Author Topic: DMF purfication question and vilsmeyer formylation  (Read 5768 times)

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Osmium

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Gattermann
« Reply #20 on: April 25, 2002, 01:38:00 AM »
There's another alternative: Gattermann

I seem to remember that you can formylate 1,4-diMeO-benzene in 70% yield.

Dissolve your precursor in a suitable solvent (toluene?), add Zn(CN)2, and bubble HCl through it. Not for the faint of heart, but it should work.

I'm not fat just horizontally disproportionate.

hest

  • Guest
Anaconto I don't think, you need something ...
« Reply #21 on: April 25, 2002, 02:40:00 AM »
Anaconto I don't think, you need something activating pare the the incomming aldehyde.

I'm Sure that Cn(Zn)2 works [edit Yes I mean Zn(CN)2 ;D  ;D  ]
From the bromocompound both BuLi and Grignard will do the job
Chloromethylation is also a way to doo it.
In tetrahedron 1993 1415-1434 they use P2O3Cl4  (and that is ??)and DMF at 100°C for 48houers

Antoncho

  • Guest
Oh, Hest!
« Reply #22 on: April 25, 2002, 03:46:00 AM »

Anaconto I don't think....I'm Sure that Cn(Zn)2 ...




Hest, this time you outspelled yourself, man! ;D  :)  ;D  ;)  (please, no offense! i don't intend to pick on you - it's just that your post really lifted my spirits when i read it :) )

As for the Gattermann - yes. But not for the "faint of heart" (what a splendid word collocation!), definitely.

I remember reading somewhere that triazine could bee used as a solid HCN substitute in this rxn, and also that it is much less toxic this way (?) - but, the possible source of triazine still remains a mystery for me.

They say it's like a soil desinfectant or herbicide of sort... well...

Antoncho


little_princess

  • Guest
I love to smell and taste my produced chemicals, ...
« Reply #23 on: April 25, 2002, 05:15:00 AM »
I love to smell and taste my produced chemicals, it is relatively safe to do so for neutral compound but not for highly toxic compound like HCN, and I haven't got a fumehood too. So I, like Antoncho, want to avoid the use of any compound with CN, so not KCN nor Zn(CN)2 for me.

mean , chloromethylation is such an otc procedure, but the consequent usage of KCN is really a bummer... if there was a way to turn a 2,5-diMeO-4-something-benzyl chloride into the corresponding benzaldehyde, that would bee a very appealing route for many non-professional bees. What do you say? Anyone else can help?

I wanna that too..

Personal I prefer the oxidation of the monobromide with hexamethyltetraamin(boil the bromide with HMTA in alcohol, then hydrolyse in acid wather) or turning the bromide into the acetat (boiling it in AcOH with NaOAc, then hydrolyse, then oxidise the alcohol )

I also used some DMSO oxidations to make the aldehyde, DMSO and CaCO3 at 100°C for a short time (5min??) i think.


Hest: can you give me much info on these reaction?
I don't understand the one with HMTA, if I chloromethylate bromo-1,4 benzene, and do that reaction, will I get 4 bromo 2,5 dmb?

thank you, lp

Rhodium

  • Guest
Tetrahedron article
« Reply #24 on: April 25, 2002, 05:18:00 AM »
Hest: Isn't that compound pyrophosphorylchloride (with the experimental in the formylations.html on my page).

hest

  • Guest
Right
« Reply #25 on: April 25, 2002, 05:40:00 AM »
Rhodium-Yes it is, I have no idear how to prepare it, but that can't bee that hard to find out.

Littel Prinses, you'r right, the HMTA turns an benzylhalogenide into an aldehyd it's caled the Sommelet reaction. Most chem. books will describe it.

little_princess

  • Guest
http://www.rhodium.ws/chemistry/dialkoxybenzaldehy...
« Reply #26 on: April 25, 2002, 06:11:00 AM »

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


 We have recently reported
the preparation of three symmetrical 2,5-dialkoxy- benzaldehydes (R = CH3CH2-, PhCH2- and HCCCH2-) via the formylation of 1,4-diethoxybenzene with
hexamethylenetetramine (HMTA)
((2a) Crozet, M. P.; Sabuco, J. F.; Tamburlin, I.; Barreau, M.; Giraud, L. Heterocycles 1993, 36, 45.
(2b) Ubeda, J. I.; Avendano, C.; Menendez, J. C.; Villacampa, M. Heterocycles 1994, 38, 2677.)

