DD294256A5 - PROCESS FOR PREPARING PYRAZOLYL SUBSITUTED TETRAZONE DERIVATIVES - Google Patents
PROCESS FOR PREPARING PYRAZOLYL SUBSITUTED TETRAZONE DERIVATIVES Download PDFInfo
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- DD294256A5 DD294256A5 DD34063090A DD34063090A DD294256A5 DD 294256 A5 DD294256 A5 DD 294256A5 DD 34063090 A DD34063090 A DD 34063090A DD 34063090 A DD34063090 A DD 34063090A DD 294256 A5 DD294256 A5 DD 294256A5
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Abstract
Die Erfindung beschreibt ein Verfahren zur Herstellung pyrazolylsubstituierter Tetrazolderivate. Heterocyclen dieses Typs sind als Zwischenprodukte zur Synthese biologisch aktiver Verbindungen von Interesse. Die Titelverbindungen werden erfindungsgemaesz hergestellt, indem man * (Formel I) in Loesungsmitteln wie Acetonitril oder Benzen mit Carbonsaeurehalogeniden (Formel II) in Gegenwart aequimolarer Mengen einer Hilfsbase wie Pyridin oder Triethylamin bei Temperaturen bis zum Siedepunkt des Reaktionsgemisches umsetzt und die hierbei gebildeten * (Formel III) mit Hydrazin oder Arylhydrazinen (Formel IV) in siedender alkoholischer Loesung in Gegenwart einer Saeure, z. B. Essigsaeure, zur Reaktion bringt.{* Zwischenprodukte; * Carbonsaeurehalogenide; Pyridin; Triethylamin; * Hydrazin; Arylhydrazine; Essigsaeure}The invention describes a process for the preparation of pyrazolyl-substituted tetrazole derivatives. Heterocycles of this type are of interest as intermediates for the synthesis of biologically active compounds. The title compounds are prepared according to the invention by reacting * (formula I) in solvents such as acetonitrile or benzene with carbonyl halides (formula II) in the presence of equimolar amounts of an auxiliary base such as pyridine or triethylamine at temperatures up to the boiling point of the reaction mixture and the * (formula III) with hydrazine or arylhydrazines (formula IV) in boiling alcoholic solution in the presence of an acid, for. As acetic acid, brings to the reaction. {* Intermediates; * Carboxylic acid halides; pyridine; triethylamine; * Hydrazine; arylhydrazines; Acetic acid}
Description
Titel der ErfindungTitle of the invention
Verfahren zur Herstellung pyrazolylsubstituierter Tetrazol derivateProcess for the preparation of pyrazolyl-substituted tetrazole derivatives
Anwendungsgebiet der ErfindungField of application of the invention
Die Erfindung betrifft ein Verfahren zur Herstellung pyrazolylsubstituierter Tetrazolderivate der allgemeinen Formel V, inThe invention relates to a process for the preparation of pyrazolyl-substituted tetrazole derivatives of the general formula V, in
1 2 31 2 3
der R einen Arylrest, R einen Alkyl- oder Arylrest und R Wasserstoff oder einen Arylrest bedeuten. Heterocyclen dieses Typs sind als Zwischenprodukte zur Synthese biologisch aktiver Verbindungen von Interesse*R is an aryl radical, R is an alkyl or aryl radical and R is hydrogen or an aryl radical. Heterocycles of this type are of interest as intermediates for the synthesis of biologically active compounds *
Charakteristik des bekannten Standes der TechnikCharacteristic of the known state of the art
Pyrazolylsubstituierte Tetrazolderivate der Formel V sind bischer nicht bekannt (vgl. F. R. BENSON, Chem. Rev. £1_ /"1947/ 1i F. R. BENSON in "Heterocyclic Compounds" /Hrsg. R. C. Elderfield/, Bd. 8, S. 1, Wiley, New York, 1967; R. N. BUTLER, Adv. Heterooycl. Chera. .21 /ί977/ 324; R. N. BUTLER in "Comprehensive Heterocyclic Chemistry" /Hrsg. A. R. Katritzky und C. W. Rees/, Bd. 5, Teil 4A, S. 791, Pergamon Press, Oxford, 1984). Für andere Pyrazolyltetrazole wurden in der Literatur folgende Herstellungsverfahren beschrieben:Pyrazolyl-substituted tetrazole derivatives of the formula V are not known from Bischer (see FR BENSON, Chem. Rev. 1947 / 1i FR BENSON in "Heterocyclic Compounds" / Ed. RC Elderfield /, Vol. 8, page 1, Wiley, New York, 1967; RN BUTLER, Adv. Heterooycl. Chera .21 / ί977 / 324; RN BUTLER in "Comprehensive Heterocyclic Chemistry" / ed. AR Katritzky and CW Rees /, Vol. 5, part 4A, p. 791, Pergamon Press, Oxford, 1984.) For other pyrazolyltetrazoles, the following production methods have been described in the literature:
