When hydroquinone monoethyl ether was formylated under the conditions of the process in accordance with the present invention, the corresponding end product was obtained in a very low yield.
Maybe Friedel-Craft would be an option then? (I really like the one with p-toluenesulfonic acid and the Dean-Stark trap)
I couldn't find anything on the 5-EtO homologue in PiHKaL, and no active level is yet known for the 2,5-diEtO homologue :P
I found this:
There are two "Tweetios" known that are related to 2C-B. (See recipe #23 for the origin of this phrase.) The 2-EtO- homologue of 2C-B is 4-bromo-2-ethoxy-5-methoxyphenethylamine, or 2CB-2ETO. The unbrominated benzaldehyde (2-ethoxy-5-methoxybenzaldehyde) had a melting point of 47.5-48.5 deg C, the unbrominated nitrostyrene intermediate a melting point of 76-77 deg C, and the final hydrochloride a melting point of 185-186 deg C. The hydrobromide salt had a melting point of 168.5-169.5 deg C. It seems that one gets about as much effect
as can be had, with a dosage of about 15 milligrams, and increases above this, to 30 and to 50 milligrams merely prolong the activity (from about 3 hours to perhaps 6 hours). At no dose was there an intensity that in any way resembled that of 2C-B.
The 2,5-DiEtO- homologue of 2C-B is 4-bromo-2,5-diethoxyphenethylamine, or 2CB-2,5-DIETO. The unbrominated impure benzaldehyde (2,5-diethoxybenzaldehyde) had a melting point of about 57 deg C, the unbrominated impure nitrostyrene intermediate a melting point of about 60 deg C, and the final hydrochloride a melting point of 230-231 deg C. The hydrobromide salt had a melting point of 192-193 deg C. At levels of 55 milligrams, there was only a restless sleep, and strange dreams. The active level is not yet known.
and this:
in general, 2-EtO : shorter duration, lower activity
5-EtO : relatively unchanged potency
2,5-di-EtO : very weak if active at all
...and there was added 40 grams of hydroquinone followed by 4 gr p-benzoquinone.
I can't figure out what is the purpose of added benzoquinone. If anybody knows, please, tell me.
Read Post 267698 (https://www.thevespiary.org/talk/index.php?topic=11482.msg26769800#msg26769800)
(Antoncho: "P-MeO-phenol from hydroquinone: part II", Novel Discourse)
It is thought that benzoquinone in acidic methanol forms an unstable hemiketal, which reacts immediately with hydroquinone to form benzoquinone and hydroquinone monomethyl ether. The benzoquinone is thus regenerated and is able to form more hemiketal.
220 ml 95% ethanol was added to a 1L beaker and magnetic stirring was commenced. To this was added, in 5 ml aliquots, 40 ml conc. H2SO4. The solution was allowed to cool to RT, and there was added 30 grams of hydroquinone followed by 3 gr p-benzoquinone.
The mixture was left stirring for 26 hours and acidified with 15% H2SO4. Some brine was added, followed by solid NaCl and extracting 4x with toluene. The solvent was evaporated in vacuo.
SWIM should have washed his organic layer with water of course, to get the traces of acid out, but he forgot :( .
So an attempt at vacuum distilling was made, but only a gram or so of purple ::) material was obtained when the boiling stopped and it was clear to SWIM that the stuff had carbonized. That flask is going to be a bitch to clean. >:( >:( >:(
Well, that'll teach him to always pay full attention next time.
some notes:
- SWIM makes his alkyl hydrogen sulfate as stated in Post 256342 (https://www.thevespiary.org/talk/index.php?topic=12158.msg25634200#msg25634200)
(Antoncho: "Methylation of hydroquinone w/NaMeSO4: good news!", Novel Discourse) but uses MgSO4 instead of Na2SO4.
- Toluene is probably not the best extraction solvent to use. After the fourth extraction the layer is still very dark. Next time SWIM will use DCM.
- One might consider taking precautions as to not letting your skin come in contact with p-MeO-phenol. It is melanocytotoxic, which means that it causes loss of pigment and skin allergy.
Read for more info http://www.ispb.ro/conferinta/engleza/occupational_vitiligo.htm (http://www.ispb.ro/conferinta/engleza/occupational_vitiligo.htm)
10 gr p-MeO-phenol was dissolved in a solution of 13 gr NaOH in 50 ml H2O with slight heating on the waterbath. The temp of the bath was raised to 60°C and there was added, dropwise, from 2 separate addition funnels, 30 gr chloroform and a sol. of 39 gr NaOH in 40 ml water (note 1) with stirring. At the end of the addition a voluminous yellow precipitate formed. The solution was heated for an hour at 60°C (bath temp.), and allowed to cool. The brown precipitate was filtered off and washed twice with a small volume of methanol (note 2). The precipitate was now dark yellow. This was dissolved in 56 ml H2O and slightly acidified with dilute HCl. This is extracted with 30 ml toluene and the solvent evaporated. This leaves a darkred oily residue, which was steam distilled (note 3) until the yellowgreen colour of the condensed water disappeared. about 200 ml of destillate were collected. This was saturated with salt, extracted with 50 ml of ether and the ether was evaporated, leaving 3 grams of a yellow oil. >:(
note 1: SWIM had run out of (pharm. grade) NaOH so he had to add 20 gr of shady drain-opener pellets he bought at 'Achmed's store' once. The package says 'Bilesimi sodyum hidroksit (Na OH)' but the resulting solution clearly had an ammonia smell. ::)
note 2: According to Patent GB1377317 (http://l2.espacenet.com/dips/viewer?PN=GB1377317&CY=gb&LG=en&DB=EPD)
note 3: I've messed around with sodium bisulfite before but never got a reasonably pure product and I always seemed to lose quite an amount in the alcohol washings.
