DD283399A5 - PROCESS FOR PREPARING PHOSPHORUSEDE DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of phosphoric acid derivatives having a strong insecticidal activity. According to the invention, compounds of the formula (I) are prepared in which R, R 1, R 2 and Y have the meaning given in the description and in the claims. The new process is simple, economical, environmentally friendly and gives good yields in high purity. The intermediates obtained in the individual process variants are storage stable. They can be isolated and reacted as needed in a simple manner to the final product. Formula {improved procedure; readily preparable intermediates, storage stable; environmentally friendly production; high yields}

Description

Z.8339 9 '

Process for the preparation of phosphoric acid derivatives Field of application of the invention

The invention relates to a novel process for the preparation of insecticides Pyrimidinyiphosphorsäurederivaten, intermediates which can be used for carrying out the process, as well as processes for the preparation of such intermediates.

Characteristic of the known state of the art

It is already known that certain pesticidal Phosphorinsäurepyrimidinester obtained by reacting corresponding Phosphorsäureesterchloride with 5-hydroxypyrimidines (see, DE-OS 26 43 262, DE-OS 27 06 127 and DE-OS 34 23 623), However, there is a need on new readily available intermediate products which can be used in a well-practicable production process for phosphoric acid pyrimidine esters.

Object of the invention

The aim of the invention is to provide an improved process for the preparation of insecticidally active phosphoric acid derivatives, which can be used to obtain in a simple and economical manner very good yields in high purity.

" ^la " 2 8 3 3 9

Explanation of the essence of the invention

The invention has for its object to find «readily accessible intermediates, which can be converted in a simple manner into the desired phosphoric acid derivatives.

It has now been found that the compounds of general formula (I)

\ II / OR ² VOP (I)

in which

jg R is hydrogen, "alkoxy, alkylamino," dialkylamino, or optionally substituted radicals, row "alkyl," "cycloalkyl," aralkyl, and aryl "

R ^{1 represents} optionally substituted radicals aue of the series alkyl "alkoxy" alkylthio "mono- or dialkylamino and phenyl"

R ^{2 is} optionally substituted alkyl and 2Q Y is oxygen or sulfur "receives"

if 2g al) compounds of the general formula (Ha)

s θ Cl

(IIa) ^ R ³

in which

R has the meaning given above « R ^{3 is} amino or the group XR ⁴ is "where Le A 25 713-foreign countries

- 3 - 2 ö 3 3 9 9

X is oxygen or sulfur and 5

R ^{4 is} methyl or ethyl,

with 1,3-diamino-2-propanol of the formula (III)

10 2 ™ 2 ^^ s

CH-OH (III)

or its acideaddialite salts,

optionally in the presence of diluents at temperatures between ^{0 0} C and 120 ⁰ C umcetzt;

a2) or when carboxylic acids of the formula (Hb)

R ⁵ -CO ₂ H (Hb)

in which

R ^{5 has} the meaning given above for R except hydrogen,

with 1,3-diamino-2-propanol of the formula (III)

30 H ₂ N-CH ₂ \

CH-OH (III)

H ₂ N-CH ₂

optionally in the presence of diluents 2 $ at temperatures between 120 ⁰ C and 250 ⁰ C converts;

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a3) if one carboxylic acid salts of 1,3-diamino-2-propanol of the formula ⁵ (lic)

[R ⁵ -CO ₂ ^e ] CH-OH (lic)

10 'HoN-CH ₂

in which

₁₅ R ^{5 has} the abovementioned meaning, heated to temperatures between 120 ⁰ C and 250 ° C,

and the forming 5-hydroxy-3,4,5,6-tetrahydropyrimidine salts of the general formula (IV)

²⁰ W- ^CH 2 \ ^

R-C C (IV)

25 in which

Z is chlorine or R ^{5 is} -CO ₂ , where R ^{5 is} as defined above, and

30 R the above angogebena meaning hiit given case «isolated and

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b) optionally with a base, the 5-hydroxy-3,4,5-tetrahydropyrimidines

the general formula (IVa)

