CH658652A5 - DAIRY pyrimidin-4-ONE ACTIVITY HERBICIDE. - Google Patents

Description

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2

CLAIMS 1) Compounds of formula

(THE)

VN, 1

11) Use of the compounds according to claim 1 as herbicides to combat weeds in crops of agricultural interest.

12) Use according to claim 11 in the pre-emergency treatment.

13) Use according to claim 11 in post-emergency treatment.

14) A herbicidal composition containing as active principle one or more compounds of claim 1 next to

ìo inert runners and other additives.

in which

R1 represents a C 1 -G 4 alkyl, a C 1 -C 4 alkyl, hydrate or amino optionally substituted with C 1 -C 4 alkyl or alkoxy groups, C 2 -C 5 alkenyl or alkynyl;

R2 represents a hydrogen atom, a C 1 -C 4 alkyl or amino possibly substituted with one or two C 1 -C 4 alkyl groups;

R3 represents a phenyl optionally substituted with one to three substituents selected from halogen atoms, Ci -C4 alkyls, Ci -C4 haloalkyls having from one to three halogen atoms, nitro, alkoxycarbonyl, CN, SO2 -C 1 -C4 alkyl ; a 2-thienyl or a 2-, 3-or 4-pyridyl.

2) Compounds according to claim 1, wherein R3 is phenyl.

3) Compounds according to claim 2, wherein R1 is the methylthio radical.

4) The compound according to claim 3, 2-methylthio-3-methyl-5-phenyl-pyrimidin-4-one.

5) Compounds according to claim 2 wherein R1 is the dimethylamino radical.

6. The compound according to claim 5, 2-dimethylamino-3-methyl-5-phenyl-pyrimidin-4-one.

7. The compound according to claim 5, 2-dimethylamino-3-amino-5-phenyl-pyrimidin-4-one.

8. Compounds according to claim 2, wherein R1 is an animate radical substituted with a C 1 -C 4 alkyl.

9. The compound according to claim 8, 2-methylamino-3-methyl-5-phenyl-pyrimidin-4-one.

10) Process for the preparation of the compounds of claim 1 wherein the substituent R1 is an alkylthio radical, consisting in reacting a compound of formula

The present invention relates to herbicide compounds and more specifically it concerns herbicide compounds belonging to the class of pyrimidin-4-oni substituted in positions 2, 3 and 5.

The invention also relates to a synthesis process of the above compounds and their use as herbicides.

Numerous herbicidal compounds belonging to various chemical classes are known.

However, as far as we know, there are no herbicides belonging to the pirimidin-4-oni class on the market.

We have now found and are the object of the present invention derivatives of pyrimidin-4-one having general formula:

25

R

»

30

(THE)

Cik

TK R

R3-C-COOR '

CH-NH2

(Iv)

wherein R3 has the meanings reported in claim 1 and R 'represents methyl or ethyl with carbon disulfide, alkyl iodide and sodium hydride in an anhydrous polar solvent, in an atmosphere of inert gas and at room temperature, to obtain a compound of formula

R3-C-COOR '

(V)

CH \

SR

N = C

\,

SR

wherein R3 and R 'have the above reported meanings and R represents an alkyl Ci - C4 which is then reacted with a compound of formula r2 - nh2

(you)

wherein R2 has the meanings set forth in claim 1, in an alcoholic solvent and at the reflux temperature of the mixture.

in which:

R1 represents a C 1 -C 4 alkyl, a C 1 -C 4 alkyl, hydrazine or amino optionally substituted with C 1 -C 4 alkyl or alkoxy groups, C 2 -C 5 alkenyl or alkynyl.

40 R2 represents a hydrogen atom, a C 1 -C 4 alkyl or amino possibly substituted with one or two C 1 -C 4 alkyl groups;

R3 represents a phenyl optionally substituted with one to three substituents selected from halogen atoms, Ci -C4 alkyls, Halo-45 kg Ci -C4 having from one to three halogen atoms, nitro, alkoxy-carbonyl, CN and S02-alkyl Ci -C4; a 2-thienyl or a 2-, 3- or 4-pyridyl.

