LV10452B - A process for the preparation of (1h-azolo-1-ylmethyl)-substituted derivatives of benzotriazoles - Google Patents
A process for the preparation of (1h-azolo-1-ylmethyl)-substituted derivatives of benzotriazoles Download PDFInfo
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- LV10452B LV10452B LVP-92-233A LV920233A LV10452B LV 10452 B LV10452 B LV 10452B LV 920233 A LV920233 A LV 920233A LV 10452 B LV10452 B LV 10452B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- 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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Description
LV 10452
CnOCOB ΠΟΠΥΗΕΗΙΊΑ nPOH3BOflHblX (1Η-Α30Π-1- -M/1METMn)-3AMELLlEHHblX 5ΕΗ30ΤΡΜΑ30Π0Β
OnncaHne Πρθρποομπκμ co3DaHna n3o6peTeHna
BonblilOM pflfl npOH3BOPHblX a30n0B BBJlBKDTCfl M3BSCTHblMH B o6nacTn b KanecTse npoTMBorpn6KOBbix cpepcTB. HepaBHO μμκοη330π, KnoTpnMa3on μ κθτοκοη330π, MneHbi Knacca MMnpa3onbHbix cpepcTB c LunpOKUM cneKTpoM aKTH8HOCTn προτΜΒ uenoro papa αροχοκθμ, ΡθρΜ3ΤθφΐΊΤ0Β M flHM0pCļD03HblX φΜδκΟΒ, ΚΘΚ 6binO COOČipeHO B "Biochemical Phannacolo»'y", 34. 1087 (1985), MHrn6npyK)T peižiCTBue φθρΜθΗΤθ apOMaTa3bi.
PoACTBeHHbie npou3BOflHbie a3onoB onucaHbi b πθτθητθχ CLUA No 4 602 025 m No 4 609 666 μ β οπγδπΜκοΒθΗΗΟΜ naieHTHoii 3aaBKe Eeponbi No 0 165 781 β κθμθοτβθ nHrnānTopoe apOMaia3bi, none3Hbix ripu neneHnn 3CTporeH-3aB^cnMbix 3a5oneBaHnii. B πθτθητθ CLUA No 4 410 539 onucbiBatOTca eme paa npon3BopHbix (1H-nMnfla3on-1-nnM0TMn)-3aMeiiļeHHbix nnponoB, koto- 2 pbie ββπβκ)τοβ none3HbiMn b κθηθοτβθ MHrnSmopoB τροΜδοκοθΗ--cnHTeia3bi.
CoepnHeHMfl HacTOfuuero u3o6peTeHMB OTnHnatOTca ot hhx τθμ, mto ohm coflep>KaT ηθμ3μθηηο 6eH30Tpna3onbHbm οοτθτοκ, n no mx cnocoūHocTM nHrnānpOBaib AeiicTBMe <t>epMeHTa-apoMaTa3bi. CoeflMHeHna HacToamero μ3ο6ρθτθημβ ββπβιοτοβ noaTOMy none3HbiMn npn TepaneBTunecKOM πθμθημμ m npeAynpe>KAeHna 3a6oneBaHKM y MneKonnTaK)Li|Mxcfl, 3aBucnMbix (3a6oneBaHMB) ot 3dporeHHbix ΓΟρΜΟΗΟΒ.
OnHcāHne ^3ο6ρθτ6ημβ
HacToamee n30āpeieHne othocmtcb k npon3BOAHbiM 6θη-30Tpna30n0B $OpMynbl
R
Λ24-λ3 |*1 1 H 4 a2 λ λ ι 1 Ar R -CH _ļ— J-N mx 0apMaueBTHHecKn npneMneMbiM cohbm npucoeAUHeHuu kuctiot n CTepeon30MepHbiM φορΜθΜ, b κοτοροίί (φορΜγπε) : A1=A2-A3=A4 ηβπβθτοβ AByBaneHTHbiM paAUKanoM, μμθφιακμ $opMyny: -CH=N-CH=CH- ( a-1 ), -CH=N-CH=N* ( a-2 ), nnw -CH=N-N=CH- (a-3 ); R ββπβθτοβ BOAopoAOM nnn C-|-6 θπκιίπομ; R1 ββπβθτοβ BOAopoAOM, C1 -1 o anKunoM, C3-7unKJioanKnnoM, Ar1, Ar2- C 1-6 anKunoM, C2-6 anKSHunoM μπμ C2-6 anKUHunoM; R2 ββπβθτοβ BOAopoAOM; C1 -1oanKunoM, Heo6a3aTenbHO 3aMeiueHHbiM τργπποιλ Ar1, C3-7UHKnoanKunoM, okcu- urrn Ci-6anKun-OKcn-rpynnoM; Ar1; C2-6anKeH^ir,OM; C2-6anKHHnnoM; C3-7uhkjio- 3 LV 10452 θπκμπομ; 6μαμκπο [2.2.1]- γθπτ3η-2-μπομ; 2,3-flnrnflpo-1H-nHfleHnnOM; 1,2,3,4-τθτρ3ΓΜΑροΗ3φτ3ΠΜΗθΜ; okch-; C2-6ariKeHnnoKCM-rpynnoii, Heo6ii3aTenbHO 38μθιαθηηομ Ar2 -rpynnoM; C2-6 θπκμημποκομ- ; nupuMMflMHunoKCM-; fln-( Ar2)- μθτοκομ-; (1-C-|-4ariKnn-4-nunepMfln-Hnn)-0Kcn-; μπμ Ci-ioanKnnoKcn-rpynnoM, Heo6fl3aTenbHO 3aMemen-hom ranoreHOM, okcm-, Ci-6anKnnoKCn, θμμηο-; moho- m fln-(Ci-6a/i-KMn)-aMMHO-rpynnoM, τρίΊφτορΜθΤΜΠΟΜ, κθρΘοκομπομ, Ci-6anKnnoKCn-KapSoHunoM, Ar1, Ar2-0-, Ar2-S-, C3-7UMKnoanKnnoM, 2,3-flMrnflpo--1,4-6eH30AH0KcnHnn0M, 1 Η-6θη3μμμαθ30πμπομ, Ci-4anKnn-3aMe-ULļ© Η H bl M 1 H-6eH3HMMAa30nnn0M, (1 ,1 '-6ΜφθΗΜΠ)-4-ΜΠΟΜ ΜΠΜ 2,3-AnrnApo-2-OKCO-1 H-6eH3HMHAa3onnnoM; R3 ββπηθτοα boaopoa, ΗΜτρο-, θμμηο-, moho- h An-(Cl-6anKl/in)· aMHHO-rpynnoii, γθπογθηομ, Ci-6ariKMnoM, okcm- μπμ Ci-6anKMnoKCM-rpynnoM; b κοτοροιί Αγ1ΠΒΠΠΘΤΟΠ φθΗΜΠΟΜ, 38ΜΘΙΜΘΗΗΗΜ φθΗΜΠΟΜ, ΗθφΤΒΠΜΗΜΠΟΜ, ΠΜρΜΑΜΗΜΠΟΜ, aMHHOnHpHAHHMnOM, HMUAa30nnriOM, TpHa30nnn0M, τμθημπομ, γθποματμθημπομ, φypaHnnoM, C-|-6aπκMnφypaHMπoM, ΓaπonAφypaHnπoM, μπμ τμθθοπμπομ; a
Ar2 πβππθτοη Φθημπομ, 3aMeuieHHbiM Φθημπομ μπμ nupn-Αμημπομ, πρΜΗθΜ y«a3aHHbiM 3aMet4eHHbm Φθημπ ββππΘτοπ Φθημπομ, 3ΘΜΘϋ4ΘΗΗΜΜ BnnOTb ΑΟ 3 38ΜΘ0ΤΜΤΘΠΘΜ , K3>KAblM ΗΘ38ΒΜΟΜΜΟ BbiānpaeMbiiži Μ3 ranoreHa, OKCM-rpynnbi, οκομμθτMna, τρΜφτορΜθΤΜΠθ, Ci-6anKnna, Ci-6anKMnoKCM-rpynnbi, C i-6anKMnoKCMKap6oHnna, Kap6oKCnna, φορΜΜΑθ, (οκομμμμηο^μθτμπθ, αμθηο-, θμμηο-, moho- μ An(Ci-6anKnn)-aMMHO- μ Hmpo-rpynn.
Hcnonb3yeMbiii b πρμβθαθηημχ Bbiiue οπρθαθπθημπχ τθρμμη γθπογθη othocmtcb κ φτopy, xnopy, 6poMy m ūOAy; τθρμμη ”Ci-6anKMn” npeAHa3HaHaeTca αππ βκπκ)ηθημπ πμηθμηο- m pa3BeTBneHHO-uenHbix HacbiLH9HHbix yrneBOAopoAHbix papuKanoB, μμθκϊιαμχ ot 1 ao 6 θτομοβ yrnepOAa, τθκμχ iok, HanpMMep, μθτμπ, stmh, Ι-μθτμπθτμπ, 1,1-αμ- ΜΘΤΜΠ3ΤΜΠ, ΠΡΟΠΜΠ, 2-ΜΘΤΜΠΠρθΠΜΠ, 6yTMn, aMMn, ΓΘΚΟΜΠ Μ TOMy noAOČHbie; τθρμμη ”Ci-ioanKwn" npeAHa3HaHaeicn απη βκπιοηθημπ Ci--ganKMnbHbix ρθαμκθποβ, κθκ sto οπρθαθπθηο Bbinie, μ mx BbicujMe γομοπογμ, μμθκμαμθ οτ 7 ao 10 3τομοβ yrnepoAa; τθρμμη 4 "03-7Ψίκπο8Πκμπ” othochtch κ uuKnonponnny, unKno5yTnny, ρνικπο-neHTnny, unKnorexcuny n uuxnorenTnny. "C2-6anKeHnn” onpenenneT ΠΜΗθΐίHO- n pa3BeTBneHHO-LļenHbie yrneBOflopoflHbie panuKanu, coflepJKaiune onny ABOi/iHyto CBB3b μ μμθκκαμθ ot 2 flo 6 θτομοβ yrnepopa, Taxwe xax, HanpuMep, 3τθημπ, 2-nponeHnn, 3-6yTeHnn, 2-6y-TeHnn, 2-πθητθημπ, 3-πθητθημπ, 3-MeTnn-2-6yieHnn n TOMy noflOČHbie; ”C2-6anxviHnn" onpenenneT nuHeiiHO- w paseeTBneHHO-uenHbie yrneBO,qopoflHbie papuKanbi, conep>xainne OflHy TpowHyio CBB3b n MMefomne ot 2 no 6 θτομοβ yrnepona, Taxne xax, HanpuMep 2-nponn-Hun, 2-6yTHHnn, 3-6yTHHnn, 2-neHTHHnn, 3-πθητμημπ, 4-neHTHHnn u TOMy nono6Hbie; a xorna C2-6anKeHnn mv\ C2-6anxm-inn 3aMemaeTcn Ha reiepoaTOMe, to Torņa yrnepoflHbivi aTOM yKa3aHHoro C2-6anKeHiina vīnu yKa3aHHoro C2-6anKMHnna, CBB3aHHbivi c yKa3am-ibiM reTepoaTOMOM, npennoHTUTenbHO nenneTcn HacbiineHHbiM. flon>KHO 6biTb noHnTHbiM, mto οοτθτοκ Tvina
R
b nanbHeviiiieM Ha3biBaeMbivi xax 1H-a3on-1-nnMeTnnbHbivi οοτθτοκ, μο>κθτ 6biTb 3aMeineHHbiM b nono>KeHvin nnčo 4,5,6, nn6o 7 6θη30-Tpna3on-reTepounKnnwecKoro uuxna. KpOMe τογο, οοθακηθημη $opMynbi (I) Moryr Tax>xe conepaoTb no CBoevi CTpyxType TayTOMepHyto cncTeMy m cnenoBaTenbHO stm οοθαμηθημβ MoryT Haxonnrbcn b xaxAoii H3 nx TayTOMepHbix φορΜ. KpOMe τογο, b npenenax ο6βθμθ Ha-CTomnero n3o6peTeHnn ηθχοαβτοη coennHeHnn $opMynbi (I) b φορΜΘ runpaTOB nnn b φορΜβχ npncoenviHeHnn pacTBopuTenn.
CoennHeHnn φopMynbι (I) MoryT 6biTb 8 6onbniviHCTBe cnyMaeB nonyneHbi nyTeM N-anKunupoeaHun a3ona φopMyπbι (III) nnn ero conb menoHHoro MeTanna c noMombto 5eH30Tpna3ona φopMyπbι (II). 5LV 10452 Η h ιΐ * R2 λ 1 ΑΝΝΧΑ f w-i“ -b. 1 0 Ν-anKnnnDOBaHne. Η (I) (II) (III) W, ncnorib3yeMbiki b peaKpHH (II) c (III) h b cneflyfou4nx cxeMax peaKLļHM, aBnaeTCB C00TBeTCTByK)uueiži yxoAameH rpynnon, τθκοη κθκ, HanpHMep, ranoreH, npeflnoMTmenbHO χπορ, δροΜ ηπη hoa, cynb$OHnnoKCn-rpynna, HanpHMep, MeTnncynbcpOHnjiOKcn- ηπη 4-MeTnn6eH3oncynb(|50HHnoKCn-rpynna.
OnncaHHoe Bbiaie Ν-θπκηπηροβθηηθ yno6HO npOBOflmca nyieM nepeMeujHBaHHa pearHpyfOinHx BemecTB b npncyTCTBnn noflxofljniiero opraHHnecKoro pacTBOpHTenn, τθκογο iok, HanpHMep, apoMaTHHecKHH yrneBOflopofl, HanpHMep, 6θη30π, ΜβτΗπδβΗ3οη, αημθτηπ6θη30π h TOMy nopoČHbie; κθτοη, HanpHMep, aueTOH, 4-MeTHn-2-neHTaHOH h TOMy nopoČHbie; npocron 3φπρ, HanpHMep, 1,4-flHOKcaH, flHSTnnoBbiH 3φπρ, TeTparnApc^ypaH h TOMy nopoČHbie; nonnpHbiH anpOTOHHbin pacTBOpHTenb, HanpHMep, Ν,Ν-ΑΗΜβτΗπφορΜθΜΗΑ (ΠΜΦΑ), Ν,Ν-αημθ-THnaueiaMHA (flMALļ), αημθτηγ^πβΦοκοηρ (flMCO), 1-μθτηπ-2- -ΠΗΡΡΟΠΗΑΗΗΟΗ, ΘΑβΤΟΗΗΤρΗΠ, ΓΘΚΟΘΜβΤΗΠφΟΟφορτρΗΘΜΗΑ (ΓΜΦΤΑ), 1,3-AHMeTHn-3,4,5,6-TeTparHApo-2-(1 Η)-πηρημηαηηοη (ΠΜΓΙΜ), 1 ,3-αη-μθτηπ-2-ημηα330πηαηηοη (J3MMM), 6βΗ30ΗΗτρππ η TOMy noAOČHbie; η ομθοη τ3κηχ pacTBOpHTeneH. Οτηοοητθπβηο noBbinieHHbie τβΜπβ-paiypbi MoryT 6biTb yMecTHbiMH, HTo6bi noBbīcnTb cKopocTb peaKpHH h b HeKOTOpbix cnyHanx peaKpna μο>κθτ 6biTb npoBeAena Aa*e npn TeMnepaiype κηπθηηπ c o6paTHbiM χοποαηπβηηκομ βοθη peaKUHOHHOH CMeCH. flo6aBneHHe cooTBeTCTByK)LLiero οοηοββηηβ, τθκογο KaK, HanpHMep, Kap6oHaT, ΓΗΑροιορδοΗθτ, rHApooKHCb, θμηα ηπμ γηαρηα LUenOMHOrO ΗΠΗ ΙΑΘΠ0ΗΗΟ3βΜβΠΒΗ0Γ0 ΜβΤΘΠΠΘ, HanpHMep, rHApOOKHCb HaTpHB, THApOOKHCb ΚΘΠΗΠ, KapOOHaT ΙΟΠΗΠ, THApHA H3TpHB Η TOMy noAoāHbie, ηπη opraHHnecKoe οοηοβθηηθ, Taxoe Kate, HanpHMep, N.N-AHMeTHn-4-nHpHAHHaMHH, Π H pH AH Η , ΤρΗ3ΤΗΠ3ΜΗΗ ΗΠΗ Ν-(1 -MeTHn3THn)-2-nponaHaMHH, Μθ>κβτ 6biTb πρπΜβΗβΗΟ, mo6bi 6
CBA3biBaTb KncnoTy, KOTopaa BbiflenfleTca b xope peaKLļHu. B HeKOTOpbix cnyMa«x μο>κθτ 6biTb none3HbiM ncnonb30BaTb κ36ητοκ a3ona (III) nnn npeBpaTmb ero po ero μθτθππμμθοκοι^ οοπθβοιλ φορΜΒΐ, b HacTHocTn, ero coneByio $opMy menoHHoro Meianna, cnepyB M3BeCTHblM B flaHHOiī OČ/iaCTH MeTOflUKaM, T3KMM KaK, HanpUMep, o6pa6opxa a3ona (III) rnApooKucbto, ariKOKCupoM nnn rn/ļpuflOM menoHHoro MeTanna.
CoepnHeHMfl $opMynbi (I), b κοτοροίί A''=A2-A3=a4 ηβπηθτοβ AByBaneHTHbiM papuKanoM $opMynbi (a-1), npuneivi yKa3aHHbie coefluHeHM?! npeflCTaBnfliOTCB φορΓν^ποΐ/ί (I-a-1), MOryT 6biTb nonyHeHbi τθιοκθ nyīeM B3anMOfleiicTBHfl 5eH30Tpna3ona 0opMynbi (II) c 3amnmeHHbiM B nonox<eHnn 1 nMnfla3onoM φopMyπbι (III-a), cneAya μθτοα^κθμ N-anKunupOBaHM^, onbīcaHHbiM Bbiiue απβ nonyMeHMH coeAHHeHmži φορΜγ/ιυ (I), hcxoa« H3 (II) n (III).
B (III-a) npeAdaBnBeT 3ammHyio rpynny, TaKyio Ka«,
HanpuMep, Ci-6an«nnKap6oHMn, Ci-6anKMnoKCHKap6oHnn, apwiKap6o-ημπ μπμ TpM-(Ci-6anKMn)-cnnnn. B HeKOTopbix cnynaBX peaKuna (III-a) c (II) CHanana AaeT 3amnmeHHyio b ποποχθημμ 1 conb MMMAa3onna φopMyπbι (IV), KOTopaa μοχθτ hh cmy, nnn ecrm >KenaiebHO, nocne BbiAeneHna μ αοποπηιίτθπβηοιλ ohhctku θθ, noABeprai"bCB yAaneHHK) 3aLunTHOū rpynnbi (Ae6noi<wpoBaTbCfl) nyieM πθρθμθιχιμβθημβ ee b BOAHOM paCTBOpe OCHOBaHMfl.
(IV) 7 L.V 10452 B (IV) W‘ ABn^eTCfl aHMOHOM, B03HHKatomnM M3 KucnoTbi, TaKOM KaK, HanpMMep, χπορμοτοβοαοροαηθβ κμοποτθ, 6p0MncT0B0fl0p0flHafl Kucnoīa, MeiaHcynb0OHOBaa KucnoTa, 4-Meτ^1π6eH30πcyπbφ0H0Ban KucnoTa m TOMy noAOČHbie KucnoTbi.
OnpefleneHHbie coeflMHeHna $opMynbi (I), b κοτοροίί a1=a2-a3=A4 BBnaeTca ,QByBaneHTHbiM paflMKanoM 0opMynbi (a-2), npuneM yxa3aHHbie coeflUHeHna npepcTaBnafOTca 0opMynoiži (T-a-2), MoryT 6biTb nonyMeHbi TaKxe nyTeM N-anKunupOBaHu^ Tpna3onaMHHa φopMyπbι (ĪH-b) 6eH30Tpna3onc>M φopMyπbι (II) n nocneflyfoaļHM αθ33μμημ-ροβ3ημθμ nonyHeHHoū tbkum o6pa30M corrn Tpna3onn3 φopMyπbι (V).
B (V) W' ΗΒΠΗΘΤΟΑ aHMOHOM, B03HUKaK)lAMM H3 KUCAOTbl, Τ3Κ0ϋ Kax, HanpuMep, xnopncTOBOfloponHaa Kucnoīa, čpOMucTOBOflOpoflHaa KucnoTa, MeτaHcyπbφoHOBaB KucnoTa, 4-M9Tnn6eH30ncyr^0H0Bafl Kucnoīa u TOMy ποαο6ημθ KucnoTbi.
PeaKuna N-anKunupoBaHua (Iil-b)c (ΓΙ) npon3BopnTCH no μθτοα^ομ, noAOČHbiM onncaHHbiM Bbime pna nonyHeHna οοθαμηθημ?ι φopMyπbι (I), hcxoah n3 (III) n (II). YKa3aHHafl peaicuufl Ae3aMUHu-posaHua yflo5HO npoBOAuTca noopepcTBOM κιίοποτηογο pacTBopa HmpuTa b npncyTCTBnn cooTBeTCTByiOLuero βοοοτθηοβητθπα. npeAnoMTUTenbHO yi<a3aHHa?i peaKuna Ae3aMUHnpoBaHu?i npoBOAHTca c noMOiMbfO βοαηογο pacTBopa a30TucT0u KucnoTbi nnn hutputhou corm b cooTBeTCTByKDLLļeiži Kucnoie b npucyrcTBuu BOCCTaHOBUTenn, τθκογο κβκ, HanpuMep, φοοφορΗΟΒθτ^ιοτΒΑ (ΓΜποφοοφορΜΟΤθΒ) KucnoTa, MypaBbM-nan KucnoTa, npu ποΗπχθΗΗοΰ TeMnepaType. 8
CoeAUHeHMfl cfiopMynbi (I) ΜΟΓγτ 6biTb nonyHeHbi τηκ>κθ nyTeM B3anMOfleižicTBnyi cnupTa $opMynbi (VI) c peareHTOM 0opMyribi (VII), T3KHM KaK, HanpuMep, 1,1 '-Kap6oHun6uc[ 1 H-uMMfla3on ].
8 OH R^-CH
R
λ2=λ\ /A1sA2 (I) (VII) (VI) B (VII) X πρθαοτθβπηθτ = 0, S unu Χί = Ο. B Ηβκο-
Topbix cnywaax peaxpus (VI) c (VII) CHanana naei ιίητθρμθαιίθτ 0opMynbi (VIII), KOTopbiū μοχθτ hh cmy nnn, ecnu >KenaTeribHO, nocne BbifleneHua m AononHmenbHoiži ohuctkm ero, npespamaibca b peneBoe coeflMHeHne φopMyπbι (I). A2-f-A3
Hl 1*4 A A
I
X
R i N v Rl-CH
II (VIII) y«a3ai-iHaa peaKpua μοχθτ 6biTb yflo6HO npOBefleHa b ποαχοαβιμθμ pacTBopuTene, tskom KaK, HanpuMep, προοτοΰ 3$np, HanpuMep, 1,4-flnoKcaH, TeTparn.flpo$ypaH; ranouflMpoBaHHbiu yrneBO-flopofl, HanpuMep, pn- unu τρΜχπορΜθτβΗ; yrneBOflOpOfl, HanpuMep, 5θη30π, μθτμπ6θη3οπ; κθτοη, HanpuMep, apeTOH, 4-μθτμπ-2-πθητ3ηοη; Ν,Ν-ΑΜΜΘΤΜΠφΟρΜΘΜΜΑ, Ν,Ν-AUMeTunaueTaMUA, UflM CMecu Τ3ΚΜΧ pacTBOpuTeneū. flna τογο, močbi noBbicuTb CKOpodb peaKpuu, μο>κθτ 6biTb >KenaTenbHbiM HarpeeaTb peaKuuOHHy(0 CMecb.
CoepnHeHMH φopMyπbι (I) anbTepHaTUBHo MoryT 6biTb nonyweHbi npn ycnoBnax, ποαο6ημμ onucaHHbiM b nuīepaType p,rm nonyHeHna 9 LV 10452 6eH30Tpna30noB, hcxoaa H3 cooTBeTCTBytomnx 0eHnneHAnaMiiiHOB nnn npOH3BOAHblX ranOHAHHTpo6eH30HOB. B 3aBHCHMOCTH OT npUpOAbl 3aMecīmena R2 b coeAUHeHHflx $opMynbi (I), KOTOpbie Aon>KHbi 6biTb nonyHeHbi, cneAyfOiAne mgtoahkh ΜΟΓγτ 6bitb, HanpuMep, ncnonb30BaHbi.
CoeAUHeHna φopMyπbι (I), β κοτοροίί R2 ηβπηθτοα boaopoaom; Cļ-ioanKunoM, Heo6a3aienbHO 33μθιαθηηβιμ rpynnoM Ar1, C3-7unKno-anKunoM, okch- μπμ Ci-6anKnnoKCn; Ar1; 02-63Πκθημ'πομ, C2-6anKM-ημπομ; C3-7UMKnoanKnnoM; 6nunKno[2.2.1]-renTaH-2-nnoM; 2,3-ah-rnApo-1 Η-μηαθημπομ; μπμ 1,2,3,4-TeTparnAPOHa$TannHnnOM, npuneM yKa3aHHbiw paAHKan npeACTaBnaeTca 3HaweHneM R2‘a, a yKa3aHHbie coeAUHeHHA 0opMynoii (I-bj, MoryT 6biTb nonyM9Hbi m cooTBeTCTBy 101140 3aMeiAeHHoro A^aMuna φopMyπbι (IX)nyTeM Atfa30Tnp0BaHHfl n nocneAyioiAeii i4UKnn3ai4uu. a2-/-a3 lh 11 4 flna30TnposaHne + A λ’ 2-a ' l4MKnM3aLļM51 r-HHR CH—L I ļi S 3 R nh2 (IX)
R
YKa3aHHaB peaKpnfl Ana30TaTHBH0iži unKnn3aunn μο>κθτ 6biTb npoBeAeHa nyieM nepeMeiiiMBaHUA AnaMUHa φορι^πΜ (IX) b kucaot-hom pacTBope mupma. npeAnoHTUTenbHO yKa3aHHaa peaKuna npOBOAH'TCA BMeCTe C BOAHbIM paCTBOpOM a30THCT0fi KMCDOTbl ΜΠΜ c nOMOlAbK) ΒΟΑΗΟΓΟ paCTBOpa HHTpUTHOii CODM, HanpMMep, HMTpma HaTpua, b npncyTCTBnn ΠΟΑΧΟΑ^ΙΑΘΜ KucnoTbi, TaKoii KaK, Hanpmviep, xnopncTOBOAopoAHaB KucnoTa, 6poMncTOBOAOpoAHafi KucnoTa, MypaebMHafl KucnoTa, yKcycHaa KucnoTa, nponnoHOBan «ncnoTa m TOMy noAOČHbie KucnoTbi npn hm3kom TeMnepaiype.
CoeAUHeHna φορινψπΜ (I), β κοτορού R2 ββπβθτοα 0Kcnrpynn0M, πρΜΗΘΜ yKa3aHHbie οοθα^ηθημη πρθαοτθβπβιοτοη φοριν^ποΛ (I-c-1), 10
MoryT 6biTb ποηγπθΗΜ πγτθΜ LiMKnn3aicooTBeTCTByK)ine 3aMemeH* ηογο a3ona φορΜγπΜ (X), KOTopbiii hh cmy μοχθτ 6biTb ποπγπθΗ πγτΘΜ B3anMOAeūCTBna MHTepMefluaTa 0opMynbi (XI) c rnApa3HHOM (XII) nnn c ero ruppaTOM. 10
NO.
(X)
ll peaKijuq
UHKnn3ai4MH B (XI) npefldaBnaeT οοοτβθτοτβυιοιαυκ) yxoflainyK) rpynny, TaKyio Ka«, HanpuMep, ranoreH, npeflnoHTUTeribHO φτορ, χπορ nnn 6pOM, cyrib0OHnnoKCM-rpynna, HanpuMep, MeTnncynb$OHnnoKCM- nnn 4-μθτμπ-6eH3oncynb$OHMnoKCn-rpynna, nnn Ci-6anKnnoKcn- v\m Ci-6anKnnTno-rpynna. PeaKunB unKnn3auuM μοχθτ 6biTb npoeeAeHa πγτβΜ nepeMemuBaHua μητθρμθαμητθ φορΜγππ (XI) βμθοτθ c rwApa3uHOM b ποαχοα^ιαθμ nHepTHOM κ peaKuhm pacTBOpuTene, τθκομ κθκ, HanpuMep, cnupT, HanpuMep, ΜθτβΗοη, βτθηοπ, 2-nponaHon, 1-6yTaHon u TOMy noAOČHbie, unu apOMaTunecKUM yrneBOAOpOA, HanpuMep, 6θη30π, μθτμπ6θη30π, AHMeTun6eH3on u TOMy noAo6Hbie. OTHoernenbHO noBbiiueHHbie TeMnepaTypbi MoryT 6biTb >KenaienbHbi, πτοδυ nosbiiuaTb CKOpocTb peaKLļMM u npeAnoHTUTenbHO peaKuua npoBOAUTca npu TeMnepaType «uneHua peaKUuoHHoū CMecu c očpaTHbiM xonoAunbHu-kom. flocne 33Βθριΐ)ΘΗΜΗ peaicuuu, peaKuuoHHafl CMecb πρθαπομ-TmenbHO oxna>KAaeTca u noAKUcnaeica KucnoTHbiM pacTBOpOM, τθκμμ KaK, HanpuMep, pacTBop xnopucTOBOAOpOHoū KucnoTbi. LV 10452 Π
CoeAUHeHUH φορΜγπΗ (I-c-I) ΜΟΓγτ 6biTb flonoriHUTenbHO O-ariKu-nupOBaHbi peareHTOM φορΜγπΜ (XIII), cneflya n3BecTHbiM b panHOiži o6nacTn MeioflMKaM, nonyHafl τβκμμ o6pa30M οοοτβθτοτβυφιαμθ οοθαμηθημβ φορΜγπυ (I-c-2), b κοτοροιλ ββπβθτοβ Heo6fl3aTenbHO 33ΜΘ111ΘΗΗΟΜ C-| -103ΠΚΜΠΟΚΟΜ-, ΗθθδΒ38ΤΘΠΒΗΟ 33ΜΘΙΑΘΗΗθίί 02-6^ΠΚΘ-HunoKCM-, C2-6ani<MHMnoKCM-, nupuMMAHHMnoKCn-, An-(Ar2)-MeTOKCH-nnn (1-Ci-4anKnn-4-nnnepMAHHnn)-OKCM-rpynnoM, πρμηθμ yi<a3aHHbiM papuKan npepciaBniieTCB 3ηθηθημθμ O-R^'b.
