HRP20020667A2 - Method for producing heterocyclic compounds - Google Patents
Method for producing heterocyclic compounds Download PDFInfo
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- HRP20020667A2 HRP20020667A2 HRP20020667A HRP20020667A2 HR P20020667 A2 HRP20020667 A2 HR P20020667A2 HR P20020667 A HRP20020667 A HR P20020667A HR P20020667 A2 HRP20020667 A2 HR P20020667A2
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- 150000002391 heterocyclic compounds Chemical class 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000003085 diluting agent Substances 0.000 claims abstract description 9
- SKCNYHLTRZIINA-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)pyridine Chemical compound ClCC1=CC=C(Cl)N=C1 SKCNYHLTRZIINA-UHFFFAOYSA-N 0.000 claims abstract description 8
- VXLYOURCUVQYLN-UHFFFAOYSA-N 2-chloro-5-methylpyridine Chemical compound CC1=CC=C(Cl)N=C1 VXLYOURCUVQYLN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000003840 hydrochlorides Chemical class 0.000 claims abstract description 7
- 239000011541 reaction mixture Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 5
- -1 2-chloro-pyrid-5-yl Chemical group 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- WTUAWWLVVCGTRG-UHFFFAOYSA-N 4,5-dihydro-1,3-thiazol-2-ylcyanamide Chemical compound N#CNC1=NCCS1 WTUAWWLVVCGTRG-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910000287 alkaline earth metal oxide Inorganic materials 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- WNTGYJSOUMFZEP-UHFFFAOYSA-N 2-(4-chloro-2-methylphenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=C(Cl)C=C1C WNTGYJSOUMFZEP-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CBXRZRYBZMXABV-UHFFFAOYSA-N ethene;2-nitroguanidine Chemical compound C=C.NC(=N)N[N+]([O-])=O CBXRZRYBZMXABV-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Description
Sadašnji izum odnosi se na novi postupak priprave poznatih heterocikličkih spojeva.
Poznata je priprava nezasićenih heterocikličkih spojeva, alkiliranjem nesupstituiranih prstenskih atoma, koja se između ostaloga može provesti u alkoholu (EP-A-259 738).
Također su poznate reakcije alkiliranja u aprotičkim otapalima (EP-A-259 738).
U tim slučajevima potrebno je naknadno čišćenje produkata za postizanje željene čistoće, a osim toga su iskorištenja koja se postižu poznatim postupcima nezadovoljavajuća.
Pronađeno je, da se spojevi formule (I)
[image]
u kojoj
R1 predstavlja vodikov atom ili neku alkilnu skupinu,
A predstavlja etilensku skupinu koja može biti supstituirana alkilom, ili trimetilensku skupinu koja može biti supstituirana alkilom,
D predstavlja nitro ili cijano,
X predstavlja kisikov ili sumporov atom ili skupine
[image]
u kojima
R3 predstavlja vodikov atom ili alkilnu skupinu,
Z predstavlja opcijski supstituiranu 5- ili 6-članu heterocikličku skupinu, koja sadrži barem dva heteroatoma odabrana između kisikovog atoma, sumporovog atoma i dušikovog atoma, ili neku opcijski supstituiranu 3- ili 4-piridilnu skupinu,
dobiju tako, da se spojevi formule (II)
[image]
u kojoj
A, D i X imaju gore navedena značenja,
pretvore s nekom bazom u nazočnosti nekog sredstva za razrjeđivanje, te se reakcijska smjesa potom pretvori pomoću
smjese načinjene od CCMP/CMP (2-kloro-5-klorometilpiridin/2-kloro-5-metilpiridin) s odgovarajućim hidrokloridima.
Neočekivano se postupkom prema izumu mogu pripraviti gore navedeni spojevi na jednostavniji način, uz manji broj koraka u postupku, te u boljem iskorištenju.
U općenitim formulama (I) i (II) predstavljaju varijable
R1 ponajprije vodik ili neku C1-C3-alkilnu skupinu, ponajbolje vodik;
A ponajprije neku etilensku ili trimetilensku skupinu, od kojih svaka može biti supstituirana nekom C1-C3-alkilnom skupinom, ponajbolje etilensku skupinu;
D ponajprije nitro ili cijano;
X ponajprije neki kisikov ili sumporov atom ili skupinu
[image]
ponajbolje neki kisikov atom ili skupinu
[image]
Z ponajprije neku halogeniranu 5- ili 6-članu heterocikličku skupinu, koja sadrži dva heteroatoma odabrana između kisikovog atoma, sumporovog atoma i dušikovog atoma, ili neku halogeniranu 3- ili 4-piridilnu supinu, posebice u prednosti neku halogeniranu tiazolilnu ili 3-piridilnu skupinu, a ponajbolje 2-kloro-pirid-5-il.
