JPS5867677A - 5-haloorotic acid compound and its preparation - Google Patents

Abstract

NEW MATERIAL:The 5-haloorotic acid compound of formulaI[R<1> is 1-4C alkyl, allyl, cyclohexyl, benzyl, or group of formula II (R<2> is 1-4C alkyl, 1-4C alkoxy, or halogen; n is 0, 1, 2, or 3); X is Cl, Br or I]. EXAMPLE:5-Chloro-1-isopropylorotic acid. USE:Pharmaceuticals, pesticides (agricultural and horticultural fungicide) and their intermediates. PROCESS:The compound of formulaIcan be prepared by reacing 5-carboxyorotic acid alkali metal salt of formula III (Me is alkali metal) with a halogenating agent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel compounds, 5-haloorotic acids, and a method for producing the same. More details.

This invention.

Formula [wherein R1 is an alkyl group having 1 to 4 carbon atoms, aryl (
In the formula, R2 is an alkyl group having 1 to 4 carbon atoms, and 1 to 4 carbon atoms.
represents an alkoxy group or a halogen atom.

5-, where n is 0.1.2 or 0), and X is chlorine, bromine or iodine;
A formula characterized by reacting a haloorotic acid and a 5-carboxyorotic acid alkali metal salt represented by (in the formula, 1Mθ represents an alkali metal and R1 has the same meaning as above) with a halogenating agent ( This is a method for producing 5-haloorotic acids represented by the formula (in which +R' and X each have the same meanings as above).

5-haloorotic acids represented by formula [1) are novel compounds and are useful as medicines, agricultural chemicals, and intermediates thereof.

Specific examples of the alkali metal salt of 5-carboxyorotate represented by formula [11] include potassium 5-carboxy-1-propylotinate and potassium 1-butyl-5-carboxyorotate.

1-butyl-5-carboxyorotic acid sodium salt,
1-Butyl-5-carboxyorotate lithium salt, 1
-Allyl-5-carpoxyorothi/acid potassium salt, 5-
Carboxy-1-cyclohexylorotate potassium salt, 5-carboxy-1-chlorohexylorotate sodium salt, 1-benzyl-5-carboxylorotate potassium salt.

5-carboquine-1-phenylorotic acid potassium salt,
5-carboxy-1-phenylorotate sodium salt, 5-carboxy-1-phenylorotate lithium salt, 5-carboxy-1-tolyrotate potassium salt +
5-carboxy-1-tolyrotinate sodium salt, 5-carboxy-1-tolyrotate lithium salt,
5-carboxy-1-(chlorophenyl)orotate sodium salt, 5-carboxy-1-(dichlorophenyl)orotate potassium salt, 5-carboxy-1-(dichlorophenyl)orotate sodium salt.

Examples include lithium salt of 5-lupoxy-1-(dichlorophenyl)orotate, potassium salt of 5-carboxy-1-(trichlorophenyl)orotate, and sodium salt of 1-ayucyl-5-carboxyorotate.

Specific examples of halogenating agents include halogens such as chlorine, bromine and iodine, hypohalous acids and their alkali metal salts such as hypochlorous acid secondary hypobromous acid and hypoiodous acid,
and N-chlorosuccinic acid.

The amount of the halogenating agent used is preferably 2 to 2.5 mol per 1 mol of the alkali metal salt of 5-carboxyorotic acid.

The reaction between the alkali metal salt of 5-carboxyorotic acid and the halogenating agent is preferably carried out using water as a reaction solvent. In some cases, a combination of an inert solvent and water may be used in the reaction of this invention. As an inert solvent, be/zene is used.

Examples include chlorobenzene, dichlorobenzene, and carbon tetrachloride.

Any method may be used for the reaction as long as the alkali metal salt of 5-carboxyorotic acid and the halogenating agent can be brought into contact at a predetermined temperature for a predetermined period of time.

As a method of contacting these raw materials, usually an aqueous solution or suspension of an alkali metal salt of 5-carboxyorotate,
- A method of adding the rogenizing agent directly, or a method of adding the rogenizing agent as an aqueous solution or a solution in the above-mentioned inert organic solvent is adopted.

