Author Topic: alkylation of quinones  (Read 21707 times)

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Captain_Mission

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alkylation of quinones
« Reply #40 on: February 08, 2002, 11:18:00 PM »

  Greetings everybody. Italian isn´t my native tongue but I think I can make a good enough translation. Here it goes:


Experimental part: Preparation of p-dimethoxybenzene from 1-4 benzoquinone

 a)reduction with Al/Hg and KOH

  To a solution of 5 grams of quinone in 80 cm3 of 80% MeOH were added, in the cold, 5 grams of Al amalgam, prepared according to Wislicenus(11), followed with slow addition of 200 grams of a 50% solution of KOH.
  The mixture is refluxed for an hour, and 30 grams of dimethyl sulfate are added in small parts, followed by the addition of 35 grams more of the KOH solution and a further 1 hour reflux.
  The solution obtained is basified (not too sure about this part) and steam-distilled; most of the p-dimehtoxy benzene distiles over and can be separated quantitatively with ether extraction of the distillate. The ether is evaporated to obtain 4 grams (~80% yield) of product mp 51 degrees. By acidifing the residue and extracting with ether 0.3 grams of hydroquinone can be obtained.
  

Then they say that to achieve these reaction conditions various concentrations and amounts of the reagents and the solvent were tried.
  

foxy2

  • Guest
Re: alkylation of quinones
« Reply #41 on: February 09, 2002, 12:19:00 AM »
Captain
Do you have thename of that journal reference and its details?
Just to know.
Thanks
Foxy

Stay Informed

(http://www.mapinc.org/)

Rhodium

  • Guest
Re: alkylation of quinones
« Reply #42 on: February 09, 2002, 02:35:00 AM »
It is a translation of

Post 265618

(poix: "Re: alkylation of quinones", Novel Discourse)
which comes from Gazz. chim. ital (1943) 73 300-305, mentioned a few posts higher up.

poix

  • Guest
Re: alkylation of quinones
« Reply #43 on: February 09, 2002, 10:40:00 AM »

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0562

SUCCINIMIDE

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0034

B-ALANINE

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0019

B-ALANINE

I think their workup with B-ALANINE is not so good. Another purification procedure is welcome.

We must speak about the amine protection too. I don't know if anhydride acetic/acetyl chloride will work because acidic medium or aqueous NaOH are used to deprotect, but I don't know the concentration. Rhodium, do you know the conditions for deprotection of these amides? I know amide are pretty stable so I hope it will not deprotect too easily and can resist two step with silver and CH3I. Also I saw in my cursus that valine could be protected with formic acid forming N-formyl valine. My question is: is HCOOH more reactive than the ac. carb. of the valine itself? otherwise in these same condition polymerisation of the valine would do polypeptide, but it doesn't. Maybe formic acid could be used for the protection, they say NaOH,H2O,0°C are the condition of deprotection, but they doesn't say the time nor the concentration, I hope it will be stable enough for the 2 steps, it would be cool to just use formic as protecting agent.

Any help with the protection/deprotection step is welcome, it is a vast subject with plenty of ref to find, especially in the resolution of amino acid. 

Fuck I'm newbee!

Antoncho

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Re: alkylation of quinones
« Reply #44 on: February 09, 2002, 12:25:00 PM »

do you know the conditions for deprotection of these amides?




AFAIK, the general proc for deacetylation is smth like 20% HCl ~1 h at reflux.

Antoncho


PrimoPyro

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Re: alkylation of quinones
« Reply #45 on: February 09, 2002, 11:21:00 PM »
Why must it be protected again? What is the problem with alkylating the quinone unprotected beta-alanine?

                                                    PrimoPyro

Vivent Longtemps la Ruche!

poix

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Re: alkylation of quinones
« Reply #46 on: February 10, 2002, 10:50:00 AM »
No 208020:
You can't dimethylate tryptamines by simply reacting them with methyl iodide (MeI) or dimethylsulfate (DMS) due to overalkylation to quaternary salts.

