a pyrazole of the general formula R3 fk- R “
“V"V
•x Λ hvori R-' og R har den ovenfor angivne betydning. Det har nu vist sig, at håndteringen at større mængder af N-halogenacetyl-N-halogenmethylaniliner er yderst ubekvem og ikke ufarlig. Stofferne er i almindelighed faste og lader sig ikke pumpe og 20 transportere gennem lukkede ledninger. Deres dampe virker stærkt irriterende på slimhinder, og kontakten med støv deraf kan forårsage hududslet. Som den sagkyndige allerede udelukkende på 1Λ653Λ 9 grund af den kemiske formel erkender, kan disse forbindelser afspalte de giftige gasser formaldehyd og chlorbrinte med vand eller i forbindelse med fugtig luft, slimhinder eller fugtig hud.• x Λ wherein R 1 'and R have the meaning given above. It has now been found that the handling of larger amounts of N-haloacetyl-N-halo methylanilines is extremely inconvenient and not harmless. The substances are generally solid and cannot be pumped and transported through closed wires. Their fumes are very irritating to mucous membranes, and contact with dust can cause skin rash. As the expert already recognizes on the basis of the chemical formula only on 1Λ653Λ 9, these compounds can decompose the toxic gases of formaldehyde and hydrogen chloride with water or in connection with moist air, mucous membranes or moist skin.
Af disse grunde kan man også kun forarbejde større mængder af disse forbindelser under anvendelse af besværlige sikkerhedsforanstaltninger .For these reasons, only large quantities of these compounds can be processed using cumbersome security measures.
Til fremstillingen af disse forbindelser kender man flere metoder. En simpel metode (US patentskrift nr. 3 637 847) består i, at man omsætter en azomethin med den almene formelSeveral methods are known for the preparation of these compounds. A simple method (U.S. Patent No. 3,637,847) consists of reacting an azomethine of the general formula
RR
Jfr**** R1 1 2 hvori R, R og R har den før angivne betydning, med et halo-genoacetylhalogenid med den almene formel x-cH9-<rf .Cf **** R1 1 2 wherein R, R and R are as previously defined, with a halo-genoacetyl halide of the general formula x-cH9- <rf.
* hvori X har den ovenfor angivne betydning. Azomethinerne syntetiseres i henhold til kendte metoder af formaldehyd og aniliner med den almene formel j^Vnh2 R^ '—' R1 10 148534 1 2 hvori R, R og R har de ovenfor angivne betydninger, og de bliver destilleret med henblik på rensning før anvendelsen deraf. Det er dog fra DE fremlæggelsesskrift nr.* wherein X has the meaning given above. The azomethines are synthesized according to known methods of formaldehyde and anilines of the general formula: wherein R, R and R have the above meanings and are distilled for purification before use. thereof. However, it is from DE submission no.
17 93 811 kendt, at nogle azomethiner, der er særligt interessante som forprodukter til fremstilling af pyrazolforbin- l delser, f.eks. der, hvor R og R hver for sig betyder en i forhold til nitrogennatomet i orto-stillingen indført methyl-2 gruppe, og R betyder et hydrogenatom, ikke er bestandige og ikke kan anvendes til syntese af andre forbindelser.It is known that some azomethines are particularly interesting as precursors for the preparation of pyrazole compounds, e.g. wherein R and R each individually represent a methyl-2 group introduced relative to the nitrogen atom in the ortho position and R represents a hydrogen atom, are not resistant and cannot be used for the synthesis of other compounds.
