possible one pot shot from isosafrol to mdma

[pinokio]

like to know if somebody did the "one pot shot from isosafrol to mdma"
 

[Rhodium]

To clarify, he's referring to Drone's Photoamination which is detailed at my page.

[CHEM_GUY]

I don't think anyone has because most bees are weary of DCB and it's purchase and handling.  A long time ago there was a lot of discussion on this matter. 

There was some discussion on the production of para-DiCyanoBenzene from OTC mothballs (para-DiChloroBenzene) and NaCN.  The acetonitrile as a solvent was debated as necessary, but I'm not sure if there could be a substitute.  You definitely wouldn't want to have any alcohol or water persent in this reaction because they would add to the alkene. 

This post is for informational purposes only an is not intended to facilitate illegal activity.

[Rhodium]

Here is a page with a HUGE amount of photoamination references for styrene derivatives:

http://www.crc.miyazaki-u.ac.jp/y1ken/pac.html

[slappy]

This can definatly be done. I have a collection of ref's on this particular subject. 1-Aryl-1-Propene's have been directly aminated with NH₃ in MeCN with p-DCB using a mercury vapour lamp in very high yield. p-DCB can be obtained fairly easily, and is relativly inexpensive.

While this process looks very attractive from a process standpoint, for the average experimentier, peracid -> Ketone then reductive amination with Sodium Triacetoxyborohydride is probably still the easiest route.

[Rhodium]

Why is the NaBH(OAc)3 reduction easier than the NaBH4 reduction in your opinion? It has far less atom economy, and is thus more expensive.

[terbium]

Why is the NaBH(OAc)3 reduction easier than the NaBH4 reduction in your opinion?
I think because he is talking about preparing the amphetamine, not the methamphetamine thus necessitating the use of a large excess of ammonium acetate and a slightly acidic environment. It seems that he is suggesting using triacetoxyborohydride as a substitue for cyanoborohydride.

[Acme]

Triacetoxy is the shit

[Dope_Amine]

Ever consider bubbling ammonia into methanol, forming the imine with a catalytic amount of acid, and then reducing with NaBH4? 

This gets around all of the normal imine formation issues that one must deal with when using NH3-acetate or NH3-HCl.
something for your mind.......

[Acme]

Catalitic amount of acid?

Use at least enough AcOH to get your soln to pH 4.5 IMO or the imine aint forming at all
ammonia sucks as a nucleophile and usu needs 5-6 eq but it is basic as all get out and Mr Schiff-Base likes 4.5

[Osmium]

Nope. Reductive amination via hydrogenation works well without added acid, even with NH3.

[Acme]

That is fine and all

but he is not proposing to do catalytic hydrogenation here is he?

and to some extent, the product may animate better than the ammonia, reacting with the ketone to produce not good things,
although if you swamp it, it should be OK

Generally, I have found it advantageous to hydrogenate catalytically with some acid (AcOH or HCl) around
to get cleaner reactions, especially for ze production of anilines from nitro's, as the free amines can blackify and it is shitty thereby, and/or your compound can glom onto the cat somewhat unless acid is there

I see it as an equilibrium thing, what is the most favorable conditions for forming the imine

b/c, NaBH₄ can reduce the ketone to the alcohol
pretty rapidly

Besides, Triacetoxy is the shit

[Osmium]

> That is fine and all
>
> but he is not proposing to do catalytic hydrogenation here is he?

The intermediate is the same.

[Dope_Amine]

Sorry, I got my info from someone who should know more than me but in this case he didn't know what the FUCK he was talking about.
something for your mind.......

[Vibrating_Lights]

Does p-DCB have any OTC uses.  Dcm Is not an alcohol or water would it be a suitable substitute for acetonitrile.  This could be a very attractive way to TMA-2.

[Rhodium]

p-Dichlorobenzene is used OTC in mothballs. p-Dicyanobenzene has no OTC uses. You can not substitute acetonitrile for alcohol or water here, perhaps if you are lucky DMSO or DMF would work, but before you try any changes to the method, DO try it out as it is written.

This should be golden rule number one:

When attempting an untried synthesis for the first time, follow the original directions to the letter. If it works, then try to change the procedure if you have the desire to do so, one parameter at the time.

[Lino]

Would photoamination work the same with alpha-methylstyrene? Or would the alpha-MS need isomerizing first? I'm unclear about the different depiction of the double bonds when I look at these two molecules.

Have you read this ref. from Tett.Lett. 42 (2001) 2505–2508. I have it as a .pdf file if anyone is interested.
Photoinduced electron transfer oxidation of a-methylstyrene with
molecular oxygen sensitized by dimethoxybenzenes: a non-singlet-oxygen mechanism
Tadashi Mori,a,* Makoto Takamoto,
Linoleum: the 13th element!  Now available at all good DIY stores… & Walmart.

[Rhodium]

alpha-methylstyrene would not produce the desired result - you would get the wrong isomeric phenylpropylamine.

