Dear Wayne Briner,

you can prepare salt with organic or inorganic acids,

just dissolve your compound in the solvent as you mention your compound is soluble in toluene, then add organic or inorganic acid to it in drop wise manner, and stir it for 30-45 min to precipitate out. then either you can filter it in inert atmosphere or directly distilled off your solvent and you will get your compound in salt form.

if still can not solve the problem, then try some formulation solvent for the formulation in mixture,

currently we are using DMSO, EtOH, cremophore, PEG, Tween 80, glucose, water, PBS, saline....so on,

hope this is helpful to you...

Dear Wayne,

A couple of questions for you! What is the molecular weight of your compound? Is it acid or base? When you have answers to these questions, it might be easier to comment further on salt formation. Regards,

Philip.

I agree with the previous comments, some more questions - what is the Pka?, does it ionise?, is it crystalline? Also, why do you think you need a salt version of your compound?

Dear Wayne

I would have to recognize the chemical structure of the compound, to suggest the conditions

Hate making solutions..and sometimes the pKa is not shown by the manufacturer. By the way I'm sure you already tried to warm it up,right?

Cheers,

Omar

Dear Wayne:

I also agree with all of above previous comments,but I think your compound not acid or base,and I think have big MW non-polar compound, again do you need to salt form to treat easily with this compound?

In terms of more detail this is an amine based compound with a weight of 585. No effect on the pH of water. It does reluctantly dissolve in water of pH 10, although I am not sure if it simply decomposes at this pH. I am not sure how to address the Pka question as so little dissolves in water, on the order of 1mg/L. In terms of a water/toluene partition, nearly 100% would be found on the toluene side.

As far as why I need a salt, I shows some interesting systemic effects when a fine suspension is injected IP, a salt would be a better choice.

I apologize if this is vague, I am a neurobiologist by training, not a chemist.

can you give the functional group of the molecule, or as sugessted by Philip Kerr

You might salt it out from toluene by addition of HCl in ether.

Bernhard is right. You can make a hydrochloride from your amine by treating it with HCl in any anhydrous solvent. Gaseous HCl would be best.

Which groups have got your novel compound.

Dear Wayne

I would have to try to dissolve the substance in pyridine.

Calculate pKa value of each ionisable group in the molecule! This is quickly checked against the value determined experimentally on 1-2 mg of sample by potentiometric titration. Knowing the pKa values, enables potential salt forming counterions to be selected, for each candidate, based on lists available in the literature!

Hello there! You must check on the molecular structure of your compound. When you check the molecular structure, make sure your molecule have ionizable groups. Given that your compound is soluble in toluene it's obvious that it do have low polarity. If it doesn't have any ionizable groups I'm afraid you can't turn it into a salt right now, however, you can modify it's molecular structure, adding some ionizable groups. After doing that, you could use simple sutitution reactions or any other synthetic method at given conditions of temperature and pH (Here it's important to find the pKa of your compound and to determinate if your compound is thermolabile). I hope this helps! Good luck! Greetings from Colombia!

Hi Wayne, your compound is a amine based compound: it is a primary, secondary or tertiary amine? Does your molecule contains also a COOH or other acidic groups??

If it is really an amino compound it should be basic and, therefore, should be better soluble in acidic solutions than at pH10. Try perhaps to make an ammonium hydrochloride by treating it with diluted HCl.

Greetings

Gilbert Reibnegger

I don't know whether by adding an aminoacid moiety would improve the solubility of your compound. We encountered a similar problem years ago with a series of highly in vitro active compounds known as tryptanthrins. We could not make them soluble. We used oil to inject directly for in vivo tests. Bioavailablity was still very poor.

Mixtures of solvents come with heat sometimes help a little, like using chloroform+methanol or ACN+water...Good luck!

What is de MW of your compund? As you're saying that it is sligthly soluble in toluene and if the recomendations given about the ionizable functional groups already present in the structure don't work, you must remember that any introudction of new ionizable groups will affect the activity of the compound. An alternative is to try the prodrug concept to imrpove the solubility while keep the activity of the molecule. There are more complex approaches to deliver your compound but it is necessary to know more about.

Without stating which functional groups are present on your compound, it is rather difficult to answer your question. I recommend re-stating your question and describing some of the functionality present on your compound, and MW as well. If it is just a hydrocarbon, then in some cases fine milling to extremely small particle sizes can assist in aqueous solvation.

Dear Wayne Briner,

You try to introduce an active methylene group into your novel compound,from which you could prepare the salt easily.

if ur compound have nitrogen with free lone pair of electron then simply add 1N HCl solution into ur compound and make pH acidic and lyophilised it. this is ur HCl salt...

What is nature of your novel compund, is it acidic / basic

I think the suggestions of Sandeep Miglani and Balkrishna Kale are correct. Please try what they advise to do!