The compounds of formula I have herbicidal activity and are suitable for use in the defense of crops useful by weeds.

It is evident to the skilled in the art how according to the nomenclature rules the compounds of formula I should be named as derivatives of (3H) -pirimidin-4-one. In the present context, however, the name of derivatives of pyrimidin-55 -4-one will be used since the presence of a substituent in position 3 (substituent R2) makes a more rigorous nomenclature superfluous, with the exception of the case in which R2 is a hydrogen atom.

The preparation of the compounds of formula I can follow various alternative routes, the choice of which depends mainly on the nature of the substituents R1 and R2.

For the sake of clarity, the following symbols are introduced in the description of the synthesis processes in order to identify the meanings of the substituents R1 and R2:

R = Ci -C4 alkyl 65 SR = Cj -C4 alkyl

NHR = monoalkyl- or alkenyl- or alkynyl-amino NR2 = dialkylamino or dialkenyl or dialkinylamino. A first synthesis procedure that lends itself to obtaining

3

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of all the compounds of formula I in which R2 is a hydrogen atom, regardless of the meanings of R1, consists in reacting a methyl or ethyl ester of a 2-formyl-arylacetic acid (II) with a salt of a base nitrogen (III) according to reaction 1:

n 3 1 base R -ÇH-COOR '+ R -C = NH. HX 1

NH

2

(III)

R = H)

(wherein R '= CH3, C2H5; HX = mineral or organic acid; R1 and R3 have the above meanings).

The 2-formyl-arylacetic esters of formula II are easily prepared compounds following the procedure described by W. Wislicenus [Berichte 20, 2931 (1887)] for ethyl 2-formyl-phenylacetate.

The compounds of formula III, depending on the meanings of R1, can be salts of S-alkyl-isothiourea (R1 = SR), of gua-nidine (R1 = NH2), of alkylguanidine (R1 = NHR or NR2) or of amides ( R1 = alkyl). They are known compounds, the preparation of which is widely described in the chemical literature.

The reaction 1 can be conveniently carried out in a protic solvent in the presence of an at least equimolar quantity, with respect to compound III, of a base and at room temperature.

Suitable catalyst-solvent systems are alkaline hydroxide in water or alkaline alcohol in alcohol (for example sodium ethylate in ethanol).

A second general process which constitutes an object of the present invention and which allows to obtain the compounds of formula I in which R1 = SR, independently of the meanings of R2, is schematized in the following reactions 2 and 3:

20

30

2)

R3-Ç-C00R '+ CS + 2NaH + 2 R-J — R3-C-C00R' (V)

2

t

CH-NH

(IV)

Ih n.n = 7

S-R

* N = C

NS-R

3> (V) + R -NH,

6

(YOU)

R

X

(I, R = alkylthio)

(wherein R = Ci -C4 alkyl; R '= CH3, C2H5; R2 and R3 have the above meanings).

The compounds of formula IV, which exist in two tautomere forms:

R3-C-COOR '

CH-NH2

R3-CH-COOR '

CH = NH

they are obtained from the 2-formyl-arylacetic esters of formula II by reaction with ammonia according to the procedure described by Dé-combe [Ann. Chim. 18, 81 (1932)] for the preparation of the compound of formula IV wherein R '= C2H5 and R3 = phenyl.

The reaction 2 is carried out in an aprotic polar solvent, for example tetrahydrofuran (THF), at room temperature and in an inert gas atmosphere.

60 A practical embodiment consists in slowly adding the compound of formula IV to an anhydrous THF suspension of sodium hydride (slightly exceeding the stoichiometric) while maintaining the reaction environment in a nitrogen atmosphere. The mixture is kept under stirring at room temperature until the hydrogen unwinding ends.

The carbon sulphide is then added and then the alkyl iodide in slight excess with respect to the sodium hydride. Once the reaction is over, the compound of formula V is isolated according to

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4

do conventional processes and is purified by crystallization or chromatography.

