NO316446B1 - Dimethyl furanecarboxyanilide derivatives and wood preservative - Google Patents

Description

Technical area

The present invention relates to new dimethylfurancarboxyanilide derivatives which exhibit an excellent antimicro-

bial effect, a wood preservative containing the dimethylfurancarboxyanilide derivative as active ingredient, and a wood preservative preparation in which dimethylfurancarboxyanilide

the derivative as one of the active ingredients is combined with any commercially available wood preservative whose effect has already been confirmed.

Known technique

Various types of inorganic or organic compounds have previously been used to preserve timber against rotting due to various wood-rotting fungi.

However, these have disadvantages such as affecting the human

body due to their high toxicity, they exhibit environmental pollution, require a high concentration when used and are expensive.

With regard to the compounds belonging to the dimethyl-furancarboxyanilide derivatives of the present invention, compounds represented by the formula below have been described in Japanese Patent Application (Kokai) Sho 50-10376

as a plant damage prevention chemical, wherein, however, R is limited to phenyl, nitro-substituted phenyl, carboxy-substituted phenyl, phenyl-substituted phenyl, methyl-substituted phenyl, halogen-substituted phenyl, or methoxy-substituted phenyl. In addition, this patent document is silent with regard to the other derivatives, and no activity of these compounds on wood-rotting fungi has been described.

Summary of the invention

An aim of the present invention is to provide a new wood preservative which is safe and which can be used effectively with a low concentration and/or at a low price.

Taking into account the above stated objective, the present inventors have made a thorough study of furan-carboxyanilide derivatives. This study resulted in the observation that the new dimethylfurancarboxyanilide derivatives represented by formula (I) below are very useful as a wood preservative, and if furthermore the dimethylfurancarboxyanilide derivatives as active ingredients are combined with any other commercially available wood preservative, an enhanced effect can be observed and a wood preservative preparation can be produced.

The compounds according to the present invention are dimethylfurancarboxyanilide derivatives characterized by general formula (I)

in which

R<1> denotes

a 3-Alkoxycarbonyl group with from 1 to 3 carbon atoms in the alkoxy part,

a 3-Alkoxymethyl group with from 1 to 3 carbon atoms in the alkoxy part,

a cycloalkylcarbonylamino group with from 4 to 6 carbon atoms in the cycloalkyl part,

a benzyl group which may be substituted with a methoxy group, a benzoyl group, or

an alkoxycarbonylalkenyl group having from 1 to 3 carbon atoms in the alkoxy part and having from 2 to 3 carbon atoms in the alkenyl part, and

R 2 denotes a hydrogen atom

The present invention further relates to a wood preservation preparation which is characterized in that it comprises a carrier in combination with an amount effective to preserve wood of a dimethylfurancarboxyanilide derivative of general formula (I') as defined below as active ingredient

in which

R<1>' denotes

a 3-alkyl group of from 2 to 6 carbon atoms,

a 3-Alkoxycarbonyl group with from 1 to 3 carbon atoms in the alkoxy part,

a 3-Alkoxymethyl group with from 1 to 3 carbon atoms in the alkoxy part,

a cycloalkylcarbonylamino group with from 4 to 6 carbon atoms in the cycloalkyl part,

a benzyl group which may be substituted with a methoxy group, a benzoyl group, or

an alkoxycarbonylalkenyl group with from 1 to 3 carbon atoms in the alkoxy part and with from 2 to 3 carbon atoms in the alkenyl part, and R<2>' denotes a hydrogen atom

The invention also relates to a wood preservative preparation which is characterized in that at least one dimethylfurancarboxyanilide derivative of general formula (I<1>) as defined in claim 3 is combined with at least one compound selected from 3-bromo-2,3-diiodo-2-propenyl- ethyl carbamate, 3-iodo-2-propynylbutyl carbamate and 4-chlorophenyl-3-iodopropargyl formal

Best method for carrying out the invention

In the general formula (I) given above, an alkyl group of from 2 to 6 carbon atoms, which is included in the definition of r\, is a straight chain or branched alkyl group such as ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, pentyl, isopentyl, neo-pentyl, hexyl, isohexyl or sec-hexyl; preferably an alkyl group with from 2 to 6 carbon atoms.

As an alkoxy group with from 1 to 3 carbon atoms contained in an alkoxyalkyl group with from 1 to 3 carbon atoms in the alkoxy group, and which is included in the definition for R<1> in general formula (I) above, a straight-chain or branched alkoxy group can be mentioned such as methoxy, ethoxy, propoxy or isopropoxy

As an alkoxycarbonyl group with from 1 to 3 carbon atoms in the alkoxy group, which is included in the definition for R<1> in general formula (I) above, methoxycarbonyl, ethoxycarbonyl or isopropoxycarbonyl can be mentioned

As a cycloalkylcarbonylamino group with from 4 to

6 carbon atoms in the cycloalkyl group, and which are included within the definition for R<1> in general formula (I) above, may be mentioned cyclobutylcarbonylamino, cyclopentylcarbonylamino or cyclohexylcarbonylamino, preferably cyclohexylcarbonylamino

New dimethylfurancarboxyanilide derivatives that can be used as an active component of the wood preservative according to the present invention are exemplified in the following table

In table 1 below, the indicated abbreviations are as follows

Among the compounds mentioned above, the preferred compounds include No. 3, 10, 20, 21, 23, 24, 25, 26, 69, 70, 71, 72, 75, 80, 81, 82, 83 and 85, and more preferably include compounds no. 3, 10, 24, 26, 69, 70, 81, 83 and 85