It will form a quaternary salts of 2CH with MeI

Antoncho

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Re: alkylation of quinones
« Reply #47 on: February 10, 2002, 01:33:00 PM »
ahem.... but in this case, acetylation also should bee of no help, no?

i mean, monomethylated 2CH ain't what we want either...

Antoncho

Greensnake

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Re: alkylation of quinones
« Reply #48 on: February 10, 2002, 02:57:00 PM »
monomethylated where? On N? That should not be of any concern, common amides could be alkylated only under somewhat harsh conditions, so unless you use excess sodium hydride as base or do something other equally perverted, amide should remain untouched while phenols are alkylated.

poix

  • Guest
Re: alkylation of quinones
« Reply #49 on: February 26, 2002, 01:13:00 AM »
Bringing back the protection subject:
At this day I think the best protecting group we can use is acetic anhydride (or acetyl chloride). We can acetylate the alanine, do the reactions, methylate with CH3I/K2CO3/sodium hydrosulfite and then deprotect with refluxing KOH. AFAIK all these reactions will work. But I don't wanna buy acetic anhydride nor acetyl chloride.
I've a DOEF synth that use magnus reagent ([CLSi(CH3)2CH2]2) for protecting the amine. Can TMSCl be used like this, as with alcools? Another protecting group I've seen is imine formation with benzaldehyde. We can make imine with acetone, can acetone be used as a protecting group? Does sodium thiosulfite reduce the imine like the carbonyl of the quinone? I don't think CH3I will add to an imine, is this true? Does the alkylating step with quinone in water interfere with these protecting group? ie does water at pH other than 4.5 deprotect the imine? is water without reflux sufficient to hydrolise the N-sylil bond? (Magnus reagent deprotection: 10% KOH, MeOH, reflux 4h)

Hope I'll have some answers from some knowledgeable bee.

PoiX

Rhodium

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Re: alkylation of quinones
« Reply #50 on: February 26, 2002, 06:50:00 AM »
Stuff worth looking into could be to protect the amine function as the phtalimide (Just react the amine with phtalic anhydride, deprotection is hydrazine or KOH soln). Another is the trifluoroacetamide (from amine + trifluoroacetic anhydride) which can be removed by mild acid hydrolysis.

Chimimanie

  • Guest
Proposed method (1) for 2C-H
« Reply #51 on: February 14, 2003, 09:08:00 PM »
Yet another theoretical 2C-H synthesis, Chimimanie

Well after some research in this area this is what I found.

This road look feasible, but it is not tested yet. The scheme I use is the same as poix proposed but it reduce to the hydroquinone and methylate in two steps, its easier like that and better I think, in fact reduction of the quinone to the hydroquinone may be view as a workup of the first reaction since its only a wash with aqueous hydrosulfite.

This synthesis may not work (but I think it will, prove me wrong), use no watched chemicals beside benzoquinone (which must be made from hydroquinone) and acetic anhydride and probably does not give stellar yield, i think it is for small scale manufacture of 2cb only, not for 1000+ doses reaction. Theoretically I think it is the shortest synthesis of 2C-H starting from hydroquinone (with the aryne road of course).

Well some theoretical background:

The ideal reaction would be reaction of quinone with beta-alanine to yield beta-ethylamine benzoquinone, but this will not work. Why? because the silver/persulfate oxydation transform amine into aldehyde[1]. So we must protect the amine. We can't protect it with formic, because formyl is easily removed by oxydation. We can also protect it with phtalimide, but I have not searched in this direction. Trifluoroacetic anhydride could be used, the last step (hydrolysis)  would be high yielding with it[6], but it is expensive. I choose acetic anhydride. I hope than the amide will be stable in this oxydative medium, I don't know because in ref [1] they didn't speak of amide but I think so.