Det har overraskende vist sig, at man ved omsætning af en anilin med den almene formelSurprisingly, it has been found that by reacting an aniline of the general formula
RR
Λ i ' ’ * 1Λ i '' * 1
* R* R
1 2 hvori R, R og R har den i krav 1 angivne betydning, med paraformaldehyd i et inert organisk opløsningsmiddel, afdestil-lation af vand og overskydende formaldehyd fra reaktionsblandingen, omsætning af et halogenacety'lhalogenid med reaktionsblandingen og yderligere omsætning af reaktionsblandingen med en pyrazol med den almene formel R3 /ίν-κ" Λ/Wherein R, R and R are as defined in claim 1, with paraformaldehyde in an inert organic solvent, distillation of water and excess formaldehyde from the reaction mixture, reaction of a haloacetyl halide with the reaction mixture and further reaction of the reaction mixture with a reaction mixture. pyrazole of the general formula R3 / ίν-κ "Λ /
H NH N
5 4 hvori R-' og R har den i krav 1 angivne betydning, og et halo-genbrintebindende middel opnår pyrazolforbindelsen i høj renhed og godt udbytte, uden at det er nødvendigt at isolere og rense de ovenfor beskrevne mellemprodukter, når man i henhold til fremgangsmåden ifølge opfindelsen isolerer pyrazolforbin - 146534 11 delserne fra de rå opløsninger deraf. Selv pyrazolforbindel-ser, der er baseret på azomethiner, hvilke i henhold til almen erfaring og i henhold til DE fremlæggelsesskrift nr.Wherein R 1 and R are as defined in claim 1, and a halo hydrogen bonding agent achieves high purity and good yield of the pyrazole compound without the need to isolate and purify the intermediates described above when the process of the invention isolates the pyrazole compounds from the crude solutions thereof. Even pyrazole compounds based on azomethines, which according to general experience and according to DE disclosure no.
17 93 811 er ubestandige, lader sig let fremstille, når de pågældende azomethiner ikke renses, destilleres eller på anden måde isoleres, men videreforarbejdes i form af en råopløsning deraf.17 93 811 are volatile, readily prepared when the azomethines in question are not purified, distilled or otherwise isolated, but further processed in the form of a crude solution thereof.
Fremgangsmåden består i, at man på i og for sig kendt måde omsætter et anilin med paraformaldehyd til en azomethin, at man afdestillerer vand og formaldehyd, at man i den samme eller en anden beholder blander den rå opløsning af azomethinen med et halogenacetylhalogenid, at man blander blandingen med en pyrazol og et halogenbrintebindende middel, og at man ifølge opfindelsen behandler blandingen med en koncentreret, vandig syre, at man separerer syren og fortynder den med vand, hvorved slutproduktet forekommer rent og i godt udbytte. Man kan naturligvis også vaske reaktionsproduktet med vand før behandlingen med syre. En variant af metoden består i, at man som halogenbrinte-bindende middel anvender en vandig base, eventuelt i nærværelse af en såkaldt fasetransfer-katalysator, hvorved man derpå naturligvis først behandler reaktionsblandingen efter separation af den vandige fase med den koncentrerede syre.The process consists of converting an aniline with paraformaldehyde into an azomethine in a manner known per se, distilling off water and formaldehyde, mixing in the same or another container the crude solution of the azomethine with a haloacetyl halide, the mixture is mixed with a pyrazole and a hydrogen peroxide-binding agent, and according to the invention the mixture is treated with a concentrated aqueous acid, separating the acid and diluting it with water, whereby the final product appears clean and in good yield. Of course, the reaction product can also be washed with water before treatment with acid. A variant of the method consists in the use of an aqueous base as a hydrogen peroxide-binding agent, optionally in the presence of a so-called phase transfer catalyst, whereby of course the reaction mixture is first treated after separation of the aqueous phase with the concentrated acid.
Fordelene ved denne metode består i, at man for det første også kan anvende ubestandige azomethiner, og især for det andet, at man ikke behøver at isolere det ovenfor angivne, problematiske mellemprodukt. Da den totale reaktionsfølge kan gennemføres i et eller to lukkede apparater, uden at man i mellemtiden behøver at isolere eller oparbejde, kommer betjeningspersonalet ikke i berøring med de farlige mellemprodukter. Hvis man ved reaktioner med flere trin ikke isolerer og renser produkterne fra de enkelte reaktionsskridt, vokser koncentrationen af forureningerne - som den sagkyndige ved - til slut så stærkt, at isolationen og rensningen af slutproduktet er vanskelig. Dette er dog i det foreliggende tilfælde ikke tilfældet, fordi man let kan rense råproduktet i henhold til fremgangsmåden ifølge opfindelsen.The advantages of this method are that, firstly, it is also possible to use volatile azomethines, and in particular secondly, that the problematic intermediate mentioned above need not be isolated. Since the total reaction sequence can be carried out in one or two closed appliances without the need to isolate or work up in the meantime, the operating personnel do not come in contact with the dangerous intermediates. Finally, if multi-step reactions do not isolate and purify the products from the individual reaction steps, the concentration of the contaminants - as the expert knows - eventually increases so strongly that the isolation and purification of the final product is difficult. However, this is not the case in the present case because it is easy to purify the crude product according to the process according to the invention.
