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All 12 posts Subject: 2CH via IBX Please login to post Down

amine
(Hive Bee)
09-10-04 18:00
No 530665
      2CH via IBX

There has been a few posts in the novel discourse of the hive, using the oxider IBX to convert benzyl alcohols into aldahydes. Post 520376 (metanoid: "Aldehydes & Ketones w/IBX", Novel Discourse)

1. (A) 1-4-dimethoxybenzene is bromomethylated using HBr and Formaldahyde as in Post 472838 (Rhodium: "Bromomethylation of 1,4-Dimethoxybenzene", Methods Discourse). Alternatively the proceedure by legos could be used: (HBr is made in-stu) Post 475109 (Lego: "Amphetamines/PEAs w/o benzaldehyde or nitroethane", Novel Discourse)

2. (B) monobromomethylated compound is reacted with KOH/NaOH to prdouce the benzyl alcohol (2,5-dimethoxybenzyl alcohol in this case)

3. (C) The benzyl alcohol is reacted with IBX Post 520376 (metanoid: "Aldehydes & Ketones w/IBX", Novel Discourse) or SIBX Post 451672 (Rhodium: "Novel Oxidative Demethylation of Eugenol", Novel Discourse) to reach the corresponding aldahyde.

4. The aldahyde undergoes a darzen condensation similar to the proceedure by barium. Post 339354 (Barium: "Check this out!!", Novel Discourse) The reaction could be modified to use methyl 2-chloroacetate instead of the methyl 2-chloropropionate.

5. The phenylacetaldehyde is converted to the more stable oxime as in https://www.rhodium.ws/chemistry/2ch.darzen.html

6. Finally the oxime is converted to the aldehyde via the Zn/NH4Cl2 or a Zn/K. Formate reduction.

The only concern I have is the demethylation of one of the methoxy groups. SIBX has found to demethylate eugenol however it seems that it only does does ortho demethylations. (Am I correct?).

IBX can be easily made from 2-iodobenzoic acid and our favorite oxone.

reduce.

armageddon
(Hive Bee)
09-10-04 18:19
No 530669
User Picture       SIBX or IBX

The only concern I have is the demethylation of one of the methoxy groups. SIBX has found to demethylate eugenol however it seems that it only does does ortho demethylations. (Am I correct?).

IBX can be easily made from 2-iodobenzoic acid and our favorite oxone.

Although SIBX has slight disadvantages (the demethylating capability you mention) in this case, its use is strongly recommended over that of regular IBX - the little "s" stands for "stabilized", as plain IBX is a rather violent explosive! shocked

(bee careful with that one!)

SIBX preparation:

"ortho-iodobenzoic acid (200g) and isophtalic acid (133g) are introduced into a solution of oxone (625g) in water (2L). The mixture is maintained under stirring at 70°C for 3 hours and then a solution of sodium benzoate (128g) in water (500ml) is added at 40°C. After cooling to 20°C, the precipitate is filtered off, washed with water (700ml) and dired in a ventilated oven at 60°C to obtain 420g (90%) of stabilized IBX composition (40% w/w of IBX)."

taken from A Stabilized Formulation of IBX (SIBX) for Save Oxidation Reactions Including a New Oxidative Demethylation of Phenolic Alkyl Aryl Esters (http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/ol0349965/ol0349965si20030623_024608.pdf)

greetz

Hehehe....

Nicodem
(Hive Bee)
09-10-04 19:05
No 530674
User Picture       A few comments

I see no particular reason for the step B/C when there are enough methods for the oxidation of benzylhalides directly to benzaldehydes. If you are interested I'll gather some references up.

And what is the point of using exotic reagents like IBX? By UTFSE, you can find an excelent PTC method for oxidizing benzyl alcohols to benzaldehydes with bleach/ethylacetate biphasic system posted by Ning some time ago.

I also see no advantage of using plain 1,4-dimethoxy-benzene since it gives a lousy yield if chloromethylated due to the dimerisation. Even though the bromomethylation gives a better yield I would still advise to halomethylate 2,5-dimethoxy-bromobenzene (or -chloro...) instead.

