The Hive > Novel Discourse

New method for P2P

(1/8) > >>

The following reactions are part of this novel synthesis of P2P:

1) An acid catalysed Aldol condensation of Benzaldehyde and Methyl Ethyl Ketone to give Methyl Phenyl Butenone:

C6H5CHO + CH3CH2COCH3 + HCl(g) ---> C6H5CH=C(COCH3)CH3
2) The unsaturated ketone undergoes the Baeyer-Villiger oxidation with peroxy acids to give the enol ester of Phenyl propanone:

3) The enol ester is then saponified with 10% NaOH solution to give Phenyl Propanone in about 35% yield based on the unsaturated ketone.

The Aldol Condensation.

The directions for this are in Organic Reactions

200 gms of Benzaldehyde and 300 gms of Methyl Ethyl Ketone are mixed in a 1 litre beaker and cooled below 5°C. HCl gas is bubbled through until 40gms has been added. The mixture goes from a clear solution to a red colour and becomes turbid so that you can't see through it. The mixture is kept over night and becomes a brown colour. It is washed with water and then 10% NaOH solution, the organic layer seperated and distilled. At 240°C a yellow oil comes accross and the temperature gradually rises to 260°C.

The oil can be crystalized by cooling in the freezer overnight. This in itself does not induce crystalization but if you also put a spoon in the freezer and then dip it in and out of the cool mixture you get some seed crystals that induce crystalization. The mass turns from an orange oil to sulfur coloured crystals, mp 38°C, 180 gms (Methyl Phenyl Butenone)

The Baeyer-Villiger Oxidation

The reaction of the above unsaturated ketone with peracetic acid was first done by Boesken reported in Rec. Trav. Chim.  55, 786 (1936). There is some discussion of this also in Patent US3980708.  Also see Organic Reactions Vols 9 & 43 I  think.  By following the directions in Patent US5670661 you will get about 35% ketone based on the weight of the unsaturated ketone used. In that patent it is suggested that by recycling a higher percentage can be achieved.

To a 1 litre flask is added 625 ml of Glacial acetic acid and 143 grms of Sodium Perborate. To this is added 100 grms of the methyl phenyl butenone with stirring and the mixture is heated to 50°C. The mixture will heat up so  care has to be taken ie cooling. However if the mix gets too cool it solidifies. Stirring and heating continued for about 6 hours. Cooled poured into 1 litre H2O and extracted with toluene or DCM. The solvent is distilled leaving a yellow oil that has a pleasant smell. This is added to 500 mls of 10% NaOH solution (50/50 H20:EtOH) and stirred for 1-2 hours extracted with toluene or DCM and distilled and the fraction boiling between 210-220°C collected Phenyl-2-Propanone (About 35 gms)

In the Organic Reactions review of the Baeyer-Villiger there is a reference to the oxidation of alpha Methyl Cinnamaldehyde using H2O2 catalysed by a nitrobenzene selenic acid or something like that to give the same enol ester as above but in 90% yield.

Here are some references for the first reaction
The product is this correct?

Preparation of 3-methyl-3-penten-2-one and its analogs.
Pishch. Prom-st. (Moscow)  (1990),   (10),  44-5.
Journal  written in Russian. 
MeCOEt condensed with RCHO (R = Me, Et, Pr, Me2CH, MeOC6H4, PhCH:CH, Ph) in the presence of H2SO4 at 60-65° to give 40-79% RCH:CMeCOMe.  Analogous reaction of R1CH2COR2 [R1R2 = (CH2)3, (CH2)10; R1 = H, R2 = Ph, CH2CHMe2; R1 = C5H11, R2 = Me] with MeCHO (from paraldehyde) gave 8.6-38% MeCH:CR1COR2. 

Aldol condensation of butanone with various aldehydes.    
Sasaki, Kazuhiro.    Kobayashi Perfum. Co.,  Ichikawa,  Japan.   
Nippon Kagaku Zasshi  (1968),  89(8),  797-804. 
Journal  written in Japanese.   
Condensation of MeCOEt (I) with various aldehydes was investigated to find the effect of conditions on the ratio of RCH:CHCOEt (II) and RCH:CMeAc (III).  Citral and I, in the presence of alkali hydroxide or NaOEt, gave products contg. >86.8% II, whereas MeOH-KOH yielded products contg. III as a main product.  Citronella (IV) and I gave similar results except that Me2C:CHCH2CH2CHMeCH2CH(OMe)CH2COEt was formed using MeOH-KOH and Me2C:CHCH2CH2CH(Me)CH2CH(OH)CHMeAc was obtained with EtONa.  The results indicate that aldol corresponding to II is more readily dehydrated than that corresponding to III.  Condensation of IV with Me2CO in the presence of MeOH-KOH gave a mixt. of Me2C:CHCH2CH2CHMeCH2CH:CHAc and Me2C:CHCH2CH2CHMeCH2CH(OMe)CH2Ac.  Similar reaction of I with Et2CO gave Me2C:-CHCH2CH2CHMeCH2CH:CMeCOEt, b0.55 101-7°.  Condensation of I with BzH, PhCH:CHCHO (V) and furfural (VI) showed that the ratio II-III is also dependent on the type of aldehyde.  III is favored when KOH-MeOH is used with BzH and V, compared with the results with aq. NaOH, but the difference is much greater with BzH.  BzH and VI always favor formation of II.  PhCH:CHCH:CHCOEt, m. 55-6°, was prepd. by a modified Wittig reaction; semicarbazone m. 200-1°; phenylhydrazone m. 89-90°.  4-(2-Furyl)-3-methyl-3-buten-2-one, b10 114-15°, and 5-(2-furyl)-4-penten-3-one, b13 122-4°, were also prepd. by this method.  Orientation of condensation was postulated to be regulated by the steric requirement.  s-Cis and s-trans conformations of some of the unsatd. ketones were detected by ir spectra. 