a) Umsetzung von 5-Hydrazino~1H-tetrazol mit Acetylaceton zum 5-(3f5-Dimethyl-1H-pyrazol-1-yl)-1H-tetrazol und dessen nachfolgende Halogenierung in 4-Stθllung des Pyrazolrestes (F. L. SCOTT, D. Q. O1DONOVAN und j; REILLY, J. Appl. Chem. 2 /Ϊ9527 368)|a) Reaction of 5-hydrazino-1H-tetrazole with acetylacetone to give 5- (3f5-dimethyl-1H-pyrazol-1-yl) -1H-tetrazole and its subsequent halogenation in the 4-position of the pyrazole radical (FL SCOTT, DQ O 1 DONOVAN and J; REILLY, J. Appl. Chem. 2 / Ϊ9527 368) |
b) Umsetzung von 3-Cyano-5-methyl-1H-pyrazol bzw. 5-Cyano-3-methyl-4-nitro-1-phenyl-1H-pyrazol mit Natriumazid zum 5-(5~Methyl-1H-pyrazol-3-yl)-1H-tetrazol (JP 7207378, C. A. IZ /Ϊ9727 5489) bzw. 5-(3-Methyl-4-nitro-1-phenyl-1H-pyrazol-5-yl)-1H-tetrazol (M. A. KHAN und A. C. C. FREITAS, Monatsh. Chem. V\2 /"1981/ 675);b) Reaction of 3-cyano-5-methyl-1H-pyrazole or 5-cyano-3-methyl-4-nitro-1-phenyl-1H-pyrazole with sodium azide to give 5- (5-methyl-1H-pyrazole) 3-yl) -1H-tetrazole (JP 7207378, CA IZ / Ϊ9727 5489) or 5- (3-methyl-4-nitro-1-phenyl-1H-pyrazol-5-yl) -1H-tetrazole (MA KHAN and ACC FREITAS, Monatsh. Chem. V \ 2 / "1981/675);
o) Umsetzung von 2-(4-Chlor-phenyl)-5-(4-morpholino-buta-1,3-dien~1-yl)-2H-tetrazol mit Tosylazid zum 2-(4--Chlor-phenyl) 5-(1H-pyrazol-3-yl)-2H-tetrazol (G. TBiARI, α. HAJOS, A.o) reaction of 2- (4-chlorophenyl) -5- (4-morpholino-buta-1,3-dien-1-yl) -2H-tetrazole with tosyl azide to give 2- (4-chlorophenyl) 5- (1H-pyrazol-3-yl) -2H-tetrazole (G. TBiARI, α. HAJOS, A.
MESSMER und A. GELLERI, Monatsh. Chem, IJj) /19887 1037).MESSMER and A. GELLERI, Monatsh. Chem, IJj / 19887 1037).
Auf Grund ihres andersartigen Substitutions- und Verknüpfungsmusters sind jedoch Pyrazolyltetrazole der Formel V nach keiner der unter a) - c) genannten Methoden herstellbar. Ein bekanntes Prinzip zum Aufbau von Pyrazolringen bestoht in der Umsetzung von Hydrazinen mit Enaminoketonen der allgemeinen Struktur R2N-CH=CR1-COR" (vgl, Y. LIN und S. A. LANG, J. Heterocycl. Chem. V^ ΖΪ9777 345} B. GRAPEE, M.-C. SACQUET, M.-C. BELLASSOUED-PARGEAU und P. MAITTE, J. Heterooyol. Chem. 22 Z"19867 1753). Pur die Synthese von Pyrazolyltetrazolen der Formel V wären nach dieser Methode Enaminoketone erforderlich, in denen R1 einen 1-Aryl-1H-tetrazol-5-yl-Rest darstellt; tetrazolylsubstituierte Enaminoketone dieses Typs sind bisher unbekannt.However, due to their different substitution and linking pattern, pyrazolyltetrazoles of the formula V can not be prepared by any of the methods mentioned under a) -c). One known principle for the construction of pyrazole rings is the reaction of hydrazines with enaminoketones of the general structure R 2 N-CH =CR 1 -COR "(cf., Y. LIN and SA LANG, J. Heterocycl. Chem. V ^ ΖΪ 9777 345} B. GRAPEE, M.-C. SACQUET, M.-C. BELLASSOUED-PARGEAU and P. MAITTE, J. Heterooyol Chem., 22 Z "19867 1753). Purely the synthesis of pyrazolyltetrazoles of the formula V would require enaminoketones according to this method, in which R 1 represents a 1-aryl-1H-tetrazol-5-yl radical; Tetrazolyl-substituted enaminoketones of this type are hitherto unknown.
Ziel der ErfindungObject of the invention
Die Erfindung hat ein Verfahren zum Ziel, mit dem pyrazolylsubstituierte Tetrazolderivate der Formel V in einfacher Weise aus leicht zugänglichen Ausgangsstoffen hergestellt werden können.The invention has for its object a method by which pyrazolyl-substituted tetrazole derivatives of the formula V can be prepared in a simple manner from readily available starting materials.