In the reaction between 5-carboxyorotic acid alkali metal salt and 7-rogenating agent, adding an alkali metal hydroxide to the reaction system improves the yield of the target product 5-roorotic acid. It is preferable to add 1 to 6 moles of metal hydroxide to the reaction system per mole of the alkali metal 5-carboxyorotic acid salt.

The alkali metal salt of 5-carboxyrotate is represented by formula (II).

1 (wherein R1 has the same meaning as above, R3 and R
4 represents an alkyl group having 1 to 4 carbon atoms, respectively) is reacted with an alkali hydroxide in water at room temperature or under heating, and then a reaction product mixture is obtained. Method of adding mineral acid (Patent application No. 55-161384 filed by the applicant of this patent)
This reaction product mixture or the reaction product mixture before mineral acid treatment may be directly subjected to the reaction of the present invention.

If the reaction temperature is too high, the yield of the target product will decrease, so it is generally preferred to be a temperature in the range of 0 to 100°C.

The reaction is usually completed in 1 to 25 hours.

The desired product, 5-haloorotic acid, is often
It is a crystal that is difficult to dissolve in water and can be isolated by filtering the mixture of the two reactions. 5-...When roorotic acid is dissolved in water 1. 5-halo- Rotic acid can be isolated. In addition, when the reaction between the alkali metal salt of '5-carboxyorotic acid and the halogenating agent is carried out by adding an alkali metal hydroxide, the mixture produced by the two reactions contains an amount of hydrochloric acid equivalent to the alkali metal hydroxide used. , 5-haloorotic acid can be isolated by adding a mineral acid such as sulfuric acid or the like and performing the above operation.

Specific examples of the 5-haloorotic acid represented by formula [I] obtained in this invention include 5-chloro-1-propylorotic acid, 5-chloro-1-phenylorotic acid, 1-
Ayucyl-5-chloroorothin L5-10 low 1~. (
chlorophenyl)orotic acid, 5-bromo-1-propylorotic acid.

5-bromo-1-butylorotic acid, 1-pencyl-5
-Promoorotic heptaic acid + 5-bromo-1-phenylorotic acid, 5-bromo-1-tolyorotic acid, 1-ayucyl-5-bromoorotic f7e.

5-Bromo-1-(chlorophenyl)orotic acid.

5-bromo-1-(dichlorophenyl)orotic acid, 5
-Iodo-1-propylorotic acid, 1-cyclohexyl-5-iodo-orotic acid, 1-allyl-5-iodo-orotic acid, 5-iodo-1=phenylorotic acid, 1-
Examples include ayusyl-5-iodoorotic acid and 1-(chlorophenyl)-5-iodoorotic acid.

Next, examples will be shown. In the Examples, the yield of 5-no-roorotic acid is the yield based on the alkali metal salt of 5-carboxyorotic acid used.

Example 1 5-carboxy-1-isopropylorotate sodium salt monohydrate was added to 30 M□l of water containing 1.52 ml of sodium salt.

3 omes of carbon tetrachloride containing 0.46 f/chlorine were added dropwise at room temperature, 20 ml of gas evolved. The mixture was heated and reacted under reflux for 1 hour.

After the reaction, the resulting reaction product mixture was filtered.

Crystals of 5-chloro-1-isopropylorotic acid monohydrate 0.25S! (yield: 17%). This was recrystallized with water to obtain colorless needle crystals with a decomposition point of 241-242°C. The elemental analysis value is shown below.
3.80 Calculated value 38.34 4.42 11.18
14.14 (as Cs HlICl 120s) Example 2 In 50 ml of water containing 2.62 fl of 5-carboxy-1-impuavirorotic acid sodium salt monohydrate, 1
Add 15m/' of specified sodium hydroxide aqueous solution, then add 7.44ml of 12% by weight sodium hypochlorite aqueous solution.
Added r. The mixture was heated and reacted under reflux for 1 hour.

After the reaction, 4 om/N of 1N hydrochloric acid was added dropwise to the resulting reaction product mixture at room temperature, and 1">Om1 of gas was generated. The mixture was filtered and 5-chloro-1-isopropylorotic acid・Crystals of monohydrate o,, a 4 y (
Yield: 18 h) was obtained. The F solution was concentrated under reduced pressure, 10 ml of water was added to the residue, filtered, and 5-chloro-1-
Crystals of inpropylorotic acid monohydrate o, 52r (
Yield: 21%) was obtained.

