Baeyer-Villiger Oxid. --> Methoxybenzaldehydes

[Aurelius]

Preparation of Methoxyphenols by Baeyer-Villiger Oxidation of Methoxybenzaldehydes

By Ian M. Godfrey and Melvyn V. Sargent, John A. Elix

J. Chem. Soc. Perkin. Trans. 1, 1353-1554  (1974)


Abstract:

Baeyer-Villiger Oxidation of methoxybenzaldehydes with m-chlorobenzoic acid in boiling DCM followed by hydrolysis of the resultant formates, is shown to be a convenient method for the preparation of methoxyphenols.

In connection with our work on depsidones we required a convenient route to some dimethoxymethylphenols.  The Baeyer-Villiger oxidation of the corresponding benzaldehydes appeared to be an attractive method since the aldehydes are easily available.  This type of oxidation had previously been carried out by using peracetic acid under a variety of conditions.^1-6 The reported yields were often low^3-4 (see however ref. 7), or the use of anhydrous peracetic acid was required.^5-6

We now report that such oxidations can conveniently be carried out by using the commercially available m-chlorobenzoic acid in boiling DCM.  Under these conditions the formates were usually produced in almost quantitative yields and they were hydrolyzed to the phenol under mild conditions.  The overall yield for the more complex compounds (see Table) were generally high.

The required benzaldehydes were easily prepared by the Vilsmeier-Haack method.  The usual literature procedure ⁸ often gave rise to a violently exothermic reaction.  The modification described (see Experimental) was found to be preferable.

Experimental:

MP’s were determined on a Kofler hot-stage apparatus.  Light petroleum refers to the fraction at BP: 58-65*C.  NMR spectra were determined for solutions in deuteriochloroform with a Varian A-60A spectrometer.

Vilsmeier-Haack Reactions

The Vilsmeier complex was prepared by the dropwise addition of freshly distilled phosphoryl chloride (55ml) to dry N,N-dimethylformamide (100ml) during 15 minutes with stirring and cooling in ice.  The complex was allowed to warm to RT and was then added during 1-1.5hours to a stirred solution of the substrate (0.5mol) in dry DMF (100ml) at 100-110*C (bath).  Heating and stirring were then continued until TLC indicated that substrate had been consumed (usually 1-2hours).  The mix was poured onto ice-water, made just basic by the addition of sodium carbonate aqueous solution and then exhaustively extracted with ethyl acetate.  The combined extracts were washed successively with dilute HCl, water, and sat. NaCl, then dried over Na₂SO₄.  The crude product was then purified by distillation under reduced pressure or by crystallization.  The following substituted benzaldehydes were obtained:


4-MeO-2,5-dimethyl (76%) as an oil that had; BP: 85-86*C/0.4mmHg (lit. ⁹ 147-149*C at 12mmHg) which crystallized on cooling

2,4-dimethoxy (99%) as pale yellow needles that had; MP: 68-69*C (from ethanol) (lit¹⁰ 71-72*C)

2,4-dimethoxy-5-methyl (84%) as needles that had MP: 65-66*C (From DCM/light petroleum) (lit¹¹ 64-66*C)

2,4-dimethoxy-3-methyl (83%) glistening needles that had; MP: 52-53*C (from light petroleum) (lit¹⁰ 54-55*C) 

2,4-dimethoxy-5-methyl (87%) from the  toluene¹² as needles that had; MP: 118-119*C (lit¹³ 117-118*C) (from methanol)

2,4-dimethoxy-3,6-dimethyl-(93%) from beta-orcinol di-O-methylether¹⁴ as needles that had; MP: 49-50.5*C (from light pet.) (lit ¹⁵ 47-48*C)

2,4,5-trimethoxy (88%) from 1,2,4-trimethoxybenzene¹⁶ as needles (from water) that had; MP: 112-112.5*C (lit¹⁷ 114*C)

2,3,4,6-tetramethoxy (86%) from 1,2,3,5-tetramethoxybenzene¹⁸ as needles (from light pet.) that had; MP: 87-88*C (lit ¹⁹88-89.5*C)




1. J. Boesken and J. Greup, Rec. Trav. Chim., (1939), 53, 528.

2. A. von Wacek and A. von Bezard, Ber, (1941), 74B, 845

3. D. G. Orphanos and A. Taurins, Canad. J. Chem., (1966), 44, 1875.

4. R. Royer, P. Demerseman, A.-M. Laval-Jeantet, J.-F. Rossignol, and A. Cheutin, Bull. Soc. Chim. France, (1968), 1026.

5. D. G. Crosby, J. Org. Chem., (1961), 26, 1215.

6. R. Hue, A. Jubier, J. Andieux, and a. Resplandy, Bull. Soc. Chim. France, (1970), 3617.

7. Y. Ogata, and Y. Sawaki, J. Org. Chem., (1969), 34, 3985.

8. N. P. Buu-Hoi, N. D. Xuong, M. Sy, G. Lejeune, and N. B. Tien, Bull. Soc. Chim. France, (1955), 1594, ; N. P. Buu-Hoi, G. Lejeune, and M. Sy, Compt. Rend. , (1955), 240, 2241.

9. G. R. Clemo, R. D. Haworth, and E. Walton, J. Chem. Soc, (1929), 2368.

10. J. P. Lambooy, J. Amer. Chem. Soc, (1956), 78, 771

11. A.Robertson and R. Robinson, J. Chem Soc. , (1927), 2196

12. D. J. Cram, J. Amer. Chem. Soc., (1948), 70, 4240

13. D. J. Cram and F. W. Cranz, J. Amer. Chem. Soc., (1950), 72, 595

18. W. Baker, J. Chem. Soc., (1941), 662

19. F. Benington, R.D. Morin, and L.C. Clark, jun, J. Org. Chem., (1955), 20, 102

[GC_MS]

It's already on Rh's page concerning Various Formylation Reactions, no?

