Sciencemadness Discussion Board

a possible oversight by meth cooks ?

CuReUS - 31-3-2015 at 01:22

everyone who has read the hive,rhodium or vespiary files,knows that drug chemists are an ingenious lot.They come up with amazing reactions and procedures.
but sometimes they can be quite stupid. Like this :
many must be familiar with the phenylacetone synthesis via phenylacetic acid and acetic anhydride.The anhydride is made by passing ketene through acetic acid
instead of doing all that,why couldn't they just react ketene with benzylmagnesium chloride to get phenylacetone ?(I agree the yield of the anhydride method is good,but still)
is it an abnormal reaction of benzyl grignards
I found an article on such abnormal reactions
so is the Mg method even possible ?

Attachment: austin1932.pdf (967kB)
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Loptr - 31-3-2015 at 03:55

I dont know about the possibility, but how many people in general work with ketene?

karlos³ - 31-3-2015 at 07:34

Quote: Originally posted by Loptr  
I dont know about the possibility, but how many people in general work with ketene?


Possibly a lot less than people who use pyrrolysis with an acetate salt for phenylacetone production. They dont care about the bad yield, its a lot less work, and they still get what they desire, so its enough for them.
Thats just my opinion, from knowing some people who are that desperate.

Cou - 31-3-2015 at 14:14

How is this not in detritus?

Molecular Manipulations - 31-3-2015 at 14:30

Quote: Originally posted by Cou  
How is this not in detritus?

Because it's an interesting topic with actual uses and because you're not a moderator.

Bot0nist - 31-3-2015 at 14:47

Well, this seems to me to be a thread discussing chemistry, and different novel routes to phenylacetone. Your of the opinion that it should be detritus because its target product is a well known and very restricted precursor to an illicit drug? But Cou, I was under the impression that discussion of procedures for CNS active compounds and their direct precursors is perfectly acceptable on this forum, so long as the discourse is scientific, not "cookery or spoonfeeding," and is not motivated by obvious desire to get high or make profits. This thread is certainly discussing clandestine drug chemistry and the ingenuity of its practitioners as they attempt to circumvent the obstacles of controlled and restricted reagents, but it does not seem to be obviously nefarious in its goal, is not written in stupid "cook" lingo, and it appears that an attempt to understand and discuss the chemistry involved was made so IMHO it seems within our guidelines.

While p2p most likely has no use in "legitimate" amateur chemistry, the ability to think outside the box in order to work around unavailable or difficult and/or expensive reagents in order to achieve success is very much applicable to the amateur home chemists struggle.

*edit* What Molecular Manipulations said...
:P

[Edited on 1-4-2015 by Bot0nist]

morganbw - 31-3-2015 at 15:05

@CuReUS
Good question.
Now I wonder as well.

Darkstar - 31-3-2015 at 22:46

This idea was mentioned here in an old thread on Grignard reactions with acetic anhydride to give ketones. (see second post) Apparently benzylmagnesium chloride + ketene would give poor yields. (one poster thought so, at least)

Also, according to the paper Rhodium posted, benzylmagnesium chloride + acetic anhydride gave phenylacetone in 52% yields. It might be worth mentioning, however, that the reaction needs to be carried out at pretty low temperatures. (-70°C in the paper) To be honest, though, if you're going to use benzylmagnesium chloride, unless the yields with ketene are actually somewhat decent, it seems like it'd just be easier to react it with dry ice to get phenylacetic acid and then go the usual PAA + acetic anhydride route.

CuReUS - 1-4-2015 at 01:41

Quote: Originally posted by Loptr  
, but how many people in general work with ketene?
Quote: Originally posted by karlos³  

Possibly a lot less than people who use pyrrolysis with an acetate salt for phenylacetone production.

then I must say that you both have not been in touch with clandestine chemistry.In the old days,almost every cook had a ketene generator at home,and the hive and DEA website are full of pictures of home made ketene generators.
there is also a story that once a cook was breaking bad when the DEA decided to give him a visit.He didn't want to rot in jail,so guess what he did,he just stuffed the output tube of his K-gen down his throat.He was dead before the cops broke down the door:o
Quote: Originally posted by Darkstar  
This idea was mentioned here in an old thread on Grignard reactions with acetic anhydride to give ketones. (see second post) Apparently benzylmagnesium chloride + ketene would give poor yields. (one poster thought so, at least)

ha ha what can I say,I guess meth cooks aren't fools after all:D
in fact I got the idea while reading this journal
http://pubs.acs.org/doi/abs/10.1021/ed026p323
in that they react C2H5MgBr with ketene to get MEK
and the reference for the reaction is
(6) STAUDINGER, H., "DieKetene," Stuttgmt, 1912.