“The real drug-problem is that we need more and better drugs.” – J. Ott

Captain_America
(Hive Bee)
09-10-04 19:11
No 530676
      OTC 2C-H
(Rated as: excellent)

If you can get p-dimethoxybenzene I'm sure you can get p-methoxyphenol, if not then it could bee made from hydroquinone and benzoquinone in OTC fashion: Post 516970 (azole: "yet another O-monoalkylation of hydroquinone", Novel Discourse) For p-benzoquinone synthesis, read this thread: Post 374635 (Cyrax: "Yes, you can find it at page 1025 in the 5 th ...", Chemistry Discourse)

Formylation of p-MeO-phenol: Post 478447 (dioulasso: "Formylation w/ Mg(MeO)2 -- translation", Methods Discourse)

...or slightly more OTC but messier, a bit unpredictible R-T process:

Once you've introduced the formyl, you could methylate the formed 2-hydroxy-5-methoxybenzaldehyde with DMS as above or methyliodide, you can make it easily in good yield: Post 301629 (Antoncho: "Two tried-and-true ways to make MeI !", Chemistry Discourse). Now it is possible to alkylate the 2-hydroxy-5-methoxybenzaldehyde with MeI: Post 348592 (Antoncho: "Methyl iodide methylation of 2-OH-5-MeO-BA.", Chemistry Discourse)

For more examples of alkylations with alkylhalides, see: Post 223641 (IudexK2: "Pihkal: Alkylation of hydroxy-benzaldehydes", Chemistry Discourse)

Now you have 2,5-dimethoxybenzaldehyde to go from. It could be coupled with nitromethane (OTC) and reduced to yield 2C-H.

When condensing nitromethane with 2,5-dimeo-benzaldehyde a catalyst is used, for highest yields and purest product employ methylamine. It could bee made from OTC ingridients: Post 323193 (RoundBottom: "Chromic’s Methylamine.HCl", Methods Discourse) based on: Post 291265 (Chromic: "just to get you started", Methods Discourse) or Fe/HCl reduction of nitromethane, see; https://www.rhodium.ws/chemistry/eleusis/methylamine27.html#Nitromethane . For making the MeAm freebase as well as reducing the amount of water in later stage, see: Post 421720 (Barium: "Not so wet methylamine", Methods Discourse)

The catalyst is now ready, and you can start making the nitrostyrene, like described in this post; Post 419399 (Barium: "High-yielding nitrostyrene catalyst", Methods Discourse).

Now you have some very good and pure nitrostyrene. One step to 2C-H from here is by employing Zn/HCl reduction: Post 406397 (Sunlight: "Test done", Novel Discourse). This work is based on Leminger's work on mescaline analogs: https://www.rhodium.ws/chemistry/leminger.html This reduction seem optimal only on 2C-compounds (nitroethene), nitropropenes give ketons as main product.

Save all aqueous phases from reactions involving iodine (swaps, etc), pool, rreduce water and re-generate the expensive iodine w/ H2O2 at pH < 7.

Good luck... And report back...

amine
(Hive Bee)
09-10-04 22:05
No 530700
      Nicoderm, from what swim read post reaction...

Nicoderm, from what swim read post reaction the 2-iodobenzoic acid is formed again and this can be reoxidized to the IBX.
Once the 2-iodobenzoic acid is obtained it makes it possible for doing a large amount of oxidiations, the oxone is OTC.

(Swims interest in this proceedure mainly resides with working with (S)IBX)

Do you think it would be possible to oxidize the halomethyl compound with (S)IBX to the aldahyde? (SWIM did 2-3 step because he is unsure of this process. References on other forms of oxidation would be great.

Question: would the halomethylation of the 1-bromo-2,5-dimehtoxybenzene yield a 4-bromo-2,5-dimethoxy-benzylbromide?

reduce.

Captain_America
(Hive Bee)
09-10-04 22:11
No 530702
      UTFSE

Question: would the halomethylation of the 1-bromo-2,5-dimehtoxybenzene yield a 4-bromo-2,5-dimethoxy-benzylbromide?

Post 472828 (Nicodem: "2,5-Dimethoxybromobenzene Chloromethylation", Novel Discourse)

And read his post in this thread:

"I also see no advantage of using plain 1,4-dimethoxy-benzene since it gives a lousy yield if chloromethylated due to the dimerisation. Even though the bromomethylation gives a better yield I would still advise to halomethylate 2,5-dimethoxy-bromobenzene (or -chloro...) instead."