Posebice u prednosti među spojevima formule (I) je spoj formule (Ia)
[image]
koji se dobije pretvorbom spoja formule (IIa)
[image]
s nekom bazom i u nazočnosti nekog sredstva za razrjeđivanje, te potom pretvorbom reakcijske smjese sa smjesom načinjenom iz CCMP/CMP s odgovarajućim hidrokloridima.
Daljnji spoj formule (I) koji je posebice u prednosti je spoj formule (Ib)
[image]
koji se dobije pretvorbom spoja formule (IIb)
[image]
s nekom bazom i u nazočnosti nekog sredstva za razrjeđivanje, te potom pretvorbom reakcijske smjese sa smjesom načinjenom iz CCMP/CMP s odgovarajućim hidrokloridima.
Kao otapala mogu se dodati protična i dipolarna aprotična otapala, ponajprije voda, alkoholi, ketoni (ponajprije MIBK), esteri (ponajprije butilni acetat), nitrili (ponajprije acetonitril, n-propionitril, butiro-nitril), piridini (ponajprije CMP), amidi (DMF), DMSO ili karbonati, ili njihove smjese s vodom. Uz dodatak alkohola kao otapala, mogu se dobiti spojevi formule (I) izravne podobne modifikacije i potrebne čistoće za primjenu kao sredstva za biljnu zaštitu.
Mogu se primjerice navesti sljedeći primijenjeni alkoholi:
- primarni alkoholi kao metanol, etanol, propanol, butanol, 2-metil-1-propanol, 1-pentanol, benzilni alkohol,
- sekundarni alkoholi kao izopropanol, sek-butanol, 2-pentanol, tert-alkoholi kao tert-butanol.
Kao otapala su posebice u prednosti alkoholi koji se ne miješaju ili se tek djelomice miješaju s vodom, kao n-butanol, amilni alkohol, ponajprije n-butanol, ili nitrili kao n-propionitril ili butironitril, ponajprije propionitril.
Postupak se opcijski provodi u nazočnosti neke baze. Kao primjeri mogu se navesti: alkalijski i zemnoalkalijski oksidi kao NaOH, KOH, Ca(OH)2, karbonati alkalijskih metala ili hidrogenkarbonati alkalijskih metala kao Na2CO3, Li2CO3, K2CO3, Cs2CO3 ili NaHCOs i KHCO3. Ponajprije treba navesti K2CO3, NaOH i KHCO3, a posebice K2CO3.
Spojevi općenite formule (II) mogu se dodati kao alkalijske ili zemnoalkalijske soli u krutom ili u otopljenom obliku.
Pri radu u vodi, smjesama voda-alkohol ili smjesama voda-nitril, provede se postupak u području pH između 6 i 13.
Kao katalizatori mogu se dodati katalizatori faznog transfera, opcijski kvarterni amonijevi halogenidi kao tetrabutilamonijev bromid ili -klorid, ili Cs-soli, itd.
Reakcija se može provesti tako, da se spojevi općenite formule (II) opcijski kao alkalijske ili zemnoalkalijske soli, zagrijavaju u nazočnosti neke baze pri temperaturama od 40°C do 130°C, opcijski u vakuumu, ponajprije pri 100 do 500 mbara, te se potom doda smjesa CCMP/CMP pri 50 do 90°C, opcijski u vakuumu, ponajprije pri 60°C do 80°C.
Reakcija se svrhovito provodi pod atmosferskim tlakom, međutim može se raditi i pod sniženim ili pod povišenim tlakom. Ponajbolja je provedba u vakuumu.
U praktičnoj provedbi postupka se primjerice pretvori l mol neke smjese CCMP/CMPP sa 0.95 do 3 mola spoja formule (II), ponajprije 1.0 do oko 2.5 mola, u otapalu kao stoje butanol, u nazočnosti od l do 3 mola, ponajprije 1.5 do 2.5 mola neke baze kao što je primjerice kalijev karbonat, te opcijski u nazočnosti nekog katalizatora kao što je tetrabutilamonijev bromid ili cezijev karbonat.