The compounds of general formula (I) may be prepared according to the procedure set forth in either the following Method A or Method B

Method A

Method B

In the formulas given above, R<1> is as defined above R<1>" denotes a C2-C6 alkyl group or benzyl group which may optionally have a methoxy substituent. The compound of formula (Ia) is that of general formula (I<1>) wherein R<1>' is R<1>" and R2 denotes a hydrogen atom The compound of formula (V) is 3od-substituted aniline X denotes a halogen atom such as chlorine, bromine or iodine, preferably chlorine X<1> denotes a halogen atom such such as chlorine, bromine or iodine, preferably bromine or iodine

The compounds according to the invention can be prepared

by well-known procedures.

Step Al consists of the preparation of a compound

of general formula (I) by reacting a compound of general formula (III) with a compound of general formula (IV) 1 a mercantile solvent 1 presence of a dehydrohalogenating agent.

A compound of formula (III) used as starting material in this step can be prepared by hydrolysis of 2,5-dimethylfuran-3-carboxylate, which can be prepared by condensation of chloroacetone with acetoacetate, followed by halogenation.

A compound of formula (IV) used as starting material in this step is an anilm derivative which is commercially available or can be prepared by well-known methods.

Examples of the inert solvents used include, for example, ethers such as ether, isopropyl ether, tetrahydrofuran or dioxane; aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as dichloromethane, chloroform or carbon tetrachloride; and mixtures of two or more of these solvents; preferably aromatic hydrocarbons (in particular toluene).

Examples of the dehydrohalogenating agents used include, for example, tertiary amines such as triethylamine, N,N-dimethylamino<p>yridine or the like, and pyridines. This reaction can be carried out in the presence or in the absence of a solvent. In order to carry out the reaction smoothly using a solvent, the reaction is carried out at a temperature of 0° C to the reflux temperature of the solvent used, preferably at room temperature to 100° C. The time required for the reaction generally takes from 30 minutes to 5 hours, preferably from 30 minutes to 2 hours.

Step B1 consists of the preparation of a compound of general formula (IV) by reacting a compound of general formula (III) with a compound of general formula (V) in an inert solvent in the presence of a dehydrohalogenating agent.

A compound of formula (IV) used as starting material in this step is an anilm derivative which is commercially available or which can be prepared by well-known methods.

The reaction conditions used in this step are similar to those used in step Al.

Step B2 consists in the preparation of a compound of general formula (Ia) by reacting a compound of general formula (VI) with a Grignard reagent of general formula: R i »MgX' in an inert solvent in the presence of a catalyst.

Examples of preferred inert solvents include, for example, ethers such as diethyl ether, isopropyl ether, tetrahydrofuran or dioxane; in particular diethyl ether.

[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride can be used as a particularly preferred catalyst.

The Grignard reagents used in this method are commercially available or can be prepared by reacting magnesium with an alkyl halide represented by the formula: R X (wherein R and X' are as defined above) according to well known methods.

The reaction is normally carried out at a temperature of 0° C to 50° C, preferably at room temperature. Although the time required for the reaction varies depending on the nature of the solvent and the reagent used, the reaction is normally completed within a period of 10 hours to 10 days.

The compounds of specified general formula (I) according to the invention have strong wood preservative activity at low concentration, compared to the activity shown by existing wood preservatives. A preparation consisting of a combination of the preceding compound (I) with a known wood preservative gives a synergistic effect, as lower concentrations of each compound are necessary than could be expected from the activity exhibited by each individual, so that the preparation exhibits an effective wood preservative activity at a low concentration. The new dimethylfurancarboxyanilide derivatives are therefore extremely effective as a wood preservative in low concentration and thereby solve one of the problems pointed out earlier.

The following examples illustrate the preparation and formulation of the compound according to the invention in more detail. These examples should not be considered as limiting the scope of the invention.

Example 1

2, 5- dime thy1furan- 3- carboxy( 3- acetylaminoanilide)

To a solution of 0.50 g of 2,5-dimethylfuran-3-carbonyl chloride in 10 ml of dichloromethane was added 0.44 ml of triethylamine and 0.47 g of 3-acetylaminoamine under ice cooling, and the resulting mixture was stirred at room temperature for 2 .5 hours, followed by heating to reflux for 4.5 hours. After the reaction mixture had cooled, it was diluted by adding 10 ml of dichloromethane. The diluted mixture was washed successively with 1N sodium hydroxide,

1N hydrochloric acid and a saturated aqueous solution of sodium chloride and was dried over sodium sulfate, followed by distillation of the solvent. The residue was purified by column chromatography through silica gel, and the desired fractions were recrystallized from ethyl acetate to give 0.51 g of the desired compound as white crystals in a yield of 59.4%. Melting point: 172.0 - 172.5° C

<1>H NMR (CDC13 + DMSO) 6 ppm:

8.4 (1H, b), 7.95 (1H, b), 7.88 (1H( m), 7.4 (1H,

m), 7.32 (1H, m), 7.25 (1H, t, J=8Hz), 6.25 (1H,

s), 2.55 (3H, s), 2.25 (3H, s), 2.15 (3H, s)

IR (KBr) cm"<1>: 3306, 1672, 1651, 1086, 781

Elemental analysis (%) : calculated for C-^H^g^O-j:

C 66.16 H 5.92 N 10.29

Found: C 66.30 H 5.98 N 10.32

By following a similar procedure as stated above, but using a suitable anilm derivative instead of 3-acetylaminoamine, the following compounds were obtained.