The alkylation proceed from a decarboxylation and generate radicals which then are scavenged by benzoquinone and alkylate it. Loss of radicals or polyalkylation are possible, read the orgsyn ref [9]. I used the orgsyn ref method in hope there is no need to use one of the variant that are in the litterature (the references of these variants are in the org syn article [9]) which use sometimes high quantity of silver and excess of acid. If this one does not work one can play with the ratios of acid/AgNO3/BQ but I think it is useless to stay with that road if it doesn't work, I will post a second road which is more reliable (ie: with no doubt that its decarboxylative alkylation work) than this. Anyway we will see, maybe this one work. (it should! ;) )

The second reaction is easy, it can be considered like the work up of the first, it is a simple quinone to hydroquinone reduction by a Na2S2O4 wash, with much ref covering it in the litterature, no problem.

Third reaction is an alkylation. Medium is acetone, alcohol nor water can't be used here because of the risk of hydrolysis of the amide. I hope this will not occur too much in acetone. Hydrolysis of the amide at this step would lead to alkylation of the free amine which is a lost of reactant.

Fourth reaction is an hydrolysis of the amide, the yield are not great for this step, they would be better if we used trifluoro-acetic anhydride[6]. An high yield hydrolysis of amide is welcome.
  
Note: after the second reaction, if the amide of the free hydroquinone compound (B) is hydrolized, we have got 2-(2,5-dihydroxy-phenyl)-ethylamine. This compound is not stable and accordingly to ref [8] it will freely oxydise itself to 5-hydroxy-indole in about 90% yield if stirred at RT in an open vessel for 10hrs. It can then be recrystallized from ether. This indole can be used for the synthesis of bufotenine or 5-MeO-tryptamine compounds.


Experimental:

Precursors:

Beta-alanine: see post

Post 267363

(poix: "Re:  alkylation of quinones", Novel Discourse)


Acetic anhydride can be synthetised from acetyl chloride and sodium acetate or with a ketene lamp, UTFSE.

Benzoquinone: see

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

, I recommend to use the chlorate/V2O5 method or the sodium nitrite/O2 one, it is very important to get quinone(bright yellow) and not quinhydrone(metallic green).

Iodomethane: see

Post 301629

(Antoncho: "Two tried-and-true ways to make MeI !", Chemistry Discourse)


N-acetyl-beta alanine: from [2]

This is the synthesis of N-acetyl-alpha alanine, it works good (tried) on beta-alanine too, same synthesis, substitute beta-alanine and Dl-alanine.

DL-Alanine (89.1 g., 1 mole) is placed in a 2L Erlenmeyer flask provided with a calcium chloride drying tube attached to the flask through a ground-glass joint. The amino acid is mixed with 900 ml. of c.p. glacial acetic acid,and brought to the boil, with gentle agitation, on an electric hot plate. The mixture is removed from the hot plate to cool for a minute or two, and 150 mL. (1.5 mole) of c.P. acetic anhydride is carefully added in portions so as to avoid superheating and explosive boiling. The resulting solution is returned to the hot plate, brought to the boil, held at this point for 2 min. longer, and then allowed to cool to 25° at room temperature. The slightly yellowish solution is then evaporated in vacuo at 40° to a syrup and the residue treated several times with water followed each time by evaporation in vacuo at 40°. After the final evaporation with the aid of benzene (Chimimanie's voice: toluene can be substituted) to remove the last traces of water, the syrupy residue is taken up in the minimum quantity of dry ethyl acetate and the solution chilled. On scratching or seeding, the acetyl-dL-alanine rapidly crystallizes. After standing for 18 hr. at 5°, the crystals are filtered rapidly with suction, and washed with dry ether which removes the last trace of yellow color. On drying in vacuo at 25° the yield of pure, white crystals of acetyl-dL-alanine is 10.5 g., or 80% of the theoretical; m.p. 136°.

Recovery of silver: [7]

Considerable quantities of silver iodide-silver oxide residues sometimes accumulate in the laboratory, for example, in methylation studies involving the use of methyl iodide and silver oxide. While silver alone is usually recovered from silver residues, iodine is valuable enough to warrant its recovery when the residue contains a large proportion of silver iodide. In the method described, the presence of silver iodide and of silver salts soluble in concentrated aqueous ammonia is assumed. If significant quantities of contaminating salts, such as silver sulfide, are present, suitable modification is required.