Pri uporabi vode u dvofaznom sustavu radi se ponajprije pri vrijednostima pH 8-10.
Reakcijsko vrijeme iznosi između 3 i 12 sati, ponajprije 5 do 10 sati. Nakon završene reakcije može uslijediti primjerice zamjena otapala. Pri tome se destilacijom ukloni najveći dio reakcijskog sredstva za razrjeđivanje u vakuumu (1-1000 mbara) i količina nadopuni nekim od gore navedenih sredstava za razrjeđivanje. Supstitucija otapala može uslijediti prije ili nakon hidrolize.
Suspenzija iz reakcije hidrolizira se na temperaturi od 50°C do 100°C, te slijedi odvajanje organske faze pri 50°C do 80°C. Ova se ohladi, istaložena djelotvorna tvar se izolira, ispere i prekristalizira.
CMP koji se nalazi u matičnici (temperaturne područje 50°C do 130°C, područje tlaka 1-1000 mbara) može se reciklirati i ponovno uvesti u proces: dobivena matičnica može se pretvoriti s razrjeđivačem za kristalizaciju (1 dio matičnice / 4 dijela otapala - 1 dio matičnice / 0.5 dijelova otapala), suspenzjia se ohladi i zaostala djelotvorna tvar se odfiltrira.
Ishodne tvari formule (II) poznate su i/ili mogu se pripraviti prema postupcima poznatima samim po sebi (usp. JACS 79 (1957) 3565; Arch. Pharm. 305 (1972) 731-736; Heterocycles 31 (1990) 1601-1604; Biosci. Biotechnol. Biochem. 57 (1993) 127-128; Biosci. Biotechnol. Biochem. 56 (1992) 364-365).
Priprava 2-kloro-5-klorometilpiridina uspješna je prema opisanom postupku (EP-A-458 109, EP-A-260 485). 2-Kloro-5-metilpiridin se klorira u nekom organskom otapalu (acetonitril, tetraklorugljik, voda kontroliranog pH) sa starterom radikala (AIBN) na toplini kuhanja. Pretvorba reakcije prekida se pri približno 40 %, zbog postizanja visoke selektivnosti na 2-kloro-5-klorometilpiridinu. Potom slijedi destilacija organskog otapala u vakuumu.
Smjesa CCMP/CMP sadrži nakon destilacije otapala 5-15 % ostatnog otapala, 30-50 % CMP i 25-45 % CCMP s odgovarajućim hidrokloridima.
Ta smjesa 2-kloro-5-metilpiridina i 2-kloro-5-klorometilpiridina i odgovarajućih hidroklorida služi kao dodatak za reakciju djelotvorne tvari. Ta se smjesa može dodati u reakciju nerazrijeđena ili u nekom sredstvu za razrjeđivanje, koje se svrhovito dodaje i u reakciju djelotvorne tvari.
Spojevi formule (I) su primjerice podobni za primljenu kao insekticidi (EP A2 0235 752, EP A2 0259 738).
Sljedeći primjeri osvjetljavaju predmet izuma, a da ga ne ograničuju ni na koji način.
Primjer 1
[image]
U 100 ml n-butanola suspendirano je 0.615 mola kalijevog karbonata i 0.3 mola 2-cijaniminotiazolidina, te je miješano pri 60°C kroz l sat. Unutar 2 sata dodano je pri 70°C 0.315 mola 2-kloro-5-klorometilpiridin/2-kloro-5-metilpiridina (CCMP/CMP, 23 % CCMP u smjesi) suspendiranih u 100 ml n-butanola, te je miješano 2 sata pri 72°C. Nakon hlađenja na 65°C dodano je 400 g vode i faze su odvojene. Potom je organska faza miješana 3 sata pri 50°C i nakon toga još 18 sati pri -5°C. Istaloženi produkt je odfiltriran i osušen; 59.6 g (78 % od teorijskog).
