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Quazepam analog

haribo1

Ex-Bluelighter
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Perusing the benzos on Wiki (with it's 100% accurate information base) I notice that quazepam has a thioamide in it's structure. Now, am I right in thinking that the route to making quazepam goes via forming the amide then using PS5 to make the thioamide? If so, that intermediate should be MORE active?

quazepam.gif
 
I've read that the thioamide oxidised and that this shortens the T1/2. Do you know the T1/2 of Sulazepam? It should be a LOT lower than diazepam (which it is the thioamide analog of).
 
Does anyone have information on the synthesis of quazepam, I cannot find a source of the appropriate benzophenone. I assume that it's made from 2 amino 2'fluoro 5 chloro benzophenone. I'm guessing that you make an amide with trifluoro acetic acid, reduce it to the amine and go from there. Pity, I have NO desire to play with trifluoro acetic acid. Same as that QI thingy that acts like alcohol, nasty, nasty reagents...
 
sorry to go off topic a bit but how many years of chemistry / which kind of chemistry does it take to be able to understand this shit? (reason i'm asking is because i'm very new to the whole chemistry subject)
 
about 2 years of organic chemistry. after a b.sc. in chemistry you should be able to understand this kind of terminology (which i dont yet).
 
BTW what are Quazepam properties compared to other benzos?
Is it similar in properties to another more common one?

From what I read, it is a hypnotic benzo, with a long half-life.....
 
jasoncrest said:
BTW what are Quazepam properties compared to other benzos?
Is it similar in properties to another more common one?

From what I read, it is a hypnotic benzo, with a long half-life.....

Comparisons with other hypnotics i found...


Temazepam:

Two benzodiazepine hypnotics, one with an intermediate elimination t1/2 (temazepam, 15 mg) and the other with a long t1/2 (quazepam, 15 mg), were evaluated in 22- night sleep laboratory studies. The effectiveness and side effects of these benzodiazepines were assessed during short- and intermediate term use. Subjects were also assessed for the presence of rebound insomnia after abrupt withdrawal. Quazepam, 15 mg, was significantly effective in improving sleep both with short- and intermediate-term use, but the effectiveness of temazepam was considerably less. Although temazepam was more effective for inducing sleep and maintaining sleep with short-term use, it was associated with an higher incidence of performance impairment, increased ratings of a 'high', and sedation along with a rapid development of tolerance with intermediate-term use. After its withdrawal, temazepam was associated with some sleep and mood disturbance on the first withdrawal night, whereas quazepam had carryover effectiveness.


Triazolam:

Quazepam, a trifluoroethylbenzodiazepine hypnotic, and triazolam, a triazolobenzodiazepine hypnotic, differ in terms of their benzodiazepine-receptor binding profile. Previous studies have suggested that quazepam produces less performance impairment than triazolam. Whether these effects are due to differences between quazepam and triazolam in terms of their benzodiazepine-receptor binding profile or to the testing of insufficient doses is unknown. The present study compared the acute behavioral effects of triazolam (0.1875, 0.3750, and 0.5625 mg), quazepam (30, 60, and 90 mg), and placebo in 12 healthy humans using a within-subjects, placebo-controlled, crossover design. Quazepam and triazolam produced comparable dose-dependent performance impairment and increased ratings of drug effect and drowsy. Quazepam, but not triazolam, increased ratings of dizzy/light-headed, performance impaired, and sleepy. Triazolam, but not quazepam, increased ratings of high. Thus, across a sufficient range of doses, the performance-impairing effects of quazepam were similar to those of triazolam. By contrast, quazepam and triazolam produced somewhat different constellations of participant-rated drug effects. These differential drug effects may be attributable to differences between quazepam and triazolam in terms of their benzodiazepine-receptor binding profile.
 
I cannot find a synthesis for Quazepam itself, but other patents all seem to use something off this page:

http://www.organic-chemistry.org/synthesis/C2S/index.shtm

I'm sure that phosphorous pentasulfide WAS in the quazepam synthesis, but time moves on and this Lawesson's Reagent stuff seem to be a good, general route. Anyway, the point is that the thioamide is made from the amide. I would BET on the non-thio intermediate being stronger. The N-2,2,2 trifluoroethyl analog of fludizepam is going to be STRONG. I mean, fludiazepam come in 0.25,0.5 & 1mg tablets, so I would assume it's 10x stronger than diazepam? A legal benzo thats made on an industrial scale (for making quazepam) that fits on blotters.... could be fun for someone.
 
^That's not the immediate precursor, where is the 2,2,2 trifluoroethyl group? As I said earlier in the thread, I assume that the amine + trifluoroacetic acid followed by reduction gets you there...
 
You'd still use 2-amino-5-chloro-2'-fluorobenzophenone as the precurser. The trifluoroethyl group isn't attached to the benzophenone structure. The immediate precursor, I assume, would be a completed benzo, sans the trifluoroethyl group.
 
rayleonard said:
sorry to go off topic a bit but how many years of chemistry / which kind of chemistry does it take to be able to understand this shit? (reason i'm asking is because i'm very new to the whole chemistry subject)

If you have the dedication, you can do it less than 2 years. If you're just interested in how things work, SARs, even basic synthetic routes, you can probably learn enough to carry on an intelligent conversation in 3-6 months. You really gotta be interested, be intelligent and love reading.

There's a website that provides a great introduction to the chemistry and structures of benzos- but I can't remember what the hell it was called. It was basically a step by step guide to benzodiazepines. It wasn't big on the "if you change the chlorine to a fluorine this happens" sort of stuff, but it provided a great overview. It was run by one guy, and I'm pretty sure the site was titled after him. He mostly talked about psychedelics, but in his chemistry section (only 2 link, I think) he had one about benzodiazepines.

Perhaps someone here knows?
 
Ham-milton said:
You'd still use 2-amino-5-chloro-2'-fluorobenzophenone as the precurser. The trifluoroethyl group isn't attached to the benzophenone structure. The immediate precursor, I assume, would be a completed benzo, sans the trifluoroethyl group.

No, it's not. You get the substituted benzophenone, form an imine with the ketone and react with bromoacetyl bromide (or chloroacetyl chloride) so you add the amide grouping beforehand. Like I said, no immediate precursor so you have to react the one you mention with trifluoroacetic acid, reduce and THEN react.
 
Hadn't noticed quazepam having a thio group in it's structure.

That makes a lot of analogues of all the well known benzo's but with the thio group. Interesting
 
haribo1 said:
No, it's not. You get the substituted benzophenone, form an imine with the ketone and react with bromoacetyl bromide (or chloroacetyl chloride) so you add the amide grouping beforehand. Like I said, no immediate precursor so you have to react the one you mention with trifluoroacetic acid, reduce and THEN react.

Oh, I'm sorry, you're right, you definitely know more about the synthetic route than I.

but on the subject of the "immediate precursor"- Will this benzophenone w/ the trifluoro substitution be commercially available? I doubt that, I was thinking of an "immediate precursor" that'd be available.

I hope this makes sense. I'm baked off of 1 hit. that's what I get for getting 20/8th swag used over the course of a month then switching to homegrown nyc diesel.
 
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