Example 2

2, 5- dimethylfuran- 3- carboxy (3- methoxycarbonylanilide)

Yield: 77.1%

Melting point: 104.0 - 106.0° C

<1>H NMR (CDC13) 6 ppm:

8.05 (1H, ra), 7.98 (1H, m), 7.8 (1H, m), 7.42

(1H, t, J=8Hz), 7.38 (1H, b), 6.1 (1H, s), 3.92

(3H, s), 2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm"<1>: 3437, 1704, 1675, 1070, 759

Elemental analysis (%) : Calculated for C-^H^i-NO^:

C 65.92 H 5.53 N 5.13

Found: C 66.02 H 5.60 N 5.08

Example 3

2, 5-dimethylfuran-3-carboxy(3-benzoylanilide) Yield: 69.1%

Melting point: 137.0 - 139.0° C

<1>H NMR (CDC13) 6 ppm:

8.05 (1H, m), 7.85-7.7 (3H, m), 7.6 (1H, m), 7.55-7.35 (5H, m), 6.1 (1H, s), 2.55 <3H, s) ,

2.25 (3H, s)

IR (KBr) cm"1: 3386, 1672, 1647, 1069, 707 Elemental analysis (%): Calculated for C20H17NO3: C 75.22 H 5.37 N 4.39

Found: C 75.38 H 5.43 N 4.38

Example 4

2, 5-dimethylfuran-3-carboxy(3-cyclohexylcarbonylaminoanilide) Yield: 45.1%

Melting point: 212.5 - 213.0° C

<1>H NMR (CDCl3) 6 ppm<*.>; 7.92 (1H, b), 7.88 (1H, b), 7.45-7.35 (2H, m), 7.25 ( 1H, t, J=8Hz), 6.22 (1H, s) , 2.55 (3H, s) , 2.25 (3H, s), 2.25-2.2 (1H, m), 2 ,0-1.2 (10H, m) IR (KBr) cm"<1>: 3238, 1651, 1639, 1076, 781 ;Elementary analysis (%): Calculated for C2<gH>24<N>2<0> 3: ;C 70.57 H 7.11 N 8.23 Found: C 70.56 H 7.26 N 8.16 ;Example 5 ;2, 5- dimethylfuran- 3-carboxy (- 3- methoxymethylanil3. d) Yield: 73.3% ;M.p.: 102.5 - 103.5° C ;<X>H NMR (CDCl 3 ) <S ppm: ;7.55 (1H, m) , 7.52 (1H, d, J=8Hz), 7.32 (1H, t, J=8Hz), 7.32 (1H, b), 6.9 (1H, d, J=8Hz), 6.1 ;<1H, s ), 4.45 (2H, s), 3.4 (3H, s), 2.55 (3H, s), ;2.25 (3H, s) ;IR (KBr) cm"<1>: 3278 , 1645, 1237, 1107, 784 Elementary analysis (%); Calculated for ci5Hi7N03: C 69.48 H 6.61 N 5.40 ; Found: C 69.22 H 7.02 N 5.37 ; Example 6 ; 2, 5- dimethylfuran- 3-carboxy( 3- ethoxymethylanilide) Yield : 64.4% ;M.p.: 85.0 - 85.5° C ;<X>H NMR (CDCl 3 ) <S ppm: ;7.65-7.55 (2H, m) , 7.38 (1H, t#iJ=8Hz), 7.35 (1H, b), 7.15 (1H, d, J=8Hz), 6.15 (1H, s), 4.55 (2H, s), 3.58 (2H, q, J=8Hz), 2.55 (3H, s), 2.25 (3H, ;s), 1.3 (3H, t, J=8Hz) ;IR (KBr) cm "<1>: 3279, 1646, 1115, 785 ;Elementary analysis (%) : Calculated for C^gH^^NO^: ;C 70.31 H 7.01 N 5.12 ;Found: C 70.14 H 7 .27 N 5.06 ; Example 7 2, 5- dimethylfuran- 3- carboxy( 3- isopropyloxymethylan lide) Yield: 92.7% ; M.p.: 68.0 - 69.5° C ; <1>H NMR (CDCl 3 ) <5 ppm: ;7.55 (1H, d, J=8Hz), 7.5 (1H, m), 7.3 (1H, t, J=8Hz), 7.3 (1H, b), 7.12 (1H, d, J=8Hz), 6.1 (1H, s), 4.5 (2H, s), 3.7 (1H, m), 2.55 (3H, s ) , ;2.25 (3H, s), 1.25 (6H, d, J=7Hz) ;IR (liquid film) cm"<1>: 3321, 1651, 1072, 785 Elemental analysis (%) : Calculated for C ^<H>2j<N>03: C 71.06 H 7.37 N 4.87 ;Found: C 70.35 H 7.14 N 4.91 ;Eczema pel 8 ; 2, 5- dimethylfuran- 3- carboxy[ 3-( 4- methoxybenzyl) anilide] Yield: 86.8% ; M.p.: 100.0 - 102.5° C ; ^■H NMR (CDC13 ) 6 ppm: ;7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, t, J=8Hz), ;7.25 (1H, b), 7.1 ( 2H, d, J=8Hz), 6.92 (1H, d, ;J=8Hz), 6.88-6.75 (1H, m), 6.82 (2H, d, J=8Hz), ; 6.05 (1H, s), 3.9 (2H, s), 3.75 (3H, s), 2.55 ;(3H, s), 2.25 (3H, s) ;IR (KBr) cm"*1: 3345, 1656, 1246, 1074, 694