N-CH ₂ \ / Ή

R- <C UVb) N-CH ₂ ^ ^V M) H

in which R has the meaning given above, releases and then

c) either

the 5-hydroxy-3,4,5,6-tetrahydropyrimidine hydro chlorides of the general formula (IV)

N-CH ₂ \ R- <

in which 30

Z is chlorine or R ⁵ -CO ₂ , where R ^{5 has} the meaning indicated above, and

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or the free 5-hydroxy-3,4,5 _# 6-tetrahydropyrimi dine of general formula (IVa)

N-CH ₂ \ "R- <C (IVa)

in which

R has the meaning given above,

optionally after isolation to give the compounds of general formula (V)

Mt W

(V)

in which

R has the meaning given above

oxidized or dehydrated and then

d) the compounds of the formula (V), if appropriate

after their isolation, with compounds of general formula (VI)

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H / or ²

Hal - P (VI)

\1

in which Hal is halogen and

Y, R ¹ and R ^{2 have} the meaning given above »

if appropriate in the presence of an acid binder and if appropriate in the presence of a solvent, and the compounds of the general formula (I) are isolated.

According to this method, it is possible to easily prepare the compounds of the formula (I) in good purity and yield. The process is very widely applicable with regard to the nature of the desired substituents. "Furthermore, the compounds to be compounded as intermediates are stable and can be well stored and handled.

Preferred sub-substituents or ranges of the radicals listed in the formulas mentioned above and below are explained below:

Alkoxy R represents straight-chain or branched alkoxy having preferably 1 to 12, in particular 1 to 6 and particularly preferably 1 to 4 carbon atoms. Example-35

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may be methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy eec-butoxy and tert-butoxy,

Mono- or di-alkylamino R is an amino group having 1 or 2 alkyl groups, preferably 2 alkyl groups, which may each be straight-chain or branched and preferably contain 1 to 5, in particular 1 to 3, carbon atoms "wherein methyl ι ethyl» η- and i-Propyl may be mentioned "Examples include dimethylamines", diethylamino, di-n-propylamino and di-i-propylamino listed.

As an optionally substituted alkyl R is straight-chain or branched alkyl having 1 to 20, preferably 1 to 12, in particular 1 to 6 and particularly preferably 1 to 4 carbon atoms "Examples include optionally substituted methyl" ethyl / n-propyl, i-propyl, n- Butyl, sec-butyl, i-butyl, tert-butyl, n-pentyl, i-pentyl and tert-pentyl called «

As optionally substituted cycloalkyl R is cycloalkyl having preferably 3 to 8, in particular 3 "5 or 6 carbon atoms" exemplify be givenfülli; nwhnl. i Lu ί ntl.HK Cyt: 1 upropyl, cyclobutyl «cyclopentyl, called cyclohexyl and cycloheptyl.

Optionally substituted aralkyl preferably contains 1 to 4 carbon atoms in the straight-chain or branched alkyl part and phenyl as the aryl part. An aralkyl group which may be mentioned by way of example is benzyl, which is preferably unsubstituted.

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As optionally substituted aryl R is aryl having preferably 6 to 10 carbon atoms in the aryl moiety. Examples are optionally substituted phenyl or naphthyl, in particular phenyl.

The substituents mentioned in the definition of R may carry one or more, preferably 1 to 3, in particular 1 or 2, identical or different substituents. As substituents for alkyl, cycloalkyl and aryl may be mentioned by way of example.

Alkoxy and alkylsulfonyl having 1 to 4 carbon atoms, such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, sec-butoxy, tert-butoxy, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, i-propylsulfonyl, n-butylsulfonyl, i-butylsulfonyl and tert-butylsulfonyl.

Also suitable as aryl substituents and cycloalkyl substituents is C ₁ -C ₄ -alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl, preferably the radicals R are unsubstituted

,

 · ·

Preferably .stands R is hydrogen, for alkoxy having 1 to 12 carbon atoms

etoffatomen, mono- or di-alkylamino having in each case 1 to 6 carbon atoms in the alkyl moiety, optionally substituted by C ₁ -C ₄ -alkyl or C ₁ -C ₄ -alkyl) alkylsulfonyl-substituted alkyl having 1 to 12 carbon atoms, optionally by C ₁ -C ₄

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6-substituted B cycloalkyl having 3 to 8 carbon atoms and for benzyl optionally substituted by C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy or C ₁ -C ₄ -alkylsulfonyl or aryl having from 6 to 10 carbon atoms.