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


A mixture of 12,2 g of 2,6-xylenol (100 mmol), 14.0 g of HMTA (aka urotropine, hexamine or hexamethylenetetramine) (100 mmol) and 150 ml of
trifluoroacetic acid was heated at reflux (83-90 C) for 12 hrs. The product were concentr. and combined with 600 ml of ice water; the resulting mixture
was stirred 15 min, made basic with Na2CO3 and extracted with ether. Evapn of the ether soln left a yellow solid which was recryst. from CHCl3-pentane
to afford 14.3 g of 3,5-dimethyl-4-hydroxy-benzaldehyde mp
113°C

It seems we can do it with HMTA. More info from you hest will bee welcome, what about performing it on other bzd?

hest

  • Guest
Duff
« Reply #27 on: April 25, 2002, 06:46:00 AM »
This is two examples on the Duff reaction, it an annalog of the Reimer-Tiemann reaction. It only works on phenol's (it put's an aldehyde ortho to an phenol)
Wont work for dimethoxy-benzen.
(using TFA might change this ??)
Iff you want's to make 2,5-DMBA OTC, it would help to know with chemicals you have acces to.
hydroquinon ? Bromine ? DMF ? Mg ? dimethylsulphat ? Zn(CN)22 Solvents ? POCl3 PCl5 FormicAcid ? methylformiat? methanol?

little_princess

  • Guest
any hope?
« Reply #28 on: April 25, 2002, 08:13:00 AM »
...SECRET...

I can procure DMSO, HMTA, formaldehyde so I could chloromethylate but not make the nitrile, if 2,5-diMeO-4-something-benzyl chloride can be turned to the corresponding benzaldehyde like antoncho said it would be very cool.

Personal I prefer the oxidation of the monobromide with hexamethyltetraamin(boil the bromide with HMTA in alcohol, then hydrolyse in acid wather) or turning the bromide into the acetat (boiling it in AcOH with NaOAc, then hydrolyse, then oxidise the alcohol )

I've got k2Cr2O4 so oxidise the alcohol is OK, KBr so chloromethylate and an halogen swap (if necessary) is doable.

I also used some DMSO oxidations to make the aldehyde, DMSO and CaCO3 at 100°C for a short time (5min??) i think.

...I could try it.

Final note: I'm interested in the 2,5 dmbenzaldehyde or 4 bromo 2,5 dmb themself; as intermediate for 4C family (4C-DOB, 4C-ALEPH-2) nor in the nitrile (2CB is for the holidays, not the exams!)

(Hmm interesting ALEPH-2 is anxiolytic by itself, wonder how his 4C congener will be...)

hest: I think that the first ref (formylation of 1,4-diethoxybenzene with hexamethylenetetramine (HMTA)) is not the same as the last (DUFF) correction: It is the same, but I will try to fetch these articles from heterocycle next week. This may be a viable way to go from 1,4 dmb to 2,5 dmb. If you have some ref with the DMSO oxydation or HMTA / bromo methylation please share, I will fetch these article at the same time.

When I will have the time I will go buy some hydrochinone, put it in methanol, take the methoxy phenol, do the aldehyde w/ Mg(OMe)2, and paraformaldehyde like lilienthal (or if it doesn't work w/ CHCl3, or buy an ultrasonic bath and play with 1,4 dmb and grignard/DMF), alkylate ala Antoncho and voila. But for now I would like to use this fucking 1,4 to get it.

thanxx

hest

  • Guest
Options
« Reply #29 on: April 25, 2002, 09:40:00 AM »
Ok, it look's like you have two options

1 the grignar with DMF Just read

Post 191789 (missing)

(element109: "Armchair chemistry: 2C-X 'cursors from hydroquinon", Novel Discourse)


2 chloromethylate and then oxidise.

I made some cut and past from the hive
From

Post 275926 (missing)

(starlight: "piperonyl chloride ---> piperonal", Chemistry Discourse)

Taken from J. Chem. U.A.R., 11, No. 3, 401-404 (1968):

SYNTHESIS OF 3,4,5-TRIMETHOXYBENZALDEHYDE FROM 3,4,5-TRIMETHOXYBENZYL CHLORIDE

B-Sommelet Method--To a solution of 11 g of hexamethylenetetramine (hexamine) in 70 mL of chloroform was added 18 g (0.07 mole) of IIb (3,4,5-trimethoxybenzyl chloride).  The solution was refluxed for 4 hr during which time a precipitate of the quaternary salt was formed.  The solvent was removed under reduced pressure and 35 mL of acetone was added.  The precipitate was filtered off and heated for 20 min with 100 mL of water.  Concentrated hydrochloric acid (17.5 mL) was added and the refluxing was continued for 5 min.  After concentration under reduced pressure and cooling the precipitated aldehyde was filtered off.  It forms colourless needles from benzene (12 g, 66% yield), mp 72-74 C.