[Edited on 1-4-2015 by CuReUS]

Attachment: reactions of ketene.docx (173kB)
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Chemosynthesis - 1-4-2015 at 04:49

At best, the jury is very much out on that first sentence. Just because someone said it doesn't make it correct, and the amount of errors made in idle speculation of chemist wannabes on the internet is unquantifiable.

I'm also not sure where you get your information, but everything I have seen over the years points away from your claim that "in the old days almost every cook had a ketene generator."
Acetic anhydride, phenylacetic acid, benzyl chloride and the like were not even not regulated until 1988 with the CDTA amendment to the Controlled Substances Act, so the risk and unnecessary effort of using a ketene generator any earlier is effectively a non-argument.
http://www.dea.gov/resource-center/meth_lab_maps/2011.jpg

After that, pseudoephedrine and ephedrine based illicit syntheses became popular throughout the 90s, resulting in several Controlled Substances Act amendments up through 2005, with a correlated shift in production towards Mexico, which some people have also connected NAFTA and cocaine supply/demand to.
PMC2757051

Other than resourcefulness in reading household product ingredients lists (even less taxing while on stimulants, I imagine), I don't understand the exultation of the clandestine "chemists" as a whole when they generally fail to perform even basic primary literary analysis of chemicals characterized and synthesized numerous decades ago (often reaching 50-60 years ago now at least), and often seem to request an inordinate amount of help in doing so. You are citing an article over a hundred years old now (1912?) and yet these people are "ingenious?" How so?

Other than slight alterations in procedure, I would say you are confusing "drug chemists" with the actual medicinal chemists who "come up with amazing reactions" and usually did so long ago without the spoonfeeding requests I see coming from many of the nonprofessional/legitimate "drug types." Maybe my background has made me a science snob, since the wannabes basically all get weeded out in a trial by fire, but the 'clandestine chemists' almost universally fail to impress in any positive sense of the word.

Bot0nist - 1-4-2015 at 12:37

Perhaps I should have said resourcefulness rather than ingenuity, Chemosythesis, as I wasn't going for exultation. I'm quite sure that the run of the mill meth cooks are not performing breakthrough, first of their kind procedures or eludicating reaction mechanisms very often. ;)

I was more trying to reference the type of flexibility and out of the box thinking that many home chemists (not just home drug chemists) often have to employ to work around their limited resources and inability to source needed reagents. This does often seem to require digging up and reverting to adaptations to much older techniques that were pioneered by truely ingenious and creative chemists with limited resources and no Sigma catalog.

All in I can't help but agree with your succinctly put post, as per usual. :P

Cou - 1-4-2015 at 12:54

Quote: Originally posted by Bot0nist  
Perhaps I should have said resourcefulness rather than ingenuity, Chemosythesis, as I wasn't going for exultation. I'm quite sure that the run of the mill meth cooks are not performing breakthrough, first of their kind procedures or eludicating reaction mechanisms very often. ;)

I was more trying to reference the type of flexibility and out of the box thinking that many home chemists (not just home drug chemists) often have to employ to work around their limited resources and inability to source needed reagents. This does often seem to require digging up and reverting to adaptations to much older techniques that were pioneered by truely ingenious and creative chemists with limited resources and no Sigma catalog.

All in I can't help but agree with your succinctly put post, as per usual. :P

I believe that the true fun/challenge in home chemistry is by preparing rare compounds with only chemicals available in stores. Common stuff like bleach, or hardware store acetone. Suppose you want an uncommon compound such as methyl salicylate. You could just order it from Sigma, and now you have it... but where's the fun in that? More fun to try making it from store-bought chemicals, as a challenge. Aspirin, acetone, methanol



[Edited on 1-4-2015 by Cou]

clearly_not_atara - 1-4-2015 at 13:16

Why on Earth would you use ketene for a reaction that proceeds on acetonitrile? Last time I checked only one of those compounds can kill you by inhalation.

PhMeMgCl + MeCN >> P2P imine

Anyway it's not used because Grignards are too hard for meth cooks.

[Edited on 1-4-2015 by clearly_not_atara]

[Edited on 1-4-2015 by clearly_not_atara]

morganbw - 1-4-2015 at 14:16

Quote: Originally posted by clearly_not_atara  
Why on Earth would you use ketene for a reaction that proceeds on acetonitrile? Last time I checked only one of those compounds can kill you by inhalation.

PhMeMgCl + MeCN >> P2P imine

Anyway it's not used because Grignards are too hard for meth cooks.

[Edited on 1-4-2015 by clearly_not_atara]

[Edited on 1-4-2015 by clearly_not_atara]


I agree mostly, ( >95% of the meth cooks )
But I promise you there are meth cooks who are also chemist. I doubt they would use Grignards but the ability is out there.