[PrimoPyro]

Uhhh, while looking around for information on p-DCB, I found this link, in japanese, looks interesting to me, but I don't know what it really means...

Can anyone here translate the top characters? Looks like names to me...

But the ref list is pretty extensive.

EDIT: Forgot to include the link, sheesh:

http://www.crc.miyazaki-u.ac.jp/y1ken/pac.html

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[PrimoPyro]

Post 12408

(CHEM_GUY: "photo-amination help...", Novel Discourse) states that no water should be present, or it will add to the alkene as well, yet the very procedure calls for a 9:1 ratio of MeCN to H2O?

What is correct?

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[PrimoPyro]

Ok, this thread is hereby changed into the photoamination of propenylbenzenes thread.

I read the patents at the bottom of the document, and am convinced that this is a wonderful process. Here are some interesting notes.

1.This process works to use ammonia or a primary or secondary amine, in conjunction with an olefin, to produce aliphatic, cycloaliphatic, heterocyclic aliphatic, or aromatic mono-, di-, and tri- amines. That is a huge spectrum of possibilities!

2.Patent number 2,749,287 deals with the addition of ammonia to aromatics, specifically benzene, toluene, and xylene, to produce aniline, toluidine, and xylidine plus hydrogen. This is not addition across the double bond, but a substitution for tacking on an amine.

3.Technically speaking, catalysts are optional. They do greatly increase yields, but the reactions proceed without their use. You really need to read the second patent, the catalyst list is huge. (thats good, for those here that dont know)

4.The wavelength of light is said to be preferrably 1600-2200A (Angstroms?) and to use other wavelengths, a photocatalyst must be employed. At this wavelength, no catalyst is needed for the reaction to take place, but it is recommended.

5.This frequency range presents a minor issue on glassware. Quartz glass does not allow too much radiation of those wavelengths to pass through, but siliate glass works perfectly. Specifically types: Corning #7940, Suprasil^(R). No prob, who uses quartz glassware??? Borosilicate pyrex should be fine.

6.Examples of lamps that produce light with the desired wavelengths are: Deuterium Lamps, Mercury Argon Lamps, and Xenon Flash Lamps. They say the xenon lamps are by far the best. Keep in mind this is for optimum wavelength.

7.Here's the good stuff! A list of organocatalysts used in these reactions. These are so simple! Examples: Ketones (they outright said they preferred acetone), Diacetone alcohol, Pyridine, Several Phosphines (read the patent), Benzene, and M-Xylene! Meta-xylene and acetone are what really caught my eye. Over the counter xylene is mostly the meta isomer, and the three isomers can actually be seperated if you want to.

8.Optimum temperature range is -10°C to 40°C, and I quote, "...but any convenient temperature may be used." Sheesh, "ya do whatever you want it'll work" Sounds good to me.  

9.Ratios of amine to olefin: can range from 1:1 to 20:1. They say preferred ratios are 5:1 through 15:1. I'd agree, not just to get the reaction to proceed, but to minimize multiple additions of your newly formed amine to another propenylbenzene.

It says that the catalysts only need be present in catalytic amounts (no fucking shit) but is generally limited by the properties of solubility of the catalysts and reactants.

This patent seems to deal with the same concept drone discussed, but makes no mention of p-DCB or acetonitrile, makiing me wonder if the reaction is indeed not so specific to those reactants.

Personally, I'd think that using an organocatalyst as a solvent would do wonderful, such as acetone or m-xylene, or a solution thereof.

So really the only question I cansee as to which catalytic solvent you use, would be to use the one that offers the highest solubility for amonia or methylamine, so you can saturate it as much as possible.

I have one question that I'd really reallyreally like someone smarter than me to answer, if you don't mind. Would it be feasible to prepare a solution of methylamine in a nonpolar solvent by reaction of methylamine salt with base IN THE NONPOLAR.

I know thatthese compounds are not soluble in nonpolars, but the reaction should proceed, as by basic rules anyway. It will produce water. So for example, specifically, if SWIPP had some acetone with MgO crystals in it, and added some methylamine sulfate, would it react to form methylamine gas and magnesium sulfate, which will suck up the water and crystallize? You could then filter your nonpolar to remove the solids, and use it for immediate reaction.

The point is not to prepare a mere methylamine solution, it is to prepare a solution beyond the saturation point. (I assume it'd just start fuming)

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[PrimoPyro]

The shortest wavelengths for ANY of these lights that I can find examples of are around ~350nm, or 3,500A which is less energy than required to proceed without a catalyst. Sodium lamps produce around ~589nm, Hg around ~549, and xenon flash ranging from ~350-800nm, all are too low in energy. (remember shorter wavelength = higher frequency = more energy)

A catalyst is going to be necessary to carry these reactions out. However if a catalyst (or several) are used, then any of these lamps, since their affects are so similar could be used. The highest recommendation in the patent was for the xenon flash lamp, undoubtedly they were referring to the higher power kind, not one producing a shitty 800nm.