Primjer 2
U 100 ml n-butanola suspendirano je 0.615 mola kalijevog karbonata i 0.3 mola 2-cijaniminotiazolidina, te je miješano pri 60°C kroz l sat. Unutar 2 sata dodano je pri 70°C 0.315 mola 2-kloro-5-klorometilpiridin/2-kloro-5-metilpiridina (CCMP/CMP, 23 % CCMP u smjesi) suspendiranih u 100 ml n-butanola, te je miješano 2 sata pri 72°C. Nakon hlađenja na 65°C dodano je 400 g vode i faze su odvojene. Potom je organska faza miješana 3 sata pri 50°C i nakon toga još 18 sati pri -5°C. Istaloženi produkt je odfiltriran i osušen. Matičnica je pretvorena u omjeru 1:1 s butanolom i ohlađena na 0°C, a pri tome nastala krutina je odfiltrirana i osušena. Ukupno iskorištenje: 66.1 g (85 % izoliranog produkta).
Primjer 3
U 300 ml vode suspendirano je 0.3 mola 2-cijaniminitiazolidina i 4.2 g tetrabutilamonijevog bromida, te je zagrijavano na 70°C. Slijedio je dodatak 0.315 mola smjese CMP/CCMP. Vrijednost pH reakcijske smjese održavana je pomoću NaOH kontinuirano na 8 do 8.5. Nakon 2 sata reakcijskog vremena pri 60°C provedeno je pri toj temperaturi odvajanje faza, te je organska faza razrijeđena sa 150 ml butanola i miješana. Unutar 3 h ohlađena je na 3°C i istaloženi produkt je odsisan; dobiveno je 58.5 g (76 % od teorijskog).
Primjer 4
[image]
U 600 g n-propionitrila preuzeto je 1.5 mola etilen nitrogvanidina (sadrži 16.5 % vode) i voda je azeotropno oddestilirana. Potom je slijedio dodatak 342 g kalijevog karbonata (2.5 mola) pri 95°C. Nakon toga dodano je 2 g cezijevog karbonata. Unutar 30 minuta dodan je 521 g CMP/CCMP (31 % CCMP) pri 95-100°C. Nakon reakcijskog vremena od 5 sati pri 100-105°C dodano je 1.2 L vode. Vrijednost pH reakcijske smjese održavana je na 6 do 7 pomoću HCl. Propionitril iz organske faze uklonjen je destilacijom pri 180 mbara. Potom je dodano 500 g n-butanola i zagrijavano je na 80°C, te su faze odvojene. Organska faza ohlađena je na 0°C. Istaloženi produkt je odfiltriran i osušen; 187.4 g (73 % of teorijskog).
Claims (1)
1. Postupak priprave spojeva formule (I)
[image]
u kojoj
R1 predstavlja vodikov atom ili neku alkilnu skupinu,
A predstavlja etilensku skupinu koja može biti supstituirana alkilom, ili trimetilensku skupinu koja može biti supstituirana alkilom,
D predstavlja nitro ili cijano,
X predstavlja kisikov ili sumporov atom ili skupine
[image]
u kojima
R3 predstavlja vodikov atom ili alkilnu skupinu,
Z predstavlja opcijski supstituiranu 5- ili 6-članu heterocikličku skupinu, koja sadrži barem dva heteroatoma odabrana iz skupine kisikov atom, sumporov atom i dušikov atom, ili neku opcijski supstituiranu 3- ili 4-piridilnu skupinu, naznačen time, da se spojevi formule (II)
[image]
u kojoj
A, D i X imaju gore navedena značenja,
pretvore s nekom bazom u nazočnosti nekog sredstva za razrjeđivanje, te se reakcijska smjesa potom pretvori pomoću smjese načinjene od CCMP/CMP (2-kloro-5-klorometilpiridin/2-kloro-5-metilpiridin) s odgovarajućim hidrokloridima.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10002049 | 2000-01-19 | ||
| PCT/EP2001/000125 WO2001053296A1 (de) | 2000-01-19 | 2001-01-08 | Verfahren zur herstellung von heterocyclischen verbindungen |
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| Publication Number | Publication Date |