[Aurelius]

Baeyer-Villiger Reactions

The benzaldehyde (10mmol) and m-chlorobenzoic acid (2.53g) were heated under reflux in dry DCM (40ml) for the specified time.  (the Reaction can be followed by NMR spec.)  Most of the DCM was removed by distillation and the residue was dissolved in ethyl acetate.  The solution was washed with sodium bicarbonate until effervescence ceased, and then with sat. NaCl and dried over Na₂SO₄.  Removal of the solvent left the crude formate which was dissolved in a little methanol and hydrolyzed under nitrogen (0.5-1hour) with a slight excess of aqueous 10% KOH at RT.  Work-up in the usual way gave the following phenols:


2-MeO : as prisms (from pentane) that had; MP: 25-26*C (lit ²⁰ 28.3*C)

3-MeO : as the oil (the aryloxyacetic acid formed needles from light pet. that had; MP: 111.5-112.5*C [lit²¹ 111-113*C]

4-MeO : as blades that had; MP: 52-54*C (lit ²² 53*C) (from light pet.) [the formate formed needles that had; MP:32-34*C (lit²³ 32-33*C) (from pentane)]

4-Cl-2-MeO-3-Me : as plates by sublimation at 30*C and 0.5mmHg that had; MP: 44-45*C

4-MeO-2,5-diMe : as needles that had; MP: 88.5-89.5*C (lit ²⁴ 90*C) (from light pet.)

2,4-diMeO : as prisms that had; MP: 25-.27*C (lit ²⁵ 28*C) (from pentane)

3,4-diMeO : as plates that had; MP: 79*C (lit ¹ 81.5*C) (from light pet.) [the formate formed prisms that had; MP: 56*C (lit ² 57*C)(from ethanol)]

2,4-diMeO-3-Me : as plates (from pentane) that had; MP: 32.5-34*C (lit⁴ BP: 132*C/15mmHg)

2,4-diMeO-5-Me : as needles (from light pet.) that had; MP: 95.3-96*C (lit ⁴ 96*C)

2,4-diMeO-6-Me : as plates that had; MP: 103-104*C (lit²⁵ 107*C) (from DCM/light pet.)

2,4-diMeO-3,6-diMe : as prisms that had; MP: 68.5-69*C (from light pet.)

3-EtOcarbonyl-2,6-diMeO-4-Me : as plates that had; MP: 83-86*C (from light pet.)  [the starting aldehyde had; BP: 150-155*C/0.8mmHg

2,3,4-triMeO : as an oil [the benzoate had; MP: 69 (lit²⁵ 70 and 80*C, dimorphic) (from DCM/light pet.)]

2,4,5-triMeO : as prisms that had; MP: 61-62*C (lit ²⁵ 62*C) (from ether/light pet.) [the formate as needles (from light pet.) that had; MP: 78-80*C (lit⁶ 78-80*C)]

2,3,4,6-tetraMeO : as plates that had; MP: 87-88*C (from light pet.)




20. W. H. Perkin, J. Chem. Soc., (1896), 69, 1025

21. C. F. Koelsch, J. Amer. Chem. Soc., (1931), 53, 304

22. H. Hlasiwetz and J. Habermann, Annalen, (1875), 177, 334

23. A. van Es and W. Stevens, Rec. Trav. Chim., (1965), 84, 1247

24. E. Bamberger and J. Frei, Ber., (1907), 40, 1932

25. E. Spath, M. Pailer, and G. Gergely, Ber. (1940), 73B, 795

26. F. Schaaf and A Labouchere, Helv. Chim. Acta., (1924), 7, 357

[Aurelius]

It was a personal request from Rhodium to have it typed.  He likes having things in ASCII format so text can be copied and worked into other formats much more easily than PDF.

[Rhodium]

GC_MS: It is not only formylation reactions, it also concerns Bayer-Villiger oxidations of benzaldehydes to phenols, which makes 4-Methoxybenzaldehyde (and extended even further, anethole from anise oil) possible precursors to the 2C-X series.

[GC_MS]

But mCPBA for Baeyer-Villiger oxidations? Your second name must be Trump I guess   .

Now we are on the B-V subject, any idea why vanillin over-oxidizes when subjecting it to a peracid oxidation, but is oxidized in nearly quantitative yield when using a Dakin-based method?

[Rhodium]

Might it be that one is performed in acidic and the other in basic solution? Most oxidizers are more aggressive at lower pH.

And regarding mCPBA - the above is mainly meant as an illustration of the procedure, inspired chemists can then try substitution of the peracid to another (such as peracetic, or maybe simple perbenzoic acid if peracetic would be too strong).

[Rhodium]

Use of Theoretical Chemistry To Explain Baeyer-Villiger Oxidations of Methoxybenzaldehydes
N. Anoune, H. Hannachi, P. Lantéri, R. Longeray, and C. Arnaud

J. Chem. Educ. 75, 1290-1291 (1998)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/baeyer-villiger.anisaldehyde.pdf)

Abstract

Part 1: A study of the Baeyer-Villiger reaction on Anisaldehyde. This portion of the study is intended to show advanced students the feasibility of using this reaction on an aromatic aldehyde. The use of monopersuccinic acid (PSA) constitutes an interesting alternative to the classical m-chloroperoxybenzoic acid (mCPBA).
Part 2: The experiment is extended to various polymethoxybenzaldehydes and theoretical calculations are used to explain their particular behaviors. In acid medium at 55°C the first step of reaction on dimethoxybenzaldehydes is rate determining. This is a special feature, as the rearrangement that constitutes the second step is usually rate determining.