A study of the reaction of butanone with benzaldehyde and p-nitrobenzaldehyde.    
Jung, Duksang.    Cheju Univ.,  Cheju,  S. Korea.  
Nonmunjip - Cheju Taehak  (1982),  14  27-31.
Journal  written in Korean.   
In alk. medium, the reaction of p-O2NC6H4CHO and MeCOEt gave three hydroxy ketones, indicating that both Me and CH2 positions were attacked to a comparable extent.  Dehydration of the intermediate hydroxy ketones is a slow step.  In acid medium, however, the addn. step of the reaction was selective, giving only 1 isomer.  Similarly, in alk. medium, PhCH(OH)CH2COEt (I) and PhCH(OH)CHMeCOMe (II), hydroxy ketone intermediates from the reaction between BzH and MeCOEt, gave PhCH:CHCOEt (III).  Treating I and II with acid gave III and PhCH:CMeCOMe, resp., with no evidence of rearrangement. 

These journal articles detail its synth also.

Double Michael addition reactions of some new 1,5-diaryl-2-alkyl-1,4-pentadien-3-ones: Part II.
Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  (2001),  40B(8),  667-673.

RuCl3 catalyzes aldol condensations of aldehydes and ketones.   
Tetrahedron  (1998),  54(32),  9475-9480. 

Synthesis of isoquinoline-1,3-dicarboxylic acid.    
Chin. Chem. Lett.  (1999),  10(11),  907-910. 
(in english)

Here is the baseic addition

Kinetics of condensation of benzaldehyde and its derivatives with acetone and methyl ethyl ketone catalyzed by aluminum oxide.   
Collect. Czech. Chem. Commun.  (1980),  45(6),  1812-19.
Journal  written in English.
The pseudo-1st-order aldol condensation kinetics of RC6H4CHO (R = H, 4-Me, 3-MeO, 4-MeO, 3-Cl,4-Cl) with excess Me2CO over Al2O3 at 60-160° and the pos. r indicated that the addn. step, to give hydroxy ketone, is rate detg.  r Decreases with increasing temp.; the isokinetic temp. is 449.8K.  At 60-90° the retroaldol reaction of PhCH(OH)CH2Ac is minor and the dehydration to PhCH:CHAc is major; the proportion of dehydration-retroaldol reaction increases with increasing solvent polarity and decreases with increasing temp.  The condensation of PhCHO with MeCOEt at 90-160° gives mostly PhCH:CHCOEt in a reaction catalyzed by the basic sites on Al2O3; the minor product, PhCH:CMeAc, formation is catalyzed by the acidic Al2O3 sites. 

Do Your Part To Win The War

This review would probably bee very helpful.

The Baeyer-Villiger oxidation of ketones and aldehydes.
Krow, Grant R.
Org. React. (N. Y.)  (1993),  43  251-798.  
A review with >1092 refs. 

Refs for the second one(partial of this article)

Sn-zeolite beta as a heterogeneous chemoselective catalyst for Baeyer–Villiger oxidations
Nature 412, 423 - 425 (2001)
The Baeyer–Villiger oxidation, first reported more than 100 years ago1, has evolved into a versatile reaction widely used2 to convert ketones—readily available building blocks in organic chemistry—into more complex and valuable esters and lactones. Catalytic versions of the Baeyer–Villiger oxidation are particularly attractive for practical applications, because catalytic transformations simplify processing conditions while minimizing reactant use as well as waste production. Further benefits are expected from replacing peracids, the traditionally used oxidant, by cheaper and less polluting hydrogen peroxide3. Dissolved platinum complexes4 and solid acids, such as zeolites5, 6 or sulphonated resins7, efficiently activate ketone oxidation by hydrogen peroxide. But these catalysts lack sufficient selectivity for the desired product if the starting material contains functional groups other than the ketone group; they perform especially poorly in the presence of carbon–carbon double bonds. Here we show that upon incorporation of 1.6 weight per cent tin into its framework, zeolite beta acts as an efficient and stable heterogeneous catalyst for the Baeyer–Villiger oxidation of saturated as well as unsaturated ketones by hydrogen peroxide, with the desired lactones forming more than 98% of the reaction products. We ascribe this high selectivity to direct activation of the ketone group, whereas other catalysts first activate hydrogen peroxide, which can then interact with the ketone group as well as other functional groups.