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| HRP20020667A2 true HRP20020667A2 (en) | 2004-12-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| HRP20020667 HRP20020667A2 (en) | 2000-01-19 | 2002-08-13 | Method for producing heterocyclic compounds |
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| Country | Link |
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| US (1) | US6667401B2 (hr) |
| EP (1) | EP1252159B1 (hr) |
| JP (1) | JP5078211B2 (hr) |
| KR (1) | KR100740983B1 (hr) |
| CN (1) | CN1182135C (hr) |
| AT (1) | ATE264857T1 (hr) |
| AU (1) | AU766982B2 (hr) |
| BR (1) | BR0107648B1 (hr) |
| CA (1) | CA2402467C (hr) |
| CZ (1) | CZ301991B6 (hr) |
| DE (1) | DE50102050D1 (hr) |
| DK (1) | DK1252159T3 (hr) |
| ES (1) | ES2215120T3 (hr) |
| HR (1) | HRP20020667A2 (hr) |
| HU (1) | HUP0203878A3 (hr) |
| IL (1) | IL150622A0 (hr) |
| IS (1) | IS6460A (hr) |
| MX (1) | MXPA02007060A (hr) |
| NO (1) | NO323827B1 (hr) |
| NZ (1) | NZ520214A (hr) |
| PL (1) | PL356715A1 (hr) |
| PT (1) | PT1252159E (hr) |
| RU (1) | RU2269526C2 (hr) |
| SK (1) | SK285671B6 (hr) |
| TR (1) | TR200401111T4 (hr) |
| UA (1) | UA75061C2 (hr) |
| WO (1) | WO2001053296A1 (hr) |
| ZA (1) | ZA200204953B (hr) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101503406B (zh) * | 2008-12-17 | 2011-03-23 | 武汉工程大学 | 1-(2,3-环氧丙基)-n-硝基亚咪唑烷-2-基胺及其制备方法和应用 |
| JP2014525422A (ja) * | 2011-09-02 | 2014-09-29 | バイエル・インテレクチユアル・プロパテイー・ゲー・エム・ベー・ハー | ［３−［（６−クロロ−３−ピリジニル）メチル］−２−チアゾリジニリデン］シアナミドを製造する方法 |
| BR112018075237B1 (pt) * | 2016-06-06 | 2022-08-23 | Bayer Cropscience Aktiengesellschaft | Processo para produzir compostos heterocíclicos |
| CN107629045A (zh) * | 2017-11-10 | 2018-01-26 | 上海生农生化制品股份有限公司 | 一种噻虫啉的水相合成方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| ZW5085A1 (en) | 1984-04-13 | 1985-09-18 | Nihon Tokushu Noyaku Seizo Kk | Nitromethylene derivatives,intermediates thereof,processes for production thereof,and insecticides |
| DE3681465D1 (hr) * | 1985-02-04 | 1991-10-24 | Nihon Bayer Agrochem K.K., Tokio/Tokyo, Jp | |
| JPH0730070B2 (ja) * | 1985-10-03 | 1995-04-05 | 日本バイエルアグロケム株式会社 | 新規複素環式化合物 |
| PH23283A (en) | 1986-02-26 | 1989-06-30 | Eisai Co Ltd | Piperidine derivative, pharmaceutical composition containing the same and method of use thereof |
| US5179095A (en) | 1986-02-26 | 1993-01-12 | Eisai Co., Ltd. | Piperidine derivative and pharmaceutical composition containing the same |
| JPH0717621B2 (ja) * | 1986-03-07 | 1995-03-01 | 日本バイエルアグロケム株式会社 | 新規ヘテロ環式化合物 |
| DE3630046A1 (de) * | 1986-09-04 | 1988-03-17 | Bayer Ag | Verfahren zur herstellung von 5-chlormethylpyridinen |
| JPH07121909B2 (ja) | 1986-09-10 | 1995-12-25 | 日本バイエルアグロケム株式会社 | 新規複素環式化合物及び殺虫剤 |
| DE3830238A1 (de) * | 1988-09-06 | 1990-03-15 | Bayer Ag | Verfahren zur herstellung von 1-substituierten 2-(nitroimino)-1,3-diazacycloalkan-derivaten |
| DE4016175A1 (de) | 1990-05-19 | 1991-11-21 | Bayer Ag | Seitenkettenchlorierung von alkylierten stickstoff-heteroaromaten |
| DE19710613A1 (de) * | 1997-03-14 | 1998-09-17 | Bayer Ag | Verfahren zur Herstellung von 5-Aminomethyl-2-chlorpyridinen |
| DE19904310A1 (de) * | 1999-01-28 | 2000-08-03 | Bayer Ag | Verfahren zur Herstellung heterocyclischer Verbindungen |
| US6307053B1 (en) | 2000-12-29 | 2001-10-23 | Sinon Corporation | Process for preparing imidacloprid |
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