Example 6 5-carboxy-1-phenylorotic acid sodium salt monohydrate 1.53 ? to 90rnl of water containing.

Chlorine 0.44 f at room temperature? Carbon tetrachloride 10W11 containing
When added dropwise, 97.5 rtt1 of gas was generated. The mixture was allowed to react for 200 hours with stirring at room temperature.

After the reaction, the resulting reaction product mixture was filtered.

Crystals of 5-chloro-1-phenylorotic acid monohydrate 0.381F (yield: 26%) were obtained. This was recrystallized from water to obtain colorless needle crystals with a decomposition point of 242-243°C. The elemental analysis values are shown below.

CHN C4 Analysis value 46,54 3.17 9.54 12. i
4 Calculated value 46.41 Self, 19 9.84 12
．． 45 (as Cu H9Ct N2O5) Example 4 Add 1N hydroxide to a water bowl containing 5.261 l-(p-anisyl)-5-carboxine orotate sodium salt monohydrate at room temperature) IJ Then, 15 m/ml of an aqueous solution of IJum (12% by weight hypochlorous acid) was added. The mixture was heated and reacted under reflux for 1 hour.

After the reaction, 40ml of 1N hydrochloric acid was added dropwise to the resulting reaction product mixture at room temperature, and 15311t1 of gas was added.
Occurred. The mixture was filtered to give 1-(p-anisyl)-
5-chloroorotic acid crystals 1,542 (yield: 52%
) was obtained. This was recrystallized with ethanol and the decomposition point was 23.
Pale yellow fine needle crystals at 6°C were obtained. The elemental analysis values are shown below.

CHN C1 Analysis value 48.97 3.12 9.42. 11.
68 calculated value 48.583.06 9.44 11.
95 (as 0,□H9C1N2'05) Example 5 90 tu of water containing 1.839 of 5~carfoxy 1-(p-chlorophenyl)orotate sodium salt monohydrate
e, 1o carbon tetrachloride containing 0.47 SF of chlorine at room temperature
ml! was added dropwise, 77.5 me of gas was generated. The mixture was allowed to react for one day with stirring at room temperature.

After the reaction, the resulting reaction product mixture was filtered.

Crystal 0.701? I got it. This was added to 50 ml of ethanol, filtered while hot, and the F solution was concentrated under reduced pressure to give crystals of 5-chloro-1-(p-chlorophenyl)orotic acid.
a2? (yield: 25%). This is recrystallized with water to form an adduct with a molar ratio of 1:1 and 2 decomposition points of 2.
Colorless crystals at 33-264°C were obtained. The elemental analysis values are shown below.

OH, NO4 Analysis value 41.65 2.36 8.76 21.5
4 Calculated value 41.40 2.5ro 8.78 22.
22 (as C!o H8CA2N20S) Example 6 50 ml of water containing 1.651 5-carboxy-1-(p-l0lophenyl)orotate sodium salt monohydrate
・7.5 m of 1N aqueous sodium hydroxide solution at room temperature
l and then 3.71 f of a 12% by weight aqueous solution of sodium hypochlorite. The mixture was heated and reacted under reflux for 1 hour.

After the reaction, 10 mg of 2N hydrochloric acid was added dropwise to the resulting reaction product mixture at room temperature, and 65 ml of gas was generated. The mixture was filtered to give 0.97 y of crystals of 5-chloro-1-(p-chlorophenyl)orotic acid monohydrate.
(Yield: 61%) was obtained.

Example 7 5-carboxy-1-isopropylorotic acid I
80ml of water containing 2.1417' of Jum salt monohydrate!
When 2 omes of carbon tetrachloride containing 1.38 r of bromine were added dropwise to the solution at room temperature, 130 ml of gas was generated.

The mixture was heated and reacted at 60° C. for 7 hours.

After the reaction, the resulting reaction product mixture was filtered.

Crystals of 5-chloro-1-isopropylorotic acid 1.2
6ti (yield: 56%) was obtained. This was recrystallized with acetonitrile to obtain colorless crystals with a decomposition point of 248 to 249° C. and acetonitrile added thereto. The elemental analysis values are shown below.