Elemental analysis (%): Calculated for C2iH21N03:

C 75.20 H 6.31 N 4.18

Found: C 75.28 H 6.32 N 4.21

Example 9

2, 5- dimethylfuran- 3- carboxy[ 3-( 2- methoxycarbonylvinyl) anilide] Yield: 63.3%

Melting point: 159.5 - 161.5° C

1 H NMR (CDCl 3 ) 6 ppm:

7.82 (1H, m), 7.7 (1H, d, J=15Hz), 7.58 (1H, m),

7.38 (1H, b), 7.35 (1H, t, J=8Hz), 7.28 (1H, m),

6.48 (1H, d, J=15Hz), 6.12 (1H, s), 3.82 (3H, s),

2.55 (3H, s), 2.25 (3H, s)

IR (KBr) cm"<1>: 3387, 1685, 1670, 1068, 800

Elemental analysis (%): Calculated for C1?H^7N04:

C 68.22 H 5.72 N 4.68

Found: C 67.55 H 5.64 N 4.62

Example 10

2, 5-dimethylfuran-3-carboxy(3-ethylanilide)

Yield: 91.0%

Melting point: 113 - 115° C

Mass (m/z): 243 (M<+>), 123.94

<1>H NMR (CDC13) «5 ppm:

7.47-6.95 (4H, m), 6.1 (1H, s), 2.66 (3H, q),

2.60 (3H, s), 2.29 <3H, s), 1.25 (3H, t)

Example 11

2, 5-dimethylfuran-3-carboxy(3- isopropylanilide)

Yield: 84.0%

Melting point: 79 - 80° C

Mass (m/z): 257 (M<+>), 149.135

<1>H NMR (CDC13) 6 ppm:

7.47-6.98 (4H, m), 6.11 (1H, s), 2.91 (1H, q,q),

2.60 (3H, s), 2.29 (3H, s), 1.26 (d, 6H)

Example 12

2,_, 5- dimethyl furan- 3- carboxy (3- hexy lam lid)

(Step 1) To a solution of 3.95 g of 2,5-dimethylfuran-3-carbonyl chloride in 60 ml of dichloromethane was added 3.45 ml of triethylamine and 2.99 ml of m-iodanyl under ice cooling and the resulting mixture was stirred at room temperature i

6.5 hours. After the reaction mixture had cooled, it was diluted by adding 50 ml of dichloromethane. The diluted mixture was washed successively with 1N sodium hydroxide, 1N hydrochloric acid and a saturated aqueous solution of sodium chloride, and

was dried over sodium sulfate followed by distillation of the solvent. The residue was subjected to column chromatography through silica gel to give 7.64 g of 2,5-dimethylfuran-3-carboxy(3-iodanilide) as pale yellow crystals in a yield of 89.9%.

(Step 2) To a solution of 0.68 g of the crystals obtained in Step 1 in 8 ml of diethyl ether was added 29.3 mg of [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride and 11 ml of IM hexyl magnesium bromide, prepared from hexyl bromide and magnesium, divided into six equal parts, and the resulting mixture was stirred at room temperature for 47 hours. After adding 2N hydrochloric acid to the reaction mixture, the catalyst was filtered off and the filtrate was extracted with diethyl ether. The extract was successively washed with an aqueous solution of natnumbicarbonate and a saturated aqueous solution of sodium chloride and was dried over sodium sulfate. After distilling off the solvent, the residue was purified by chromatography through silica gel and then a D-ODS-5, YMC packed column to give 316 mg of the desired compound as white crystals in a yield of 52.8%.

Melting point: 71.5 - 72.0° C

1 H NMR (CDCl 3 ) 6 ppm:

7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, b), 7.22

(1H, t, J=8Hz), 6.95 (1H, d, J=8Hz), 6.1 (1H, s), 2.65-2.5 (2H, m), 2.55 (3H , s), 2.25 (3H, s),

1.7-1.5 (2H, m), 1.4-1.2 (6H, m), 0.85 (3H, t,

J=7Hz)

IR (KBr) cm"<1>: 3310, 1643, 1077, 788

Elemental analysis (%): Calculated for C^gH^NC^:

C 76.22 H 8.42 N 4.68

Found: C 76.15 H 8.54 N 4.55

Following a similar procedure as above, but using a suitable Grignard reagent instead of hexylmagnesium bromide, the following compounds were obtained.