Particularly preferred is

R is hydrogen, alkoxy having 1 to 6 carbon atoms "mono- or dialkylamino having in each case 1 to 4 carbon atoms in the alkyl moiety or optionally by methoxy" ethoxy, methylsulfonyl or ethylsulfonyl-substituted alkyl having 1 to 6 carbon atoms "for optionally substituted by methyl or ethyl cycloalkyl with 3 to 6 carbon atoms and benzyl or phenyl which is optionally substituted by methyl, ethyl, methoxy, ethoxy, methylsulfonyl or ethylsulfonyl

Very particularly preferred

R for methyl isopropyl and tert-butyl (preferably tert-butyl) ♦

R has the same general and preferred meanings as R; however, hydrogen is excluded.

The optionally substituted alkyl groups R ¹ and R ² preferably contain 1 to 6, in particular 1 to and more preferably 1 or 2, carbon atoms

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2 833 9

Examples include methyl, ethyl, η- and i-propyl, η-, i-, B- and t-butyl (preferably ethyl and s-butyl) called ·

The alkyl groups of the optionally substituted alkyl and dialkylamino groups R ¹ preferably have the meaning given above for the alkyl groups R * and R ^ above. By way of example, mention may be made of methyl, ethyl, n-propyl and i-propylamino, and of dimethyl, diethyl and methylethylamino.

The alkoxy and alkylthio radicals R * preferably contain 1 to 6, in particular 1 to 4 and particularly preferably 1 or 2 carbon atoms, by way of example methoxy, ethoxy, n- and i-propoxy and methylthio, ethylthio and

N- and i-propylthio (preferably ethoxy) called. 20

The optionally substituted radicals R ¹ and R ² may carry one or more, preferably 1 to 3, in particular 1 or 2, identical or different substituents. Ale substituents are exemplified: alkyl (does not apply to the case in which R ¹ and R ^{2 is} alkyl) having preferably 1 to 4, in particular 1 or 2 carbon atoms, such as methyl, ethyl, η- and i-Prooyl, and n, i, β and t-butyl alkoxy having preferably 1 to 4, in particular 1 or 2 carbon atoms.

such as methoxy, ethoxy, n- and i-propyloxy and n-, i-, β- and t-Butyloxyj alkylthio having preferably 1 to 4, in particular 1 or 2 carbon atoms, such as methylthio, ethylthio, n- and i-Propylthio and n-, i-, s- and

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t-butylthio; Halogen »preferably fluorine» chlorine »bromine and iodine» in particular chlorine and bromine; Cyano and Nitro, Preferably, the radicals R ¹ and R ^{2 are} unsubstituted.

Hal in the general formula (VI) is fluorine "chlorine" bromine and iodine "preferably fluorine" chlorine and bromine "in particular chlorine"

Y is preferably sulfur and X is preferably oxygen.

The compounds to be used as starting materials in process step (a) are generally defined by the formula (Ha), (lib) or (lic). In this formula R has preferably the meanings »already ira connection with the description of substances of the formula

(I) have been mentioned as preferred for this substituent.

Examples of the compounds of formula (Ha) in which R stands for amino are the following compounds:

Q θ

₂ cl

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35

table

30

- 13 -

10

15

20

25

H CH ₃

^C 2 ^H 5 C ₃ H ₇ -H

C ₃ H ₇ -IC ₄ H ₉ -n C ₄ H ₉ -IC ₄ H ₉ -BC ₄ H ₉ -IC ₅ H _n -n

OCH OC ₂ H ₅ O ₃ H ₇ -n OC ₃ H ₇ -I-CH ₂ OCH ₃ -CH ₂ CH ₂ OCH ₃ -CH ₂ OC ₂ H ₅ -CH ₂ CH ₂ OC ₂ H ₅ -CH ₂ SO ₂ CH ₃ -CH ₂ CH ₂ SO ₂ CH ₃ -CH ₂ CH ₂ SO ₂ C ₂ H ₅ -N (CH ₃ ) ₂ -N (C ₂ Hg) ₂

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The compounds of formula (Ha) are generally known or can be prepared by known processes (cf. Org Synthesis Coll Vol I, page 5 (1951);.... Beilstein Vol 2, p 185; Vol. 2 /. III , p. 452; Bd, 2/111 , S, 478; Vol. 9, p. 280; U.S. Patent No. 4,012,506 ).