Nicodem
(Hive Bee)
09-11-04 07:41
No 530813
User Picture       Nevertheless...

Question: would the halomethylation of the 1-bromo-2,5-dimehtoxybenzene yield a 4-bromo-2,5-dimethoxy-benzylbromide?

You get both theoreticaly possible products, the 4-bromo- and 6-bromo-2,5-dimethoxy-benzylcloride. But off course due to some steric hinderance the 4-bromo- is somewhat prevalent.
You must read Post 299551 (karel: "Chloromethylation", Chemistry Discourse).

Nicoderm, from what swim read post reaction the 2-iodobenzoic acid is formed again and this can be reoxidized to the IBX.
Once the 2-iodobenzoic acid is obtained it makes it possible for doing a large amount of oxidiations, the oxone is OTC.

Yes sure you can regenerate it if you spend some extra work with the recycling. The point was that there are simpler methods which does not use reagents with such a high MW. You would need more (S)IBX by weight than your benzyl alcohol!
I will get you some references soon. Well, meanwhile UTFSE to find some yourself.

“The real drug-problem is that we need more and better drugs.” – J. Ott

amine
(Hive Bee)
09-13-04 22:36
No 531185
      Thanks Nicoderm, yes I have looked and found...

Thanks Nicoderm, yes I have looked and found several alternatives to IBX, the DMSO route looks interesting.

My main concern is the demethylation of the methoxy groups, looking at, does the DMSO route look gentle enough to leave the methoxy's alone?

Also why exactly is the 2-5,-dimethoxyphenylacetylaldehyde stable? (I guess I don't understand why it does not polymerize like other phenylacetylaldehydes)

reduce.

amine
(Hive Bee)
09-18-04 18:39
No 532015
      How about some o-anisaldehyde.

o-anisaldehyde is not to pricey around 100$ for 500g of the compound, and could be used as a route to 2CH.

Proposal:
1. o-anisaldehyde is brominated at the 5th position, the methoxy group is para to this and the aldahyde is meta, (it directs to 3 as well in the ortho/meta position) but it seems that the para/meta would be more prevelent.
(I'm sure a oxone/NaBr method would work here since).

2. the 5-bromo-o-anisaldehyde can be then undergo a substitution via the Cu(i)/NaOMe method to give the 2,5-dimethoxybenzaldehyde compound. This substition seems to work well for bromine which is meta towards the aldehyde.

It seems that o-anisaldehyde is not very watched according to swim's information.

reduce.

Rhodium
(Chief Bee)
09-18-04 18:49
No 532016
User Picture       2,5-dimethoxyphenylacetaldehyde

Also why exactly is the 2-5,-dimethoxyphenylacetylaldehyde stable? (I guess I don't understand why it does not polymerize like other phenylacetylaldehydes)

Neither will polymerize as you watch - if pure, and stored cold/dark, phenylacetaldehyde will keep for a year or more.
It will easily polymerize if containing acidic/basic impurities or when heated.

2,5-dimethoxyphenylacetaldehyde synthesis/preparation: https://www.rhodium.ws/chemistry/25-dimethoxy-paa.html

^{The Hive - Clandestine Chemists Without Borders}

Captain_America
(Hive Bee)
09-18-04 22:46
No 532051
      5-bromo-2-methoxybenzaldehyde

That idea occured to me too when I wanted to look at possible ways to tweetios of 2C-X. 2-ethoxy compounds of this family could bee prepared easily from p-methoxyphenol. The problem was that the only practical OTC way to aldehydes I knew then was Reimer-Tiemann. Unfortunately, the application of R-T on p-ethoxyphenol gives very poor yields for some reason. So, the solution for 5-ethoxy tweetio problem would bee bromination of 2-methoxybenzaldehyde followed by ethoxide swap. Anyways, following bromination gave crappy yield, for better yield and nicer procedure see the ref*:

5-Bromo-2-methoxybenzaldehyde was prepared from o-anisaldehyde (2.6 g, 20 mmol) and Br₂ (1.2 molar equiv) in glacial CH₃COOH. A portion (0.927 g) of the crude product was heated to dissolution in absolute EtOH (ca. 18-20 mL), and the solution was filtered, treated with H₂O (ca. 10 mL), and allowed to stand at rT. The material that separated was isolated (0.776 g) and recrystallized again from absolute EtOH, and dried in air: pale yellow crystalline solid (0.573 g); mp 113.5-116.5 °C (lit. mp 116-119°C)

*For in situ bromination of o-methoxybenzaldehyde with oxone and NaBr in high yield see: Koo, Bon-Suk; Kim, Eun-Hoo; Lee, Kee-Jung; Synth.Commun.; 32; 15; 2002; 2275 - 2286.