146534 12146534 12
Fremgangsmåden ifølge opfindelsen til rensning af pyrazolfor-Mndelser egner sig selfølgeligt også til rensning af råopløsninger, som er fremkommet på anden måde, f.eks. i henhold til DE offentliggørelsesskrift nr. 27 04 281, og den fører også i forbindelse med disse til enorme arbeidslettelser.The process of the invention for the purification of pyrazole compounds is, of course, also suitable for the purification of crude solutions obtained by other means, e.g. in accordance with DE publication no. 27 04 281, and in connection with these, it also results in enormous work relief.
De følgende eksempler viser simpelheden og tilforladeligheden af fremgangsmåden ifølge opfindelsen.The following examples show the simplicity and reliability of the method according to the invention.
Eksempel 1 5100 dele (vægtdele) N-chlormethyl-2,6-dimethylchloracetanilid og 11000 dele toluen blandes med 1900 dele 4-methylpyrazol og omrøres derpå i 3 timer ved 40 til 60° C. Man tilsætter 2130 dele triethylamin, rører 3 timer ved 60° C og natten over ved stuetemperatur (20°). Reaktionsblandingen vaskes to gange med 10 000 dele vand og extraheres en gang med 12000 dele 37 % (vægt-?é) saltsyre. Man lader under omrøring extrakten løbe til 60 000 dele vand og suger bundfaldet fra. Efter tørringen opnår man 4750 dele 95 % N-(4-methylpyrazolyl-(l)-methyl)-2,6-dimethylchloracetanilid med smeltepunkt 98-100° C.Example 1 5100 parts (parts by weight) of N-chloromethyl-2,6-dimethyl chloroacetanilide and 11000 parts of toluene are mixed with 1900 parts of 4-methylpyrazole and then stirred for 3 hours at 40 to 60 ° C. 2130 parts of triethylamine are added, stirred for 3 hours. 60 ° C and overnight at room temperature (20 °). The reaction mixture is washed twice with 10,000 parts water and extracted once with 12000 parts 37% (wt) hydrochloric acid. While stirring, the extract is allowed to run to 60,000 parts of water and the precipitate is sucked off. After drying, 4750 parts of 95% N- (4-methylpyrazolyl- (1) -methyl) -2,6-dimethylchloroacetanilide are obtained, mp 98-100 ° C.
Eksempel 2 1300 dele N-chlormethyl-2-ethy1-6-methylchloracetanilid og 3000 dele toluen blandes med 540 dele 4-methoxypyrazol. Man holder temperaturen i 4 timer ved 60° C, tilsætter 500 dele triethylamin, rører 4 timer ved 60° C og natten over ved stuetemperatur. Man sammenrører med 2000 dele vand og suger de derved udfaldende krystaller fra, således at der efter vask med vand og tørring fremkommer 750 dele rent N-(4-methoxypyrazolyl-(l)-methyl)-6-ethyl-2-methylchloracetanilid med smeltepunkt 96-97° C. Den organiske fase af filtratet separeres og extraheres en gang med 950 dele 37 % saltsyre. De ved inddrypningen af extrakten i 6 000 dele vand udfældende krystaller frembringer efter frasugningen og tørringen endnu en gang 660 dele U6534 13 98 % N-(4-methoxypyrazolyl-(l)-2-ethyl-6-methylchloracetanilid med smeltepunkt 92-93° C.Example 2 1300 parts of N-chloromethyl-2-ethyl-6-methylchloroacetanilide and 3000 parts of toluene are mixed with 540 parts of 4-methoxypyrazole. The temperature is maintained for 4 hours at 60 ° C, 500 parts of triethylamine added, stirred for 4 hours at 60 ° C and overnight at room temperature. 2000 parts of water are stirred and the crystals thus precipitated are extracted so that, after washing with water and drying, 750 parts of pure N- (4-methoxypyrazolyl- (l) -methyl) -6-ethyl-2-methylchloroacetanilide are obtained, m.p. 96-97 ° C. The organic phase of the filtrate is separated and extracted once with 950 parts of 37% hydrochloric acid. The crystals precipitated by the extraction in 6,000 parts of water after extraction and drying again produce 660 parts of 98% N- (4-methoxypyrazolyl- (1) -2-ethyl-6-methylchloroacetanilide, m.p. 92-93 ° C.