Example 13

2, 5-dimethylfuran-3-carboxy(3-butylanilide)

Yield: 36.4%

Melting point: 77.0 - 80.0° C

<1>H NMR (CDC13) 6 ppm:

7.45 (1H, m), 7.35 (1H, m), 7.25 (1H, b), 7.22 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.55 (2H, m), 2.55 (3H, s), 2.25 (3H, s), 1.6 (2H, m ), 1.35 (2H, m), 0.92 (1H, t, J=7Hz) IR (KBr) cm"<1>: 3285, 1646, 1075, 702 Elemental analysis (%) : Calculated for Cj^H ^N<C>^: C 75.25 H 7.80 N 5.16

Found: C 75.13 H 7.87 N 5.13

Example 14

2, 5-dimethylfuran-3-carboxy(3-sec-butylanilide) Yield: 38.1%

Melting point: 80.0 - 81.0° C

1 H NMR (CDCl 3 ) <5 ppm:

7.4 (1H, m), 7.38 (1H, m), 7.25 (1H, b), 7.22 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.5 (1H, m), 2.55 (3H, s), 2.25 (3H, s), 1.68-1.5 (2H, m), 1.25 (3H, d, J=7Hz), 0.85 (3H,

t, J=7Hz)

IR (KBr) cm"<1>: 3255, 1647, 1078, 791 Elemental analysis (%): Calculated for C^<I>^^<N>C^: C 75.25 H 7.80 N 5.16

Found: C 75.19 H 7.68 N 5.14

Example 15

2, 5-dimethylfuran-3-carboxy(3-pentylanilide) Yield: 18.3%

Melting point: 97.0 - 97.5° C

1 H NMR (CDCl 3 ) 6 ppm:

7.45 (1H, m), 7.35 (1H, m), 7.28 (1H, b), 7.25 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.5 (2H, m), 2.55 (3H, s), 2.25 (3H, s), 1.7-1.5 (2H, m), 1.4-1.2 (4H,m), 0.88 (3H, t, J=7Hz)

IR (KBr) cm"<1>: 3304, 1644, 1077, 710

Elemental analysis (%) : Calculated for C-^H^NC^:

C 75.76 H 8.12 N 4.91

Found: C 75.77 H 8.18 N 5.06

Example 16

2, 5- dimethylfuran- 3- carboxy-( 3- cyclohexylanilide)

Yield: 52.7%

Melting point: 113.0 - 114.5° C

"hi NMR (CDCl 3 ) 6 ppm:

7.48 (1H, m), 7.35 (1H, m), 7.28 (1H, b), 7.25

(1H, t, J=8Hz), 6.98 (1H, d, J=8Hz), 6.1 (1H, s),

2.58 (3H, s), 2.55-2.45 (1H, m), 2.25 (3H, s),

1.95-1.68 (5H, m) , 1.55-1.15 (5H, m)

IR (KBr) cm"<1>: 3324, 1646, 1230, 1074, 791

Elemental analysis (%) : Calculated for ci<jH23N02:

C 76.74 H 7.80 N 4.71

Found: C 76.62 H 7.78 N 4.67

Example 17

2, 5-dimethylfuran-3-carboxy (3-benzylanilide)

Yield: 59.8%

Melting point: 123.0 - 125.0° C

1 H NMR (CDCl 3 ) 6 ppm:

7.45 (1H, m), 7.38 (1H, m), 7.35-7.15 (7H, m),

6.95 (1H, d, J=8Hz), 3.98 (2H, s), 2.55 (3H, s),

2.25 (3H, s)

IR (KBr) cm"<1>: 3314, 1640, 1078, 777, 701

Elemental analysis (%): Calculated for C21H19N02:

C 78.66 H 6.27 N 4.59

Found: C 77.76 H 6.28 N 4.55

Reference example 1

Ethyl-2,5-dimethylfuran-3-carboxylate

To a suspension of 2.4 g of sodium hydride (60% dispersion in mineral oil) in 10 ml of N,N-dimethylformamide (hereafter abbreviated as DMF) a solution of 6.5 ml of ethyl acetate in 5 ml of DMF was added dropwise with stirring and under ice-cooling, and 5.97 ml of chloroacetone was added dropwise with stirring and under ice-cooling. After stirring at room temperature for 3 hours, the reaction mixture was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and was dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was distilled in vacuum to form 8.01 g of ethylacetonitrile-acetoacetate with a boiling point of 105°C/2 mmHg in a yield of 86%.

To a solution of the thus obtained ester in 20 ml of ethanol was added 2 g of p-toluenesulfonic acid and the resulting mixture was heated under reflux for 2 hours. The reaction mixture was allowed to cool to room temperature and the solvent was distilled off under reduced pressure. The residue was dissolved in ethyl acetate and the solution was washed with a saturated aqueous solution of sodium chloride, followed by drying over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by column chromatography through silica gel using a 10:1 mixture of n-hexane and ethyl acetate as eluent, yielding 5.14 g of ethyl 2,5-dimethylfuran-3-carboxylate in a yield of 71%.

Reference example 2

2, 5- dimethylfuran- 3- carboxylic acid

A mixture of 3.2 g of ethyl 2,5-dimethylfuran-3-carboxylate, 35 ml of ethanol and 20 ml of 2N sodium hydroxide was stirred at room temperature for 1.5 hours, followed by heating under reflux for 1 hour. After the reaction mixture was cooled to room temperature, it was concentrated under reduced pressure. The residue was dissolved in water and acidified with dilute sulfuric acid. The precipitated crystals were collected by filtration, washed with water and dried to give 2.27 g of 2,5-dimethylfuran-3-carboxylic acid in a yield of 85%.