The reaction 3 is carried out in an alcoholic solvent at the reflux temperature and using a slight excess of compound of formula VI (ammonia R2 = H, amine R2 = alkyl, hydrazine R2 = NHR).

The method described above has proved particularly advantageous for the synthesis of the compounds of formula I wherein R2 is an amino group.

Finally, some of the compounds of formula I can be useful as intermediates for the preparation of other compounds of formula I.

For example, the compounds of formula I wherein R2 is a hydrogen atom can be alkylated in position 3 by reaction with an alkyl halide according to reaction 4.

4) I (R2 = H) + R — X I (R2 = R) + HX

(R = C 1 -C alkyl; X = halogen preferably iodine).

The reaction 4 is carried out in an aprotic polar solvent such as dimethylformamide, dimethylsulfoxide or tetrahydrofuran and in the presence of a base such as for example sodium hydride.

In a practical embodiment, the reaction is carried out by preparing in the anhydrous solvent a suspension of the alkaline salt of the compound of the starting formula I, by adding alkaline hydride, in slight excess with respect to the stoichiometric value, to the solution of the pyrimidinone in the solvent.

The alkylating agent (alkyl iodide) is slowly added to the suspension kept under strong stirring at about 0 ° C. Once the addition is complete, the temperature is allowed to rise spontaneously to room values and is left under stirring until the reaction is completed. We then work according to usual techniques to separate and purify the product.

The compounds of formula I in which the substituent in position 2 (R ') is an alkylthio (SR) group can serve as starting products for the preparation of the compounds of formula I replaced in position 2 by a possibly substituted amino group or hydrazine.

The preparation is carried out by moving the thioalkyl group by means of the appropriate amine according to the reaction 5.

5) I [R1 = SR] + NH (R ') 2 »-I [R1 = N (R') 2] + RSH

(R = C 1 -C 4 alkyl; one or both R 'are H or C 1 -C 4 alkyl, or one is H and the other is alkoxy or NH 2).

The reaction 5 is particularly useful when the amine is a primary amine (NH2R ') or dimethylamine [NH (CH3) 2],

The reaction 5 can be carried out according to different practical embodiments.

In a first embodiment, the reaction is carried out in solvent, preferably in methyl or ethyl alcohol, at the reflux temperature and using a strong excess of anhydrous amine. With sterically hindered primary or secondary amines it is preferable to carry out the reaction under autogenous pressure operating at temperatures between 90 and 150 ° C and maintaining a high concentration of amine in solution.

In another practical embodiment, the operation is solvent-free by using the amine in the form of acetate and in strong excess with respect to the stoichiometric (from 2 to 10 times).

The reaction is carried out at temperatures between 120 and 160 ° C.

The reactions 1 to 5 described above are illustrated below by representative examples.

As previously mentioned, the pyrimidin-4-oni of formula I are endowed with herbicidal activity.

Their activity has useful characteristics that make it possible to use it in the agricultural field in the defense of useful crops from weeds.

These characteristics can be summarized in a high and versatile herbicide action, in a broad spectrum of action and in selectivity towards agricultural crops.

The herbicide compounds of formula I, in fact, are active both in pre-emergence and in post-emergence and this characteristic, uncommon among known herbicides, allows an appropriate choice of treatment according to the various factors that can occur in practice farm.

Furthermore, they are active both against dicotyledon and monocotyledon weeds and this is another characteristic not common among known herbicides.

For practical uses in agriculture, the compounds object of the invention can be used as such or, according to normal practice, in the form of a suitable composition.

In the compositions, in addition to the compound of formula I as an active principle, inert carriers are present which can be both solid and liquid and possibly other additives for agricultural use.

According to the normal formulation practice, the compositions can be presented in the form of liquid concentrates, emulsifiable concentrates, suspensions, formulated in powder or wettable powder and granular formulations.

If desired to address specific situations, it is possible to add other active substances useful in agriculture such as fertilizers, fungicides or other herbicides to the compositions, for example those belonging to the class called chloroaceta-nilides herbicide.