Procedure:

A) Preliminary treatment of residue:

Ag2O + 4 NH3 + H2O -> 2 Ag(NH3)2OH

The residue containing silver iodide is freed from organic matter by extraction with a suitable solvent, dried, and ground to pass a 40-mesh sieve. The powdered residue is shaken with sufficient concentrated ammonia (sp. gr. 0.90) to dissolve all soluble silver salts. The suspension is filtered on a Buchner funnel and the filtrate (1) is reserved for subsequent recovery of silver by reduction with sodium dithionite solution.
The insoluble silver iodide is washed with water on the filter, dried, and weighed. (It is desirable to know the weight of silver iodide because a subsequent reaction involving the reduction of iodic acid with sodium dithionite requires exact quantities.)

B) Recovery of silver:

AgI + Cl2 ---aqua regia---> AgCl + ICl
AgCl + 2 NH3 -> Ag(NH3)2Cl
2 Ag(NH3)2Cl + Na2S2O4 + 2 H2O -> 2NaCl + 2Ag + 2(NH4)2SO3

The powdered silver iodide (40-mesh) is treated with excess aqua regia (under hood). A solution consisting of 81 mL of concentrated nitric acid (sp. gr. 1.42) and 216 mL of concentrated hydrochloric acid (sp. gr. 1.19) is suitable for each 100 g. of silver iodide*. The reaction proceeds vigorously but not violently. The mixture should be shaken frequently for 5 minutes until the initial vigorous reaction has subsided. The suspension is then heated gently on the steam bath for 25 minutes, with occasional shaking**. The contents of the reaction vessel are then diluted with 330 ml. of distilled water and cooled in ice. The silver chloride is filtered on a Buchner funnel and washed with distilled water on the filter. The filtrate (II) is reserved for recovery of iodine. Silver chloride obtained in the reaction is dissolved in concentrated aqueous ammonia and combined with the previous ammoniacal filtrate (I)***. This solution is treated with an excess of a 6 per cent solution of sodium dithionite, (ammonium formate works too) which quantitatively precipitates pure silver as a grey powder. The silver is washed with distilled water and dried. This method of recovering silver from silver chloride appears preferable to reduction with zinc or by other agents involving heterogeneous reactions.

* The quantities given in the subsequent description apply to 100g-lots of silver iodide.
** If the silver iodide contain no lumps, this treatment suffices for practically complete conversion to silver chloride. However, a test for completion of the reaction may be made by removing a small quantity of the precipitate, which after washings with water should all dissolve in concentrated ammonia solution.
*** Any residue remaining undissolved in ammonia should be treated again with aqua regia. Ammoniacal silver chloride solutions should not be allowed to stand too long before precipitating the silver since some insoluble material separates, which, on occasion, has produced violent explosions.  :o

Chimimanie

  • Guest
next
« Reply #52 on: February 14, 2003, 09:08:00 PM »
C) Recovery of iodine:

5 ICl + 6 NaOH -> 2 I2 + NaIO3 + 5 NaCl + 3 H2O
6 NaIO3 + 5 Na2S2O4 + 2 H2O -> 3 I2 + 6 Na2SO4 + 4 NaHSO4

To the filtrate (II) from the aqua regia treatment, cooled in ice, 20% sodium hydroxyde solution is slowly added, with stirring, until the solution is slightly basic. Then hydrochloric acid is added dropwise until the solution is just acid to litmus. This causes 80 per cent of the iodine to precipitate. To the suspension is added a solution containing exactly 12.3 g. of sodium dithionite (calculated as Na2S204), which precipitates the remaining 20 per cent of the iodine. The acidity is adjusted as before. Excess sodium hydroxide must be avoided to prevent solution of some iodine. The precipitated iodine is filtered from the ice-cold solution by means of a hardened paper on a Buchner funnel. The filtrate is tested for complete precipitation of iodine by dropwise addition of sodium dithionite. The calculated amount may not have been quite sufficient, probably because of the oxidizing action of some chlorine or hypochlorous acid. Excess sodium dithionite is to be avoided, however, to prevent loss of iodine by reduction to soluble iodide. The iodine is washed with cold water, filtered, and dried in a desiccator over concentrated sulfuric acid. If further purification is desired, sublimation may be employed. The recovery of silver and iodine from silver iodide by this method is quantitative except for slight manipulative losses.