The compound with general formula (I) mentioned above and the preparation containing the compound (I) as active ingredient and to which the present invention relates, can be used by mixing with carriers, or if necessary, with any other additive, followed by the preparation of formulations that are usually used, such as oil solution, emulsifiable concentrate, solubilizer, paste, wettable powder, flowable material, dry flowable material, spray and paint, and the formulation can then be used according to any known method of wood preservation treatment. As additives which are suitably used to improve the properties of the formulation and to strengthen the wood preservative effect, mention can be made of cationic, anionic and non-ionic surface-active agents, various high-polymeric compounds such as methyl cellulose and vmylacetate resin, and water-repellent agents such as such as silicone oil and paraffin. Needless to say, combined application may be possible with other wood preservatives, fungicides and bactericides, including organic iodine compounds such as "Sanplas", "lF-1000" and "Troysan", azole compounds such as "Propiconazole" and "Tebuconazole". , "Thiabendazole", "Dichlofluanid" and quaternary ammonium salt compounds; with insecticides including pyrethroids such as "Permethrin", "Etofenprox", "Cypermethrin", "Silaneophen", "Tralomethrin", organophosphorus compounds such as "Chloropyrifos", "Phoxim" and "Propetamphos" and "Imidacroprid"; and with potentiating agents such as bis-(2,3,3,3-tetrachloropropyl)ether. An increased effect can be expected with combined use in this way. Although the content of the compound according to the invention can vary within a wide range, depending on the formulation or on the object, when applied it can usually be appropriate to use from 0.1 to 95% by weight, preferably from 0.2 to 60% by weight. These formulations are usable by common methods of wood treatment: for example coating, dispersing, dipping, mixing, impregnating or mixing treatment with an adhesive.

The subsequent compounds according to reference examples 3 and 4 were prepared in the same way as in example 1

Reference example 3

3'-ethyl-2,5-dimethylfuran-3-carboxanilide

Yield 91.0%

Mp 113-115 °C

Mass (m/z) 243 (M+), 123.94

<X>H NMR (CDCl 3 ) 5 ppm

7.47-6.95 (4H, m), 6.1 (1H, s), 2.66 (3H, q), 2.60 (3H, s), 2.29 (3H, s), 1 .25 (3H, h)

Reference example 4

3'-isopropyl-2,5-dimethylfuran-3-carboxanilide

Yield 84.0%

Mp 79-80 °C

Mass (m/z) 257 (M+), 149.135

<X>H NMR (CDCl 3 ) 5 ppm

7.47-6.98 (4H, m), 6.11 (1H, s), 2.91 (1H, q, q), 2.60 <3H, s), 2.29 (3H, s) , 1.26 (d, 6H)

Reference example 5

3'-hexyl-2,5-dimethylfuran-3-carboxanilide

(Step 1) To a solution of 3.95 g of 2,5-dimethylfuran-3-carbonyl chloride in 60 ml of dichloromethane, 3.45 ml of triethylamine and 2.99 ml of m-iodaniline were added under ice-cooling, and the resulting mixture was stirred at room temperature 1 6.5 hours After the reaction mixture was cooled, it was diluted by adding 50 ml of dichloromethane. The diluted mixture was washed successively with 1 N sodium hydroxide, 1 N hydrochloric acid and a saturated aqueous solution of sodium chloride and was dried over sodium sulfate followed by of distilling off the solvent The residue was subjected to column chromatography 1 through silica gel forming 7.64 g of 2,5-dimethylfuran-3-carboxy(3-iodanilide) as pale yellow crystals 1 a yield of 89.9%

(Step 2) To a solution of 0.68 g of the crystals obtained in step 1 in 1 8 ml of diethyl ether, 29.3 mg of [1,1<1->bis(diphenylphosphino)ferrocene]palladium(II) chloride was added and 11 ml of 1 M hexyl magnesium bromide, prepared from hexyl bromide and magnesium,

divided into six equal parts, and the resulting mixture was stirred at room temperature for 47 hours. After addition of 2 N hydrochloric acid to the reaction mixture, the catalyst was filtered off, and the filtrate was extracted with diethyl ether. The extract was successively washed with an aqueous solution of sodium bicarbonate and a saturated , aqueous solution of sodium chloride and dried over sodium sulfate After distilling off the solvent, the residue was purified by chromatography through silica gel and then D-ODS-5, YMC packed column to give 316 mg of the desired compound as white crystals in a yield of 52, 8%

Mp 71.5-72.0 °C

<X>H NMR (CDCl 3 ) 5 ppm

7.45 (1H, m), 7.35 (1H, ra), 7.25 (1H, b), 7.22 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.5 (2H, m), 2.55 (3H, s), 2.25 (3H, s), 1.7-1.5 (2H, m) , 1.4-1.2 (6H, m), 0.85 (3H, t, J=7Hz)

IR (KBr) cm"<1> 3310, 1643, 1077, 788

Elemental analysis (%) Calculate for C19H25NO2 C 76.22, H 8.42,

N 4.68 Found C 76.15, H 8.54, N 4.55

By following a similar procedure as described above, but using a suitable Grignard reagent instead of hexylmagnesium bromide, the following compounds were obtained

Reference example 6

3'-butyl-2,5-dimethylfuran-4-carboxanilide

Dividend 36.4%

Mp 77.0-80.0 °C

<X>H NMR (CDCl 3 ) 5 ppm

7.45 (1H, m), 7.35 <1H, m), 7.25 (1H, b), 7.22 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.55 (2H, m), 2.55 (3H, s), 2.25 (3H, s), 1.6 (2H, m ), 1.35 (2H, m), 0.92 (1H, t, J=7Hz) IR (KBr) cm"<1> 3285, 1646, 1075, 702