Darlegung des Wesens der ErfindungExplanation of the essence of the invention
Der Erfindung liegt die Aufgabe zugrunde, PyrazolyltetrazoleThe invention is based on the object Pyrazolyltetrazole
1 21 2
der Formel V, in der R einen Arylrest, R einen Alkyl- oder Arylrest und R^ Wasserstoff oder einen Arylrest bedeuten, aus geeigneten 1,5-disubstituierten Tetrazolen herzustellen. Die Aufgabe wird erfindungsgemäß daduroh gelöst, daß man !-substituierte 5-(2-Diraethylamino-vinyl)-1H-tetrazole der Formel I, in der R einen Arylrest darstellt, in Lösungsmitteln wie Acetonitril oder Benzen mit Carbonsäurehalogeniden der Formel II, in der R einen Alkyl- oder Arylrest und X ein Halogenatom, vorzugsweise Chlor, bedeuten, in Gegenwart äquimolarer Mengen einer Hilfsbase wie Pyridin oder Triethylamin bei Temperaturen bis zum Siedepunkt des Reaktionsgemisches umsetzt und die hierbei gebildeten 1-arylsubstituierten 5~(1-Aoyl-of the formula V in which R is an aryl radical, R is an alkyl or aryl radical and R ^ is hydrogen or an aryl radical, from suitable 1,5-disubstituted tetrazoles. The object is achieved according to the invention daduroh, that! -Substituted 5- (2-diraethylamino-vinyl) -1H-tetrazoles of the formula I in which R is an aryl radical, in solvents such as acetonitrile or benzene with carboxylic acid halides of the formula II, in the R is an alkyl or aryl radical and X is a halogen atom, preferably chlorine, in the presence of equimolar amounts of an auxiliary base such as pyridine or triethylamine is reacted at temperatures up to the boiling point of the reaction mixture and the resulting 1-aryl-substituted 5 ~ (1-Aoyl-
- 3 - Z9UM - 3 - Z9UM
2-dimethylamino-vinyl)-1H-tetrazole III mit Hydrazin (Formel IV, R3 = H) oder Arylhydrazinen (Formel IV, R3 = Aryl) in siedender alkoholischer (z.B. m'ethanolisoher oder ethanolischer) Lösung in Gegenwart einer Säure, z.B. Essigsäure, zur Reaktion bringt.2-dimethylamino-vinyl) -1H-tetrazoles III with hydrazine (formula IV, R 3 = H) or arylhydrazines (formula IV, R 3 = aryl) in boiling alcoholic (eg m'ethanolisoher or ethanolic) solution in the presence of an acid, For example, acetic acid, brings to the reaction.
Die Zwischenprodukte III fallen beim Einengen des Reaktionsgemisches in fester kristalliner Form zusammen mit dem Hydrohalogenid der Hilfsbase an und werden von diesem durch Waschen mit Wasser befreit; sie können jedoch auch ohne Abtrennung des tert.-Arainsalzes weiter zu V verarbeitet werden. Die aus III und Hydrazin (IV, V? = H) resultierenden Pyrazolyltetrazole V, R^ » H liegen - wie generell N-unsubstituierte Pyrazole (vgl. J. ELGUERO in "Comprehensive Heterocyclic Chemistry"The intermediates III are obtained on concentration of the reaction mixture in solid crystalline form together with the hydrohalide of the auxiliary base and are freed from this by washing with water; However, they can also be processed without separation of the tert-Arainsalzes to V. The pyrazolyltetrazoles V, R 1 H 'resulting from III and hydrazine (IV, V 1 = H are - as in general N-unsubstituted pyrazoles (compare J. ELGUERO in "Comprehensive Heterocyclic Chemistry").
/Hrsg. A. R. Katritzky und C. W. Ree§7, Bd. 5, S. 167 ff, Pergamon Press, Oxford, 1984) - als Gleichgewichtsgemische zweier Tautomerer vor, was in der Nomenklatur entsprechend zum Ausdruck gebracht wird; Formel V, R^ = H repräsentiert folglich nur eine der beiden tautomeren Formen./ Edit. A. R. Katritzky and C.W. Ree§7, Vol. 5, p. 167 et seq., Pergamon Press, Oxford, 1984) - as equilibrium mixtures of two tautomers, which is correspondingly expressed in the nomenclature; Formula V, R ^ = H thus represents only one of the two tautomeric forms.
Im Falle der Umsetzung von III mit Arylhydrazinen (IV, R^ a Aryl) zeichnet sich das erfindungsgemäße Verfahren dadurch aus, daß es ausschließlich zu Pyrazolyltetrazolen der Formel V und nicht zu den formal möglichen Isomeren oder zu Isomerengemischen führt. Die Ausgangsverbindungen I sind durch Umsetzung von 3-Halogen-In the case of the reaction of III with arylhydrazines (IV, R ^ a aryl), the inventive method is characterized in that it leads exclusively to Pyrazolyltetrazolen of formula V and not to the formally possible isomers or mixtures of isomers. The starting compounds I are obtained by reaction of 3-halogen
prop-2-en-1-ylidendimethyliminiumsalzen mit überschüssigem Natriumazid in alkoholischer Lösung leicht zugänglich (DD 268690; vgl. G. W. FISCHER und M. HERRMANN, J. prakt. Chem. £20 /"1988/ 963).Prop-2-en-1-ylidenedimethyliminiumsalzen with excess sodium azide in alcoholic solution readily available (DD 268690, see G.W. FISCHER and M. HERRMANN, J. prakt. Chem., 20 / "1988/963).
Die Erfindung wird nachstehend an 5 Ausführungsbeispielen erläutert; die hierin angegebenen Ausbθμtθn an V beziehen sich auf die eingesetzten 1-Aryl-5-(2-diniv?thylamino-vinyl)-1H-tetrazole I.The invention will be explained below with reference to five embodiments; the hereinbefore specified amounts of θO to V refer to the 1-aryl-5- (2-dinivinylamino-vinyl) -1H-tetrazoles I.