Eksempel 3 a) 14 dele 94 % N-(pyrazolyl-(1)-methyl)-2,6-dimethyl-chlor-acetanilid med smeltepunkt 72-75° C, hvis indhold blev bestemt protonresonansspektroskoplsk, opløses i 140 dele toluen og udrystes en gang med 40 dele 60 % svovlsyre. Man lader den svovlsure extrakt løbe til 240 dele vand under god omrøring, suger de udfældede krystaller fra, vasker med vand og tørrer. Man opnår 100 % N-(pyrazolyl-(1)-methyl)- 2,6-dimethylchloracetanilid med smeltepunkt 83° C.Example 3 a) 14 parts 94% N- (pyrazolyl- (1) -methyl) -2,6-dimethyl-chloro-acetanilide, m.p. 72-75 ° C, the content of which was determined by proton resonance spectroscopic, is dissolved in 140 parts of toluene and shaken. once with 40 parts 60% sulfuric acid. The sulfuric acid extract is allowed to run to 240 parts of water with good stirring, the precipitated crystals are sucked off, washed with water and dried. 100% N- (pyrazolyl- (1) -methyl) -2,6-dimethyl chloroacetanilide is obtained, mp 83 ° C.
b) 14 dele 94 % N-(pyrazolyl-(l)-methyl)-2,6-dimethylchloracetanilid opløses i 140 dele toluen og extraheres to gange med 40 dele 50 % svovlsyre hver gang. De forenede svovlsure extrakter hydrolyseres med vand. Det udfældede bundfald frasuge s, vaskes med vand og tørres, hvorved man opnår 13 dele 100 % produkt med smeltepunkt 83° C.b) 14 parts of 94% N- (pyrazolyl (1) methyl) -2,6-dimethylchloroacetanilide are dissolved in 140 parts of toluene and extracted twice with 40 parts of 50% sulfuric acid each time. The combined sulfuric acid extracts are hydrolyzed with water. The precipitated precipitate was filtered off, washed with water and dried to give 13 parts of 100% product, mp 83 ° C.
Eksempel 4 a) 100 dele af en sort, fedtet masse, der var fremkommet ved en uregelmenteret forløbende fremstilling af N-(pyrazo-lyl-(l)-methyl)-2,6-dimethylchloracetanilid, røres godt med 180 dele 37 % saltsyre i en halv time. Efter frasug-ningen extraheres filtratet med 50 dele toluen, og syren dryppes i 100 vægtdele vand. Man opnår efter frasugnin-gen og tørringen 60 dele 93 % N-(pyrazolyl-(1)-methyl)- 2,6-dimethylchloracetanilid med smeltepunkt 77° C.Example 4 a) 100 parts of a black, greasy mass produced by an irregularly progressive preparation of N- (pyrazolyl- (l) -methyl) -2,6-dimethylchloroacetanilide is well stirred with 180 parts of 37% hydrochloric acid for half an hour. After the suction, the filtrate is extracted with 50 parts of toluene and the acid is dripped into 100 parts by weight of water. After extraction and drying, 60 parts of 93% N- (pyrazolyl- (1) -methyl) -2,6-dimethylchloroacetanilide are obtained, m.p. 77 ° C.
b) 100 dele af den under a) angivne, fedtede masse sainmenrø-res godt .med 150 dele"toluen og filtreres. Filtratet udrys-tes en gang med 180 dele 37 % saltsyre. Saltsyrefasen dryp- 146534 14 per man i 900 dele vand, suger fra og tørrer. Man opnår 54 dele 97 % N-(pyrazolyl-(l)-methyl)-2,6-dimethylchloraceta-nilid med smeltepunkt 78° C.b) 100 parts of the greasy mass specified in (a) is stirred well with 150 parts of toluene and filtered. The filtrate is once shaken off with 180 parts of 37% hydrochloric acid. The hydrochloric acid phase is dripped into 900 parts of water. , suction and dry, 54 parts of 97% N- (pyrazolyl- (1) -methyl) -2,6-dimethylchloroacetanilide are obtained, m.p. 78 ° C.
