A Mild and Efficient Method for the Preparation of 3-( 2 ’-Aminoaryl ) pyrazoles from 4-Chloroquinolines

Pyrazoles and their derivatives are widely used as pharmaceutical1-5 and agrochemical agents6 and consequently a large number of synthetic routes to pyrazoles has been reported.7-13 However, there is still great interest in finding milder and more efficient methods to these valuable compounds. Amino groups undergo various reactions, and as such are excellent and general starting points for the development of chemical libraries.14 In particular, 3-(2’aminoaryl)pyrazoles (1) are useful precursors of more elaborate pyrazolic molecules.15 A preparation of 3-(2‘aminophenyl)pyrazoles was first described by Alberti15 from 4-hydroxyquinolines. 4-Chloroquinolines16,17 on treatment with substituted hydrazines gave 1-substituted-3-(2aminophenyl)pyrazoles. All these reactions occurred under drastic conditions using autoclave or sealed tubes.15,16 Later, other workers reported ring opening reactions of 4hydroxyquinolines13 and the preparation of the compound 3-(2‘-aminophenyl)pyrazole by the reduction reaction of 3(2-nitrophenyl)pyrazole.18 Our research group has developed a route to 3-(2’aminoaryl)pyrazoles under mild conditions from 4chloroquinolines (2) and hydrazine in a one-pot process.


Results and Discussion
The 4-chloroquinolines 19 (3) are readily prepared from 4-hydroxyquinolines (2) and can be stored for long periods.The 4-hydroxyquinolines, 20 in turn, can be readily made from quinolones via the Gould-Jacobs method. 21,22Our one-pot synthesis of (1a-i) involves reactions of 4-chloroquinolines with an excess of hydrazine in diethyleneglycol initally at 90-100 ºC for one hour.Substitutions of the chlorine atom in 3 by hydrazine occur in this temperature range to generate intermediate 4-hydrazinoquinolines, which on raising the temperature to 130-140 ºC, react further over a period of six hours to afford the desired products 1a-i, see Scheme 1.
As shown in Table 1, isolated yields range from good to excellent, with electron withdrawing substituents resulting in the higher yields and electron donating substituents resulting in lower yields as expected for a nucleophilic aromatic substitution reaction.
Products were generally identified by 1 H NMR, 13 C NMR, FT-IR spectroscopies, mass spectrometry and elementary analysis.Specifically, confirmation of the structure of 1a was gained by X-ray diffraction. 23,24Atom arrangements are shown in Figure 1.
Overall the molecules are nearly planar with the angles between the best planes of the two rings in the order of 12º and torsional angles ranging from 0.06 (0.40) to 12.34 (0.45)º.Intramolecular N3X-HAX…N1X (X=A or B) hydrogen bonds help to cement the planar arrangements of the two molecules.Intermolecular N2A-H2A…N3B and N2B-H2B…N3A hydrogen bonds link the two independent molecules, alternatively, into molA…molB…molA chains (Figure 2).

Conclusions
In conclusion we would like to reiterate that the method is a simple and efficient one, not requiring special equipment or harsh conditions.The respectable yields in these reactions also make it a viable method for the synthesis of 3-(2-amino-aryl/hetaryl)pyrazoles.Following this procedure, eight new compounds (1a-f, 1h-i) were thus prepared.

Table 1 .
Yields of compounds 1a-i