Author Topic: future of safrole  (Read 25296 times)

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homeslice

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Ive said it above, i think more than once,...
« Reply #60 on: July 12, 2004, 08:20:00 PM »
Ive said it above, i think more than once, that i dont think the eugenol demethylation/remethylation procedure is as hard as ppl say it is. Its just another example of the information being there and everyone theorizing about it, but noone testing it out. Any of the "small scale" cooks out there that have been around for a couple of years probably have drums of sassy in the shed in their back yards, so they could care less about eugenol. I think one bee out there is going to break it all open, possibly writing a newbee-friendly pictorial writeup similar to the wackers and aminations on how to demethy/remethylate. Its probably going to be a newbee as the older bees are the ones with the drums in their toolshed.  :)


armageddon

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too difficult
« Reply #61 on: July 13, 2004, 12:52:00 AM »
Hi! I don't think the eugenol demethylation/methylenation is as easy and suited for "backyard chemistry" as you think: especially the demethylation reactions require pyridine, nitrobenzene, lithium diphenylphosphinate or similar (not very OTC) chemicals, and the only "simple" methylenation reactions are those using a PTC (DMSO isn't exactly one of the compounds every newbee has access to  :) ) - and these difficulties in obtaining the needed chems, in connection with the multiple bad-yielding steps (at least with the routes that use more common chemicals, i.e. using DCM instead of DBM), are the reasons why unexperienced newbees might not be able to arrive at satisfactory results with this route...

(and I think the more xperienced bees would rather use said reagents in the synthesis of some 3,4,5-trimethoxybenzaldehyde rather than making piperonal..  ;) )

..But maybe the LiCl2/DMF eugenol demethylation, together with a KF catalyzed methylenation, would be the way to go for making "homemade" safrole? The reagents seem to be a *lot* more OTC than DMSO/DBM/pyridine and so on...

Greetz A


ApprenticeCook

  • Guest
Re: especially the demethylation reactions...
« Reply #62 on: July 13, 2004, 07:42:00 AM »

especially the demethylation reactions require pyridine, nitrobenzene, lithium diphenylphosphinate or similar (not very OTC) chemicals


What about the AlI3 method from rhods site, easy enough and OTC.


methylenation reactions are those using a PTC (DMSO isn't exactly one of the compounds every newbee has access to )


DMSO is not as hard sourced as it is made out to be. Would DMSO work as the PTC for such reaction?

DIM and DBM can be made from DCM via NaI/NaBr in warm acetone, making a better yielding methylation rxn than by using DCM. (that right?? DCM + 2NaI -->warm acetone--> DIM + 2NaCl sorry cant remeber where i read that)

Personally have not tried it yet but sassy supplies are running a bit low so ill get around to putting my money where my mouth is some time soon. And safe suppliers are running thin...

All up Al foil and I2 are easy enough and DCM, NaI, acetone are easy enough, only problem is PTC, someone come up with something on the PTC req and we will be set...

-AC




methymouse

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fabric softener
« Reply #63 on: July 13, 2004, 08:02:00 AM »
Most fabric softeners are supposed to work as PTC's.  Just look for one with a "cationic sufactant" and little else in it.  UTFSE for "fabric softener".


ApprenticeCook

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methylmouse, seen that many times from ...
« Reply #64 on: July 13, 2004, 08:54:00 AM »
methylmouse, seen that many times from utfse'ing for otc ptc's but i was looking for another way...

how would one go about synth of tetrabutylammonium iodide?
NH4I + 4BuOH -->H+??-->NBu4I + 4H2O ??
doubt it... but would be nice. i tried google for it but came up with no info on synth only use. UTFSE here came up wth nothing direct on synth.

Otherwise it looks like my safrole will come out all silky and smooth, and what a smell...... safrole + fabric softner....

-AC


Rhodium

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Nicodem

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didecildimethylammonium chloride?
« Reply #66 on: July 13, 2004, 09:12:00 AM »
Fabric softeners sucks as PTC, because they are very long chain quarternary amines. This makes them much more soluble in the organic phase than water slowing the transition beetwen the two. Not to mention the enourmous molecular mass making a 5 mol% weight more than the  reactant.