The in process step (a) to be used as starting materials iminoalkyl (thio) ether hydrochlorides are also generally defined by the formula (Ha). In this formula, R ^{3 is} the group XR ⁴ and X and R ⁴ preferably have the meanings which have already been mentioned as preferred in connection with the description of the compounds of the formula (II) for X and R ⁴ .

As examples of the compounds of the formula (Ha), in

which R ^{3 is} XR ⁴ 20

R-C

Cl

and for the compounds of formula (Hb) 25

R ⁵ -CO ₂ H (lib)

be named: 30

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table

R and R ⁵ R and R ', respectively

H (for formula I Ia)

CH-;

C, H

2 "5 C ₃ H ₇ -n C ₃ H ₇ -IC ₄ H ₉ -n C ₄ H ₉ -IC ₄ H ₉ -BC ₄ H ₉ -t C ₅ H _n -n

CCH

OC ₂ H ₅

OC ₃ H ₇ Ti OC ₃ H ₇ -I-CH ₂ OCH ₃ -CH ₂ CH ₂ OCH ₃ -CH ₂ OC ₂ H ₅

-CH ₂ SO ₂ CH ₃ -CH ₂ CH ₂ SO ₂ CH ₃ -CH ₂ CH ₂ SO ₂ C ₂ H ₅ -N (CH ₃ ) ₂ -N (C ₂ Hg) ₂

CH-

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The imincalkyl (thio) ether hydrochlorides of the formula (Ha) are generally known compounds of organic chemistry, or can be prepared by known processes (cf., ürg Synthesis Coll, Vol I, page 5 (1951); Beilstein Bd 2, p 182, Vol 2, S, 245, Bd, 2 / III p 451, Bd, 2 p 618, Bd, 2 / l1 p 675, US Patent 4,012,506 ). ,

Dae m process step (a) to be used as starting material ί. _# 3-diamino-2-propanol of formula (III) is known <vj *. U.S. Patent 3,432,553). The in the process step

a) as starting materials to be used alternatively acid addition salts of the forms? (III) are well known compounds of organic chemistry. Examples which may be mentioned are: 1S-diamino-propanol hydrochloride, "di-p-toluenesulfonate,

ί, S-diamino-propanol dihydrochloride, "di-picrate 1 * 3-diamino-2-propanol dihydrobromide | 1,3-diamino-2-propanol-bisulfate.

The salts of the compound of formula (XIl) with the carboxylic acids of formula (lib) are obtainable by the generally customary salt formation methods.

The process step (a) according to the invention for the preparation of the compounds of the general formula (IV) is preferably carried out in the presence of diluents. Suitable diluents are preferably:

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Alcohols such as methanol, ethanol, n- and i-propanol, tert-butanol, aliphatic and aromatic, optionally halogenated hydrocarbons such as pentane, hexane, heptane, cyclohexane, petroleum ether, gasoline, ligroin, benzene, toluene, xylene, methylene chloride, ethylene chloride , Chloroform, carbon tetrachloride, chlorobenzene and o-dichlorobenzene, ethers such as diethyl and dibutyl ether, glycoldimethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane, nitriles such. For example, acetonitrile and propionitrile, amides, such as. B "dimethylacetamide and N-methyl-pyrrolidone, and tetramethylene sulfone.