Elemental analysis (%) Calculate for C17H2iN02 C 75.25, H 7.80,

N 5.16 Found 75.13, H 7.87, N 5.13

Reference example 7

3'-sec-butyl-dimethylfuran-3-carboxanilide

Dividend 38.1%

Mp 80.0-81.0 °C

<X>H NMR (CDCl 3 ) 5 ppm

7.4 (1H, m), 7.38 (1H, ra), 7.25 (1H, b), 7.22 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.5 (1H, m), 2.55 (3H, s), 2.25 (3H, s), 1.68-1.5 (2H, m), 1.25 {3H, d, J=7Hz), 0.85 (3H, t, J=7Hz)

IR (KBr) cm"<1> 3255, 1647, 1078, 791

Elemental analysis (%) Calculate for Ci7H2iN02 C 75.25, H 7.80,

N 5.16 Found C 75.19, H 7.68, N 5.14

Reference example 8

3'-pentyl-2,5-dimethylfuran-3-carboxamide

Dividend 18.3%

Mp 97.0-97.5 °C

<X>H NMR (CDCl 3 ) S ppm

7.45 (1H, m), 7.35 (1H, rn), 7.28 (1H, b), 7.25 (1H, t, J=8Hz), 6.95 (1H, d, J= 8Hz), 6.1 (1H, s), 2.65-2.5 (2H, ra), 2.55 (3H, s), 2.25 (3H, s), 1.7-1.5 (2H, m) , 1.4-1.2 (4H, rn), 0.88 (3H, t, J=7Hz)

IR (KBr) cm"<1> 3304, 1644, 1077, 710

Elemental analysis (%) Calculate for Ci8H23N02 C 75.76, H 8.12,

N 4.91 Found C 75.77, H 8.18, N 5.06

Test examples of wood preservation

The effectiveness of the wood preservatives according to the present invention is concretely illustrated by the following examples.

(1) According to the test method for wood preservation described 1 the Japan Industrial Standards [JIS A-9201 (1991)], each of the test compounds was dissolved to a defined concentration 1 methanol. The solution was impregnated under reduced pressure 1

Sugi (Japanese cedar) sapwood (2x2x1) cm and was then air dried. Each test was repeated 10 times in which one cycle of the treatment was stirring 1 water 1 8 hours and then heating 1 16 hours at 60° C. The test material was placed on the flora of Serpula lacrymans which had previously been cultivated

on a quartz sand medium (2% malt extract, 1% glucose, 0.3% peptone and 0.2% yeast) and was forced to putrefy at 20°C

for 12 weeks. From the difference between the dry weight of the test material before the test and after the test, the degree of weight reduction was obtained. Table 2 shows the results. The test was carried out using 9 samples for each condition, and the values shown in Table 2 are the mean values calculated from 9 samples.

Control compound 1: 4-chlorophenyl-3-iodopropargylformal Product of Nagase Co.f Ltd.: IF-1000

From the data shown above, the compound of general formula (I) prevented decay of the wood samples due to wood-rotting fungi to a significant extent. (2) Each of 0.1 w/v% methanol solutions of the compound of the invention and the control agent were impregnated into the test material (a Sugi (Japanese cedar) sapwood, 2 x 2 x 0.5 cm) under reduced pressure and then air dried. Each test was repeated twice, in which one cycle of the treatment was washing (about 2 liters added per minute) with water for 5 hours, and then heating for 19 hours at 60° C. After dry air sterilization, the test samples were prepared.

The test materials were placed on a flora of

Coriolus versicolor which is a lignm-decomposing fungus,

and of Tyromyces palustris, which is a cellulose-decomposing fungus, and where both are recognized fungal species for testing the wood preservative effect. Both fungi had previously become

grown on an agar medium (2% malt extract, 1% glucose and 0.5% peptone). After the wood samples were forced to weaken at 26°C for 3 weeks, the effectiveness was determined from the degree of hyphal growth on the test material, and the presence or absence of reduced maximum crushing strength. Table 3 shows the results.

The three-preventive activity was judged by the following criteria.

+: No hyphal growth was observed on the test material, and no difference was found in the maximum crushing strength from the healthy wood sample.

+: A slight hyphal growth was observed on the test material, or a slight reduction was found in the maximum crushing strength.

Hyphal growth was observed on the test material, or a clear reduction was found in the maximum crushing strength.

Coritrol compound 2: 3-bromo-2,3-diiodo-2-propenylethyl carbonate

Product of Sankyo Co., Ltd.: "Sanplas"

When the preparation according to the invention is to be used, the combination ratio can be suitably chosen depending on the type of wood and the type of wood material to be treated with the wood preservative, or treatment method (for example coating, dipping, dispersing, impregnation, mixing and mixing with an adhesive). Generally, the combination ratio between dimethylfurancarboxyanilide and any other wood preservative may be from 240:1 to 1:35, preferably from 30:1

to 1:10, and preferably from 5:1 to 1:5.

The content of the preparation according to the invention can be changed within a wide range depending on the formulation. In general, the content may be from 0.1 to 95%, preferably

from 0.2 to 60%, in the formulation.