Alkyloxy swap is analogus as w/ 5-Br-vanillin.

amine
(Hive Bee)
09-18-04 23:26
No 532056
      Bromination of Electron Rich Benzaldehydes

Here is article referenced by Captain America in post:
Post 532051 (Captain_America: "5-bromo-2-methoxybenzaldehyde", Methods Discourse)

Bromodecarbonylation and Bromodecarboxylatoin of electron-rich benzaldehydes and benzoic acid with Oxone and sodium bromide.
SYNTHETIC COMMUNICATIONS. Vol. 32, No. 15, pp. 2275–2286, 2002.
Bon-Suk Koo, Eun-Hoo Kim, and Kee-Jung Lee

Abstract:
Benzaldehydes and benzoic acids bearing ortho- and paraelectron donating substituents having unshared electron-pair have undergone bromodecarbonylation or bromodecarboxylation on treatment with sodium bromide in the presence of Oxone aqueous methanol.

General procedure for the reaction of benzaldehydes with Oxone and Sodium Bromide:
To a stirred solutions of benzaldehydes (5 mmol) in aqueous methanol (70mL, 1 : 1 by volume) was added NaBr (2.57 g, 25 mmol) and Oxone (3.07 g, 5 mmol or 6.14 g, 10 mmol). The reaction was continuously monitored by thin-layer chromatography and stirred at r.t. for generally 4–24 h. The reaction mixture was quenched with aqueous sodium thiosulfate and extracted with ether (350 mL). The combined organic layers were washed with water, dried over anhydrous MgSO4, filtered, and concentrated in vacuo.

For the purposes in this thread (bromination of o-anisaldehyde to 5-bromo-o-anisaldehyde), it is worth noting that the yield was 72% by using a 1 equiv. of oxone.

reduce.

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	All 12 posts		Subject: 2CH via IBX		Please login to post		Down


		amine (Hive Bee) 09-10-04 18:00 No 530665				2CH via IBX
						There has been a few posts in the novel discourse of the hive, using the oxider IBX to convert benzyl alcohols into aldahydes. Post 520376 (metanoid: "Aldehydes & Ketones w/IBX", Novel Discourse) 1. (A) 1-4-dimethoxybenzene is bromomethylated using HBr and Formaldahyde as in Post 472838 (Rhodium: "Bromomethylation of 1,4-Dimethoxybenzene", Methods Discourse). Alternatively the proceedure by legos could be used: (HBr is made in-stu) Post 475109 (Lego: "Amphetamines/PEAs w/o benzaldehyde or nitroethane", Novel Discourse) 2. (B) monobromomethylated compound is reacted with KOH/NaOH to prdouce the benzyl alcohol (2,5-dimethoxybenzyl alcohol in this case) 3. (C) The benzyl alcohol is reacted with IBX Post 520376 (metanoid: "Aldehydes & Ketones w/IBX", Novel Discourse) or SIBX Post 451672 (Rhodium: "Novel Oxidative Demethylation of Eugenol", Novel Discourse) to reach the corresponding aldahyde. 4. The aldahyde undergoes a darzen condensation similar to the proceedure by barium. Post 339354 (Barium: "Check this out!!", Novel Discourse) The reaction could be modified to use methyl 2-chloroacetate instead of the methyl 2-chloropropionate. 5. The phenylacetaldehyde is converted to the more stable oxime as in https://www.rhodium.ws/chemistry/2ch.darzen.html 6. Finally the oxime is converted to the aldehyde via the Zn/NH4Cl2 or a Zn/K. Formate reduction. The only concern I have is the demethylation of one of the methoxy groups. SIBX has found to demethylate eugenol however it seems that it only does does ortho demethylations. (Am I correct?). IBX can be easily made from 2-iodobenzoic acid and our favorite oxone. reduce.



