Benzhydrol from Diphenhydramine

Quote: Originally posted by Jackson

Hi, I have been looking to try and synthesize Benzhydrol from diphenydramine

this is a good way to get benzhydrol from an OTC compound.Brilliant find

Quote: Originally posted by UC235

On the other hand, working out an OTC reduction of benzophenone would be a much better approach.

I think urushibara nickel should be usable, shouldn't it? Because the preparation of it is quite OTC and it's claimed to also work great at atmospheric pressure

[Edited on 19-1-2019 by Tellurium]

Quote: Originally posted by Tellurium

Quote: Originally posted by UC235   On the other hand, working out an OTC reduction of benzophenone would be a much better approach. I think urushibara nickel should be usable, shouldn't it? Because the preparation of it is quite OTC and it's claimed to also work great at atmospheric pressure

There is a generic benadryl brand for sale on amazon, 50 mg/pill, 1000 pills, and sold for 16 freedom bucks. Assuming 100% yield that's 50g of diphenhydramine hydrochloride, which is a sizable amount at a low cost.

I actually attempted to extract from these pills about seven months ago, but I ran into some issues (my clumsiness eventually put the final nail in the coffin for that experiment but I don't need to ask whether or not I should avoid knocking over my setup this time around). The first issue I ran into was the gelatin capsule itself. I had planned to use distilled water as the solvent for the extraction (because I had no other solvents, calling it a plan is a stretch) and so I decided I would manually cut open all thousand pills with pliers and sift off the heavily dyed (and water soluble) gelatin fragments. The five hours this process took made my hands cramp to high hell (clearly my gloves were not compatible with repetitive motion injuries ). My second issue was the "decision" to use water as the extraction solvent in the procedure. These pills are full of binders that gummed up my filter paper very quickly. Since I didn't have much in the way of equipment or chemicals, my solution to this was to wait a week for everything to filter through. After that week, everything had filtered through, and I then proceeded to knock everything over on accident as I turned away from another project (should've put that in the "when chemistry goes wrong" thread). I decided I would put this project on the backburner but I bought another bottle of pills for when I finally decided to try again. Apart from effectively addressing my allergies, the pills haven't been put to much use and are gathering dust as I type this.

I think that now is a wonderful time to try this experiment again, and perhaps I can contribute something useful to this community that has helped me on so many occasions, but I have some questions first:

1) Are there better solvents for extraction of DPH hydrochloride out there? I mean obviously there's always a better solvent but I mean in terms of OTC solvents like methanol, ethanol, isopropanol, n-butanol, acetone, ethyl acetate, and methyl ethyl ketone. I have access to all of these solvents but I do not know where to find literature detailing their suitability for this experiment, perhaps DPH hydrochloride solubility in various solvents can be part of what I contribute to this forum's knowledge base if it isn't listed somewhere. In the meantime, help would be appreciated!

I guess my second question of whether or not "the solvent" is good enough that I can skip the pliers and go to the coffee grinder will be easily answered once I know which solvent is "the solvent." Heck I could google gelatin solubility in all of the solvents listed but it's pushing 2:00 a.m. here. If experimentation to determine an appropriate solvent is necessary I'm going to bet that isopropyl alcohol will give best results because I always see that used for extraction of pharmaceutical hydrochloride salts, though I have no idea what the solubility of gelatin is within IPA.

After the DPH is extracted/purified I have one other question: Would HBr work to cleave the ether bond and form diphenylmethyl bromide in one step? I plan to react benzhydrol with HBr anyways to experiment with the Grignard reaction but if it is possible to do this all in one step things would be far simpler. I know that HBr cleaves ether bonds but the dimethylethanolamine side product is something I have no idea of the reactivity of in the presence of HBr.

All information is appreciated, I look forward to finally being able to use that nice large pill bottle these capsules are in for storage of other compounds!

Thank you!

Quote: Originally posted by UC235

On the other hand, working out an OTC reduction of benzophenone would be a much better approach

Quote: Originally posted by Mothman

Quote: Where would you get that much diphenhydramine to make this worthwhile? There is a generic benadryl brand for sale on amazon, 50 mg/pill, 1000 pills, and sold for 16 freedom bucks. Assuming 100% yield that's 50g of diphenhydramine hydrochloride, which is a sizable amount at a low cost.

exactly what I was going to say.You can buy a shit ton of drugs online cheaply.Also,its not a watched drug so it shouldn't set any phones ringing.

Quote: Originally posted by Mothman

The first issue I ran into was the gelatin capsule itself. I decided I would manually cut open all thousand pills with pliers and sift off the heavily dyed (and water soluble) gelatin fragments. The five hours this process took made my hands cramp to high hell.

yes

[Edited on 20-1-2019 by CuReUS]

Ok, here are the ingredients on the capsule:

Black Iron Oxide
D&C Red No. 28
FD&C Blue No. 1
FD&C Red No. 40
Gelatin
Lactose Monohydrate
Magnesium Stearate
Silicon Dioxide
Sodium Lauryl Sulfate

So if by "Shake and Bake" you mean blending everything up and chucking in some sulfuric acid and water as compared to an iodine/phosphorous reduction style deal...I was skeptical at first but this actually looks like it could work based on what would happen to a lot of these compounds in acidic conditions. The benzhydrol would fall out of solution as it was formed and the extra crud would react away with the acid and then remaining solids would be mostly benzhydrol and whatever happened to the gelatin present. Organic solvent extraction ought to be simple from that point forward and any stearic acid produced could be removed via a lye wash of the final product...and if one wanted the dimethylethanolamine they could basify and distill the remaining reaction mixture, or run an acid/base extraction...And I could always purify the benzhydrol before reacting with HBR, as this process doesn't sound like too much of a hassle really.

I won't make the mistake of using all of my pills like I did last time, just 100 of them for a nice 5g of DPH hydrochloride in the starting material.

Question: Best water to acid ratio? I haven't used H2SO4 for ether hydrolysis before but I know it requires water to be present. Would it be best to use dilute (10% w/w) sulfuric acid for this process or is a higher concentration needed?

I think I know what I'm going to be doing today

EDIT: Also I don't know if there are other brands, but determining if this brand is suitable should not take too long nor would it be too expensive. If I have to I'll buy a different brand but this stuff is what I have.

[Edited on 20-1-2019 by Mothman]

Quote: Originally posted by Jackson

Im trying to synthesize diphenylmethyl bromide from benzhydrol to use in the synthesis of a lignand. Could I just reflux sodium bromide, H2SO4, and diphenhydramine HCL, then filter out the diphenyl methyl bromide and recrystalize from an alcohol to obtain a more pure product?

Quote: Originally posted by Mothman

Quote: Benzhydryl bromide is apparently not all that stable, however. What do you mean by unstable? Are there special storage conditions to meet for the compound? How long does it last?

Quote: Originally posted by Mothman

Question: Best water to acid ratio?