Ausführungsbeispieleembodiments
5-(5-Methyl-1(2)H-pyrazol-4-yl)-1-phenyl-1H-tetrazol (V, R1 « Ph,5- (5-Methyl-1 (2) H -pyrazol-4-yl) -1-phenyl-1H-tetrazole (V, R 1 "Ph,
R2 a Me, R3 β H)R 2 a Me, R 3 β H)
Eine heiße Lösung von 2,15 g (10 mmol) 5-(2-Dimethylamino-vinyl)-A hot solution of 2.15 g (10 mmol) of 5- (2-dimethylamino-vinyl) -
1-phenyl-1H-tetrazol (I, R = Ph), in 5 ml absol· Acetonitril und 0,95 g (12 mmol) trockenem Pyridin wird mit 0,94 g ( 12 mmol) Acetylchlorid (II, R « Me, X = Cl) versetzt und unter Feuchtigkeitsausschluß 2,5 Std. bei 80 0C auf dem Wasserbad erhitzt· Anschließend zieht man das Lösungsmittel 1· Vak. ab, digeriert den verbleibenden Rückstand mit Wasser, saugt ab, wäscht mit Wasser und trocknet über Po0c. Die Lösung des so1-phenyl-1H-tetrazole (I, R = Ph) in 5 ml of absolute acetonitrile and 0.95 g (12 mmol) of dry pyridine is treated with 0.94 g (12 mmol) of acetyl chloride (II, R «Me, X = Cl) and heated under exclusion of moisture 2.5 hrs. At 80 0 C on the water bath · Then, the solvent is drawn 1 × Vak. from, the remaining residue is digested with water, filtered off, washed with water and dried over P o 0 c. The solution of the so
ι 2 5 ρ erhaltenen Zwischenproduktes III, R « Ph, R « Me in 30 ml Ethanol erhitzt man nach Zugabe von 0,67 g (10 mmol) 72prozo Hydrazinhydrat (IV, R3 - H) und 2,40 g (40 mmol) Essigsäure 2 Std# unter magnetischem Rühren am Rückfluß und destilliert dann 25 ml Ethanol ab. Der Rückstand wird mit Diethylether aufgenommen, die organische Phase mehrmals mit Wasser gewaschen, mit Natriumsulfat getrocknet und eingeengt, wobei sioh das Reaktionsprodukt kristallin absoheidet. Ausbeute 1,26 g (56%)? farblose Kristalle (aus Acetonitril), Schmp, 183-184 0Cι 2 5 intermediate obtained ρ III, R 'is Ph, R "Me in 30 ml of ethanol is heated after the addition of 0.67 g (10 mmol) of hydrazine hydrate 72proz o (IV, R 3 - H) and 2.40 g (40 mmol) of acetic acid for 2 h # with magnetic stirring at reflux and then distilled off 25 ml of ethanol. The residue is taken up with diethyl ether, the organic phase is washed several times with water, dried with sodium sulfate and concentrated, whereby the reaction product is precipitated in crystalline form. Yield 1.26 g (56%)? colorless crystals (from acetonitrile), m.p., 183-184 0 C.
Analog werden erhalten:Analog receive:
1 -(4-Me thy 1- phenyl) -5-( 5-methyl-1 (2)H-pyrazol-4-yD-1H-tetrazol (V, R1 « 4-Me-C6H4, R2 » Me, R3 = H) Ausbeute 69%· Farblose Kristalle (aus Acetonitril), Schmp· 177-178 0C.1- (4-methyl-1-phenyl) -5- (5-methyl-1 (2) -H-pyrazol-4-yD-1H-tetrazole (V, R 1 -4-Me-C 6 H 4 , R 2 »Me, R 3 = H) · yield 69% colorless crystals (from acetonitrile), m.p. · 177-178 0 C.
1 -(4-Methoxy-phenyl)-5-(5-methyl-1(2)H-pyrazol-4-yl)-1H~ tetrazol (V, R1 = 4-MeO-CgH4, R2 = Me, R3 = H) Ausbeute 67%· Farblose Nadeln (aus Methanol), Schmp· 166-167 0C1- (4-methoxyphenyl) -5- (5-methyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-MeO-CgH 4 , R 2 = Me , R 3 = H) Yield 67% · Colorless needles (from methanol), mp 166-167 0 C.
1-(4-Fluor-phenyl)""5-(5-methyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 β 4-F-C6H4, R2 - Me, R3 = H)1- (4-Fluoro-phenyl) "" 5- (5-methyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R "1" β "4"-FC 6 H 4 , R 2 - Me, R 3 = H)
Ausbeute 88%· Farblose Nadeln (aus Acetonitril), Schmp. I76-177 0CYield 88% · Colorless needles (from acetonitrile), mp. I76-177 0 C
1-(4-Chlor-phenyl)-5-(5-methyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 - 4-Cl-C6H4, R2 = Me, R3 β H)1- (4-chloro-phenyl) -5- (5-methyl-1 (2) H-pyrazol-4-yl) -1H-tetrazole (V, R 1-4-Cl-C 6 H 4, R 2 = Me, R 3 β H)
Ausbeute 56%· Farblose Kristalle (aus Methanol), Sohmp« 152— 153 0CYield 56% · Colorless crystals (from methanol), Sohmp 152-153 0 C
1-(4-Brom-phenyl)-5-(5-methyl-1(2)H-pyrazol-4-yl)-1 H-tetrazol (V, R1 = 4-Br-C6H., R2 = Me, R3 = H)1- (4-bromo-phenyl) -5- (5-methyl-1 (2) H-pyrazol-4-yl) -1 H-tetrazole (V, R 1 = 4-Br-C 6 H, R 2 = Me, R 3 = H)
Ausbeute 78%» Farblose Kristalle (aus Methanol), Sohmp. 183-184 0CYield 78% »Colorless crystals (from methanol), Sohmp. 183-184 0 C
1-(4-Iod-phenyl)-5~(5-methyl-1(2)H~pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-1-C6H4, R2 = Me, R3 = H)1- (4-iodo-phenyl) -5 ~ (5-methyl-1 (2) H ~ pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-1-C 6 H 4, R 2 = Me, R 3 = H)
Ausbeute 81%. Farblose Kristalle (aus Methanol), Schmp. 187-188 0C.Yield 81%. Colorless crystals (from methanol), mp 187-188 0 C.