What about didecildimethylammonium chloride?
It's OTC and available all over the world as a disinfectant. It has a similar molecular mass like TBAB. Does anybee have any experience with it?


armageddon

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misunderstood?
« Reply #67 on: July 13, 2004, 09:53:00 PM »
Hi! In my above post I wrote:

"the only "simple" methylenation reactions are those using a PTC (DMSO isn't exactly one of the compounds every newbee has access to)"

On this a bit of clarification  :) : I referred to DMSO being used as a solvent in connection with DCM/KOH (500ml for 110g catechol are used) - the PTC reaction doesn't need DMSO, nor did I mean using DMSO as kind of PTC (sorry for expressing myself rather unclear, App.Cook..)

But what about using potassium fluoride catalyst with DCM in DMF solvent? Looks pretty OTC to me, too - at least more newbee-friendly than DMSO. And yields are around 90% of theory (calculated from catechol). No PTC needed, and the demethylation can also bee done w/o PTC in case one has already some DMF at hand - lithium chloride is not that hard to get at all. (but then again, yields are only 50% with LiCl2) - seen from this point of view, the only difficulty would be aquiring some DMF..

Greetz A


ApprenticeCook

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Rhodium......... isnt there an easier ...
« Reply #68 on: July 14, 2004, 07:51:00 AM »
Rhodium......... isnt there an easier way................
the 3 chems req for those methods are not the easiest to source....

armageddon, ahhh no i see.... sorry bout that, didnt read it carefull enough...

DMF solvent? Looks pretty OTC to me


Nope, DMF is not an easy thing to get in oz, cat 2 on our restricted chems list. DMSO is not on any of our restricted chems list in oz so its easy enough to get, just got to look hard enough in the right places.
So no PTC req? whats your reference for this? Sounds interesting if one can get the DMF and KF.

Nicoderm, im looking at the PTC your talking about... does anyone know anything about this?

-AC




armageddon

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good ole Rhodium's
« Reply #69 on: July 15, 2004, 02:40:00 AM »
Hi!

My reference for the DMF/KF methylenation is

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation-kf-ch2x2.html

....  ;)

"To date, the ionizing base for catechols has always been an alkoxide, alkali hydroxide or carbonate. Our method offers an alternative route to methylenation involving the use of an alkali metal fluoride and DMF via an H-bonding mechanism. The method is fast, efficient, provides high recoverable yields and avoids strongly basic conditions. Furthermore, it would seem that by using caesium fluoride and dichloromethane, intermolecular condensations may be kept to a minimum. These results offer further striking evidence for the potential general significance of the method of H-bond assisted reactions to synthetic chemistry."
(Yield for 3,4-dihydroxy-BA->piperonal is 90%, for catechol->benzo-1,3-dioxole 80%)

 (every time again surprising what gems Rhods site contains)

And DMF can be made by heating dimethylammonium formate - which in turn can be made via a tweaked methylamine procedure (usually these methods use certain tricks to suppress dimethylamine formation and favor the formation of MeAmine - for example using excess ammonium chloride, keep temp. below certain level. I would guess that a lot of dimethylamine would be made if these conditions were "reverted", i.e. heating to over 190°C or using excess formaldehyde/hexamine/whatever..). The so obtained diMeAm*HCl is easily converted to the formate salt by dripping a amine*HCl solution onto solid NaOH and directing the gaseous diMeAm (stinks heavily, like dog urine!!) into dil. formic acid, then concentrating the formate salt solution under vacuum to get crystalline diMeAm-formate..

But this would mean having to perform three time-consuming (and maybe not-so-high yielding) steps only to get the solvent. Much work.

So maybe the PTC route is the better choice - if one can get hold of a good PTC...

(BTW I think KF is quite easy to obtain in large quantities, at least it is not watched - or is it? And if lithium chloride is obtainable, too - make LOADS of DMF, demethylate eugenol with DMF/LiCl2 and methylenate with KF/DMF, and ready is the OTC route, unluckily involving several days of DMF production  ::)  - but Eugenol, DCM, hexamine, HCl, alcohol, NH4Cl, LiCl2, KF and some formic acid is a manageable "to-buy-list", even if OTCness is desired - right?)

