Use 5 or 6 equivalent of hydrazine w.r.t. ester and reflux in methanol or ethanol for 6 hrs and then concentrate the solution and keep inside the refrigerator.

Your idea is good, but You do not need  absolute alkohol, usual 96% is normal solvent for this reaction. The reaction in reflux aloholic solution us quite fast, and usually after 30-40 min finished. Have a TLC controll for monitoring the reaction

Neat hydrazine hydrate can be used at Reflux to prepare a hydrazide see ARKIVOC 2002, 227.

from an ester see compound 3 in the attached doc (a benzoate is hydrolysed as well, so you can only do it with an ester that does not have sensitive functional groups)    

Kirill I. Petko

Matthew Mcgrath

thank you ..but i didnt get the hydrazide ...it stil get looks llike solution or i get Precipitate but its have the same ester melting point ..

i hop i get more Details of  the reaction

my ester with 214 Molecular weight

 and the hydrazein haydrat have 50 molcular wait

so do i have use 1: 1 ?

The amount of the solvent  affect on the raction ?

You can take some excess (40-60% or up to 2 mol) of hydrazine (calcuate it from hydrate).  And a solvent.... may be minimum volume  to diisolve the ester. Hydrazone may be dropped as a solid but may be not, so TLC control is good

Hi Abdo Kareem

If you tried using abs. ethanol and you did not obtained the hydrazide, try to use neat condition (without solvent) with excess hydrazine under reflux for 5-6 h.

Good luck

I faced this problem, but I obtained hydrazide after increasing the time of reflux to 12 hrs.

i Just prefer the hydrazide .. the problem was with hydra zen the reaction need new and fresh hydra zen ... its need = 1 hour reflux   and put the round in the freezer

thx # Rokaia Abdullah

# Talaat I. El-Emary

Kirill I. Petko

Use 5 or 6 equivalent of hydrazine w.r.t. ester and reflux in methanol or ethanol for 6 hrs and then concentrate the solution and keep inside the refrigerator.

use 5 or more equivalent of hydrazine hydrate (90%) with ethanol solvent at room temp. 24 hrs you get ppt.

Hi,

I am also trying to synthesize Hydrazides from aminoacid methyl esters, but although I followed all the above suggestions, I was not able to get it properly. The problem is that I have the same starting mass and the product mass LC-MS say nothing and since I use Lysine methyl ester.2HCL, I am not able to see anything on TLC. There is this washing process with (3:1) DCM / isopropanol solution which is supposed to get my product but I only obtain a really little amount ( from 50 mg material only 4 mg )

Can anybody suggest me any solutions?

Thanks!

Try Using excess hydrazine ( 20 folds) without solvent (neat) and reflux for about 10h.

Synthesis, characterization and preliminary pharmacological evaluation of new non‐steroidal anti‐inflammatory pyrazoline derivatives.European Journal of Chemistry 6 (4) (2015) 461‐467

Monther Faisal Mahd, Ayad Mohammed Rasheed Raauf and Noor Muneer Mohammed

European Journal of Chemistry 6 (4) (2015) 461‐467

I would recommend to reflux your ester plus 10Eq of hydrazine in dried ethanol or methanol. Sometimes dried THF as cosolvent is needed

Usually I let it stir overnight, you will get a precipitate that you filter it off

Recrystallization from ethanol might be necessary.

Good luck!

www2.hhu.de/Janiak/Pdf/248.pdf

please find attached.

The best procedure and condition to prepare hydrazide by heating an ester and hydrazine in equimolar proportion in ethanol or methanol on water bath at 70 oC for about one and half hours. On cooling white needles of hydrazides separate out, filter , wash with little alcohol to get hydrazide in a pure form.

Abdo Kareem

I face the same problem, how can i prepare fresh hydrazine hydrate?

Try using excess hydrazine hydrate(at least 10 times) and use minimum volume of solvent(dried ethanol) to dissolve the ester. After 17 hours reflux and following cooling I have got desired product. The reaction is monitored through TLC technique.

Best of luck.

Abdo Kareem

Why excess hydrazine hydrate (10 times ) is used in this reaction??

Thanks in advance Sir.

Davide Benedetto Tiz

@Hasan Al Banna

I remember that excess of hydrazine is used to facilitate the attack of hydrazine to the ester "OMe or OEt" leaving group. To sum up, if you have more molecules of hydrazine around the ester the reaction has more chances to occur. Moreover the excess can be easily got rid by evaporation or filtration when your product is a precipitate.

Instead of 10 also 5 Eq are also found in literature (see this example) :

https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.mdpi.com/1420-3049/15/10/6759/pdf-vor&ved=2ahUKEwjp58bfjaHvAhWNkhQKHa0xAeMQFjAGegQIChAM&usg=AOvVaw09KHbq1hAvSd1HhjPH5Vad

Good luck!

Add hydrazine hydrate 6 equilibrium in Ethyl ester and refulx for 10-12 hr with dry methanol. Measure the reaction with TLC . After completing of reaction keep reaction mixture in refrigerator for overnight. Sometimes we get solid ppt or some times we get in liquid form.

Separate out the solid product by filtration or liquid product will be extract out with ethyl acetate.

Davide Benedetto Tiz ,

It's my pleasure to have an accurate answer .Thanks a lot.

But according to my little knowledge, If we don't use excess amount of hydrazine hydrate ,then there is possibility of formation of dimer and perhaps we don't get our desired product.

@Hasan Al Banna interesting perspective. It can be that an excess of hydrazine prevents the formation of dimer.

l prepare hydrazide by stirring the mixture of hydrazine with ester at room temprture fir 24h than evaporated the solvent

Actually, this reaction is one of the easiest that I've had ever performed.

Add 5-10 equimolar amount of hydrazine hydrate to the ester and heat the reactants in ethanol at Reflex for 3 hours, then allow it to cool to room temperature overnight. You will notice the wonderful prisms the next day.

What if your product is in liquid form?

How to collect it?

If product is low polar liquid then how can we crystallize it?

I prepared succinic hydrazide by MWI through 10 min. In the ethanol as solvent.