1-Phenyl-5-(5-phenyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 = R2 =Hi» R3 « H)1-phenyl-5- (5-phenyl-1 (2) H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = R 2 = Hi "R 3" H)
2,15 g (10 mmol) 5-(2-Dimethylamino-vinyl)-1-phejuy 1-1 H-tetrazol (I, R =» Ph) werden in 10 ml absol. Benzen mit 1,21 g (12 mmol) wasserfreiem Triethylamin und 1,69 g (12 mmol) Benzoylohlorid (II, R = Ph, X = Cl) 4 Std. unter Feuchtigkeitsausschluß rückfließend erhitzt. Anschließend destilliert man die reichliche Hälfte des Lösungsmittels i. Vak, ab und läßt in der Kälte kristallisieren« Das Kristallgemisch wird abgesaugt, durch Waschen mit Wasser von Triethylaminhydrochlorid befreit und getrocknet· Die Lösung des so erhaltenen Zwischenproduktes III, R β R2 = Ph in 30 ml Methanol erhitzt man nach Zugabe von 0,67 ß (10 mmol) 72proz. Hydrazinhydrat (IV, R3 = H) und 2,40 g (40 mmol) Essigsäure 2 Std. unter magnetischem Rühren am Rückfluß und destilliert dann 25 ml Methanol ab· Aus dem Rückstand scheiden sioh beim Abkühlen, tropfenweisen Versetzen mit Wasser und Anreiben 2,26 g (78%) Reaktionsprodukt ab. Umkristallisation aus Acetonitril liefert farblose Kristalle vom Schmp. 170-171 0C,2.15 g (10 mmol) of 5- (2-dimethylamino-vinyl) -1-phejuyl 1-1H-tetrazole (I, R = »Ph) are dissolved in 10 ml of absolute. Benzen with 1.21 g (12 mmol) of anhydrous triethylamine and 1.69 g (12 mmol) Benzoylohlorid (II, R = Ph, X = Cl) for 4 hrs refluxing with exclusion of moisture. Then distilled the copious half of the solvent i. Vak, from and allowed to crystallize in the cold "The crystal mixture is filtered off with suction, freed from triethylamine hydrochloride by washing with water and dried. The solution of the resulting intermediate III, R β R 2 = Ph in 30 ml of methanol is heated after addition of 0, 67β (10 mmol) 72% Hydrazine hydrate (IV, R 3 = H) and 2.40 g (40 mmol) of acetic acid for 2 hours under magnetic stirring at reflux and then distilled off 25 ml of methanol from the residue sioh on cooling, dropwise addition with water and trituration 2 , 26 g (78%) of the reaction product from. Recrystallization from acetonitrile gives colorless crystals of mp. 170-171 0 C,
1 -(4-Methyl-phenyl)-5-(5-phenyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 =» 4-Me-C6H4, R2 =. Ph, R3 = H)1 - (4-Methyl-phenyl) -5- (5-phenyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R 1 = »4-Me-C 6 H 4 , R 2 =. Ph, R 3 = H)
Eine heiße Lösung von 2,29 g (10 mmol) 5-(2-Dimethylamino-vinyl)-1-(4-methyl-phenyl)-1H-tetrazol (I, R1 = 4-Me-C6H4) in 5 ml absol. Acetonitril und 0,95 g (12 mmol) trockenem Pyridin wird mit 1,69 g (12 mmol) Benzoylchlorid (II, R2 » Ph, X » Cl) versetzt und unter Feuohtigkeitsaussohluß 3 Std. bei 80 0C auf dem Wasserbad erhitzt. Danach zieht man das Lösungsmittel i. Vak. ab,A hot solution of 2.29 g (10 mmol) of 5- (2-dimethylamino-vinyl) -1- (4-methylphenyl) -1H-tetrazole (I, R 1 = 4-Me-C 6 H 4 ) in 5 ml absolute. Acetonitrile and 0.95 g (12 mmol) of dry pyridine is treated with 1.69 g (12 mmol) of benzoyl chloride (II, R 2 »Ph, X» Cl) and heated under flooding for 3 hours at 80 0 C on a water bath , Then draw the solvent i. Vak. from,
digeriert den Rückstand mit kaltem Wasser, saugt ab, wäscht mit Wasser und trocknet über Ι*2Ο5· D:i·0 11031111S des so erhaltenen Zwischenproduktes III, R = 4-Me-CgH., R2 = Ph in 30 ml Ethanol erhitzt man nach Zugabe von 0,67 g (10 mmol) 72proz. Hydrazinhydrat (IV, R3 = H) und 2,40 g (40 mmol) Essigsäure 2 Std. unter magnetischem Rühren am Rückfluß und destilliert dann 25 ml Etha*- nol ab. Beim Abkühlen und tropfenweiser Wasserzugabe unter Anreiben kristallisieren 2,23 g (74%) Reaktionsprodukt. Nach Umkristallisation aus Methanol resultieren farblose Kristalle vom Schmp. 177-178 0C.digested the residue with cold water, filtered off, washed with water and dried over Ι * 2 Ο 5 · D: i · 0 11031111 S of the resulting intermediate III, R = 4-Me-CgH., R 2 = Ph in 30 ml of ethanol is heated after addition of 0.67 g (10 mmol) 72proz. Hydrazine hydrate (IV, R 3 = H) and 2.40 g (40 mmol) of acetic acid for 2 hours under magnetic stirring at reflux and then distilled from 25 ml of ethanol * - nol. Upon cooling and dropwise addition of water with trituration crystallize 2.23 g (74%) of the reaction product. Recrystallization from methanol gives colorless crystals of mp. 177-178 0 C.