Greetz A


Rhodium

  • Guest
Methylenations
« Reply #70 on: July 15, 2004, 06:30:00 AM »
But this would mean having to perform three time-consuming (and maybe not-so-high yielding) steps only to get the solvent. Much work.

The authors also informs us that "a number of workers have reported the high-yield methylenation of several substituted catechols using dimethylsulphoxide on N,N-dimethylformamide as solvent", so I believe that you can use any dipolar aprotic solvent here, not only DMF. Try acetonitrile or DMSO if you have easier access to them than DMF.

So maybe the PTC route is the better choice - if one can get hold of a good PTC...

Polyethyleneglycols such as PEG-200 and PEG-400 are good PTC's if you cannot get any quaternary amine PTC's - but you should really have no problem with that -

UTFSE for "OTC PTC"



I think KF is quite easy to obtain in large quantities, at least it is not watched - or is it?

You might need to sign an "End user declaration" as it can be used in the prep of certain nerve agents:

Post 519153 (missing)

(Vitus_Verdegast: "Monitored for reagents used in chem weapons", Law and Order)


And if lithium chloride is obtainable, too - make LOADS of DMF, demethylate eugenol with DMF/LiCl2

Please note that lithium chloride has the formula LiCl and not LiCl2 as you have written in a few of your latest posts.


ApprenticeCook

  • Guest
every time again surprising what gems Rhods...
« Reply #71 on: July 15, 2004, 07:21:00 AM »
every time again surprising what gems Rhods site contains
Tis isnt it.... never even know some of these things are there coz i just read straight over it.... tisk tisk tisk.

And DMF can be made by heating dimethylammonium formate
Sounds good...
made via a tweaked methylamine procedure
Sounds nice... how would you seperate diMeAm and the now impurity MeAm???
Or would you bother? if you could turn the tables of yields far enough you would get a end product of methylformamide and DMF which could be seperated by disto??? hmmmm.....
theres this recently from a newbee, watch for answers...

Post 519452

(r2e3: "extracting dimethylamine hydrochoride", Newbee Forum)

This is the answer (i think!)-->

If formaldehyde is present in excess, at least some of the methylamine is converted to dimethylamine. If too little formaldehyde is present, the methyleneimine polymerizes to its trimer, (CH2=NH)3. Trimethylamine is never formed, as long as the temperature of the solution never exceeds 110°C. With an excess (4 moles) of formaldehyde, enough water and a reflux temperature of 115°C, dimethylamine is the main product, as the temperature rises, more dimethylamine is formed. Dry heating of paraformaldehyde and ammonium chloride produces trimethylamine through reaction of dimethylamine with formaldehyde, giving rise to tetramethylmethylenediamine and formic acid, and the base further reacts with HCl, giving trimethylamine hydrochloride and methyleneimine hydrochloride. A mixture of HMTA and HCl boils between 105 and 110°C, while NH4Cl/CH2O boils at 115°C. No temperature control is really necessary in the former case, as long as your heating plate isn't too hot. If the reaction is carried out at a lower temperature, less dimethylamine is formed, and the yield is higher. Vacuum reflux and distillation can yield at least 95% yield, in contrast to the 45% gotten at 104°C.


What is thought??? so keeping it a wet reflux of 4 moles of formaldehyde to ammonium chloride will produce a nice yield of dimethylamine for use as described.... and running the freebase through formic acid (dilute?? i would say rather conc instead....) to produce formate salt then heating to dehydrate to the formamide(s).

As for KF i dont think it is... not on any of my lists....
As for liCl only LAH and Li metal is on the list for Oz...
The process to make DMF shouldnt be too difficult and yields would be reasonable enough to sustain production, the purchase of DMF in oz is a no go... so this sounds good to me...

-AC




armageddon

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yep that's what I was thinking
« Reply #72 on: July 15, 2004, 09:16:00 AM »
Hi!