		armageddon (Hive Bee) 09-10-04 18:19 No 530669				SIBX or IBX
						The only concern I have is the demethylation of one of the methoxy groups. SIBX has found to demethylate eugenol however it seems that it only does does ortho demethylations. (Am I correct?). IBX can be easily made from 2-iodobenzoic acid and our favorite oxone. Although SIBX has slight disadvantages (the demethylating capability you mention) in this case, its use is strongly recommended over that of regular IBX - the little "s" stands for "stabilized", as plain IBX is a rather violent explosive! (bee careful with that one!) SIBX preparation: "ortho-iodobenzoic acid (200g) and isophtalic acid (133g) are introduced into a solution of oxone (625g) in water (2L). The mixture is maintained under stirring at 70°C for 3 hours and then a solution of sodium benzoate (128g) in water (500ml) is added at 40°C. After cooling to 20°C, the precipitate is filtered off, washed with water (700ml) and dired in a ventilated oven at 60°C to obtain 420g (90%) of stabilized IBX composition (40% w/w of IBX)." taken from A Stabilized Formulation of IBX (SIBX) for Save Oxidation Reactions Including a New Oxidative Demethylation of Phenolic Alkyl Aryl Esters (http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/ol0349965/ol0349965si20030623_024608.pdf) greetz Hehehe....



		Nicodem (Hive Bee) 09-10-04 19:05 No 530674				A few comments
						I see no particular reason for the step B/C when there are enough methods for the oxidation of benzylhalides directly to benzaldehydes. If you are interested I'll gather some references up. And what is the point of using exotic reagents like IBX? By UTFSE, you can find an excelent PTC method for oxidizing benzyl alcohols to benzaldehydes with bleach/ethylacetate biphasic system posted by Ning some time ago. I also see no advantage of using plain 1,4-dimethoxy-benzene since it gives a lousy yield if chloromethylated due to the dimerisation. Even though the bromomethylation gives a better yield I would still advise to halomethylate 2,5-dimethoxy-bromobenzene (or -chloro...) instead. “The real drug-problem is that we need more and better drugs.” – J. Ott



		Captain_America (Hive Bee) 09-10-04 19:11 No 530676				OTC 2C-H (Rated as: excellent)
						If you can get p-dimethoxybenzene I'm sure you can get p-methoxyphenol, if not then it could bee made from hydroquinone and benzoquinone in OTC fashion: Post 516970 (azole: "yet another O-monoalkylation of hydroquinone", Novel Discourse) For p-benzoquinone synthesis, read this thread: Post 374635 (Cyrax: "Yes, you can find it at page 1025 in the 5 th ...", Chemistry Discourse) Formylation of p-MeO-phenol: Post 478447 (dioulasso: "Formylation w/ Mg(MeO)2 -- translation", Methods Discourse) ...or slightly more OTC but messier, a bit unpredictible R-T process: Once you've introduced the formyl, you could methylate the formed 2-hydroxy-5-methoxybenzaldehyde with DMS as above or methyliodide, you can make it easily in good yield: Post 301629 (Antoncho: "Two tried-and-true ways to make MeI !", Chemistry Discourse). Now it is possible to alkylate the 2-hydroxy-5-methoxybenzaldehyde with MeI: Post 348592 (Antoncho: "Methyl iodide methylation of 2-OH-5-MeO-BA.", Chemistry Discourse) For more examples of alkylations with alkylhalides, see: Post 223641 (IudexK2: "Pihkal: Alkylation of hydroxy-benzaldehydes", Chemistry Discourse) Now you have 2,5-dimethoxybenzaldehyde to go from. It could be coupled with nitromethane (OTC) and reduced to yield 2C-H. When condensing nitromethane with 2,5-dimeo-benzaldehyde a catalyst is used, for highest yields and purest product employ methylamine. It could bee made from OTC ingridients: Post 323193 (RoundBottom: "Chromic’s Methylamine.HCl", Methods Discourse) based on: Post 291265 (Chromic: "just to get you started", Methods Discourse) or Fe/HCl reduction of nitromethane, see; https://www.rhodium.ws/chemistry/eleusis/methylamine27.html#Nitromethane . For making the MeAm freebase as well as reducing the amount of water in later stage, see: Post 421720 (Barium: "Not so wet methylamine", Methods Discourse) The catalyst is now ready, and you can start making the nitrostyrene, like described in this post; Post 419399 (Barium: "High-yielding nitrostyrene catalyst", Methods Discourse). Now you have some very good and pure nitrostyrene. One step to 2C-H from here is by employing Zn/HCl reduction: Post 406397 (Sunlight: "Test done", Novel Discourse). This work is based on Leminger's work on mescaline analogs: https://www.rhodium.ws/chemistry/leminger.html This reduction seem optimal only on 2C-compounds (nitroethene), nitropropenes give ketons as main product. Save all aqueous phases from reactions involving iodine (swaps, etc), pool, rreduce water and re-generate the expensive iodine w/ H2O2 at pH < 7. Good luck... And report back...