Molecular Manipulations - 1-4-2015 at 14:31

Meth cooks mostly just follow a "recipe" and don't care what reactions are going on. Sure there's certainly a few who were first chemists and realized the profit they could make, and decided to cook meth, and others probably cooked meth first and then decided they liked chemistry and chose to learn more. However this is the minority, most just want some bank and decide cooking is for them.
Benzylmagnesium chloride isn't that easy to get, and they want as little steps as possible.

morganbw - 1-4-2015 at 14:46

Quote: Originally posted by Molecular Manipulations  
Meth cooks mostly just follow a "recipe" and don't care what reactions are going on. Sure there's certainly a few who were first chemists and realized the profit they could make, and decided to cook meth, and others probably cooked meth first and then decided they liked chemistry and chose to learn more. However this is the minority, most just want some bank and decide cooking is for them.
Benzylmagnesium chloride isn't that easy to get, and they want as little steps as possible.


Agree in total.

CuReUS - 2-4-2015 at 05:13

Quote: Originally posted by clearly_not_atara  
Why on Earth would you use ketene for a reaction that proceeds on acetonitrile? Last time I checked only one of those compounds can kill you by inhalation.

PhMeMgCl + MeCN >> P2P imine

and pray tell me dear ,from where you you are going to get acetonitrile.AFAIK,humans don't shit it out.
and even if you got the nitrile and made the imine,you would have to use a non aqueous reduction method(although I have never heard of reducing a grig intermediate),like hydride or H2/catalyst,or your precious imine will get frapped
Quote: Originally posted by Molecular Manipulations  

Benzylmagnesium chloride isn't that easy to get, and they want as little steps as possible.

it isn't that hard either

like BOtanist,I praised the cooks for their ingenuity,I didn't say they were geniuses.And what I meant by saying that they came up with "amazing reactions" was their effort to search for reactions from literature,in a "pre" internet era.Imagine sitting in the library the whole day,with no google to help you and no pdfs to save.It was a tough time indeed and for that they should be praised.Also many didn't know shit about chemistry when they started,but they went on to become decent cooks.They were not taught in Ivy league colleges,with state of the art facilities by nobel laureates.They learnt what they could and they applied it .

[Edited on 2-4-2015 by CuReUS]

karlos³ - 2-4-2015 at 06:19

In a pre-internet era you could just buy the phenylacetone ;).
At least in europe.
Piperonylacetone too.
Methylamine, also no problem, not just then, still no problem to buy.

As for ingenuity, the reaction from bought phenylacetone and methylamine is even described in the organikum.
Just one book to pick, not hours or even days in the library, most pharmaceutic chemistry books also have this "recipe".

Quote:
: Originally posted by clearly_not_atara
Why on Earth would you use ketene for a reaction that proceeds on acetonitrile? Last time I checked only one of those compounds can kill you by inhalation.

PhMeMgCl + MeCN >> P2P imine

and pray tell me dear ,from where you you are going to get acetonitrile.AFAIK,humans don't shit it out.
and even if you got the nitrile and made the imine,you would have to use a non aqueous reduction method(although I have never heard of reducing a grig intermediate),like hydride or H2/catalyst,or your precious imine will get frapped


Just skip the hydrolysis, transfer the imine to an anhydrous methanolic NaBH4 solution?
Its not that complicated.
Also, just buy the acetonitrile, its cheap and an ordinary solvent.


[Edited on 2-4-2015 by karlos³]

Chemosynthesis - 2-4-2015 at 13:01

I definitely agree with Bot0nist and Cou that being limited in reagent selection can be intellectually stimulating, and solving such a problem is rewarding in itself. I wish it weren't necessary for hobby chemistry, but at least one should try and enjoy what they cannot change.

I knew some undergrads and even a few med/grad school students who at least openly considered supplementing their tutoring money/stipends with illicit synthesis. It wasn't really a common discussion, and I think only a couple probably followed through (one getting caught misappropriating research equipment by their PI during work hours). I have read some trial excerpts where prosecution claimed professional chemists synthesizing illicit chemicals for profit was thought to be rare, and I believe this to be the case for a number of reasons.
Quote: Originally posted by CuReUS  