c) 100 dele af den under a) angivne, fedtede masse opløses i 180 dele methylenchlorid, extraheres en gang med 180 dele og derpå med 60 dele 37 % saltsyre. De forenede saltsure extrakter vaskes med henblik på fjernelse af methylenchlorid en gang med 50 dele toluen. Man hydrolyserer som under a) og b) beskrevet og opnår 56,5 dele mere end 99 % N-(py-razolyl-(1)-methyl)-2,6-dimethylchloracetanilid med smeltepunkt 83° C.(c) 100 parts of the greasy mass specified in (a) are dissolved in 180 parts of methylene chloride, extracted once with 180 parts and then with 60 parts 37% hydrochloric acid. The combined hydrochloric acid extracts are washed to remove methylene chloride once with 50 parts of toluene. Hydrolyzes as described in (a) and (b) to obtain 56.5 parts of more than 99% N- (pyrazolyl- (1) methyl) -2,6-dimethyl chloroacetanilide, mp 83 ° C.
Eksempel 5Example 5
Til en opløsning af 202 dele bromacetylbromid i 150 dele li-groin drypper man en rå opløsning af 133 dele N-(2,6-dimethyl-phenyl)-methylanimin i en toluen-cyclohexan-blanding. Da der i stedet for det ønskede krystallinske N-brommethyl-2,6-dimethyl-bromacetanilid kun udfælder en vanskeligt isolerbar olie, tilsætter man 450 dele toluen og 75 dele pyrazol, opvarmer 2 timer til 60° C, tildrypper 110 dele triethylamin, opvarmer til 60° C, vasker med vand, derpå med 5 % saltsyre og derpå endnu engang med vand og inddamper, hvorved man opnår 248 dele af en sej olie. Denne opløses i 500 dele toluen og extraheres med 250 dele 37 % saltsyre. Extrakten hydrolyseres med 1500 dele vand, hvorved der fremkommer 190 dele N-(pyrazolyl-(l)-methyl)- 2,6-dimethylbromacetanilid med smeltepunkt 86° C.To a solution of 202 parts of bromoacetyl bromide in 150 parts of li-groin is added a crude solution of 133 parts of N- (2,6-dimethyl-phenyl) -methylanimine in a toluene-cyclohexane mixture. Since instead of the desired crystalline N-bromomethyl-2,6-dimethyl-bromoacetanilide, only a difficult insulating oil precipitates, 450 parts of toluene and 75 parts of pyrazole are added, heated for 2 hours to 60 ° C, 110 parts of triethylamine, heated to 60 ° C, wash with water, then with 5% hydrochloric acid and then again with water and evaporator to give 248 parts of a cool oil. This is dissolved in 500 parts of toluene and extracted with 250 parts of 37% hydrochloric acid. The extract is hydrolyzed with 1500 parts of water to give 190 parts of N- (pyrazolyl- (l) -methyl) -2,6-dimethyl bromoacetanilide, m.p. 86 ° C.