		amine (Hive Bee) 09-10-04 22:05 No 530700				Nicoderm, from what swim read post reaction...
						Nicoderm, from what swim read post reaction the 2-iodobenzoic acid is formed again and this can be reoxidized to the IBX. Once the 2-iodobenzoic acid is obtained it makes it possible for doing a large amount of oxidiations, the oxone is OTC. (Swims interest in this proceedure mainly resides with working with (S)IBX) Do you think it would be possible to oxidize the halomethyl compound with (S)IBX to the aldahyde? (SWIM did 2-3 step because he is unsure of this process. References on other forms of oxidation would be great. Question: would the halomethylation of the 1-bromo-2,5-dimehtoxybenzene yield a 4-bromo-2,5-dimethoxy-benzylbromide? reduce.



		Captain_America (Hive Bee) 09-10-04 22:11 No 530702				UTFSE
						Question: would the halomethylation of the 1-bromo-2,5-dimehtoxybenzene yield a 4-bromo-2,5-dimethoxy-benzylbromide? Post 472828 (Nicodem: "2,5-Dimethoxybromobenzene Chloromethylation", Novel Discourse) And read his post in this thread: "I also see no advantage of using plain 1,4-dimethoxy-benzene since it gives a lousy yield if chloromethylated due to the dimerisation. Even though the bromomethylation gives a better yield I would still advise to halomethylate 2,5-dimethoxy-bromobenzene (or -chloro...) instead."



		Nicodem (Hive Bee) 09-11-04 07:41 No 530813				Nevertheless...
						Question: would the halomethylation of the 1-bromo-2,5-dimehtoxybenzene yield a 4-bromo-2,5-dimethoxy-benzylbromide? You get both theoreticaly possible products, the 4-bromo- and 6-bromo-2,5-dimethoxy-benzylcloride. But off course due to some steric hinderance the 4-bromo- is somewhat prevalent. You must read Post 299551 (karel: "Chloromethylation", Chemistry Discourse). Nicoderm, from what swim read post reaction the 2-iodobenzoic acid is formed again and this can be reoxidized to the IBX. Once the 2-iodobenzoic acid is obtained it makes it possible for doing a large amount of oxidiations, the oxone is OTC. Yes sure you can regenerate it if you spend some extra work with the recycling. The point was that there are simpler methods which does not use reagents with such a high MW. You would need more (S)IBX by weight than your benzyl alcohol! I will get you some references soon. Well, meanwhile UTFSE to find some yourself. “The real drug-problem is that we need more and better drugs.” – J. Ott



		amine (Hive Bee) 09-13-04 22:36 No 531185				Thanks Nicoderm, yes I have looked and found...
						Thanks Nicoderm, yes I have looked and found several alternatives to IBX, the DMSO route looks interesting. My main concern is the demethylation of the methoxy groups, looking at, does the DMSO route look gentle enough to leave the methoxy's alone? Also why exactly is the 2-5,-dimethoxyphenylacetylaldehyde stable? (I guess I don't understand why it does not polymerize like other phenylacetylaldehydes) reduce.



		amine (Hive Bee) 09-18-04 18:39 No 532015				How about some o-anisaldehyde.
						o-anisaldehyde is not to pricey around 100$ for 500g of the compound, and could be used as a route to 2CH. Proposal: 1. o-anisaldehyde is brominated at the 5th position, the methoxy group is para to this and the aldahyde is meta, (it directs to 3 as well in the ortho/meta position) but it seems that the para/meta would be more prevelent. (I'm sure a oxone/NaBr method would work here since). 2. the 5-bromo-o-anisaldehyde can be then undergo a substitution via the Cu(i)/NaOMe method to give the 2,5-dimethoxybenzaldehyde compound. This substition seems to work well for bromine which is meta towards the aldehyde. It seems that o-anisaldehyde is not very watched according to swim's information. reduce.