Dia reaction temperature may be in the process coulter ride (al) within a substantial range varies "in general carried out between 0 ⁰ C and +120 ⁰ C, preferably at +40 ⁰ C to +80 ⁰ C. The inventive process is in general carried out at normal pressure ,

For carrying out the process (al) according to the invention, the starting materials are usually used in equimolar amounts "An excess of one or the other reaction component brings no significant advantages." The work-up and optionally desired isolation is done by conventional methods, z "B" by distilling off the solvent under reduced pressure, whereby the product of formula (IV) is present as a residue «

Surprisingly, the novel 5-hydroxy-3,4,5,6-tetrahydropyrimidine hydrochlorides of the general formula (IV) can be obtained a great deal by process (a) according to the invention

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obtained easily and in good yields and in high purity. They are therefore particularly suitable for use in process steps (b) and (c).

If, for example, isobutyramidine hydrochloride and 1,1-diamino-2-propanol are used as starting materials in process step (al) according to the invention for the preparation of the compounds of general formula (IV), the reaction can be outlined by the following formula scheme:

CHq I

NH ₂ -CH ₂ - NH

N-CH ₂ \

^CH3 1n-ch / noh

CH ₃ I

H χ HCl

The process steps (a2) and (a3) according to the invention for the preparation of the compounds of the general formula (IV) are preferably carried out in the presence of diluents which form an azeotrope with water. The water which forms during the reaction is preferably removed continuously from the reaction mixture.

AIb diluents are preferably in question:

Chlorobenzene, o-dichlorobenzene, xylenes (ortho, meta »para, possibly mixtures), toluene, methylcyclohexane, decahydronaphthalene, anisole, ethylbenzene, isopropylbenzene.

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The reaction temperature is generally between 120 ⁰ C and 250 ⁰ C. To avoid too long reaction times "is advantageously carried out above 135 ⁰ C, preferably between 135 ⁰ C and 200 ⁰ C,

It can be carried out at normal pressure »but also at elevated or reduced pressure.

When carrying out process step (a2), 1.5 to 3, preferably 2 to 2.5, moles of the carboxylic acid of the formula (IIb) are used per mole of diaminopropanol of the formula (III) or its carboxylic acid salt.

The workup and isolation of the compounds of formula (IV) is carried out by filtering off or separating the forming phase which contains the compounds of formula (IV).

If, for example, isobutyric acid and 1,3-diamino-2-propanol are used as starting materials in process step (a2) according to the invention, the first

25

Stage of the reaction by the following formula scheme skiz

be graced:

OH

CH ₂ -CH-CH ₂

30

2 (CH ₂ ) ₂ CH-CO ₂ H + NH ₂ NH ₂

J -

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If, for example, the di-pivalic acid salt of 1,3-diamino-2-propanol is used as starting material in process step (a3) according to the invention, the reaction can be outlined by the following formula scheme:

H ₃ N-CH ₂ \ 120-250 ⁰ C

CH-OH

_{Γ θ Ί} CH-OH

(CHQ) oC "COoS -2H₂O

^{L 3 3 2 J} 2 H ₃ N-CH ₂

(CH ₃ ) ₃ CC0 ₂

C (CH ₃ ) ₃

Surprisingly, according to the process step (a2) according to the invention, the 5-hydroxy-3,4,5,6-tetrahydropyrimidine derivatives of the formula (IV) can be obtained in good yields and high purity. «

In particular, it was not to be expected by the skilled worker "that the carboxylic acids of formula (lib) react readily at a relatively low temperature," even though the literature was known "that an analogous reaction with

Diaminopropane requires temperatures of 225 ° C (EP-PS

117 882).

Moreover, in order to obtain a monoacylation, diaminopropane is preferably used in large excess in the abovementioned patent application

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It is surprising to see that despite the excess use of the carboxylic acid of formula (I), the reaction proceeds in such good yield. "

The process according to the invention is furthermore to be described as extremely surprising because the person skilled in the art had to reckon with the dehydration of the secondary alcohol group or with an esterification of the alcohol group with the carboxylic acids of the formula (IIb) under the acidic reaction conditions.

