Author Topic: Novel route to P2P from alpha-methylstyrene  (Read 2078 times)

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Rhodium

  • Guest
Novel route to P2P from alpha-methylstyrene
« on: September 08, 2004, 05:55:00 PM »
This originally incredibly cryptic patent (I have edited out half of the text, which was confusing blurb anyway) tells of a procedure for oxidizing alpha-methylstyrene [2-phenyl-1-propene] to phenylacetone, using an aromatic Iodine(III) compound together with catalytic cobalt(II) salt and a mineral acid.

alpha-methylstyrene and cobalt acetate are cheap and readily available, and an example of a suitable Iodine(III) oxidant is Iodosyl Acetate, which can be made in high yield by oxidizing Iodobenzene with peracetic acid - One straightforward procedure is available in

Organic Syntheses, CV 5, 660

(http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0660)

Spent Iodosyl Acetate becomes Iodobenzene again and can be recycled, and Iodobenzene itself is in turn available through several different routes, see this thread:

Post 459094

(java: "Re: Novel easy preparations of Iodobenzene.....", Novel Discourse)



Method for Oxidizing Unsaturated Aromatic Compounds
Shimizu et al.,

Patent US4967009



Abstract
This invention relates to a method for manufacturing aromatic compounds having the following formula Ar-C(R2)(R3)-CO-R1 (II) comprising the step of reacting an unsaturated aromatic compound having the following formula Ar-C(R1)=CR2R3 (I) with an aryl compound containing an iodosyl group or the salt thereof within a temperature range of from -50° to 200°C.


Background of the Invention

(1) Field of the Invention
This invention relates to a novel method for oxidizing unsaturated aromatic compounds. There are many oxidized products useful for an intermediate material for various agricultural chemicals, pharmaceuticals and the like which are obtained by oxidizing unsaturated aromatic compounds.

For example, an arylacetone such as 4-hydroxy-3-methoxyphenylacetone, 3,4-dimethoxyphenylacetone, 3,4-dihydroxyphenylacetone or the like is a compound used as an intermediate for manufacturing L-?-methyldopa which is employed as an antihypertensive agent.


(2) Description of the Prior Art
Among these useful compounds, arylacetones exhibiting high utility and for which various manufacturing methods have heretofore been proposed will be described hereinbelow as a specific example thereof. There have been proposed the following typical methods as ones for manufacturing arylacetones.

(1)

Patent GB1119612

discloses a method in which a peroxide such as peracetic acid or the like is allowed to act on 1-(3,4-dimethoxyphenyl)propylene, and the resulting diol type product is treated with an acid material such as zinc chloride to obtain 3,4-dimethoxyphenylacetone.
(2)

Patent FR1450200

discloses a method in which 3,4-dimethoxybenzaldehyde is reacted with ?-chloropropionic acid ester in the presence of a strong alkali, and the reaction product is then treated with a strong acid to obtain 3,4-dimethoxyphenylacetone.
(3) J. Am. Chem. Soc. 77, 700 (1955) describes a method in which 3,4-dimethoxyphenylacetonitrile is reacted with sodium ethoxide in a solvent such as ethyl acetate thereby to transform the former into an acetyl-member, and then the acetyl-member thus obtained is hydrolyzed to obtain 3,4-dimethoxyphenylacetone.
[This has been posted in

Post 388662

(Rhodium: "Phenylacetonitriles -> Phenylacetones", Methods Discourse)
]



Detailed Description of the Invention

The method of the present invention is carried out by using an easily available unsaturated aromatic compound as a raw material, and reacting the same with an aryl compound having an iodosyl group or the salt thereof.

The raw material of the present invention is an unsaturated aromatic compound having the following general formula; Ar-C(R1)=CR2R3 (I)