So personally, I'd say go for the Xenon flash lamps as long as you can find one with enough wattage to get the job done. I think a large one would be quite expensive, whereas a sodium bulb that produces ~589nm at over twice the lumens experimented with, will only cost ~$20.00 USD.

EDIT: Found a Hg lamp at ~360nm, so I know they get that powerful. I think a thin tubular Xenon lamp (strobing) the thickness of slightly larger than a pencil, actually suspended (maybe two or three even) into the reaction mixture would provide the best results, as long as you protected the bulbs from direct contact (coat them in something). This would also solved the problems of the correct glass worry, as the rays do not have to pass through any glass to reach the reaction mixture, and also the rod will not overheat, as the reaction mixture is cooled to 10°C, which keeps the rods cool.

To do it this way, with a suspended rod tube, you obviously couldnt do it in a flask, keep that in mind.

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[halfapint]

Real prodigious, Primo.

Got a possible issue on the glass types. Suprasil isn't exactly a silicate glass; it's a fused silica glass. Like fused quartz, it's composed of little but SiO2, not sodium silicate or borosilicate. To say "Borosilicate pyrex should be fine" may not bee entirely accurate.

Here's one alternative: "quartz" heaters have nice (fused) quartz tubes enclosing nichrome heater elements. I know your patent source complained about its low transparency up around 160 nm, but that is the best you're going to find, without directly subsidizing your glassmaking conglomerate with big bux. Quartz does approach the short wavelength passband of interest; in other words, it gets close enough to work. Fused silica of course is best, but does not grow on trees and cannot bee found in garage sales. Other glass types, I'm afraid, are way out of the picture. If somebody has a big natural quartz crystal, plus the equipment and skills to bore it out, that presents another possibility to make a vessel for short-wave UV reactions.

This is the situation as I understand it: fused silica is best; fused quartz is better than nothing; all other glass is nothing. Sorry. The only option remaining is working in an open container, with the UV light source over it.

Thank you very, very much for the tips on acetone and m-xylene. Most appreciated. Didn't want to fool with dicyanobenzene, plus have a distinct recollection of some bee pushing the m-isomer in preference to p-DCB, which added to my confusion.

Edit: Second time today I had a post I was working on, beat to the wire by another poster. The xenon flash lamps which are so highly recommended, are those used to excite ruby, YAG, or other solid-state lasers. This isn't the same as your photographic flash units!
turning science fact into <<science fiction>>

[PrimoPyro]

Here's some more good information on the details of this reaction:

1.Another catalyst specifically stated to projmote this reaction is ammonium bromide and/or iodide. Iodide is much preferred.

2.I quote, ""In general, the mole ratio of ammonia or amine to photocatalyst is 20:1 to 500:1 with a ratio of 100:1 to 400:1 being preferred."

3.I quote, ""It has been found that any light absorbing-ketone impurity which may be present in the amonium halide as a result of the method of its manufacture must be removed, usually by salt recrystallization, since such impurity substantially affects the olefin conversion to amine."

4.I quote, ""It has been found that ammonium chloride and amonium flouride are promoters and not true catalysts since their use produces no more than a stoichiometric yield of product."

Now am I correct in nderstanding that that translates to: Moles amine produced = or < moles halide employed. That's what that means right? Yuck.

5.I quote, ""Double bonds adjacent to groups that can stabilize free radicals are said to activated, and these generally react much more readily than unactivated double bonds."

Interesting, and good to remind yourself of, but this applies to all kinds of reactions involving olefins, so it's nothing earth-shattering.

6.This is great! They answered a question in my mind about increasing solubility: What about PTCs?

Well we all have our lovely quaternary ammonium salt PTCs that we all love so much, and guess what! They are employed here!  

To increase the solubility of the catalyst and the amine so that they can more readily react with the olefin, a quaternary ammonium phase transfer catalyst is employed, as long as it does not interfere with the reaction.

Preferred PTCs are tetra-alkyl ammonium bromides and iodides, more preferrably iodides.

Specific favorites: "Especially tetra-n-butyl ammonium iodide, and tetra-n-heptyl ammonium iodide."

They also mention that the chloride catalyst forms the hydrochloride salt of the produced amine and is harder to isolate, but I really think they were referring to isolating the hydrochloride for reuse, not isolating the product of the reaction.

                                                   PrimoPyro
Vivent Longtemps la Ruche!

[PrimoPyro]

O yea, and the photoamination proceeds "at any convenient pressure."

Specific parameters are between 0 and 600 PSI. Preferred pressure is 100-400PSI. (Mods, don't jump down my throat for nonmetric units, they are stated in the patent as such)

I was wondering if there might be a way to make this mechanism enantioselective? That would be awesome, being able to tweak optical isomer formation... But alas, the very concept of such catlysis is beyond my grasp at this point. But I wanted to bring the idea up.

                                                  PrimoPyro
Vivent Longtemps la Ruche!