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Methoxybenzene in one pot from aniline?
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64bandil
Busy Bee
Joined: 22 Mar 2005
Posts: 35
1508.72 Points

Tue Mar 22, 2005 5:36 am
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Hi All!

The current MMA (3-methoxy-4-methyl-amphetamine) route is a tad long for my lazy ass.

There are really two ways to go from tolualdehyde.

1: Swamp with AlCl3 and brominate in ~45% yield. Swap with sodium methoxide to yield methoxymethylBA (somewhat easy, but very low yielding)

2: Nitrate in high yield, reduce to amine, do a sandmeyer to get the diazotiated intermediate. Hydrolyze and methylate... Yeilds are ok, but its a loooong procedure.

Anything wrong with doing the sandmeyer, and plunking the N2+ complex directly into some methanolic sodiummethoxide? Shouldnt this know nitrogen of, leaving nothing but methoxylated compounds and some good old sodium chloride?

Regards
Bandil
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anime

Joined: 13 Apr 2005
Posts: 131
Location: Planet Earth
3517.62 Points

Thu Apr 14, 2005 10:03 pm
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Bandil,

The bromination of the aldehyde can be done in higher yields using NBS, FeCl3 in CH3CN. I have the details if you would like, deactivated groups are brominated in high yields (90%+).

Not sure on the yields for the Methoxide substitution, how low are the yields?
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Dr.Bunsen

Joined: 20 Feb 2005
Posts: 14
280.86 Points

Fri Apr 15, 2005 2:27 am
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m-Methoxybenzaldehyde has been prepared by the reaction of diazotized m-aminobenzaldehyde with methanol. Noelting, Ann. chim., ( 8 ) 19, 541 (1910)

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0564


64bandil wrote:
Hi All!

The current MMA (3-methoxy-4-methyl-amphetamine) route is a tad long for my lazy ass.

There are really two ways to go from tolualdehyde.

1: Swamp with AlCl3 and brominate in ~45% yield. Swap with sodium methoxide to yield methoxymethylBA (somewhat easy, but very low yielding)

2: Nitrate in high yield, reduce to amine, do a sandmeyer to get the diazotiated intermediate. Hydrolyze and methylate... Yeilds are ok, but its a loooong procedure.

Anything wrong with doing the sandmeyer, and plunking the N2+ complex directly into some methanolic sodiummethoxide? Shouldnt this know nitrogen of, leaving nothing but methoxylated compounds and some good old sodium chloride?

Regards
Bandil
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