In process variants (a3), the process conditions (solvents »temperatures, work-up and isolation) are carried out as in process (Hb)«

As examples of the compounds of the formula (IV) obtainable according to the invention, the following compounds are listed:

_2

R-C C (IV)

H Z

Z-Cl, R ⁵ CO ₂ 30

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table

R and R *

R and R ⁵

10

15

25

H (Z * Cl) CH ₃

C ₂ H ₅ C ₃ H ₇ -n

C ₃ H ₇ -i C ₄ H ₉ -n C ₄ H ₉ -IC ₄ H ₉ -BC ₄ H ₉ -I ^C 5 ^H 11 ⁿ

OCH

30

OC ₂ H ₅

OC ₃ H ₇ -n OC ₃ H ₇ -i-CH ₂ OCH ₃ -CH ₂ CH ₂ OCH ₃ -CH ₂ OC ₂ H ₅ -CH ₂ CH ₂ OC ₂ H ₅ -CH ₂ SO ₂ CH ₃ -CH ₂ CH ₂ SO ₂ CH ₃ -CH ₂ CH ₂ SO ₂ C ₂ H ₅

CH-

35

The process for preparing the compounds of the general formula (IV) according to process step (a1) (a2) and (a3) is not yet known from the literature and

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Also part of the present invention are the compounds of the general formula (IV), except those compounds in which R is hydrogen, methyl or chloromethyl and Z is chlorine "new, and part of the present invention"

These compounds can be used, for example, in process step (c). "

The compounds of the general formula (IVa) which are likewise to be employed in process stage (c) are in some cases known. Thus, it is already known that 1,3-diamino-propan-2-ol is treated with ethyl acid cesium acetate to give 5-hydroxy-3,4,5 , 6-tetrahydropyrimidine condensed and yields with Eseigsäureethylester 5-hydroxy-2-methyl-1,3,4,5,6-tetrahydropyrimidine (see, J. Org. Chem ,, 3838 -C339, (1966)). The disadvantages of this method are the moderate yields and the elaborate processing of the end products «

Ee it has been found that the 5-hydroxy-3,4,5,6-tetrahydropyrimidines of the general formula (IVa)

N-CH ₂ \ sT \ RC C (IVa)

H 30

in which

R has the meaning given above 35

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if one obtains 5-hydroxy-3,4,5,6-tetrahydropyrimidine hydrochlorides of the general formula (IV)

N-CH ₂ / H RC C (IV)

^Η β I θ

H Z 10

in which

R and Z have the meanings given above,

with a base, preferably with an aqueous solution of alkali hydroxide, in particular of sodium hydroxide and / or potassium hydroxide.

It is to be described as awe-inspiring, that after the

Process step (b) according to the present invention gives the newly obtained 5-hydroxy-3, 4, 5, 6-tetrahydropyrimidines in good yields and in a high degree of purity in a technically simple manner "since it was known" that 3 "4" 5 "6-tetrahydro -5-hydroxy-

pyrimidine and 3,4- 5,6-tetrahydro-2-methyl-5-hydroxypy-25

hydrolyze rimidine very easily.

Is used in the inventive process step (b), for example, 3 »4,5» 6-tetrahydro-2-isopropyl-5-pyrimidinol hydrochloride as starting material and

Sodium hydroxide as base »so the reaction can dae by

following equation scheme are sketched:

N-CH ₂ \ xH NaOH N-CH ₂ \ CH ₃ -CH-C C -CH ₃ -CH-C I is N-CH ₂ ^ ^ -OH I N-CH ₂

CH ₃ I 'CH ₃ I

H χ HCl H

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Examples of the compounds of the formula (IVa) obtainable according to the invention are the free bases of the compounds of the formula IV given in Table 3,

When carrying out the process according to the invention for preparing the compounds of the general formula (IVa), the starting material of the formula (IV) is preferably introduced into water and the aqueous alkali metal hydroxide solution (preferably sodium hydroxide solution or potassium hydroxide solution) is added dropwise.

In carrying out process step (b) according to the invention, one mole of starting material of the formula (IV) is reacted with 1 to 2 mol of _1, preferably 1 to 1.5, mol of alkali lye.

The reaction is carried out at room temperature or slightly elevated temperatures.

In general, one works between 10 ⁰ C and 50 ⁰ C, but preferably between 10 ⁰ C and 30 ⁰ C. In particular, is reacted at room temperature «

The concentration of the aqueous alkali metal hydroxide solution can be between 10% and 50 K, but preferably between 20 % and 45 % (percentages are by weight).