From

Post 228725

(foxy2: "Re: Piperonyl Chloride Question", Methods Discourse)

Chloromethylation of 1,3-benzodioxole in the presence of micellar catalysts.  
Yingyong Huaxue  (2000),  17(5),  563-565. 
CODEN: YIHUED  ISSN: 1000-0518.  Journal  written in Chinese.

Abstract
1,3-Benzodioxole was monochloromethylated directly by aq. formaldehyde and hydrogen chloride gas in CCl4 in the presence of quaternary ammonium salts: c16H33(CH3)3NX (X = Br, Cl), C12H25(CH3)3NCl, C12H25(CH3)2(C6H5CH2)NCl and (C4H9)4NBr.  With hexadecyltrimethylammonium bromide at temp. 60°-65° for 15 h of reaction, 1,3-benzodioxole was converted to piperonyl chloride with conversion >98% and selectivity up to 97%.  The method has advantages of high selectivity, high conversion, negligible byproducts and easy workup of the mail product.



Flavoring materials contain the title compd. (I).  I, which has strong and continuous floral fragrance, is stable and useful for various uses, e. g. cosmetics, hair prepns., soaps, detergents, drugs, etc.  Treatment of 366 g methylenedioxybenzene with 99 g paraformaldehyde in MePh with feeding HCl at 25-35° for 4 h gave 423.6 g crude 3,4-methylenedioxybenzyl chloride

Hope that help's
;D

little_princess

  • Guest
just made a decision
« Reply #30 on: April 25, 2002, 04:19:00 PM »

Thank you hest you really helped me to sort this out

As I don't have any ultrasonic bath I've chosen to go with the chloromethylation route.

I will try to chlorinate 1,4 to 1-chloro-2,5-dmbenzene w/ bleach/NaCl in situ or preformed in CHCl3, do the chloromethylation to yield the benzyl chloride and then do the sommelet or the DMSO /NaHCO3 oxydation (which one is the heigher yielding?).

I hope that the chloro benzene will resist beaker's reduction. It resist to NaBH4 AFAIK but does it resist the Pd/C HCOONH4 hydrogenation? Hopefully it will yield 2C-C or 4C-DOC...

Anyone has a ref to make chloro-1,4 dmb?

cu lp

hest

  • Guest
Yeald
« Reply #31 on: April 25, 2002, 04:25:00 PM »
1. Don't have the yeald's right here, i'll look them up
Chlorinate the amphetamin instead, nothing to wory abouth, and more 'safe' workup
I only made DOC once, chlorinated with liquid Cl2
(bp -32°C ?) yeald high.

Rhodium

  • Guest
DOC with CL2
« Reply #32 on: April 25, 2002, 04:31:00 PM »
From:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/doc.synth.html



A german research team wanted to create a better synthesis of DOC than the procedure featured in Pihkal #64 as they thought it was cumbersome to generate the liquid chlorine required for that synthesis, and analysis of the resulting chlorinated 2,5-DMA indicated that the product consisted of 35% monochlorinated, 35% dichlorinated and 5% trichlorinated product (the rest was unreacted starting material). They concluded that the use of elemental chlorine was not suitable for the selective 4-chlorination of 2,5-DMA.

foxy2

  • Guest
Aromatic halogenation reactions
« Reply #33 on: April 25, 2002, 06:43:00 PM »
Simple and Practical Halogenation of Arenes, Alkenes and Alkynes with Hydrohalic Acid/H2O2 (or TBHP)
Tetrahedron, Volume 55, Issue 36, 3 September 1999, Pages 11127-11142
Nivrutti B. Barhate, Anil S. Gajare, Radhika D. Wakharkar and Ashutosh V. Bedekar

Standard Procedure for aromatic halogenation:
A solution of TBHP(tertbutylhydroperoxide)(70% aqueaous, 0.15mL, 1.17 mmol) was added to a cooled mixture of HBr (48% aqueaous, 0.2 mL, 1.17 mmol) in methanol (5 mL) and the mixture stirred for 5 min.  To this cold solution 1.17 mmol of the aromatic is added, stirred for 30 min. and then refluxed for 6 hours.  Extract with DCM and they purify by column chromatography.