Proposed synthesis:

N-acetyl-beta-aminoethyl benzoquinone, (A): adapted from [9]

All glassware should be washed three times with distilled H2O before use.

In a 500 ml 2-necked RBF, fitted with a thermometer and a pressure equalized graduated dropping funnel, is placed 13.1 g (0.1 mole) of (recrystallised) N-Acetyl-beta-alanine, 10.8 g (0.1 mole) of pure *1 yellow 1,4-benzoquinone, 2g of AgNO3 and 250 ml of dH2O. The mixture is then stirred and heated to 60-65°C until dissolution is complete. A little CH3CN can be added if dissolution can't be achieved. The resulting solution is stirred vigorously while a freshly prepared *2 solution of 27.4g (0.12 mole) of ammonium peroxydisulfate in 50 ml of dH2O is added at a rate *3  of 1 mL per minute for the first 40 minutes and then at a rate of 0.5 mL per minute for the last 20 minutes. Throughout the addition, the reaction mixture is maintained at 60-65°C.
After the addition is complete the mixture is stirred for 5 minutes at 65°C and then cooled to 5-10°C in an ice bath. The precipitated solid is collected by suction filtration *4, washed with 50 mL of cold dH2O and pressed to remove most of the liquid. Inorganic contaminants (if any) are removed by dissolving the solid in boiling acetone and filtering the hot solution from the insoluble. Acetone is evaporated under vacuum to give a product which is crystallized from a suitable solvent (EtOH?). After cooling to 5°C the crystals are collected by filtration and air dried on buchner. Recrystallisation from a suitable solvent (EtOH?) should give (A).

*1 Freshly recrystallised or sublimed, it has to be yellow, not the green stuff as the green stuff is quinhydrone. While quinhydrone as some use in a wacker reaction it hasn't here, only yellow benzoquinone work.
*2 (NH4)2S2O8 solution are not stable, they should be prepared a short time before use.
*3 A 3 mL/min rate
might be used
*4 If the product separe as a gum, as an oil or is partly soluble in water an extraction procedure is used.



N-acetyl-beta-aminoethyl hydroquinone, (B): adapted from [3]
19.3 g of (A) (0.1 mole) in enough Et2O to dissolve it (200-300 mL) was shaken with a solution of sodium hydrosulfite (made from 35 g (200 mmole) of Na2S2O4 in 500mL water). If the color doesn't disappear fully, add some more Na2S2O4 in water. After discolouration the organic layer is separated and the water solution is extracted once with 50 mL Et2O. The combined Et2O fractions are washed once with brine and dried over anhydrous MgSO4. The ether is distilled under vacuum to yield (B).


N-Acetyl-2C-H, (C): adapted from [4]
To a stirred mixture of 19.5g of (B) (0.1 mole) dissolved in acetone (~150 mL) and anhydrous potassium carbonate (28g, 0.203 mole) is added rapidly with stirring 30g of CH3I *5 (~0.21 mole, ~13.2 mL). The whole mixture is then refluxed for ~6 hrs *6.
The mixture is then cooled and filtered, the remaining inorganic salts are washed once with acetone. The acetone is evaporated under reduced pressure *7. Some Et2O is added to dissolve the resulting product, the ether layer is washed twice with aqueous 0.1 mol NaOH solution *8, then twice with aqueous 0.1 mol HCl *9, once with water and once with brine. The ether is decanted, dried over anhydrous MgSO4, filtered and evaporated under reduced pressure to yield N-Acetyl-2C-H (C). The N-Acetyl-2C-H can be recrystallised from EtOH, nitrated like in ref [5], reduced and subjected to the sandmeyer reaction to give 2C-C (or the other halides too). It can be nitrated then hydrolized to give 2C-N. Or it can be simply hydrolized to give 2C-H.