Nice - you found a post describing more exactly what I was thinking - cool to read that my above rambling wasn't that wrong (where did you copy this text passage from? I hope the source is reliable?)...  ;D

for separation of mono- and dimethylamine just extract the solid amine*HCl mixture several times by boiling with chloroform (maybe DCM works too, dunno), the combined CHCl3 extracts contain the dimethylamine, leftover is pure methylamine..




Rhodium: this would mean DMF isn't a must? But what's the rationale behind using it? Is plain formamide aprotic/dipolar btw?

(D'oh! Li(1)Cl of course!  :-[ )

And about PEGs as PTCs: What about this one - a *really* OTC approach?


Methylene chloride is, of course, the halide of choice for large-scale preparation, and Laskina12 worked out a procedure for methylenating catechol with this halide at atmospheric pressure. With ethylene glycol as solvent, sodium carbonate as base, and with a temperature of 122-124°C, the yield was 38-43% after 8-12 hr. To maintain the high temperature, methylene chloride was introduced gradually.(...)
References
(...)
12)

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.laskina-2.html

"



(taken from

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylenation.bonthrone-cornforth.html

- BTW READ THIS ONE, App.Cook!)

I like these russian methods using automatic separators/traps and other fancy glassware, together with rather easily obtained chemicals - elegance and simplicity, together with additional economical benefits and a lot of fancy lab-tech to play with/lots of possibilities for tweaking the rxn/lots of fun for the little child inside me.. :)

Greetz A


ApprenticeCook

  • Guest
Good source
« Reply #73 on: July 15, 2004, 10:10:00 AM »
Its on the notes of the methylamine FAQ from rhodiums site...

https://www.thevespiary.org/rhodium/Rhodium/chemistry/methylamine.html



Well the DMF synth sounds easy enough, apart from making HUGE volumes of it, ie several litres, would be a pain...

What about the demthylation... could there be another way to do this apart from LiCl and AlI3 (req ptc)?
LiCl method shows a pain with the volumes and amounts of addition req.... time is rather lengthy and yields are somewhat eh....

A solution of 354 ml (2.30 mmol) of eugenol and 292 g (6.89 mol) of lithium chloride in 3.7 L of N,N-dimethylformamide was refluxed for a total of 44 hours (h), and after 4 h, 18 h and then 7 h, a further 292 g (6.89 mol) of lithium chloride were added each time. (!!!!) After cooling, 2 L of toluene were added and the resultant precipitate was filtered off with suction and extracted with toluene. The organic extracts were combined and concentrated on a rotary evaporator. After flash chromatography (ether/pentane, 1:1, Rf = 0.37) on silica gel, 173 g (50%) of 4-allylcatechol were obtained


For 354mL eugenol you need to add 3.7L DMF and 1168g LiCl is req?!?!? or am i reading this wrong......

As for PTC for AlI3 method, polyethylene glycol???
Could the PEG in auto coolant be used? (dont know type of PEG sorry)
EDIT: UTF google and answered my question... PEG-200 = polyethylene dimethyl ether correct?
so polyethylene glycol could be made to PEG-DME by methanol and a few drops of conc sulphuric acid catalyst? i dont know im just spurting shit coz im so tired... ill look at this more after i get some sleep. Night all.

Armageddon, the methylenation reaction is well covered and shouldnt be a problem, but the demethylation.... well...
As i said above, hope im reading it wrong because using ~1.1Kg's LiCl per ~350mL of eugenol in 3.7L of DMF is not great... and a 50% yield for this? nah....

-AC

EDIT: Couldnt help myself....
TBAB - as you said rhodium... TBAB by tributylamine + butylbromide = TBAB...... hmmmm we only need a tiny bit so.....
NH4Br + Butanal --> Butanimene
Butanimene + 2Butanal --> Tributylamine bromide
Would this work the same as -
"Dry heating of paraformaldehyde and ammonium chloride produces trimethylamine"
As per the methylamine synth??

Butylbromide would just simply have to be bought or made from n-butanol? as would the butanal from the previous step or oxidised from n-butanol.

So buy n-butanol, oxidise some to butanal and covert some to butylbromide and should be right to go?

