Pyrazoles 3,5-dihydroxy

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

A recent paper by Singh et al. summarized the mechanism of the pyrazole formation via the Knorr reaction between diketones and monosubstituted hydrazines. The diketone is in equilibrium with its enolate forms 28a and 28b and NMR studies have shown the carbonyl group to react faster than its enolate forms.Computational studies were done to show that the product distribution ratio depended on the rates of dehydration of the 3,5-dihydroxy pyrazolidine intermediates of the two isomeric pathways for an unsymmetrical diketone 28. The affect of the hydrazine substituent R on the dehydration of the dihydroxy intermediates 19 and 22 was studied using semi-empirical calculations. ... 

Tetraazafulvalenes bearing two pyrazole subunits could be prepared by an original way. Tlius, treatment of benzylidene acetophenone with iso-pentylnitrite leads to an A, A -dihydroxy-bipyrazolyl-A, A -oxide, which in turn can be oxidized to TAF of type 100 (72CC961, 79JOC3211). Another type of oxidative dimerization was observed by the reaction of the electron-rich l-methyl-2,4-bis(dimethylamino)imidazole with silver salts (83TL3563). A bis-cation was isolated in 30% yield in the presence of sodium tetrafluo-roborate an unsymmetrical structure 101 was predicted from its NMR data (Scheme 40). 

Isophthaisaure 2,6-Dimethyl-4-dimethylamino- -bis-nitriloxid E5, 1591 (aus Bis-oxim) Malonsaure (Amino-benzylamino-methylen)- -methylester-nitril E15/2, 2156 (CC13 - NH-R) I,3i4-Oxadiazol 5-Morpholino-2-phenyl- E8c, 573 (Ar — CO — NH-NH-CO-NR2/POCl3) Phthalazine l,4-Dihydroxy-6-pyrrolidino- E9a, 752 (subst. Phthalanhydrid + N2H4) lH-Pyrazol 5-Carboxy-l-methyl-4-(4-methyl-anilino)- E8b, 633 (4-Br -> 4-NH-Ar)... 

Amino-4,6-dihydroxy-5-nitropyrimidine, 1436 2-Carbamoyl-2-nitroacetonitrile, 1116 5 -Chloro-1,3-di methy 1-4-nitro-1 A-pyrazole. 1864 Mercuiy(II) 5-nitrotetrazolide, 0981 1 -Methylamino-1 -methy lthio-2-nitroethene, 1596 Methy Initrothiophene, 1850 Nitroacetaldehyde, 0763 2-Nitroethanol, 0871... 

Methyl-l H-pyrazole werden aus l,4-Dihydroxy-2-buten oder 3-Hydroxy-l-alkinen mit Hydrazin bzw. substituierten Hydrazinen in 80%iger Schwefelsaure und in Gegenwart von Iod oder Iodiden gebildet, z. B. entsteht aus 1,4-Dihydroxy-2-buten und Hydrazin 3 (5)-Methyl-1 H-pyrazol (69%)2411. 

Aryl-3,5-dihydroxy-l H-pyrazole sind in guten Ausbeuten auch aus Malonsaure und substituierten Malonsauren zuganglich, wenn sie mit l-Acetyl-2-aryl-hydrazin und Phos-phor(III)-chlorid bis zur Beendigung der ChlorwasserstofT-Entwicklung erhitzt werden (Was-serbad), z.B. ... 

Kohlensuboxid reagiert wie Malonsaure-diester mit Phenyl-hydrazin zu 3,5-Dihydroxy-1-phenyl-lH-pyrazol (Bd.Vlll4, S. 301). 

Die katalytische Hydrierung von 4,5-Dioxo-4,5-dihydro-lH-pyrazolen an Palladium in Eisessig fiihrt zu 4,5-Dihydroxy-lH-pyrazolen, z.B. zu 4,5-Dihydroxy-3-methyl-l-phenyl-1 H-pyrazol (Schmp, 190°)1063. 

Die Reduktion von 4-Oxo-4H-pyrazol-l,2-dioxiden mit Zink in Essigsaure ergibt 4-Hydroxy-lH-pyrazole, mit Natriumhydrogensulfit 1,4-Dihydroxy-lH-pyrazole1376, von 4H-Pyr-azol-l,2-dioxiden mit Titan(III)-chlorid 1-Hydroxy-1 H-pyrazole1588. 

Wird die Saure-katalysierte Reaktion in Gegenwart von Acetanhydrid durchgefiihrt, konnen die 4,5-Dihydroxy-lH-pyrazole als 4-Acetoxy-5-hydroxy-lH-pyrazole gewonnen wer-den1052. 

Startprodukte fur dieses Ring-System sind 3-Amino-1 H-pyrazole. So werden aus l-Acyl-3-amino-5-hydroxy-1 H-pyrazolen und oc-Brom-carbonyl-Verbindungen oder a-Brom-carbonsau-re-estern durch Alkylierung der Amino-Gruppe und RingschluB zur CH-aciden 4-Position 2-Acyl-3,4-dihydroxy-2,4,5,6-tetrahydro-[Pg.658]

Uber die Cyclisierung von 3(5)-(3-Oxo-alkanoylamino)-lH-pyrazolen werden die 5-Hydroxy-Isomeren erhalten2171. Aus 3(5)-Amino-5(3)-hydroxy-l H-pyrazol und 3-Oxo-butansaure-ethyl-ester ist 2,7-Dihydroxy-5-methyl-(pyrazolo[l,5-a]pyrimidin (74% Schmp. > 300°) zugang-lich2174. 3,5-Diamino-lH-pyrazole kondensieren unter analogen Bedingungen zu 2-Amino-7-hydroxy-5-methyl-2165 2175 ... 

Amino-3-aminocarbonyl-5-hydroxy-lH-pyrazole cyclisieren beim Erhitzen in Formamid auf 180-190" zu 3,7-Dihydroxy-2H-2390. 

---