Steam distillation is the way to go for purification.
This was saturated with salt, extracted with 50 ml of ether and the ether was evaporated, leaving 3 grams of a yellow oil. >:(
No reason to be mad, yet. In my experience, Reimer-Tiemann formylation is one of these things you have to practise a couple of times before you can yourself a "master". I can't remember my first Reimer-Tiemann reactions to yield something of interest... Tar formation is a major problem, unless you know the tricks.
Ahem.... I am fairly certain that the yields may bee further improved. Maybee you, guys, aren't so patient w/steam-distillation? It's a SLOW process. SWIM usually added salt to speed it up.
Also - just to bee sure - good care should bee taken to thoroughly saturate the post-distillation mixtr w/NaCl when xtracting.
Actually, why don't you try out this variation Post 330714 (https://www.thevespiary.org/talk/index.php?topic=7674.msg33071400#msg33071400)
(Antoncho: "A patented improvement", Chemistry Discourse) - i once told it didn't work well, but SWIM used real dirty p-MeO-phenol, i think if you use the white stuff, everything should bee okay.
I also remember reading that RT works actually better in alcoholic alkali - the book said that it "improved the yield, minimized side-rxns and required less time and alkali conc. as well as lower temperature". Alas, i can't remember where i read it, but will try to find the ref...
Antoncho
TITLE The Reimer-Tiemann Reaction, Enhanced by Ultrasound
AUTHORS Cochran, John C.; Melville, Margaret G.
SOURCE Synth.Commun. 1990, 20: 4 609-616
ABSTRACT Significant improvement in yields for Reimer-Tiemann reactions are obtained when the reaction is carried out in the presence of ultrasound.
Full Text: (https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_imgs/djvu.gif)
TITLE THE REIMER-TIEMANN REACTION IN SLIGHTLY HYDRATED SOLID-LIQUID MEDIUM: A NEW METHOD FOR THE SYNTHESIS OF FORMYL AND DIFORMYL PHENOLS
AUTHORS Thoer, A.; Denis, G.; Delmas, M.; Gaset, A.
SOURCE Synth.Commun. 1988, 18: 16-17 2095-2102
DOCUMENT TYPE Journal
CODEN SYNCAV
LANGUAGE EN
CNR 5738003
ABSTRACT Formylation of phenol in weakly hydrated heterogeneous solid-liquid medium makes it possible to transform phenol into salicylaldehyde and parahydroxybenzaldehyde with a ratio of 4.5/1 with excellent yield.Use of methanol as cosolvent modifies the orientation of this reaction, which leads for the first time to simultaneous synthesis of salicylaldehyde and
parahydroxybenzaldehyde, of 2-hydroxy 1,3-benzenedicarboxaldehyde, and of 2-hydroxy 1,3-
benzenedicarboxaldehyde. Experimental conditions make it possible to easily extract each of these molecules.
TITLE Photoformylation of Phenols
AUTHORS Fahmy, A. M.; Mahgoub, S. A.; Aly, M. M.; Badr, M. Z. A.
SOURCE Indian J.Chem.Sect.B 1984, 23: 5 474-475
DOCUMENT TYPE Journal
CODEN IJSBDB
LANGUAGE EN
CNR 5574527
ABSTRACT Photoformylation of phenol, o-, p- and m-cresols, p-chlorophenol, p-bromophenol, p-nitrophenol and p-hydroxydiphenyl with chloroform in the presence of aq.KOH or pyridine affords the corresponding aldehydes; formyl group entering the position ortho to OH function.A
plausible mechanism, different from that of well known Reimer-Tiemann, has been suggested.
TITLE Reimer-Tiemann reactions of guaiacol and catechol in the presence of â-cyclodextrin
AUTHORS Divakar, S.; Maheswaran, M. M.; Narayan, M. S.
SOURCE Indian J.Chem.Sect.B 1992, 31: 8 543-546
DOCUMENT TYPE Journal
CODEN IJSBDB
LANGUAGE EN
CNR 5751452
ABSTRACT Fairly high selectivities with respect to para-product are achieved when guaiacol and catechol are subjected to Reimer-Tiemann reaction in the presence of â-cyclodextrin (BCD).
Although the presence of BCD does not enhance the total aldehyde production, it reduces the proportion of other isomeric aldehydes formed in favour of the para-product.Thus the reaction in the presence of BCD yields 32% more vanillin in the case of guaiacol and 25% more
protocatechuic aldehyde in the case of catechol in comparison to the one in the absence of BCD.