CS274008B1 - New derivatives of 2-methylene butanedioic acid and method of their preparation - Google Patents

Abstract

The invention concerns derivatives of 2-methylene butanedioic acid of general formula 1, where Rl is substituted alkoxyl, the substituted anilino group and R2 is the hydroxy, amino, substituted anilino of phenoxy group. The substances are prepared by reaction of the acid or its reaction derivative with hydroxy compounds or amines. The substances are used as fungicides.<IMAGE>

Description

The invention relates to novel 2-methylene-1,4-butanedioic acid derivatives and to a process for their preparation.

2-Motylenebutendic acid has been described, e.g., by Moritsu H., et al., Eur. J. Appl. Microbiol. Biotechnol 10, 358 (1980) as the product of Aspergilus terreus. Some of its derivatives, such as mono- and diesters or imides, are described, for example, in European Patent Specification No. 34556 or Belgian Patent Specification No. 613,136, which discloses fungicidal activity and stimulation of plant growth for these substances.

The present invention provides novel 2-methylenebutanedioic acid derivatives of formula I, ch ₂ = C - cor ₂

AND

_CH2 - CORjl / 1, wherein when R represents a straight or branched alkoxy with an alkyl of C ^ to Cg, optionally substituted by chlorine, or methoxy, then R ₂ is hydroxy, amino, mono- or disubstituted phenoxy, the substituents R and R ' wherein R 'and R' are methyl, chloro, nitro, ethoxycarbonyl in ortho, meta and para positions, an ethyleneimino group, anilino group mono- or disubstituted with aromatic substituents. R 1 and R 2, wherein R and R 2 are methyl, ethyl, chlorine or nitro in ortho, meta and para positions, wherein R on nitrogen is hydrogen, 1-methoxy-2-propyl, or 1- ( l-methoxycarbonyl) ethyl, and when R represents an anilino group mono- or disubstituted by R ^V and R ^VI, wherein R ^ and R ^ are methyl, ethyl, chloro, fluoro, trifluoromethyl, methoxy or nitro group at the ortho, meta and para thereafter R ₂ represents a hydroxy group.

The compounds of the present invention are prepared by reacting 1 to 3 molar parts of 2-methylenebutanedioic acid or a reactive derivative thereof as anhydrides or methyl (3-chloroformyl) -3-buteonate with 1 to 8 molar parts of a nucleophilic compound of formula II,

Rj - Nu / II wherein when Nu represents a hydroxy group, then R 6 is a straight or branched C 1 -C 8 alkyl optionally substituted by chlorine or methoxy, phenyl mono or disubstituted independently by nitro, ethoxycarbonyl, methyl or chlorine when Nu represents an amino group then R 1 is hydrogen, phenyl, phenyl mono or disubstituted independently with fluoro, chloro, nitro, methyl, ethyl trifluoromethyl or methoxy and if Nu is imino then R 1 is ethylene or R 1 is simultaneously two substituents, phenyl disubstituted independently methyl, ethyl and 1-methoxy-2-propyl or 1- (1-methoxycarbonyl) -ethyl, at -30 ° C to 100 ° C for 5 minutes to 6 hours.

The compounds of formula I exhibit fungicidal activity. For this reason, these compounds can be used as plant protection agents.

The details of the various methods of preparation are given in the following examples without being limited to these. The structure of the compounds was confirmed

NMR, IR spectra and elemental analysis.

Example 11 1- (3-Methoxy-2-proplyl) -3-methylenebutanedioate

A mixture (13 g, 0.1 mol) of 2-methylenebutanedioic acid (53 g, 0.6 mol) of 3-methoxy-2-propanol and (15.7 g, 0.2 mol) of acetyl chloride was heated at 65 ° C for 20 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was distilled under reduced pressure. 18 g of product (89%) with a boiling point of B7 ° C at 0.53 kPa were obtained.