Analog werden erhalten:Analog receive:
1-(4-Ethyl-phenyl)-5-(5-phenyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-Et-G6H4, R2 = Ph, R3 = H)1- (4-ethylphenyl) -5- (5-phenyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-Et-G 6 H 4 , R 2 = Ph, R 3 = H)
Ausbeute 82%. Farblose Kristalle (aus Acetonitril), Schmp. 194-195 0C.Yield 82%. Colorless crystals (from acetonitrile), mp 194-195 0 C.
1-(4-Methoxy-phenyl)-5-(5-phenyl-1(2)H-pyrazol-'4-yl)-1H-tetrazol (V, R1 = 4-MeO-G6H4, R2 = Ph, R3 = H)1- (4-methoxyphenyl) -5- (5-phenyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-MeO-G 6 H 4 , R 2 = Ph, R 3 = H)
Ausbeute 71%. Farblose Kristalle (aus Acetonitril), Schmpe 171-172 0C.Yield 71%. Colorless crystals (from acetonitrile), mp 171-172 0 C. e
1-(4-Fluor-phenyl)-5-(5-phenyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-F-C6H4, R2 = Ph, R3 = H)1- (4-Fluoro-phenyl) -5- (5-phenyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-FC 6 H 4 , R 2 = Ph , R 3 = H)
Ausbeute 75%. Farblose Kristalle (aus Acetonitril), Schmp. 186-187 0C.Yield 75%. Colorless crystals (from acetonitrile), mp. 186-187 0 C.
1-(4-Chlor-phenyl)-5-(5-phenyl-1(2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 « 4-Cl-C6H4, R2 =» Ph, R3 « H)1- (4-Chloro-phenyl) -5- (5-phenyl-1 (2) H -pyrazol-4-yl) -1H-tetrazole (V, R 1 "4-Cl-C 6 H 4 , R 2 = "Ph, R 3 " H)
Ausbeute 90%. Farblose Kristalle (aus Acetonitril), Schmp. 191-192 0C.Yield 90%. Colorless crystals (from acetonitrile), mp 191-192 0 C.
1-(4-Brom-phenyl)-5-(5-phenyl-1(2)H-pyrazol-4-yl)-iH-tetrazol (V, R1 - 4-Br-C6H4, R2 = Ph, R3 = H)1- (4-Bromo-phenyl) -5- (5-phenyl-1 (2) H -pyrazol-4-yl) -iH-tetrazole (V, R 1 -4-Br-C 6 H 4 , R 2 = Ph, R 3 = H)
Ausbeute 74%. Farblose Kristalle (aus Acetonitril), Sohmp. I96-197 0CYield 74%. Colorless crystals (from acetonitrile), Sohmp. I96-197 0 C
1-(4-Iod-phenyl)-5-(5-pheny1-1 (2)H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-1-CgH4, R2 a Ph, R3 « H)1- (4-iodo-phenyl) -5- (5-phenyl-1- (2) -H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-1-CgH 4 , R 2 a Ph , R 3 «H)
Ausbeute 70%· Farblose Kristalle (aus Acetonitril), Schmp. 193-194 0C.Yield 70% · Colorless crystals (from acetonitrile), mp. 193-194 0 C.
5-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-1H-tetrazol (V, R1 = R3 =» Ph, R2 = Me)5- (5-methyl-1-phenyl-1H-pyrazol-4-yl) -1-phenyl-1H-tetrazole (V, R 1 = R 3 = »Ph, R 2 = Me)
2,15 g (10 ramol) 5-(2~D:bnethylamino«vinyl)-1-phenyl-1 H-tetrazol (I, R « Ph) werden gemäß Beispiel 1 in 5 ml absol. Acetonitril und 0,95 g (12 mmol) trockenem Pyridin mit 0,94 g (12 mmol) Aoetylchlorid (II, R = Me, X » Cl) zum Zwischenprodukt III,2.15 g (10 mmol) of 5- (2 ~ D: bnethylamino "vinyl) -1-phenyl-1H-tetrazole (I, R" Ph) are in accordance with Example 1 in 5 ml of absolute. Acetonitrile and 0.95 g (12 mmol) of dry pyridine with 0.94 g (12 mmol) of aoetyl chloride (II, R = Me, X »Cl) to give Intermediate III,
1 2 R a Ph, R β Me umgesetzt. Letzteres erhitzt man in 30 ml Ethanol mit 1,08 g (10 mmol) Phenylhydrazin (IV, R3 = Ph) und 2,40 g (40 mmol) Essigsäure 2 Std. unter magnetischem Rühren am Rückfluß und destilliert dann 25 ml Ethanol ab. Beim Abkühlen und tropfenweiser Wasserzugabe unter Anreiben kristallisieren 1,54 g (51%) Reaktionsprodukt. Umkristallisation aus Methanol liefert farblose Nadeln vom Schmp. 113-114 0G.1 2 R a Ph, R β Me implemented. The latter is heated in 30 ml of ethanol with 1.08 g (10 mmol) of phenylhydrazine (IV, R 3 = Ph) and 2.40 g (40 mmol) of acetic acid for 2 hours under magnetic stirring at reflux and then distilled off 25 ml of ethanol , Upon cooling and dropwise addition of water with trituration crystallize 1.54 g (51%) of the reaction product. Recrystallization from methanol gives colorless needles of mp. 113-114 0 G.