The quantity of compound of formula I to be used in the defense of crops useful from weeds depends on various factors. Among these we can mention the type and degree of infestation, the type of treatment (pre-emergency or post-emergency), the relative efficacy of the specific product of formula I used also according to the above factors, the type of crop to weed, the formulation used and climatic and environmental factors.

In general, satisfactory results are obtained by using a quantity of compound of formula I of between 0.5 and 6 kg / ha.

With the aim of better illustrating the invention, the following examples are now provided:

Example 1

Preparation of the compound 2-methylthio-5-phenyl-3H-pyrimidin-4-one (Compound # 1) according to reaction 1.

q \ -CH-C00C2H5 + | (NH2-Ü-SCH3) 2.H2SO4 -

'CHO

(a) (b)

NaOH.

-H

(1)

SCH

3

To a solution of 40 g of NaOH (1 mole) in 660 ml of water kept under strong stirring at room temperature, 127 g (0.66 mol) of 2-formyl-phenyl ethyl acetate (a) and 91 are added, 7 g (0.33 moles) of S-methyl-isothiourea sulfate (b).

5

10

15

20

25

30

35

40

45

50

55

60

65

5

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The obtained suspension is left under stirring for 8 hours at room temperature.

The reaction mixture is then acidified with hydrochloric acid. A solid precipitate is formed which is separated by filtration, washed with water and dried. 5

126 g of compound n. 1 as a crystalline solid (m.p. = 249-250 ° C).

IR significant bands at 1642, 1550 and 1285-1300 cm "1.

Example 2 me

Preparation of the compound 2-methylthio-3-methyl-5-phenyl-pyrimidin-4-one (Compound # 2) according to reaction 4.

+ CH J

C-N / H3

A suspension of 95 g (0.43 moles) of the compound n. 1 (prepared as described in Example 1) and 31.3 g (0.65 moles) of sodium hydride (NaH) in 50% oil, in 150 ml of anhydrous dimethylformamide.

To the suspension, kept under stirring in a nitrogen atmosphere at a temperature between 0 and 5 ° C, 120 g (0.85 mol) of methyl iodide are added by drop.

The temperature is then left to rise to room value and stirred for 6 hours.

The mixture is then diluted with 500 ml of water, and cooled around 0-5 ° C.

A solid precipitates which is prepared by filtration and recrystallized from isopropyl alcohol.

56.2 g of the compound n are thus obtained. 2 in the form of a crystalline solid (m.p. = 75 ° C).

IR: significant bands at 1660, 1510, 1420 and 1095 cm "1. 'H-NMR (CDCh. TMS)

ô (ppm): 2.6 (s, 3H, S-CH3)

3.6 (s, 3H, N-CHa)

Ô (ppm): 7.2-7.9 (m, 5H, aromatic protons)

8 (s, IH, CH)

(s = singlet,

m = multiplet).

Example 3

Preparation of the compound 2-dimethylamino-3-methyl-5-phenyl-pyrimidin-4-one (Compound # 3) according to reaction 5.

25 254 ml (4.42 moles) of glacial acetic acid are added by dripping to 554 ml (8.19 moles) of anhydrous dimethylamine keeping the temperature between 0 and 5 ° C. The excess dimethylamine is then removed at room temperature.

The dimethylammonium acetate thus obtained is added

30 joints 127 g (0.544 moles) of 2-methylthio-3-methyl-5-phenyl-

pirimidin-4-one (Compound # 2 obtained as in Example 2).

The mass is heated for 2.5 hours at 165 ° C. After cooling to room temperature, 500 ml of water are added.

35 A solid is separated which is isolated by filtration.

114.5 g of the compound n. 3 in the form of a crystalline solid (m.p. = 149-150 ° C).

IR significant bands at 1650, 1550 and 1150 cm "1. ^ -NMR (CDC13, TMS)

40 5 (ppm): 2.91 [s, 6h, N (CH3) 2]

3.55 (s, 3H, CO-N-CH3)

7.75-7.22 (m, 5H, aromatic protons)

7.82 (s, IH, CH)

45 Example 4

Preparation of the intermediate 3- (bis-methylthio-methylene amino) -2-phenyl-ethyl acrylate (d) according to reaction 2.