it isn't that hard either

Yet I have seen self-avowed "meth cooks" act as though a Grignard were a 'holy grail' rite of passage for organic chemists, while arguing against people who seemed educated in the subject. Any sophomore level first year organic chemistry student at a community college should have performed a Grignard as part of their academic work. It doesn't take an Ivy League Nobel Laureate trained chemist, and you are quite correct in a Grignard reaction not being all that difficult.
Quote:
like BOtanist,I praised the cooks for their ingenuity,I didn't say they were geniuses.And what I meant by saying that they came up with "amazing reactions" was their effort to search for reactions from literature,in a "pre" internet era.Imagine sitting in the library the whole day,with no google to help you and no pdfs to save.It was a tough time indeed and for that they should be praised.Also many didn't know shit about chemistry when they started,but they went on to become decent cooks.They were not taught in Ivy league colleges,with state of the art facilities by nobel laureates.They learnt what they could and they applied it .
Back in those times, despite a lack of internet access, there were still card catalogs, inter-library loans, and printed ACS archives (that exist today). Literary research was more time consuming, but everyone did it... not just the chemical literati. Ask any Baby Boomer if they visited the library in high school, and they should tell you that they were quite capable of using these systems. Should they be praised too?

The history of most outlaw motorcycle groups, the ones history seems to suggest ruled the meth trade in the 60s on through the 90s, is one of returning veterans. There are rumors perpetuated in outlaw motorcycle circles that the GI bill allowed gang members to attend college enough to learn how to "cook" meth. This makes sense. The knowledge was then passed on in an apprenticeship fashion.

I can't cite this, but you can ask someone in relevant law enforcement and see if they tell you the same thing I've been told. You see this today where most "cooks" caught by law enforcement in rural America, if you ask them, are supposed to smurf for themselves and maybe a couple other people. They often claim to learn the same way. I find this a very different standard from someone who actually learned some chemistry, illicit drug producer or not, which I believe to be pretty rare. People interested in chemistry learn chemistry. They may have additional interest in money, drugs, or whatever... but people solely interested in the above probably don't want to bother really learning chemistry any more than as a means to an end.

CuReUS - 2-4-2015 at 20:38

Quote: Originally posted by karlos³  
In a pre-internet era you could just buy the phenylacetone ;).
At least in europe.
Piperonylacetone too.
Methylamine, also no problem, not just then, still no problem to buy.

karlos,please U2U me where you live,I might retire there:D
Quote:
As for ingenuity, the reaction from bought phenylacetone and methylamine is even described in the organikum.
Just one book to pick, not hours or even days in the library, most pharmaceutic chemistry books also have this "recipe".

reductive amination was the reaction that kick started the trade,just like the first telephone or car.There were many more developments that can't be found so easily
ex-have you heard of lithium triethyl borohydride or reactions using tetra nitro methane.
Quote:
Just skip the hydrolysis, transfer the imine to an anhydrous methanolic NaBH4 solution?
Its not that complicated.

maybe that's why NaBH4 is a watched chemical
Quote:
Also, just buy the acetonitrile, its cheap and an ordinary solvent.

it is not "cheap" everywhere

by the way,did anyone manage to get the german reference on ketene .Let's stick to the chemistry.

I found something interesting
Quote:
Phenylmagnesiuni Bromide and (A). First Experiment.
-Twenty-five cc. of absolute ether (distilled from a
Grignard preparation) and 8.5 g. (0.06 mole) of the ketene
were mixed. Then 0.06 mole of phenylmagnesium bro-
mide was dropped into it. Following the vigorous
reaction, the soluticin was refluxed for one-half hour, then
stirred with dilute sulfuric acid. The ether layer was re-
moved, washed with dilute sodium carbonate and dried
over calcium chloride and distilled. Vacuum distillation
(11 mm.) of the residue gave these fractions: (1) 70-120°,
3 g.; (2) 120-170°, 7 g. Redistillation of the 3 g. fraction
revealed no constant-boiling material. It distilled be-
tween 90-120' (11 mm.). The 7-g. fraction was chiefly
ethyl a-benzoylbutyrate.'* Si grams of it was collected
at 159-162" (11 mm.). Its Identity was established as
follows: (1) its saponification number was 215 (calcd.
210); (2) it was refluxed for 2.5 hours with a 5% solution
of potassium hydroxide, then ether extracted, the extract
dried and the ether removed. The 2 g. of residue con-
tained some diphenyl but it was largely phenyl n-propyl
ketone. It gave a semicarbazone, m. p. 184-185"

so ketene with phenyl grig will give a beta keto ester and not a ketone directly.the B-keto has to be hydrolysed to get the ketone

http://pubs.acs.org/doi/abs/10.1021/ja01314a005

[Edited on 3-4-2015 by CuReUS]

cal - 3-4-2015 at 10:38

Quote: Originally posted by morganbw  
Quote: Originally posted by Molecular Manipulations  
Meth cooks mostly just follow a "recipe" and don't care what reactions are going on. Sure there's certainly a few who were first chemists and realized the profit they could make, and decided to cook meth, and others probably cooked meth first and then decided they liked chemistry and chose to learn more. However this is the minority, most just want some bank and decide cooking is for them.
Benzylmagnesium chloride isn't that easy to get, and they want as little steps as possible.