*5 Caution! iodomethane is toxic!
*6 Maybe more, maybe less, I dont know, it should be monitored by TLC.
*7 Caution! it remains some unreacted iodomethane
*8 These washes remove the phenolates, they could be remethylated once more with CH3I.
*9 These washes remove the deprotected amines which may be present.



2C-H: from [5]
5.6 g of N-Acetyl-2C-H (C) (~0.025 mole) in aq. NaOH (from 25g NaOH and 125 mL water) and ethylene glycol (250 mL) is heated under reflux for 15 hrs and then cooled. The solution is extracted in ether, washed twice with water, extracted with aq. HCl (pH 1), washed twice with ether, basified to pH 12, extracted in ether, dried over MgSO4 and gassed with anhydrous HCl to give 2C-H.HCl. Alternatively the crude solution can be simply extracted in ether, washed twice with water, dried and then the freebase purified by distillation under reduced pressure.

Bromination give 2C-B and iodination with silver/iodine give 2C-I.

And dont forget to recover your silver from the alkylation (you can add some KI to the filtrate of the first reaction to precipitate AgI) and/or from the iodination (if you wanted some 2C-I).

Reference:
[1] Unknown book with title "organic peroxyde", p324
[2] Unknown book with title "chemistry of the amino acids"
[3] J chem soc perkin trans I, 1982 + a lot of others ref with same reaction
[4] J chem soc 1958, 1602; J Chem soc 1959, 3376 and 3380
[5] Can j chem 51 1973 1402

Post 405601

(Chimimanie: "DOM analogs (Can J chem 51 1402 1973)", Novel Discourse)

[6] unknown ref, synthesis of DOEF by shulgin
[7] Recovery of silver and iodine from silver iodide residues, J R Spies, Inorganic synthesis, vol unknown, p 6
[8] Darstellung und oxidation von 2-(2,5-dihydroxy-phenyl)-ethylamin-Derivaten II, Z. Naturforsch 42 b, 1567-1577 (1987)
[9] Organic synthesis collective vol 6 p890

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0890




I am open to discussion: what you guys do you think of that road, what critics have you got, what comments and the like...?

Who want to try it first?  ;)

imp

  • Guest
Reductive Methylation of Quinones
« Reply #53 on: October 13, 2003, 07:09:00 AM »

Post 264123

(Antoncho: "Re: alkylation of quinones", Novel Discourse)


Here's an "exact proc." :

A solution of 17.5 g 1,4-naphthaquinone in 200 mL MeOH was heated to the boiling point, and treated with 28.5 g stannous chloride at a rate that maintained a continuous rolling boil.  At the completion of the addition, the reaction mixture was saturated with anhydrous hydrogen chloride, and held at reflux on the steam bath for 2 h.  The reaction mixture was poured into 700 mL H2O and treated with aqueous NaOH.  During the addition there was transient development of a curdy white solid which redissolved when the system became strongly basic.  This was extracted with 3x200 mL CH2Cl2 and the pooled extracts were washed first with H2O, then with dilute HCl, and finally again with H2O.  Removal of the solvent under vacuum yielded 15.75 g of a low melting black flaky crystalline material which was distilled at 160-180 C at 0.05 mm/Hg to give 14.5 g of an amber, solid mass with a mp of 78-86 C.  Recrystallization from 75 mL boiling MeOH provided 1,4-dimethoxynaphthalene as white crystals melting at 87-88 C.


Does anyone want to guess where SWIM got that from??

Perhaps this will work equally well for benzoquinone to 1,4-dimethoxybenzene? Maybe we can even replace the SnCl2 with sodium dithionite.

Doesn't anybody have some trifluoroacetic acid and benzoquinone??

Rhodium

  • Guest
Pihkal?
« Reply #54 on: October 13, 2003, 03:09:00 PM »
at a rate that maintained a continuous rolling boil

The only chemist expressing himself as graphic as that must be Sasha, right?

imp

  • Guest
;-) Of course. See 2C-G-N.
« Reply #55 on: October 13, 2003, 05:45:00 PM »
;)  Of course. See 2C-G-N.

