The present invention concerns a process for producing l,4-bisaryl-butane-l,4-diones having the general formula

0 0

H II

R - C - CH ₂ - CH ₂ - C - R' (I)

where R and R' independently denote aryl having 6-20 carbon atoms, alkyl, thioalkyl, oxyalkyl, dialkyl amino having from 1 to 20 carbon atoms, halogen or hydroxyl, substituted or unsubstituted aromatic or heteroaromatic groups consisting of 1-5 rings, and where the heteroatoms independently may be O, NR", S, Se, where R" is H or an alkyl group having from 1 to 20 carbon atoms, preferably 1-10 carbon atoms, or an aryl group having from 6 to 20 carbon atoms, preferably from 6 to 12 carbon atoms, and

poly(arylene-butane-l,4-diones) having the general formula

where R has the same meaning as stated above, and p means an integer between 1 and 50 000, preferably between 15 and 20 000, and in particular between 15 and 2000, from, respectively, l,4-bisaryl-butyne-l,4-diols having the general formula

where R and R ' have the meanings stated above, or

poly( arylene-2-butyne-l, 4-diols having the general formula

where R and p have the meanings stated above.

1,4-Bisaryl-butane-1,4-diones having the general formula I have previously been produced in various ways from different _^ starting- compounds. E.g. 1,4-diphenyl butane- 1,4-dione has been produced by a Zn-Cu-activated coupling of phenacyl bromide, or by acylating of phenacyl malonate succeeded by hydrolysis and decarboxylation. (Aust. J. Chem. 1976, 29, 339-356).

According to the authors it goes for the first of these methods that in spite of comprehensive experimental work it has not been succeeded to obtain yields in excess of 50%, and the lastmentioned of the methods is not general, and according to the authors the synthesis of the starting compounds is rather cumbersome.

Further, it is possible to produce compounds having the formula I by a Michael-reaction between an oxazole-5-on anion and a 1,4-unsatura ed ketone. (Aust. J. Chem. 1976, 29, 339-356).

Finally, e.g. 1,4-diethienyl-l, 4-dione can be produced by a reaction between 3-dimethyl-amino-l-(2-thienyl)- propanone and thiophene-2-carbaldehyde. (Synth. Commun. 14(1), 1-9, 1984).

These two lastmentioned methods are ultistep syntheses, which not only hampers the production of the desired compounds, but also results in poor yields. As regards the Michael-addition yields can e.g. only be obtained up to 35%, and in many cases the yields is lower.

Chemistry of Heterodyclic Compounds, 16. 1974 pp 831-832. Isomerization of acetylenic diols; 1,4-di(2'-pyridyl)-2- butyne-l,4-diol, by George R. Newkome et al., describes a process for producing 1,4-di(2' -pyridyl )-l,4-butanedione from 2-pyridine carboxaldehyde, the 2-pyridine carbox- aldehyde being treated with bis-magnesium bromide in an ether solution. This process, however, is entirely specific for the above compound, and furthermore a number of by-products are produced.

Further, a process is known for producing 1,4-dimethyl- butane-1,4-dione from the corresponding 1,4-dimethyl-2- butyne-l,4-diol. This process is described in Tetrahedron Letters, Vol. 30, No. 16 pp 2109-2112, 1989. Isomerization of Propargylic alcohols catalyzed by an iridium complex, by Danwei Ma et al. By this process it is possible to obtain a fairly good yield of 1, 4-dimethyl-butane-l,4- dione. However, the process is very costly, since it requires use of irridium compounds, which generally are very expensive.

Furthermore, a process is described in Journal of Organic

Chemistry, Vol. 40, pp 1131-1136, 1975. Generalized Syntheses of r-diketones, by Walter B. Sudweeks et al., for producing e.g. 1, 4-diphenyl-butane-l, 4-dione from 1,1-

diphenyl-butyne-l,4-diol in a two-step process comprising first reducing l,4-diphenyl-butyne-l,4-diol and subse¬ quently oxidizing the reduction product.

The reduction process requires use of a catalyst, such as platinum, palladium or nickel, which metals are either very costly or useless to work with, since they may be allergy inducing.