When trying to avoid the use of peracids for the Baeyer–Villiger reaction, the methodology developed up to now involved catalysts able to activate hydrogen peroxide, H2O2. Amongst homogeneous catalysts, complexes of molybdenum8 and rhenium9 have been shown to activate H2O2, but their turnover numbers (TONs) and selectivities are relatively low (TONs are below 20 for overall reaction times ranging from 12 to 24 hours). Pt complexes achieve TONs of about 50 within 5 hours, but are not chemoselective when other functional groups are present10. Concerning heterogeneous catalysts, supported Pt complexes11 and TS-112 have been used, but have shown only limited activity and selectivity, respectively. Acid zeolites such as H-beta and USY activate hydrogen peroxide for the Baeyer–Villiger oxidation, but show selectivities of less than 60–70% (ref. 5). MeReO3 (ref. 13), TS-13 and Pt complexes14 are excellent epoxidation catalysts in the presence of H2O2 and consequently, epoxidation is favoured over the Baeyer–Villiger oxidation when using unsaturated ketones as starting material.

1. Baeyer, A. & Villiger, V. Einwirkung des Caro'schen Reagens auf Ketone. Chem. Ber. 32, 3625-3633 (1899).
2. Renz, M. & Meunier, B. 100 years of Baeyer-Villiger oxidations. Eur. J. Org. Chem. 737-750 (1999).
3. Arends, I. W. C. E., Sheldon, R. A., Wallau, M. & Schuchardt, U. Oxidative transformations of organic compounds mediated by redox molecular sieves. Angew. Chem. Int. Edn Engl. 36, 1145-1163 (1997).
4. Strukul, G. Transition metal catalysis in the Baeyer-Villiger oxidation of ketones. Angew. Chem. Int. Edn Engl. 37, 1198-1209 (1998).
5. Fischer, J. & Hölderich, W. F. Baeyer-Villiger-oxidation of cyclopentanone with aqueous hydrogen peroxide by acid heterogeneous catalysis. Appl. Catal. A 180, 435-443 (1999).
6. Chang, C. D. & Hellring, S. D. Production of lactones and omega-hydroxycarboxylic acids. US Patent No. 4870192 (1996).
7. Hoelderich, W., Fischer, J., Schindler, G. -P. & Arntz, D. Preparation of lactones by Baeyer-Villiger oxidation of cyclic ketones. German Patent DE 19745442 (1999).
8. Jacobson, S. E., Tang, R. & Mares, F. Oxidation of cyclic ketones by hydrogen peroxide catalysed by group 6 metal peroxo complexes. J. Chem. Soc. Chem. Commun. 888-889 (1978).
9. Herrmann, W. A., Fischer, R. W. & Correia, J. D. G. Multiple bonds between main-group elements and transition metals. Part 133. Methyltrioxorhenium as a catalyst of the Baeyer-Villiger oxidation. J. Mol. Catal. 94, 213-223 (1994).
10. Gavagnin, R., Cataldo, M., Pinna, F. & Strukul, G. Diphosphine-palladium and -platinum complexes as catalysts for the Baeyer-Villiger oxidation of ketones: effect of the diphosphine, oxidation of acyclic ketones, and mechanistic studies. Organometallics 17, 661-667 (1998).
11. Palazzi, C., Pinna, F. & Strukul, G. Polymer-anchored platinum complexes as catalysts for the Baeyer-Villiger oxidation of ketones: preparation and catalytic properties. J. Mol. Catal. A 151, 245-252 (2000).
12. Bhaumik, A., Kumar, P. & Kumar, R. Baeyer-Villiger rearrangement catalysed by titanium silicate molecular sieve (TS-1)/H2O2 system. Catal. Lett. 40, 47-50 (1996). 
13. Herrmann, W. A. Essays on organometallic chemistry, VII. Laboratory curiosities of yesterday, catalysts of tomorrow: organometallic oxides. J. Organomet. Chem. 500, 149-150 (1995).
14. Frisone, M. D. T., Pinna, F. & Strukul, G. Baeyer-Villiger oxidation of cyclic ketones with hydrogen peroxide catalyzed by cationic complexes of platinum(II): selectivity properties and mechanistic studies. Organometallics 12, 148-156 (1993).

Do Your Part To Win The War

Not sure if this one will work, but there are some other reactions in there that might bee of interest to bees.  Benzaldehydes to phenols.

Baeyer-Villiger oxidation of b-aryl substituted unsaturated carbonyl compounds with hydrogen peroxide and catalytic selenium dioxide.
Synth. Commun.  (1995),  25(14),  2121-33.

A simple and cheap oxidative procedure using 30% H2O2 and catalytic SeO2 allows to transform 2-aralkylidenecycloalkanones and hydroxy- or alkoxybenzaldehydes to give, in high yields, enol lactones and aryl formates, resp. 
Do Your Part To Win The War

Yes a-Methylcinnamaldehyde should work in the Oxidation also.

Do Your Part To Win The War


[0] Message Index

[#] Next page

Go to full version