Specific examples of the unsaturated aromatic compounds having the above described formula (I) include arylethylenes such as styrene, 1-aryl propylenes such as 1-phenylpropylene, 2-aryl propylenes such as 2-phenylpropylene, 1-aryl-1-butenes such as 1-phenyl-1-butene, or such compounds obtained by forming a ring structure from R1, R2 or R3 in the aforesaid formula (I) with Ar such as 1,2-dihydronaphthalene, indene, and 1,2-dihydroanthracene. According to the method of the present invention, the above-mentioned unsaturated aromatic compounds are oxidized to obtain the corresponding oxides. These products thus oxidized have the following general formula; Ar-C(R2)(R3)-CO-R1 (II) wherein Ar, R1, R2 and R3 have the same meanings as defined in the above formula (I), respectively. Specific examples of the oxidized products manufactured in accordance with the method of the present invention are the compounds oxidized corresponding to said unsaturated aromatic compounds and which include, for example, aryl acetaldehydes, 2-aryl-propionaldehydes, arylacetones, 2-aryl-butyraldehydes, 1-aryl-2-butanones, 3-aryl-2-butanones, 2-aryl-2-methylpropionaldehydes, and diaryl ethanones which correspond to arylethylenes, 1-arylpropylenes, 2-arylpropylenes, 1-aryl-1-butenes, 2-aryl-1-butenes, 2-aryl-2-butenes, 1-aryl-2-methylpropylenes, and 1,1-diarylethylenes, respectively.

In the present invention, an aryl compound having at least one iodosyl group or the salt thereof is reacted with an unsaturated aromatic compound having said formula (I). The aryl compound having an iodosyl group is represented by the following general formula; Ar-I=O (IV) wherein aryl group Ar is an aromatic hydrocarbon residue such as phenyl, and these aryl groups may be substituted by one or more of lower alkyl groups and the like. A specific example of the aforesaid aryl compound having an iodosyl group includes iodosylbenzene, These aryl compounds having iodosyl groups may be used either without any modification or in the form of salts. A salt of the aryl compound having an iodosyl group has the following general formula; Ar-I(X)2 (IV) wherein Ar is an aromatic hydrocarbon residue such as phenyl and the like; and ion X is an acid residue. Specific examples of said salt of aryl compound include acetates such as iodosylbenzene diacetate, haloacetates such as iodosylbenzene di(chloroactate), benzoates such as iodosylbenzene, besides iodosylbenzene di(p-toluenesulfonate), iodosylbenzene dinitrate, and the like. Furthermore, the compounds each having an iodosyl group or the salts thereof according to the present invention may be high polymeric organic substances. More specifically, they may be a high polymeric organic substance to which has been added at least one compound containing an iodosyl group or the salt thereof.

A specific aryl compound containing the aryl group with which may be linked a high polymeric organic backbone chain means a polymer or copolymer of styrene or the derivative monomer thereof. In these organic high-molecular weight compounds, an iodosyl group is introduced into the compounds by post-treating the polymer or copolymer of styrene or the derivative thereof, and then the iodosyl group may be transformed into a salt. Specifically, a method for introducing an iodosyl group by means of the after-treatment can be effected in accordance with a method described, for example, in Angew. Makromol. Chem. 27(431), 223 (1972). Moreover, a method for converting the iodosyl group introduced into a salt can be specifically effected in accordance with a method described, for example, in Die Makromolekulare Chemie, 153-162 (1972).

It is required to use at least one equivalent of an aryl compound having an iodosyl group or the salts thereof with respect to a raw material unsaturated aromatic compound, and in general about one equivalent is sufficient for such unsaturated aromatic compound. Since there is no upper limit of an amount of the aryl compound to be used, even if the amount exceeds one equivalent, no obstacle is observed. However, the use of an excessive amount of such aryl compound is merely uneconomical, so that it is not desirable. On the other hand, when an amount of the aryl compound used is less than one equivalent, a raw material unsaturated aromatic compound remains unreacted in a ratio corresponding to such insufficient amount of the aryl compound so that it is undesirable. After the reaction of the present invention, an aryl compound having an iodosyl group or the salts thereof become aryl iodides which can be easily recovered by distillation or filtration from the reaction products.

In the present invention, a catalyst may be used for the sake of accelerating the reaction, if necessary. As a reaction catalyst, a salt of transition metals such as cobalt, manganese, copper, iron and the like is used, and cobalt is preferably used as such a transition metal dibenzoate. Specific examples of such catalyst as described above include cobalt, manganese, copper, or iron acetates. An amount of such catalyst to be used is preferably 0.05-10% by weight with respect to a raw material unsaturated aromatic compound. In the case where an amount of the catalyst used is less than the lower limit of such range, the reaction does not proceed sufficiently. Furthermore, an acid may be allowed to exist in order to promote the reaction. Specifically, an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, sulfonic acid or the like is used.

A reaction temperature range from -50°C to +200°C, and preferably from 0°C to +100°C. In the method of the present invention, although it is not necessarily required to use a solvent for the reaction, an inert solvent with respect to the reaction may be used in order to improve contact efficiency of the aryl compound having an iodosyl group or the salts thereof with an unsaturated aromatic compound.