R R
2-b YKa3aHHoe 0-anKnnnpOBaHne yao6ho nposopuTca b ποαχοαηιαθμ μηθρτηομ κ peaKpnn pacreopmene nnn b CMecu t3khx pacTBOpMTeneii. noAXOAfliunMn nHepTHbiMn κ peaKpnn pacTBopmennMH BBnflfOTca, HanpuMep, apoMaTHHec«m)i yrneBOAopoA, HanpuMep, 6θη30Π, μθτιίπ5θη30π, AHMeTnn6eH3on n TOMy πθΑθδι-ibie; HH3iunii θπκθηοπ, HanpuMep, μθτθηοπ, βτθηοπ, 1-6yiaHon n TOMy noAoOHbie; normpHbm anpOTOHHbm pacTBopmenb, HanpuMep, N,N-ακμθτ/πΦορμθμμα, Ν,Ν-AHMeTnnaueTaMHA, ΓΘΚΟθΜβΤΙΊΠφοαφΟρΤρΜΒΜΜΑ, Α^Μθτι^πογπΒφ-okcma; m TOMy noAo6Hbie. Πρθαποητμτθπβηο b npncyTCTBnn coot-BeTCTBytouiero ocHOBaHua, τθκογο κθκ, HanpuMep, rnppup, anKOKCHA. rnApooKMCb, rnApOKap6oHai, Kap6oHaT nnn θμμα menoHHoro nnn iuenoHHO-3eMenbHOro MeTanna. Μοχθτ 6biTb xenaienbHbiM npeAaa-puTenbHO npeBpaTUTb (I-c-1) b ero coneByio φορΜγ Meianna, npeAnoHTmenbHO HaTpneByfo conb, ο6μηημμ οποοοδοΜ, HanpuMep, ηγτβΜ B3anMOAeiicTBHB (I-c-lj c MeTannHHecKHM οοηοβθημθμ, TaKHM K3K THApOOKHCb HaTpHB H TOMy nOA06Hbie, H nocne 3ΤΟΓΟ HCn0nb30BaTb yKa3aHHyio conb Metanna b peaKUHH c (XIII). 12
Coe/ļHHeHUfl cf)OpMynbi (I-b) anbTepHaTUBHo MoryT 6biTb nonyHeHbi nyīeM BOCCTaHOBJieHMH οοθαμηθημβ (ļ>opMynbi (I-c-1), norunāsi τθκμμ o5pa30M coeflUHeHne 0opMynbi (I-b), b κοτοροίί R^aenfleTCfl boaopoaom, n, ecnn AononHmenbHo ttenaienbHO, noABeprafOT nonyMeHHoe τθκμμ o5pa30M οοθαμηθημθ cpopMynbi (I-b-1) B3anMOAeižicTBHKD c peareHTOM R2-c w (XIV), nonyMafl raKUM o6pa30M coeAUHeHne $opMynbi (I-b-2).
R
R
N I N
PeaKLiMfl -> BOCCTaHOBneHUfl N- anKunupOBaHun +R2'c W(XIV) ->
B (XIV) W ^μθθτ paHee onpeAeneHHbie 3Ha4eHHfl, a R^-c μμθθτ paHee onpeAeneHHoe 3HaneHne R%'a ripu ycnoBnn, ητο oho ηθ sļBnaeTCH boaopoaom. yxa3aHHaa peaKUHB βοοοτθηοβπθημβ μο>κθτ 6blTb npOBeAeHa, HanpUMep, nyieM KOHTa«THpOB3HH3 COeAUHeHUii $opMynbi (I-c-1) c boaopoaom b npncyTCTBnn cooTBeTCTByK)iuero Kaīann3aTOpa, τθκογο iok, HanpuMep, HHKenb Ρθηθη, OKHCb nnaTUHbi (IV), nnaTUHa, nannaahm m TOMy noAOČHbie, b npncyTCTBnn HHepTHoro κ peaKMMH opraHunecKoro pacTBopuTena, τθκογο iok hh3ujmm aniOHon, HanpuMep, MeTaHon, βτθηοπ n TOMy noAoSHbie. yKa3aHHoe BoccTaHOBneHne anbTepHaTUBHo μοχοτ 6biTb προβθαθηο nyieM B3aHM0ASMCTBMH ΜΟΧΟΑ^ΟΓΟ ΒΘΙΑΘΟΤΒΘ (I-C-l) C XnOpMCTblM THT3H0M (III-BaneHTHbiM) Unu xnopucibiM οποβομ (II) b xnopnCTOBOAOpoAHOŪ «ncnoTe, Heo5a3aTenbHO b npncyTCTBnn μηθρτηογο k peaxunn pacTBopuTe/ifl. npeAnoHTUTenbHO yKa3aHHoe BoccīaHOBneHne 13 LV 10452 npOBOflUTCfl ΠγΤΘΜ O'BnKMDUpOBaHUfl (I-C-l) C nOMOLUbtO ΠΘΓΚΟ OKUCAflfOiAeiiCH rpynnbi, τθκοη κβκ, HanpuMep, Ci-6anKnnoKCn-KapSoHunMeTunbHafl w τομυ nopoGHbie rpynnbi, η πθρθμθιιιμβθημ?) nonyweHHbix Ta κ n m o6pa30M nHTepMefluaTOB b ποαχοα^ιαθμ opraHunecKOM pacTBOpMTene, Hanp/Mep, AHMeTnncynb$OKCnfle, Ν,Ν-ΑΚΜΘΤΜΠφορΜΘΜΜΑβ M TOMy ΠΟΑθ6ΗΗΧ, B npUCyTCTBUU OCHOBaHHfl, TaKoro κ3κ, HanpuMep, Kap6oHaT, rnApoKap6oHaT, rnApooKMCb, anKOKCMA nnn aMHA msnoMHoro nnn tAenoHHO-3eMenbHoro MeTanna.
PeaKLiufl N-anKunupOBaHUfl (I-b-1) c noMOiubK) (XIV) μοχθτ 6biTb ΠρΟΒβΑΘΗΟ OČblHHbIM CnOCOČOM, HanpMMep, ΠγΤΘΜ nepeMeiAUBaHH^ pearnpyioiAMx βθιαθοτβ πρθαποητμτθπβηο npn oTHOCUTenbHO noBbiLLieHHbix TeMnepaTypax b cooTBeTCTByfou4eM OpraHunecKOM pacTBopuTene, τβκομ iok, HanpuMep, nonapHbm anpoTOHHbiū pacTBOpnīenb, HanpuMep, AHMeTnncynb$OKCMA, α^μθτμπΦορμθμμα h tomy noAoāHbie, b npncyTCTBnn οοοτβθτοτβυκ)ιαθγο οοηοβθηιίβ, τθκογο Kax, HanpuMep, γμαρμα, rnApooKucb, KapčoHaT nnn bmha ιαθποηηογο MeTanna.
CoeAUHeHUJi φορΜγη^ (I-a-1) ΜΟΓγτ 6biTb nonyHeHbi TaioKe πγτβΜ ΑΘΟγΠΒφγρΜρΟΒΘΗΜίΙ ΜΗΤΘρΜΘΑ^ΘΤΘ φΟρΜγΠΜ (XV) OČblHHbIM CnOCO-6ομ, HanpuMep, οδρθδοτκοκ nHTepMeA^aTa HHKeneM Penen b npncyTCTBnn cnHpTa, HanpuMep, STaHona, v\nv\ οδρθδοτκοΡί ncxoAHbix coeAHHeHHPi hmtphtom naipHB b npncyTCTBnn a30THcm «HcnoTbi b boahom cpeAe.
(xv)
> (I-a-1) R5 b (XV) aBnaeica Ci-6anKnnoM. 14
CoeflMHeHna <ļ>opMynbi (I) MOiyr 6biTb npeBpaiAeHbi τβιοκβ b ppyr ppyra, cneflya n3BecTHbiM b αθηηομ oSnacTn μθτοαμιομ npeBpameHUB cpyHK;i4MOHanbi-ibix rpynn. Ρβα τθκμχ MeiopnK 6ypyT onncaHbi HM>xe čonee πορροδΗΟ.
CoeAMHSHua $opMynbi (I), coAep^amne cno>KHO-30MpHyKD rpynny, MoryT 6biTb npeBpameHbi b cooTBeTCTByiomMe «McnoTbi, cneAyfl n3BecTHbiM b α^ηηομ očnacTn μθτοαμκθμ OMbineHna, HanpMMep, nyieM oāpačoTKM μοχοαηογο οοθαμηθημβ βοαημμ menoHHbiM μπμ BopHbiM KMCnOTHblM paCTBOpOM. M HaočopoT, KapčoKCunbHaa rpynna KMcnoTbi μοχθτ 6biTb npespameHa β οοοτβθτCTByiomyfO cnox<HO-3$npHyK) rpynny, cneflya M3BecTHbiM b α3ηηομ oCnacTM MeTOflUKaM ΒτβρΜφΜίοιίΜΜ. HanpuMep, KapSoHOBaa Kucnoia μο>κθτ 6biTb npeBpameHa b peaKunoHHoenocoČHoe npon3BOAHoe, κοτοροθ BnocneACTBMvi noABepraeTca ββθμμοαθμοτβμκ) c cooTBeTCTByK)LLļnM ariKai-ιοποΜ; μπμ nyieM B33M moabmctbm 5i Kap6oHOBOž KucnoTbi m anKaHona βμθοτθ c ποαχοαηιαμμ peareHTOM, CnOCOČHbIM 06pa30BblBaTb CHO>KHbie SCpMpbl, HanpMMep, AHUMKnOreKCMn-KapČOflMMMMAOM, 2-ΧΠ0ρ-1-ΜΘΤΜΠΠΜρΜΑΜΗΜΜ-Μ0Α^Α0Μ M TOMy'ΠΟΑΟδ-HblMM. Οοθαμηθημβ φopMynbι (I), cQAepx<amMe φopMMΠbHy^o rpynny, MoryT 6biTb npeBpameHbi b cooTBeTCTByroiuMM okcmm, cneAya μ3βθοτηβιμ b AaHHoiži oSnacTM μθτοαμκθμ, HanpMMep, οδρθδοτκοΜ μοχοαηογο ΟΟΘΑΜΗΘΗΜΒ TMApOKCMnaMMHOM ΜΠΜ βΓΟ ΟΟΠβΒΟΜ φΟΡΜΟΜ npM npMcoeAMHeHMM KMcnoTbi, b npMcyTCTBMM ocHOBaHMB, HanpMMep, γμαροοκμομ, KapčoHaTa μπμ TMApoKap6oHaTa menoHHoro Meianna.
CoeAMHeHMa φopMynbι (I), copepaoiuMe anKMHMnbHyto rpynny, MoryT 6biTb npeBpaiueHbi b cooTBeTCTBytomMe οοθαμηθημα, μμθφιαμθ anKeHMnbHyK) rpynny, nyieM KaTanMTMnecKoro γμαρμροβθημπ μοχοαηογο οοθαμηθημβ β ποαχοα^ιμθμ MHepTHOM κ peaKUMM pacTBOpMTene, COrnaCHO M3BeCTHblM Β A3HH0M OānaCTM ΜβΤ0ΑΜΚ3Μ Κ3Τ3ΠΜΤΜΗβΟΚΟΓΟ rMApMpOBaHMR. ΠΟΑΧΟΑΗΙΑΜΜΜ Κ3Τ3ΠΜ33Τ0ρ3ΜΜ 53ΒΠ53hOTCSB, HanpMMep, nannaflMM Ha ApesecHOM yrne, nnaTMHa Ha ApeeecHOM yrne m TOMy noAOČHbie.
CoeAMHeHMH φopMyπbι (I), b kotopom πΒΠΒβτοπ boaopoaom, MoryT 5biTb npeBpaLAeHbi β οοθαμηθημπ, b KOTopbix R^ πβππθτοπ ΗΜτρο- 15 LV 10452 rpynnoM, nyieM nepeMeujMBaHMa μοχοαηογο οοθαμηθημπ b pacTBOpe a30TMCT0M KMCHOTbl B npncyTCTBMM COOTBeTCTByKDLL(©M KMCHOTbl, HanpMMep, cepHOM KMcnoTbi, μπμ ομθομ yKcycHOM kmchotu m aHrnflpnfla yKcycHOM κμοποτμ. 5
CoeflUHeHMB $OpMynbl (I) HMetOT OCHOBHbie CBOMCTBa M, cneflOBaTenbHO, ohh MoryT 6biTb npespameHbi b mx TepaneBTMnecKM aKTMBHbie HSTOKCMHHbie coneBbie φορΜΒΐ npn npucoeflUHeHnn kuchot nyTeM očpačOTKM c cooTBeTCTByiomMMM κμοποτθμμ, tbkmmm Kax, 10 HanpMMep, HaopraHunecKue KucnoTbi, TaKne xax ranoMAOBOAOpOAHaa Kucnoīa, HanpMMep, χπορμοτοβοαοροαηθη, SpoMMCToeoAopoAHan m TOMy noAo6Hbie, m cepHaR κμοποτθ, a30THaa Kucnoīa, φοοφορΗθπ Kucnoīa m TOMy noflo5Hbie; μπμ οργθημηθοκμθ KucnoTbi, τθκμθ κθκ, HanpMMep, yKcycHaa, προπμοηοβθπ, γπμκοπθβθπ, μοποηηθπ, nMpOBMHorpaflHaa, 15 maBeneBaa, ManoHOBaa, BHTapHaa, φyMapoBaa, ManeMHOBaa, aānoHHaa, βμηηθπ, πμμοηηθπ, MeτaHcyπbφOHOBaπ, ^τaHcyπbφOHOBaa, 6eH30πcyπbφ0H0Baa, 4-MeτMπ6eH30πcyπbφoH0Bafl, ^MκπoΓeκcaHcyπbφaMMHOBaa, 2-0KCM6eH30MHan, 4-θμμηο-2-οκομ6θη-30MHaa m TOMy noAOČHbie KMcnoTbi. 20 Οοθαμηθημβ φopMynbι (I), coAepx<ainMe κμοπημ προτοΗ, ΜΟΓγτ 6biTb TaKx<e npeBpameHbi b mx TepanesTMHecKM aKTMBHbie HeiokCMHHbie μθτθππμηθοκμθ cohm μπμ aMMH-3aMeiueHHbie cohm nyieM οβρθβοτκΜ c noMOiubio cooiBercTByKDmMX οργθημηθοκμχ μπμ HeopraHMHecKMX ocHoeaHMM. 1/1 Ηθοδοροτ, μθτθππμηθοκθπ μπμ aMMH-3aMemeHHaa 25 coneBan 0opMa μοχθτ 6biTb npespamena b CBo6oflHyio KMcnoTHyio φopMy nyieM oāpačOTKM κμοποτομ. Ρβα μητθρμθαμθτοβ μ μοχοαημχ βθιαθοτβ b πρμβθαθηημχ Bbiiue
ΜΘΤΟΑΘΧ nOnyHeHMa ΠΒΠΠΙΟΤΟΗ M3BeCTHblMM COeAMHeHMnMM, KOTOpbie 30 MoryT čbiTb nonyneHbi no M3secTHbiM b ashhom oSnacTM μθτοαμκθμ nonyHeHMB yKa3aHHbix μπμ noAOČHbix οοθαμηθημμ, a HeKOTopbie MHTepMeAMaTbl ΠΒΠΠΙΟΤΟΠ HOBbIMM. PaA Τ3ΚΜΧ ΜΘΤΟΑΟΒ nOnyHeHMB 6ynyT onMcaHbi ημ>κθ 6onee ποαροΟηο. 16
HcxoflHbie eemecTBa 0opMynbi (II) υαο6ηο MoryT 6biTb nonyHeHbi no cneflyiomefi nocneflOBaienbHocTn peaKunii. ArībperuA Unu κθτοη 0opMynbi (XVI) BoccTaHaBnuBaeTCR c noMOiAbto cooTBeTCTByK)mero BoccīaHOBUTenB, TaKoro KaK, HanpuMep, ruppuA antOMUHun unu 6opa, unu KOMnneKCHbiPi γμαΡ^α, HanpuMep, nuTMManfOMUHMuruApuA, SopruApnA HaTpua, AaBasļ npu stom cnupT $opMynbi (XVII), u b AanbHeūiueM npeBpamaaTCR b 6eH3QTpua3on 0opMynbi (VI-c-1), cneAya μθτοα^κθ L4MKnn3ai4Mu, onucaHHoPi Bbuue ahr npeBpameHHa (XI) B (I-c-l). Ecrm >KenaTenbHO, nonyHeHHbiū τθκμμ o6pa30M 6eH30Tpna3on μοχθτ 6biTb Aanee npeBpaLAeH b c00TBeTCTByf0Luuū UHTepMeAuaT $opMynbi (VI-c-2), (VI-h-1) unu (VI-b-2), cneAya τθμ «e μθτοα^κθμ, onncam-ibiM απn npeBpaiAeHUR (I-c-l) b (I-c-2), (I-c-1) b (I-b-l) n (I-b-1) b (I-b-2). UeneBbie ncxoAHbie BGLuecTBa 0opMynbi (II), b κοτοροΰ W npsACTaB/iRGT yxoA«LAyto rpynny, MoryT 6biTb 3aieM nony<HeHbi nyTeM npeepameHMR oKcu-ocTaTKa 6eH30Tpna3onoB 0opMynbi (VI) b peaKI4M0HH0Cn0C06Hbllžl CnOXHbl5 30H p, CneAy^ CTaHAapTHbIM MeTOAUKaM, M3BecTHbiM b AaHHoii oānaciu. TanoreHUAbi b SonbīuMHCTBe cnynaeB nonyHaK)TCR nyieM B3auMOAeūcTBUR (VI) c cooTBeTCTByiomuM ranonAnpytoi4HM pearei-ιτοΜ, tbkum iok, HanpuMep, xnopucTbiu τμοηιίπ, cynb0ypnn xnopucTbm, naTi/ixnopncTbm φοοφορ, nRTMāpoMucTbm φοοφορ, φοοφορκη xnopncTbm, χπορμοτοβοαοροαηθα KucnoTa, āpoMMcroBOAOpOAHaR KucnoTa m TOMy noAo6Hbie. KorAa yxoAflinaR rpynna ηβπβθτοβ moauaom, to OHa npeAnoHTmenbHO nonyHaeTCR M3 cooTBeTCTByK)mero xnopwAa unu čpOMupa nyieM 38μθφθημη θτογο ranoreHa ūoaom. /ļpyrne peaKLļnoHHocnocoSHbie cno>KHbie 30npbi, TaKne xax MeīaHcynb0OHaTbi m 4-MeTnn6eH3oncyrib0OHaTbi nonyHaiOTCR nyTeM B3anMOAeiicTBHR cnupTa c cooTBeTCTBytomnM cynb0OHun-ranoreHMAOM, τθκιίμ iok, HanpMMep, MeiaHcynb0oHnnxnopnA u 4-MeTnn6eH3oncynb0OHnnxnopnA- LV 10452
B BbiuuenpuBefleHHOii οχθμθ peaKunn R1, R^-b n r2-c 3Bna(OTC5ļ T3KHMH >κθ, hto n paHee onncaHHbie.
KpoMe onncaHHOiži Bbiiue μθτοαμκκ, MHTepMeAnaTbi <#opMynbi (II), B KOTOpOlži R^ ΒΒΠΒΘΤΟΒ Ρ3ΑΜΚ3Π0Μ 0OpMyHbl R^-a, MOryT 6blTb nonyHeHbi TaioKe m3 cooTBeTCTByiomnM o6pa30M 3aMeiueHHoPi 6βΗ3θΡίΗθίί KucnoTbi 0opMynbi fXVĪH), cornacHO cneAyKDiueū nocne-AOBaTenbHOCTn peaKunii. Μητθρμθαμθτ 0opMynbi (XVIII) noAeepra-
eTCfl B3aHMOAeŪCTBHKD C COOTBeTCTByiOmHM 3MHH0M (ļ)OpMynbl (XIX), cneAya μ3βθο·ηημ b α^ηηοιϊ o6nacTi/i μθτοα^κβμ N-anKunupoBaHua n BnocneACTBun noABepraeTCB peaKunn βοοοτβηοβπθημβ HHTporpynnbi b aMHHorpynny, nonyMaa μητθρμθαμθτ cpopMynbi (XXI). Ποοπθαημμ npeBpaiuaeTCB b npon3BOAnoe 6eH30Tpna30na φopMyπbι (XXII), cornacHO noAo6HbiM μθτοακιομ unKnn3aunn, mto h onncaHHbie Bbiuie ΑΠΒ nonyHeHHfl (I-b). KapčoKCunbHaa <$yHKunoHanbHafl κμοποτηθβ rpynna 6eH30Tpna3ona (XXII) npeBpamaeTCB 3aieM b C00TBeTCTByx)LuyK) cnnpTOByio rpynny (VI-b-3) oābiHHbiM nyTeM, HanpuMep, nyieM BOCCTaHOBneHUH c noMombfO cooTBeTCTByioii4ero BOCCTaHOBUTenfl, HanpUMep, ΠΜΤΜΡίθΠΙΟΜΜΗΚίίΓΙ'ΙΑΡΗΑδ, B ΠΟΑΧΟΑ^ίΑΘΜ pacTBopuTene, HanpuMep, TeiparnApo$ypaHe. Ecnn AononHMTenbHO 18 xenaTenbHO, οοοτβθτοτβυκκακμ 3aMecTMTenb R1 μο>κθτ 6biTb ββθαθη πγτθΜ npeBpaiAeHUB oKCUMeTunbHoro ociaTKa $opMynbi (VI-b-3) b $opMnnbHbiM odaTOK c noMombK) noAxoAfliuero OKMcnmenn, HanpuMep, okucu MapraHpa (IV) μπμ nepMaHraHaTa «am-in, h peaKi4neū ποπγπθΗΗΟΓΟ t3khm o6pa30M anbAerHAa (XXIII) c anKunoM Meianna, HanpuMep, cpeHnnnnineM, nnn c κομππθκοημμ θπκμπομ Meianna nnn apunoM Meianna b ποαχοα^ηαθμ pacTBOpmene, HanpuMep, TeTparnApo$ypaHe. UeneBbie MmepMeAHaTbi cpopMynbi (Il-b) μο(7ϊ 6biTb nonyHeHbi 3θτβΜ πγτβΜ πρθβρθιαθημβ cnnpT0B0li <ļ>yHKt4HOHanbHoii rpynnbi (VI-b-3) mv\ (Vl-b) b cooTBeTCTByKDmyK) yxoAflU4yto rpynny, cneAyn očbiHHbiM μθτοαηκθμ, οπμοθηηημ Bbiiue.
MHTepMeAHaTbl (ļ)OpMynbl (IX) MOryT 6blTb CMHTe3HpOBaHbl c nOMOLLļbK) pa3nHHHblX MeTOAHK. HanpMMep, OHM MOryT 6blTb nonyHeHbi no cneAyioiAMM nocneAOBaienbHOCTBM peaKUHH. Μητθρμθακβτ 0opMynbi (XVII) npespamaercn b peaKLļHOHHoenocočHbm cno>KHbm 19 LV 10452 scfinp φορΜγπΜ (XXIV) n noflBepraeicfl peaKunn c 1H-a3onoM $opMynbi (III), tom xe μθτοα^κθ, hto h onncaHHbie Bbiiue απη ποπυηθημ^ (I), hcxoah n3 (II) μ (III), nonyHaa μητθρμθαμβτ $opMynbi (XI). Ποοπθαημ noABepraeTca peaKLļnn c cooTBeTCByioiAWM θμμηομ cf>opMynbi (XIX), cneAy« n3secTHbiM b ρ,άηηο\λ oOnacīn μθτοακκθμ N-apnnnpoBaHHFi n BnocneACTBHn noAsepraeicfl οτθηαθρτηομ peaKunn βοοοτβηοβπθημη HnTporpynnbi b aMHHorpynny, nonyHafl ueneBbie ncxoAHbie BemecTBa φopMyπbι (IX). (XVII) _^ NO. —f— A Ιΐχ ι· AVN^A (III)
NO. (XIX) R1-a-NH.
PeaKUM« N-an-KunuposaHun (XXIV)
,2-a
PeaKLinfl ___- ^ BOCCTaHOB- ΠΘΗΜΒ
.2-a NH.
B φopMyne (XXIV) wl m W μμθιοτ οπμοθηηηθ paHee 3Η8ηθημη. YnOMaHyTbie Bbiuje peaxuuu βοοοτβηοβπθημβ HHTporpynnbi b aMUHO-rpynny b 6onbLunHCTBe cnyMaeB npoBOABTca nyT9M nepeMemuBaHua ncxoflHbix coeAUHeHUM b cpepe, copep^ameiži boaopoa, b npncyrcTBnu cooTBeTCTByHDLnero Konuneciea cooTBeicTByK)iAero KaTann3aTOpa, TaKoro Kate, HanpuMep, nnaTUHa Ha ApesecHOM yrne, nannaAnii na ΑΡΘβθοηομ yrne, HUKenb Ρθηθα u TOMy noAoOHbie. KpOMe τογο, BoccTaHOBneHne μοχθτ 6biTb προβθαθηο TaioKe nyieM nepeMeiu'uBaHMH ΜΟΧΟΑΗΟΓΟ COeAMHeHMfl C CyΠbφHAOM HaTpMfl MJ1H AUTMOHMTOM HaTpUfl 20 (HaipneBan conb authohobom Kucnoibi) b ποαχοαβιμθμ pacTBOpmene, TaKOM KaK, HanpMMep, Bopa, MeiaHon, aiaHon w TOMy noflOāHbie.
Bo Bcex BbimenpnBefleHHbix μθτοα3χ ποπυηθημη, npOflyKTbi peaKunH MoryT 6biTb BbifleneHbi u3 peaKUMOHhom CMecu n, ecnu Heo6xopnMO, flononHMTenbHO OHntneHbi, cornacHO μθτοακιομ, b Ooribiuni-icTBe cnynaeB n3BecTHbiM b flaHHoii očnacTH.
McxoflHbie BemecTBa n nHTepMefluaTbi, ncnonb3yeMbie bo Bcex npeflixiecTByfomnx μθτοαμκθχ, pna κοτορυχ KOHKpeTHbie μθτοακκμ ΠΟΠγΗθΗΜΒ ΗΘ npeflCTaBn^lOTCB B flaHHOM OnncaHMkl, B 6onbUJMHCTBe cnynaeB ββπηιοτοβ n3BecTHbiMw h/μπμ MoryT 6biTb nonyHeHbi ece, cneAya n3BecTHbiM b flaHHOM oOnacTM μθτοαμιομ, onucaHHbiM b nmepaType ΑΠnonyMeHHB ποαο6ηβιχ n3BecTHbix coeAUHeHuft.
CoeAUHeHna $opMynbi (I) n HeKOTOpbie μητθρμθα^ιατβι b stom M3o5peieHnn MoryT MMeTb acuMMeipunecKM/ aTOM yrnepoAa no CBoeii CTpyKīype. 3tot xnpanbHbiiži ρθΗτρ μοχθτ HaxoAHTbca b R- m S-KOH0nrypaunM, npuneM 3Ta R- n S-cncieMa o6o3HaneHni/i ηβχοαμτοβ b cooTBeTCTBun c npaBunaMM, onncaHHbiMM Κθηομ, IdHronbAOM n flpenorOM fR.S. Cahn, C. Ingold and V. Prelog in Angew. Chem., Int. Ed. Engl.., 5,385,511 11966)1.
CoeAUHeHna $opMynbi (I), copepaoigne anKeHOBbiii οοτβτοκ, MoryT HaxoAmbCB b "E" nnn “Z" φορΜΘ, npuneM yi<a3aHHafl ’Έ"- m "Z"- cncTeMa o6o3HaneHnii nMeeT 3η3ηθηιίβ, onncaHHbie b J. Org. Chem., 35* 2849-2868 (1970).
HncTbie CT6peoxnMHHecKM n30MepHbie φορΜΜ οοθακηθηιίμ 3τογο n3o6pereHna ΜΟΓγτ 6biTb nonyneHbi πρμμθηθημθμ u3BecTHbix b a3hhom oānacTu μθτοα^κ. flnacTepeon30Mepbi MoryT 6biTb pa3AeneHbi 0n3HMecKHMn MeTOAaMu pa3AeneHWB, t3khmh κάκ ceneKTUBHaa KpncTannn3aunB n xpOMaTorpa$nwecKne μθτοαβι, HanpHMep, npoTUBOTOHHoro pacnpeAeneHUB; 3HaHTnoMspbi MoryT 6biTb pa3AeneHbi Apyr ot APyra c noMOiAbto οθπθκτκβηομ KpncTannn3auun nx AnaciepeoMepHbix coneft c οπτμηθοκιί aKTUBHbiMn KucnoiaMu, Ohm MoryT 6biTb nonyneHbi TaioKe H3 cooTBeTCTByfomnx nncTbix CTepeOXMMHseCKM H30MepHblX φορΜ ΟΟΟΤΒΘΤΟΤΒγΚ3ί111ΊΧ MCXOAHblX BemecTB, npu ycnoBnn, hto peaxuna προτθιοΘτ cTepeocneu^nnecKH. 21 LV 10452 Οοθαιίηθηκη φορΜγπι=ι (0, nx cpapMaLļSBTUHecKu npneMneMbie conu npn πρ^οοθαμηθημμ kuchot h B03M0>KHbie CTepeoxnMnnecKn M30MepHbie $opMbi μμθιότ BecbMa nHTepecHbie Φθρμθκοπογμηθοκκθ CBoiicTBa. Ohm nHru6npyK)T αθηοτβμθ Φθρμθητθ apoMaTa3bi, «OTOpbm «aTanu3npyeT o6pa30BaHne scTporeHOB H3 aHAporeHHbix CTepouflos y MneKonnTa(Oiiinx. OčmenpuHnTO, hto scTporeHbi cnHTe3npyK)Tcn H3 θηαρογθηοβ πγτθΜ noTepu C-19 aHryrmpHOM μθτμπβηοη rpynnbi h o6pa30BaHMB A-Konbua. 3th peaKunn Tpe6ytOT NAJļPH n Φθρμθητ apOMaTa3y. MHrn6npOBaHne o6pa30BaHH3 scīporeHa H3 aHflpocieHfluoHa n recTOcrepOHa μοχθτ 6biTb npOAeMOHCTpupOBaHO c noMOLAbfo mh Brnpo--μοπμτθημμ nnn hh βμβΟ'ΜΟπμτθημμ Ha μπθκοπμτ3Κ)ιαμχ, ī3khx Ka< coSaKu, Kpbicu, mulum m koiukm. Mh βμτρο-μηγμΘμροβθημθ θκτμβηοοτμ apoMaia3bi μοχθτ 6biTb npofleMOHCTpupOBaHO, HanpuMap, aHann30M ΑΘι/ictbmm οοθαμηθημη ηθοτοηιαθγο μ3ο6ρθτθημβ Ha npeBpameHne f1,23H>aHApocTeHAnoHa nnn [414Cļ-aHApocTeHAnoHa b acīpOH n acTpaAMon b npncyTCTBnn nnaueHTanbHbix mmkpocom ηθποβθκθ.
Mh βμβο-μηγμ6μροβ8ημθ θκτμβηοοτμ apoMaia3bi μο>κθτ 6biTb npoAeMOHCTpupoBaHO, HanpuMep, n3MepeHneM cynpeccnn (ποααβπθημβ) KOHueHTpaunu acTporeHa nna3Mbi y Kpbic-caMOK. MccneAOBaHue "Mh Bmpo-nHrn6npoBaHMfl aKTHBHOCTH apOMaTa3bi" m nccneAOBaHne ”Mh BHBO-nHrn6npoBaHna θκτμβηοοτμ apOMaia3bi”, onMcaHHbie ημ>κθ, noKa3biBaKDT 3CTporeH-nHrn6npyK)iAne cBOMCTBa οοθαμηθημμ φορΜγπbi (I) h ocHOBbiBatorca Ha 8biiueyKa3aHHbix npHHUnnax.