CHN Br Analysis value 36.47 3.75 12.19 S,
7.33 Calculated value 36.32 3.56 11.77
26.84 ((as 4HgBrN204 JCH3CN)) Example 8 To 25 ml of water containing 0.749 sodium l-(n-butyl)-5-carboxyorotate monohydrate, water containing 0.43 f of bromine was added under water cooling. Upon addition of 10 ml!, 451,111 gases were evolved.The mixture was allowed to react at room temperature with stirring for 200 hours.

After the reaction, the resulting reaction product mixture was filtered to obtain crystals of 5-bromo-1-(n-butyl)orotic acid monohydrate.
．． 29y (yield: 35%) was obtained. This was recrystallized from water to obtain pale yellow massive crystals with a decomposition point of 218-219°C. The elemental analysis values are shown below.

CHN Br Analysis value 35.08 4.03 9.05 25.9
2 Calculated value 34.97' 4.24 9.06'
25.85 (as C9H13BrN20S) The P solution was concentrated under reduced pressure, 5 m/of water was added to the residue, filtered, and 5-bromo-1-(n-butyl)10tinic acid.
Crystals of monohydrate o, ir (yield: 12%) were obtained.

Example 9 100 ml of water containing 2.15 f of 1-benzyl-5-carboxyorotic acid sodium salt monohydrate under water cooling,
20m/! of water containing 1.351 bromine! When added dropwise, 3601111 gases were generated. The mixture was allowed to react for 5 hours while stirring at room temperature.

After the reaction, the resulting reaction product mixture was filtered.

1-benzyl-5-bromoorotic acid crystals 1.422
(yield: 63%). This was recrystallized from ethanol to obtain orange massive crystals with a decomposition point of 255-256°C. The elemental analysis values are shown below.

OHN Br Analysis value 44.56 2.86 8.44 24.7
8 Calculated value 44. Ro2 2.79 8.61 24.
57 (as C!12 Hg Br N204) Example 10 1 ooml of water containing 1.67 5-'carboxy 1-phenylorotate potassium salt monohydrate! to N at room temperature.
- After adding 0.88 f of bromosuccinimide, the mixture was stirred at room temperature and 320 ml of gas evolved. The mixture was allowed to react for 1.5 hours with stirring at room temperature.

After the reaction, the resulting reaction product mixture was filtered.

1 ml of concentrated sulfuric acid was added to the tear fluid, and the two separated crystals were filtered to obtain 0.22 f crystals of 5-bromo-1-phenylorotic acid monohydrate (yield: 1%). Which was recrystallized with ethanol to obtain colorless needle crystals with a decomposition point of 260-262°C. The elemental analysis values are shown below.

CHN Br Analysis value 40.33 2.73 8.35 24.5
1 Calculated value 40.14 2.75 8.51 24.
30 (as CoH9BrN20s) Example 11 5-carboxy-1-phenylorotic acid sodium salt monohydrate in some water containing 1.48 f.

While cooling with water, 10 ml of water containing 0.94 S' of bromine was added dropwise. The mixture was allowed to react for 1 hour with stirring at room temperature.

After the reaction, the resulting reaction product mixture was filtered.

Crystal 17 (yield: 61%) of 5-bromo-1-phenylorotic acid monohydrate Th was obtained.

Example 12 Potassium 5-carboxy-1-(pl-lyl)orotate monohydrate 1.39S' in water 30me.

After adding N-bromosuccinimyl-'0.81 F at room temperature, the mixture was stirred at room temperature and 92 ml of gas was added.
Occurred. The mixture was heated and reacted under reflux for 15 minutes.

After the reaction, the resulting reaction product mixture was filtered.

The P solution was concentrated under reduced pressure, and 10 ml of water was added to the residue and filtered to obtain crystals of 5-bromo-1-(p-tolyl)orotic acid o,s4r' (yield: 38%). . This was recrystallized with ethanol to obtain colorless needle-shaped crystals with a decomposition point of 242° C. as an adduct with ethanol in a molar ratio of 1:1. The elemental analysis values are shown below.

OHN Br Analysis value 45.30 4.08 7.53 21.4
6 Calculated value 45.30 4.07 7.55 21.
53 (as C+tH+s BrNz Os) Example 1
Otsu 50me of water containing 5-carboxy-1-(p,-tolyl)orotate potassium salt monohydrate 0.64 f/,
After 10 ml of water containing 0.43 f of bromine was added dropwise under ice cooling, the mixture was reacted for 20 hours with stirring at room temperature.

