Diazo-pyrazoles

Diazopyrazoles can be converted into very stable diazonium salts (chloride or bromide) upon treatment with the corresponding concentrated acid at room temperature (76JOC3781 84JHC957). Stable diazonium tetrafluoroborate [87JOC5538], platinichloride, and aurichloride [14JCS(105)435] can be isolated. Only in the case of the unstable 3-diazo-pyrazole was it necessary to operate at low temperature and in non aqueous solvents (61CB1036). 

Products (Yield %) of 5-/-Butyl-3-DiAzo-PYRAZOLE with Monosubstituted Benzenes"... 

Recently it was shown that, in a buffered solution where the pyrazole cation was in equilibrium with basic pyrazole, a diazonium group could be directly substituted into the 4-position of 3,5-dimethylpyra-zole by nitrous acid,602,0O2 in the same way that this group had been introduced into phenols.603 For the properties of 3-, 4-, and 5-diazo-pyrazoles see Knorr,77 Alberti,318 Fusco,527 and others.571- 572 597 ... 

We shall first discuss the preparation of heterocyclic diazo compounds as a class and shall then consider separately the individual characteristics of the various types, e.g., diazopyrroles, diazo-pyrazoles, etc. 

Diazotisation of 4-amino-pyrazoles, then deprotonation yields isolable diazo-pyrazoles. ... 

Another example of fragmenting carbenes is provided by the 3 Jf-pyrazolylidenes. The 3/f-diazo-pyrazole (234), on pyrolysis, yielded the carbene 235 probably stabilized as shown below. Although the carbene can undergo typical carbene reactions, such as insertion into a C—H bond, ultimately yielding 236 with cyclohexane, it can also decompose to the 2 -azirine 237. The methyl cyanocarbene subsequently yields acrylonitrile. 

Pyrazoles and imidazoles exist partly as anions (e.g. 108 and 109) in neutral and basic solution. Under these conditions they react with electrophilic reagents almost as readily as phenol, undergoing diazo coupling, nitrosation and Mannich reactions (note the increased reactivity of pyrrole anions over the neutral pyrrole species). 

Diazotization of aminoazoles with free cyclic NH groups can give diazo anhydrides which show many of the normal reactions of diazoniums (67AHC(8U). In the pyrazole series these diazo anhydrides are particularly stable. 

A Hammett relationship of the form ApK = 5.8am has been proposed for 4-substituted pyrazoles (74TL1609) in order to explain the effect of 4-nitro ApK = 4.5, am = 0.71) and 4-diazo groups (Apiifa = 10.0, am = 1.76). The acidity constants of a series of pyrazolidine-3,5-diones have been determined (75AJC1583) and the 4- -butyl-1,2-diphenyl derivative phenylbutazone has a pK of 4.33. 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

The behaviour of pyrazoles towards nitrosation is similar to their behaviour described above towards diazo coupling, i.e. aminopyrazoles and pyrazolones readily react with nitrosation agents, like alkyl nitrites (81FES1019), to afford stable nitroso derivatives. Some simple nitrosopyrazoles have been isolated, for example the blue-green 3,5-dimethyl-4-nitrosopyrazole, and many others have been proposed as reactive intermediates in the direct conversion of pyrazoles into diazonium or diazo derivatives (Scheme 25) (B-76MI40402). 

Pyrazoles are formed when the diazo compounds react with alkynes or with functionalized alkenes, viz. the enols of /3-diketones. Pyrazolenines (353 Section 4.04.2.2.1) are isolated from disubstituted diazomethanes. Many pyrazoles, difficult to obtain by other methods, have been prepared by this procedure, for example 3-cyanopyrazole (616) is obtained from cyanoacetylene and diazomethane (7iJCS(C)2i47), 3,4,5-tris(trifiuoromethyl)pyrazole (617) from trifluorodiazoethane and hexafluoro-2-butyne (8lAHC(28)l), and 4-phenyl-3-triflylpyrazole (618 R =H) from phenyltriflylacetylene and diazomethane (82MI40402). An excess of diazomethane causes iV-methylation of the pyrazole (618 R = H) and the two isomers (618 R = Me) and (619) are formed in a ratio of 1 1. 

Methylvinyldiazirine (199) rearranges at room temperature in the course of some days. Formation of the linear isomer is followed by electrocyclic ring closure to give 3-methyl-pyrazole. The linear diazo compound could be trapped by its reaction with acids to form esters, while the starting diazirine (199) is inert towards acids (B-71MI50801). 

In general, it is diffieult to prediet the outeome of eyelizations of alkynylpyrazole diazonium salts, even with elosely related arrangements of funetional groups, sinee reaetion ean oeeur at both the a- and /3-earbon atoms of the aeetylenie substituent. Moreover, it is known that the eleetrophilieity of the diazo group and the nueleophilieity of a triple bond markedly depend on their positions in the pyrazole ring and that this ean affeet both the eourse and ease of eyelization and even its viability (83IZV688). 