Example 1
A reaction vessel was charged with 2-phenylpropylene (3 mmol) as a raw material unsaturated aromatic compound, iodosylbenzene diacetate (3 mmol) as a salt of an iodosyl compound and 30 ml of 60% aqueous acetic acid as a solvent, and the reaction was carried out under such condition of 25°C. reaction temperature and 2 hour reaction time in nitrogen atmosphere.

After completing the reaction, the reaction solution was poured to water, and then an oily matter was extracted with ether. After removing the ether by distillation, a degree of reaction of the raw material 2-phenylpropylene and an yield of phenylacetone being the product to be produced were 30% and 26%, respectively, as a result of a gas chromatograph analysis, and in this case iodobenzene being a by-product in the reaction was also observed.

Examples 2-8
Each reaction was carried out by using the starting material and the like enumerated in the following Table in accordance with the above described manner in Example 1, and the results are shown in the same Table.

Example 9
A reaction was effected by employing cobalt acetate as the catalyst in glacial acetic acid in accordance with the reaction of Example 1. After the reaction, the resulting product was post-treated in accordance with the manner in Example 1. As a result of the same analysis, a degree of reaction and an yield were 100% and 44%, respectively.

Examples 10-31
Each reaction was carried out by using the starting material and the like enumerated in the following Table in accordance with the above described manner in Example 9, and the results are shown in the same Table.

Examples 32-40
Each reaction was carried out by using the catalyst or the reaction solvent enumerated in the following Table in accordance with the above described manner in Example 9, and the results are shown in the same Table.

Example 41
A reaction vessel was charged with 2-phenylpropylene (3 mmol) as an unsaturated aromatic compound (raw material), modified polystyrene beads 15% of which are occupied by a unit having an iodosyl group (2.85 g), cobalt acetate (0.05 mmol) as a catalyst and 100 ml of glacial acetic acid as a solvent, and the reaction was carried out under such condition of 25°C. reaction temperature and 2 hour reaction time in nitrogen atmosphere.

After completing the reaction, the modified beads and the catalyst were filtered off, and then the filtrate was extracted with ether. After removing the ether by distillation, a degree of reaction of the raw material 2-phenylpropylene and an yield of phenylacetone being the product to be produced were 55% and 15%, respectively, as a result of a gas chromatograph analysis.

Example 42
A reaction vessel was charged with 2-(3,4-dimethoxyphenyl)propylene (3 mmol) as an unsaturated aromatic compound (a raw material), modified polystyrene beads 25% of which are occupied by a unit in which acetic acid has been added to an iodosyl group (1.6 g) as a high-molecular weight aromatic compound, cobalt nitrate (0.05 mmol) as a catalyst and 100 ml of 60% aqueous acetic acid as a solvent, and the reaction was carried out under such condition of 25°C. reaction temperature and 2 hour reaction time in nitrogen atmosphere. As a result of the post-treatment in accordance with the above described manner in Example 41, the degree of reaction and the yield were 43% and 12%, respectively.




What is claimed is:

1. A method for manufacturing aromatic compounds having the following formula Ar-C(R2)(R3)-CO-R1 (II) comprising the step of reacting an unsaturated aromatic compound having the following formula Ar-C(R1)=CR2R3 (I) with an aryl compound having at least one iodosyl group or a salt thereof within a range of a reaction temperature of from -50°C to 200°C, wherein Ar is an aryl or substituted aryl group, each of R1, R2 and R3 is hydrogen atom, a lower alkyl group having 1-4 carbon atoms or an aryl or substituted aryl group, and R1, R2 and R3 may be the same or different groups, respectively.
2. The method for manufacturing aromatic compounds as claimed in claim 1 wherein the aryl group Ar in said unsaturated aromatic compound is an aromatic hydrocarbon residue in which 1-3 hydrogen atoms of the aromatic ring thereof are substituted by a substituent or substituents selected from the group consisting of hydrogen atom, halogen atom, nitro group, amino group, lower alkyl group and lower alkoxy group.
3. The method for manufacturing aromatic compounds as claimed in claim 2 wherein said aromatic hydrocarbon residue is a phenyl group.
4. The method for manufacturing aromatic compounds as claimed in claim 1 wherein said reaction is conducted in the presence of a reaction catalyst, wherein said reaction catalyst is a salt of a transition metal selected from the group consisting of cobalt, manganese, copper and iron.
5. The method for manufacturing aromatic compounds as claimed in claim I wherein said aryl compound having an iodosyl group or the salts thereof have either the following formula Ar-I=O (III) or formula Ar-I(X)2 (IV), respectively; in the above formulae, Ar is aryl group, and ion X is an acid residue.
6. The method for manufacturing aromatic compounds as claimed in claim 5 wherein said aryl compound having an iodosyl group or the salts thereof are iodosyl benzene or iodosyl benzene diacetate.
7. The method for manufacturing aromatic compounds as claimed in claim 1, wherein said aryl compounds having an iodosyl group or the salts thereof are polymeric aromatic compounds.
8. A method for manufacturing aromatic compounds as claimed in claim 5 wherein said ion X is carboxylic acid ion, nitric acid ion or sulfonic acid ion.