The oxidation process can be carried out in various ways, most of which produce a large number of side-products, which results in a low yield. According to the article the preferred oxidation process is the Sarett-Collins process, since by using this process rather high yield percentages are obtainable. However, the Sarett-Collins process requires use of chromium trioxide,. which is undesirable environmentally-wise and working-wise. Further, the process is unsuited for large scale production of 1,4- aryl-1,4-diones.

All in all, the reduction-oxidation-process described above is very costly, inappropriate as regards the environment, including the working environment, and inapplicable to large scale production of 1,4-aryl-l,4- diones.

Poly(arylene-butane-l,4-diones) having the formula II are known from EP patent application No. 340 826 which also mentions a process for producing the compound from 1,4- diacetyl aryl, dimethyl amine and formaldehyde. However, this is a very costly process for producing compounds having the formula II, since the starting compound "diacetyl aryl" is a very expensive compound. Therefore the process is commercially unacceptable.

It has now surprisingly been found that the compounds having the formula I and the formula II can be produced in a significantly simpler way which is advantageous both commercially and environmentally.

The object of the present invention is thus to devise a process for producing l,4-bisaryl-butane-l,4-diones and poly(arylene-butane-l,4-diones) having the respective general formulas I and II from, respectively, 1,4-bisaryl- 2-butyne-l,4-diols having the general formula

OH OH

I I

R - CH - C ≡ C - CH - R' (III)

where R and R' have the meanings stated above, or poly(arylene-2-butyne-l,4-diols) having the general formula

where R and p have the meanings stated above, which process does not require use of heavy metals, provides a good total yield of the desired compound, and further is applicable to large scale production.

This object is achieved by the process according to the invention which is of the kind stated in the introductory portion of claim 1 and is characterized by what is stated in the characterizing portion of claim 1.

The inventive process is particularly suited for producing compounds having the formula I, where R and R ¹

independently denote aryl having from 6 to 12 carbon atoms, alkyl, thioalkyl, oxyalkyl, dialkyl amino having from 1 to 10 carbon atoms, substituted or unsubstituted aromatic or heteroaromatic groups consisting of 1 or 2 rings, and where the heteroatoms independently may be 0, R", S or Se, where R" is H or an alkyl group having from 1 to 10 carbon atoms, or an aryl group having from 6 to 12 carbon atoms, the compounds in which the heteroatoms are 0, S or NR", where R has the meaning stated above, being particularly preferred, and p is an integer between 15 and 20 000, and in particular between 15 and 2000.

By reaction medium is understood a liquid reaction medium. The reaction medium which is used in the process according to the invention may be a pure compound or a mixture of several different compounds, the reaction medium, however, having to possess three capacities, which will be explained in more detail below.

Primarily, the reaction medium must be capable of dis¬ solving the starting compound having the formula III or IV at ^" least partially. To achieve an acceptable reaction rate the reaction medium must preferably be capable of dissolv¬ ing more than 0.5 W/W of the starting compound, and in particular more than 5% W/W of the starting compound when the starting compound has the general formula III. Consequently, .the reaction medium must preferably contain at least one component having dissolution promoting capacity. Particularly suited reaction medium components having dissolution promoting capacity include lower aliphatic alcohols having from 1 to 5 carbon atoms, such as MeOH and EtOH; halogenated hydrocarbons having from 1 to 5 carbon atoms, such as 1,2-dichlorethane; ethers having from 1 to 10 carbon atoms, such as tetrahydrofuran, dioxane and diethox ethane, as well as aromatic solvents preferably selected from halogenated benzenes, alkyl

substituted benzenes, where alkyl has from 1 to 25 carbon atoms, or dephenyl ethers having from 1 to 25 carbon atoms, such as chlorobenzene and toulene and acetonitrile.

The reaction medium must further allow proton exchange, which really means that it must be protogenic. The reaction medium must thus comprise at least one H-donating component, since preferably at least 1 vol-%, and in particular at least 40-60 vol-%, of the reaction medium shall be constituted by this H-donating component which may constitute as much as 100% of the reaction medium.