Agree in total.


There are two types of meth manufactures, 1. Cooks whom have been shown a recipe and follow it because that is what they know. 2. A knowledgable person in chemistry who can pick and choose from available starting chemicals .
There are about 13 different methods to produce p2p from over the counter chemicals in natural state or that can be removed easly from a combination of other chemicals. Ketene was just a simple device and yield was not a deciding reason, because the street value was about $ 10,000.00 a pound, so even a 32% yeild gave a return many times greater than the investment.

byko3y - 19-4-2015 at 17:00

Ketene lamp is not just another device, it's just another way to perform suicide. One breath of it can easily be lethal. Along with cyanides, phosgen generators, thionyl chloride, phosphoryl chloride, phosphine, hydrogen sulfide and many other fun chemicals.
LC50 for acetic anhydride is 1,000 ppm/4h, while LC50 for ketene is 300ppm/1min (0.08ppm/1h), just 10 000 times lower. This one should be used only in a well ventilated hood with a gas filter, because without the filter a leakage will kill someone else.
Totaly agree that phenylacetic acid + acetic acid is the easiest and safest way with a good yield of P2P. And AFAIK phenylethanol is not controlled in any way, so you can just go straight via hypochlorite. And even if the phenylethanol is banned - you can use styrene to get either phenylethanol via something like anti-Markovnikov halobromination or Willgerodt-Kindler, so why the hell anyone would even think about handing ketene?
Odor threshold for ketene is about 12 ppm, so you need 30 minutes to become completely dead without noticing the odor.

[Edited on 20-4-2015 by byko3y]

karlos³ - 19-4-2015 at 21:21

I would say the easiest and safest way is to reduce 1-phenyl-2-nitropropene, also very great yielding?

byko3y - 19-4-2015 at 23:13

Yes, I'm just wondering why it is not on the DEA precursors list... but who does sell it? I can't seem to find any major chemical provider who sells P2NP, while you can get a relatively cheap nitroethane after filling end user declaration ;)
And nitroethane synthesis is a pain in the ass, while you can reach the P2P in 3 steps using 100% OTC chemicals. So basically we end up in the 1995 when you could just purcahse the goddamn P2P.

CuReUS - 20-4-2015 at 05:12

Quote: Originally posted by byko3y  

And AFAIK phenylethanol is not controlled in any way, so you can just go straight via hypochlorite.

how ? I thought hypochlorite was only strong enough to oxidise it to aldehyde.
Quote:
you can use styrene to get either phenylethanol via something like anti-Markovnikov halobromination

even if you do anti marko using peroxide and HBr ,in the hydrolysis step,the carbocation will again form at the benzylic position.You could do hydroboration oxidation though.wonder from where you would get borane;)

byko3y - 20-4-2015 at 08:46

Hypochlorites give carboxylic acids as a thermodynamically favored product.
On primary carbons there's no carbocations, because those would be to unstable to form. Primary halide undergoes only Sn2 reaction, for this reason primary alkyl halide, benzyl halide, allyl halide, etc are the best alkylating agents.
Feel free to proof me wrong.

CuReUS - 21-4-2015 at 03:13

Quote: Originally posted by byko3y  
Hypochlorites give carboxylic acids as a thermodynamically favored product.

reference ?
Quote:
On primary carbons there's no carbocations, because those would be to unstable to form. Primary halide undergoes only Sn2 reaction

there will be a rearrangement

Templar - 21-4-2015 at 07:21

Quote: Originally posted by Cou  
How is this not in detritus?


While you're at it, you can confine yourself there was well. Science is still science, regardless if the "state" deems it to be "evil".

Ketene is not fun to play with. Aside from its high toxicity and probably carcinogenic nature, the coils of nichrome used need to be cleaned regularly due to pyrolysis products and carbon that deposits on it from side reactions with the acetone.

Purging the apparatus, opening it, cleaning carbon off nichrome, and then resuming. There is high potential for exposure.

Maybe the platinum wire method could be cleaned by simply running current through it while air is blown over it, or oxygen.

I never found out how well the sulfur/bromine and sodium acetate method for acetic anhydride worked. Cool reaction, but probably quite messy.

DJF90 - 21-4-2015 at 09:07

Quote: Originally posted by byko3y  

On primary carbons there's no carbocations, because those would be to unstable to form. Primary halide undergoes only Sn2 reaction, for this reason primary alkyl halide, benzyl halide, allyl halide, etc are the best alkylating agents.
Feel free to proof me wrong.