BcneACTBHe MX CnOCOČHOCTM HHrMāMpOBaTb 6MOCMHTe3 3CTpO-γθηοβ, οοθαμηθημη HacīoaiAero n3o6peieHna MoryT 6biTb ncnonb-30BaHbi npH πθηθημμ 3ciporeH-3aBncnMbix paccTpoiicTB, τθκμχ ιοκ, HanpHMep, paK rpypn (μοποηηομ >xene3bi), 3HAOMeTpno3 (AoāpoKasecTBeHHaa onyxonb χκθηοκομ ποποβομ οφθρΜ, οοο6θηηο M3TKH), 3HA0MeTpnanbHbm pax (pax οπμ3μοτομ ο6οποηκμ μθτκμ), nonnny3blpHaB (nOnHUHCTHTHaa) 6one3Hb ΒΜΗΗΜΚΘ, 6one3Hb rpyAH (μοποηηομ >xene3bi) b πθγκομ φορΜθ, γμηθκομθοτμπ (>κθηοκμθ rpyAM y My>KHHH), nenoMHOMa m TOMy noAOČHbie. 22
BnaroTBopHoe AefiCTBne hh™6htopob apoMaia3bi n/nnn aHTuacTporeHOB b sthx paccTpoiicTBax, οοο6θηηο npn neweHnn paxa rpyAn, onucbiBaeTCfl, HanpnMep, Cancer Research, 42, Suppl. 8: 3261s (1982). 5 (lpoTnBoonyxoneBafl aKTMBHOCTb, οοο6θηηο b 3CTporeH-3aBncn-
Mbix onyxonflx, μοχθτ 6biTb npofleMOHCTpupoBaHa m bubo, HanpnMep, MHflyi4npyeMbi(i c noMombio flMBA onyxonn μοπομηοη wene3bi y Kpbic--caMOK BUfla Sprague-Dawley.
Benfly ποπθ3ηοοτμ coeAnHeHnn HacToamero M3o6peieHna npn 10 πθηθημκ 3CTporeH-3aBMCMMbix paccTponcTB, ββπηθτοη οηθβηαηημ, hto HacToauiee n3o6peieHne npeAnaraei cnoco6 neHeHna ΜΠθκοηητβιο-U4nxca, cnrpaAaK)mux ot yKa3aHHbix 3CTporeH-3aBncnMbix paccTponcTB. yKa3aHHbiiži cnoco6 βκπκηθθτ οηοτθμηοθ Ha3HaHeHne MneKonuTato-liļuMCfi coeAUHeHna $opMynbi (I), ero φθρΜθΑβΒτηπΘΟκη πρηθΜπβΜΟη 15 conn npn npucoeAUHeHnn κηοποτ nnn bo3moxhož ciepeoxnMUMecKn Η30ΜθρΗ0η $OpMbl B ΚΟΠηΗΘΟΤΒΘ, 3φφθΚΤΗΒΗ0Μ HpM ΠβΗΘΗηη 30ΤρθΓβΗ- 3aBncnMbix pacTpcmcTB. B MacmocTn, npepnaraeica cnoco5 nHrn6npoBaHnfl cnHTe3a 3CTporeHa y μπθκοπμτθιοιαμχολ, KOTOpbin βκπκ)μ3θτ οκοτθμηοθ Ha3HaneHne (npneM) yKa3am-ibiM ΜΠθκοηητβιο-20 lummc?i οοθαηηθηηη φορΝ^ΠΜ (I) b KommecTBe, αοοτθτοηηομ απη MHrnānpoBaHua cnHTe3a scTporeHa, 6onee κοηκρθτηο, b κοπμηθοτβθ, AOCTaTOMHOM απα MHrn6npoBaHMfl apoMaīa3bi.
KpoMe BbimeyKa3aHHoro, HeKOTopbie οοθαιιηθηκη φopMyπbl (I) προ^ΒΠΑκίτ nHrn6npytomee AencTBne nnn 6ηοοηητθ3 TpoMČOKcaHa A2-25 BBMAy nx none3Hbix φapMaκonoΓHHecκnx cbohctb, οοθαηηθηηα HacTOHiuero n3o6peTeHnn MoryT 6biTb peuemnpoBaHbi b pa3HO-o6pa3Hbix φ3ρΜ3ΐ4θΒτηπθοκηχ φορΜβχ απα npneMa. HTOČbl npurOTOBHTb φ3ρΜ314ΘΒΤΙ/1ΜΘ0ΚΙ/1Θ Κ0ΜΠ03ηΐ4ηη ΗΘΟΤΟΗ-30 mēro μ3ο6ρθτθημα, 3φφθκτηΒΗ0θ KonnnecTBO οπρθαθπθηηογο coeAH-hshuh, b φορΜβ ocHoeaHUfl nnn coneeon φορΜθ npn npncoeAHHeHnn KucnoT, b KanecTBe θκτηΒΗοή cocTaBHon Hadu, CMeoinBaeTCH b OAHopoAHyto CMecb c φβρΜθρθΒτηΗθοκη npneMneMbiM ηοομτθπθμ, KOTOpbiii (HocnTenb) μο>κθτ npnHmviaTb uinpOKoe pa3H00čpa3ne φορΜ, 35 3aBnc?uAnx ot φορΜΗ npenapaTa, xenaTenbHoro απη npneMa. 8τη 23 LV 10452 cpapMaueBTMHecKMe κομπο3ηι4ηη ηθχοαητοη x<enaTenbHo b eflUHHHHO fl03MposaHHoii φορΜΘ, npuroflHOM, npeAnoMTUTenbHO, ΑΠΒ npneMa nepopanbHO, peKTanbHO, πθρκγτθΗΗΟ (wepe3 κο>κγ), ηπη πγτθΜ napeHTepanbHoii ΗΗνΘκρηη. HanpuMep, πρη ηρηΓΟτοΒΠβΗηη-κοΜπο-3MUMM B nepOparibHOM A03npOBaHHOH φορΜΘ ΜΟ)ΚΘΤ ČbITb npUMeHeHa ntočaa H3 očbiHHbix φθρΜθρθΒτηΗθοκηχ cpep, τβκηχ κθκ, HanpuMep, BOfla, γπμκοπμ, Macna, cnnpTbi n TOMy nopo^Hbie b cnynae nepopanbHbix χηρκηχ npenapaTOB, τθκκχ iok cycneHcnn, cnponbi, anniccnpu n pacTsopbi; nnn TBepAbie ηοομτθπμ, τθκηθ xax KpaxManbi, caxapa, KaonuH, CMa30HHbie Macna, CBB3yK)iAne, AS3nHTerpnpyiomne BeiuecTBa n TOMy noAo6Hbie b cnyMae ποροιυκοΒ, πμπκρπθμ, Kancyn n τθδπθτοκ. 1/13-3a nerKoern nx npneMa, Ta6nen<n n Kancynbi npepcTaBJinfOT Han6onee >KenaienbHyK3 nepopanbHyKD θαμηηηηο A03npOBaHHyK) φορΜγ, b cnynae KOTOpOH ΟΗΘΒΗΑΗΟ npMMeHfllOTCfl TBepAbie φβρΜθρθΒΤηΗΘΟΚΗΘ Hocmenn. JUnn napeHTepanbHbix KOMno3Hunn Hocmenb oObmno αοπχθη BKntoHaTb cTepnnbHyfo boay, no MeHbiaen Mepe b 3HaHHTenbH0n CTeneHn, xotsr Apyrne cociaBHbie nacin, HanpuMep, HTOčbi cnocočcTBOBaTb pacTBOpnMOCTn, MoryT 6biTb BKmoneHbi. HHbeunpyeMbie pacTBOpbi, HanpuMep, MoryT 6biTb npnroToeneHbi, b κοτορβιχ Hocmenb BKntonaeT φη3ηοπθΓΗΗβοκΗΗ padBOp rni0K03bi nnn CMecb φΐ43ΜθποΓηΗβοκοΓθ pacTBopa n pacTBopa rnK)K03bi. MHteLļnpyeMbie cycnencnn TaioKe MoryT 6biTb npnroToeneHbi, b cnynae KOTopbix MoryT 6biTb npnMeHeHbi cooTBeTCTByK)mne χηακηθ Ηοοητβπη, cycneHAnpyioinne BemecTBa n TOMy noAOČHbie. B κομπο3ηι4ηβχ, npnroAHbix απη nepKyTaHHoro bboab, Hocmenb Heo6a3aTenbHO BKniOHaeT eemecTBO, noBbiiuatomee npoHnKHoeeHne, n/nnn cooTBeTCTByiomnn cManneaienb, Heo6fl3aienbHO CMemnBaeMbie c ποΑΧΟΑ^ίΑΜΜΜ Ao6aBKaMn πιοδοη npnpOAbi b He3HaHmenbHbix KonnHecTBax, KOTopbie (AOāaBKn) ηθ Bbi3biBaiOT 3HaHHTenbHoro speAHoro B03AeiicTBnn Ha κοχ<γ. ΥιοΒθηηβιθ AOāaBKn MoryT cnocočcTBOBaTb npoHnKHOBeHne nepe3 κο>κγ n/nnn MoryT 6biTb none3HbiMn pnn npnroTOBneHnfl ueneBbix κομπο3ηι4ηη. 3τη κ0ΜΠ03ηρηη MoryT 6biTb npnHBTbi pa3nnHHbiMn πγτ^Μη, HanpnMep, b Bnpe TpaHCAepManbHoro 6pnKeTa, b Bnpe ηρηΜΟπκη (a spot-on), b snps Ma3n. 24 Οοο6θηηο >κθπ3τθπι>ηο peuenTupoBaTb BbiweynoMBHyTbie φθρΜθίΙΘΒΤΜΗΘΟΚΙΙΘ K0Mn03HLļMH B eflMHMHHO fl03Mp0BaHH0M φΟρΜΘ flHfl ο6πθγμ©ημ3 npnevia n oahopoahoctm fl03MpOBKM. Eahhmhho A03npoBaHHafl φορΜ3, KOTopaa ncnonb3yeTCB b onncaHHM m nyHKTax φopMyπbι n3o6peieHna, othocmtcb k Φμ3μηθοκμ AMCKpeTHbiM eflUHnuaM, npurOflHblM B ΒΜΑΘ eAHHMHHblX A03MpOBOK, ΓφΜΗΘΜ Ka>KAafl eAHHUl^a coAep>KMT 3apaHee οπρθαθπθηηοθ κοπμηθοτβο θκτμβηομ οοοτθβηομ MacTM, paccMmaHHOM Ha co3AaHne xenaeMoro TepaneBTunecKoro ΑΘμοτβμη βμθοτθ c TpeāyeMbiM Φ3ΡΜ3Ι4Θβτμηθοκμμ ηοομτθπθμ. npMMGpaMM Τ3ΚΜΧ ΘΑ^ΗΜΗΗΟ A03MpOBaHHblX φθρΜ ΑΒΠΒΚΠΌΒ ΤθδΠθΤΚΜ (BKmoHaa TaSneTKM c 3apy6xaMn kinn noKpbiTbie TačneTKH), Kancynbi, ΠΜΠΙΟΓΗΊ, naKeTMKH C nOpOLUKaMM, SpUKeTbl, MHbei4MpyeMbie paCTBOpbl ΙΊ cycneHCMn, ποπηβιθ donosbie πο>κκμ, nonHbie načiHbie ποχκμ m TOMy noAoāHbie, n OTAenbHbie MHoroo6pa3M?i mx.
CneLinanncT b AaHHoii očnacTn npn πθηθημμ 3CTporeH-3aBncnMbix paCCTpOMCTB ΜΟ>ΚΘΤ ΠΘΓΚΟ OnpeAenmb 3φφθΚΤΜΒΗ0θ ΚΟΠΜΗΘΟΤΒΟ H3 pe3ynbTaTOB μοπητθημμ, npeAdaBneHHbix ημ>κθ. B o6iumx nepTax npeAnonaraeTCfl, mto θΦΦθκτμβηοθ κοπζηθοτβο αοπ>κηο cocTaBnaTb οτ 0,0001 μγ/κγ αο 10 μγ/κγ >κμβογο sēca, n Sonee npeAncmuTenbHO οτ 0,001 μγ/κγ αο 0,5 μγ/κγ χμβογο Beca.
CneAytOLqne npuMepbi npeACTaBnatOTCfl απβ ποηοηθηιιβ, a ηθ ana τογο, ητο6βι orpaHUHMBaTb oābeM μ3ο6ρθτθημβ. Ecnn ηθ yKa3aHO oco6o, ece nacTH b ashhom onncaHun ββπαιοτοβ βθοοβημμ, 25 LV 10452 9KcnepnMeHTanbHaa sačib
A. flonVHeHHe HHT6PM6flMaT0B
IlpuMep 1 a) PacTBop 14 sacieti (4-χπορ-3-ΗκτροφβΗκπ)(4-φτορφθ-Hnn)MeiaHOHa b 69 saciax 2-nponaHaMHHa nepeMeiunBatOT b TeseHne hohh npn TeMnepaiype KnneHHa c o6paTHbiM xonoflnnbHHKOM. PeaKunoHHyio CMecb BbinuBaiOT b Bopy. Bbinapaiomnti ocaflOK οτφκηΒΤ-poBbisatoT n npOMbiBafOT BOfloti, BbicyLunBafOT, φnπbτpyκ)τ n BbinapuBaiOT, nonysan 14,7 sacieti (97,2 %) (4-φτορφ0Ηΐ^π)'[4-[(1--ΜΘΤΙΊΠ3ΤΙΊΠ)-3ΜΙΊΗθ]-3-ΗΙΊΤρθφθΗΙΊΠ]·ΜΘΤ3ΗΟΗ3 B BMfle ΟΟΤ3ΤΚ3 (HHTep-Mepnai 1). 6) PacTBop 14/saCTeti (4-φΤ0ρφθΗΜΠ)-[4-[(1-Μ8ΤΜΠ3ΤΜΠ)-3Μ11Η0> -3*ΗΜΤρθφΘΗΜΠ 1*ΜΘΤ3Η0Η3 B 120 SaCTBX STaHOna rHflpnpyKDT npn AaBneHnn 2.10$ fla c noMoiiļbio 3 sacieti Kaiann3aiopa - Hnxena PeHea. Ilocne nornomeHua Bbisncnet-moro KonnsecTBa Bopopofla, xaiann3aiop cn^mībTpOBbiBaioT Hap AHaTOMOBoti 3eMneti n φι^τρθτ BbinapnBaiOT, nonysaa 12,3 sacieti (92,1 %) f3-aMMHO-4-f(l-Meinn3Tnn)-aMHHO> •φθΗΙΊΠ 1·(4*φΤ0ρφθΗΜΠ)*ΜβΤ3Η0Η3 B ΒΜββ OCTaTKa (ΜΗΤβρΜΘΑΜΘΤ 2). b) K nepeMeujMBaeMOMy n oxnaxAaeMOMy (5 °C) pacTBOpy 12,3 sacieti f3-3MHHO*4-f( 1 -ΜβΤΜΠ3ΤΜΠ)*3ΜΜΗ0 Τ-φβΗΜΠ 1·(4-φΤ0ρφθΗΜΠ)-ΜβΤ3-HOHa b 150 sacTBx 6 N pacieopa conaHoti xncnoibi Ao6aBnaiOT 4,7 sacieti Hmpma Haipnn. riocne 3aBepiueHna Ao6aBnei-mfl, nepeMe-ujMBaHue npoAonxatoT b Tesem/ie 1 saca ripu κομηθτηομ TeMnepaiype. CMecb o6pa6aTbiBa»OT pacTBopoM KapāoHaia Kanna ao pH 9 n npc>AyKT peaKunn 3KCTparnpyK)T ΑκχπορΜβτθΗΟΜ. 3xcTpaxT BbicyujnBatOT, φnπbτpy^oτ n BbinapnBatOT, nonysaa 17 sacieti (100 %) (4-φτορφβΗκπ)--fl-(l-Meinn3Tnn)-1H'5eH30Tpna3on-5-nnļ-MeiaHOHa b enpe ociaTKa (nmepMeAnaT 3).
r) K nepeMeiunBaeMOMy padBopy 17 sacieti (4-φτορφβΗΐΊπ)-[1--(l-Meinn3Tnn)-1H-6eH30Tpna3on-5-nnļ-MeiaHOHa b 80 saciax siaHona AOČaBnaKDT 3,4 sacieti SoprnApnAa Haipna. Ilocne nepeMeiunBaHnn b TeseHne 1 saca npn KOMHaiHoti TeMnepaiype peaKLļnoHHyto CMecb Hetiipann3yfOT ao pH 7. PeaxLļnoHHyto CMecb KOHueHTpnpyK)T n npOAyxT 26 peaKLļMM 3KCTparnpyioT θτμπθρθτθτομ. 3KCTpaKT BbicyujMBaiOT, 0nnbipyioT u BbinapneaiOT. Οοτθτοκ οημιμθιοτ c noMOiflbto κοποηοηηομ xpOMaiorpaOnn Hafl cnnm<arenbio, ncnonb3ya CMecb αμχπορμθτθηθ m μθτθηοπθ (98 : 2 no oāteMy) b KanecTBe antoeHTa. Hncībie $paxunn cočupatOT μ 3πκ3Θητ BbinapMBaKDT, nonynafl 10,7 MacTeii (62,5 %) a-(4--φτορφ0Ημιπ)·1-(1*ΜΘΤΜΠ3τ/η)-1 H-6eH30Tpna3on-5-MeiaHona b Bufle ocTaTKa (μητθρμθαμθτ 4). noflOČHbiM o6pa30M nonynaK)T τβιοκβ : 1-ρΚΚΠ0Πρ0ΠΙ4Π-α-(4-φΤ0ρφθΗΜΠ)-1Η-6θΗ30ΤρΜ330Π-5-ΜΘΤ3Η0Π B BHfle ociaTKa (nHTepMefluai 5); u 1-Ι4ΜΚΠΟΓΘΚ0ΜΠ-α·(4·φΤθρφθΗΜΠ)-1Η-6θΗ3ΟΤρΜ33ΟΠ-5-ΜΘΤ3ΗΟΠ B BUfle ociaTKa (nHTepMefluaī 6). (IpuMep 2 а) CMecb 50 Māciet 4-xnop-3-HHTpo6eH30MHoPi KucnoTbi m 222 nacTeii 1-6yiaHaMHHa nepeMeuunBaiOT β τθηθημθ 3 nacoB npn τθμπθ-paType «nneHnn c oSpaTHbiM xonoflunbHu«OM. Ilocne oxnaxfleHun n BbinapuBaHMB n36biTKa 1-6yTkaHaMHHa, peaxLļMOHHyK) CMecb noflKHcnntOT 2 N pacTBopOM cepHOū «ncnoTbi po pH 1. BbinaflaioinkM b ocaflOK npOflyKT peaKunn οτΦμπβτροβηβθιοτ u BbicyiunBaHDT, nonynaa 59 nacTert (100 %) 4-(5yinnaMMHo)-3*HHTpo6eH3oiiHOw KucnoTbi (μητθρμθα^βτ 7). б) CMecb 50 nacTefi 4-(6yTMnaMHHo)-3-HMTpo6eH3oiiHOM KucnoTbi n 240 HacTeū μθτθηοπθ rnflpnpyfOT b annapaie llappa npn αθβπθημμ 3.105 na n npn κομηθτηομ TeMnepaType c noivioiflbK) 40 nacieiži Kaiann3aTopa - ημκθπα Ρθηθβ · β βτΜοοφθρθ a30Ta. ilocne πογποιαθημβ BbiHncneHHoro KonunecTBa BOflOpofla, Kaiann3aTop οτφΐ/ΐπΒτροΒ^ΒθΚ)τ Hafl fluaTOMOBOū 3eMneiži n φι-ιπΒτρθτ BbinapuBafOT flocyxa, nonyHan 43,7 nacTeiži (100 7r.) 3-3μμηο-4-^τμπ3μκηο)-6θη30ι/ι-ηοι1 KucnoTbi; τ.ππ. 158 °C (MHTepMefluaT 8). β) K nepeMeujMBaeMOM m oxna>KflaeMoii CMecu 43,7 nacieii 3-aMMH0-4-(6yTnnaMMH0)-6eH30iiH0ki KucnoTbi m 200 nacTeii 6 N pacT-eopa consHoii KucnoTbi no xannnM floāaBnniOT paCTBop 22 nacieii HmpMTa HaTpMB b ManoM KonunecTBe BOflbi. Ilocne 3aBepweHnn flo6aBneHnn peaxLļnoHHyK) CMecb nepeMemuBafOT β τθηθημθ 4 nacoB npw 10-20 °C. flpoflyKT peaxuwu οτφι^τροΒ^Β8Κ5τ, npOMbrnatOT c 27 LV 10452 noMouļbto 30 nācies BOflbi n KpncTannn3yiOT U3 CMecu aueTOHa m STunaueTara, ΠροΑγκτ peaKunu οτφΜΠΒτροΒΒΐΒ8Κ)τ n BbicyiunBaK)T, nonynaa 33,3 HacTeii (72,6 %) 1-6yTnn-1H-6eH30Tpna30n-5-Kap60H0B0ii KucnoTbi; τ.ππ. 192,5 °C (μητθρμθαμβτ 9). r) K nepeMemuBaeMoii n oxna>KAaeMOM (0 °C) cycneH3nu 23,4 MacTeii nmniiamoMMHMiirMApnAa b 270 Hacrax cyxoro TeTparnApo-φγρ3Η3 AoāasnaiOT no nopunaM 45 MacTeiū 1-6yTnn-1H-6eH30Tpwa3on-5--KapčoHOBOii KucnoTbi. (locne 3aBepweHna αο63βπθηκα, nepeMemn-BaHue προΑοηχοιοτ b TeneHne 1 naca npn 0 °C. PeaKL|noHHyK) CMecb rnAponn3yfOT c noMombKD 50 MacTeii BOAbi. CoAepx<MMoe φι^τργιοτ n npOMbiBatOT CMecbto α^χπορμθτθηθ m MeiaHona (90 : 10 no o6beMy). OunbTpaT BbinapnsatOT Aocyxa v\ οοτθτοκ οημιαθιοτ c noMombto κοποΗΟΗΗΟϋ χροΜθτοΓρθφΐΊΜ H3A cnnwKarenb(o, ncnonb3ya CMecb AnxnopMeTaHa m MeiaHona (98 : 2 no o6teMy) b KanecTse smoema. HncTbie φρ3ΚΑ^Μ coānpaioT m arnoem BbinapneaiOT, nonyMaa 18 sacieti (42,7 %) 1-6yTnn-1H-6eH30Tpna3on-5-MeTaHona b βμαθ μθοπβημοτογο ocīaTKa (nHTepMeAnaT 10). floAOČHbiM o6pa30M nonynaK)T Taxxe :
No HHTep- MeflM- aTa R2 P OcHOBaHue/conb T. nn. (°C) 11 -CH3 7 ocHOBaHue 106 12 -(CH2)3-CH3 7 ocHOsaHue odaTOK 13 -(CH2)3-CH3 6 ocHOBaHue 0CT3T0K 14 -CH3 4 ocHOBaHue ociaTOK 15 -CH3 5 οοηοβθημθ 0CT3T0K 16 -CH3 6 ocHOBaHue Macno 17 -(CH2)3-CH3 _ 4 ocHOBaHue ociaTOK 28 B BbnuenpuBefleHHOM η cneflytomnx Ta6nnuax SKcnepnMeHTanbHon MacTn ”P” npeflCTaBnaeT ποποχθηηθ 33μθιι1θημβ Ha 6θη30Πβηομ ociaTKe 6eH30Tpna3onbHoro reiapoLļUKna. npuMep 3 а) K nepeMeiuMBaeMoPi CMecn 7,4 HacTeii nepMaHraHaia Kanna, 0,6 HacTen 2-(2-μθτοκομ3τοκοη)-Ν,Ν-6μο-[2-(2-μθτοκοι3τοκοη)-3τηπ}· 3ϊ3η3μμη3 n 130 HacTen flnxnopMeTaHa no KannaM flo6aBnaiOT pacTBop 7,6 HacTen ΐ-ΜΘτηπ-ΙH-6eH30Tpna3on-7-MeTaHona b flnxnopMeiaHe. Ποοπθ 3aBepiueHna fločaBneHna, nepeMeiunsanne προβοπχοιοτ b τθηθηι/ιθ 2 sacoB. PeaKunoHHyK) CMecb $nnbTpytOT Hafl αηθτομοβοη 3θΜΠΘή n npoMbiBatOT flnxnopMeTaHOM. OpraHnnecKnn cnoPi npOMbieaiOT 30-K) ηθοτβμη 2 N pacTBopa οοπβηοη KncnOTbi, a 3aieM pacTBOpOM KapčoHaTa HaTpnn, BbicyujnBaK)T1 cf>nribTpyK>T n BbinapnsaiOT. OciaTOK OHmuaHDT c noMombio κοποηοηηοη χροΜθτοΓρθφηη Hafl cnnnKarenbK), ncnonb3ya CMecb flnxnopMeiaHa n MeTaHona (98 : 2 no o6beMy) b κθηθοτβθ antoeHTa. HncTbie cppaKunn coānpaiOT n 3π>οθητ BbinapneatoT, nonynaa 3,5 nacTen (46,6 %) 1-Meinn-1H-6eH30Tpna3on-7--KapčoKcanbflernfla; t. nn. 126 °C (nHTepMeflnaT 18). б) K nepeMemnBaeMOMy n KnnnmeMy c oSpaTHbiivj. χοπο-flnnbHnKOM peaKTHBy ΓρηΗ-bapa, 3apaHee nonyHeHHOMy ηοχο,ηη n3 8,15 nacTeiži 1-6ροΜ-3-φτορ6θΗ3θΠ8, 1,2 nacTen MarHna n Manoro KonnnecTBa flnsTnnoBoro 3$npa, floSaBnafOT pacTBop 5 nacien 1-Μθτηη--1 H-6eH30Tpna3on-7-Kap6oKcanbflernfla b 80 Haciax flnamnoBoro 3$npa. flocne nepeMeiunBaHna b τθηθημθ 2 nacoB npn KOMHaTHon TeMnepaType peaKLinoHHyto CMecb BbinuBatOT b 300 ηθοτβχ BOflbi. npoflyKT peaKpnn 3KCTparnpyioT Tpnxflbi c noMOiflbto 65 nacTen flnxnopMeTaHa. CoeflnHeHHbie SKCTpaKTbi Bb^iunBaiOT, φnnbτpy^oτ n BbinapnBaioT. OciaTOK nepeMeiunsaiOT β τθηθηιιθ 15 mhHyT b 100 nacTax BOflbi n 13 wacTax neTponenHoro 3φηρθ npn κομηθτηοΛ TeMnepaType. npoflyKT peaKflnn οτφηπΒτροΒΒΐΒ3Κ)τ n BbicywnBaK:T, nonynaa 7,6 nacien (95,2 %) α-(3-φτορφθΗηπ)-1-Μθτηπ-1Η-6θΗ3θ· Tpna3on-7-MeTaHona; t, nn. 152 °C (nHTepMeflnaT 19). 29LV 10452 flOAOČHbiM o6pa30M ποπγΜβιοτ TaKxe :
R I N 2
nN II - N
No m- τβρ- ΜΘ- flU- aTa R1 R2 P OCHOBa- Hne/conb T.nn. (°C) 20 φθΗΙΊΠ -(CH2)3'CH3 7 ocHoaaHue 125 21 φθΗΙΊΠ -ch3 7 ocHOBaHue 0CT3T0K 22 H3C- -CH3 7 0CH0B3HHS 126 23 H3C- -(CH2)3-CH3 7 ocHOBaHue ocTaTOK 24 3-C1-C6H4- -(CH2)3-CH3 7 ocHOBaHue 112,0 25 4-C1-C6H4- -(CH2)3-CH3 6 οοηοβθημθ odaTOK 26 4-F-C6H4- -(CH2)3-OH3 6 ocHOBaHue 0CT3T0K 27 3-F-C6H4- -(CH2)3-CH3 6 ocHOBaHue OdaTOK 28 3-F-C6H4- -(CH2)3-CH3 7 ocHoeaHMe 116 29 3-C1-C6H4- -ch3 7 ocHOBaHue 128 30 3-C1-C6H4- -(CH2)3-CH3 6 ocHOBaHue OdaTOK 31 3-F-C6H4- -ch3 5 ocHOBaHue OdaTOK 32 CH3-(CH2)2- -ch3 5 ocHOBaHue OdaTOK 33 3-CI-C6H4- -ch3 5 ocHOBaHue OdaTOK 34 3-CI-C6H4- -CH3 6 ocHOBaHue OdaTOK 35 4-F-C6H4- -ch3 6 ocHOBaHue OdaTOK 36 4-CI-C6H4- -ch3 6 ocHOBaHue OdaTOK 37 CH3-(CH2)2· -ch3 6 ocHOBaHue OdaTOK 38 3-Br-C6H4- -ch3 5 ocHOBaHue Macno 39 3-F-C6H4- -ch3 6 ocHOBaHue 0CT3T0K 40 3-CI-C6H4- -(CH2)3-CH3 5 ocHoeaHMe OdaTOK 30