The H-donating component must further not possess essential base neutralizing capacity. The H-donating component must thus preferably have a pKa value between 9.5 and 20. In particular H-donating components are preferred which contain one or more OH-groups, and in particular H^O and lower alcohols having from 1 to 5 carbon atoms are preferred, such as MeOH and EtOH, and polyols having from 1 to 5 carbon atoms, such as ethylene glycol, H«0 in particular being used in combination with MeOH, EtOH or ethylene glycol.

The third demand on the reaction medium is that it must be basic. This is achievable by adding a base which is completely or partly soluble in the reaction medium. To avoid undesired side-reactions, and to avoid that the base is neutralized by the H-donating component in the reaction medium, the preferred bases have a pKa-value between 9.5 and 16. In particular cheap inorganic bases, such as Na _^ S, NaOH, and K ₂ C0 ₃ , are preferred.

The demands on the reaction medium to the effect that it must be H-donating, basic and capable of dissolving the starting compound, may either be met by one and the same component, or they may be met by using a mixture of two or

more components as reaction medium. When choosing reaction medium it is further necessary that the constituent component(s) does/do not give rise to undesired side- reactions. Thus, e.g. primary amines which true are H- donating, basic and capable of dissolving compounds having the formula III or IV, cannot be used, since the keto- groups in the compounds having the formulas I/II are capable of forming Schiff-bases with amines, which is undesirable.

All in all the preferred reaction media consist of from 1 to 100 vol-% of compounds or combinations of compounds selected from lower alcohols, or polyalcohols having from 1 to 5 carbon atoms, or H^O, preferably selected from compounds such as H^O, MeOH, EtOH or ethylene glycol, and 0-99 vol-% of compounds or combinations of compounds selected from halogenated hydrocarbons having from 1 to 5 carbon atoms, ethers having from 1 to 10 carbon atoms, and aromatic solvents preferably selected from halogenated benzenes, alkyl substituted benzenes, where alkyl has from 1 to 25 carbon atoms, or diphenyl ethers having from 1 to 25 carbon atoms, and acetonitrile, preferably compounds selected from 1,2-dichlorethane, tetrahydrofuran, dioxane, diethoxy ethane, chlorobenzene, toulene and acetonitrile, and containing a base having a pKa-value between 9.5 and 16, preferably bases selected from Na„S, NaOH and K-CO-,, in an amount of 0.5-20, preferably 1-10 eqv. relatively to the 1,4-OH groups in the starting compound having the formula III or IV.

The reaction by the process according to the invention is energetically favourable in that by the rearrangement described two keto-groups occur which each separate one will form part of a conjugated system with the aromatic/ heteroaromatic groups Ar/Ar ^r .

A possible reaction mechanism is as stated in the following:

III IV

OH OH OH OH

XOH

R -C = C = C R' -> R — C = C = C — R' - θ

H H H

V VI

0 OH 0 OH II base II

R —ιC— C = C R* > R -C- C = C R' -

I I I I θ

H H H H H

VII VIII

0 OH O H OH

1 θ I XOH 8 I I R - C - C - C - C - R* > R - C - C - C = C - R* →

I I I I H H H H

IX

o

R - - C - R'

The reaction mechanism shown consists of a repeated sequence comprising a deprotonation step (III→IV and VII VIII) succeeded by an electron shift (IV→V and VIII→IX), a reprotonation (V→VI and IX→X), and an enol- ketone rearrangement (VI→VII and X-»I). It should be noted that this mechanism is in agreement with what has been experimentally demonstrated: that both base and H-donating reaction medium are necessary, and that the base has catalytic effect.

The reaction mechanism is only shown for the compounds having the formulas III→I. A similar reaction mechanism will progress for the compounds having the formulas IV→II.