Under typical reaction conditions, the SN2 reaction is greatly favoured over the SN1 pathway. This does not mean that both cannot occur simultaneously, just that the rate of the SN2 pathway is much much faster. Itis worth noting that CH3+ and CH5+ have both been observed experimentally, but under very different conditions compared to what is employed for a typical nucleophilic displacement reaction. Benzylic and allylic halides are great electrophiles because not only are they primary halides, they are also activated enough to undergo the SN1 pathway, and in the case of allylic halides, an SN2' pathway also exists.
Quote: Originally posted by CuReUS  

there will be a rearrangement


No there won't, but under basic conditions you may observe E2 elimination leading back to styrene...

CuReUS - 22-4-2015 at 03:21

I always have this confusion.Why won't there be a rearrangement. ?
suppose you had a primary halide with a tertiary carbon next to it.when you hydrolyse it,wont you end up with a tertiary alcohol instead of a primary one. ?
no take the case of phenyl ethy lbromide.When you hydrolyse it,the primary carbocation formed will rearrange to a more stable benzyl carbocation,and you will end up with a secondary alcohol instead of the expected product

DJF90 - 22-4-2015 at 03:34

I suspect it depends largely on the conditions for hydrolysis, and is probably substrate specific. There should be very little primary carbocation formed from phenethyl bromide (unless you're using a halophilic lewis acid like Ag+), although I suspect you will see minor quantities of 1-phenylethanol from the benzylic carbocation (via 1,2-hydride shift) I would expect the SN2 pathway to be the dominant one but wouldn't be surprised if styrene formed as a significant byproduct (via E2 pathway).

[Edited on 22-4-2015 by DJF90]

byko3y - 22-4-2015 at 04:20

CuReUS, do you know what Sn1 and Sn2 are? Because it looks like you don't.
Do you have a real-world example of a primary halide with a ternary carbon adjacent, which rearranges on a hydrolysis?
UPD: and you wanted a reference for alcohol oxidation to acid, here it is https://www.erowid.org/archive/rhodium/chemistry/ether2ester...

[Edited on 22-4-2015 by byko3y]

morganbw - 22-4-2015 at 18:15

Quote: Originally posted by byko3y  
CuReUS, Because it looks like you don't.

[Edited on 22-4-2015 by byko3y]


Behave,
it is better to give gentle guidance.
None of us know all.

CuReUS - 18-5-2015 at 09:02

while searching for a method to convert aryl halides to phenols,I stumbled upon this old hive thread,where rhodium and other bees discussed about making a pseudo 2C-B.
http://chemistry.mdma.ch/hiveboard/serious/000122771.html
although a lot of input along with a ton of reference was given,I think they overlooked somethings.
Quote:
Rhodium
Administrator posted 11-27-98 02:05 PM
--------------------------------------------------------------------------------
Okay, thanks. My original thinking shrunk down to this approach:
(a) Nitrobenzene (I) ==Brominate==>
(b) 3,5-Dibromo-nitrobenzene (II) ==NaOMe=>
(c) 3,5-Dimetoxy-nitrobenzene (III)

1.rhodium suggested substitution of the dibromo with dimethoxy with NaOMe.But the bromine atoms are meta to the NO2,so the e-withdrawing effect of the nitro group should not work,right ?

2.drone 342,who was very active in the discussion,was excited that he had come up with a synthesis,by nitrating a phenethylamine,followed by bromination,methoxylation,reduction of the nitro,diazotisation followed by CuBr
Quote:
Here's a whole new approach, complete with gleanings from Beilstein:

1) nitration of phenethylamine with HNO3 and H2SO4
2)bromination using FeBr2
3)methoxylation, using CuBr as a catalyst, DMF as the solvent, and MeOH as the reagent. 110 deg C, 6 h, 95% yields
4)Formation of a diazonium complex, follwed by the Sandmeyer reduction to convert the nitro into a bromo substituent in a one-pot-shot
That's it! That's all there is to it! 4 Steps! Now that's good chemistry! I guess I may have been to hasty when I said it'll never be as easy as its 2,5-counterpart. I underestimated myself. Okay, maybe the last step constitutes 5 steps, but they're easy steps to do!
-drone #342

drone 342
Member posted 11-28-98 03:06 PM

but I have two questions
1.while methoxylation,is there a chance that the side chain amine might get methylated(as MeOH is used)
2.while diazotising,the side chain amine should convert to OH,shouldn't it ?
rhodium seemed to think so too
Quote:
Rhodium
Administrator posted 12-13-98 10:10 PM
--------------------------------------------------------------------------------
But the nitration of PEA aren't going to be selective at the 4-position, or? And don't you think the aliphatic amine needs to be protected before going through all those steps?