50

(2) l:

COOC2H5 + CS2 + 2NaH + 2CH3J

CH-NH

(C)

3 + (CH3) 2 ^ H2 CH3C0 ° "

-COOCH d 5

(D)

vc (

SCH "

SCH "

65 To a suspension of 4.2 g (0.0863 mol) of sodium hydride (in 50% oil) in 60 ml of anhydrous THF 5.5 g (0.0287 mol) of 3-amino-2- are added ethyl phenylacrylate (c) and then dropwise 2 ml (0.0328 moles) of carbon disulphide.

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6

The mixture is kept under stirring for 1 hour at room temperature, then 3.7 ml (0.06 mol) of methyl iodide are quickly added to it, containing the exothermic solution with an external bath of water and ice. After another 8 hours of stirring, the solvent is removed by evaporation under reduced pressure. The residue is taken up in ethyl ether, washed with water and dried over anhydrous Na2SO4.

After elimination of the solvent under reduced pressure, an oil is obtained which is purified by chromatography on silica gel (eluent: n-hexane: ethyl acetate 9: 1).

2.5 g of the intermediate (d) are thus obtained in the form of a yellow solid (m.p. = 53-55 ° C).

IR significant bands at 1700, 1595, 1510, 1250 and 1050 cm'1. 'H-NMR (CDCI3, TMS)

5 (ppm): 1.3 (t, 3H, CH3-CH2)

2.33 (s, 6H, SCH3)

4.2 (q, 2H, CH3-CH_2)

7-7.5 (m, 5H, aromatic protons)

7.87 (s, IH, = CH)

(s = singlet, t pletto).

triplet, q = quartet, m = multi-

Example 5

Preparation of the compound 2-methylthio-3-amino-5-phenyl-pyrimidin-4-one (Compound # 4) according to reaction 3.

(D)

C-COOC H

IH 25 \ .c / SCH *

NSCH

3

+ NH -NH .HO 2 2 2

A solution of 2 g (0.0067 moles) of 3- (bis-methylthio-methylene amino) -2-phenylacrylate of ethyl (intermediate d prepared as in example 4) and 0.76 ml (0.0156 moles) of hydrazine hydrates in 30 ml of ethanol, is heated under reflux for 6 hours.

After cooling, a solid is separated which is isolated by filtration. 0.6 g of compound n. Are thus obtained. 4 in the form of a crystalline solid (m.p. = 198-200 ° C).

IR: significant bands at 3300, 3260, 3200, 1680, 1500, 1485 and 1390 cm-1.

45

Example 6 Preparation of the compound 2-dimethylamino-3-amino-5-phenyl-pyrimidin-4-one (Compound 50 n.5) according to the reaction 5.

; (CH3) 2NH->

(4)

SCH

A solution of 0.6 g (0.00257 moles) of 2-methyl-3-amino-5-phenyl-pyrimidin-4-one (Compound No. 4 prepared as in Example 5) and 10 ml (0.15 moles) of anhydrous dimethylamine in 20 ml of absolute methanol is heated in a closed tube for 8 hours at 100 ° C.

After cooling, a white solid separates and is isolated by filtration.

(ÒVA- NH2 ♦ CH3SH

Y

0.4 g of compound 5 are thus obtained in the form of a crystalline solid (m.p. = 178-179 ° C).

IR: significant bands at 3280-3200, 1640, 1540 and 1410 cm1.

65

Example 7

In the following Table 1 some compounds according to the invention are reported.

7

658 652

The preparation of the compounds from 1 to 5 is described in detail in the previous examples, the preparation of the remaining compounds was carried out according to the procedures reported in the previous examples.