Thanks everyone, this had given me some great ideas!

1.Since if one can want to make salt its necessary to know that how is nature of

prepared compound either acidic or basic.

2.Since our novel compound is not soluble in water but it is soluble in toluene.

3. I think we should dissolved this compound in toluene and extracted the toluene with

water,

4. Now check the pH value of extracted water by pH meter or pH paper

5. either it is acidic or basic which gives you a tentative idea of functional group present in a molecule.

6.once we get the nature of our functional group we can prepared the salt either by using acid or base.

First of all you have to mention about the functional groups in your compound. Then whether it is acidic or basic. Have you tried with alcohols ( ethanol)? Why do you want to prepare a salt? if its slightly soluble in toluene then try to change the parameters I mean temperature, time, pH etc. Just try and see whether its soluble or not. If its a biological then care must be taken.

I agree with Richard walker, needs to see the chemical structure of the molecule. By viewing the structure, I can be able to give you better scheme for both acidic, basic and neutral compounds. By viewing your information, the molecule looks like neutral in nature, highly lipophilic and insoluble in water predicts very poorly ionizable drug. It means u need to prepare a esterification or conjugation of polymers that improves solubility and hydrophilicity. This information might be useful to you.

If it possible to carry mannich base reaction for your compound then do it.

As i have read the other suggestion , i will also be very clear after knowing the structure.

Why don't you try your novel compound as a ligand so that you can prepare a complex salt with any transition metal

If the cpd is basic in nature, dissolve the cpd in ether then pass HCl gas through the solution , the hydrochloride salt should be separated

Sir, I can recommend to you teh book by P. Heinrich Stahl and Camille G. Wermuth: Pharmaceutical salts published by International Union of Pure and Applied Chemistry (IUPAC) in Wiley-VCH 2002. 374 pages. This is the best source for your question. Best regards Wolfgang Froestl

If you don't want to work with HCl gas you can use commercially available waterfree HCl solutions in ether or dioxane (e.g., from Aldrich) to precipitate your compound from toluene as a chloride salt.

Thanx again everyone for your help, you have pointed me in the right direction.

Dear Wayne Briner,

you can prepare salt with organic or inorganic acids,

just dissolve your compound in the solvent as you mention your compound is soluble in toluene, then add organic or inorganic acid to it in drop wise manner, and stir it for 30-45 min to precipitate out. then either you can filter it in inert atmosphere or directly distilled off your solvent and you will get your compound in salt form.

if still can not solve the problem, then try some formulation solvent for the formulation in mixture,

currently we are using DMSO, EtOH, cremophore, PEG, Tween 80, glucose, water, PBS, saline....so on,

hope this is helpful to you...

I wonder why do you want a salt? Could you give us more info? Is because bioavailibility or some requirement for oral adminsitration? Becuase if you have activity and all you want to do is to deliver the compound, there are other approaches without making a salt.

Dissolve in ether followed by drop wise addition of etherial HCl. or dissolve in isopropanol followed by passage of HCl gas in

Compound is soluble in toluene, dissolve compound in toluene and pass HCl gas in cooling, after saturation of HCl gas in the mass hydrochloride salt precipitate out than remove excess HCl gas with Nitrogen and filter out.

yes .... i strongly agree with Mr. solanki ... this the best method.

i have prepared many salts like TFA And HCL . this is the best way ..

You should first be sure the nature of yr compound if it is basic or acidic. If it is basic I would suggest to pass HCl gas directly onto yr toluene solution of the compound, HCl salt would ppt.

First do elemental analysis of compound than prepare salt accordingly

The best way, in case of basic compound, is either to

1) Dissolve in toluene (either on cold or under reflux then cooling) followed by passage of HCl gas. Or

2) Dissolve in ether (if soluble), followed by dropwise addition of etherial HCl.

if you have a basic amine (aliphatic) then making a HCL salt is probably the way to go.

to make HCl salt

1) dissolve your compound in ether 2-3 mL per 100 mg or as per the solubility.

2) then filter it through pasteur pipette fitted with glass wool inside.

3) filter the material in a round bottom flask.

4) after this you can either use a 2M HCl in ether or you can make your own.

4.a) to make HCL solution in ether: take a conical flask. add 30-50 mL of ether. put the conical flask on a ice bath. then carefully pass HCl gas over it for 5 min. initially all the gas will get dissolved then as the solution become saturated more of the gas will start to eveolve and that is the end point . you HCl ether solution is ready.

5) then using a pasteur pipette add dropwise this HCl solution to your ether solution of compound of interest.

6) with every addition you will see instant salt formation.

7) stop as soon as the salt formation is over and dry it under reduced pressure it should be a free flowing powder.

Other possibility, pupple HCl gas in tert-butylmethylether, and add your compound in any organic solvent, salt will be formed as ppt.