GC_MS
(Hive Addict)
02-27-03 10:23
No 412323
      Can benzaldehydes be made via Fries rearrangement?
(Rated as: excellent)
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Yes, they can. It took me a damn long time to find some sort of reliable article supporting my "dreams"...

What is the Fries rearrangement? - Esters of phenols on heating with anhydrous AlCl3 (a typical Lewis acid) undergo rearrangement to give phenolic ketones. A typical example is rearrangement of phenyl acetate to give mixture of o- and p-hydroxy acetophenone. [...] The mechanism of Fries reaction is not certain. There is evidence for an intermolecular mechanism, but recently it has been shown that the rearrangement is at least partly intramolecular. It would appear that the mechanism is best regarded as a combination of the two mechanisms occuring simultaneously. [...] An example is the synthesis of 2-hydroxy-4,6-dimethylacetophenone in 80% yield. A synthetically useful example of this process is the preparation of 2,5-dihydroxyacetophenone from hydroquinone diacetate in good yield. 2,5-dihydroxyacetophenone can not be prepared by Friedel-Crafts acetylation of hydroquinone. (taken from: Organic Reaction Mechanisms. VK Ahluwalia, RK Parashar. Alpha Science, Pangbourne Engeland, 2002)

References:
- K Fries, G Fink. Berichte 41 (1908) 4271
- K Fries, W Platendorf. Berichte 43 (1910) 212
- AH Bhat. Chem Rev 27 (1940) 429

Can aromatic aldehydes be prepared from aryl formates via the Fries rearrangement? - The original article has been published in Zeitschrift fuer Naturforschung, so I guess yet again it is a small number of elite bees who can have a taste of some really nice chemistry *cough* *cough*
Original article: G Ziegler, E Haug, W Frey, W Kantlehner. Orthoamide, LVII. Lassen sich aromatische Aldehyde nach Fries aus Arylformiaten herstellen? Z Naturforsch 56b (2001) 1178-1187
Abstract: The aromatic hydroxyaldehydes 3a-3g, 5a-5f, 8, 10 can be prepared by the action of BCl3, BBr3 or trifluoromethanesulfonic acid, on the aryl formates 1a-1f, 4a-e, 7, 9 via Fries rearrangement. BBr3 is more effective than BCl3. The activating ability of BBr3 can be improved by addition of FeCl3. Rearrangements which are induced by trifluoromethanesulfonic acid can give rise to the formations of regioisomers, which might be different from the products formed when the reaction is performed with Lewis acids. The yields of the aldehydes are lowered by subsequent condensation reactions. This view was confirmed by the isolation of a condensation product, which was characterized as a dibenzo[a,j]xanthene derivative 6 by crystal structure analysis. For the Fries rearrangement of formyl groups a new mechanism is proposed. 2-Hydroxy-1-naphthaldehyde 5c can be obtained in good yield from formic acid, BBr3, and 2-naphtol.
Translated Capita Selecta: [...] The usual Lewis acids that have been applied in the Fries rearrangement are AlCl3, FeCl3, BF3, SnCl4, TiCl4 and ZnCl2. Since recently, trifluoromethanesulfonic derivatives of rare metals have found an application as well. However, we were very surprised when we didn't find any reported use of BCl3 nor BBr3 as Fries catalyst.
In a first setup, 3,5-dimethoxy-O-formyl phenol (1a) has been reacted with BCl3 (1:1.2) using DCE as solvent. Temperatures varied between 5 and 20. Benzaldehyde 3a was isolated in 94% yield.
3-methoxy-O-formyl phenol (1b) has been reacted with BCl3 in a similar way, although the corresponding benzaldehyde 3b could only be isolated in 27% yield. Using BBr3 instead increased the yield to 59%. Also using BBr3, we could obtain benzaldehyde 3d from 1c in 72% yield.

3a - 2-hydroxy-4,6-dimethoxybenzaldehyde: to 7.28 g (0.040 mol) 1a in 20 mL DCE, 50 mL 1 M BCl3 (in DCE) is dropped while cooled in an ice bath. The ice bath is removed and the mixture allowed to react for an additional 2 hours at RT. The mixture is hydrolyzed with 100 mL water and filtered. The organic phase is isolated, washed with 20 mL water and dried over Na2SO4. The solvent is removed at 12 Torr and the residue is recrystallized from water/IPA (1:4). Yield: 94%, mp 69.
3b - 2-hydroxy-4-methoxybenzaldehyde (via BBr3): To a solution of 4.62 g (0.030 mol) 1b in 25 mL DCE, 7.50 g (0.030 mol) BBr3 in 5 mL DCE is added dropwise at a temperature between -10 and 0. After having stirred for three hours, the mixture is stirred for another 20 hours at 20 to pour it in 500 mL water (containing some ice and 8.4 g NaHCO3). An additional 5 mL DCE is added and the mixture acidified with a small amount HOAc. The organic phase is isolated, and the aqueous phase extracted with 50 mL DCE. The unified organic fractions are washed with water and stripped from solvent under vacuum. The target compound is obtained via steam distillation, filtered off and dried. Yield: 59%, mp: 43.
3d - 2-hydroxy-4,5-dimethoxybenzaldehyde: To 1.82 g (0.010 mol) 1c in 20 mL DCE, a solution of 1.1 mL BBr3 in 5 mL DCE (at -14) is added dropwise. When the addition is completed, the temperature is allowed to rise to 15 during the next 1.5 hours. The reaction mixture is hydrolyzed by pouring it into a solution of 0.1 mol NaHCO3 in 200 mL water. The organic phase was isolated and the aqueous phase treated twice with 50 mL DCE. The unified DCE fractions are washed with 50 mL water and dried over Na2SO4. After distillation of the solvent, 1.30 g of 3d can be retrieved. It is spectroscopically pure (1H-NMR) and can be recrystallized from water/MeOH (1:8). Yield: 72%, mp: 104

Structures:
        
O-X
              |
              C
           /    \
          C      C---Y        1a: X=-CHO : Y=-H
          |      |            3a: X=-X   : U=-CHO
          |      |
   H3CO---C      C---OCH3
           \    /
              C
             
              O-X
              |
              C
           /    \
      Y---C      C            1b: X=-CHO : Y=-H
          |      |            3b: X=-X   : U=-CHO
          |      |
          C      C---OCH3
           \    /
              C
             
              O-X
              |
              C
           /    \
      Y---C      C            1c: X=-CHO : Y=-H
          |      |            3d: X=-X   : U=-CHO
          |      |
          C      C---OCH3
           \    /
              C
              |
              OCH3



Conclusion: I know there are easier (and certainly much cheaper!) alternatives that can be used to obtain "exotic" benzaldehydes. However, there always are bees with plenty of cash, too much chemical curiousity, ... I stumbled on the article when I was looking for a way to obtain benzaldehydes via the Fries rearrangement (they told me it was impossible, mwuahahahahahaha) and while looking for some routes to asaraldehyde. Voila, that's it... Enjoy.



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