Disciple

  • Guest
Hydroquinone
« Reply #56 on: October 14, 2003, 09:46:00 AM »
Surely one of the easiest ways would have to be the alkylation of the hydroquinone, which at least where i am is easier to get than the benzoquinone. I realise this may not be universally applicable to everyones use, but hey. :-)
Couldn't the hydroquinone be reacted with 2 equivalents of base giving the phen-1,4-dioxide (? @ naming) and reacting it in dmf with an alkyl halide, namely halomethane or haloethane. To give 1,4 dimethoxy benzene. Comments and rebuttals welcome, as its all a learning process.

Rhodium

  • Guest
Yes, but that's different.
« Reply #57 on: October 14, 2003, 01:58:00 PM »
If you already have the hydroquinone, yes, then it is simply a double phenol alkylation.

The above was a nifty way of going from the para-quinone to the para-dimethoxyarene in one step, without first having to reduce the quinone to the hydroquinone.

no2meth

  • Guest
ideas
« Reply #58 on: October 29, 2003, 12:53:00 PM »
Rhodium: do you know the exact mechanism of the rxn? If it involves alpha-carbonyl hydrogens, then CF3COOH won't react (and I think it does and in fact the mechanism is similar to free radical induced coupling of acetone and benzene at the alpha-carbonyl site with subsequent decarboxylation). Would manganese (III) acetate work as a catalyst then?

Another idea: reacting the quinone with cyanoacetic acid, simultaneous methylation-reduction and finally energetic reduction of the nitrile would be a quick route to 2C-H.

And then... maybe acetone methylimine would react as well... Then reduction with sodium dithionite (or what have u, maybe thiourea dioxide) and final methylation.

imp

  • Guest
Mechanism???
« Reply #59 on: December 10, 2003, 05:27:00 AM »
Rhodium, or anyone, SWIM is curious about the mechanism of this reaction....

A solution of 17.5 g 1,4-naphthaquinone in 200 mL MeOH was heated to the boiling point, and treated with 28.5 g stannous chloride at a rate that maintained a continuous rolling boil.  At the completion of the addition, the reaction mixture was saturated with anhydrous hydrogen chloride, and held at reflux on the steam bath for 2 h.  The reaction mixture was poured into 700 mL H2O and treated with aqueous NaOH.  During the addition there was transient development of a curdy white solid which redissolved when the system became strongly basic.  This was extracted with 3x200 mL CH2Cl2 and the pooled extracts were washed first with H2O, then with dilute HCl, and finally again with H2O.  Removal of the solvent under vacuum yielded 15.75 g of a low melting black flaky crystalline material which was distilled at 160-180 C at 0.05 mm/Hg to give 14.5 g of an amber, solid mass with a mp of 78-86 C.  Recrystallization from 75 mL boiling MeOH provided 1,4-dimethoxynaphthalene as white crystals melting at 87-88 C.


SWIM could only think of something like this...

The SnCl2 reduces the double bond of the quinone forming 1,4-naphthahydroquinone and SnCl4. Anhydrous HCl is then gassed in and the formed SnCl4, being a lewis acid, reacts with the MeOH and HCl to form in situ methyl chloride. The methyl chloride then methylates the hydroquinone.

It seems to be the only thing that makes sense to SWIM. Can anyone think of another mechanism?

If this is the case, then might it be possible to just dissolve hydroquinone in MeOH, add some lewis acid (perhaps ZnCl2??), then gas with anhydrous HCl? Seems like that could work on any phenol.

That means the SnCl2 needs to be anhydrous, and not the dihydrate. Or could the dihydrate work? SnCl4 forms a pentahydrate, so there would be room for anhydrous material. Maybe adding some silica gel wouldn't hurt.

BTW. SWIM has an article where they alkylate benzoquinone using free radicals generated from dialkyl sulphoxides. DMSO yielded mono, and poly methylated benzoquinone.