The starting compounds having the general formulas III and IV can be produced in several different ways, preferably from aldehydes. The starting compounds having the general formulas can e.g. be produced by using one of the processes which are disclosed in US patent 3 452 499, Bergmann, E; Selecta Chimica 1950 No. 9 p. 24-38, Agocs,

P; Koczka, K; Acta Physica et Chemica 13, 3-4 p. 113-15, 1967, Krupowicz, J; et al., Ann. Univ. Mariae Curie- Sklodowska, Sect. AA 1975, 29-30 p. 271-4. From CA 87:134 892x 1977, or Viehe, H.G; Reistein M; Berichte 95, 2257-1962.

Compounds having the formula III can thus e.g. be produced by letting a compound having the formula

CH≡CH

react with a compound having the formula

R-CH0

where R has the meaning stated above, in a solvent such as CH ₂ C1 ₂ in the presence of K0H.

The compounds having the formula III can e.g. also be produced by condensation between a dianion of acetylene, such as the dilithium salt of acetylene and an aryl carbaldehyde.

The compounds having the formula IV can e.g. be produced by condensation between a dianion of acetylene, such as the dilithium salt of acetylene and a diformyl aryl compound, such as terephthal aldehyde.

The compounds having the general formula I and the general formula II have many applications.

The compound having the general formula II is especially used for producing conducting polymers, which use is described in more detail in the previously mentioned EP application No. 340 826.

The compounds having the general formula I are also especially suited as starting material when producing conducting polymer, the 1,4-dike one part in the compounds having the formula I being converted to a heterocyclic ring, by a ring closure as described in Journal of Organic Chemistry, Vol. 40, No. 8, 1975, pp 1131-1136. Generalized Syntheses of r-diketones, by Walter B. Sudweeks et al., or in Polymer Papers Vol. 28, 1987, pp 179-182. Substi- tutional alloys' of organic polymeric conductors, by John P. Ferraris et al. Hereafter the monomers are polymerized as described e.g. in the lastmentioned article or in US patent specification-. No. 488 625.

Some of the compounds having the formula I are also useable for producing fungicides, phototoxic bactericides and other interesting, commerciably useful compounds. This is described in more detail in Photochemistry and Photo- biology, Vol. 39, No. 4, pp 521-524, 1984. Comparison of the phototoxicity of α-terthienyl with that of a selenium and of an oxygen analogue, by F. . Garan et al,

Tetrahedron, Vol. 41, No. 10 pp 1919-1929, 1985. Synthesis and 13C NMR characterization of some ir-Excessive Hetero- polyaromatic compounds, by Adriano Carpita et al., and in

Journal of Organic Chemistry, 1982, 47, pp 2201-2204. Synthesis of 3,2' :5' ,3"-terthiophene and Other terthio- phenes by the thiopenecarboxaldehyde -» ethynylthiophene — dithienylbutadiyne route, by Jan-Pierre Beny et al.

In the following the process of the invention will be illustrated in more detail by way of some examples.

EXAMPLE 1

505 mg l, ^" 4-di(2-thienyl )-2-butyne-l,4-diol were dissolved in 20 ml MeOH. Then 2.5 g Na-S x 9H ₂ 0 were added and heating to reflux was performed for 3 hours. This was succeeded by evaporation to dryness and addition of 50 ml

water, followed by extraction with 3 x 20 ml CH ₂ C1 ₂ . There were performed drying with MgSO., filtration and evapora¬ tion, which yielded 423.3 mg 1,4-di(2-.thienyl )-butane-l,4- dione (83%). Identification by IR-spectroscopy and by NMR.

EXAMPLE 2

67.5 mg 1,4-di(2-thienyl)-2-butyne-l,4-diol were dissolved in 2 ml MeOH whereafter 135 g K ₂ C0 ₃ were added and heated to reflux for 2 hours. This was followed by evaporation to dryness and addition of water, succeeded by extraction with 3 x 2 ml CH C1~ . There were performed drying with MgSO., filtration and evaporation, which yielded 51 mg l,4-di(2-thienyl )-butane-l,4-dione (75%). Identification by IR-spectroscopy and by NMR.