During this time, gas was generated at 35 mA'.

After the reaction, the resulting reaction product mixture was filtered.

5-Bromo-1-(p-4')orotic acid crystals 0
．． 19 ft (yield: 29 ft) was obtained.

Example 14 80 Wll of water containing 1.74 f of 1-'(p-anisyl)-5-carboxyorotic acid sodium salt monohydrate
When 20 WLl of water containing 0.85 f of bromine was added dropwise at room temperature, 58 m/ml of gas was generated. The mixture was allowed to react for one day with stirring at room temperature.

After the reaction, the resulting reaction product mixture was filtered.

Crystals of 1-(p-anisyl)-5-bromoorotic acid 0
．． 949 (yield: 52%) was obtained. This was recrystallized with ethanol to obtain yellow needle-shaped crystals with a decomposition point of 266-268°C as an adduct with ethanol/ethanol in a molar ratio of 1:1.

The elemental analysis values are shown below O CHN Analysis value 43.80 3.8j 7.05 Calculated value 45.43 3. ．． 90 7.24 ((44
H15BrN406) Example 15 50 ml of water containing 1.33 f of 5-carboxy 1-(p-chlorophenyl) orotate potassium salt monohydrate
! After adding 10 all of water containing 0.631 bromine to the mixture under water cooling, the mixture was stirred at room temperature.

The reaction was allowed to proceed for 20 hours. During this time, 45ml of gas was generated.

After the reaction, the resulting reaction product mixture was filtered.

Crystals 1.o8f (yield near 6%) of 5-7'' lomo 1-(p-chlorophenyl)orotic acid monohydrate were obtained.

This was recrystallized from water to obtain pale orange massive crystals with a 2-decomposition point of 235-237°C. The elemental analysis values are shown below.

CHN Analysis value 66.79 2.45 7.78 Calculated value Ro6.34 2.22 7.71 (CHH8B
as rOtN206) Example 16 5-Calhoki7-1-(3,5-dichlorophenylene).

l) To 70 wt 1 of water containing 1.81 of sodium orotate monohydrate, add 1 of water containing 1.09 f of bromine under ice cooling.
After adding 0 m6 dropwise, 1 m6 was added while stirring the mixture at room temperature.
The reaction was allowed to proceed for 8 hours. During this time, 190 gases were generated.

After the reaction, the resulting reaction product mixture was filtered.

1.987 crystals of 5-fromo-1-(3,5-dichlorophenyl)orotic acid (yield near 6%) were obtained.

This was recrystallized with ethanol to obtain colorless needle-like crystals with a two-decomposition point of 230 to 232°C as an adduct with ethanol in a molar ratio of 1:1. The elemental analysis values are shown below.

Q HN Analysis value 36.27 2.44 6.51 Calculated value 36.65 2.60 6.58 (C13Hu
BrC1zNzOs) Example 17 To 50ml of water containing 5-carboquine-1-isopropylorotic acid sodium salt monohydrate i, 31f, 17.5ml of 1N sodium hydroxide solution was added at room temperature, Then 1.27 fi' of iodine was added.

The mixture was heated and reacted under reflux for 2.5 hours.

After the reaction, 2N hydrochloric acid 10
ml was added and filtered to obtain 0.799 crystals of 5-iodo-1-ingurovirorotic acid (yield: 49 crystals).

Recrystallize this with ethanol.

2 decomposition point 2 as an adduct with ethanol in a molar ratio of 1:1
Colorless needle crystals with a temperature of 42-244°C were obtained. The elemental analysis values are shown below.

OHN Analysis value 32.63 4.02 7.72 Calculated value 32.44 4.08 7.57 (C'1OH
Example 18 5-bis(ethoxycarbonyl)methylene-cyclohexylhydantoy 73.68 f wo," After adding to 44 ml of a 1N aqueous solution of sodium hydroxide, the mixture was heated, The reaction was carried out under reflux for 1 hour.

After the reaction, 2.767 g of iodine was added to the mixture produced by the two reactions under water cooling, and the mixture was heated again and reacted under reflux for 4 hours.