No MH- Tep- ΜΘ- J0M- aia Rl R2 P OcHOBa- Hne/conb Τ.ΠΠ. (°C) 41 H3C- -(CH2)3-CH3 5 ocHOBamie ociaTOK 42 H3C- -CH3 6 ocHOBaHue 0CT3T0K 43 3-F-C6H4- -(CH2)3-CH3 5 ocHOBaHue ociaTOK 44 4-F-C6H4- -(CH2)3-CH3 5 ocHOBaHue 82 45 4-CI-C6H4- -(CH2)3-CH3 5 OCHOBaHUe 0CT3T0K 46 4-Br-C6H4- -(CH2)3-CH3 5 ocHOBaHue 0CT3T0K 47 4-C1-C6H4- -CH3 5 ocHOBaHue 0CT3T0K 48 3-Br-C6H4- -CH3 6 ocHOBaHue 0CT3T0K 49 4-Br-C6H4- -CH3 6 ocHOBaHue 0CT3T0K 50 4-Br- C6H4- -CH3 5 ocHOBaHue 0CT3T0K 51 4-CF3-C6H4- -CH3 6 ocHOBaHue ociaTOK 52 2-CI-C6H4- -CH3 6 ocHOBaHue ociaTOK 53 4-CH3-C6H4- -CH3 6 ocHOBaHue 0CT3T0K 54 2-Η3φΤ3ΠΜΗΜΠ -CH3 6 OCHOBaHMB ociaTOK 55 4-CH30-C6H4- -CH3 6 ocHOBaHue ociaTOK μ a-[4-(4,5-flnrnflpo-4,4-AMMeTnn-2-OKCoa3onnn)-$eHnn]-1 -Meinn--1 H-6eH30Tpna3on-6-MeTaHon b BUfle ociaTKa (nHTapMefluaT 56). 5 flpuMep 4 a) CMecb 36,5 MacrreM 1-6yTnn-1H-6eH30Tpna3on-5-MeTaHbna, 35 nacTeii okucu MapraHpa (IV) n 390 nacTetf flnxnopM8TaHa πθρθΜΘΐιΐΜΒ3Κ3τ b τθηθημθ 12 wacos npn κομηθτηοη TeMnepaType. 0«ncb MapraHua (IV) οτφκπΒτροΒΒίΒβίΟτ Hap α^θτομοβομ 3ΘΜΠΘίί, a 10 Apyryto nacTb n3 35 sacieti okucu MapraHua (IV) Ao6aBnafOT k $nnbTpaiy. ilocne nepeMeLUMBaHMB b τθηθηιίθ 12 sacoB npn κομηθτηομ TeMnepaType, coAep>KHMoe 0nnbTpyfOT n 0nnbTpaT BbinapuBafOT. OdaTOK OHULuaKDT c noMombfo KonoHOHHoti χροΜθ-τοτρθφΜΜ H3A cunuKarenbfo, ncnorib3ya AnxnopMeTaH b κθηθοτβθ amoema. HncTbie 15 φρεικunn cočupatOT w θπιοθητ BbinapuBatoT, nonysaa 15,3 sacieti (42,2 31 LV 10452 %) 1-6yTun-1H-6eH30Tpna30n-5-Kap60KcanbAeruAa b βκαθ ociaTKa (ιιητθρμθαμθτ 57). 6) K nepeMemnBaeMOMy n oxna>KAaeMOMy (-78 °C) pacTBOpy 7,2 sacieti 3-5poMīwo$eHa b 70 saciax AH3TunoBoro acfinpa AoSaBnatoT 30 sacieti 1,6 M padsopa 1-6yTunnmnfl b γθκοθηθ. (locne nepe-MeuunBaHMB b τθηθη^θ 20 MMHyT npn aioti HH3Koti TeMnepaiype, pacTBop 6 sacieti 1-6yTun-1H-6eH30Tpna3on-5-Kap6oKcanbAeruAa b AMSTunoBOM 3$npe αο68βπβκ)τ κ npeAbiAymeti cMecn. PeaKunoHHyto CMecb nepeMeamBaioT b TeseHue 2 sacoB npn -78 ~ -40 °C. CoAepx<nMoe BbinuBatci b 200 sacieti neproti BOAbi n npoAyKT peaKunn 3KCTparnpyioT Tpn>KAbi c noMoiAbfo 56 sacieti AnsTunoBoro strupa. OčbeAUHeHHbie 3KCTpa«Tbi BbicyujnBaK)T, iļmnbTpyfOT m BbinapuBaioT. OciaioK osuinatOT c noMOuibio κοποι-iosHOti xpOMa-Torpacpun H3A cunuKarenbto, ucnonb3ya CMecb αμχπορμθτθηθ n MeiaHona (98 : 2 no o6beiviy) b KasecTBe smoema. HucTbie cppaicuuM co6npaiOT μ 3πκ)θητ BbinapuBatOT. OciaioK Kpnciannu3yK)T H3 Ann3onponnnoBoro scpupa. npOAyKT peaKLļnn oTCļDunbTpoBbiBaioT n BbicyiiiHBaKDT, nonysaa 5 sacieti (58,9 %) 1-6yTnn-a-(3-TMeHMn)-1H--6eH30Tpna3on-5-MeiaHon; τ. nn. 80 °C (nHTepMeAnai 58). IIOAOČHbiM o6pa30M nonysaiOT Taxxe : 1-6yTMn-a-(2-TneHun)-1H-6eH30Tpi/ia3on-5-MeTai-ion b βμαθ ociai-xa (nHTepMeAnai 59); 1-Meinn-a-(2-TneHnn)-1H-6eH30Tpna3on-6-MeTaHon b bua© ociaT-xa (nHTepMeAnai 60); u 1-Meinn-a-(3-TneHnn)-1H-6eH30Tpna3on-6-MeiaHon b bha® οοτθτ-Ka (nHiepMeAnai 61). npMMep 5 a) K nepeMeiiinBaeMoti CMecu 496 sacieti xnopncioro θπκιμμημλ b 900 sadax 6eH3ona no ιοππαμ αο6θβπαιοτ pacTBop 256 sacieti xnopndoro 4-0Top-3-HHTpo6eH3ouna b 225 saciax 6eH3ona npn + 10 °C. riocne 3aBepiueHM?i AoSaBneHus, nepeMeuinBai-Me προΑοηχοιοτ CHasana b Tesem-ie 1,5 sacoe b neA^Hoti 6aHe, a 3aieM b TeseHue 8 sacos npn KOMHaTHoti TeMnepaiype. CMecb HarpeeaiOT ao 60 °C, oxnax<AatoT 38ηοβο m BbinneaiOT b pa3Apo6neHHbiti neA h 180 sacieti 32 Κ0ΗΙ_1ΘΗΤρΜρ0Β3ΗΗ0Μ COflflHOM KMCflOTbl. Pa3AeneHHblPi ΟρΓΘΗΜΗΘΟΚΜΜ cnoPi BbicyLunBaK)T, φnπbτpyκ)τ m KOHneHTpnpytOT. KoHueHTpaT pacTBOpaioT b 2100 ηθοτηχ Ann3onponnnoBoro 3$npa, pacTeop o6pa6aibiBaK5T ακθτομοβοΡι 3eMnePi μ θκτμβμροβθηημμ ApeeecHbiM yrneM. ilocne $nnbTpaunn cfiunbTpaT KOHueHTpnpyK>T. KpncTannn3y-(omniicB npoAyKT peaKLļnn OT0nnbTpoBbiBaiOT n BbicyujMBaK)T, nonyMaa 223 nacTePi (73 %) (4-$TOp-3-Hmpo$eHnn)$eHnnMeiaHOHa; τ. nn. 59 °C (nHTepMeAnai 62). 6) K oxna>KAaeMOMy (πθα^ηομ 6aHePi) pacTBopy 24,5 nacTePi (4-$Top-3-HMTpo$eHnn)$eHnnMeTaHOHa b 120 HacTax μθτθηοπθ Αο53βπβκ)τ no HacTBM 1,5 naciePi āopruApMAa HaTpua. ilocne 3aBepiueHnn AoāaBneHnn nepeMemuBaHue npoAonx<atoT b τθηθημθ 15 MHHyT npH 0 °C. PacTBOp 3 nacTePi yi<cycH0ii KucnoTbi b 25 Hacrnx BOAbi AOčaBnnkDT no ιοππημ κ CMecn. ilocne 3asepLueHnn AOāaBneHnn CMecb KOHueHTpnpyfOT. K ociaTKy αο63βπβκ)τ BOAy n npoAyKT peaKLinn 3KCTparnpyK)T AuxnopMeTaHOM. 3KCTpaKT BbicyujMBaK)T, $nnbTpytoT m KOHL\eHTpnpyiOT1 nonynan 25,1 nacTePi (100 %) 4-φτορ-3-ΗΜτρο-α-—φθΗΜΠ6θΗ30ΠΜΘΤ3Η0Π B BV\Re MacnOO6pa3H0lO 0CT3TKa (ΚΗΤθρΜΘΑΜΑΤ 63). b) CMecb 25 nacTePi 4-φτορ-3-ΗΜτρο-α-φβΗκη6βΗ3θΠΜθΤ3ΗθΠ3, 20 Madei* rnApa3MH MOHornApaia m 80 naciePi aiaHona nepeMeiuMBatOT b TeneHne 1,5 nacoB npn TeMnepaiype κμπθημα c oSpaTHbiM xonoAnnbHMKOM. riocne οχπθχαθημα ΑΟδθΒπηιοτ 20 naciePi 10 N pacTBopa connHoPi KucnoTbi. Ilocne KOHueHTpupoBaHun, οστθτοκ npoMbiBaKiT Aaa>KAbi c noMombio 50 nacTePi BOAbi m pacTBOpaiOT b pacTBope 300 nacTePi MeiaHona (10 %) b χποροφορΜβ. OpraHunecKuPi cnoPi BbicyujMBatOT, φwπbτpyκ)τ m KOHueHTpnpyioT, nonyMan 23,8 nacTePi (98,6 %) 1-OKCM-a^eHnn-1H-6eH30Tpua3on-6-MeTaHona b βμαθ ociaTKa (MHTepMeAnaT 64). r) K nepeMewnBaeMOMy pacTBopy 1,2 HaciePi γμαροοκμομ HaTpun b 40 HacTHx MeiaHona Ao6aBnmoT 7,8 nacTePi 1-οκαι-α-φβΗΜπ-1Η* -6eH30Tpna3on-6-MeTaHona. nocne KOHuempupoBaHun κ KOHueHTpaiy AoāaennKDT 18 nacTePi Tonyona. PacTBopmenb BbinapuBatOT 38ηοβο u 0CT3T0K paCTBOpBIOT B 27 HaCTnX Ν,Ν-ΑΜΜβΤΜΠφθρΜ3ΜΜΑ3. ΗβΜβΑΠθΗΗΟ AOāaBnntOT 5,52 nacTePi 1-Pi0A6yTaHa n coA9p>KviMoe 33 LV 10452 nepeMeujMBaioT b τθηθημθ 30 MMHyT npi* 50 °C. Ilocne κοηιιθη-TpupoBaHMB nočaBnaiOT 30 sacieti BOflbi. 3aiBepAeBaK)mnti προηγκτ peaKUMM 0ΤφΜΠΒΤρ0ΒΒΙΒ3Κ)Τ, npOMblBatOT BOflO? U paCTBOpflKDT B βΜχηορΜθτθΗθ. OpraHusecKuti cnoti BbicyiuuBaK)T, $nnbTpyioT n 5 BbinapnsafOT. Οοτθτοκ Kpuciannn3yioT H3 17,5 sacieti flwn30npo-nnnoBoro 3φΐΊρθ. ilpoflyKT peaKLļnn cmpunbīpoBbiBaKJT h BbicytunBaK3T, nonysan 7,8 sacieti (87,4 %) 1-6yT0Kcn-a^eHnn-1H-6eH30Tpna30n-6--MeiaHona; τ. nn. 89,2 °C (nHTepMefluaT 65). flofloČHbiM o6pa30M nonysaiOT TaioKe :
10 1-3TOKCM-a^eHnn-1H-6eH30Tpna3on-6-MeTaHon; τ. nn. 102,5 °C (nHTepMefluaT 66); 1-(1-MeTnn3T0Kcn)-a.^eHnn-1H-6eH30Tpna30n-6-MeiaH0n; τ. nn. 109,6 °C (nHTepMeAnai 67); 1 -MeTOKCH-(Χ-φθΗΜΠ-1 Η-6ΘΗ30ΤρΜ330Π-6-ΜΘΤ3Η0Π; τ. ππ. 89,4 °C 15 (nHTepMefluai 68); μ a^eHnn-1-nponoKCu-1H-6eH30Tpna3on-6-MeTaHon; τ. nn. 104,1 °C (MHTepMefluaT 69). (IpMMep 6 20 a) K nepeMeujMBaeMOMy pacTBOpy 5,2 sacieti 1-οκαι-α-φβΗΜΠ- -1 H-6eH30Tpna3on-6-MeiaHona b 30 sacmx ΑΚΜβτΜπονπΒφοκοΜΑθ AoSaanniOT 0,96 sacieti 50%-Hoti Ancnepcnn rnApnAa HaTpun. PeaKL(noHHyK) CMecb nepeMemuBatOT ao Tex nop, noxa He nepeciaHei BbiAennTbcn ΒοροροΑ- (locne AOčaBneHnn 3,34 sacieti βτμποβογο 3φΜρθ 25 2-6poMyKcycHoti Kucnoibi, coAep>KWMoe nepeMemuBatoT b TeseHne 30 μmHyi npn KOMHaiHoti TeMnepaiype. /HoāaenaiOT 1,38 sacieti KapGoHaia Kanna n nepeMemnBainne npoAonx<atOT b TeseHne 3 sacoB npn 50 °C. ΠnMeτnncyπbφoκcnAHbιti cnoti BbinapMBaKJT n ociaTOK pacTBopnioT β βοαθ n 20 sacmx 1 N pacTBopa conaHOti «McnoTbi. 30 i1poAyKT peaKLļnn 3KCTparnpyiOT cMecbto χποροφορΜβ n MeiaHona (90 : 10 no o6beMy). SKCipaKT BbicyuinBaioT, φnπbτpyκDτ n KOHi4eHTpnpyiOT. KoHueHTpaT Kpnciannn3yK)T n3 32,5 sacieti α^χπορμθτθηθ. npOAyKT peaKunn c^nnbīpoBbiBafOT n BbicyiunBafOi, nonysan 3,1 sacieti (68,8 %) σ.-φβΗΜη-1 H-6eH30Tpna3on-5-MeiaHona; τ. nn. 143,0 °C 35 (nHTepMeAnai 70). 34 6) CMecb 22,5 sacieti a-$eHnn-1H-6eH30Tpna3on-5-MeTaHona, 4,8 sacieti 50%-hoū pncnepcnn ruppupa HaipMfl m 90 sacieti N,N-nnMeTnn0opMaMHAa nepeMeuutiBaioT po τθχ nop, noKa ηθ npeKpaTUTca o6pa3oeaHne Boflopoaa. ilocne AOČaBneHna 14,2 sacieti ižioAncroro MeTuna, nepeMeujUBaHue προΑοηχοκπ· b τθηθημθ 30 MHHyT npM κομηβτηομ TeMnepaīype. CMecb KOHi4eHiptipytOT. KoHueHTpaT pacTBopyiK3T b 50 saciax βοα^ι h npoAyKi peaKunn 3KCTparnpytoT AnxnopMeTaHOM, 3«CTpaKT BbicyiunBaiOT, 0nnbTpytOT n KOHi4eHTpnpytOT. KoHueHTpaT osnma>OT $nnbTpauneiži nap, cunuKarenbKD, ticnonb3ya CMecb χηοροφορΜθ h MeTaHona (9 : 1 no o5'beMy) β «aseciBe smoeHTa. UeneByio $paKLļHKD co6npaiOT n sntoeHT BbinapueaioT. flea ti30Mepa pa3AenaK)T nyieM KpncTannn3ai4nn H3 STunapeiaia. riepBbifi ti30Mep AononHMTenbHo osmuatoi nyieM KpncTannn3aunn n3 3TnnaueTaTa. ripoAyKT peaKpnn OT$nnbTpOBbiBaK)T n BbicyLUHBatOT, nonysafl 3 sāc™ (12,5 %) 1-MeTnn-a.-$eHnn-1H-6eH30Tpna3on-6-MeTaHona; τ. nn. 145 °C (nHTepMeAnaT 71). flpyroii Μ30ΜΘΡ COČMpaiOT H KpHCTannH3yiOT TptDKAbl M3 STunaueTaTa. npOAyKT pea«utiti OT$nnbTpOBbiBaiOT m BbicyuunBaiOTI nonysaa 3,3 sacieti (13,8 %) 1-Meinn-a-$eHnn-1H-6eH30Tpna3on-5'Me-TaHona; τ. nn. 129 °C (μητθρμθαμθτ 72). flpuMep 7 K nepeMeiuMBaeMOMy pacTBOpy 6,5 sacieti 1-5yT44n-a-(3- -ΧΠΟρφβΗΜΠ) -1 Η-6θΗ3ΟΤρΜ33ΟΠ*6-ΜΘΤ3Η0Π3 Β 45 HaCTflX ΤΘΤρθΓΜΑΡΟ-φypaHa Ao5aenaK)T 3,7 sacieti xnopndoro TMOHuna npn κομηθτηομ TeMnepaiype. flocne nepeMeujMBaHua β τθηθημθ 1 saca pea«i4tiOHHyto CMecb KOHi4eHTpnpyK)T. ripoAyKT peaKUMM 3KCTpartipytOT 3Tnnai4eiaTOM. Θκοτρθκτ npoMbieaioT pa3čaBneHHbiM pacTBOpOM rtiAP0Kap60Haia HaTpMfl, BbicyujMBaK)T, φ^lπbτpyκ)τ m BbinaptiBaiOT, nonysafl 6,2 sacieti
(88,3 %) 1^ΤΜΠ-6-ΓχΠ0ρ-(3-ΧΠθρφθΗΜΠ)-ΜΘΤΜΠΐ-1Η-6θΗ30ΤρΜ330Π3 B Β\Αβθ odaTKa (μητθρμθαμθτ 73), 35 LV 10452 (10Ao6HbiM o6pa30M nony4aK)T TaioKe :
No coe- flUHe R1 R2 P OcHOBa- Hne/conb T. nn. (°C) 1 2 3 '4 5 6 74 φθΗΜΠ -0-CH-(CH3)2 6 HC1 Macno 75 φθΗΜΠ -och3 6 HC1 ociaTOK 76 φθΗΜΠ -0-CH2-CH3 6 HC1 0CT3T0K 77 φθΗΙΛΠ -0-(CH2)2-CH3 6 HC1 Macno 78 φθΗΜΠ -ch3 6 οοηοβθημθ Macno 79 φβΗΙ/ΙΠ -0-(CH2)3-CH3 6 HC1 Macno 80 φθΗΜΠ -ch3 5 ' ocHOBaHue Macno 81 Η- -(CH2)3-CH3 7 0CH0B3HHe 0CT3T0K 82 φθΗΙ/ΙΠ (CH2)3-CH3 7 ocHOBaHue ociaTOK 83 Η- co X 0 1 7 ocHOsaHue ociaTOK 84 φθΗΜΠ -ch3 7 ocHOBaHue 0CT3T0K 85 ch3- -ch3 7 ocHOBaHue 0CT3T0K 86 ch3- -(CH2)3-CH3 7 ocHOBaHue 0CT3T0K 87 3-CI-C6H4· •(CH2)3-CH3 7 ocHOBaHue 0CT3T0K 88 4-Cl-C6H4- '(CH2)3-CH3 6 οοηοβθημθ 0CT3T0K 89 Η- -ch3 4 ocHOBaHue ociaTOK 90 4-F-C6H4- -(CH2)3-CH3 - 6 ocHOBaHue 0CT3T0K 91 3-F-C6H4- (CH2)3-CH3 6 οοηοβθημθ 0CT3T0K 92 3-F-C6H4- -(CH2)3-CH3 7 ocHOBaHue 0CT3T0K 93 CH-(CH2)2- -(CH2)3-CH3 6 ocHOBaHue Macno 94 3-F-C6H4- -ch3 7 ocHOBaHue ociaTOK 95 3-C]-C6H4- -ch3 7 οοηοβθημθ ociaTOK 36 1 2 3 4 5 6 96 3-F-C6H4- -ch3 5 οοηοβθημθ ΟΟΤΘΤΟΚ 97 CH3-(CH2)2 ch3 5 οοηοβθημθ ΟΰΤΘΤΟΚ 98 3-CI-C6H4- -ch3 5 οοηοβθημθ ΟΟΤΘΤΟΚ 99 4-F-C6H4- -ch3 5 οοηοβθημθ ΟΟΤΘΤΟΚ 100 3-CI-C6H4- -ch3 6 οοηοβθημθ ΟΟΤΘΤΟΚ 101 4-F-C6H4- -ch3 6 οοηοβθημθ ΟΟΤΘΤΟΚ 102 4-CI-C6H4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 103 CH3-(CH2)2· -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 104 3-Br-CgH4- -ch3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 105 3-F-C6H4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 106 3-CI-C6H4- -(CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 107 ch3- •(CH2)3‘CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 108 ch3- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 109 3-F-C6H4- '(CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 110 4-F-C6H4- (CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 111 H- '(CH2)3-CH3 4 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 112 4-CI-C6H4- '(CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 113 3-τμθημπ -(CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 114 4-Br-C6H4- '(CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 115 2-τμθημπ -(CH2)3-CH3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 116 4-CI-C6H4- -ch3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 117 4-F-C6H4- -CH-(CH3)2 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 118 3-Br-C6H4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 119 4-Br-C6H4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 120 4-Br-C6H4- -ch3 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 121 4-F-C6H4- -LlHKnOnpOnnn 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 122 4-F-C6H4- -UUKnoreKCnn 5 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 123 4-CF3- -c6h4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 124 2-CI-C6H4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 125 4-CH3- -C6H4- -ch3 6 ΟΟΗΟΒΘΗΜΘ ΟΟΤΘΤΟΚ 37 Ι_ν 10452 1 2 3 4 5 6 126 2-Ha<ļ)Ta- -CH3 6 ocHOBaHue 0CT3T0K ΠΜΗΜΓΙ 127 4-CH3O- -CH3 6 ocHOBaHue ocTaTOK -c6h4- H 6*(6ρθΜφθΗΙ1ΠΜΘΤΜΠ)-1 - ΜΘΤΜΠ-1 Η-6βΗ30ΤρΐΊ330Π3 ΜΟΗΟβρΟΜ-rnflpaT (nHTepMeAnaT 128); n 6-ΓΧΠθρ-Γ4-(4ι5·ΑΜΓΜΑρθ-4ι4-ΑΜΜΘΤΜΠ-2-0Κ0330ΠΜΠ)-φθΗΜΠ]Μ6ΤΜΠ]-5 -1-Meinn-1H-6eH30Tpna3on b βμαθ ociaTKa (nHTepMeAnai 129). (IpuMep 8 CMecb 245 nacTeii α-(4-χπορφΘΗΚπ)-ί-ΜθΤΜπ-1Η-6θΗ3θτρΐΊ33θΠ-6--MeiaHona n 1500 Macieiži pacTBOpa GpoMucioBOAopoAHoPi κμοποτβι b 10 yi<cycHOŽ KucnoTe nepeivieujuBatOT b τθηθημθ 2,5 MacoB npw 40 °C. PeaKi4noHHyto CMecb BbinapuBatOT npn 60 °C μ οοτθτοκ nepeMeiAMBaKrr b AnxnopMeTaHe. (locne oxna>KAeHMB ao 10 °C BbinaAatomufi b ocaAOK npOAyKT peaKunn c^unbTpOBbiBaiOT m BbicymuBaK)T, nonyHafl 285 nacTeii (76,6 7<.) MOHoāpOMruApaTa 6-Γ6ρθΜ-(4-χπορφβΗΜη)-Μ8™π]-1- -15 MeTw>1H-6eH30Tpna3ona (nHTepMeAnai 130). (IpMMep 9 а) K nepeMeiunBaeMOMy w oxnax<AaeMOMy pacTBOpy 58,1 MacTevi (4-χπορ-3-ΗΜτροφθΗΜπ)-φΘΗΜΠΜθΤ3ΗθΗ3 b 240 sacTHx MeiaHona 20 AoSaBfiHKDT no naciBM 4,4 sacieti 6opornApaTa HaTpua. Ποοπθ 3aBepmeHMB Ao6aBneHMH nepeMeiunBaHue προΑΟπχοκιτ β τθηθημθ 30 MHHyT npw KOMHaTHOM TeMnepaType. PeaKunOHHyio CMecb Bbinapn-eatOT. OcTaTOK pacTBopaiOT β βοαθ m npOAyxT peaKiļnn 3KCTparnpyiOT AMXnOpMeTaHOM. 3KCTpaKT BblCyilJMBaKDTI φnπbTpy^oτ M BbinapMBaiOT, 25 nonyHaa 58 sacieti (99,9 %) 4-xnop-3-Hmpo-oHt>eHun-6eH3onMeiaHona β βμαθ ociaTKa (μητθρμθαμ8τ 131). б) Civiecb 58 sacieti 4-xnop-3-HHTpo-a^eHnn6eH3onMeTaHona n 450 sacieti 48 %-ηογο pacTBOpa āpOMMCTOBOAOpOAHOti KucnoTbi β βοαθ nepeMeuiMBaiOT β· τθμθημθ 45 MWHyi npw TeMnepaType κμπθημβ c 38 oāpaTHbiM xonoflnnbHHKOM. flocne oxnax<AeHHB npoAyKT pea«unu 3KCTparnpyK3T ακχπορμθτθηομ. θκοτρβκτ BbicywnBafOT, $nnbTpytoT u BbinapHBafOT, nonyHan 71,4 nāciet (99,3 %) 4-(6ρομΦθημπμθτμπ)-1- -xnop-2-HHTpo6eH3ona b BUfle ociaTKa (nHTepMGfluaT 132). b) CMecb 31,9 nacTeii 4-(6ρθΜφΘΗΜΠΜΘΤΜΠ)-1-ΧΠθρ-2-ΗΜΤρθ6βΗ-3ona, 49,3 nacTeii 4-MeTnn-1H-nMHfla3ona n 120 nācies aueTOHmpuna nepeMeiunBaioT b τθηθημθ 24 nacoB npn TeMnepaType κκπθηιίπ c o6paTHbiM xonoAnnbHHKOM. PeaKunoHHyic CMecb KOHi4eHTpnpyiOT n KOHueHTpaT pacTBOpanDT b 150 ηθοτπχ βοα^ι. [1poAyKT peaKunn 3KCTparnpyfOT α^χπορμθτθηομ. 3KCTpaKT BbicyiunBatOT, φ^1ΠbTpy^oτ n BbinapMBaiOT. OCTaTOK OHHLL(aK)T C nOMOUļbKD κοποηοηηοιζι χρομθτο-τρβφm H3A cunuKarenbto, ncnonb3yn CMecb χποροφορΜθ, μθτθηοπθ μ MeiaHona, HacbimGHHoro θμμιίθκομ (98 : 1 : 1 no očbeMy) b «anecTBe sntoeHTa. UeneBbie φρθκρκκ cočupatoT μ 3πκ>θητ BbinapHBatOT. Οοτθτοκ npeBpaiAaioT b maBeneBOKncnyio conb b 80 ηθοτβχ 2-npo-naHona. Conb οτφι^τροΒ^ΐΒθίοτ, npoMbiBafOT 2-nponaHonoM m BbicyiunBaK)T, nonynan 22,8 nāciet (54,5 %) (1:1) maBeneBOKHcnoii COHM 1 -[(4-ΧΠθρ-3-ΗΜΤρθφθΗΜΠ )-φθΗΙ^ΠΜΘΤΜΠ]-4-ΜΘΤΜΠ-1 H-MMMA33ona; τ. nn. 105 °C (nHTepMeAnaī 133). noAočHbiM o6pa30M nonyHafOT Tao<e:
1 -[(4-ΧΠθρ-3·ΗΜΤρθφθΗΙΊΠ)-ΜΘΤΜΠ1·1 Η-ΜΜΜΑ330Π, Τ. ΠΠ. 81,7 °C (MHTepMeAnaT 134); 1 -f(3*ΧΠθρ-4-ΗΜΤρθφθΗΜΠ)-φθΗΜΠΜΘΤΜΠ]* 1 Η-ΜΜΜΑ330Π, (HHTGpMG* AnaT 135); 1 - f(4-χηθρ·3-ΗΜΤρθφθΗΜΠ)-φθΗΜΠΜΘΤΙ/ΙΠΐ-1 Η-ΙΊΜΜΑ330Π, (ΜΗΤθρΜΘ* AnaT 136); 1-Γ(4-ΧΠθρ-3-ΗΜΤρθφθΗΙΐη)-ΜΘΤΜπ1-2-ΜΘΤΜΠ-1 H-HMMAa30n, Τ. ΠΠ. 102 °C (MHTepMeAnaT 137); 1-Γ(4-ΧΠθρ-3-ΗΜΤρθφθΗΜΠ)-φθΗΙ1ΠΜΘΤΜΠ]-5-ΜΘΤΜΠ-1 H-HMMAa30n, τ. ππ. 164 °C (MHTepMeAnaT 138); 1-Γ(3-ΧΠ0ρφθΗΜΠ)-(4-ΜΘΤ0Κ0Μ-3-ΗΜΤρ0φθΗΜΠ)-ΜΘΤ11πΜ H-MMUA-a3on b BHAe ociaTKa, (ιίητθρμθακθτ 139); m
LuaBeneBOKucnan conb (1:1) 1-Γ(3-χπορ-4-ΗΜτροφθΗΜπ)-(4-χπορ-Φθημπ)-μθτμπ1-1 H-MMHAa3ona (μητθρμθαμθτ 140). 39 LV 10452 ΠρΜΜΘρ 10 K nepeMemnBaeMOMy pacTBopy 10 MacTePi 4-χπορ-α-ΜθΤΜη-3- -HHTpo6eH3onMeTaHona b 90 ηθοταχ TeTparnppo$ypaHa AoSaBnntOT 8 MacTePi 1,1'-Kap6oHnn-6nc-f1H-HMHfla3onal. ilocne nepeMeuuMBaHua b 5 τθμθημθ 4 nācos npM TeMnepaType κμπθημη c oāpaTHbiM χοπορμπβημκομ, TeTparMApc^ypaHOBbiPi cnoPi BbinapMBaioT. Ilocne noāaBneHMfl 90 MacTePi MeTnn6eH3ona pea«i4MOHHyio CMecb nepeMeujuBatOT b τθμθημθ 75 nacoB npM κμπαμθημμ c o6paTHbiM xonoflnnbHMKOM. PeaKunoHHyto CMecb BbinapMBatoT μ οοτθτοκ 10 pacTBOpfltoT b Bope. Οοαθρ>κμμοθ 06pa6aTbiBaK)T pacTBOpOM ruppo* OKMCM 3MM0HMB H npOflyKT peaKLJMM 3KCTparnpyiOT ΑΜΧΠΟρΜΘΤΘΗΟΜ. SKCipaKT BbicyujMBaK)T) $nnbTpyKDT m BbinapMBaiOT. Οοτθτοκ ομμιαθκη c noMombio κοποηομηοΡϊ xpOMaTorpa$nn Hap CMnuKarenbJO, Mcnonb3yn CMecb χποροφορΜβ n Me.TaHona, HacbimeHHoro θμμμθκομ, (95 : 5 no 15 o6‘beMy) b «anecTBe snfoeHTa. flepByio 0paKunK) coOnpatOT μ θπιοθητ BbinapuBaioT. Octstok KpncTannn3yiOT n3 84 nacTePi ακθτμποβογο 30npa. llpoAyKT peaKumi OT$nnbTpOBbiBaiOT m BbicyiiiMBaiOT, nonynan 4,2 nacTeiži (33,3 %) 1-(Ί-(4-χηορ-3-ΗΜτροφθΗΜπ)-3ΤΜη]-1Η-ΜΜΜΑ33θΠ3 (nHTepMepnaT 141). 20 llpnMep11 CMecb 2,52 nacTePi 4H-1,2,4-TpMa3on-4-aMMHa, 8 nacTePi 4-xnop- -