TABLE 1 Formula compounds (1)

0

<X:

VS, 1

Compo- R1 R2 R3 m.p. (° C) (2) IR (cm'1) 131

I'm no

1

SCH3

h c6h5

249-250

1642, 1550, 1300, 1285

2

SCH3

ch3

C6H5

75

1660, 1510, 1420, 1095

3

n (ch3) 2

ch3

C6H5

149-150

1650, 1550, 1150

4

SCH3

nh2

C6H5

198-200

3300, 3260, 3200, 1680, 1500,

5

n (ch3) 2

nh2

C6H5

178-179

3280, 3200, 1640, 1540, 1410

6

SCH3

C2H5

C6H5

oil

1665, 1500, 1440, 1390, 1300

7

SCH3

iso-C3H7

C6H5

oil

1667, 1510, 1405, 1405, 1370,

8

SCH3

n. C4H9

C6H5

oil

1670, 1500, 1395, 1305

9

nh-ch3

ch3

C6H5

260-262

3380, 1650, 1635, 1527

10

nh-C2H5

ch3

csh5

151-154

3400, 1640, 1530, 1375

11

NH-C4H9 (n)

ch3

cfihs oil

3320, 1650, 1590, 1530

12

NH-C4H9 (iso)

ch3

C6H5

162-164

3310, 1650, 1550, 1525

13

nh-ch2-ch = ch2

ch3

C6H5

110-112

3270, 1635, 1580, 1520

14

n (ch3) 2

C2H5

C6H5

oil

1665, 1530, 1405, 1150

15

nh2

H

C6H5

250-dec.H)

3350, 1690, 1630, 1570

16

nh-ch3

H

C6H5

282-284

1650, 1615, 1580, 1370

17

N (ch3) 2

H

C6H5

215-217

1630, 1610, 1505, 1350

(1) Elemental analysis of all reported compounds and H-NMR spectroscopy data are consistent with the assigned structures

(2) The melting point value was incorrect

(3) Only the most significant bands are reported

(4) goddesses. = decomposition

Example 8 Determination of the herbicidal activity.

Pots with a diameter of 10 cm and a height of 10 cm containing sandy soil were prepared.

One of the following weeds was sown in each of the pots:

A - Stellaria media (dicotyledon)

B - Jpotema spp (dicotyledon)

C - Vigna sinensis (dicotyledon)

D - Echinochloa crusgalli (monocotyledon)

E - Avena fatua (monocotyledon)

Water was added to each jar in quantities necessary for good seed germination. The jars were then divided into three groups.

ss The first group was not treated with any herbicide and was used as a comparison (witness).

The second group was treated one day after sowing with a hydroacetonic dispersion (20% by volume of acetone) of the compounds of the invention at a dose corresponding to 60 to 6 kg / ha in the field, to evaluate the herbicidal activity in pre-emergence.

The third group was treated 15 days after sowing (i.e. when the seedlings depending on the species already had a height of 5-10 cm) with a hydroacetonic dispersion 65 (20% of acetone by volume) of the compounds of the invention to a dose corresponding to 6 kg / ha in a field, to evaluate the herbicide activity in post-emergency.

During the whole period of the tests performed the jars are

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were stored in a conditioned environment between 15 and 24 ° C, 70% relative humidity, photoperiod in 12 hours and a luminous intensity of 2500 lux.

Every two days the pots were uniformly watered to ensure a sufficient degree of humidity for a good development of the plants.

After 28 days from the treatment with the compound according to the invention, the surveys of the vegetative stage of the plants were carried out. The herbicidal activity of the compounds of the invention was assessed by comparing the growth and vegetative stage of the treated plants compared to the untreated plants (witness) and was expressed according to a scale of values from 0 (zero herbicidal activity, growth equal to that of the witness) to 4 (complete arrest of the growth or death of the plant), the intermediate values representing intermediate situations of vegetative development.

Table 2 shows some significant data.

TABLE 2

Herbicidal activity of compounds of the invention at a dose of 6 kg / ha expressed on a scale of values from 0 to 4.

5

Compound n. Weed treatment

(see Tab. 1) A B C D E

2 post-emergency 4 4 4 4

3 pre-emergency 4 4 4 4 4

3 post-emergency 4 4 4 4

4 post-emergency 4 4 4

5 pre-emergency 4 4 4 3 2 5 post-emergency 4 4 4 4

9 pre-emergency 4 4 4 4 4

9 post-emergency 4 4 4 4