The resulting reaction product mixture was filtered, and 4 ml of concentrated hydrochloric acid was added to the p solution at room temperature, followed by filtration to obtain 3.51 crystals of 1-cyclohexyl-5-iodoorotic acid (yield: 88%). This was recrystallized with ethanol to obtain pale yellow fine needle crystals with a decomposition point of 239-240°C as an adduct with ethanol at a molar ratio of 1:1.

The elemental analysis values are shown below.

CHN Analysis value Ro8.08 4.67 6.81 Calculated value Roa, o 6 4.67 6.83 (013H
(as I91N205) Example 19 3-71J-5-bis(ethoxycarbonyl)methylenehydantoin in 16 tnl of water containing 1.12.

Aqueous solution of 1N hydroxide at room temperature 14fi/
After adding, the mixture was heated and reacted under reflux for 1 hour.

After the reaction, the resulting reaction product mixture was cooled with water.

After adding 0.941 i' of iodine, the mixture was heated.

The reaction was carried out under reflux for 4 hours.

After the reaction, add 1.5 ml of concentrated hydrochloric acid to the reaction product mixture at room temperature.
was added and filtered to obtain 1-allyl-5-iodoorotic acid.
Decahydrate crystal 0.65? (Yield: 53 cm) was obtained. This was recrystallized with 15 m/h of water.

Yellow needle-shaped crystals with a decomposition point of 185-186°C were obtained.

The elemental analysis values are shown below.

CHN Analyzed value 29.12 2.42 8.43 Calculated value 29.02. 2.44 8.46 (as 08H7EN2O4.+H20) Example 20 5-carboquine-1-phenylorotic acid sodium salt monohydrate 5071111' containing 1.51% of water was added with 0.0% sodium hydroxide at room temperature. Add 2f, then iodine 1.2
After adding 99% of the mixture, the mixture was heated and reacted under reflux for 4 hours.

After the reaction, add 0.5 salt to the resulting reaction product mixture at room temperature.
ml was added and filtered to obtain 1.71 t (yield: 94%) of crystals of 5-iodo-1-phenylorothi/acid. This was recrystallized with ethanol, and the molar ratio with ethanol was 1.
:1 colorless needle crystals with a decomposition point of 258-260°C were obtained as an adduct of 1. The elemental analysis values are shown below.

CHN engineering analysis value 38.87 3.24 6.99 61.6
5 Calculated value 38.63 3.24 6. φroro1.
40 (as CII3 HI3 Engineering N2O5) Example 21 After adding 80 wLl of a 1N aqueous solution of sodium hydroxide to 6.659 mL of 5-bis(ethoxycarbonyl)methylene/-self-phenylhydantoin at room temperature.

The mixture was heated and reacted under reflux for 1 hour.

After the reaction, 5.0% iodine was added to the resulting reaction product mixture at room temperature.
8 f was added. Heat the mixture under reflux to 4.5
Allowed time to react.

After the reaction, the mixture of the two reactions was cooled to room temperature and filtered. 40 WL of 2N hydrochloric acid was added to the p solution and filtered to give 6.92 kg of crystals of 5-iodo-1-phenylorotic acid.
y (yield: 97%) was obtained.

Example 22 5-(p-anisyl)-5-bis(ethoxycarbonyl)hydantoin (3.629 ml of tr water, 1N hydroxide at room temperature) AOm
After adding g, the mixture was heated and reacted under reflux for 1 hour.

After the reaction, 2.542 g of iodine was added to the mixture of the two reactions at room temperature, and the mixture was heated and reacted under reflux for a period of time.

After the reaction, the reaction product mixture was allowed to cool to room temperature and filtered.
When 20 rnl of 2N hydrochloric acid was added to the liquid, crystals precipitated and gas was generated in Bow 1. The mixture was filtered and 1-(
Crystals of p-anisyl)-'5-1 odorotic acid 6.3
(yield: 85%). This was recrystallized with ethanol to obtain yellow needle-shaped crystals with a decomposition point of 9 and 263° C. as an adduct with ethanol in a molar ratio of 1:1. The elemental analysis values are shown below.