3- Hmpo6eH30nMeTaHona μθτθι^πβΦοηθτθ (cno>KHbiPi 3φΜρ) m 40 nacTePi aueTOHnTpuna nepeMeuiMBaraT b τθμθημθ 3 nacoB npM 25 TeMnepaType κμπθημβ c oāpaTHbiM χοποαμπβημκομ. ilocne οχπθχαθημβ npOAyKT peaKUMM οτφΜΠΒτροΒΜΒθίοτ, npoMbieatOT aueTOHMTpMnoM m BbicyujMBaKDT, nonynan 9,9 nacTePi (94 %) MeτaHcyπbφoHaτa 4-θμμηο-1-1(4-χπορ*3-ΗΜτροφΘΗΜη)-ΜθΤΜη1-1,2,4-TpMa30nMn; τ. πη. 163,9 °C (MHTepMepnaT 142). 30 6) K nepeMeniMBaeMOMy pacTB0py 8,75 nacTePi MeτaHcyπbφoHaτa 4- 3ΜΜΗΟ-1-[(4-ΧΠθρ-3-ΗΜΤρθφθΗΜΠ)-ΜΘΤΜΠ]-1,2,4-ΤρΜ33θηΜη B 85 nacTnx 1 N pacTBopa connHoPi KMcnoTbi AoSaBnntOT 7,15 nacTePi 50 %-hoPi φοΰφΜΗΟΒοΡι KMcnoTbi. Ilocne οχπθχαθημβ Ha nbpy pacisop 3,5 nacTePi ημτρμτθ HaTpMii b 15 MacTflx BOAbi Ao6asnnK)T b peaKUMOHHyK) CMecb. 35 CMecb nepeMeujMBatOT β τθμθημθ 2 Mačos npM κομηθτηομ Tetvmepa-Type. H36biTOK KOHiļeHTpMpOBaHHoPi tmapookmcm θμμοημη ΑοόθΒηηιοτ -μ 40 ΠθρθΜΘΟΙΜΒΘΗΜΘ ΠρΟΑΟΠΧΘΙΟΤ Β ΤΘΗΘΗΜΘ 15 MHHyT. npOflyKT peaKLļMM ΟΤφΜΠΒΤρΟΒΒΙΒΘΙΟΤ, npOMblBBKDT ΒΟΑΟΜ, 2-ΠρθΠ3ΗθΠΟΜ Μ ΑΗΜ30Πρ0- nnnoBbiM 30npoM μ KpMCTannM3yfOT Μ3 8 nacTefi 2-nponaHona. npc>AyKT peaKLļnn οτφΜΠΒτροΒΒίΒθιοτ m BbicyiunBaK)T, nonyHaa 5 ηθοτθμ (83,3 %) 1-[(4-xnop-3-HHTpc^eHMn)-MeTnnl-1H-1,2,4-Tpna3ona; τ. nn. 98,9 °C (nmepMeAuaT 143). noAo6HbiM o6pa30M nonyMaiOT Taxxe: 1-[(4-ΧΠθρ·3·ΗΜΤρθφθΗΜΠ)·φθΗΜΠΜΘΤΜΓΐ]-1 H-1,2,4-Tpna30/1 B ΒΜΑΘ Macnoo6pa3Horo οοτθτκθ (μητθρμθαμθτ 144). ΠρΜΜθρ 12 K 184 nacTBM χοποαηομ (10 °C, neA^naa 6θηβ) κοηαθητρμ-poBaHHOū cepHOM KMcnoTbi Ao6aβπβκ)τ no nacTAM 75 HacTeii MOHOHHTpaTa W(3-MeTOKC^eHnnj-MeTun]-1H-MMMAa3ona β τθηθημθ 1 naca. Ποοπθ 3aBepmeHHB αοΟθβπθημα πθρθμθιιιμβθημθ npoAonxaiOT b τθηθημθ 30 MHHyT npn 10 °C. Πο KannaM β τθηθημθ 30 MHHyT npn 15 °C ΑοδθΒΠΒίοτ 15 ηθοτθμ κοηαθητρμροβθηηομ a30THOki κμοποτβι. ilocne 3aBepmeHMfl αο68βπθημη οοαθρχμμοθ nepeMeujMBaiOT β τθηθημθ 30 MHHyT npn 10 °C. PeaKLļnoHHyto CMecb BbinuBatOT b 1500 nacTeii pa3Apo6neHHoro nbAa m οοαθρχμμοθ o6pa6aTbiBa(OT pacTBOpOM rMApOOKMCM aMMOHMB. npOAyKT peaKLJMM 3KCTparHpyK)T Α^ΙΧΠΟρ-μθτθηομ. Θκοτρθκτ BbicyniMBaK)T, φMΠbTpy^oτ m BbinapuBatOT. Οοτβτοκ OHHUļatOT C nOMOlAbK) ΚΟΠΟΗΟΗΗΟΜ ΧρΟΜΘΤΟφθφΜΜ H3A CUnMKarenbK), ncnonb3ya CMecb θτμπθαθτθτθ, μθτθηοπθ μ μθτθηοπθ, ηθοηιαθηηοβογο aMMnaKOM, (95 : 2,5 : 2,5 no o6beMy) β ιοηθοτβθ amoeHTa. HncTbie φρθΚΑΜΜ COČMpatOT Μ 3ΠΙΟΘΗΤ BbinapMBaiOT ΠΟΑ B3KyyM0M. OCTaTOK nepeMeiunBaiOT β 45 ηθοτηχ STunaLieiaia. BbinaAaioīnMM b ocaAOK npOAyKT peaKunn οτΦμπβτροβηβθιοτ, npoMbisaiOT Ann3onponnnoBbiM οφιιροΜ m BbicyiuMBaK)T, nonyHaa 28,2 ηθοτθμ (40,3 %) 1-((3-μθτοκομ-4--ΗΐίίτροφθΗΜπ)*μθτμπ]- 1 H-MMHAa3ona (MHTepMeAuaT 145). npMMep 13 CMecb 8 ηθοτθμ 1-[(4-xnop-3-HHTpo0eHnn)-MeTnnļ-1H-MMHAa3ona n 42 ηθοτθμ αμκπογθκομπθμμηθ nepeMeiunBaiOT β τθηθημθ 2 nācos npM teMnepaType κμπθημβ c oāpaTHbiM χοποαμπβημκομ. CMecb 41 LV 10452
BbinapuBanDT μ οοτθτοκ nepeMeujuBaioT b flnn3onponnnoBOM a$npe. BbinanaioinnM b ocaAOK προΑγκτ pea«unn oTcļDunbTpOBbiBaKJT, npOMblBaiOT BOAOM H AHH30np0nnn0BblM 3Cf)HpOM H OHmiļaKDT C nOMOLUbtO ΚΟΠΟΗΟΗΗΟΜ Χρ0Μ3Τ0Γρ3φΜΜ ΗΘΑ CMnMKarenbK), MCnonb3ya CMeCb 5 χποροφορΜθ n MeiaHona (90 : 10 no o6teMy) b κθηθοτβθ smoema. HncTbie Φρθκαμμ co6npa(OT μ θπιοθητ BbinapneaiOT. Οοτβτοκ nepeMeiiiMBatoi b CMecu Anu3onponnnoBoro 3dpv\pa n aTnnapeTaia. i1poAyKT peaKLinn οτφκί^τροΒΜΒΒίοτ, npoMUBaioī STunaueTaTOM n AHH30np0nnn0BblM 3φκρθΜ H BblCyiilHBaiOT ποα Ba«yyMOM npn 60 °C, 10 nonyHaa 9,5 wacTew (93,8 %) N-unKnoreKCnn-4-(1H-HMHAa3on-1-nn--Meinn)-2-HMTpo6eH3onaMHHa; t. nn. 121,1 °C (μητθρμθαμθτ 146). floAočHbiM o6pa30M nony4atoT τθιοκθ:
15
No. coe- m- ηθ- HMH Rl R8 R9 OcHOBa- Hne/conb Τ,ππ °C 1 2 3 4 5 6 147 H- -NH-(CH2)3'CH3 -NO2 ocHOBaHue 117.5 148 H- •NO2 -NH-(CH2)3-CH3 ocHOBaHue 89,1 149 H- -NH-iinKnoreKCnn -N02 · ocHoeaHue 134,7 150 H- -NH-C6H5 -NO2 ocHOBaHue 150,8 151 ch3- -NO2 -NH-(CH2)3'CH3 HNO3/H2O 84,7 152 φθΗΜΠ -NO2 'NH-(CH2)3-CH3 ocHOBaHue OCTa- TOK 153 φβΗΜΠ -NH-(CH2)3'CH3 -NO2 ocHOBaHue Mac- no 42 1 2 3 4 5 6 154 φΘΗΜΠ -NH-CH-(CH3)2 -NO2 οοηοβθημθ Mac- no 155 Η- -ΝΗρΜκποπροπΜΠ -NO2 οοηοβθημθ 111,6 156 Η- -NH-CH-(CH3)2 -NO2 οοηοβθημθ 101,6 157 Η- -NH-(CH2)2-CH3 -NO2 οοηοβθημθ 98,9 158 φθΗΜΠ -nh-ch3 -NO2 ocHOBaHue ocTa- TOK 159 Η- -NH-CH2(4-C1- -NO2 οοηοβθημθ 124,7 -c6h4) 160 Η- -NH-(CH2)2- -NO2 οοηοβθημθ 75,4 -CH(CH3)3 161 Η- -NC>2 -NH-(CH2)2-CH3 οοηοβθημθ 98,4 162 Η- -NO2 -NH-CH-(CH3)2 οοηοβθημθ 98,3 163 Η- -NO2 -NH-(CH2)2-C6H5 ocHOBaHue 100.5 164 Η- -NH-CH2(4-F- -NC^ ocHOBaHue 111,0 -C6H4) 165 Η- -nh-ch2-ch3 -NC^ οοηοβθημθ 106,2 166 Η- -NH-CH2(3-F - -N02 οοηοβθημθ 95,4 •c6h4) 167 Η- -NH-CH(CH3)- -N02 οοηοβθημθ Oda- -ch2-ch3 TOK 168 Η- -NH-6mlimk- -NO2 οοηοβθημθ 130,7 ποΓ2.2.11γθπ- -TaH-2-nn 169 φθΗΜΠ -ΝΗίιμκπογθκομπ -NOjj οοηοβθημθ ocTa- TOK 170 Η- -ΝΗ-ίΙΜΚΠΟΠΘΗΤΜΠ -N02 οοηοβθημθ 81,9 171 Η- -ΝΗ-1,2,3,4-τθτ- -N02 οοηοβθημθ 118.0 parunpo-1 ·Η3φ - τθπμημπ 172 Η- -nh-ch2- -ch=ch2 -NO2 οοηοβθημθ 86,4 43 LV 10452
1 2 3 4 5 6 173 H- -NO2 -NH-CH2-C6H5 ocHoeaHue ocTa- TOK 174 H- -ΝΗ-θΗ2*υΜΙ<ηο' -NO2 ocHoeaHue 101,4 nponnn 175 H- -NH-OH2'2-Tne· -NO2 ocHoeaHue ocTa· TOK 176 H- -NH-(CH2)3-°h -NO2 ocHoeaHue 107.0 177 H- -NH-CH2*c' -NO2 ocHOBamie 113.7 -(CH3)3 178 H- -NH-(CH2)2‘N- -NO2 ocHoeaHue 111.6 -(CH 3)2 179 H- -NH-2,3-flnrnnpo- •NO2 ocHOBaHue 200,2 -IH-HHfleH-1-ΜΠ 180 4-CI-C6H4- -NH-CH-(CH3)2 -NO2 (COOH)2 110,9 181 4-CI-C6H4- -NH-uUKnoreKCnn -NO2 (COOH)2 114,4 182 4-Cl-C6H4- •ΝΗ-φβΗΜΠ -NO2 ocHOBaHue Mac- no 183 4-Cl-C6H4- -NH-CH(CH3)· -NO2 ocHOBaHue ocTa- -C6H5 TOK 184 4-Cl-C6H4- -NH-CH2-(4-Cl- -NO2 ocHoeaHue ocTa- -C6H4) TOK 185 4-CI-C6H4- -NH-CH2-C6H5 -NO2 OCHOBaHMS ocTa TOK (1pnMep14
Cviecb 7,9 nacTefi Ν-ι4ΜΚΠΟΓΘκομπ-4-(1Η·μμμα33οπ-1-μπμθτμπ)-2--HMT.po6eH3onaMMHa, 22,9 nacTeii AUTnOHHTa HaTpufl, 288 'Mac-Tefl 5 sTaHona n 240 nacieti BOflbi nepeMeiuHBatOT npn κομηθτηομ TeMnepaiype. flocne 3aBepweHnfl peaKUnn 3TaHonbHbiĪi cnoii BbinapuBatOT. BoAHbifi cnoft pa36aBnafOT pacTBopoM KapSoHaia Kanna. Coflep>KHMoe 3KCTparnpyioT flBa>Kflbi : nepBbm pa3 αμχπορμθτθηομ, a 3aTeM CMSCbto xnopo$opMa u MeiaHona (90 : 10 no o6teMy). 10 OčteAMHeHHbie SKCTpaKTbi BbicyujnBaK)T, $nnbTpyioT u BbinapuBatOT. OcTaTOK pacTBOpatOT b MeTnn6eH3one (Tonyone) m pacTBopmenb 44
BbinapuBaiOT οηοβθ, nonyHaa 7 ηθοτθμ (98 %) N '-ι4μκπογθκομπ-4-(1Η--MMMfla3on-1-nnMeTnn)-1,2^eHnneHAnaMHHa b Bufle ociaTKa (μητθρμθ-AnaT 186). noAo6HbiM o6pa30M nonyMaiOT τθιοκβ : 10
No. coe-aM-He-hmh Rl R8 R9 OcHoea- HMe/conb T.nn. °c 1 2 3 4 5 6 187 -H -NH2 -NH-CH3 OCHOBSHUe ocTaTOK 188 -H -NH-(CH2)3CH3 -NH2 OCHOBaHUS 0CT3T0K 189 -H nh2 -NH-(CH2)3CH3 ocHOBaHue ocTaTOK 190 -H -ΝΗ-14ΜΚΠΟ- -NH2 OCHOBaHUS οοτβτοκ reKCnn 191 -H -NH-C6H5 -NH2 OCHOBaHMS 0CT3T0K 192 -H -NH-CH2-C6H5 -NH2 ocHoeaHue οοτβτοκ 193 C 6^5 -NH2 -NH-(CH2)3CH3 OCHOBaHMS OCT3TOK 194 ch3 -NH2 -NH-(CH2)3CH3 0CH083HH6 0CT3T0K 195 -c6h5 -NH-(CH2)3CH3 -NH2 OCHOBaHMd ocTaTOK 196 -C6H5 -NH-CH(CH3)2 -NH2 ocHOBaHue OCT3TOK njH? OCHOBaHMS OCT3TOK 197 •H -ΝΗ-μμκπο- nponnn 198 -H -NH-CH(CH3)2 -NH2 ΟΟΗΟΒ3ΗΜβ ocTaTOK 199 -H -NH2 -NH-CH2- C6H5 ocHoeaHMe ocTaTOK 15 46 ΠρΜΜβρ 15 10 CMecb 9 nacTeii 2,3-AnrMApo-N-f5-(1H-HMMna3on-1-nnMeTMn)- hmt-ροφθΗΜπ]-1 H-MHfleH-1-aMMHa, 2 HacTeii pacTBopa τιιοφθΗ3 b μθτθηοπθ (4 %-hom) m 200 HacTeii μθτθηοπθ rnApnpy*OT npw o6biHHOM αθβπθημμ m npM KOMHaTHOM TeMnepaType C HOMOlUblO 2 HaCTeii 5 %ΉΟΓΟ Kaiann3aTOpa nnaTUHbi Ha αρθβθοηομ yme. riocne πογποιαθημβ BbmucneHHoro KonunecTea BOAOpOfla Kaiann3aTop cr^unbTpoBbiBaiOT m Φμπβτρθτ BbinapueatOT, nonyHaa 8 sacTeū (97,3 %) Ι\|2-(2,3-αμγμαρο-1Η--MHAeH-1-Mn)'4-(1H-MMMAa3on-1-nnMeTMn)-i,2^eHnneHAnaMHHa b bha© odaTKa (μητθρμθαμθτ 216). nc>A06HbiM o6pa30M nonyHaioT TaioKe: 15 o“ •H ,_( 20
No OCHOBa- Τ.ΠΠ. C06~ flM- R R8 R9 Hne/conb °C He- 1 2 3 4 5 6 217 -φθΗΚΠ -NH-CH3 -NH2 ocHoeaHue 0CT3T0K 218 -H -NH2 -NH(CH2)2-ch3 ocHoeaHue οοτθτοκ 219 -H -NH2 -NH-CH(CH3)2 οοηοβθημθ OCT3TOK 220 -H -NH-CH2-CH3 •NH2 ocHOBaHue 0CT3T0K -NH2 ocHOBaHue 0CT3T0K 221 -φβΗΙΊΠ -NH-um<no- reKCnn -NH2 -NH-CH2-C6H5 ocHoeaHue οοτθτοκ 222 -φΘΗΙΙΠ 45 LV 10452 1 2 3 4 5 6 200 -Η -NH-(CH2)2CH3 -nh2 ocHOBaHue 0CT3T0K 201 -Η -NH-CH2-(4-Cl- -nh2 ocH08.aHne οοτθτοκ -c6h4) 202 -Η -NH-(CH2)2- -nh2 ocHOBaHue 0CT3T0K -CH(CH3)2 203 •Η •NH2 NH(CH2)2C6H5 ocHOBaHue οοτθτοκ 204 -Η -NH-CH2.(4-F- -nh2 ocHOBaHue οοτθτοκ -c6h4) 205 -Η -NH-CH2.(3-F- -nh2 OCHOB3HHB 0CT3T0K •c6h4) 206 -Η -NH-CH(CH3)- -nh2 ocHOBaHue οοτθτοκ -ch2.ch3 -nh2 OCHOBaHUB οοτθτοκ 207 -Η -NH-6mlimk- ποΓ2.2.ΠΓβπτ- -nh2 OCHOBaHHB ocTaTOK -2-nn 208 -Η •ΝΗ-μμκπο- -nh2 ocHOBaHue οοτθτοκ πθητμπ 209 -Η -1,2,3,4-TeTpa-rnapo-1-Ha<ļ>- -nh2 OCHOBaHHB 0CT3T0K TannHnn 210 -Η •NH-CH2- -nh2 OCHOBaHHB οοτθτοκ -CH=CH2 211 -Η -NH-CH2-limk- -nh2 OCHOBaHHB οοτθτοκ nonponnn 212 -Η -NH-(CH2)3-OH -NH2 OCHOBaHHB οοτθτοκ 213 4-Cl-C6H4- (5-MeTnn-2- <ļ>y-paHnn)-Me- -nh2 ocHOBaHue οοτθτοκ TMnaMMHO 214 4-CI-C6H4- -NH-CH2-(4-Cl- -c6h4) -nh2 OCHOBaHHB οοτθτοκ 215 4-Cl-C6H4- -NH-unKno- -nh2 OCHOBaHHB 0CT3T0K nponnn 47 LV 10452
1 2 3 4 5 6 223 -Η -NH-CH2-2- -ΤΜΘΗΜΠ -nh2 ocHoeaHue OCT3TOK 224 -Η -NH-CH2- -C(CH3)3 -NH2 οοηοβθημθ ocTaTOK 225 4-Cl-C6H4- -NH-CH(CH3)2 -NH2 ocHoeaHue 0CT3T0K 226 4-C1-C6H4- -ΝΗ-μμκγιο- reKcnn -NH2 ocHOBaHue ociaTOK 227 •Η -NH(CH2)2- -N(CH3)2 -NH2 ocHOBaHue ocTaTOK 228 4-C1-C6H4- •NH-C6H5 -nh2 οοηοβθημθ 0CT3T0K 229 4-C]-C6H4- -NH(CH2)2- -CH(CH3)2 -nh2 οοηοβθημθ OCT3TOK 230 4-C1-C6H4- -NHCH(CH3)- -c6h5 -nh2 ΟΟΗΟΒΘΗΜΘ ocTaTOK 48 npMMep 16
PadBOp 10 nācies 6-ixnop-[4-(4,5-AnrnApo-4,4-flHMefnn-2-OK-ca3onnn)-cpeHnn]-MeTnnļ-1H-6eH30Tpna3ona n 10 sacieti 1H-nMHAa3ona b 80 nacTflx aueTOHmpnna nepeMeujuBaiOT b τθηθημθ 4 nācos npn ΤΘΜΠβρθΤγρθ KUneHHfl C OČpaTHblM XOAOAHnbHMKOM. PeaKl4HOHHyK> CMecb BbinapuBatoT η προργκτ peaKpnn 3KCTparnpyK)T STnnaueiaTOM. SKCTpaKT npoMbieaiOT pa36aBneHHbiM pacTBopoM KapāOHaia Kanna, BbicyujnBatOT, φι^τργκ>τ n BbinapnBaroT. OciaTOK onnmatOT c noMOmbio κοποηοηηοΛ xpOMaiorpa<J)nn ηθα cnnnKarenbīo, ncnonb3ya CMecb AnxnopMeiaHa η μθτθηοπθ (98 : 2 no o6teMy) b KaneCTBe smoema. HncTbie cppaKpnn cočnpaiOT n 3πκ)θητ BbinapnBatOT, nony<Haa 7,1 sacieti (65,6 c/() 6-f f4-(4,5-AnrnApo-4,4-AHMeTnn-2-OKca3onnn)-0eHnn]-(1H-n-MHAa3on-1-nn)-Menin]-1 H-5eH30Tpna3ona b bha© ocTaTKa (nmepMe-AnaT 231). 49 LV 10452 B. ΠοπνΜΘΗΐΐθ KOHesHbix coeflUHei-mti 5 ΠρΜΜβρ 17 CMeCb 4 MaCTeii 5-(ΧΠ0ρφΘΗΜΠΜΘΤΜη)-1-ΜβΤΜη-1Η-6βΗ30ΤρΜ-a3ona, 5,65 sacieti lH-MMHfla3ona m 20 sacieti aueiOHmpMna nepeMemuBatOT b TeseHne 1,5 sacoe npu TeMnepaiype KuneHna c 10 o6paTHbiM xonoflnnbHMKOM. Ilocne KOHuempupoBaHHB βοβθΒΠΗίοτ 50 sacieti BOflbi n npoflyKT peaKunn 3KCTparnpyiOT flnxnopMeiaHOM. SKCTpaKT BbicyiUMBaK)T v\ KOi-meHTpMpyioT. OciaTOK osmuatOT c noMOiMbio 0nnbTpai4nn Hafl cvuiMKarenbK), ncnonb3ysR CMecb χηοροφορινιβ m MeiaHona (95 : 5 no o6teMy) b KasacTBe sriKcema. Hncibie φρθκι,ΐΜΜ 15 co6wpatoi u antoem BbinapuBaiOT. OciaTOK npeBpamaioT b HmpaTHyio conb b 45 sacTax τeτpaΓ^1flpoφypaHa. Conb οτφι^τροΒ^Β3Κ)τ, npOMbiBatOT τeτpaΓHflpoφypaHOM m BbicywnBaK)T, nonysaa 3,9 sacieti (80,2 %) 5'f(1H-nMHfla3on-1-nn)^eHnnMeTMnļ-1-MeTnn-1H-6eH30TpM-a3on MOHOHmpai; t. nn. 111,9 °C (coefluHeHne 1). 20 flofloČHbiM o6pa30M nonysatoT iaxxe:
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PacTBOp 203 nacTei/ί MOHočpOMruppaTa 6-[6ροΜ-(4-χπορφΘ-Hnn)MeTnnļ-1-MeTnn-1 H-6eH30Tpna3ona v\ 170 HacTeii 1H-nMHfla30na b 1350 nacTax Tonyona nepeMeiunBatoT b Tewei-me 28 nacOB npu TevmepaType κμπθημ?ι c o6paTHbiM xonoAnnbHHKOM. PeaKpnoHHoii CMecu no3Bon?uoT oxnaAUTbca ao 80 °C, a 3θτθμ BbinapnsaiOT 3Ty CMecb. MaenanncTbifi οοτθτοκ pacTBOpatoT b α^χπορμθτθηθ. OpraHu-necKuii cnoii npOMbiBatOT pa36aBneHHbiM pacTBopoM οοπβηομ κμοποτμ. Pa3AeneHHbiM BOAHbm cnoči 06pa6aTbiBatOT pacTBopoM tuapookmcu HaTpMH h 3KCTparnpyioT α^χπορμθτθηομ. OSbeAUHeHHbie Auxnop· μθτθηοβηθ cnon npOMbiBafOT boaom, BbicyiunBaK)T1 φnπbτpy^oτ n BbinapuBakdt. Οοτθτοκ onmuaiOT c noMombio κοποηοηηομ xpoMa-τοτρθφΜΜ H3A cunuKarenbto, ncnonb3yfl CMecb αμχπορμθτθηθ h μθτθηοπθ (95 :5 no o6beMy) b κθηθοτβθ θπιοθητθ. HucTbie φρβκρκνι coSnpajoT n 3ΠΚ)Θητ BbinapMsaioT. K 0CTaTKy Ao6aBriflK)T 210 ηθοτθμ 55 LV 10452 Ρμθτμποβογο 3$npa n copep>KMMoe ocTaenaKiT CTOflTb b τθηθημθ ynKeHfla (οτ nRTHmļbi po noHeperibHMKa). TBeppbiPi προργκτ peaKLļMM OT$nnbTpoBbiBaiOT m BbicyiDMBaK)T npM 50 °C, nonyHafl 48,1 nacTePi (29,7 %·) 6-ί(4-ΧΠ0ρφθΗΜΠ)-(1Η-ΜΜΜΡ330Π-1-ΜΠ)-ΜΘΤΜΠ]-1-ΜΘΤΜΠ-1Η-6θΗ-5 30Tpna3ona; τ. nn. 87,7 °C (οοθρμηθημθ 63). npMMep 20 K nepeMewnBaeMOMy pacTsopy 28,4 nacTePi 1H-Tpna3ona-1,2,4 b 135 HacTBx N.N-flUMeTuncfcopMaMMfla ροδθΒΠΗίοτ 11,4 nacTePi 80 %-hom 10 pncnepcnH ruppupa HaTpua b θτμοοΦθρθ a30Ta. Ilocne πθρθμθιβμ-βθηιία b τθηθημθ 1 nāca npM KOMHaTHoPi TeMnepaiype pacTBOp 40 nacTePi 6-(χπορ-(4-χπορΦθημπ)-μθτμπ]-1-μθτμπ-1Η-6θη30ΤΡΜ330Π3 b 90 HaCTHX Ν,Ν-ρΜΜΘΤΜΠφΟρΜΘΜΜρθ ροδθΒΠΗΙΟΤ K ΟΜΘΟΜ. Οθρθρ>ΚΜΜΟΘ nepeMeujMBatoT b τθηθημθ 1 naca npM 60 °C. Ρθθκρμοηηυκ) CMecb 15 pa36aBnflK)T 50 nacTBMM eopbi m copepacMMoe BbinapMBatOT. Οοτθτοκ 3KCTparMpytOT θτμπθρθτθτομ. Θκετρβκτ npoMbieaiOT Βοροίί, BbicyiuM-BatOT, φΜΠΒΤργίΟΤ M BbinapMBatOT. OCTaTOK OHMliļaiOT C nOMOīpbK) ΚΟΠΟΗΟΗΗΟΜ χρΟΜθΤΟΓρθφΜΜ ΗΘΡ CMHMKarenbtO, MCnonb3ya CMecb ΑΜΧΠ0ΡΜΘΤ3Η3 Μ ΜΘΤΘΗΟΠΘ (99 ! 1 ΠΟ Οβ^θΜγ) B ΙΟΗΘΟΤΒΘ ΘΠΙΌΘΗΤΘ. 20 HMCTbie φρθΚΑΜΜ COČMpaiOT Μ 3ΠΚ)ΘΗΤ BbinapMBaiOT. OCTaTOK KpMCTannM3yKDT M3 ομθομ aueTOHa μ ρμθτμποβογό 3φΜρθ. Προργκτ peaKLļMM οτφΜΠΒτροΒΒΐΒ3Κ}τ μ βbicytunΒ3Κ)τ, nonyHaa 13 ηθοτθμ (29,2 %) 6-[(4·ΧΠ0ρφθΗΜΠ)-(1Η-1,2,4-ΤρΜ330Π-1-ΜΠ)-ΜΘΤΜΠ]-1-ΜΘΤΜΠ-1Η-6θΗ30-TpMa3ona; τ. πη. 178,9 °C (οοθρμηθημθ 64). 25 npMMep 21 K nepeMewMBaeMOMy pacTBOpy 4,25 nacrrePi 1H-1,2,4-TpMa3ona b 47 HaCTBX Ν,Ν-ρΜΜΘΤΜΠφθρΜ3ΜΜΑ3 ρθ63ΒΠΒΚ)Τ 2 Η30ΤΜ 50 %-ΗθΡί PMC-nepcMM rMppMpa HaTpMa b θΤΜΟοφθρθ a30Ta. Copep>KMMoe nepe-30 MeiiiMBaKDT b τθηθημθ 10 ΜΜΗγτ npM KOMHaTHoPi TeMnepaType m pacTBop 6 nacTePi 6-[χπορ-(3-χπορφθΗΜπ)-ΜθΤΜπ1-1-ΜθΤΜη-1Η-6θΗ3θ-τρΜ33θΠ3 b 47 HaCTBX Ν,Ν-ΑΜΜΘΤΜΠφθρΜ3ΜΜρ3 ρθ6θΒΠΒΚ3Τ K ΟΜΘΟΜ. ΟθΡθρ>ΚΜΜΟΘ ΠθρθΜΘ11ΙΜΒ3Η3Τ Β ΤΘΗΘΗΜΘ 1 ΗΘΟβ ΠρΜ 50 °C, Ά 3ΘΤΘΜ OX-na>KpaiOT ΑΟ κομηθτηοΡι TeMnepaTypbi. Προργκτ peaKUMM 3KCTparMpyK3T 35 3ΤΜΠ314ΘΤ3ΤΟΜ. 3«CTpaKT BblCyUiMBaiOT, φΜΠΒΤργίΟΤ Μ BbinapMBatOT. 56
OdaTOK OHMmatOT C nOMOUJbtO KOnOHOSHOti ΧρΟΜΘΤΟΓρθφΜΜ Hafl cunuKarentKD, ncnonb3ya CMecb αμχπορμθτθηθ μ μθτθηοπθ (95 : 5 no o6teMy) b KasecTBe antoema. HncTbie cf)paKunn coSnpatOT n amoem BbinapuBaiOT. Οοτθτοκ npeBpaujafOT b maBeneBOKncnyio conb b aue-τοηθ. Conb OT$nnbTposbiBaK)T n KpncTannn3ytOT n3 CMecn aueio-HHTpuna n αμ9τμποβογο 3$npa. ilpoflyKT peaxunn οτΦιίπβτροββιββιοτ n BbicyLunBaK>T, nonysan 2,8 sacieti (33,7 %) maBenesoKncnoti conn (1:1) 6-[(3-χηορφΘΗΜη)-(1 H-1,2,4-Tpna3on-1-nn)-Meinn ]-1 -MeTnn-1 Η-6θη30-Tpna3ona; t. nn. 125,0 °C (coeAUHeHne 65).