		Rhodium (Chief Bee) 09-18-04 18:49 No 532016				2,5-dimethoxyphenylacetaldehyde
						Also why exactly is the 2-5,-dimethoxyphenylacetylaldehyde stable? (I guess I don't understand why it does not polymerize like other phenylacetylaldehydes) Neither will polymerize as you watch - if pure, and stored cold/dark, phenylacetaldehyde will keep for a year or more. It will easily polymerize if containing acidic/basic impurities or when heated. 2,5-dimethoxyphenylacetaldehyde synthesis/preparation: https://www.rhodium.ws/chemistry/25-dimethoxy-paa.html ^{The Hive - Clandestine Chemists Without Borders}



		Captain_America (Hive Bee) 09-18-04 22:46 No 532051				5-bromo-2-methoxybenzaldehyde
						That idea occured to me too when I wanted to look at possible ways to tweetios of 2C-X. 2-ethoxy compounds of this family could bee prepared easily from p-methoxyphenol. The problem was that the only practical OTC way to aldehydes I knew then was Reimer-Tiemann. Unfortunately, the application of R-T on p-ethoxyphenol gives very poor yields for some reason. So, the solution for 5-ethoxy tweetio problem would bee bromination of 2-methoxybenzaldehyde followed by ethoxide swap. Anyways, following bromination gave crappy yield, for better yield and nicer procedure see the ref: 5-Bromo-2-methoxybenzaldehyde was prepared from o-anisaldehyde (2.6 g, 20 mmol) and Br₂ (1.2 molar equiv) in glacial CH₃COOH. A portion (0.927 g) of the crude product was heated to dissolution in absolute EtOH (ca. 18-20 mL), and the solution was filtered, treated with H₂O (ca. 10 mL), and allowed to stand at rT. The material that separated was isolated (0.776 g) and recrystallized again from absolute EtOH, and dried in air: pale yellow crystalline solid (0.573 g); mp 113.5-116.5 °C (lit. mp 116-119°C) For in situ bromination of o-methoxybenzaldehyde with oxone and NaBr in high yield see: Koo, Bon-Suk; Kim, Eun-Hoo; Lee, Kee-Jung; Synth.Commun.; 32; 15; 2002; 2275 - 2286. Alkyloxy swap is analogus as w/ 5-Br-vanillin.



		amine (Hive Bee) 09-18-04 23:26 No 532056				Bromination of Electron Rich Benzaldehydes
						Here is article referenced by Captain America in post: Post 532051 (Captain_America: "5-bromo-2-methoxybenzaldehyde", Methods Discourse) Bromodecarbonylation and Bromodecarboxylatoin of electron-rich benzaldehydes and benzoic acid with Oxone and sodium bromide. SYNTHETIC COMMUNICATIONS. Vol. 32, No. 15, pp. 2275–2286, 2002. Bon-Suk Koo, Eun-Hoo Kim, and Kee-Jung Lee Abstract: Benzaldehydes and benzoic acids bearing ortho- and paraelectron donating substituents having unshared electron-pair have undergone bromodecarbonylation or bromodecarboxylation on treatment with sodium bromide in the presence of Oxone aqueous methanol. General procedure for the reaction of benzaldehydes with Oxone and Sodium Bromide: To a stirred solutions of benzaldehydes (5 mmol) in aqueous methanol (70mL, 1 : 1 by volume) was added NaBr (2.57 g, 25 mmol) and Oxone (3.07 g, 5 mmol or 6.14 g, 10 mmol). The reaction was continuously monitored by thin-layer chromatography and stirred at r.t. for generally 4–24 h. The reaction mixture was quenched with aqueous sodium thiosulfate and extracted with ether (350 mL). The combined organic layers were washed with water, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. For the purposes in this thread (bromination of o-anisaldehyde to 5-bromo-o-anisaldehyde), it is worth noting that the yield was 72% by using a 1 equiv. of oxone. reduce.

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