Eksempel 6Example 6
Fra en blanding af 10890 dele 2,6-dimethylanilin og 4050 dele paraformaldehyd fjerner man med 50000 dele af en toluen-cyclohexan-blanding på i og for sig kendt måde 1620 dele vand ved kogning under tilbagesvaling. Efter den hurtige afkøling til stuetemperatur omsætter man den således fremkomne opløsning af N-(2,6-dimethylphenyl)-methylenimin med sine forureninger 146534 15 på i og for sig kendt måde med 10800 dele chloracetylchlorid i 10000 dele toluen. Man tilsætter derpå 6800 dele pyrazol, rører 5 timer ved 50° C, tilsætter derpå 10000 dele triethyl-amin, rører i 5 timer ved 50° C og natten over ved stuetemperatur. Derpå vaskes reaktionsblandingen med 30000 dele 5 % saltsyre, og den separerede organiske fase extraheres med 30 000 dele 37 % saltsyre. Extrakten indrøres i 180 000 dele vand. Det udfældede bundfald frasuges, vaskes med vand og tørres.From a mixture of 10890 parts of 2,6-dimethylaniline and 4050 parts of paraformaldehyde, with 50,000 parts of a toluene-cyclohexane mixture, 1620 parts of water are boiled under reflux in a manner known per se. After the rapid cooling to room temperature, the solution of N- (2,6-dimethylphenyl) methylenimine thus obtained is reacted with its impurities in a manner known per se with 10800 parts of chloroacetyl chloride in 10000 parts of toluene. 6800 parts of pyrazole are then added, stirred for 5 hours at 50 ° C, then 10000 parts of triethylamine are added, stirred for 5 hours at 50 ° C and overnight at room temperature. The reaction mixture is then washed with 30000 parts of 5% hydrochloric acid, and the separated organic phase is extracted with 30,000 parts of 37% hydrochloric acid. The extract is stirred in 180,000 parts of water. The precipitated precipitate is aspirated, washed with water and dried.
Man opnår 17840 dele 96 % N-(pyrazolyl-(l)-methyl)-2,6-dime-thylchloracetanilid med smeltepunkt 78° C.17840 parts of 96% N- (pyrazolyl- (1) -methyl) -2,6-dimethyl chloroacetanilide are obtained, m.p. 78 ° C.
Eksempel 7 121 dele af en stærkt forurenet charge af N-(pyrazolyl-(l)-methyl)-2-ethyl-6-methylbromacetanilid opløses i 300 dele toluen, extraheres med 200 dele 37 % saltsyre, hvorpå extrakten hydrolyseres med vand. Man opnår 67 dele af det rene produkt med smeltepunkt 71 til 73° C.Example 7 121 parts of a highly contaminated charge of N- (pyrazolyl- (1) methyl) -2-ethyl-6-methylbromoacetanilide are dissolved in 300 parts of toluene, extracted with 200 parts of 37% hydrochloric acid, and the extract is hydrolyzed with water. 67 parts of the pure product are obtained, mp 71 to 73 ° C.
Eksempel 8Example 8
Af 6050 dele 2,6-dimethylanilin og 2400 dele paraformaldehyd fjerner man ved hjælp af en toluen-cyclohexan-blanding 900 dele vand som i eksempel 6. Den fremkomne opløsning tilsætter man til 6000 dele chloracetylchlorid i 6000 dele toluen, sætter efter afslutning af reaktionen 3800 dele pyrazol til, holder 4 timer ved 50° C, tilsætter 5500 dele triethylamin og opvarmer i 6 timer til 50° C. Man vasker med fortyndet saltsyre (5 %) og suger blandingen fra en vis mængde remanens. Toluenfasen i filtratet extraheres to gange med hver gang 13 000 dele 60 % svovlsyre. Man indrører extrakten i 300 000 dele vand. Det udfældende bundfald frasuges og tørres og giver anledning til dannelsen af 8800 dele 98 % N-(pyrazolyl-(l)-me-.thyl)-2,6-dimethyl-chloracetanilid med smeltepunkt 81-83° C.Of 6050 parts of 2,6-dimethylaniline and 2,400 parts of paraformaldehyde, 900 parts of water are removed by means of a toluene-cyclohexane mixture as in Example 6. The resulting solution is added to 6000 parts of chloroacetyl chloride in 6000 parts of toluene, after completion of the reaction. Add 3800 parts of pyrazole, hold for 4 hours at 50 ° C, add 5500 parts of triethylamine and heat for 6 hours to 50 ° C. Wash with dilute hydrochloric acid (5%) and suction the mixture from a certain amount of residue. The toluene phase in the filtrate is extracted twice with 13,000 parts of 60% sulfuric acid each time. The extract is stirred in 300,000 parts of water. The precipitated precipitate is aspirated and dried to give 8800 parts of 98% N- (pyrazolyl- (1) -me-methyl) -2,6-dimethyl chloroacetanilide, mp 81-83 ° C.