CS 274 008 Bl

H-nmr (ω ₃ ) ₂ ) ωt = δ, 3; 5.8; (s) 3.31 (S) 5.03 m, 3.42 (s), 1.17 (d); 9,2,1 (bs)

Example 2 to

Analogously to Example 1, the following derivatives were obtained

A \

C /

H '= C - C0, HI ^L

CH ₂ - CORj

Example R = Yield /% T.v. 1 H-NMR,

° C / kPa ^h a> ^h b 2 Cl / CH _2/3 -0- 72 90 / 0.13 6. , 30; 5.84 3 C1 / _{CH2 /} -0- 81 98 / 0.13 6, , 32; 5.90 4 2-isooctyl-O- 91 60 ° C 6. , 28; 5.78

Example 5

4- (2,4-dinitrophenyl) -1-methyl-3-methylenebutanedioate

A mixture of methyl 3-chloroformyl 3-butenoate (1.62 g, 0.01 mol), 2,4-dinitrophenol (1.84 g, 0.01 mol) and triethylamine (1.01 g, 0.01 mol) The mixture was stirred for 2 hours in benzene at room temperature and the product was distilled under reduced pressure. 2.1 g (69%) of a substance with a boiling point of 120 to 121 ° C at 0.013 kPa were obtained.

^I H-NMR / DMSO-d / = 6.15, 5.75 (s), 3.58 (s), 3.35 (s) 8.86 to 8.38 (m)

Examples 6 to 23

In analogy to the procedure of Example 5, the following derivatives were obtained

C - COR

AND

CH ₂ -CO ₃ CH-j

Example R ₂

Yield /% _ / Tv resp.Tt HNMR S ° C / mm Hg, respectively. ° CH _A Ηθ

135 / 0.013 6.48; 6, OB

142 / 0.53 6.03; 5.62

CS 274 008 Bl

8 -nh - <(5) -no ₂ 54 67 6.18; 5.80 9 73 132 / 0.052 6.45; 6.06 10 -nh- (5) -no ₂ 64 121 to 122 6.11; 5.78 11 -N - ^> 63 76 to 78 6.04; 5.66 12 -NH ^ 63 143 / 0.065 6.04; 5.65 13 -ΝΗ-Ηβ) Cl Cl 67 24 6.08; 5.69 14 -NH-fo \ 61 110 6.00; 5.61 15 Dec - <T 61 oil 6.23; 5.81

ch ₃ and ₂ ch / ch ₃ / n - ^^

ch ₃ and ₂ ch / ch ₃ / n- ^)

CH ₃ CH ₂ CH / CH ₃ / N-

CH, OOCCH (CH3) N, ⁵

0C0CH _CH3 / _CH3 / N <0

-NH

- <o

-NH- ^ O)

F

Cl

-NHCH "^

Cl

-NHnfe) ^- 'NO',

164 / 0.065

142 / 0.065

104 / 0.026

176 / 0.065

178 / 0.065

132 / 0.052

131 / 0.052

140 / 0.039

128 to 132

5.21; 4.98

5.20; 5.09

6.15

6.15; 5.28

5.29; 4.83

5.59; 5.54

5.90; 5,56

5.95; 5.54

5.85; 5.65

Example 25

3- (2-Trifluoromethylphenylcarbamoyl) -2-methylenepropanoic acid

To a solution of 2-methylenebutanedioic anhydride (1.12 g, 0.01 mol) in benzene (50 ml) was added at room temperature 1.61 g (0.01 mol) of 2-trifluoromethylaniline. The mixture was stirred for 2 hours and a solid precipitated which was recrystallized from ethanol. 2.3 g (87%) of m.p. 147 ° C.

^{Σ Η} - NMR / DMSO-d₆ / 6.17; 5.79 (s), 3.36 (s), 7.76 - 7.42 (m) 9.55 (bs)

CS 274 008 Bl

Examples 26 to 35

In analogy to Example 26, the following derivatives were obtained

A ^{with A} C = C - C0, H si 4

H „ ¹

B CH _Z - CORj

Example R ^ Extract M.p. respectively. ° C resp . T.v. . ° C / kPa ¹ H-NMR ^h and ^h b 26 ._- - -nh) 91, 187 až 189 6.17; 5.77 27 Mar: 89 175 až 179 6.18; 5.78 ClMl 28 'ΝΗ-Ο 83 157 6.09; 5.96 29 ' - _NH -? - no ₂ Cl 67 173 6.20; 5.79 30 CF, .87 136 6.19; 5.77 31 ^ ₂ 73 187 až 189 6.19; 5.77 32 0CH ₃ 88 147 6.14; 5.71 33 89 166 6.28; 5.84 ^{34 CH} 3 R 1 -nh-Vq) Cl 78 187 6.12; 5.72 35 • 'ΝΜ'Ο 86 148 6.15; 5.71 36 'F -nh- ^ 5) 88 163 6.34; 5.87

• F

81 274 008 81

Example 37

Methyl 3-carbamoyl-3-butenoate

To the liquefied ammonia (0.68 g, 0.04 mol) was gradually added methyl 3-chloroformyl-3-butenoate (3.24 g, 0.02 mol) in diethyl ether (30 ml) at -30 ° C. Acetone (100 ml) was then added to the reaction mixture and the mixture was heated at reflux for 5 minutes. The solid was filtered off, the filtrate was concentrated in vacuo and the oily residue was recrystallized from benzene-hexane. 2.2 g (77%) of melting point 73-74 ° C were obtained.