In addition to the publications previously mentioned, reference should be made to JP-A-05112406 (D3) which describes 2,5-dimethylfurancarboxylanilide derivatives which are stated to have wood preserving properties JP-A-5010376 (D4) describes substituted 2,5- dimethylfurancarboxyanilide derivatives indicated to be plant protectants although their activity on wood-rotting fungi has not been described

Reference must also be made to a further document, GB

1 592 837, which describes N-haloalkylthio derivatives of 2,5-dimethylfurancarboxyanilide compounds which are indicated to have wood preservative activity, as well as intermediates for their preparation Some of these intermediates are compounds which in the present application have been shown to have excellent wood preservative activity As pointed out below, there is nothing in GB 1 592 837 which would lead the person skilled in the art to assume that the compounds in question, which are 3<1->alkyl-2,5-dimethylfurancarboxyanilide derivatives, could have other uses than intermediates in the synthesis of N- the haloalkylthio compounds described in the indicated publication

The closest publication is without a doubt D3 The activity of the compound 2,5-dimethylfuran-3-carboxyanilide described in D3 was compared with respect to the wood preservative activity with some of the closest structural analogues from the compounds of formula (I) and formula (I <1>)

In a first experiment, the wood preservative activity of the known compound 2,5-dimethylfuran-3-carboxyanilide was compared with that of 3'-isopropyl-2,5-dimethylfuran-3-carboxyanilide, where the latter compound is a compound of formula (I<1>) Their activity against Coriolous versicolor and Serupula lacrymans was tested according to the procedure indicated in the description The results are shown below These data clearly show that the compounds of formula (I') according to the invention exhibit a significantly improved wood preservative activity compared to the known compound, and that this improved activity cannot in any way be derived from the known technique

In the following, a further test is described with regard to wood preservative activity for compounds according to the invention compared to the closest known compound, 2,5-dimethylfuran-3-carboxyanilide

In the experiments according to the test method for wood preservation described in Japan Industrial Standards [JIS A-9201 (1991)], each of the test compounds was dissolved to a defined concentration in methanol. The solution was impregnated under reduced pressure in Sugi (Japanese cedar) flint wood (2x2x1 cm) and was then air-dried A weather test was repeated 10 times in which one treatment cycle was stirring in water for 8 hours and then heating for 16 hours at 60 °C

The test material was placed on the flora of Conolus versicolor or Tyromyces palustns, both of which are fungal species for testing the wood preservation effect. Both fungi had previously been grown on a quartz sand medium (malt extract 2%, glucose 1%, peptide 0.3% and yeast 0.2% ) or an agar medium (malt extract 2%, glucose 1% and peptone 0.5%) After the wood samples were forcibly weakened at 26 °C for 8 weeks, the effectiveness of the test compound was determined from the difference between the dry weight of the test material before the test and that after the test, where the degree of weight reduction was obtained The subsequent tables show the results The test was carried out on 9 samples of each test compound, and the values shown in the tables are the mean values calculated from the 9 samples

In the following tables, compound A is 2,5-dimethylfuran-3-carboxyanilide

Claims (7)

1 Dimethylfurancarboxyanilide derivatives, characterized by general formula (I) in which R<1> b<e>signs a 3-Alkoxycarbonyl group with from 1 to 3 carbon atoms in the alkoxy part, a 3-Alkoxymethyl group with from 1 to 3 carbon atoms in the alkoxy part, a cycloalkylcarbonylamino group with from 4 to 6 carbon atoms in the cycloalkyl part, a benzyl group which may be substituted with a methoxy group, a benzoyl group, or an alkoxycarbonylalkenyl group having from 1 to 3 carbon atoms in the alkoxy part and having from 2 to 3 carbon atoms in the alkenyl part, and R<2> denotes a hydrogen atom 2 Dimethylfurancarboxyanilide derivative of general formula (I) according to claim 1, characterized in that the specified derivative is 31-benzyl-2,5-dimethylfuran-3-carboxyanilide 3 Wood preservation preparation, characterized in that it comprises a carrier in combination with an amount effective to preserve wood of a dimethylfurancarboxyanilide derivative of general formula (I<1>) as defined below as active ingredient in which R<1>' denotes a 3-alkyl group with from 2 to 6 carbon atoms, a 3-alcocaylcarbonyl group with from 1 to 3 carbon atoms in the alkoxy part, a 3-Alkoxymethyl group with from 1 to 3 carbon atoms in the alkoxy part, a cycloalkylcarbonylamino group with from 4 to 6 carbon atoms in the cycloalkyl part, a benzyl group which may be substituted with a methoxy group, a benzoyl group, or an alkoxycarbonylalkenyl group with from 1 to 3 carbon atoms in the alkoxy part and with from 2 to 3 carbon atoms in the alkenyl part, and R<2>' denotes a hydrogen atom 4 Wood preservation preparation according to claim 3, characterized in that the indicated dimethylfurancarboxyanilide derivative is 3'-isopropyl-2,5-dimethylfuran-3-carboxyanilide 5 Method for preserving wood, characterized in that the wood is applied with a preparation comprising an amount that is effective for treating wood of a dimethylfurancarboxyanilide derivative of general formula (I') as defined in claim 3 6 Method for preserving wood according to claim 5, characterized in that the indicated dimethylfurancarboxyanilide derivative is 3<1->isopropyl-2,5-dimethylfuran-3-carboxyanilide 7 Wood preservation preparation, characterized in that at least one dimethylfurancarboxyanilide derivative of general formula (!'} as defined in claim 3 is combined with at least one compound selected from 3-bromo-2,3-diiodo-2-propenylethylcarbamate, 3-iodo-2-propynylbutylcarbamate and 4 -Chlorophenyl-3-j odopropargyl formal