Analog werden erhalten:Analog receive:
1-(4-Methyl-phenyl)-5-(5-methy1-1-pheny1-1H-pyrazol-4-yl)-1H-1- (4-methyl-phenyl) -5- (5-methy1-1-pheny1-1H-pyrazol-4-yl) -1H-
tetrazol (V, R1 « 4-Me-C6H4, R2 = Me, R3 = Ph)tetrazole (V, R 1 -4-Me-C 6 H 4 , R 2 = Me, R 3 = Ph)
Ausbeute 65%. Farblose Nadeln (aus Methanol), Schmp. 131-132 0C.Yield 65%. Colorless needles (from methanol); mp. 131-132 0 C.
1-(4-Methoxy-phenyl)-5-(5-methy1-1-pheny1-IH-pyrazol-4-yl)-1H-1- (4-methoxy-phenyl) -5- (5-methy1-1-pheny1-IH-pyrazol-4-yl) -1H-
tetrazol (V, R1 = 4-MeO-C6H4, R2 » Me, R3 = Ph)tetrazole (V, R 1 = 4-MeO-C 6 H 4 , R 2 »Me, R 3 = Ph)
Ausbeute 90%. Farblose Nadeln (aus Methanol), Schmp. 145-146 0C.Yield 90%. Colorless needles (from methanol); mp. 145-146 0 C.
1 -(4-Chlor-phenyl)-5-(5-methy1-1-phenyl-1H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-Cl-C6H4, R2 = Me, R3 = Ph) Ausbeute 77%. Farblose Kristalle (aus Methanol), Schmp. 100-101 0C.1 - (4-chloro-phenyl) -5- (5-methy1-1-phenyl-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-Cl-C 6 H 4, R 2 = Me, R 3 = Ph) Yield 77%. Colorless crystals (from methanol); mp. 100-101 0 C.
1~(4~Brom-phenyl)-5-(5~methyl~1-phenyi-1H-pyrazol~4-yl)-1H-tetrazol (V, R* =» 4-Br-C6H4, R2 = Me, R3 = Ph) Ausbeute 51%. Farblose Kristalle (aus Methanol), Schmp. 128-129 0C1 ~ (4 ~ bromo-phenyl) -5- (5 ~ methyl ~ 1-phenyl-1H-pyrazol ~ 4-yl) -1H-tetrazole (V, R * = "4-Br-C 6 H 4, R 2 = Me, R 3 = Ph) Yield 51%. Colorless crystals (from methanol); mp. 128-129 0 C.
1 -(4-Iod-phenyl)-5-( 5-methyl-1 -pb.enyl-1 H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-1-C6H4, R2 « Me, R3 » Ph) Ausbeute 86%, Farblose Kristalle (aus Acetonitril), Sohmp. 157-158 0C.1 - (4-iodo-phenyl) -5- (5-methyl-1 -pb.enyl-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-1-C 6 H 4 , R 2 «Me, R 3 » Ph) Yield 86%, colorless crystals (from acetonitrile), Sohmp. 157-158 0 C.
1-Phenyl-5-(1,5-diphenyl~1H-pyrazol-4~yl)-1H-tetrazol (V, R1 » R2 a R3 = Ph)1-phenyl-5- (1,5-diphenyl-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 R 2 a R 3 = Ph)
2,15 g (10 mmol) 5~(2-Dimethylamino-vinyl)-1-phenyl-1H-tetrazol (I, R = Ph) werden in 5 ml absol. Acetonitril und 0,95 g (12 mmol) trockenem Pyridin analog Beispiel 3 mit 1,69 g (12 mmol) Benzoylchlorid (II, R » Ph, X = Cl) zinn Zwischenprodukt III,2.15 g (10 mmol) of 5 - (2-dimethylamino-vinyl) -1-phenyl-1H-tetrazole (I, R = Ph) are dissolved in 5 ml of absolute. Acetonitrile and 0.95 g (12 mmol) of dry pyridine analogously to Example 3 with 1.69 g (12 mmol) of benzoyl chloride (II, R »Ph, X = Cl) tin intermediate product III,
1 2 R = R =» Ph umgesetzt. Letzteres erhitzt man in 30 ml Ethanol mit 1,08 g (10 mmol) Phenylhydrazin (IV, R3 = Ph) und 2,40 g (40 mmol) Essigsäure 2 Std. rückfließend unter magnetischem Rühren und destilliert dann 25 ml Ethanol ab. Aus dem Rückstand kristallisieren 2,57 g (86%) Reaktionsprodukt. Nach Umkristallisation aus Acetonitril resultieren farblose Nadeln vom Schmp, 178-179 0C.1 2 R = R = »Ph implemented. The latter is heated in 30 ml of ethanol with 1.08 g (10 mmol) of phenylhydrazine (IV, R 3 = Ph) and 2.40 g (40 mmol) of acetic acid for 2 hrs refluxing with magnetic stirring and then distilled off 25 ml of ethanol. From the residue, 2.57 g (86%) of the reaction product crystallize. After recrystallization from acetonitrile colorless needles of mp result, 178-179 0 C.
Analog werden erhalten:Analog receive:
1 -(4-Methy1-phenyl)-5-(1,5-diphenyl-1H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-Me-C6H4, R2 = R3 = Ph)1- (4-methylphenyl) -5- (1,5-diphenyl-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-Me-C 6 H 4 , R 2 = R 3 = Ph)
Ausbeute 82%. Farblose Nadeln (aus Acetonitril), Schmp. 172-173 0C.Yield 82%. Colorless needles (from acetonitrile), mp 172-173 0 C.