but drone was confident(or should I say too confident)
Quote:
drone 342
Member posted 12-15-98 02:49 PM
--------------------------------------------------------------------------------
Nitration *can* be selective, and in fact, it is fairly so using the techniques described in the methods I listed -- provided a person is careful in their nitration, the para position is much more favored than ortho. The amine would not have to be protected at all, as far as I can see; nitration doesn hurt it, bromination doesn hurt it, the aromatic substitution-elimination won't hurt it, reduction is obviously safe, and even the last step is one pertaining to aryl amines. So, it should be just fine hanging out there.
-drone #342


[Edited on 18-5-2015 by CuReUS]

byko3y - 25-5-2015 at 16:33

1. It's hard to perform deactivated aromitics halogenation, and even harded to do that with heavily deactivated aromatic, which is a bromonitrobenzene.
2. >bromination using FeBr2
Bromination of deactivated nitro-aromatic with amino-group will make a huge mess. And there's also a benzylic carbon, that is much more susceptible to halogenation.
Doing nitration and halogenation on such an unsubstituted ring will lead to a lot of isomers. Toluene nitration gives close to 7:4 ratio of ortho to para isomers most of the times.
Diazotation can lead to phenols, as well as halobenzenes in case of sandmeyer reaction, and also thiophenols, and even can be aminated with primary-secondary amine.
Also, I've tried to look at some of his nitration references and I see no nitration there.

CuReUS - 26-5-2015 at 00:58

yes byko,that's exactly what I thought.you seem to have read my mind:)
I find it funny and strange at the same time that they struggled so much(Rhodium himself)to make a compound that can be made in four steps(according to me),all steps giving yields >90%,starting from resorcinol methyl ether(you could start from resorcinol and methylate that,but both are dirt cheap,resorcinol is 8$/kg while the ether is 10$/kg,so I think it would be bettter to just buy it instead of working with dimethyl sulphate).but I have to admit I used reactions discovered recently,which were not known in 1998.you could still make it with simple reactions,but in that case six steps are needed and it gives lesser yields(50-70%).


[Edited on 26-5-2015 by CuReUS]

byko3y - 26-5-2015 at 01:42

I have no idea about how you are going to do 3,5-diMeO-alkylbenzene, because resorcinol can't be substituted at meta position, and nucleuphilic substitution doesn't work on meta to nitro position, as you've already noticed.

CuReUS - 26-5-2015 at 02:34

well byko,organic chemistry is full of reactions that give unexpected results,you just have to patient enough to find them;)
I don't think posting the route here would be a good idea,as others might misinterpret it as drug discussion,but it can be done.

[Edited on 26-5-2015 by CuReUS]

Morkva - 26-5-2015 at 04:13

Cureus, you seem to have a strainge confidence, an odd swagger!

Might I suggest you are possessed by demons?

An "oversight by meth cooks" is a suggestive phrase: these could not be a homogenous group: a club, cabal, a guild, or union. Their strategy is not fixed in their rule-book. Am I splitting hairs? Yes, of course, but the point remains, there can be no such "oversight by meth cooks".

Unfortunately, the substance is one that destroys many lives - and unfortunately, there is absolutely nothing you can do to stop it. The bottom line is the substance is a construction of three atoms of carbon, one atom of amine, and the benzene ring. The situation is similar to American prohibition in the 1920's, which failed for no other reason than because the preparation (of ethyl alcohol) is to let sugar-water rot. Though more involved, the cooks' ingredients and their plausible combinations are potentially infinite given the simplicity of the desired molecule! If more citizens, or lawmakers, were aware of this simple conclusion, we could see a more benign technique for dealing with those souls. These situations are not fully analogous - but organized crime found other business, as far as we know, though having flourished it can not be eradicated, and poisonous contaminants in alcohol cause less of a human toll (for better or worse).

I hesitate to provide concrete examples, but a vague one illustrates. Direct CH functionalization is a technique in chemistry. It may be possible to attach acetone, or even isopropyl amine itself directly to benzene. Phenylalanine, which can probably be cleaved to phenyl acetic acid, is present in some plants and animals. See here, the principle is immutable: simple product means a diversity of practical routes: the unenforcable laws breed contempt for the law as a whole, and for society: contempt for law and society causes social unrest, and benefits 1. the owners of prisons and attached industries such as manufacturers of supplies, builders, iron smiths specialized in shackles, and law enforcement (if viewed as an industry: sure, well intentioned as a whole, but economists, entrepreneurs etc. probably slip in.) and 2. the rich, fearing pitchforks of the educated and otherwise capable, who would rather distract and dazzle the aspiring communists with crime, and feed them into what is unlikely to become in America, but was, in the Soviet Union under Stalin a system of slave labor - from what I have read the result of an irreproachable Party, censorship, lack of transparency, and poor education of the liberated peasants.

