3.5- Dimethylpyrazole, preparation

Dimethylpyrazole (III) may be prepared from acetylacetone (I) and hydrazine (II) (produced from hydrazine sulphate and aqueous alkali). The reaction may be represented as ... 

Another example is a claim of possible industrial appHcation for preparing l-cyclohexyl-3,5-dimethylpyrazole [79580-49-7] (75) and similar compounds from 1,2,6-thiadiazine-l,1-dioxide (74) by extmsion of SO2 (eq. 20) (48). This process has the added advantage of not requiring hydrazine derivatives as reactants. 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

With an activated C—C triple bond two successive additions can occur if the intermediate alkene is reactive enough. DMAD and 3,5-dimethylpyrazole give an initiaj fumarate (255) which reacts further at the other end to form regioselectively the succinates (256). On the other hand, methyl ethynyl ketone reacts twice at the same carbon atom with pyrazole to form 1,1-pyrazolylbutanone (258) (68ZC458). The probable intermediate, a pyrazolide vinylogue (257), can be prepared from methyl chlorovinyl ketone and pyrazole, in a reaction which is similar to acetylation (Section 4.04.2.1.3(x)). 

Phosphorus derivatives of different structures have been prepared including pyrazol-1-ylphosphines PPzs, PhPPz2 and Ph2PPz (Pz for pyrazolate anion (72CRV497,80MI40402)). By transamination with tris(dimethylamino)phosphine, pyrazoles and indazole are converted into (291) and (292), respectively (67CR(C)(265)1507). 3,5-Dimethylpyrazole reacts with amidodichlorophosphates to yield triamides (293) whereas 1-substituted pyrazolones yield amidophosphates (294) (71LA(750)39). 

In the reaetion of methyldiaeetylene with hydrazine hydrate, both 3-ethylpyrazole (14) and 3,5-dimethylpyrazole (15) were formed in a 4 1 ratio (73DIS). Both pyrazoles were preparatively isolated (3,5-dimethylpyrazole is erystalline and ethylpyrazole is a liquid) and identified by eomparison with authentie samples. These data show that primary attaek of monosubstituted 1,3-diynes by hydrazine is mainly direeted toward the terminal aeetylenie bond. 

Stmcturally novel pyrazole derivatives include the propellene 2,3,4,5,6-pentakis(pyrazol-r-yl)pyridine 1 and the corresponding 3 ,5 -dimethylpyrazole derivative 2<96T11075>. Poly(pyrazol-l-ylmethyl)benzenes, such as 3, have been prepared as multidentate ligands <95AJC1587>. Solid phase synthesis of structurally diverse 1-phenylpyrazolones was reported, with application to combinatorial synthesis <96SL667>. 

The recent report of a chiral bis(l-pyrazolyl)methane provides the first example of L not based on pyrazole or 3,5-dimethylpyrazole.13-14 The substituted bis(pyrazolyl)methane was prepared by Method A, which gave... 

The preparation of N-(2-p-toluenesulfonylethyl)-3,5-dimethylpyrazole is described elsewhere in this volume.5 l,l,3,3-Tetramethyl-2-thiourea and other reagents are available from the usual commercial sources. 

Bis(pyrazole) (169) was prepared by the reaction of 3,5-dimethylpyrazole with formaldehyde (a 4-CH2OH derivative is the probable intermediate) (84ICA99). 

Scheme 7 Preparation of an a-Amino Aldehyde by Reduction of the Corresponding 3,5-Dimethylpyrazole Derivatives 251...

Preparation of a N -Protected a-Amino Aldehyde via Reduction of the Corresponding N -Protected a-Amino Add 3,5-Dimethylpyrazole Derivative General Procedure 25 ... 

The effects of the substituents near the donor site is to reduce the number of coordinated ligand molecules from six to four or less. Tetrakis complexes with substituted pyrazoles and imidazoles are prepared using a large excess of the ligands, and, in the cases of 1,2-dimethylimidazole and 3,5-dimethylpyrazole derivatives, anhydrous reactants. Most of die mono and bis adducts may be conveniently prepared under anhydrous conditions and with the nickel salt in excess. 

In the case of amine nucleophiles, the products from the reaction with co-ordinated cyanates are carbamates or ureas (Fig. 4-34), and this provides a particularly convenient method for the preparation of carbamate complexes. An example of this behaviour is seen in the reaction of 3,5-dimethylpyrazole with cyanate in the presence of copper(n) salts (Fig. 4-35). Similar reactions are observed with co-ordinated thiocyanates and other heterocumulene s. 

Trimethylsilylmethylguanidinium nitrate, which is easily prepared by displacement of the pyrazole moiety from l-guanyl-3,5-dimethylpyrazole by MSMA, has been found to... 

Dimethylpyrazole has been prepared from acetylacetone and hydrazine hydrate in ethanol3 or hydrazine sulfate in aqueous alkali.4 6 The latter method is preferred, because the reaction with hydrazine hydrate is sometimes violent.3 4 3,5-Dimethyl-pyrazole has also been prepared by hydrolysis and decarboxylation of the 1-carbamido- or 1-carboxamidine derivatives, obtained by reaction of semicarbazide 7 or aminoguanidine 8 with acetylacetone. 

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