PlpuMep 22 CMecb 9,1 sacieti MOHOčpOMruApaTa 6-(6ροΜφθΗηηΜβ™η)-1-•MeTnn-1H-6eH30Tpna3ona, 10,25 sacieti (4-Memn-1 H-nMHAa3on-1sļ>e-HunMeiaHOHa n 64 sacieti aueTOHmpuna nepeMeiuneaiOT b leseisne 3 sacoB npn TeMnepaiype κμπθηκα c oāpaTHbiM χοποαιίπβημκομ. Apeio-HmpunbHbiti cnoti BbinapuBaKDT n OdaTOK nepeMemuBatoT b TeseHne hosu npn KOMsamoti TeMnepaType b CMecu 16,6 sacieti Kap6oHaia Kanna n 80 sacieti BOAbi. ilpoAyKT peaKunn 3KCTparnpyiOT Anxnop-μθτθηομ. CKdpaKT BbicyujnBaK)TI φnπbτpyκ)τ n BbinapnsaiOT. OciaTOK osniuatOT c noMombio KonoHOSHOti χροΜ3τοφ3φιιη ηθα cnnnKarenbK), ncnonb3ya CMecb χποροφορΜθ n Meiasona (98 : 2 no o6beMy) b KasecTBe amoema. UeneByto Φρθκαμο cočnpafOT n antoem Bbina-pnBaKDT. OciaTOK osnmatoi c noMouļbio 05pan/iM0^a30B0ti χροΜθτο-φβφκκ (>KXBfl) H3A φ33θΛ τι/ma Li Chroprep RP 18, ncnonb3ya CMecb MeiaHona, τeτpaΓHApoφypaHa n aueiaia aMMOHna (30 : 5 : 65 no o6teMy) b KasecTBe amoema. Hncibie φρθκρίΊΐΊ coOnpatoi n antoem BbinapnBatOT. OciaTOK AononHmenbHO osninafOT c nOMOiiļbio κοπο-HOSHoti χροΜθτοτρθφΜΜ H3A cnnnKarenbK), ncnonb3ya CMecb χποροφορΜθ n MeiaHona (95 : 5 no očbeMy) b KasecTBe antoema. HncTbie φρθκΐίκκ co6npaiOT n sntoeHi BbinapneaKDi. Οοτβτοκ npeBpamatcn b iAaeeneBOKncnyto conb b τeτpaΓHApoφypaHe. Conb ot-φnnbτpoBblBaιoτ n BbicyuJHBaiOT b BaxyyMe npn 80 °C, nonysaa 3,1 sacieti (35,8 %) maeeneBOKncnoti conn (1:1) 1-Μβτηπ-6-Γ(5-Μβτιιπ-1Η--nMMAa3on-1-nn)^eHnnMeTnnļ-1H-6eH30Tpna3ona; t. nn. 120,7 °C (co· eAnHeHne 66). 57 LV 10452 npMMep 23 ŪMecb 8,2 HacTefi MOHOčpoMruflpaTa 6-(6ρομΦθημπμθτμπ)-1--MeTnn-1H-6eH30Tpna3ona, 3,45 ηθοτθμ 4H-1,2,4-Tpna3on-4-aMHHa m 64 nacTeiŽi aueTOHHTpuna nepeMemuBaKDT cHanana b τθηθημθ 2 nācos npn TeMnepaType κμπθημη c oSpambiM xonoAnnbHHKOM, a 3θτθμ b τθηθημθ hohh npn κομηθτηομ TeMnepaType. BbinaAatomMM ocaflOK οτφΜΓ^τρο-BbiBafOT n φnnbτpaτ KOHueHTpnpyiOT, nonyHaa āpOMucTbiii 4-aMMHO-1--[(1 -μθτμπ-Ι H-6eH30Tpna3on-6-nn)^eHnnMeTnnļ-4H-1,2,4-Tpna3onnii. K nepeMewnBaeMOMy pacTBopy ποοπθαηθγο οοθακηθημη, 7,3 nacTefi 50 %-Horo pacTBopa φοοφΜΗΟΒοίί KucnoTbi n 7,3 sacTeii 12 N pacTBopa con^HOM KucnoTbi b 40 nacm MeiaHona m 20 wacT?ix BOflbi AoSaBJiatOT no Kann^M pacīBop 3,45 ηθοτθμ nmpma HaTpMB b 20 ηθοτβχ BOAbi. riocne 3aBepweHUfl αο63βπθημβ nepeMemuBaHue npoAon>KajOT b ΤΘΗΘΗΜΘ 30 MMHyT ΠρΜ K0MH3TH0M TeMnepaType. MeTaHOAbHblM cnoii BbinapMBatOT μ οοτβτοκ o6pa6aTbiBatoT pacTBopoM tmapookmcm θμμο-hmh. (1poAyKT peaKUMM 3KCTparMpytoT AnxnopMeTaHOM. 3κοτρ3κτ BbicyiiiMBaK)T, φMΠbτpy^oτ m BbinapMBatoi. OcTaiOK OHMmatOT Aea^Abi c noMOLUbio κοποΗΟΗΗοίί χρομθτογρβΦμμ Hap CMAMKareribio, Mcnonb3yfl CM8Cb χποροφορΜθ μ μθτθηοπθ (98 : 2 no o6teMy) b «anecTBe snfoeHTa. HMCTbie φρθΚΑΜΜ COČMpaKDT Μ 3ΠΚ)ΘΗΤ BbinapMBaiOT. 0CT3T0K npespa-mafOT b LuaBeneBOKMcnyfo conb b 36 ηθοτβχ τeτpaΓMApoφypaHa. Conb οτΦμπβτροββιβ3Κ)τ m KpMCTannM3ytOT M3 45 nacTeti STM/iapeTaTa. l1poAyKT peaKLļMM οτΦμπβτροββιβ3Κ)τ m BbicyiuMBaK)T, nonyHaa 3,1 nacTSM (40,7 %) ιμθβθπθβοκμοπομ cohm (1 : 1) 1-ΜΘΤΜΠ-6-ΓφβΗΜπ-(1Η* -1,2,4-TpMa3on-1-Mn)-MeTMnl-1H-6eH30TpMa3ona; t. nn. 164,9 °C (οοθαμ-ΗΘΗΜΘ 67). ΠρΜΜθρ 24 K nepeMeujMBaeMOMy m HarpeBaeMOMy pacTBopy 3,3 ηθοτθμ 1-ΜΘΤΜΠ-α.-(2-τΜΘΗΜπ)-1 H-5eH30TpMa3on-6-MeTaHona b 45 nacTflx TeTpa-ΓMApoφypaHa Ao6aBn?i(OT 4,2 ηθοτθμ 1,1 '-Kap6oHMn-6Mc(1 H-MMMAa3ona b 3ΤΜθθφ©ρ8 a30Ta. riocne πθρθμθιιιμββημβ b τθηθημθ 30 MMHyT npM 50 °C, peaKi4MOHHyio cMecb BbinapMBaKDT. l“lpoAyKT peaKLļMM SKCTpa-fMpyiOT 3ΤΜΠ3Ι4ΘΤ3ΤΟΜ. 3<CTpaKT npOMbIBafOT pa36aBneHHblM paCTBO- 58 poM rnflpoKap6oHaTa HaTpua, BbicyiunBaK)T, 0nnbTpyKDT m BbinapuBaKDT. OdaTOK OHUluaKDT C nOMOlUblO ΚΟΠΟΗΟΗΗΟίί ΧρΟΜΘΤΟΓρθφΜΜ Hafl cunuKarenbK), Mcnonb3ya CMecb αμχπορμθτθηθ μ μθτθηοπθ (98 : 2 no oābeMy) b KaneciBe θπιοθητθ. HncTbie φρβκρΜΜ coČMpafOT m antoeHT BbinapuBatoT. Οοτθτοκ KpncTannn3ytoT n3 aueTOHa. npOAyKT peaKunn OT$nnbTpoBbiBaiOT m BbicymnBaioT, nonynafl 1,9 naciePi (49,5 %) 6-[(1H--nMHAa3on-1-nn)-(2-TneHnn)-MeTnnļ-1-MeTnn-1H-6eH30Tpna3ona; τ. nn. 157,2 °C (οοθαμηθημθ 68). floAoāHbiM o6pa30M nonynaK)T τθιοκθ: 6-[(1Η-μμμα330π-1-μπ)-(3-τμθημπ)-μθτμπ1-1-μθτμπ-1Η-6θη30τρμ-a3on, τ. nn. 160,5 °C (οοθαμηθημθ 69); 5-f(6MC-(1H-MMMAa3on-1-Mn)-MeTMnļ-1-6yTMn-1H-6eH30TpMa3on, τ. nn. 180,1 °C (οοθαμηθημθ 70); m 5-(1-(1 H-MMMAa3on-1 -Mn)-2-6yTMHMnļ-1 -ΜΘΤΜΠ-1 H-6eH30TpMa3on, τ. nn. 155,5 °C (οοθαμηθημθ 71). npMMep 25 CMecb 1,6 nacTSM 4-(lH-MMMAa3on-1-MnMeiyn)-N2-$eHMn-1,2--φΘΗΜΠΘΗΑΜ3ΜΜΗ3, 20 Η30ΤΘΜ yKCyCHOM KMCnOTbl M 1,08 Η30ΤΘΜ Κ0ΗΙ4ΘΗΤρΜρ0Β3ΗΗ0Μ ΟΟΠΠΗΟΡί KMCnOTbl ΟΧΠΘΧφΘΙΟΤ B ΠΘΑ^ΗΟΜ 63ΗΘ npM 12-16 °C, PacTBOp 0,83 nacTePi HMTpMTa ηθτρμπ b 7 ηθοτπχ BOAbi AoāaBnnioT no KannsRM. Ποοπθ 3aBepiueHMn AočaBneHMn pea«i4M0HHy(0 CMecb οοτθβπη kdt aoctmrHyTb κομηθτηομ TeMnepaTypbi npM nepeMeoiMBaHMM. PeaKUMOHHyK) CMecb ββιπμβθιοτ b noAmenoHeHHyio neAnHyto BOAy μ προΑγκτ 3KCTparMpytOT αμχπορμθτθηομ. 3KCTpaKT BbicyajMBaKDT, φMnbτpy^oτ m BbinapMBaK)T. Οοτθτοκ ohmmatOT c noMombio κοποηοηηομ χροΜ3τοτρ3φΜΜ H3A CMHMKarenbK), Mcnonb3yn CHanana CMecb χποροφορΜθ m MeTaHona, HacbiiAeHHoro θμμμθκομ, (97,5 : 2,5 no o6teMy), a 3θτθμ CMecb 3TnnaqeTaTa, μθτθηοπθ μ μθτθηοπθ, HacbiiAeHHoro θμμμθκομ, (95 : 2,5 : 2,5 no o6teMy) b κθηθοτβθ βπιοθητοβ. HkicTbie Φρθκαμμ coČMpafOT μ θπιοθητ BbinapMBaiOT. Οοτθτοκ pacTBopnioT b ομθομ aueTOHa μ αμμ30προπμποβογο 3φΜρθ. ΠρΟΑΥΚΤ peaKLļMM 0ΤφΜΠΒΤρ0ΒΗΒ3Κ)Τ, npOMbIBafOT AMM30np0nMn0BblM 3φΜροΜ μ BbicyoiMBaK)T B BaxyyMe npM 60 °C, nonyHaa 0,81 nacTePi 59 LV 10452 (49,0 %) 6-(1H-MMHAa3on-1-nnMeTnn)-1-0eHnn-1H-6eH3OTpna3ona; τ. ππ, 110,1 °C (coeAUHeHne 72), noflOČHbiM o6pa30M nonyHaiOT τθιοκθ: 1 -LļHKnoreKcnn-6-(1 H-nMHfla3on-1 -nnMeTnn)-1 H-6eH30Tpna30n; τ. ππ. 109,3 °C (coeflUHeHne 73); 1-6yTwn-5-[(1H-MMHfla3on-1-nn)-0eHnnMeTnn]-1H-6eH3OTpua3on; τ. ππ. 83,6 °C (οοθαμηθημθ 74); maBeneBOKncnyto conb (1 : 1) 1-6yTnn-6-[(1H-nMMfla3on-1-un)--$eHnnMeinnļ-1H-6eH30Tpna3ona; τ. ππ. 109,0 °C (οοθαμηθηκθ 75); u4aBeneBOKncnyto conb (1 : 1) 6-(1H-uMUfla3on-1-nn)-cf)eHnnMe-Tnn-1-(1-MeTnn3Tnn)-1H-6eH30Tpna3ona; τ. ππ. 123,1 °C (οοθακηθηκθ 76); MOHOHUTpaT 6-f(4-xnop$eHnn)-(1H-nMHAa3on-1-nn)-MeTnn]-1-$e-Hnn-1H-6eH30Tpna3ona; τ. ππ. 166,7 °C (οοθαηηθηκθ 77); μοηοημτρθτ 6-f(4-xnop$eHnn)-(1H-MMHAa3on-1-nn)-MeTnn]-1-($e-Hnn9Tnn)-1H-6eH30Tpna3ona; τ. ππ. 160,7 °C (οοθαηηθημθ 78); m MOHOHUTpaT 6-f (4-ΧΠ0ρφθΗΙ^ΙΠ)-(1 Η-ΜΜΗΑ330Π*1 -ΜΠ)*ΜΘΤΜΠ]-1-(4* -xnop$eHMn)-MeTnn-1H-6eH30Tpna3ona; τ. ππ. 185,9 °C (οοθαμηθημθ 79); flpHMep 26 Κ nepeMeiuHBaeMOM h oxnax<AaeMoii (0 °C) ομθομ 3,9 HacTefi 4-(1 Η-ΜΜΜΑ330Π"1 -ΜΠΜΘΤΜΠ)- Ν^-(φθΗ ΜΠΜΘΤΜΠ )-1,2*φΘΗΜΠΘΗΑΜ3ΜΜΗ3 Μ 9,6 ΗΘΟΤΘΜ KOHLļeHTpupOBaHHOH ΟΟΠΗΗΟΜ KHCnOTbl ΠΟ «annflM AOČaBnnfOT pacTBOp 1,86 nacTePi HHTpuTa HaTpun b 8 ηθοτπχ BOAbi. Ποοπθ 3aeepujeHnn AoāaBneHna πθρθμθιιιμββημθ προΑοπχοιοτ b τθηθημθ 10* 15 MHHyT npM SToiži HM3KOIŽI TeMnepaType. Ρθθκαμοηηομ ομθομ πο3Βοππκ)τ AOCTnmyTb κομηβτηομ TeMnepaTypbi m BbinuBaiOT 3Ty CMecb b BOAy. CoAep>KHMoe 3KCTparnpyioT αμχπορμθτθηομ. Βοαημμ KMcnoTHbm cnoPi o5pa6aTbiBaiOT κοηαθητρμροβθηηημ pacTBOpOM rnAPOOKHCM aMMOHHn, npM 3tom oxnax<Aan cMecb, m npoAyKT ρθθκαμμ 3KCTparnpyK)T αμχπορμθτθηομ. SKCTpaKT BbicyuiMBafOT, φnπbτpy^oτ m BbinapHBatOT. Οοτθτοκ οημιαθιοτ nyTeM φMΠbτpa^MM hbr cunuKarenbK), ncnonb3yn CMecb χποροφορΜθ h MeTaHona (95 : 5 no o6teMy) b KanecTBe θπιοθητθ. HMCTbie Φρθκαμμ coSnpatoT μ θπιοθητ BbinapuBaiOT. 60 Οοτβτοκ AononHMTenbHO OMniuaiOT c nOMombio kojiohohhom xpOMaTorpa$nn Hafl cnnm<arefibK), ncnonb3yfl cMecb ainnaLieTaia, MeiaHona n μθτθηοπθ, HacbimeHHoro θμμμθκομ, (95 : 2,5 : 2,5 no o6beMy) b «anecTBe antoema. HncTbie Φρθκαιίμ co6upaiOT μ θπιοθητ BbinapuBatOT. Προαγκτ peaKunn οτφΜΠΒτροΒΒίΒβιοτ, npoMbieaiOT AMH3onponnnoBbiM 3φΜρθΜ ιί BbicyiunBaiOT b eaKyyMe npn 50 °C, nonynaB 1,6 nacTeii (40,9 %) 6-(1Η-μμμα330π-1-μπμθτμπ)-1--( Φθηιίπμθτιιπ)-1 H-6eH30Tpna3ona; τ. ππ. 85,4 °C (οοθαμηθημθ 80). ilofločHbiM o6pa30M nonyHaKDT TatoKe:
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% CO X O _CM CM X 0 1 X % co Xo Ό- X X 1 X » X 1 X ( 1 X 1 X s X CO CM X X X X X X <D X 0 X & ·& co O) 99 0 CM co n co r-» cn CD 0 CM co Ό- «I— 0 0 0 0 0 0 0 0 O O r- 1— t— T- T” T“ T— LV 10452 131.1 132.5 162,0 235.2 260,4 163.8 110.6 170.9 0CT3T0K 164.9 175.3 188,6 117 co ωα) 9,ωωω ω ω O r\i SS s s CM CM co i i rt rt x x I χ 0 co co Ο O ra ra to ra cc m ^ CŪCŪfT OCŪCDCD a B n· O φ ο o -ļ- I; ooo ο ο § η 1 τ i CM cm j—iii oo CJooo ο υ O OO 3^000 Ο Ο χ in 6 6 6 6 5 6 5 5 6 5 5 5 5 6 6 6 X X X X X X X X X I I I I I χ χ ο οοοο οοου οοοοοοο II II II II II II II II II II II II II II π π Ζ ΖΖΖΖ ΖΖΖΖ Ζ Ζ Ζ Ζ Ζ 2 ζ I 1 » » 1 1 1 \ \ 1 1 II I ~ I XXXI ΧΧΧΧ I I I I I χ χ ο οοοο οοοο οοοοοοο II II II II II II II II II II II II II II η Μ X ΧΧΧΧ ΧΧΧΧ I I I I I χ Ζ Ο ΟΟΟΟ ΟΟΟΟ Ο Ο Ο Ο Ο ' · co S k i i . i £ « iic £ Z o 11¾ 1 s C\J <X) 1 , —L 1 1 μ- 1 , 5 Q- 1 t 1 2 η ο X X ^XIcvi«XX^g«XX 5 ' 5 I X | ? s ! 3 ^ ~ § 4? fe o§° S 5 ? co — to CM CM • i * C C »1,1 · | · i , i 'M-'tfSO ^ Μ- I ^ 'M'rv.'M··^· X. ^ I I i £ I I χ I ΧχΧΧ,χΙ ± OOss?OOoO Οο^ΟχοΟ _ι, . χ. q > X. OOSs'oo^O o 2 ο o b? o -<4 4r ^ χ τι1 n co 4 4 s 4 4 ^ TT - 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 -2,3-flnrnflpo6yTaHflnoaT (1 : 1) = (±) -βμηηοκμογι3η conb (1:1) Ν co tn 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 ΧΧΧΧΧΧΧΧΧΧΧ X X X X ooooooooooo oooo II II II II II II II II II II II || II || || ZZZZ'ZZZZZZZ zzzz I < I 1 1 1 1 1 1 1 1 , , , ΧΧΧΧΧΧΧΧΧΧΧ zzzz OOOOOOOOOOO Miīniī II II II II II II II II II II II X X X X zzzzzzzzzzz oooo co CM X , <9j o i X Φ ± 1 . . . x τ Ο ΐ) ί ' 1 O , coconcO(j c\j cm „ V . , co c\j χχχχχνχ—υ^-f- χ χ x — οουο-ρο^όχ ο o £ ο « ο | Ο Ο =3- CSJ 1 1 ^ , 1 1 1 » C .1.1 sTT (D (βΙΙΙΙΙ ΰ χ X χ X ītbcoO OCDCOCDCDtDg ^ ļ?> Ιό 199^099909 | * 9 9 9 9 »7Cl,IXXxc3o0004 '9090 T-" - 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 LV 10452 65 ΠρΜΜβρ 27 K nepeMeninBaeMOMy n oxna>KAaeMOMy (5 °C) pacTBOpy 5,2 5 nacTePi 4-[(lH-nMMAa3on-1-nn)-$eHnnMeinnļ-1,2-$eHnneHAnaMHHa b 4,8 nacTflx yi<cycHoPi KMcnoTbi n 20 HacTnx BOflbi ΑΟδθΒπηιοτ pacTBOp 1,38 nacīePi HHTpma HaTpua b 10 HacT«x BOflbi. Coflep>KHMoe nepeMe-mnBaiOT b τθηθημθ 1 naca npu κομηβτηομ TeMnepaType. PeaKunoHHyK) CMecb 05pa6aTbiBaf0T pacTBopoM ruppoKapčoHaTa HaTpua m npoflyKT 10 peaKLļnn 3«cTparupyiOT αμχπορμθτθηομ. 3«CTpaKT BbicyujnBaK}T, $nnbTpyKDT w BbinapnsafOT. OciaīOK KpncTannn3yfOT H3 64 nacTePi STMnaueiaia. npOAyKT peaKpnn OTCļDunbTpoBbiBaioT n BbicyujnBaKDT, nonynaa 4,7 nacrrePi (85,3 %) 5-f (1H-MMHAa3on*1-nn)^eHnnMeTnnļ-1H--6eH30Tpna3ona; τ. nn. 178,8 °C (coeAUHeHne 146). 15 noAOČHbiM o6pa30M nonyHatOT τθιοκθ: 1-6yTnn-6-(1H-nMHAa3on-1-nnMeTnn)-1H-6eH30Tpna3on; τ. nn. 49.2 °C (coeAnneHvie 147); n 1-6yTnn-5-(1H-HMHAa3on-1-nnMeTnn)-1H-6eH30Tpna3on; τ. nn. 74.3 °C (coeAUHeHne 148). 20 25 30 35 66 flpuMep 28 CMeCb 4,3 HaCTeii 1-f 1-(4-ΧΠθρ-3-ΗΜΤρθφθΗΜΠ)-9ΤΜΠ1-1Η-ΜΜΜΑ-a3ona, 3,42 sacieti MOHoruApaia rnflpa3HHa n 40 saciet 1-6yiaHona nepeMemuBaHDT b TeseHue 12 sacoB npn TeMnepaiype κμπθημβ c o6paTHbiM xonoflnnbHHKOM. (locne οχπθχαθημη Ao6aBjiBK)T 3 sacieti 10 N pacTBopa conaHoū KucnoTbi. Pa3AeneHHbiū opraHusecKMti cnoti BbinapuBafOT. OciaTOK nepeMeiuuBaiOT b sinnaueiaie. f1pOAyKT peaKLļnn c^unbTpoBbiBaioT m BbicywnBaK)Tt nonysaa 4,5 sacieti (99,0 %) MOHOxnoprnApaia 6-f 1-(1H-MMMAa3on-1-3Tnnļ-1H-6eH30Tpn-a3on-1-ona (coeAUHeHne 149). floAoāHbiM o6pa30M nonysaiOT TatOKe:
No coe- flMHe HMfl R1 -Α1=Α2-Α3=Α4- P OCHOBa- Hne/conb T. nn. (°C) 150 φθΗΜΠ -CH=CH-N=CH- 5 ocHoeaHue ociaTOK 151 H- -CH=CH-N=C(CH3)- 6 ocHOBaHue 157 152 H- -N=CH-N=CH- 6 ocHoeaHue 222 153 φθΗΜΠ -N=CH-N=CH- 6 ocHOBaHue 185 154 φθΗΜΠ -CH=C(CH3)-N=CH- 6 ocHosaHMe 200 155 φθΗΜΠ -C(CH3)=CH-N=CH- 6 ocHOBaHue ociaTOK 156 Η- -CH=CH-N=CH- 5 ocHOBaHue ociaTOK 157 φθΗΜΠ -CH=CH-N=CH- 6 HC1 ociaTOK LV 10452
PlpuMep 29 CMecb 6,5 nacTePi 1-[(4-φτορ-3-ΗΜτροφθΗκπ)-ΜθΤΜη]-1Η-ΜΜΜβ-a3ona, 6,01 nāciet MOHornflpaTa ruApa3HHa n 80 HacTePi 3TaHona nepeMeiunBaioT μ κμπητητ c očpaTHbiM xonoAnnbHHKOM b τθηθημθ 5 nācos. Ποοπθ oxna>KAeHMfl Ao6aBnatoT 12 nacTePi 5 N pacTsopa οοπηηομ KkīcnoTbi. Οοαθρ>κμμοθ BbinapuBaioT. Οοτθτοκ nepeMeujusaiOT βμθοτθ c 30 HacTHMu BOAbi n BbinaAatomuPi b ocaAOK προΑγκτ peaKUUM οτφΜΠΒτροΒΒΐΒ3Κ)τ μ κμπβτβτ b 40 nacTax 2-nponaHona. flOČaBnBIOT 2-nponaHOn, HaCbllueHHblPi XnOpMCTblM BOAOpOAOM. Conu Π03Β0Πλ(ΟΤ
KpncTannn30BaTbCfl npw κομηθτηοΡι TeMnepaType. KpucTannbi οτΦμπβτ-poBbiBatoī m BbicyninBafOT, nonyHafl 4,1 nacTePi (54,3 %) μοηοχπορ-rnApaTa 6-(1 H-nMHAa3on-1-nnMeTnn)-1 H-6eH30Tpna3on-1-ona; t. nn. 207,4 °C (οοθα^ηθημθ 158). (lOAOČHbiM o6pa30M nonyMaK)T τθιοκβ: 6-Γ(3-ΧΠ0ρφθΗΚΠ)-(1Η·ΜΜΜΑ330Π-1-ΜΠ)-ΜβΤΜΠΗΗ-6βΗ30ΤρΜ330Π- -1-οπ (οοθαμηθημθ 159). 68 ΠρίΊΜΘρ 30 CMecb 3,2 sacieti 6-(1H-MMMfla3on-1-MnMeTnn)-1H-6eH30Tpna3on--1-ona, 1 nāc™ KapāoHaia Kanna κ 27 sacieti Ν,Ν-αμμθτμπΦορμθμ^ nepeMeoiMBaioT b τθηθημθ 30 MHHyT npn κομηθτηοκ TeMnepaiype. floāaBnsiKDT 2,1 sacieti 1-(xnopMeimi)*3-Meinn6eH3ona n nepeMe-liiMBaHue npoflon>KaKDT b TeseHne 3 sacoe npn KOMHamoti τβΜπβ-paiype. CMecn πο3βοπβκ)τ cioaib b TeseHne hosm npn κομηθιηοϊι TeMnepaiype n nocne sioro ee BbinapuBaioi. OciaioK pa36aBnaioT BOfloti n npoflyKT peaKUMM 3KCTparnpyK)T AnxnopMeiaHOM. 3KdpaKT BbicyujMBaK)T, ct>nnbTpyK>T n KOHueHTpnpyK)T. KoHLļeHTpai osumatOT c nOMOlAblO KOnOHOSHOti χρΟΜΘΤΟφθφηη H3A cnnnKarenbK), ncnonb3ya CMecb χποροφορΜθ n MeiaHona (95 : 5 no o6beMy) b Kaseciee smoema. HncTbie φρ3κΐ1ΜΜ cočupatOT η amoem BbinapnBatOT. TBepAbiti ociaiOK Kpnciannw3yiOT n3 CMecn 3Tnnaueiaia n Ann3onponnnoBoro 3φηρθ (10 : 20 no o6beMy). f1poAyKT peaKpnn οτφηπΒτροΒΗΒθίοτ, npOMbieatOT Ann3onponnnoBbiM 3φιιροΜ n BbicyiunBaiOT, nonysaa 3,4 sacieti (70,9 %) 6·(1 Η-ηΜηΑ33ΟΠ-1-ηΠΜβΤηπ)-1-Γ(3-ΜβΤηΠφβΗηΠ)-ΜβΤΟΚ0η1-1Η--6eH30Tpna3ona; t. nn. 120,1 °C (coeAMHeHne 160). floAoāHbiM o6pa30M nonysatoi Τ3κ>κβ:
LV 10452
03 CO c c μ oo co in co co -r- CM T- σ> CM CM. CD in T“* 0 00 ^r CD 1n Tļ- cm' •M· co co' co" Γ*·' cm' co' 0" co 0 co O 0 UD O cm T— CM ▼— co CM 03 CM co -r- 1— T— T— τ- T— 1— ▼— t— T“ T- 1— ·<— T— CM r— cd Φ CD CD CD CD CD CD CD CD CD CD 1 J3 s X X X CM CM s X X X CM X X X X (0 c X I I I —r~ I X I I *T“ I X I X CŪ 0 CŪ CŪ CŪ CŪ X X CŪ CO CŪ CŪ X CŪ CŪ CŪ 0 CŪ 0 0 lO CŪ CŪ CD CD 0 0 CD CŪ CŪ co 0 co CŪ CŪ X CD I 0 Īd s 0 X 0 X 0 X 0 1 0 0 0 1 0 X 0 X 0 X 0 0 X 0 X 0 X CM 0 1 0 X 0 0 0 0 u 0 0 0 0 c_> CJ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
< II co CM < II ΧΧΧΧΧΧΧΧΧΧΧΧΧΧΧΧοϋοοοοοοϋουοοοοο II II II II II II II II II II II II II II II II zzzzzzzzzzzzzzzz I I I I I > I I I > I I I I I Iχχχχχχχχχχχχχχχχ0000000000000000 II II II II II II II II II II II . II II II II IIχχχχχχχχχχχχχχχχoooooooooooooooo CMai co C\JX0 coXo CM CM 1 CM 1 CM CM CM CM X 0 X 0 CM X Γ3 CM X 0 X o X 0 1 CM X CM X 1 X X 0 \ X 0 1 9 0 X X CM 0 0 0 Ό" X co 0 1 co X co 0 co 1 "šf X co 0 0 1 0 1 CD 0 II X 0 X 0 9 X co 0 1 0 1 0· X co 0 1 0· X CO 0 OJ 10 X CD X CD 0 1 0 X co 0 ό X 0 X 0 9 X co LO X LO X co X 1 \ t \ 0 co X co X CM 1 1 CM 0 co o CD 0 0 1 co Tf co 0 1 CM 0 or
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X X 1— CM co CD co σ> co T“ H" LV 10452 72 ΠρίΊΜθρ 31 CMecb 3,23 MacTeii 6-(1H-nMnfla3on-1-nnMeTnn)-1H*(5eH30Tpn-a3on-1-ona, 2,07 nacTen KapāOHaia Kanna n 20 nacien αμμθτμπ-cynb$OKCHfla nepaMemnBaiOT b TeHeHne 10 Mw-iyT npn KOMHaTHon TeMnepaType. 3aieM floāaBnatoT 2,55 nacien 2-PioflnponaHa n nepeMeiunBaHMe npoflon>KatOT CHanana b τθηθημθ 15 MHHyT npn KOMHaTHoPi TeMnepaType, a 3Θτθμ b τθμθημθ 1 naca npn 50 °C. PeaKunoHHyio CMecb BbinapneaioT. floOaBnmoT 50 nacien BOflbi. (1poflyKT peaKLļnn 3KCTparnpyK)T βηχηορΜθΤθΗΟΜ. θκοτρβκτ Bbicywn-BaKDT, $nnbTpytOT n BbinapnBaiOT. Oct3tok onninaroT c noMOiubto κοηοΗΟΗΗοη xpOMaTorpa$nn ηθα cnnnKarenbīo, ncnonb3ya CMecb xnopocpopMa n MeTaHona (95 : 5 no o6"beMy) b KasecTBe amoema. HncTbie φρθκρηη co6npaioT n amoem BbinapnBaioT. Οοτβτοκ KpncTannn3yiOT n3 14 nacTen finamnoBoro acpnpa. l1poflyKT peaKpnn OT0nnbTpoBbiBaK)T n BbicyiunBaioT, nonyHaa 3,3 nacien (85,5 %) 6-(1H--nMnpa3on-1 -ηπΜΘτηπ)-1 -(1 -Μβτηπ3τοκοη)-1 H-6eH30Tpna30na; τ. ππ. 114,3 °C (coeflnHeHne 195). noflOČHbiM o6pa30M nonyHaioT TaKx<e:
No coe- Αμηθ- R1 R2-b -A1=a2-A3=A4- OcHOBa- Hne/conb T.nn. (°C) 1 p 3 4 5 6 196 H- 3-nnpnflnHnn-CH2· -CH=CH-N =CH- ocHoeaHue 120.6 197 H- CH3-CH2- -(CH3)CH- -CH=CH-N=CH- HNO3 133,3 198 H- CH3-CH2-°'C(=0^ -CH2- -CH=CH-N=CH- HNO3 143,3 199 H- CH3'CH2-°'C(=0)· tCMoh -CH=CH-N=CH- ocHoeaHne Mac- no 73 LV 10452 1 o 3 4 5 6 200 H- CH3-CH2-0-C(=°)* -CH=CH-N=CH- ΟΟΗΟΒβΗΜβ Mac- -(CH2)3- no 201 H- CH3-(ch2)4* -CH=CH-N=ČH- hno3 115,2 202 H- CH3'(ch2)5- -CH=CH-N=CH- HN03 93,9 203 H- CH3*(CH2)8- -CH=CH-N=CH- HN03 90,0 204 H- Br-(CH2)2- -CH=CH-N=CH- HN03 131,3 205 H- 2-nMpMflMHMn-CH2· •CH=CH-N=CH- ΟΟΗΟΒ3ΗΜβ 81,7 206 H- CH3'(ch2)6' -CH=CH-N=CH- HN03 80,7 207 H- C6H5-(CH2)3- -CH=CH-N=CH- (COOH)2 135,7 208 H- C6H5'(ch2)2- -CH=CH-N=CH- (COOH)2 136,0 209 H- 1-ΜβΤΜΠ-4·ΠΜΠβ- -CH=CH-N=CH- 2HN03 176,9 ρΜΟΜΗΜΠ 210 ch3·. CH3-CH 2-0-0(=0)- -CH=CH-N=CH- OCHOB3HMe ocTa- -CH2- TOK 211 φβΗΜΠ CH3-CH2· -N=CH-N=CH- 0,5(COOH)2 92,1 212 φβΗΜΠ CH3-CH2- -CH=C(CH3)- HN03 125,8 -N=CH- 213 φβΗΜΠ C6H5-CH2- -C(CH3)=CH- ocHosaHMe 156,2 -N=CH- 214 φβΗΜΠ CH3-CH2-CH2- -CH=C(CH3)- HNO3 126,9 -CHp- -N=CH- ripuMep 32 5 CMecb 4,5 nacTeii μοηοχποργμαρθτθ 6-[1-(1H-MMHAa3on-1-nn)- -3Tnn]-1H-5eH30Tpna3on-1-ona, 3,12 MaciePi Ριοαμοτογο 3Tnna, 3,7 nacTePi Kap6oHaTa HaTpufl n 63 HacTeū Ν,Ν-αμμθτμπΦορμθμμαθ nepeMeiuMBaioT b τθηθημθ 4 nācos npn κομηθτηοΡι TeMnepaiype. PeaKunoHHyto CMecb BbinapuBatOT n oct3tok pa36aBnfliOT b βοαθ. 10 npoflyKT peaKpnn 3KCTparnpyiOT TonyonoM. 3KCTpa«T BbicywuBaK)T, $nnbTpytoT m BbinapuBaiOT. Οοτθτοκ KpncTannn3yiOT M3 CMecu 27 naGiePi 3TnnaueTaia m 21 nacin flnn3onponnnoBoro scpupa. npofly«T peaKunn οτΦμγ^τροβμβθκοτ n BbicyujMBaioT, nonynaa 2,26 nacTePi 74 (51,6 %) 1-3tokch-6-[ 1-(1H-nMHfla3on-1-nn)-3Tnnļ-1H-6eH30Tpna3ona; τ. nn. 81,1 °C (coeflUHeHne 215).