-AC (seriously, going to bed now...)




armageddon

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typo/correction
« Reply #74 on: July 15, 2004, 11:12:00 AM »
I once read somewhere (maybe it was even in this thread) that the mentioned writeup has several typos - 4h, 18h and then 7h isn't exactly what I call linear timetable!

The right text should read:


Demethylation of Eugenol to 4-allylpyrocatechol with LiCl/DMF

LiCl (292 g, 6.89 mol) was added to a solution of eugenol (354 mL, 2.30 mmol) in DMF (3.7 L), and the mixture was refluxed for 44 h, with additional portions of LiCl (292 g, 6.89 mol) being added after 4 h, 22 h and 29 h. The reaction mixture was allowed to cool down to room temp., and diluted with toluene (2 L). The formed precipitate was filtered off and washed with toluene, the washings were combined with the organic solution and concentrated in a rotary evaporator. Silica-gel FC (Et2O/pentane, 1:1, Rf = 0.37) provided 4-allylpyrocatechol (173 g, 50%).



Hmm, 354ml eugenol being 2.3mmol?? Must again be some typo..
And I agree in that the amounts of reagents are more suited for preparing analytical samples!  :(


But luckily, I have this demethylation procedure on my HD  :)  (but it's of course available at Rhod's too):


2,3-dimethoxybenzaldehyde (1.0g; 6.0mmol) and LiCl (0.76g; 18mmol) are heated in boiling DMF (10ml), the reaction being monitored by GLC (2m SE30 packed column). When the starting material has disappeared (22h), 10% aequous NaOH solution (30ml) is added, the solution is washed with Et2O (2x25ml), then acidified with 10% aequous HCl (50ml) and extacted with Et2O (2x25ml). The organic phase is washed with brine (30ml) dried (Na2SO4) and concentrated in a rotavapor; yield {of 2-hydroxy-3-methoxy-benzaldehyde} 0.88g (98%); mp 42°C, mixture MP with a commercial sample (Aldrich): 42°C."


full text:

https://www.thevespiary.org/rhodium/Rhodium/pdf/ether.cleavage.licl-dmf.pdf



Still much (~3.8L) DMF is used, but at least not >27 moles LiCl any more - only ~290g necessary for 2.3 moles of eugenol..

I wonder if the above demethylation won't do anything to eugenol - or if it will work just fine (with 2,3-diMeO stuff, the meta-located MeO is cleaved, but with m-MeO-p-OH compounds, it could be different..)

(does anybody know?)

Greetz A


armageddon

  • Guest
other demethylation procedures
« Reply #75 on: July 15, 2004, 12:53:00 PM »
Hi!

Just searched a few minutes - there are many other demethylations:

a) SIBX-mediated oxidation (SIBX is a mixture of 22 parts benzoic acid, 29 parts isopthalic acid and 49 parts o-iodoxybenzoic acid)

https://www.thevespiary.org/rhodium/Rhodium/pdf/eugenol.demethylation.sibx.pdf

, especially entry 4a in table 5 (page 3), eugenol demethylation with 77% yield...

b) Ni/Zn-mediated dealkylation

https://www.thevespiary.org/rhodium/Rhodium/pdf/ether.cleavage.zn-nicl2.pdf


(It seems that a nitrogen atom has to be present in the molecule to be dealkylated; maybe usable when first 3-hydroxy-4-methoxy-phenyl-2-nitropropene would be made through Knoevenagel/EtNO2, followed by borohydride reduction to the nitropropane, and then by cleavage of the 4-MeO and methylenation to arrive at 3,4-methylenedioxyphenyl-2-nitropropane? Sounds nice - but will it work? Or what about making 3-OH-4-MeO-P2P oxime, then demethylation/methylenation?)

c) selective mono- or di-demethylation using methanesulfonic acid (CH3SO3H) and microwaves

https://www.thevespiary.org/rhodium/Rhodium/pdf/ether.cleavage.msoh.mw.pdf



d) demethylation with TMS/I (trimethylsilane/iodine; -> in situ formation of trimethylsilyl iodide)

https://www.thevespiary.org/rhodium/Rhodium/pdf/ether.cleavage.tms-i.pdf




(...)