Anisole to 4-BromoAnisole 76%
1,4-dimethoxybenzene to 2-Br-1,4-dimethoxybenzene  89%
4-methylphenol to 2-Bromo-4-methylphenol  74%

The following was done with 4 equivalents of TBHP and 4 Eq. HBr
1,4-dimethoxybenzene to 2,5-diBr-1,4-dimethoxybenzene  98%

With 4 equivalents of H2O2 and 4 Eq. HBr
1,4-dimethoxybenzene to 2,5-diBr-1,4-dimethoxybenzene  99%

With 4 equivalents of H2O2 and 4 Eq. HCl
1,4-dimethoxybenzene to 2,5-diCl-1,4-dimethoxybenzene  73%

With 4 equivalents of TBHP and 4 Eq. HCl
1,4-dimethoxybenzene to 2Cl-1,4-dimethoxybenzene  71%
This had no detectable dichloro impurity

Its too bad they didn't run more reactions with H2O2

This reference might bee good to get
Ho T-L, Balaram Gupta BG, Olah GA.  Synthesis 1977:676

Says they halogenate aromatics with H2O2, hydrohalic acid, 1 eq Calcium Halide and phase transfer catalysis.

Foxy

Those who give up essential liberties for temporary safety deserve neither liberty nor safety

hest

  • Guest
Chlorination
« Reply #34 on: April 26, 2002, 01:16:00 AM »
I think I used CHCl3 as a solvent, I chlorinated at -78°C and just let it reach room temp. My yeald was in the 70's and it was pure on gcms. I have read the german article, can't remember the solvent they use. I think that the procedure they use is quite different from pikhal.

little_princess

  • Guest
Foxy you are incredible!
« Reply #35 on: April 26, 2002, 06:17:00 PM »

Foxy you are incredible! where have you got all your ref! Have you got a bio-chip in your brain that is connected to chem archive? Anyway I must produce TBHP now... more work to do!

Hest: you made liquid chlorine by generating chlorine and condensed it with a CO2/acetone condenser... If I bubbl it directly in Chcl3, wouldn't it be easier? The chlorine will dissolve in chloroform and stay here nop? And then I can measure the density of the chloroform/Cl2 and take exactly the good amount, no meassy work with liquid chlorine. I can add dropless this Cl2/ChCl3 solution to the ChCl3/2,5 dma or 1,4 dmb, it's easier and more clean like that isn't it? What do you think?

Ho and what about 2C-C, anybee have dreamed of it? What are the effect vs 2C-B? This is a not so speak about chemical, but it is on my list of potential prefered substance! All the human info I have is from pihkal, erowid has not any single trip on 2C-C! what a shame....

anyway thanx to you all, you gave quick and interesting replies..

lp


foxy2

  • Guest
Look
« Reply #36 on: April 26, 2002, 07:05:00 PM »
princess
Did you see the H2O2 sneak in there?
It may work fine with H2O2!!!

"With 4 equivalents of H2O2 and 4 Eq. HBr
1,4-dimethoxybenzene to 2,5-diBr-1,4-dimethoxybenzene  99%"

I wouldn't bee surprised if 1 equivalent of H2O2 nad 1 equivalent HBr works just as well as TBHP.

I am here to inspire the worker Bee's to make things happen
;D
May the honey flow freely
Foxy

Those who give up essential liberties for temporary safety deserve neither liberty nor safety

little_princess

  • Guest
Yes but the problem is that I want the ...
« Reply #37 on: April 26, 2002, 11:41:00 PM »
Yes but the problem is that I want the mono-chlorinated benzene. There are plenty of ref on mono bromation and di bromation but only one ref on mono chloration, and it use TBHP. I will not make grignard so the brominated product have less use to me. I'm afraid that if I mono brominate some Br will not resist the future step(beaker synth) and I must rebrominate again at the end or I will have a mixture of the brominated and no-brominated product.  But the Cl will stick to the ring afaik. The only thing I can do with the mono brominated compound is to transform the br-aldehyde to 4-alkylthio aldehyde. If I can't chlorinate it I will do that and get the thio compound. Another thing I could hve done is iodinate but it's more expensive and Hest had trouble with it and I have a final bromination step that muist be prformed too. If I put an halogen on the ring I wanna it stay there, so chloro is the sole solution

hest

  • Guest
Chlorination
« Reply #38 on: April 27, 2002, 04:13:00 AM »
L.P. Sure it will work, I used liquid Cl2 course it was easy to weight.
But I still can't see the point why you all wants to halogenate the dimethoxycompound instead of the amphetamin.

little_princess

  • Guest
But I still can't see the point why you all wants ...
« Reply #39 on: April 27, 2002, 04:48:00 AM »
But I still can't see the point why you all wants to halogenate the dimethoxycompound instead of the amphetamin.

It's because I must put an halogen on the ring before the chloromethylation otherwise I would get a dichloromethylated product.