IlofločHbiM o6pa30M nonyHaK3T Τ3Κ>κθ; 5- f(1H-nMHfla3on-1-nn)-$eHnnMeTnn 1-1-(1-μθτμπ3τοκομ)-1Η-6θη-5 30Tpna3on; τ. nn. 85,7 °C (coeflMHeHne 216); l-3TOKcn-5-f(1H-nMHfla3on-1-nn)-$eHMnMeTMnļ-1H-6eH30Tpna3on; τ. nn. 85,5 °C (οοθαμηθημθ 217); 6- f 1 -(1 H-MMMfla30n-1 -ΜΠ)-3ΤΜΠ ]-1 -(φθΗΜΠΜΘΤΟΚΟΜ)-1 Η-6θΗ30ΤρΜ-a3on; τ. ππ. 128,6 °C (coeflUHeHne 218); μ 10 (+)-BMHHOKncnyK> conb 6-ri-(1H-MMHfla3on-1-nn)-9Tnn]-1-(2-MeT- 0KCM3T0Kcn)-1H-6eH30Tpna30na; τ. nn. 140,0 °C (οοθαμηθημθ 219). ΠρΜΜθρ 33
K nepeMeujMBaeMOM m HarpeBaevioPi (50 °C) ομθομ 2,81 nacTeii 15 6-(1H-MMMfla3on-1-MnMeTMn)-1M-6eH30Tpna3on-1-ona n 22,5 sacieti Ν,Ν-βΜΜθΤΜΠφορΜθΜΜβθ ΑοδθΒπηιοτ 0,69 sacieti flucnepcnn rnApnfla Haipna. PeaKunoHHyto CMecb nepeivteujtiBatOT ao τβχ nop, noxa He npeKpaTMTcn BbifleneHne Boflopofla. floāaenntoT npw κομηθτηομ TeMnepaType 1,28 sacieti 1-xnop-2-MeTOKCH3TaHa v\ nepeMenmBaHue 20 npoflonxaK)T b TeseHue ecero βτογο βρθμθημ. 3θτθμ AOčaBnatOT 22 sacieti AHMeτnπcyπbφoκcnAa n 0,04 sacieti 2-(2-MeTOKcn3TOKCH-N,N--6ncf2-(2-MeTOKCM3TOKCn)-3Tnnļ-3TaHaMHHa. PeaKunoHHyio CMecb nepeMeniMBaioT b TeseHtie hohm npn 50 °C, a 3θτθμ BbinuBatOT b BOAy. npOAyKT peaKpnn 3KCTparnpyt0T AuxnopMeTaHOM. 3xcTpaKT Bbicy-25 inusaiOT, φMΠbτpyκDτ tt BbinapnsaioT. OciaTOK osmuatoi c noMombio κοποΗΟΗΗοΡί χροΜ3τοτρ3φΜΜ H3A ctmtiKarenbīo, ncnonb3ya CMecb χποροφορΜ3 ti MeiaHona (95 : 5 no o6t>eMy) b KasecTBe antoema. HncTbie φρθΚφΐΜ cočtipatoT ti 3πκ)Θητ BbinaptieatoT. OciaTOK KpncTannn3yioT ti3 CMecu STtinapeiaia u A^n3onponnnoBoro 3dpwpa (1 30 : 3 no o6heMy). npoAyxi peaKLļnn οτφ^^τροΒυΒθίοτ, npOMbiBatOT CMecbKD STunapeTaTa u Ann3onponwnoBoro 3φκρθ (1 : 3 no oč'beMy) n AMM3onponnnoBbiM 3φΜροΜ, a 3aieM BbicyujnBa(OT b Ba«yyMe npn 50 °C, nonysaa 1,66 sacieti (46,7 %) 6-(1H-tiMtiAa3on-1-nnMeTtin)-1-(2--MeT0KCM3T0Kcn)-1H-6eH30Tpna30na; τ. nn. 77,0 °C (οοθαμηθημθ 220). 35 75 LV 10452 ΠρίΊΜθρ 34 K nepeMeiunBaeMoii CMecu 4,5 ηθοτθμ 5-(1 H-HMMfla3on-1--nnMeTnn)-1 H-6eH30Tpna3on-1-ona n 94 naciefl Ν,Ν-αμμθτμπΦορμ-aMUAa AoSaBnatOT no ηθοτπμ 1 MacTb 50 %-hom fincnepcnn rnflpnfla HaTpua. (locne 3aBepiueHMn αο6θβπθημβ, nepeMemuBaHue προΑΟπχθκοτ AO τθχ nop, noKa ηθ npeKpaTMTCH BbiAeneHue BOAopoAa. Cpa3y AočaenflKDT 1,3 HacTePi Ριοαμοτογο μθτμπθ m nepeMeuu.nBaHue ΠρΟΑΟΠΧΟΙΟΤ npM K0MH3TH0M TeMnepaType. Ν,Ν-ΑΜΜΘΤΜΠφθρΜ8ΜΜΑΗΜΜ cnoPi BbinapuBaKDT n οοτθτοκ pacTBopatOT b βοαθ n ομθομ χποροφορΜθ, MeiaHona m MeiaHona, HacbimeHHoro θμμμθκομ (90 : 5 : 5 no o6b>eMy). i1poAyKT peaKUMu 3KCTparnpyfOT cMecbio χποροφορΜθ, μθτθηοπθ m MeTaHona, HacbiiAeHHoro 3μμμ3κομ (90 : 5 : 5 no o6t>eMy). 3κοτρεκτ BbicyiiinBatoT, $nnbTpyioT n BbinapuBafOT. Οοτθτοκ οημιαθκτγ c noMOLiļbK) κοποηοηηομ χρομθτογρθΦμμ H3A CMnMKarenbīo, ncnonb3ya CHanana χποροφορΜ, a 3aTeM CMecb χποροφορΜθ n MeTaHona (90 : 10 no o5teMy) b KanecTBe 3πκ}θητοβ. HncTbie Φρθκαμμ coāMpatoT μ θπιοθητ BbinapneatoT. Οοτθτοκ nepeMeiuMBaiOT β αμμ3οπροπμποβομ 3φΜρθ. flpOAyKT peaKLļnn οτΦμπβτροβηβθιοτ m BbicyuiMBaK)T b BaxyyMe npn 50 °C, nonyHan 3,1 HacTePi (64,3 %) 5-(1Η-μμμα33οπ-1-μπμθτμπ)-1--MeT0Kcn-1H-6eH30Tpna30na; t. nn. 94,3 °C (οοθαμηθημθ 221). noAoāHbiM o6pa30M nonynaK)T τθκχθ: 5-(1 Η-ΜΜΜΑ330Π-1 -ΜΠΜΘΤΜΠ)-1-(φθΗΜΠΜΘΤΟΚΟΜ)-Ι Η-6θΗ30ΤρΜ3- 3θπ; τ. ππ. 113,7 °C (οοθαμηθημθ 222); U4aBeneBOKMcnyio corib (2 : 3) 6-[(3-χπορΦθημπ)-(1Η-μμμα330π-1--ΜΠ)-ΜΘΤΜΠ]-1 - (φθΗΜΠΜΘΤΟΚΟΜ) -1 Η-6θΗ30ΤρΜ330Π3; Τ. ΠΠ. 169,3 °C (ΟΟΘΑΜΗΘΗΜΘ 223); μ maBeneBOKMcnyio conb (1:1) 1^τοκομ-6-[(3-χπορΦθημπ)-(1Η--MMMAa30n-1-Mn)-MeTMn1-1H-6eH30TpMa3ona; τ. ππ. 96,5 °C (οοθαμηθημθ 224). ΠρΜΜθρ 35 Κ nepeMewMBaeMOMy pacTBopy 0,46 ηθοτθμ ηητρμη β 24 ηθοτπχ MeTaHona ΑοδθΒηπιοτ 4,3 ηθοτθμ 6-(1Η-μμμα330π-1-μπμθτμπ)-1Η--5eH30TpMa3on-1-ona. CMecb nepeMeiuMsatOT β τθηθημθ 10 MMHyT, a 33τθμ BbinapMBaiOT. K ocT3TKy ΑοδθΒππιοτ 9 ηθοτθμ Tonyona m 76 coflep>KMMoe CHoea BbinapMBatOT. K οοτθτκγ fločasnaioT 9 μθοτθμ N,N-AHMeTnn$opMaMnfla, a 3aieM pacTBop 3,12 ηθοτθμ μοαμοτογο 3Tnna b 4,5 nacTflx N ,Ν-αμμθτμπΦορμ3μμα3. Οοαθρχμμοθ nepe-MemuBaioT b τθηθημθ 1 naca npn 50 °C n BbinapneatOT. fločaBnatOT 60 ηθοτθμ BOAbi n προΑγκτ peaKunn 3KCTparnpyioT αμχπορμθτ8ηομ. 3«CTpaKT BbicymnBaK)T, φΜΠΒτργιοτ m BbinapneaiOT. OciaTOK OMniMaiOT c noMOLUbio κοποηομηομ xpoMaTorpacf)un naA cunuKarenbīo, ucnonb3yfl CMecb χηοροφορΜθ m MeiaHona (95 : 5 no ο6ϊ>θμυ) b κθμθοτβθ amoema. Hndbie 0paxunn coSnpatoT m θπιοθητ BbinapMBaioT. Οοτβτοκ npeBpaiAatOT b xnopncTOBOAOpOAHyio conb b 2-nponaHone μ 4-μθτμπ--2-neHTaHOHe. Conb οτφΜΠΒτροΒΜΒΒίοτ n BbicyujnBaiOTt nonyHaa 4,5 ηθοτθμ (80 %) MOHOxnoprnApaia 1-3τοκομ-6-1Η-μμμα330π-1-μι1μθτμπ)-•1H-6eH30Tpna3ona; τ. nn. 140,2 °C (οοθαμηθημθ 225). IIoAOČHbiM o6pa30M nonywaiOT TaioKe: MOHOxnoprnApaT 1-6yTOKCn-6-(1 H-nMHAa3on-1-nnMeTnn)-1 Η-6θη-30Tpua30na; τ. nn. 124,2 °C (οοθαμηθημθ 226); MOHOxnoprnApaT, nonyrnApaT 6-(1 Η-μμμα330π-1-μπμθτμπ)-1--nponOKCn-1H-6eH30Tpna3ona; τ. nn. 130,5 °C (οοθαμηθημθ 227); m 6-(1 H-MMnAa30n-1 -nnMeTnn)-1 -(Φθημπμθτοκομ)-Ι H-6eH30Tpna30-na; τ. nn. 113,8 °C (οοθαμηθημθ 228). flpMMep 36 K ΠΘΡΘΜΘΙΑΜΒΘΘΜΟΜ ΟγΟΠΘΗΟΜΜ 4,7 ΗβΟΤΘΜ 6*(1 Η-ΜΜΜΑ830Π-1 --MnMeTMn)-1H-6eH30TpMa30n-1-ona β 60 ηθοτβχ θτθηοπθ AoāaBnatOT 22,5 ηθοτθμ 1 Ν pacTBOpa γμαροοκμομ ηθτρμβ. Οοαθρχμμοθ nepeMeujMBaiOT ΑΟ τθχ πμρ, noxa ηθ ποπυημτοβ npo3paHHbm pacTBop. CMecb BbinapMBatOT AOcyxa. Οοτθτοκ pacTBopnKDT b 18 ηθοτβχ Ν,Ν-αμμθ- ΤΜΠφθΡΜ3ΜΜΑ3. K ΠΟΠγΗΘΗΗΟΜγ ΤΘΚΜΜ 06pa30M paCTBOpy ΑΟβθΒΠΒΙΟΤ cpa3y pacTBop 3,2 ηθοτθμ μοαμοτογο μθτμπθ β 9 Ηβοτηχ Ν,Ν-ΑΜΜΘΤΜΠφΟρΜΘΜΜΑΘ. ΠΟΟΠΘ ΠθρθΜΘΙΙΙΜΒΘΗΜΒ Β ΤΘΗΘΗΜΘ 30 ΜΜΗγΤ ΠρΜ Κ0ΜΗ3ΤΗ0Μ ΤΘΜΠθρθΤγρθ ΟΟΑθρΧΜΜΟΘ BbinapMBaiOT. 0CT3T0K OHMmatOT C nOMOlAbK) ΚΟΠΟΗΟΗΗΟΜ χρΟΜΘΤΟΓρθφΜΜ H3A ΟΜΠΜΙΟΓΘΠΒΚ), ncnonb3yn CMecb χποροφορΜθ m MeiaHona (95 : 5 no o6teMy) β KaneciBe θπιοθητθ. HMCTbie Φρθκαμμ coāMpafOT μ θπιοθητ BbinapMBafOT. OCTaTOK ΚρΜ0Τ3ΠΠΜ3γΚ)Τ M3 8 ΗΘΟΤΘΜ 4-ΜΘΤΜΠ-2-ΠΘΗΤ3ΗΟΗ3. ΠρΟΑγΚΤ 77 LV 10452 peaKpnn OTCpMnbTpoBbiBaiOT n BbicyujnBa(OT, nonyHaa 3,3 nacTePi (65,4 %) 6-(1H-MMHAa30n-1-nnMeTMn)-1-MeT0KCn-1H-6eH30Tpna30na; τ. nn. 132,4 °C (οοθαμηθημθ 229).. npMMep 37 CMecb 5,85 nacTePi 6-[φθΗηπ-(1Η-1,2,4-τρη33θπ-1-ηη)-Μβτηπ]-1Η--6eH30Tpna3on-1-ona, 1,4 naciePi Kapāonaia Kanna n 27,5 nacTePi AHMeTnncynbCpOKCHAa nepeMemnBaiOT b τθηθημθ 30 MHHyT npn 50 °C. flocne oxna>KAeHHfl AOāaBnaioT 3,55 naciePi STnnoBoro scfinpa 2-5poMyKcycHoPi KncnoTbi n coAep>KHMoe nepeMeujnsatoT b τθηθημθ 2 nacoB npn κομηθτηοΡι TeMnepaiype. flpyryio nopunio 1,4 naciePi KapčoHaTa Ao6asnaK)T κ CMecn. nocne nepeMeiiīnBaHna b τβΗθΗηθ 3 nacoB npn 50 °C CMecb οχπ3>κα3Κ)τ n AoSaBnatOT 2,0 nacrn κοΗρΘΗτρηροΒθΗΗοΡί conaHoPi KncnoTbi. flnMemncynb$OKcnAHbiPi cnoPi BbinapnBafOT. OciaTOK pa36aBnatoT b 25 nacTax eopbi n 130 nacTax ΑηχπορΜΘτβΗβ. Pa3AeneHHbiPi opraHMHecKnPi cnoPi BbicywnBaiOT, 0nnbTpyioT n BbinapnearaT. Οοτβτοκ onniuatOT c noMombio κοποηοηηοΡϊ xpoMaTorpa$nn Hap cnnnKarenbK), ncnonb3ya CMecb χηοροφορΝ/ο, MeiaHona η μθτθηοπθ, HacbiiAeHHoro aMMnaKOM, (92 : 4 : 4 no o6beiviy) b KanecTee sntoeHTa. HncTbie φρβκρηη co6npaK>T η 3πκ)θητ BbinapnBaKiT. Οοτθτοκ Kpnciannn3yK)T n3 20 nacTePi 4-MeTnn-2-neHTa-HOHa. (1poAyKT peaKunn οτφηπΒτρΟΒΒίθθίΟτ n BbicymnBaK)T, nonynaa 4,4 nacTePi (79,6 %) 5-[φβΗηπ-(1Η-1,2,4-τρη83θπ-1-ηη)-Μβτηπ]-1Η-6θΗ3θ-Tpna3ona; τ. nn. 182,7 °C (coeAnHeHne 230). noAOāHbiM o6pa30M nonynatOT τθκ>κθ: 5-f1-(1H-nMnAa3on-1-nn)-3Tnn]-1H-6eH30Tpna3on; τ. nn. 165,3 °C (coeAnHeHne 231); 5-[(2-Memn-1H-nMnAa3on-1-nn)-MeTnn]-1H-6eH30Tpna3on; τ. nn. 214,3 °C (coeAnHeHne 232); n 5-r(4-Memn-1H-nMnAa3on-1-nn)^eHnnMeTnnļ-1H-5eH30Tpna3on; τ. nn. 166,7 °C (coeAnHeHne 233). flpnMep 38 CMecb 4,3 HacīePi MOHOxnoprnApaia 6-(1 H-nMnAa3on-1-nnMe-Tnn)-1H-6eH30Tpna3on-1-ona n 120 HacTePi MeiaHona rnApnpyK)T npn 78 o6biHHOM βθΒΠΘΗΜΜ μ πρκ 50 °C c noMombio 2 MacTeii 5 %-ΗΟΓΟ KaTann3aTopa nnaTMHbi Ha αρθβθοηομ yrne. riocne πογποιμθημη BbNucneHHoro KonusecTBa eoflopofla Kaiann3aTop 0T$nnbTp0BbiBat0T m φι/^τρβτ BbinapuBatOT. Οοτθτοκ KpMCTanmi3yi0T flBaxflbi M3 STaHona. 5 npoflyKT peaKunn OT$nnbTpoBbiBaiOT n BbicywnBaK>T, nonyHaa 2,9 MacTeii (72 %) MOHOxnoprnApaTa 5-(1Η-μμμα330π-1-μπμθ™π)-1Η-6θη30-Tpna3ona; t. nn. 230,4 °C (οοθαμηθημθ 234). 10 ΠρΜΜθρ 39 npn nepeMeiuMBaHMM κ 30 ηθοτβμ flbiMBiAeii a30THotf κμοποτη βθ63ΒΠΒΚ3Τ ΠΟ nOpUHHM 2,47 ΜΘΟΤΘΜ 5-(1 Η-ΜΜΜΑ330Π-1-ΜΠΜΘΤΜη)-ΐΉ--6eH30Tpna3ona. nocne 3aBepiueHMfl αοΟθβπθημβ npOAonxatOT nepe-MeujMBaHue b τθηθημθ hohm npn κομηθιηομ TeMnepaType. PeaK-15 unoHHyto CMecb BbinneatOT b 100 saciet pa3Apo6neHHoro nbAa n a30T nponycKa(OT nepe3 CMecb b τθηθημθ 30 MHHyT. BbinaASiomi/iii b ocaAOK npOAyKT peaKunn OT$nnbTpOBbiBaK)T, npOMbieaiOT boaom μ οημιαθιοτ c noMOunbto o6paTMMO-0a3OBOM xpOMaTorpacf)MH (>KXBfl) HaA φθ30Μ Tuna Li Chroprep RP 18, ncnonb3ya CMecb MeTaHona, aueTOHMīpuna n 20 0,5 %-Horo pacTBOpa aueTaTa θμμοημβ (17 : 8 : 75 no οβΐ>ΘΝψ) b
KanecTBe smoema. UeneByio φρΒκρκιο cočupatoT m anioeHT Bbina-puBatoT. OdaTOK nepeivieiuuBaiOT b μθτθηοπθ h Ann3onponnnoBOM 3φΜρΘ. BbinaAaiomnM b ocaAOK npoAyKT peaKpuM οτΦιίγ^τροβμβθιοτ m κκπΒΤΗτ b MeiaHone. npoAyKT peaKLļnu οτφκπΒτροΒΝΒβκπ, npoMbiBaioT 25 μθτθηοπομ n Ann3onponnnoBbiM 3φι/ιροΜ n BbicyiiinBaK)T b BaKyyMe npn 50 - 60 °C, nonyHan 0,05 nacTePi (1,6 %) 5-(1 H-nMHAa3on-1-nnMeTnn)--6-HHTpo-1 H-6eH3HMUAa3ona; t. nn. 286,0 °C (pa3n.) (οοθακηθηιίθ 235). 30 flpuMep 40
CMecb 3,2 sacTePi sTunoeoro 3φκρθ 4-[[6-(1H-uMHAa3on-1-nnMeTnn)-1 H-6eH30Tpna30n-1-nn)ļ-0Kcn]-6yTaH0B0ii KucnoTbi, 25 naciefi 1 N pacTBOpa γμαροοκμοι HaTpun n 20 naciePi STaHona nepeMeuinBaioT b τθμθη/θ 1,5 nacoB npH κομηθτηοΡι TeMnepaType. flo6aBnatOT 25 35 nacTePi 1 N pacTBOpa conai-ioPi KucnoTbi v\ coAepxnMoe K0Hi49HTpnpyt0T 79 LV 10452 flo očbeMa npuMepHO 20 naciePi. BbinapaKDiiļuPi b ocaflOK προβγκτ peaKLļnn, κοτορΗΜ o6pa3yeTca npn KOHueHTpupoBaHun, OT0nnbTpo* BbIBaKJT, npOMblBatOT BOflOii, 2-npOnaHOnOM H flUaTUDOBblM 3φΜρ0Μ, a 3aieM BbicyiuwBaK3T, nonyHan 2,1 sacieti (71 %) 4-((6-(1 H-MMMAa3on-1-5 -nnMeTMn)-1H-6eH30Tpua3on-1-nnļ-OKCn]-6yTaHOBOii κμοποτη; τ. nn. 170,5 °C (coeAUHeHne 236). noAočHbiM o6pa30M nonynaK)T τθιοκθ: 5-ff6-(1H-HMHAa30n-1-nnMeTnn)-1H-6eH30Tpna3on-1-nn]-0KCMļ--neHTaHOByio KncnoTy; τ. nn. 132,7 °C (coeAnneHne 237). 10 npuMep 41
PacTBop 7,1 sacTePi 6-[(4-(4,5-αμγμαρο-4,4-AMMeTMn-2-OKca-30πμπ)-Φθημπ ļ-( 1 H-MMMAa3on-1 -μπ)-μθτμπ]-1 -μθτμπ-1 H-6eH30TpMa3ona b 100 HacTHx 3 N pacTBOpa connHoPi KucnoTbi nepeMemuBatoT β τθηθημθ 15 hohh npn TeMnepaType κμπθημβ c o6paTHbiM xonc>AnnbHHKOM. PeaKunoHHyKD CMecb BbinapMBatOT AOcyxa, nonyHaa 8,9 nacieM (100 %) MOHOxnoprnApaTa 4-Γ(1 Η-μμμα330π-1-μπ)(1-μθτμπ-1 H-6eH30TpMa3on-6--nn)-MeTnn]-6eH30PiH0Pi KMcnoTbi β βμαθ οοτθτκθ (οοθακηθημθ 238). 20 ΠρνίΜθρ 42
PacTBop 8,9 nacTePi MOHOxnoprnApaTa 4-((1 Η-μμμα330π-1-μπ)(1--MeTnn-1H-6eH30Tpna3on-6-nn)-MeTMnl-6eH3oPiHoPi KucnoTbi b 32,4 HacTiix xnopndoro τμοημπθ nepeMemneaioT β τθηθημθ 1 naca npn KOMHaTHoii TeMnepaiype. PeaKUMOHHy»o CMecb BbinapuBaiOT. PacTBop 25 ocTaTKa b 80 HacTnx aiaHona nepeMetnusafOT β τθηθημθ 1 naca npM 60 °C. PeaKi4MOHHyK) CMecb KOHueHTpMpyK)T. KoHpeHTpaT pa36aBnnK)T b pa36aBneHHOM pacTBope Kap6oHaia ιοπμη m npoAyKT peaKLļMM 3KCTparMpytoT αμχπορμθτθηομ. 3κοτρθκτ BbicyujMBaK)T, φMΠbτpy^oτ m BbinapMBaKDT. 0CT3T0K ΟΗΜΙΑΘΙΟΤ C nOMOlUblO ΚΟΠΟΗΟΗΗΟΜ XpOMaTO-30 τρΒφΜΜ H3A CMnMKarenbīo, Mcnonb3yn CMecb α^χπορμθτθηθ m Meianona (98 : 2 no o6beMy) b ιοηθοτβθ θπιοθητθ. HMCTbie φρ3καΜΜ coSMpaiOT m θπιοθητ BbinapMBaJOT. OcrraTOK npespamaraT b maBeneBOKMcnyK> conb. Conb οτφΜΠΒτροΒΒίβθίοτ m BbicyinMBaK)T, nonynafl 1 HaCTb (8,5 %) maseneBOKMcnoPi οοπμ (1 : 1) 3τμποβογο 3φΜρθ 4-((1 Η-μμμα330π-1-μπ)- 80 -(1-MeTMn-1H-6eH30Tpna30n-6-nn)-MeTnnļ-6eH30iĪH0ti κιίοποτβι; t. ππ. 155,5 °C (coeflUHeHne 239). ΠρΜΜΘρ 43 5 CMecb 7 MacTeii 5-f 1-(1H-nMMAa3on-1-nn)-2-6yTHHnn]-1-M0Tnn- -1H-6eH30Tpna3ona, 0,1 nacin χμηοπμηθ, 54 nacTePi STunaueTaia m 32 nacTePi aiaHona rnflpnpyfOT npn AaeneHHu 931,00 fla n npn κομηβτηομ TeMnepaiype c noMombio 0,3 HacTePi 10 %-ηογο KaTann3aiopa nannapna Ha αρθβθοηομ yrne. Ilocne nomoiueHna BbmucneHHoro KonunecTBa 10 BOflOpopa 0T$nnbTp0BbiBat0T Kaiann3aT0p Han α^τομοβοΡι 3eMnePi n cfiunbTpaT BbinapuBaKDT. Octbtok onmuaiOT c noMombto κοποηοηηομ xpoMaTorpa$nn Hafl cunuKarenbto, ncnonb3ya CMecb pnxnopM0TaHa n MeTaHona (95 : 5 no o6beMy) β κθηθοτβθ antoeHTa. HncTbie φρθΚφΉΊ cočupaioT n antoeHT BbinapuBafOT. Οοτθτοκ «pncTannn3ytOT H3 CMecu 15 AnxnopMeTaHa n αιίθτιίποβογο 3$npa. npOAyKT peaKpuu OTCļDuribTpo-BbisaiOT u BbicyninBaK)T, nonynaa 1,4 nacTePi (19,7 %) 5-[1-(1H--nMHAa3on-1-nn)-2-6yieHnnļ-1-MeTnn-1H-6eH30Tpna3ona, τ. ππ. 104 °C (οοθα^ηθημθ 240). 20 ΠρΜΜβρ 44 CMecb 2,6 MacTeū 4-f (1Η-μμμα330π-1-μπ)-(1-μθτμπ-1Η-6θη30-Tpna3on-5-nn)-MeTnnl-6eH3anbAernAa, 0,85 HacTePi MOHOxnoprnApaTa rnApOKcunaMMHa, 16 nācies 3TaHona m 3,4 nacTePi Kap6oHaTa Kanna nepeMeiunBatOT β τθμθημθ 1 naca npn 50 °C. PeaKunoHHyfo CMecb 25 $nnbTpytOT κ $nnbTpaT BbinapneatOT. Οοτθτοκ onmuaiOT c noMombio κοποηοηηομ xpOMaTOfpa$nn H3A cnnnKarenbto, ncnonb3ya' CMecb χποροφορΜθ n MeTaHona (95 : 5 no o6beMy) β κθηθοτβθ θπιοθητθ. HncTbie Φρθκαμμ co6npatoT n antoeHT BbinapnBatoT. Οοτθτοκ KpncTan-nn3yK)T M3 aueTOHa. npOAyKT peaKunn οτφΜΠΒτροΒΜΒθίοτ n Bbicy-30 LUMsatOT, nony4aa 1,7 nacTePi (63,9 %) OKcnivia 4-[(1H-KMHAa3on-1-nn)--(1-MeTnn-1H-6eH30Tpna30n-5-nn)-MeTnnļ-6eH3anbAernAa; τ.ππ. 149,5 °C (coeAUHeHne 241). 35 81 LV 10452 B cDaPMaKonorHHecKHe npuMeobi ΠθΠΘ3Ηθθ MHrn6npOBaHMe aKTMBHOCTM apOMaia3bl COefll/ΙΗΘΗΜίί $opMynbi (I) μο>κθτ 6biTb npofleMOHCTpMpoBaHO b cneAy(omnx 5 ΜΘΤ0ΑΜΚ3Χ HCnblTaHUM. ΠρΜΜθρ 45:
McnbuaHue mh bhtpo- HHrn6npOBaHMa aKTUBHOCTH apQMaTa3bi
HanpuMep, mo>kho nccneAOBaTb AencTBne coeAHHeHnn HacToa-10 mēro n3o6peTeHna Ha npeBpameHne 1,2-[3H]-aHAp0CTeHAH0Ha b sctpoh n scTpaAnon b npncyTCTBnn nnaueHTapHbix mukpocom nenoseKa, cneAya MeTOAUKaM, θηθπογμηηβιμ onncaHHbiM b J. Steroid Biochem., 7, 787, 1976). flnaueHTapHbie MUKpocoMbi ηθποβθκθ pa36aBnnK)T b 6y$epHOM 15 pacTBope φοοφβτΒ Kanna (0,1 M, pH 7,4), mtoSbi nonywnTb npnMepHO 50 %-HyK) KO.HBepcnio θηαρογθηοβ b acTporeHbi (coAep>KaHne 6enKa: npnMepHO 0,5 μγ). HeTbīpe μπ nnai4eHTapHbix ΜηκροοοΜ ηθποβθκθ nHKy6npytoTca b κοηθηηομ ο6ϊ>θμθ 5 μπ βμθοτθ c 0,2 mkKh (Μηκροκιορη) 1,2-[3Η1-3ηαρορτθηαηοηομ, 2 μκγ aHApocTeHAnoHOM η 5 20 μκπ ncnbiTyeMoro coeAnHeHna n/nnn AHMemncynb0OKcnAa (flMCO). KpoMe τογο, nHKy6aunoHHaa CMecb copep^m N AflPH-pereHepnpy-(omyto cncieMy, cocTomiļyio n3 ΑΤΦ (θΑβΗΟΒηΗ-τρηφοοφθτ) (2,48 MMonb), NAflP (0,97 MMonb), Γπιοκθ3Η-6·φορφ3Τ3 (8,22 MMonb), ΓΠΚ)κο3Βΐ-6-φοοφ3Τ-ΑθΓηΑρθΓθΗ33Βΐ (0,98 epnHnu) n MgCl2 (2,46 25 MMonb). PeaKLļnio nHnunnpyiOT AoāasneHneM aHApocTeHAnoHa n OHa προτθΚθβτ b τθΗΘΗηβ 30 MnHyT npn 37 °C. Bo BpeMa nHKy6ai4nOHHoro nepnopa CMecb ra3npyi0T B03AyxoM. B stom ncnbīTaHnn apOMamaauna aHApocTeHAnoHa npnsoAUT κ co3AaHnio Γ3Η1-Η20, KOTopbin βμαθπβθτοβ nyīeM δκοτρθκρηη o6pa3i40B c noMombio χποροφορΜΒ, HTo6bi ypannTb 30 CBo6oAHbin cieponA- 06pa3ubi OTCHnTbiBatOTca b χηρκοΜ cunHTnnrm-pnoHHOM οπβκτροΜθτρθ n npoueHT nHrn6npOBaHna onpepenneica nyieM cpasHeHna pe3ynbTaTOB c KOHTponbHbiMn o6pa3uaMn, nHKy-ānpoeaHHbiMn (BbipameHHbiMn) 6e3 nHrnāmopa. flencTBna coeAnneHnn HacTomAero n3o6peTeHna npepciaBnaiOTca 35 b Ta6nnLļe 1, κοποηκθ (a) b enpe KOHueHTpaunn β ΜηκροΜοηηχ (mkM) 82 coeflMHeHMfl, Tpe6yeMoro flnn nonyHeHnn 50 %-ηογο MHrn6npOBaHMsi cnHT93a acTporeHa (ICso-BenMHHHbi). ΠρΜΜθρ 46: 5 Μη BHBO-MHrUČUPOBaHHe aKTHBHOCTM aD0MaTa3bl
Heflopa3Bmbix Kpuc-caMOK Bnciapa βθοομ 120 r MHbei4npyiOT ποακοχηο c 200 M.E. (Me>KflyHapoflHbix θαμημα) roHaflOTponnHa n3 CbiBopoTKM xepe5oū KOčbīnbH (ΓΟ>ΚΚ). CnycTH 90 sacoB, 1 μγ/κγ ncnbiTyeMoro οοθαμηθημη, pacTBopeHHoro b 0,5 μπ 20 %-ηογο pacTBopa 10 Π0ΠΜ3ΤΜΠΘΗΓΠΜΚ0Π3 B ΒΟΑΘ, BBOA«T nepopaHbHO ΚΟρΜΠΘΗΜΘ Ηβρβ3 30Hfl. KoHTponbHbie >KHBOTHbie nonyHann TOAbKO 20 %-Hbiii ποπμοτμπθη-rnuKonb. CnycTfl ABa naca nocne npneMa neKapCTBa mv\ nnaueāo Kpbic y6biBaioT AeKanmapneii (o6e3rnaBnnsaHneM) h KpOBb W3 TynoBnma co6npaioT Ha οπρθαθπθημθ renapHHa. KoHueHTpauHH scrrpaAuona b 15 nna3Me n3M8pstOT c noMOLUbto daHAapTHbix paAno-nMMyHonornHecKnx μθτοαμκ. npoueHT BbiAeneHmi acTpaAuona no OTHOuueHmo κ KOHTponbHbiM onHCbiBaeTCH b κοποηκθ (6) Ta6nnLļbi 1. Pe3yribTaTbi b 3τοίί Ta6nnue npeACTaBfifliOTCfl ηθ απη ογρθημηθημ* caMoro n3o6peieHH3, a TonbKo HTo6bi cny>KMTb npMMepOM none3Hbix 20 cftapMaKonornHecKux cbomctb βοθχ οοθαμηθημμ b npeAenax oāteMa <t>opi\/iynbi(I).
