Formation of One Bond

Treatment of resin-bound a-arylazobenzhydryl 488 with a Lewis acid at room temperature followed by acidic cleavage furnished indazole 489 in quantitative yield, the reaction being monitored by single bead IR microspectroscopy (Equation 98) 1996TL8325 . Unsymmetrical azines 490 thermally cyclized to fused pyrazoles 491 (Equation 99) 2002TL6431 . Indazoles 493 were obtained from thermal cyclizations of (2-alkynylphenyl)triazenes 492 in the presence of methyl iodide as a solvent other solvents were tested where either no reaction or complex mixture of products was obtained (Equation 100) 2002JOC6395 . 

The cycloaddition of azides to C=C and C=C bonds has become the most important and versatile synthetic route to a wide range of 1,2,3-triazoles and triazolines, and is discussed in detail 

Numerous organic and inorganic azides undergo 1,3-dipolar cycloaddition to alkynes to give 

3- triazoles. The regioselectivity of the reaction is low and regioisomers are usually obtained. This is easily understood in terms of the mechanism and energies of the HOMO-LUMO interactions B-84MI 401-01 . 

Cycloaddition of p-methoxyphenyl azide to alkynic dipolarophiles at room temperature gives triazoles (697) and (698) (Equation (54)). A regiospecific addition is only observed in the case of Z = CH(OMe)2 89H(29)967 . Phenyl azide and substituted benzyl azides undergo 1,3-dipolar cycloadditions with DM AD, phenylacetylene, and ethyl propiolate to afford 1-phenyl- and 1-benzyl- 

Cycloaddition of a variety of alkynes to the azido function of 3 -azido-2, 3 -dideoxythymidine and 3 -azido-2,3-dideoxyuridine yields products (e.g., 716) with a 1,2,3-triazol-l-yl substituent in the 3 -position (Equation (60)). By contrast to the parent compounds, these triazolyl derivatives have no appreciable activity against human immunodeficiency virus 89JHC1635 . Cycloadditions of 4-azido-6-methyl-2//-pyran-2-one with alkynes leads to triazoles (717) 93JHC317 . 

One clear example of synthesis of pyrazoles by formation of the N,—Nj bond 84CHEC-I(5)167 is the ring closure of iminohydrazones (1-azadienes) to N f-pyrazoles (201) 86JHC459 . 

A new synthetic way, found by a computer-assisted organic synthesis program, to prepare 

5-diphenyl-4-hydroxypyrazole (203) from diphenylpropanetrione (202) and ammonia failed 88AQ285 . A rationale for the failure is provided by MNDO calculations. 

An original synthesis of A -substituted-3,4-trimethylenepyrazoles (204) from iminophosphoranes 

The very interesting synthesis of 3-R-4-trifluoromethylpyrazoles (214) from hydrazones has the limitation that position 5 has to remain unsubstituted 88JOC519,88TL528l . 

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The different possibilities for the creation of the pyrazole ring according to the bonds formed are shown in Scheme 46. It should be noted that this customary classification lacks mechanistic significance actually, only two procedures have mechanistic implications the formation of one bond, and the simultaneous formation of two bonds in cycloaddition reactions (disregarding the problem of the synchronous vs. non-synchronous mechanism). 

Pyrazolines can be prepared from the reaction between a hydrazine and two carbonyl compounds, one of them having at least one hydrogen atom a to the carbonyl group. Formally, these reactions correspond to the [NN + C + CC] class. However, if one considers the different steps in the ring formation, they more properly belong to the [CNN + CC] (Section 4.04.3.1.2(ii)), the [CCNN + C] (Section 4.04.3.1.2(i)), or the formation of one bond (Section 4.04.3.1.1) classes. 

Formation of One Bond between Carbon and a Heteroatom S.03,2.2.1 Displacement reactions... 

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