References Cited

FR1450200
GB1119612
Kinneary et al., J.A.C.S. 110, 6124-6129 (1988)
Collins et al., J. Chem. Soc. Chem. Commun. 803-804, (1987)
Koola et al., J. Org. Chem. 52, 4545-4553 (1987)
Tai et al., J.A.C.S. 108, 5006-5008 (1986)
G. A. Stein et al., J. Am. Chem. Soc. 77, 700-703 (1955)
V. M. L. Hallensleben, Die Angewandte Makromolekulare Chemie, 27, 223-227 (1972)
Y. Yamada et al., Die Makromolekulare Chemie, 152, 153-162 (1972)


PastorFuzz

  • Guest
Sweeeet...
« Reply #1 on: September 15, 2004, 01:26:00 PM »
Holy fuck that's pretty amazing...Probably the most efficient method I've ever seen. Well, for the times we're living right now I believe it is. Could somebody elaborate on the procedure a bit more?

Captain_America

  • Guest
Probably the most efficient method I've ever...
« Reply #2 on: September 15, 2004, 01:54:00 PM »
Probably the most efficient method I've ever seen.

This route is not good, IMO. See the P2P compilation for much better methods, esp fridel-crafts w/ chloroacetone/benzene or for p-dimethoxybenzene:

Post 205055

(Antoncho: "P2Ps from benzene, acetone and Mn(AcO)3", Novel Discourse)

Rhodium

  • Guest
That's not a good pick
« Reply #3 on: September 15, 2004, 02:30:00 PM »
much better methods, esp fridel-crafts w/ chloroacetone/benzene

That's even worse - you will achieve at best a 35% yield, and that after working with a volatile tear gas...

Reference:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#chloroacetone




PastorFuzz

  • Guest
I'm sayin...
« Reply #4 on: September 15, 2004, 02:57:00 PM »
Yeah I was just looking at Benzene...doesn't seem like the type of chemical I wanna work with. alpha-methylstyrene seems a whole lot less likely to turn me into one of those monsters from 28 Days Later. Plus, look at them yields. ::)  Can anybody elaborate on the procedure a bit? I imagine it got fucked off in the translation process somewhere...

Captain_America

  • Guest
The reaction....
« Reply #5 on: September 15, 2004, 10:27:00 PM »
That's even worse - you will achieve at best a 35% yield, and that after working with a volatile tear gas...

The reaction w/ chloroacetone could bee preformed on a balcony at late hour, see also: 

Post 507959

(Nicodem: "Chloroacetone is OK", Chemistry Discourse)
Vitus usually sniff on in when he is bored: 

Post 505470

(Vitus_Verdegast: "as a sidenote :-)", Chemistry Discourse)
I also have discovered that inhalation of small amount of bromine vapours helped me when my sinuses were clogged when I catch cold.

I wouldn't complain about the yield, considering the cheapness of the starting materials. It is also more OTC than the method of this thread since you could use the Al or zink

Post 408642

(Kinetic: "Zinc promoted Friedel-Crafts acylation", Novel Discourse)
to make the LA in situ

Post 517686

(Polverone: "Dolgov's articles on F-C with Al shavings and HCl", Chemistry Discourse)
, or see organikum's post on SnCl4

Post 511779

(Organikum: "SnCl4 - stannic chloride, anhydrous", Chemicals & Equipment)
. Only problem here is benzene which is not OTC, but nor is iodobenzene. Neither do I know where to get cobalt acetete OTC, nor a-methystyrene, but I admit I haven't looked for these compouds. I can't even get strong acetic acid OTC.

If you really want an OTC route see: 

Post 443814

(Lego: "P2Pol from toluene and ethanol", Novel Discourse)