CHN Analysis value Ro9.05 Ro,52 6.26 Calculated value Ro8.73 Ro,48 6.45 (014HI
Example 23 50 ml of water containing 1.65 f of 5-carboxy-1-(p-chlorophenyl)orotate sodium salt monohydrate
17.5% of a 1N aqueous solution of sodium hydroxide at room temperature.
After adding m/ and then 1.279 iodine, the mixture was heated and reacted under reflux for 7 hours.

After the reaction, the reaction product mixture cooled to room temperature was filtered and F
When 10ml of 2N hydrochloric acid was added to the solution, crystals were separated. This was filtered and 1-(p-?lorophenyl)-5-
1.572 iodooroti/acid crystals (yield: 80%) were obtained. This was recrystallized with ethanol and the decomposition point was 268.
Yellow microneedle crystals of ~270°C were obtained. The elemental analysis values are shown below.

CHN Analysis value 33.00 1.94 7.18 Calculated value 33.66 1.54 7.14 (as CoHaC7eN2O4) Example 24 5-bis(ethoxycarbonyl)methylene-6-(p-
chlorophenyl)hydantoin 7.349 at room temperature.
After adding to the specified aqueous solution BOml of sodium hydroxide,
The mixture was heated and reacted under reflux for 1 hour.

After the reaction, 5.081 g of iodine was added to the mixture of the two reactions at room temperature, and the mixture was heated again and reacted under reflux for 5 hours.

After the reaction, the reaction product mixture was cooled to room temperature and filtered.

When 40jx/i' of 2N hydrochloric acid is added to solution F.

Crystals separated. This was filtered to give crystals of +1 (p-chlorophenyl)-5-iodoorotic acid, 73y(
Yield: 86%) was obtained.

Next, to demonstrate that the 5-roorotic acids of this invention are useful as agricultural and horticultural fungicides.

The following reference example is shown. In the reference examples, 2 parts indicates parts by weight.

Reference example (1) Preparation of test emulsion 20 parts of 5-haloorotic acid, 5 parts of toxanone.

75 parts of xylene were mixed to obtain 100 parts of an emulsion.

(2) Control test diameter b for cucumber powder blight
Plant one cucumber per pot in a cm synthetic resin pot (variety:
Cultivate cucumber seeds (Sagami half-day set cultivation) and sow cucumber seeds.
The emulsion prepared by the above method (5-haloorotic acid concentration: 11,000 pp) was sprayed on 7-day-old seedlings. Next, after air-drying, each seedling was infected with cucumber powdery mildew fungus (5 phae
rottheca fuliginea) [conidia dropped from the leaf surface of cucumber powdery mildew-affected leaves into a Petri dish with a soft brush were added to distilled water in one field of view under an optical microscope (
A spore suspension prepared so that 10 spores per sample (magnification: 150 times) was uniformly inoculated by spraying. After inoculation, the seedlings were left in an isolated glass greenhouse, and after about 11 days, the number of spots of powdery mildew on the first true leaves of Kicuri was investigated, and 5-haloorotic acid was calculated using the 9th equation. The control rate was now 1. The results are shown in Table 1 as a control effect index.

5 91~100 4 81~ 9゜6 61~
8.

Table 1 Patent applicant: Ube Industries Co., Ltd.

Claims (1)

[Claims] (1) Formula [In the formula, R1 is an alkyl group having 1 to 4 carbon atoms, an allyl group. Cyclohexyl group, benzyl group is ico(R2)n
(In the formula, R2 is an alkyl group having 1 to 4 carbon atoms,
4 represents an alkoxy group or a halogen atom. n represents a group represented by 0, 1.2 or holo), and X represents chlorine, bromine or iodine]5
-Haloorotic acids. [In the formula, Me represents an alkali metal and R1 has 1 carbon number
-4 alkyl group, allyl group, cyclohexyl group. benzyl group or -Q(R2)n (wherein R2 represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, and n is 0, 1, 2 or 3); 5-carboxyorotic acid alkali metal salt represented by the following formula: A formula characterized by reacting a halogenating agent
O 1 [In the formula, Hl is an alkyl group having 1 to 4 carbon atoms, allyl (in the formula + R2 is an alkyl group having 1 to 4 carbon atoms, 1 to 4 carbon atoms)
represents an alkoke group or a halogen atom. n is 0, 1.2 or O), and X is chlorine, bromine or iodine].
Process for producing haloorotic acids.