[Edited on 26-5-2015 by Morkva]

zed - 29-5-2015 at 15:03

Hnuh? Acetonitrile isn't a hard get. And, while Benzyl Chloride isn't fun to work with, it isn't hard to use it in a Grignard. Of more concern, would be comments made about the procedure, by my erstwhile buddy Dr. Death..."Nasty" and "Miserable", come to mind.

CuReUS - 29-5-2015 at 23:51

Quote: Originally posted by zed  
Hnuh? Acetonitrile isn't a hard get.

it isn't hard to get,but it isn't cheap either
Quote:
And, while Benzyl Chloride isn't fun to work with, it isn't hard to use it in a Grignard.

true,but from where do you plan to get Mg turnings for the grignard.DEA has already put it on the watchlist
Quote:
Of more concern, would be comments made about the procedure, by my erstwhile buddy Dr. Death..."Nasty" and "Miserable", come to mind.

interesting character,I wonder who he is ?

zed - 7-6-2015 at 12:19

I'm not saying. It is unlikely, but possible, that Dr.Death has survived these many years, since our last encounter. If so, I'm disinclined to cause trouble for him.

Can't get Mg turnings? Find another hobby.

byko3y - 7-6-2015 at 12:32

http://www.ebay.com/bhp/magnesium-anode
And I would be really glad if someone have tested the acetonitrile preparation. Without ussage of inorganic cyanides, of course.
I'm sure chinese could make acetonitrile for price not higher than 5$ per 1L. The reason why it's so costly is because you are not making it. I'm talking to everybody here who thinks acetonitrile is costly.

karlos³ - 7-6-2015 at 13:30

Some computer parts are made of pure Mg, did you really meant to say Mg turnings are hard to get ANYwhere?? I cant think of much else that is nearly as easy to get than magnesium...
Acetonitrile in my country costs about 30€ per liter, and its analytical grade, and that from a reseller(so a bit more expensive).

byko3y - 7-6-2015 at 15:48

30$ is relatively expensive for a solvent. I would be glad to see some success storries about acetonitrile and pyridine preparation, but for some reason I don't see even failures.
The life of many home chemists would be more peacefull if they had some well-developed protocols. And nowadays those, who actually could develop the synthesis, just don't care.

CuReUS - 22-7-2015 at 03:22

I have a few questions that have been bothering me

1.In total synthesis 2,strike describes the conversion of safrole to the bromo derivative by reacting the alkene with HBr(from NaBr+H2SO4) at reflux.
won't the HBr or H2SO4 cleave the MD ether ?

2.Suppose someone does a formylation reaction on catecol to make the corresponding benzaldehyde.The next step would be to make the MD bridge using DCM or DBM.all the methods I have seen use strong bases at high temp.Isn't there a chance of a cannizaro reaction.

3.I found out that safrole is carcinogenic.How were people mad enough to deliberately ingest a cancer causing substance(I guess MDMA wouldn't have been carcinogenic,but still.)

Scr0t - 22-7-2015 at 04:11

Quote: Originally posted by CuReUS  

The next step would be to make the MD bridge using DCM or DBM.all the methods I have seen use strong bases at high temp.

MeI2 in DMSO at ~80°C with K2CO3 as the base works well enough.
Quote: Originally posted by CuReUS  

I found out that safrole is carcinogenic.How were people mad enough to deliberately ingest a cancer causing substance(I guess MDMA wouldn't have been carcinogenic,but still.)

Maybe they didn't know.
There's all sorts of carcinogenic compounds naturally occurring in our diet or are formed during its preparation e.g. acrylamide in fried foods.

CuReUS - 22-7-2015 at 05:44

Quote:
MeI2 in DMSO at ~80°C with K2CO3 as the base works well enough.

are you talking about this
http://www.sciencemadness.org/talk/viewthread.php?tid=11786#...
Quote:
Maybe they didn't know.

Its not a recent finding
Quote:
In 1960, the FDA banned the food use of safrole -- the main component in sassafras root bark -- when the volatile compound was found to cause cancer in animals.

from http://articles.latimes.com/2005/feb/14/health/he-supp14

Scr0t - 27-7-2015 at 12:38

Quote:
are you talking about this
http://www.sciencemadness.org/talk/viewthread.php?tid=11786#...

No, something I tried when making myristicinaldehyde.
Quote:

Its not a recent finding

Yeah, I know. Since you didn't say who or when these "people" were it seemed like an adequate response.