EXAMPLE 3

1 g l,4-di(2-thienyl )-2-butyne-l,4-diole were dissolved in 40 ml MeOH, whereafter 9.7 g Na ₂ S x 9H ₂ 0 were added and heated to reflux for 3 hours. 200 ml water were discharged, extracted with 4 x 50 ml CH ₂ C1 ₂ , dried, filtered and evaporated, which yielded 0.74 g l,4-di ^' (2- thienyl)-butane-1, 4-dione (74%). Identification by IR- spectroscopy and by NMR.

EXAMPLE 4

71 mg 1,4-diphenyl-2-butyne-l, 4-diol were dissolved in 1 ml MeOH, whereafter 15 mg NaOH were added and heated to reflux for 2 hours. This was followed by evaporation to dryness and addition of 2 ml water, succeeded by extract- ion with 3 x 2 ml CH ₂ C1 ₂ . There were performed drying, filtration and evaporation, which yielded 26.2 mg 1,4- diphenyl-butane-1,4-dione (85%). Identification by IR- spectroscopy and by NMR.

EXAMPLE 5

0.653 g poly-(phenylene-2-butyne-l,4-diol were dissolved

in 50 ml MeOH, whereafter 1.5 g NaOH were added. Heating was to 80°C, which temperature was kept for 10 hours. Thereafter 2 molar aqueous HC1 were discharged, filtered, washed with Et _? 0, and dried at a pressure of 1 mm Hg and 50°C for 6 hours. The yield was 0.530 g poly-(phenylene- butane-1,4-dione) (81%). Identification by IR- spectroscopy.

EXAMPLE 6 179 mg l,4-di-(4-methylphenyl)-2-butyne-l,4-diol were dissolved in a reaction medium consisting of 2 ml MeOH with 5 eqv. NaOH (160 mg, 85% NaOH) and heated to 80°C for 2 hours. Then it was cooled, which resulted in a crystal¬ line precipitate. The precipitate was filtered off, washed and dried. The precipitate was identified by NMR as being l,4-di-(4-methylphenyl)-2-butane-l,4-dione. The yield was 79.4 mg (44%).

EXAMPLE 7 139 mg l,4-di-(2-naphthyl)-2-butyne-l,4-diol were dis¬ solved in a reaction medium consisting of 2 ml MeOH with 5 eqv. NaOH (95 mg, 85% MaOH) and heated to 80°C for 3 hours, whereafter it was treated as in example 6, which yielded 85 mg (61%) of the desired compound l,4-di-(2- naphthyl)-2-butane-l,4-dione. The compound was identified by NMR.

EXAMPLE 8

159 mg l,4-di-(4-dimethylaminophenyl)-2-butyne-l,4-diol were dissolved in a reaction medium consisting of 2 ml MeOH with 5 eqv. NaOH (70 mg, 85% NaOH) and heated to 80°C for 24 hours. Then it was cooled, and the precipitate was filtered off, washed with cold MeOH and thereafter with ether, and air dried, which yielded 44.5 g (28%) l,4-(4- dimethylaminophenyl)-butane-l,4-dione. The compound was identified by NMR.

EXAMPLE 9

50.2 mg 1,4-di(2-thienyl )-2-butyne-l,4-diol were dissolved in 2 ml CH-CN containing 2 vol-% H-O. There were performed aeration with N„, and addition of 9.3 mg NaOH, and heating to reflux for 2 hours. The reaction mixture was thereafter discharged in 15 ml H ₂ 0 and extracted with 5 x 5 ml CH«C1 ₂ . Thereafter it was evaporated, filtered and dried, which yielded 28,6 mg 1,4-di( 2-thienyl)-2-butyne-l,4-dione (57%). The compound was identified by IR-spectroscopy and by NMR.

EXAMPLE 10

5 experiments were carried out with production of 1,4-di- (2-thienyl)-butane-l,4-dione from 1, 4-di-( 2-thienyl)-2- butyne-l,4-diol.

The starting compound was dissolved in MeOH added with NaOH, and heated to reflux, whereafter it was cooled, filtered, washed and dried. The 1, 4-di-(2-thienyl)-butane- 1,4-dione was identified by NMR. Statements of amount, reflux times and yields appear from Table 1.

TABEL 1