2-Pyrazolines. synthesis

Pyrrolidino[l,2-6][l,3,4]oxadiazoline, 5-phenyl-biological activity, 6, 1024 Pyrrolidino[2,1 -6][1,3]oxazolidines synthesis, 5, 137 Pyrrolidino[l,2-6]pyrazolines synthesis, 5, 148... 

Rurack K, Bricks JL, Schulz B et al (2000) Substituted l,5-diphenyl-3-benzothiazol-2-yl-A2-pyrazolines synthesis, X-ray structure, photophysics, and cation complexation properties. J Phys Chem A 104 6171-6188... 

A mild procedure was developed for polysubstituted pyrazolines synthesis from 2,5-diaryltetrazoles (addition to Section 6.07.5.2.2) <20070L4155>. This procedure involved the in situ photoactivated generation of the reactive nitrile imine dipoles, followed by spontaneous cycloaddition with 1,3-dipolarophiles. 

Pyrazolines, synthesis from aliphatic diazocompounds 85MI4. 5-Pyrazolone couplers for color photography 87YGK151. 

Scheme 15.114 Pyrazoline synthesis via a one-pot hydrohyrazination/nucleophilic substitu-tion/oxidation sequence.

Pyrazolines substituted at position 4 or 5 with hydroxy or amino groups readily eliminate a molecule of water or amine yielding pyrazoles. The 4-substituted derivatives are relatively more stable than the 5-substituted ones, because for the last group the lone pair at N-1 assists the elimination (407) -> (408) -> (409). The sulfonyl group at position 1 is also easily eliminated and this property is taken advantage of in Dorn s elegant synthesis of 3-aminopyrazole (Section 4.04.3.3.1). 

The important synthesis of pyrazoles and pyrazolines from aldazines and ketazines belongs to this subsection. Formic acid has often been used to carry out the cyclization (66AHQ6)347) and N-formyl-A -pyrazolines are obtained. The proposed mechanism (70BSF4119) involves the electrocyclic ring closure of the intermediate (587) to the pyrazoline (588 R = H) which subsequently partially isomerizes to the more stable trans isomer (589 R = H) (Section 4.04.2.2.2(vi)). Both isomers are formylated in the final step (R = CHO). 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

Owing to their particular interest two individual reactions will now be discussed separately. The reaction of methoxycarbonylhydrazine and 3-bromo-2,4-pentanedione affords, in addition to the expected pyrazole (608), a pyrazolium salt (609), the structure of which was established by X-ray crystallography (74TL1987). Aryldiazonium salts have been used instead of arylhydrazines in the synthesis of pyrazolines (610) and pyrazoles (611) (82JOC81). These compounds are formed by free radical decomposition of diazonium salts by titanium(n) chloride in the presence of a,/3-ethylenic ketones. 

Hydrazoyl halides are useful reagents for the synthesis of pyrazolines and pyrazoles (80JHC833). The elimination of HX, usually with triethylamine, is now the preferred method for the generation of the nitrilimine (621) in situ. Although in some cases it is not clear if the mechanism involves a nitrilimine (621) (as for example in the Fusco method in which sodium salts of /3-diketones are used), in other reactions it is the most reasonable possibility. For example, the synthesis of pyrazolobenzoxazine (633) from the hydrazoyl halide (631) probably occurs via the nitrilimine (632). Trifluoromethylpyrazoles (634) have been prepared by the reaction of a hydrazoyl halide and an alkynic compound in the presence of triethylamine (82H(19)179). 

The synthesis of A -pyrazolines by reaction of a 1,2-disubstituted hydrazine, formalin and a carbonyl compound, known as the Hinman synthesis, probably proceeds by the mechanism shown in Scheme 57 (69BSF3300). 

Pyrazoline-3-carboxylic acid, 5-oxo-ethyl ester synthesis, 5, 142... 

Pyrazoline-5-thiones photoelectron spectroscopy, 5, 205 Pyrazolinium salts reduction, 5, 254 Pyrazolinium salts, 1,2-dimethyl-synthesis, 5, 276... 

Synthesis of pyrazolines in reactions of a,(3-enones with diazomethane and hydrazines 97KGS747. 

DCA reactions are an important means of synthesis of a wide variety of heterocyclic molecules, some of which are useful intermediates in multistage syntheses. Pyrazolines, which are formed from alkenes and diazo compounds, for example, can be pyrolyzed or photolyzed to give cyclopropanes. 

The general method for the preparation of diphenylpyrazolines is shown in Scheme 11.8, in which X is a suitable leaving group, usually chloro but sometimes dialkylamino. This reaction normally proceeds readily, although pH control may be important. Preparation of the substituted ketone and hydrazine intermediates needed for the synthesis may involve lengthy and complicated sequences. Further reactions are often required to modify the substitution in ring B after formation of the pyrazoline ring. The preparation of compound 11.26 shown in Scheme 11.9 illustrates one of the simpler instances. 

The photoelimination of nitrogen from 1-pyrazolines is one of the most thoroughly investigated photoreactions and it has been used extensively in the synthesis of cyclopropane derivatives.334 Both stereospecific and non-stereospedfic processes have been observed and these are believed, at least in simple 1-pyrazolines, to correspond to singlet and triplet excited states, respectively. Two reaction pathways have been proposed in the azoalkane 405335 direct excitation via a thermally activated S, state affords the C6H6 isomers 406 to 409, whereas triplet-sensitized excitation results in a tem-... 

Photoelimination of nitrogen from 1-pyrazolines has also been employed in the synthesis of tricyclo[3.2.1.02,4]oct-6-ene,338 prismane,339 quadri-cyclane,340 snoutene ,341 and marasmic acid.342 The trimethylenemethanes 414 have been prepared by photolysis of azoalkanes 415 and characterized spectroscopically.343 Dimerization and cycloaddition to alkenes of these biradicals have been reported.344... 

Extension of the 1,3-DC approach to the synthesis of novel pyrazoline-fused chlorin 78 by the reaction of P-nitro-meso-tetraphenylporphyrin le with diazomethane has also been explored by Cavaleiro and co-workers (Scheme 27) <02S 1155>. The resulting chlorin 78 could be further converted into the pyrazole-fused porphyrin 79 by treatment with DBU or into the methanochlorin 80 by refluxing in toluene. 

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