The work-up and optionally desired isolation of the compounds of the general formula (IVa) is carried out by customary methods, for example by suction.

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The compounds of the general formula (IVa) can also be obtained from the salts of the formula (IV) with the aid of strongly basic ion exchangers. Conventional (commercially available) ion exchangers can be used for this purpose. "The reaction is carried out by conventional methods. Preferably, aqueous solutions of the compounds of the formula (IV) are stirred with a sufficient amount of the ion exchanger, the ion exchanger is filtered off and the water is removed from the filtrate (for example by gently distilling off or, in the case of very sensitive bases, by freeze-drying).

The compounds of general formula (V) to be used in process stage (d) are known or can be prepared by generally known methods.

Thus, θε is already known that 5-hydroxy-pyrimidines obtained when reacting 5-methoxy-pyrimidines int autoclave, at temperatures between 180 ⁰ C and 200 ⁰ C under basic conditions (see, for example, DE-OS 26 43,262 and Coll. Chem. Comm. 40, 1078 et seq. (1975)). The disadvantages of these processes are that the yields and purity of the reaction products are often unsatisfactory and, moreover, extreme reaction conditions are required.

It is also known that the 5-hydroxy-pyrimidines can also be prepared in the presence of alkali metal hydroxides and glycol from 5-methoxy-pyrimidines. In this method, temperatures of about 200 ⁰ C are required. Other disadvantages are the elaborate processing of

Final products and the moderate yields (cf., z, B, J, Le A ^ 5 713-Foreign countries

Chem. Soc. ) 196O . 4590 ff and Chem, Ber. 9j, 803 ff (1962)). In addition, working in polar high boiling solvents such as glycol requires special efforts: wastewater treatment.

Furthermore, it is known that S-hydroxy-pyrimidines can also be prepared with hydrogen in the presence of hydrogenation catalysts from 4-chloropyrimidine derivatives. The disadvantage of this method lies in the expensive preparation of 4-chloropyrimidines (cf .. DE-OS 34 23 623).

It has been found that the 5-hydroxypyr-.nididines of the general formula (V)

in which

R has the meaning given above,

when one obtains either substituted 5-hydroxy-3,4, -5,6-tetrahydropyrimidine salts of the general formula (IV)

N-CH ₂ \ / H RC C (IV) ^ ^

in which

R and Z have the meanings given above

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or 5

5-Hydroxy-3,4,5,6-tetra-yl-pyridines of the general formula (IVa)

N-CH ₂ \ / Ή

R- <C (IVa) N-CJ "^

in which

R has the meaning given above,

optionally after their isolation, with oxidizing agents, optionally in the presence of dehydrogenation catalysts and optionally in the presence of Ver-ZO

thinners at temperatures between 5 ⁰ C and 150 ⁰ C converts.

Surprisingly, it is possible with the aid of this method *, which corresponds to process step <c) and which is part of the present invention, under relatively mild conditions to obtain the 5-hydroxypyrimidines of the general formula (V) in very high purity Process are the recovery of the catalysts and the use of

inexpensive and environmentally friendly diluents.

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If, for example, roan uses 3,4,5, e-tetrahydro-tert-butyl-S-hydroxypyrimidine as starting material and oxygen as oxidizing agent for the process according to the invention, then the reaction can be sketched schematically by the following formula:

(CH ₃ ) ₃ C- <C> (CH ₃ ) ₃ C-C /) ~ 0H + 2H ₂ O

NCH ^ N) HN *

For the preparation of the compounds of general formula (V) from the compounds of general formulas (IV) and (IVa) it is preferred to use water as the solvent.

The Oxiditätsmitel or dehydrating agents for the process according to the invention are known per se (Organikum, VEB German Verlag der Wissenschaften, Berlin 1977, pages 430-471). Examples include nitric acid, oxygen and its peroxygen compounds (hydrogen peroxide, metal peroxide, inorganic and organic peracids), sulfur, selenium dioxide, chlorine, bromine, hypohalous acids, chloric acid, periodic acid, metal compounds of higher valence states [egg (II) compounds, manganese dioxide, Kaiiurapermanganat, Chromic acid, anhydride, lead dioxide and lead tetraacetate], tetrachloro-p-benzoquinone and dichlorodicyanobenzoquinone (DDQ). Preferred oxidizing agents are potassium permanganate, ammonium, sodium or potassium peroxodisulfate and chromium trioxide.