1-(4-Methoxy-phenyl)-5-0»5-dipheny1-1H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-MeO-CgH4, R2 = R3 = Ph) Ausbeute 68%. Farblose Nadeln (aus Acetonitril), Schmp. 159-160 0C.1- (4-methoxy-phenyl) -5-0 "5-dipheny1-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-MeO-CGH 4, R 2 = R 3 = Ph ) Yield 68%. Colorless needles (from acetonitrile), mp 159-160 0 C.
1-(4-Pluor-phenyl)-5-(1,5-diphenyl-1H-pyrazol-4-yl)-1H-tetrazol (V, R1 β 4-F-C6H4, R2 = R3 = Ph)1- (4-Pluorophenyl) -5- (1,5-diphenyl-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 β 4-FC 6 H 4 , R 2 = R 3 = Ph)
Au8beu",o 81%. Farblose Nadeln (aus Acetonitril), Schmp. 184-185 0C-.Au8beu ", o 81% Colorless needles (from acetonitrile), mp 184-185 0 C-.
1-(4-Chlor-phenyl)-5-(1,5-dipheny1-1H-pyrazol-4-yl)-1H-tetrazol (V, R1 β 4-Cl-C6H4, R2 β R3 a Ph)1- (4-Chloro-phenyl) -5- (1,5-diphenyl-1-H-pyrazol-4-yl) -1H-tetrazole (V, R 1 β 4-Cl-C 6 H 4 , R 2 β R 3 a Ph)
Ausbeute 80%. Farblose Nadeln (aus Acetonitril), Sohmp. 198-199 0CYield 80%. Colorless needles (made of acetonitrile), Sohmp. 198-199 0 C
1-(4-Brom-phenyl)-5-(1,5-diphenyl-1H-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-Br-C6H4, R2 = R3 = Ph)1- (4-bromo-phenyl) -5- (1,5-diphenyl-1H-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-Br-C 6 H 4, R 2 = R 3 = Ph)
Ausbeute 72%. Farblose Nadeln (aus·Acetonitril), Schmp. 194-195 0CYield 72%. Colorless needles (from · acetonitrile), mp. 194-195 0 C
1-(4-Iod-phenyl)-5-(1,5-diphenyl-iH-pyrazol-4-yl)-1H-tetrazol (V, R1 = 4-1-G6H., R2 = R3 = Ph)1- (4-iodo-phenyl) -5- (1,5-diphenyl-iH-pyrazol-4-yl) -1H-tetrazole (V, R 1 = 4-1-G 6 H, R 2 = R 3 = Ph)
Ausbeute 76%. Farblose Nadeln (aus Acetonitril), Schmp. 215-216 0C.Yield 76%. Colorless needles (made from acetonitrile), m.p. 215-216 0 C.
5-/5-Methyl-1-(4-nitrqphenyl)-1H-pyrazol-4-yl7-1-phenyl-1H-tetrazol (V, R1 = Ph, R2 = Me, R3 = 4-O2N-C6H4) Ausbeute 47%. Blaßookerfarbene Kristalle (aus Acetonitril), Schmpo 166-167 0C.5- / 5-Methyl-1- (4-nitriphenyl) -1H-pyrazol-4-yl-7-1-phenyl-1H-tetrazole (V, R 1 = Ph, R 2 = Me, R 3 = 4-O 2 NC 6 H 4 ) Yield 47%. Pale aureus-colored crystals (from acetonitrile), Schmpo 166-167 0 C.
1-Phenyl-5-Z"1-(4-nitro-phenyl)-5-phenyl-1 H-pyrazol-4-yl7-1 H-tetrazol (V, R1 = R2 = Ph, R3 = 4-O2N-C6H4) Ausbeute 73%. Blaßockerfarbene Kristalle (aus Acetonitril), Schmp. 224-225 0C1-phenyl-5-Z "1- (4-nitro-phenyl) -5-phenyl-1H-pyrazol-4-yl-7-1H-tetrazole (V, R 1 = R 2 = Ph, R 3 = 4 -O 2 NC 6 H 4) yield 73%. Pale ocher crystals (from acetonitrile), mp. 224-225 0 C.
Claims (1)
H3CH 3 C x
H 3 C
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD34063090A DD294256A5 (en) | 1990-05-14 | 1990-05-14 | PROCESS FOR PREPARING PYRAZOLYL SUBSITUTED TETRAZONE DERIVATIVES |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD34063090A DD294256A5 (en) | 1990-05-14 | 1990-05-14 | PROCESS FOR PREPARING PYRAZOLYL SUBSITUTED TETRAZONE DERIVATIVES |
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| Publication Number | Publication Date |
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| DD294256A5 true DD294256A5 (en) | 1991-09-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| DD34063090A DD294256A5 (en) | 1990-05-14 | 1990-05-14 | PROCESS FOR PREPARING PYRAZOLYL SUBSITUTED TETRAZONE DERIVATIVES |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9156837B2 (en) | 2011-07-29 | 2015-10-13 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| CN107778262A (en) * | 2016-08-24 | 2018-03-09 | 尹玉新 | 1,5 disubstituted tetrazole compounds and its preparation method and application |
-
1990
- 1990-05-14 DD DD34063090A patent/DD294256A5/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9156837B2 (en) | 2011-07-29 | 2015-10-13 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| CN107778262A (en) * | 2016-08-24 | 2018-03-09 | 尹玉新 | 1,5 disubstituted tetrazole compounds and its preparation method and application |
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