^T H HMR / CD _3/2 C0 5.96; 5.56 (s); 3.58 (s); 3.32 (s); 6.87 (bs)

Examples 38 to 39

In analogy to the procedure of Example 37, the following derivatives were obtained

AND\

C = C - con ₂

Ho '' ^{1 B} CH ₂ - CORjl

Example ^R 1 Extract /% / M.p. / ° C / ³ H NMR ^h and ^h b 38 -0- / CH _2/7 CH 66 59 to 61 5.81; 5,51 39 -O-CH / CH ₃ CH // _2/5 CH 64 60 5.86; 5.49

Antifugural activity was determined on fungi Alternaria alternata, Botrytis cinerea and Fusarium nivale by the canvas dilution method.

substance ^-1 ° ^{9 εθ} 50 P ° ^{48 h} / gdm ' ³ / in example A. alternata 8.cinerea F. nivale

8 3.85 3.9 3.95 11 3.00 3.9 - 12 3.45 3.6 3.8 16 3.00 3.0 3.0 17 3.00 3.0 3.0 14 3.00 3.5 3.0 ¹⁸ . 3.1 3.4 3.0 10 «, 1 4.4 4.1 23 3.55 . 4.05 3.8 21 3.90 4.35 4.1 8 3.6 4.1 4.3 25 3.5 4.15 4.4 24 3.3 3.8 4.0 fundazol 4.0 4.7 4.7 29 3.0 3.1 3.0 31 3.45 3.5 3.0 36 3.85 4.35 4.1 39 3.50 3.20 3.0

CS 274 008 B1 6

Claims (3)

1. New 2-methylenebutanedioic acid derivatives of the general formula I: CH, = C - COR, / CH ₂ - COR ₁ wherein when R ₁ represents a straight or branched alkoxy group with an alkyl group of C 1 -C 8 optionally substituted by chlorine or methoxy, then R ₂ represents a hydroxy, amino, mono- or disubstituted phenoxy group having substituents R 'and R''whereinR' and R 'are methyl, chloro, nitro, ethoxycarbonyl in ortho, meta and para positions, ethylenimino, anilino mono- or disubstituted with substituents on the aromatic nucleus R' and R 6, where R 'and R 6 ^V represents methyl, ethyl, chlorine or nitro in ortho, meta positions. and para, wherein R on the nitrogen is hydrogen, 1-methoxy-2-propyl group or a l- (l-methoxycarbonyl) ethyl, and when R represents an anilino group mono or disubstituted by R ^V and R ^V ^ wherein R ^ and represent methyl, ethyl, chloro, fluoro, trifluoromethyl, methoxy or nitro group at the ortho, meta and para then R ₂ is hydroxy. 2. A process for the preparation of novel 2-methylenebutanedioic acid derivatives according to claim 1, characterized in that 1 to 3 molar parts of 2-methylenebutanedioic acid or a reactive derivative thereof such as anhydride or methyl (3-chloroformyl) -3-buteonate are reacted with 1 to 3. 8 molar parts of a nucleophilic compound of formula II R ₃ - Nu (11) wherein when Nu represents a hydroxy group, then R 6 is a straight or branched C 1 -C 8 alkyl optionally substituted by chlorine or methoxy, phenyl mono or disubstituted independently by nitro, ethoxycarbonyl, methyl or chlorine when Nu represents amino, then R1 is hydrogen, phenyl, phenyl mono or disubstituted independently by fluorine, chlorine, nitro, methyl, ethyl, trifluoromethyl or methoxy and if Nu is imino then R1 is ethylene or R1 is simultaneously two substituents . -phenyl disubstituted independently by methyl, ethyl and 1-methoxy-2-propyl or 1- (1-methoxycarbonyl) ethyl, at -30 ° C to 100 ° C for 5 minutes to 6 hours. 3. The process according to claim 2, wherein if the reactive derivative of 2-methylenebutanedioic acid methyl (3-chloroform) -3-butenoate is added to the reaction mixture 1 to 1.6 molar parts of the organic base.