Armageddon, the methylenation reaction is well covered and shouldnt be a problem, but the demethylation.... well...

Huh?  ;)  Simply everything about this topic is covered in

https://www.thevespiary.org/rhodium/Rhodium/pdf/ether.dealkylation.review.pdf

...

(nothing more to add)


greetz A


amalgum

  • Guest
Look people, methyleneation isn't the problem.
« Reply #76 on: July 16, 2004, 11:58:00 AM »
Look people, methyleneation isn't the problem.  It's easy and OTC, and according to several patents SWIM has looked at you don't even need DMSO or DMF.  Methyleneation can be done with alkali metal hydroxides in plain ol' H2O.  Beleive it or not.  Couple that with an already made amine thats protected and a salt and theres no need for a PTC. That amine being 3,4-HO-methylamph for those in the know about my endeavours in that area (and boy it's looking like SWIM is going to have some juicy long-awaited details very soon, bwahahahaha).
Really the problem is, is there is no problem.  It's just time we stop griping about a safrole problem and do what we do best, that is work around it.  The hardest part is just actually doing it.
Right now eugenol to me is looking to be a very viable 3,4-methoxylated amphetamine precursor, as well as viable starting point for both TMA's, and mescaline.  Screw safrole, we don't need it.


armageddon

  • Guest
not the only one
« Reply #77 on: July 16, 2004, 01:14:00 PM »
Right now eugenol to me is looking to be a very viable 3,4-methoxylated amphetamine precursor, as well as viable starting point for both TMA's, and mescaline.  Screw safrole, we don't need it.

What about vanillin?

Greetz A


amalgum

  • Guest
What about it? Yes it's a viable precursor as...
« Reply #78 on: July 17, 2004, 12:56:00 PM »
What about it? Yes it's a viable precursor as well, but above I meant isoeugenol oxidation by chromic acid or something similar, which gives vanillin.
But vanillin in SWIMS opinion would be more viable to get to mescaline than any amphetamine.  Mainly just because it is an aldehyde, and to SWIM it is less attractive to have to synthesize nitroethane to proceed from the aldehyde to nitropropene and so on.  Any other route would just add more steps than it'll be worth IMHO.  So as far as the amphetamines go like MDMA, it's probably within your best interest to start from an allyl- or propenylbenzene (aka eugenol/isoeugenol).

armageddon

  • Guest
probably right - but how 'bout sharing knowledge??
« Reply #79 on: July 17, 2004, 04:11:00 PM »
Yup, when the nitroethane has to be synthed by yourself, it may be advisable to avoid going via nitropropene->ketone->amine and probably easier to start with propenylbenzenes instead - but I would at any time prefer mescaline over MDMA  ;) ..

And vanillin hasn't only drawbacks (besides of requiring NE to arrive at amphetamines) - it usually is sold in "very pure" grade AT LEAST, whereas eugenol has to be distilled (several times maybe) to get a pure starting compound...

But your idea of first making the dihydroxy secondary amine and THEN methylenating it is pretty cool, dare I say - I would guess that my proposed "x-nitropropene -> x-nitropropane -> methylenation of x-nitropropane / reductive amination" will work too? Or is the nitro group more easily attacked (espcially with Zn/Ni), compared to the secondary amine protection you suggest?

Look people, methyleneation isn't the problem.  It's easy and OTC, and according to several patents SWIM has looked at you don't even need DMSO or DMF.  Methyleneation can be done with alkali metal hydroxides in plain ol' H2O.  Beleive it or not.

Actually it is hard to believe, because you didn't back up your statement with any facts or details..

(heaven can be coloured red by throwing open cans of red paint into the air - believe it or not!  ;D )

And yes, now it has been posted several times that the methylenation is well covered and no problem (why did some bee ask about it then?) - amalgum: how about sharing some of your knowledge by giving the patent numbers instead of just talking about having read'em!? Just writing down vague details isn't exactly what helps - and referencing to patent numbers is the simplest of all things!! Espacenet!

I mean: you know about a patent dealing with exactly the problem several bees seem to have (OTC and easy methylenation) - and don't share this knowledge??

...égoiste...

:)  A