In contrast, the structurally similar and equally powerful diene, 3,5-diphenyl-4//-pyrazol-4-one (24), generated in situ by the thermolysis of l,3-bis(diazo)-l,3-diphenylacetone, affords only a modest yield of the [4 + 2] e ifo,ant/-cycloadduct 25.262... 

Electrocyclization of certain a,/ y,<5-unsaturated diazo compounds, in which one of the double bonds is embedded in an aromatic ring, affords benzodiazepines. The diazoalkenes 1, produced by heating the sodium salts of the corresponding tosylhydrazoncs, can undergo two kinds of cyclization, [1,5] to yield 3//-pyrazoles, and [1,7] to give diazepines. 

Balli and Felder (1978) and Balli and Ritter (1981) showed that diazo transfer can be applied advantageously to the diazotization of sufficiently nucleophilic heteroaromatic compounds such as 5-hydroxy- and 5-amino-3-methyl-l-phenyl-pyrazole if 3-ethyl-2-azido-benzthiazolium tetrafluoroborate (2.50) is used as diazo transfer reagent (for other applications of this diazo transfer reagent see Zollinger, 1995, Secs. 2.6-2.8). The diazonio group is introduced in the 4-position (2.51). 

There is much evidence that the mechanism" of the 1-pyrazoline reactions generally involves diradicals, though the mode of formation and detailed structure (e.g singlet vs. triplet) of these radicals may vary with the substrate and reaction conditions. The reactions of the 3 f-pyrazoles have been postulated to proceed through a diazo compound that loses N2 to give a vinylic carbene." ... 

Protected 6-amino-hexahydro-l,7-dioxopyrazolo[l,2-4]pyrazole-2-carboxylic acid 274 is available by a thermolytic decomposition of diazo compound 273 via the Wolff rearrangement. The starting compound is simply available by alkylation of racemic 272 with the corresponding bromoacetoacetate and subsequent diazo transfer reaction (Scheme 35) <1996TL4891>. 

H-Pyr azoles readily undergo photochemically induced elimination of nitrogen to yield the corresponding cyclopropenes, often by way of detectable vinyl diazo intermediates. l-Aryl-3-methyl-2-phenyl-l-diazobut-2-enes have, in fact, been prepared in this way from the appropriate pyrazoles.345 The vinyl diazo compounds 416, obtained by irradiation of the 3//-pyrazoles 417, were further converted to cyclopropenes 418 via vinylmethylene intermediates 419 by irradiation at 10°C.346 1-Acylcyclopropenes have been... 

Literature reports on diazaquinones derived from o-benzoquinone are very rare. Compound 74 was suggested to be a common intermediate formed during heating of 2,5-bis(diazo)-3,4-diketoadipate 73 with isopropanol and with various bases (76T269). Direct reduction of the intermediate with isopropanol provided pyridazine 75. A base-catalyzed benzilic acid rearrangement of 74 followed by decarboxylation of 76 afforded pyrazole 77 (Scheme 18). 

A different method of generating pyrazoles was reported by Aggarwal et al. and is shown in Scheme 47 [90]. Reaction of diazo compound 176 (derived from benzaldehyde 165) with an alkynylbenzene enabled cyclization to pyrazole 177. 

Reaction of ethyl 5-amino-3-methylthio-l//-pyrazol-4-carboxylate 267 with sodium nitrite in the presence of hydrochloric acid gives the diazo intermediate 268, which on treatment with active methylenic compounds such as ethyl a-chloroacetate or a-chloroacetylacetone affords the hydrazonyl chlorides 269 and 270, respectively, whose reaction with triethylamine in refluxing ethanol convert them into ethyl 4-hydro-2-methylthiopyrazolo[5,l-c]-[l,2,4]triazole-3,6-dicarboxylate 271 and ethyl 6-acetyl-4-hydro-2-methylthiopyrazolo[5,l-c][l,2,4]triazole-3-carboxy-late 272 (Scheme 23) <2001MI1>. 

Four 4-diazo-1,2,3-triazole derivatives, though stable in dichloromethane solution, exploded violently when heated as solids [1], Several diazo-triazoles, -pyrazoles and -imidazoles were found to be explosively unstable in varying degrees [2],... 

Amino-3-phenyl-l,2,4-triazole, Nitrous acid 5 -ieri-Buty 1-3 -diazo-3 H-pyrazole 5 -Cy ano-4-diazo-4// -1,2,3-triazole... 

Buten-l-yl diazoacetate, 2377 tert-Butyl diazoacetate, 2423 tert-Butyl 2-diazoacetoacetate, 3009 5-/er/-Butyl-3-diazo-3//-pyrazole, 2831 Cyanodiazoacetyl azide, 1346 5-Cyano-4-diazo-4//-l,2,3-triazole, 1345 Diazoacetaldehyde, 0710 Diazoacetonitrile, 0675 Diazoacetyl azide, 0679... 

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