146534 16146534 16
Eksempel 9Example 9
Era 121 dele 2,β-dimethylanilin og 45 dele paraf ormaldehyd i 250 dele af en toluen cyclohexan-blanding fjerner man som beskrevet i eksempel 6 18 dele vand. Efter den hurtige afkøling til stuetemperatur lader man den således fremkomne opløsning af N-(2,6-dimethylphenyl)-methylenimin på i og for sig kendt måde reagere med 113 dele chloracetylchlorid i 100 dele toluen og man efterrører 1/2 time ved 80° C. Derpå tildrypper man ved stuetemperatur en blanding af 44 dele NaOH, 75 dele pyrazol og 6,8 dele af en blanding af 35 % (vægt-#) aimethyldibenzylam-moniumchlorid, 15 % trimethylbenzylammoniumchlorid, 40 % vand og 10 % methanol i 200 dele vand og rører i 4 timer ved stuetemperatur. Efter separationen af den organiske fase fra vand vasker man denne to gange med 200 dele vand og extraherer den derpå en gang med 350 dele og derpå med 175 dele 55 % svovlsyre. De forenede svovlsure extrakter indrøres i 3000 dele vand, det udfældede bundfald bliver frasuget, vasket med vand og tørret i vakuum ved 50° C.Era 121 parts 2, β-dimethylaniline and 45 parts paraformaldehyde in 250 parts of a toluene cyclohexane mixture are removed as described in Example 6 18 parts of water. After the rapid cooling to room temperature, the solution of N- (2,6-dimethylphenyl) methylenimine thus obtained is reacted in a manner known per se with 113 parts of chloroacetyl chloride in 100 parts of toluene and stirred for 1/2 hour at 80 °. C. Then, at room temperature, a mixture of 44 parts of NaOH, 75 parts of pyrazole and 6.8 parts of a mixture of 35% (wt) of ethyl methyldibenzylammonium chloride, 15% trimethylbenzylammonium chloride, 40% water and 10% methanol is added dropwise. divide water and stir for 4 hours at room temperature. After separating the organic phase from water, it is washed twice with 200 parts of water and then extracted once with 350 parts and then with 175 parts 55% sulfuric acid. The combined sulfuric acid extracts are stirred in 3000 parts of water, the precipitated precipitate is extracted, washed with water and dried in vacuo at 50 ° C.
Man opnår 210 dele 98 % N-(pyrazolyl-(l)-methyl)-2,6-dimethyl-chloracetanilid med smeltepunkt 82° C.210 parts of 98% N- (pyrazolyl- (1) -methyl) -2,6-dimethyl-chloroacetanilide are obtained, m.p. 82 ° C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2849442 | 1978-11-15 | ||
| DE19782849442 DE2849442A1 (en) | 1978-11-15 | 1978-11-15 | METHOD FOR PRODUCING MOST PURE PYRAZOLIC COMPOUNDS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK481279A DK481279A (en) | 1980-05-16 |
| DK146534B true DK146534B (en) | 1983-10-31 |
| DK146534C DK146534C (en) | 1984-04-09 |
Family
ID=6054668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK481279A DK146534C (en) | 1978-11-15 | 1979-11-14 | PROCEDURE FOR PREPARING PURE SUBSTITUTED N-METHYL-PYRAZOL-ACETANILIDES |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0012216B1 (en) |
| JP (1) | JPS55129270A (en) |
| AR (1) | AR226546A1 (en) |
| AT (1) | ATE164T1 (en) |
| BR (1) | BR7907345A (en) |
| CA (1) | CA1120043A (en) |
| CS (1) | CS208793B2 (en) |
| DD (1) | DD146948A5 (en) |
| DE (2) | DE2849442A1 (en) |
| DK (1) | DK146534C (en) |
| HU (1) | HU178450B (en) |
| IL (1) | IL58625A (en) |
| PL (1) | PL119268B2 (en) |
| SU (1) | SU860699A1 (en) |
| UA (1) | UA7045A1 (en) |
| YU (1) | YU279479A (en) |
