Hi,

1) Suspending your Guanidine hydrochloride in anhydrous liquid ammonia, adding sodium metal and stirring for 1-1.5 hours will do the trick. NaCl can be filtered off and ammonia evaporated, resulting in free base guanidine. The advantage of using the free metal (potassium could also be used) directly is that the reaction is kept anhydrous (free guanidine is hygroscopic), thus giving higher yields. However, working with sodium metal is of course dangerous.

2) A less risky procedure could be the addition of 2 equiv. of finely powdered NaOH to said hydrochloride in anhydrous liquid ammonia (or ~95 % NH3), stir for the same duration as above, filter off NaCl and evaporate to yield the free base guanidine.

http://www.freepatentsonline.com/2334151.pdf

ADDITION: NaCl is soluble in liquid ammonia, but of course much less soluble than in water. If 1) or 2) is used, one might need to filter off NaCl again during evaporation.

best regards,

JR

I think you can directly added  molar equivalent weight of the base(NaOH) to your guanidine salt in organic solvent to get the Nacl as appt. then simple decantation or separation then evaporation the solvent .

The easiest way you should try is to neutralize it using NaOH or another base such as NaHCO3 in water. After this, you can concentrate the obtained solution, and add excess of a organic solvent to precipitate the inioganic salt (using ethanol or another water-miscible organic solvent). After filtration, the dissolved free guanidine can be obtained by solvent evaporation.

Hi,

1) Suspending your Guanidine hydrochloride in anhydrous liquid ammonia, adding sodium metal and stirring for 1-1.5 hours will do the trick. NaCl can be filtered off and ammonia evaporated, resulting in free base guanidine. The advantage of using the free metal (potassium could also be used) directly is that the reaction is kept anhydrous (free guanidine is hygroscopic), thus giving higher yields. However, working with sodium metal is of course dangerous.

2) A less risky procedure could be the addition of 2 equiv. of finely powdered NaOH to said hydrochloride in anhydrous liquid ammonia (or ~95 % NH3), stir for the same duration as above, filter off NaCl and evaporate to yield the free base guanidine.

http://www.freepatentsonline.com/2334151.pdf

ADDITION: NaCl is soluble in liquid ammonia, but of course much less soluble than in water. If 1) or 2) is used, one might need to filter off NaCl again during evaporation.

best regards,

JR

@Jan, I've read that patent (US2334151 A) but I don't have access to liquid ammonia. Do you have any other idea of how to do this?

@Alaa and Joao, thank you for the input. I'll have to use NaOH since the pKa of guanidine is around 12.5. 

Alright. The problem is that Guanidine as well as Guanidine hydrochloride is soluble in water and alcohols and the hydrochloride is also soluble in DMF (Palmer, D.C., e-EROS Encyclopedia of Reagents for Organic Synthesis, DOI: 10.1002/047084289X.rg013) ...which in turn is miscible with water and alcohols.

I've seen in articles that guanidine is just liberated by base and immediately used for further synthesis. One example is

http://www.arkat-usa.org/get-file/29375/

This doesn't help you much, though, but I was thinking (in addition to what João Paulo dos Santos Fernandes already said) that one way would perhaps be to make sure to add so much base (e.g., NaOH in EtOH) that the guanidine hydrochloride would be completely converted to guanidine, then filter off NaCl and obtain the free base exclusively after evaporation. "Trial and error"?

My 2 cents 4 in the morning.

Best regards

JR 

Whatever is done, when free guanidine base is used it must be carried under an inert atmosphere (Ar, N2) due to the extreme prone to capture CO2 from air resulting with guanidine carbonate. Anyway, a fresh batch of guanidine base should be prepared every time when it is required as the solution inevitably darkens during the storage. These observations were made in both methanolic and ethanolic solutions after addition of sodium or potassium hydroxide to guanidine hydrochloride and attempts to store the solution under Ar for more than 1 day. The reaction we required guanidine for was conversion of methylester into amide.

Totally agree with Eduards Bakis and Jan-Erik Raitanen.  If you intend to use the guanidine free base as a catalyst only, i would recommend instead the TBD (1,5,7-Triazabicyclo[4.4.0]dec-5-ene ). I had good results in transesterification with TBD, without having to deal with the guanidine instability issues.

In the past, I've used phenomenex Strata XC (strong cation polymeric)SPE columns to free base my salts. You condition with methanol, load your guanidine salt (dissolved in methanol), rinse with methanol to wash away the HCl salt then elute into a separate flask with an ammonia methanol solution. When you rotovap, the ammonia will be pulled away and you should be left with free base. The polymer matrix is good for use with methanol because it won't dissolve like silica. 

Guanidium is a very strong base (pKb=13) and this is the reason for his reaction with CO2 (ac). I think that you must not do it this in water. Is better use KOH (1eq) in MeOH as base. Then add toluene for the azeotropic elimination of produced water (1eq) and then you must evaporate the MeOH. Finally the extaction of the guanidium is posible by the use of an apolar solvent (CHCl3, CH2Cl2, hexane, heptane) that will not dissolve the KCl. Concentration and concervation over Ar is necesary or you may work with the standar solution.

Hi all,

For the last 20 years I am looking for the best transtererification catalyst.

Not doubt DBTO is the best , but the main problem is the high toxicity of the organic tin compounds.

by the way , guanidine carbonate works so good like free guanidine base.

regards

Norberto

Though late but this one is good.

This is the method that I have been using many times...

Take dry ethanol and add 1.01 Meq sodium metal to make NaOEt. When the solution is clear, add 1 MEq of Guanidine HCl and let the mass stirr for and hour or so. NaCl has least solubility in Ethanol as compared to methanol. NaCl, thus precipitated, can be filtered off and the ethanol can be then evaporated leaving behind Guanidine free base. But please take care that guanidine free base is hygroscopic and thus can cause error in weighing.