Taānmja 1
CoeAUHeHne BenMHHHbi IC50 (mkM) % BbiAeneHMH scīpaAnona 1 2 3 225 0,0100 19 226 0,0067 19 227 0,0074 19 228 0,0052 - 195 0,0120 19 196 0,0110 - 197 0,0110 - 198 0,0180 - 83 LV 10452 1 2 3 201 0,0067 19 202 0,0071 21 203 0,0170 - 204 0,0092 19 206 0,0030 - 2 0,0160 20 4 0,0160 - 6 0,0120 - 207 0,0073 26 208 0,0110 - 7 0,0257 7 147 0,0076 21 176 0,0120 - 191 0,0234 - 179 0.0232 - 75 0,0242 27 76 0,0347 9 87 0,0269 5 89 0,0150 5 90 0,0227 5 91 0,0088 - 92 0,0087 15 15 0,0226 2 93 0,0105 8 17 0,0182 7 97 0,0131 10 99 0,0178 11 23 0,0075 - 100 0,0143 3 101 0,0174 7 102 0,0317 2 103 0,0163 5 28 0,0253 6 84 1 2 3 29 0,0159 7 30 0,0222 7 31 0,0342 8 104 0,0206 9 33 0,0246 5 105 0,0198 14 213 0,0362 - 106 0,0244 8 107 0,0141 6 108 0,0152 3 109 0,0262 - 188 0,0182 - 111 0,0143 19 113 0,0188 4 48 0,0166 6 50 0,0183 1 51 0,0222 7 115 0,0144 22 55 0,0188 3 56 0,0215 8 116 0,0249 20 64 0,0257 3 117 0,0125 9 69 0,0290 5 77 0,0176 21 220 0,0200 - 120 0,0089 - 59 0,0180 - 5 85 LV 10452 ΦΟΡΜΥΠΑ H30EPETEHH3 1. Cnocoč nonyHeHnsq npoM3BOAHbix (1Η-33οπ-1-μπμθτμπ)-38μθ-iiļ9HHbix 6eH30Tpna3onoB $opMynbi 5 8 a2—Lx Ι»1 ' II λ λ 3
n nx 0apMaueBTMHecKn npneMneMbix coneii npucoeflUHeHUB kuchot μπμ ciepeoxnMMMecKn μ30μθρηομ φορΜΒΐ, b κοτοροίί 15 a1=A2-A3=a4 ββπβθτοβ AByBaneHTHbiM papuKanoM φopMyπbl -CH=N-CH=CH- (a-1), -CH=N-CH=N· (a-2), nnn -CH=N-N=CH- (a-3); R ΠΒΠΠΘΤΧΗ BOAOpOflOM ΜΠΜ C 1-βθΠΚΜΠΟΜ, 20 Rl ββπηθτοβ BOfloponoM, Ci-ioanKnnoM, C3-7i4MKnoanKnnoM,
Ar1, Ar2-Ci.6anKnnoM, 02-63πκθημπομ μπμ C2-6anKMHnnoM; R2 αβπβθτοβ boaopoaom; Ci-ioanKunoM, Heo6fl3aTenbHO 3aMe* tAeHHbiM rpynnoM Ar1, C3-7i4MKnoanKnn, okch μπμ C-|-6anKM/ioKCn; Ar1; 02-6®πκθημπομ; 02-63πκμημπομ; C3-7UMKnoanKMnoM; 6μι4ΜκποΓ2.2.1 ]-25 -rerrraH-2-ΜΠθΜ; 2,3-αμγμαρο-1Η-μηαθημπομ; 1,2,3,4-τθτρ3ΓΜΑροΗ3φ-τθπμημπομ; okcm; 02-63πκθημποκομ, Heo6n3aienbHO 3aMemeHHbiM rpynnoM Ar2; C2-6ar)KHHnnOKCn; nupuMUAHHunoKCn; αμ-(Αγ2)-μθτ· okcm; (1 -C1 -4anKMn-4-nMnepMAMHMn)-OKCM; μπμ Ο-μοθπκμγιοκομ, Heo6iR3aTenbHO 38μθιμθηημμ γθπομαηομ, okcm, Ci-6anKMnoKCM, θμμηο-, 30 MOHO- M A'M-(C 1-6anKMn)-aMMHO-, ΤρΜφΤΟρΜΘΤΜΠΟΜ, KapČOKCMilOM, Ci-6anKMnoKCMKap5oHMnoM, Ar1, Ar2-0-, Ar2-S-, C3-7UMKnoan- ΚΜΠΟΜ, 2.3-ΑΜΓΜΑΡΟ-1,4-6eH30AM0KCMHMnOM, 1 Η-6θΗ3ΜΜΜΑ830ΠΜΠ0Μ, Ci-4anKMn-3aMemeHHbiM 1Η-6θη3μμμα330Πμπομ, (1 ,Γ-δΜφβΗΜπ)-4--ΜΠΟΜ ΜΠΜ 2,3-ΑΜΓΜΑΡΟ-2-ΟΚΟΟ-1Η-6βΗ3ΜΜΜΑ330ΠΜΠΟΜ; 86 R.3 ΗΒΠΗΘΤΟΗ BOflOpOflOM, HMTPO-, 3MMH0-, ΜΟΗΟ- Μ flM-(Cl-6an*
Ki/m)-aMUHo-, ranonnoM, Ci-6anKnnoM, okcm- μπμ C1-6anKnnoKCn-rpynnoM; B KOTOpOM Al^ ΒΒΠΒΘΤΟΒ φθΗΜΠΟΜ, 3aMeiUeHHblM φθΗΜΠΟΜ, ΗθφΤΘΠΜΗΜΠΟΜ, ΠΜρΜΑΜΗΜΠΟΜ, aMMHOnupUflMHMnOM, MMMAa3GnnnOM, Tpna3ominoM, τμθημπομ, γθποματμθημπομ, φνρβΗΜΠΟΜ, Ci-6anKnn-φγρ3ΗΜΠ0Μ, Γ3/10ΜΑφνρ3ΗΜΠ0Μ ΜΠΜ ΤΜ830ΠΜΠ0Μ; Μ
Ar2 ΠΒΠΠΘΤΟΠ φθΗΜΠΟΜ, 38ΜΘ111ΘΗΗΒΙΜ φθΗΜΠΟΜ ΜΠΜ ΠΜρΜΑΜΗΜΠΟΜ, ΠρΜΗΘΜ yKa3aHHblM 38ΜΘΙΑΘΗΗΒΙΜ φθΗΜΠ ΗΒΠΠΘΤΟΠ φθΗΜΠΟΜ, 3aMeiMeHHblM BnnOTb no 3 3aMeCTMTennMM, Ka>KAblM ΗΘ33BMCMMO Bbi6MpaeMbiM Μ3 ranoMAa, okcm-, οκομμθτμπθ, τρΜφτορΜθΤΜΠθ, Ci-6an-KMna, C 1-63πκμποκομ-, Ci-6anKMnOKCMKap6oHMna, KapāOKCMna, φορ-MMna, (OKCMMMMHO)-MeTMna, UM3H0-, 3MMH0-, ΜΟΗΟ- M AM-(Cl-βθΠΚΜΠ)--aMMHO- M HMTpO-rpynnbi; 0ΤΠΜΗ3Κ)ΙΑΜΜ0Π ΤΘΜ, HTO!
I. a) N-anKMnMpyioT a3on φopMyπbι R i1 λ4 (III)
B μπμ ero conb menoHHoro MeTanna, c noMouļbto 6eH30TpMa3ona φopMyπbι
b κοτοροΜ W npeACTaanaeT peaKUMOHHOcnoco6Hyio yxoAfliuyK) rpynny, b μηθρτηομ κ peaKLļMM cpeAe; 6) N -anKMnMpyiOT 3aiMMlneHHblM B ΠΟΠΟ>ΚΘΗΜΜ 1 ΜΜΜΑ330Π φopMyπbl
87 LV 104 b κοτοροίί npeACTaBnaeT 3ammHyto rpynny, c noMombio 6eH30Tpna3ona φopMyπbι (II) b μηθρτηομ k peaKunn cpepe, npuneM yKa3aHHa?) peaKuna προτθκθθτ b HeKOTopbix cnyHaax Mepe3 MHTepMeAnaT φορινψπΜ
(iv) B κοτοροίί W' ΗΒΠΗΘΤΟΗ 3HM0H0M, B03HHKai0lUHM H3 KMCnOTbl, KOTOpbM (MHTepMefluai) μο>κθτ hh cnTy, mv\ ecnn «enaTenbHO, nocne Bbipenenna n AanbHeižiujeii ohhctkh ero, 6biTb npeBpameH, moSbi nonyHMTb οοθαμηθημθ φopMyπbι
R
b) N-anKnnnpyK)T Tptia3onaMMH φopMyπbι
(Ill-b) c noMoiiļbto 6eH30Tpna3ona φορινψπΗ (II), b MHepTHoii κ peaKAMM cpeAe, m BnocneACTBMn Ae3aMHHnpyioT nonyMeHHyio τθκμμ o6pa30M conb Tpna3onna φορινψπΒΐ 88
♦ w (v) B KOTOpOŪ W ' ΗΒΠΗΘΤΟΗ ΒΗΜΟΗΟΜ, Β03ΗΜΙΟΚ)Ιφ4Μ M3 KUCHOIbl, B KucnoTHOM hhtpmthom pacTBope, HTOčbi nonywnTb coeAUHeHne $opMynbi
R
II. pearnpyeT 6eH30Tpua3on <ļ>opMynbi .
R
OH
-CH
R
(VI) c peareHTOM cfiopMynbi
*X «X 1 , Ν-Χ-Ν 4 ✓
(VII) 89 LV 10452 b κοτοροΜ X npeflCTaBfifleT /C=0, S μπμ /8=0, b ΜΗβρτΗοίί κ peaKunn cpefle, npimeM yKa3aHHaa peaKuna προτθιοθτ b ηθκοτορμχ cnyHaax nepe3 μητθρμθακθτ 0opMynbi 5 10
(VIII) 15 KOTOpbIM (MHT9pM9flMaT) ΜΟΧΘΤ MH CMTy, ΜΠΜ 90ΠΜ >K9naT9nbH0, ΠΟΟΠΘ BblflenaHMa M AanbH9MLU9M OHMCTKM ΘΓΟ, 6blTb ΓφθΒρθΙΑΘΗ, MT06bl nonyMMTb co9ahh9hmb cf>opMyjibi (I); III. noAaepraiOT unKnM3aunn ausmuh $opMynbi 20 25 s
NHR NH, 2-a (IX) b KucnOTHOM HHTpuTHOM pacTBope, nonyHafl τθκμμ o6pa30M coeAn-HeHne $opMynbi
30 R
(I-b) 35 90 Β κοτοροίί R^a ΒΒΠΑβΤΟλ BOflOpOflOM; Cļ-1 OanKUriOM, Heo6B3aTenbHO 3aMeiueHHbiM rpynnoū Ar*, C3-7unKnoariKMnoM, okcm mdm Ci-6anKwnoKCn; Ar*; 02-63πκθημπομ; C2-6anKl/1HMriOM, C3-7unKno-anKunoM; 6μαμκπο-Γ2.2.1]-γθπτ3η-2-μπομ; 2,3-αμγμαρο-1Η-μηαθημπομ; ΜΠΜ 1 ,2,3 ΑΤΘΤρθΓΜΑρΟΗθφΤΘΠΜΗΜΠΟΜ; IV. noABepratOT unKnuaaunu μητθρμθαμβτ φορΜγηυ
R
(X) KOTopbifi hh cmy μοχθτ 6biTb nonyHeH nyieM N-anKMnupoBaHua HHTepMeAnaia φοριν^π^
R
(XI), b κοτοροίί Wl πρθαοτθβπαθτ peaKLļnoHHOcnoco6Hyfo yxoAfltnyK) rpynny, βμθοτθ c rnApa3HHOM (XII) nnn c ero rnApaTOM, β μηθρτηομ κ peaKLļnu pacTBOpmene, nonynaa tbkum o6pa30M coeAUHeHne φοριν^η^
R
91 LV 10452 V. noflBepratoT Aecynb0ypnpoeaHMK) MHTepMefluaT 0opMynbi
R
(XV) b κοτοροίί aBnaeica Ci-6anKnnoM, b μηθρτηομ k pea«i4nn cpefle, nonyHafl τ3κμμ o6pa30M οοθαμηθημθ 0opMynbi (I-a-1); nnn VI. a) noflBepraKDT Ο-βπκμπμροβθημκ) οοθαμηθημθ 0opMynbi (I-c-1) c noMoiAbK) peareHTa φopMynbι W-R2-b (XIII), b κοτοροίί W npeACTaBnaeT peaKAMOHHOcnoco6Hyio yxoAflmyio rpynny, b μηθρτηομ k peaKLļnn pacTBopmene, nonyHaa τθκμμ o6pa30M οοθαμηθημθ φopMyπbι
R
b κοτοροΜ -0-R2-b ββπαθτοβ Heo6?i3aTenbHO 38μθιμθηηομ Ci-ioariKun-okcm-, Heo6?i3aTenbHO 3θμθιμθηηομ 02-63πκθημποκομ-, C2-6anK^HMn· okcm-, nupuMHAMHunoKcn-, αμ-(Αγ2)-μθτοκομ- nnn (1-C ι-48πκμπ-4--nnnepnA^Hnn)-OKCn-rpynnoPi; 6) BOccTaHaenuBatoT οοθαμηθημθ φopMynbι (I-c-1) c noMombio BOCCTaHOBmena b μηθρτηομ κ peaKLļnn pacTsopuTene, nonyHafl tbkmm očpa30M οοθαμηθημθ φορινψΠΒΐ 92
R
10 b) N-anKnnnpyfOT οοθαηηθηηθ cf>opMynbi (I-b-1) c noMombio peareHTa $opMynbi W-R2*c (XIV), b κοτοροίί W npepcTaBAneT peaKunoHHOcnoco6Hyio yxofl?unyK) rpynny, b μηθρτηομ κ peaKLļnn pacTBopmene , nonynaB τθκμμ o6pa30M οοθαηηθημθ cpopMynbi
R
20 b κοτοροπ R2-c «βπαθτοα τθκημ >κθ, mto h R2*a πρπ ycnOA.nn, hto OTnHHaeTcn ot eopopopa; 25 ηπη Heo6fl3aTenbHO panee npeBpamaioT οοθαηηθηηα cpopMynbi (I) b flpyr npyra, cnenyn H3BecTHbiM β αθηηοη o6nacTH μθτοαηκβμ npeBpaiueHHn rpynn, h, ecnn >KenaTenbHo, npespaipatoT οοθαηηθηηη $opMynbi (I) b TepaneBTHHecKH aKTMBHyto hbtokchm^kd coneByio (f)opMy npH ΠρΗΟΟΘΑΗΗΒΗΗΗ KHCflOT nyTeM o6pa60TKH COOTBeTCTByK)tiļOH 30 KHcnoTOH ηπη, HaočopOT, npeBpaipaKDT conb πρηοοθαηηθηηοη KHcnoTbi b CBo6oAHyto 0CH0BHyfo $opMy c noMombto ιαθπομη; η/ηπη nonyMatoī ciepeoxHMHHecKH M30MepHbie φορΜΒΙ hx. 35 93 10 15 LV 10452 f1pon3BOflHbie (1H-a3on-1-nnMeTnn)-3aMemeHHbix 6θη30τρμ-a3onoB, κομπο3μι4μμ, coflepacatnne 3Tn coeflUHeHna, n cnocoābi ΠΘΜΘΗΜΒ 3CTporeH-3aBHCHMblX paCCTpOMCTB. 20
Claims (1)
- 5 LV 10452 (ĪH-AZOL-I-ILMETID-AIZVIETOTU BENZOTRIAZOLU ATVASINĀJUMU IEGŪŠANAS METODE PATENTA FORMULA 10 1. (lH-azol-l-ilmetil)-aizvietotu benztriazolu atvasinājumu ar formulu I ,kurā 15 R20 A1=a2 - A3= A4 ir divvērtīgs radikāls ar formulu: -CH=N-CH=CH- (a-1), -CH=N-CH=N- (a-2), vai -CH=N-N=CH- (a-3); R ir ūdeņradis vai Ci-6alkils 25 Rl ir ūdeņradis, Cl-IOalkils, C3-7cikloalkils, Ari, Ar2 ir Cl-6alkils, C2-6alkenils vai C2-6alkinils 30 R2 ir ūdeņradis; Cl-10alkils, neobligāti aizvietots ar grupu Ari; C3-7cikloalkils, hidroksi- vai Cl-6alkiloksi-grupa; Ari; C2-6-alkenils; C2-6alkinils; C3-7cikloalkils; biciklo-f2.2.1 ]-heptān-2-ils; 2,3-dihidro-lH-indenils; 1,2,3,4-tetra-hidronaftalinils; hidroksigrupa; C2-6alkeniloksigrupa, neobligāti aizvietota ar Ar2-grupu; C2-6alkiniloksigrupa; pirimidiniloksigrupa; di(Ar2)metoksigrupa; (l-Cl-4alkil-4-piperidiniDoksigrupa; vai Ci-ioalkiloksigrupa, neobligāti aizvietota ar halogēnu, hidroksi-, Cl-6alkiloksi-, amino-grupu, mono- un di(Cl-6alkil)amino-grupu, trifluormetilu, karbonilu, Cl-6alkiloksikarbonilu, Ari, Ar2-0-, Ar2-S-, C3-7cikloalkilu, 2,3-dihidro-l,4-benzodioksinilu, lH-benzimidazolilu, Ci-4a 1 ki 1 u, aizvietotu ar lH-benzimidazolilu, (1,1 -bi-fenil)-4-ilu vai ar 2,3-dihidro-2-okso-lH-benzimidazolilu; 35 5 2 R3 ir ūdeņradis, nitro-, amino-, mono- vai di(Cl-6al-kil)amino-grupa, halogēns, Ci-6alkils, hidroksi- vai Cl-6al-kiloksi-grupa; 10 kurā Ari ir fenils, aizvietots fenils, naftalinils, piridinils, aminopiridinils, imidazolils, triazolils, tienils, halogentienils, furanils, Ci-6alkilfuranils, halogenfuranils vai tiazolils; un Ar^ ir fenils, aizvietots fenils vai piridinils, pie kam dotais aizvietotais fenils ir fenils, kas aizvietots ar līdz pat 3 aizvietotājiem, kur katrs neatkarīgi izvēlēts no halogēna, hidroksi-, hidroksimetil-, trifluormetil-, Ci-6alkil-, Ci-6alkoksi-, Ci-6alkiloksikarbonil-, karboksil-, formil-, (hidroksiimino)metil-, ciano-, amino-, mono- un di(C 1 -6alkil)amino- un nitro-grupām; 15 un to farmaceitiski piemērotu atbilstošu skābju sāļu vai stereoķīmisko izomēru formu iegūšanas metode atšķirīga ar to, ka 1. a) N-alkilē azolu ar formulu III: 20 RH 25 vai tā sārmu metāla sāli ar benzotriazola ar formulu II palīdzību, W-CH —V— 11¾(II) 30 kurā W apzīmē reaģēt spējīgu atšķeļamu grupu, vidē, kas inerta reakcijas apstākļos; b) N-alkilē 1-pozicijā aizvietotu imidazolu ar formulu Ill-a 35 r4-n (IH-a) 5 LV 10452 3 kurā R4 apzīmē aizsarggrupu, ar benzotriazola ar formulu II palīdzību vidē, kas inerta reakcijas apstākļos, pie kam dotā reakcija dažos gadījumos notiek pār starpproduktu ar formulu:(iv) 10 kurā W ir anjons, kas veidojas no skābes , kurš (starpprodukts) var šķīdumā vai, ja vēlams, pēc izdalīšanas un tālākas tā attīrīšanas tikt pārvērsts tā, lai iegūtu savienojumu ar formulu: 15 κ20 c) N-alkilē triazolamīnu ar formulu : N-NH i 1 25 ar benzotriazola ar formulu (II) palīdzību, vidē, kas inerta reakcijas apstākļos, un pēc tam dezaminē tādā veidā iegūto triazolija sāli ar formulu 3035 4 kura W ir anjons, kas rodas no skābes skābā nitrīta šķīdumā, lai iegūtu savienojumu ar formulu: 4 RII. reaģe benzotriazols ar formulu: .2R -CH (VI) ar reaģentu ar formulu: (VII) A2·*1^ /A^A2 R -K ^ Ν-Χ-Ν 4— T3.a4- vJ3 kurā X pārstāv C=0, S vai S=0 , vidē, kas inerta reakcijas apstākļos, pie kam dotā reakcija dažos gadījumos notiek pār starpproduktu ar formulu :(vīli) kurš (starpprodukts) var šķīdumā vai, ja vēlams, pēc izdalīšanas un tālākas tā attīrīšanas tikt pārvērsts tā, lai iegūtu savienojumu ar formulu (I); LV 10452 5 III. pakļauj ciklizacijai diamīnu ar formulu: RNH. NHR 2 2-a (IX) skābā nitrīta šķīdumā, iegūstot tādā veidā savienojumu ar formulu: RR (I-b) (I-b) kurā R^a ir ūdeņradis; Ci-ioalkils, neobligāti aizvietots ar grupu Ari, C3-7cikloalkilu, hidroksi- vai Ci-6alkiloksi-grupu; Ari; C2-6alkenils; C2-6alkinils, C3-7cikloalkils; biciklo-f2.2.lļ-heptān-2-ils; 2,3-dihidro-lH-indenils; vai 1,2,3,4-tetrahidronaftalinils; IV. pakļauj ciklizācijai starpproduktu ar formulu: R:-NH. R (X) 2 kurš var tikt iegūts šķīdumā, N-alkilējot starpproduktu ar formulu: 6 5(XI)/ 10 15 kurā Wl pārstāv reaģēt spējīgu atšķeļamu grupu, kopā ar hidrazīnu (XII) vai ar tā hidrātu, vidē, kas ir inerta reakcijas apstākļos, iegūstot tādā veidā savienojumu ar formulu:(i-c-l)/ 20 25 V. pakļauj desulfurēšanai starpproduktu ar formulu: R(XV) 30 kurā R5 ir Ci-6alkils, vidē, kas ir inerta reakcijas apstākļos, tāda veidā iegūstot savienojumu ar formulu (1-a-l); vai VI. a) pakļauj O-alkilēšanai savienojumu ar formulu (1-c-1) ar reaģenta ar formulu W-R2-b (XIII) , kurā W pārstāv reaģēt spējīgu atšķeļamu grupu, palīdzību vidē, kas ir inerta reakcijas apstākļos, iegūstot tādā veidā savienojumu ar formulu: R(I-c-2) 35 LV 10452 7 kurā -0-R2‘b ir neobligāti aizvietota Ci-ioalkiloksigrupa, neobligāti aizvietota C2-6alkeniloksi-, C2-6alkiniloksi-, pirimidiniloksi-, di-(Ar2)-metoksi- vai (1-C l-4alkil-4-piperidinil)-oksi-grupa; b) reducē savienojumu ar formulu (1-c-l) ar reducētāja palīdzību reakcijas apstākļos inertā šķīdinātājā, iegūstot tāda veidā savienojumu ar formulu: sc) N-alkilē savienojumu ar formulu (1-b-l) ar reaģenta ar formulu W-R2'c (XIV) , kurā W pārstāv reaģēt spējīgu atšķeļamu grupu, palīdzību šķīdinātājā, kas ir inerts reakcijas apstākļos, iegūstot tādā veidā savienojumu ar formulu : Rkurā R2'c ir tāds pats, kā R2*a, pie noteikuma, ka atšķiras no ūdeņraža; vai neobligāti tālāk pārvērš savienojumus ar formulu (I) vienu otrā, sekojot šajā jomā zināmām grupu pārvēršanas metodēm, un, ja vēlams, pārvērš savienojumus ar formulu (I) terapeitiski aktīvā netoksiskā sāļu formā, apstrādājot ar atbilstošu skābi vai, otrādi, pārvēršot attiecīgās skābes sāli bāzes 5 8 10 15 20 25 30 formā ar sārma palīdzību; un/vai iegūst to stereoķīmisko izomēru formas. 35
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US5602187A | 1987-06-01 | 1987-06-01 |
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JP (1) | JPH0662612B2 (lv) |
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CA (1) | CA1307271C (lv) |
CY (1) | CY1866A (lv) |
DE (1) | DE3884055T2 (lv) |
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FI (1) | FI90078C (lv) |
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HU (2) | HU201056B (lv) |
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CA2026792A1 (en) * | 1989-11-01 | 1991-05-02 | Michael N. Greco | (6,7-dihydro-5h-pyrrolo[1,2-c]imidazol-5-yl)- and (5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl) substituted 1h-benzotriazole derivatives |
US5066656A (en) * | 1989-11-01 | 1991-11-19 | Janssen Pharmaceutica N.V. | Pharmacologically active (6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)- and (5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl) substituted 1H-benzotriazole derivatives |
NZ236440A (en) * | 1989-12-15 | 1993-07-27 | Merck & Co Inc | Reversal of sexual phenotype in poultry using an inhibitor of steroid biotransformation and/or aromatase inhibitor, poultry produced by this process |
AU7124691A (en) * | 1990-02-27 | 1991-08-29 | Ciba-Geigy Ag | Benzofurans |
DE4010797A1 (de) * | 1990-04-04 | 1991-10-10 | Hoechst Ag | Substituierte azole, verfahren zu deren herstellung, diese enthaltende mittel und deren verwendung |
EP0457716A1 (de) * | 1990-04-20 | 1991-11-21 | Ciba-Geigy Ag | Naphthalinderivate |
TW224461B (lv) * | 1990-09-18 | 1994-06-01 | Ciba Geigy Ag | |
US5162337A (en) * | 1990-10-05 | 1992-11-10 | Merck & Co., Inc. | Animal growth promotion |
TW210334B (lv) * | 1990-12-12 | 1993-08-01 | Ciba Geigy Ag | |
CH683151A5 (de) * | 1991-04-24 | 1994-01-31 | Ciba Geigy Ag | Antikonzeption bei weiblichen Primaten ohne Beeinflussung des menstruellen Zyklus. |
DE69230225T2 (de) | 1991-09-02 | 2000-05-31 | Yamanouchi Pharmaceutical Co., Ltd. | Triazolylierte tertiäre aminverbindungen oder ihre salze |
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JP2700595B2 (ja) * | 1992-05-21 | 1998-01-21 | 呉羽化学工業株式会社 | アゾール誘導体を含有する抗アロマターゼ剤 |
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IT1286866B1 (it) * | 1996-10-28 | 1998-07-17 | Menarini Farma Ind | Composti furano-eterociclici,loro preparazione ed uso come inibitori di aromatasi |
WO1998028257A1 (fr) * | 1996-12-24 | 1998-07-02 | Chugai Seiyaku Kabushiki Kaisha | Derives d'amine aromatiques ayant une action inhibitrice a l'egard des nos |
AU2001264223A1 (en) * | 2000-06-28 | 2002-01-08 | Ssp Co., Ltd. | Imidazole derivatives or salts thereof and drugs containing the derivatives or the salts |
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1988
- 1988-05-19 NZ NZ224714A patent/NZ224714A/xx unknown
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-
1992
- 1992-11-27 LV LVP-92-233A patent/LV10452B/lv unknown
-
1993
- 1993-10-18 BG BG98159A patent/BG60429B2/bg unknown
- 1993-12-16 LT LTIP1625A patent/LT3950B/lt not_active IP Right Cessation
-
1995
- 1995-06-29 HU HU95P/P00533P patent/HU211482A9/hu unknown
- 1995-07-13 HK HK114795A patent/HK114795A/xx not_active IP Right Cessation
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