| ZA (1) | ZA796137B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2610589A1 (en) * | 1987-02-09 | 1988-08-12 | Savard Franck | Directional wheel hub making it possible to give or adjust the caster independently of the caster angle, and appended systems making it possible to vary various parameters on a 2-wheeled vehicle |
| US5250503A (en) * | 1989-07-29 | 1993-10-05 | Basf Aktiengesellschaft | Monoclinic metazachlor and composition |
| DE3925253A1 (en) * | 1989-07-29 | 1991-01-31 | Basf Ag | MONOCLINES METAZACHLOR AND METHOD FOR THE PRODUCTION THEREOF |
| DE4436293A1 (en) | 1994-10-11 | 1996-04-18 | Basf Ag | Stable mixture containing water and metazachlor |
| DE10210409A1 (en) * | 2002-03-09 | 2003-09-18 | Feinchemie Schwebda Gmbh | Purely triclinic metazachlor and process for its manufacture |
| DE10343277A1 (en) | 2003-09-18 | 2005-04-21 | Piesteritz Stickstoff | N- (1H-Azolyl-methyl) amides, process for their preparation and their use as nitrification inhibitors |
| LT1840145T (en) | 2006-03-30 | 2018-02-26 | Fmc Corporation | Acetylene carbamide derivatives-polyurea polymers and microcapsules and formulations thereof for controlled release |
| EP2802566B1 (en) | 2012-01-13 | 2016-03-16 | Basf Se | Process for preparing acetanilides |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2704281A1 (en) * | 1977-02-02 | 1978-08-03 | Bayer Ag | Herbicidal N-heterocyclyl-methyl-halo-acetanilide derivs. - prepd. from a N-halomethyl-chloro:acetanilide and a heterocycle |
-
1978
- 1978-11-15 DE DE19782849442 patent/DE2849442A1/en not_active Withdrawn
-
1979
- 1979-11-02 IL IL58625A patent/IL58625A/en unknown
- 1979-11-06 AT AT79104325T patent/ATE164T1/en not_active IP Right Cessation
- 1979-11-06 EP EP79104325A patent/EP0012216B1/en not_active Expired
- 1979-11-06 DE DE7979104325T patent/DE2960705D1/en not_active Expired
- 1979-11-12 UA UA2841459A patent/UA7045A1/en unknown
- 1979-11-12 SU SU792841459A patent/SU860699A1/en active
- 1979-11-13 JP JP14613379A patent/JPS55129270A/en active Granted
- 1979-11-13 BR BR7907345A patent/BR7907345A/en unknown
- 1979-11-13 PL PL1979219574A patent/PL119268B2/en unknown
- 1979-11-14 ZA ZA00796137A patent/ZA796137B/en unknown
- 1979-11-14 YU YU02794/79A patent/YU279479A/en unknown
- 1979-11-14 DK DK481279A patent/DK146534C/en not_active IP Right Cessation
- 1979-11-14 HU HU79BA3885A patent/HU178450B/en unknown
- 1979-11-14 DD DD79216896A patent/DD146948A5/en unknown
- 1979-11-14 CS CS797794A patent/CS208793B2/en unknown
- 1979-11-15 CA CA000339923A patent/CA1120043A/en not_active Expired
-
1982
- 1982-01-01 AR AR22654682D patent/AR226546A1/en active
Also Published As
| Publication number | Publication date |
|---|---|
| PL219574A2 (en) | 1980-09-08 |
| PL119268B2 (en) | 1981-12-31 |
| IL58625A0 (en) | 1980-02-29 |
| BR7907345A (en) | 1980-07-15 |
| IL58625A (en) | 1982-08-31 |
| UA7045A1 (en) | 1995-03-31 |
| DE2960705D1 (en) | 1981-11-19 |
| YU279479A (en) | 1983-01-21 |
| AR226546A1 (en) | 1982-07-30 |
| DD146948A5 (en) | 1981-03-11 |
| SU860699A1 (en) | 1981-08-30 |
| ATE164T1 (en) | 1981-09-15 |
| EP0012216A1 (en) | 1980-06-25 |
| JPS55129270A (en) | 1980-10-06 |
| DE2849442A1 (en) | 1980-05-29 |
| ZA796137B (en) | 1980-11-26 |
| JPH0316346B2 (en) | 1991-03-05 |
| DK146534C (en) | 1984-04-09 |
| EP0012216B1 (en) | 1981-08-26 |
| HU178450B (en) | 1982-05-28 |
| CS208793B2 (en) | 1981-09-15 |
| DK481279A (en) | 1980-05-16 |
| CA1120043A (en) | 1982-03-16 |
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