Sciencemadness Discussion Board

Pyrazoline synthesis

NexusDNA - 1-12-2015 at 08:44

Hello! I'm trying to make a 1,3,5-triaryl pirazoline from the condensation of a chalcone (1,3-diaryl-2-propenone) and benzoic hydrazide.

I tried 4 methods: in refluxing GAA (as catalyst and solvent), refluxing ethanol with a few drops of AcOH, in the microwave with AcOH and in the MW with GAA and ammonium acetate. None of them is working, no product is formed. I am very disappointed :(

What would you suggest me to do???

btw, the machanism is not quite elucidated. It is thought that the NH2 of the hydrazide attacks the carbonyl first, as no open product was isolated in the literature, as far as i know.

Boffis - 1-12-2015 at 10:11

@NexusDNA, Can you provide us with a reference please. Some years ago I did some work on substituted pyrazolone from beta-ketoesters and substituted phenylhydazines following a paper from a couple of Indian authors and while the simple ones worked I found the heavily substitute one difficult or impossible to cyclotise.

NexusDNA - 1-12-2015 at 10:54

RAGHAV, N. GARG, S. N-formylpyrazolines and N-benzoylpyrazolines as novel inhibitors of mammalian cathepsin B and cathepsin H. Bioorganic Chemistry, 2014.

SRINIVAS, M. et al. Microwave adsisted synthesis and antimicrobial activity of some novel quinoxaline compounds. India: Mother Teresa College of Pharmacy, 2013.

first one is themal, second one MW. In my case I'm using 1-(3,5-dimethoxy-phenyl)-3-(2-naphtyl)-propenone.

Boffis - 1-12-2015 at 11:36

@ Nexus, Let me look into these refs.

NexusDNA - 5-12-2015 at 18:02

btw an update: I got it going, and it is beaaaautiful!! :D:D

20151204_194843.jpg - 1.8MB

UC235 - 5-12-2015 at 20:08

Gorgeous color. Reminds me of 2,4-dinitrophenylhydrazine which is a bit darker and more wine-ish

chemrox - 11-12-2015 at 18:33

Did you do this with 1,3-diaryl-2-propenone and benzoic hydrazide? I'm not familiar with this cyclization. The ones I do require strong base. Did you insert a catalyst? Does it cyclize due to stearic and energetic factors? Like everybody else I love the color! All my products are white and bitter. What does it taste like? Pyrazoline looks like a very interesting intermediate for medicinal chemistry. I would like to make an acyl halide from the stuff. No telling what wonderful activity might be evolved.
@mods: if words like halide aren't in our dictionary could we at least have an "ignore" option in the spell check? Maybe some kind person could edit the dictionary so that chemical terms aren't underlined with color of UC235's product. Congratulations UC! Good job.

chemrox - 11-12-2015 at 18:41

N' methoxy pyrazinyl-3,4-methylenedioxyphenylpropanamine anyone?

NexusDNA - 18-12-2015 at 02:40

Sorry for the late reply!

It doesnt require strong catalysts at all, in the literature they use GAA as a mild acid catalyst. I could not obtain the desired product with benzoic hydrazide, so i broke the procedure in two steps: reacting the chalcone with hydrazine hydrate and then reacting the formed pyrazoline with benzoyl chloride.

side note: I've seen some articles in which they test N-tosyl derivatives (instead of benzoyl chloride, TsCl) as potential MAO inhibitors with excellent results. I won't try bioassaying my product though!! :P

Here is the mechanism though to be operative:

20151218_083841-1.jpg - 2.3MB

[Edited on 18-12-2015 by NexusDNA]