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It may also be advantageous to carry out the process according to the invention in the presence of hydrogenation catalysts. Metal catalyst is preferably used.

^S ators of VIII, subgroup of the periodic table, such as platinum, the Pa lad ium, optionally on conventional support materials, such as activated carbon, silica or alumina »used.

The reaction temperatures can be varied within a substantial range when carrying out the process according to the invention. In general, one works at temperatures between +10 ⁰ C and +180 ⁰ C, preferably at temperatures between + 20 ° C and +150 ⁰ C, in particular between + 20 ° C and +100 ⁰ C.

The erfindur.gsgemäße process is generally carried out at atmospheric pressure. However, under certain conditions, especially with the use of dehydrogenation catalysts, it may be advantageous to operate under elevated pressure,

To carry out the erfindungcgemäßen method sets

in general, to 1 mol of 5-hydroxy-3,4,5,6-tetrahydropyrimidine or, hydrochloride of the formula (IV) or (IVa) between 0.5 and 5 mol, vorzusweise between 0.6 and 4 moles of oxidizing agent and / or between 0.01 and

1 mole, preferably between 0.05 and 0.5 moles of dehydrogenation catalyst,

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In a particularly preferred embodiment, the oxidation (dehydrogenation) of the compounds of the general formula (IV) and (IVa) to the compounds of the general formula (V) is carried out with oxygen as the oxidant. In a very particularly preferred embodiment, the dehydrogenation is carried out with oxygen (air) in the liquid phase in the presence of a solvent and a base. The addition of a heavy metal salt (preferably a transition metal compound) proves to be advantageous.

By this process variant of process step (c), it is surprisingly possible «to produce the 5-hydroxypyrimidines in a particularly high yield and high purity. This process step further characterized by the ready availability of the starting components ι by a cheap and easy-to-use oxidant, by mild reaction conditions and by a very simple workup.

Solvent for the inventive method for

Preparation of (V) by dehydrogenation of (IV) or (IVa) with oxygen in process step (c) are those which do not react with oxygen or react only comparatively slowly and at least partially dissolve the starting materials. Examples are

called: Alcohols «Ether alcohols, hydrocarbons« chlorinated hydrocarbons! Amines "nitriles, amides, ethers, polyethers, esters, sulphoxides, sulphones, lactones" lactams, etc. Of these, preference is given to alcohols,

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2 8 13

Ether alcohols, amines, sulfoxides, sulfones, amides, ethers and polyethers, in particular alcohols, amines, amides, sulfoxides and sulfones used, individual examples from the field of alcohols and ether alcohols are: methanol, ethanol, n- and i-propanol, 1-butanol, 2-butanol, tert-butanol, isopentyl alcohol, isohexanol, isooctanol, diethylene glycol, tetraethylene glycol, etc., Examples of amines include triethylamine, dibutylamine, ethylenediamine, tetramethylethylenediamine, permethyldiethylenetriamine, pyridine, picoline, quinoline, dimethylaniline, diphenylamines Di- and tribenzylamine · Individual examples from the field of sulfoxides and sulfones are dimethylsulfoxide, methylphenylsulfoxide, dimethylsulfone, etc. Single examples from the field of amides are formamide, acetamide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, etc. Individual examples from the range ether and polyether are: methyl tert-butyl ether, di-tert-butyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethy Ether etc. Particularly preferred are the solvents t-butanol, dimethyl sulfoxide and said amines and amides, in particular dimethylformamide, N-methylpyrrolidone, pyridine and picoline, and mixtures of these solvents.

As bases for the dehydrogenation with Sauei ».off is a variety of known bases such as amines, Metal1 carbonate, metal hydroxides, metal alkoxides, metal amides, quaternary ammonium hydroxide, etc." The choice of base depends in particular on the choice of reaction conditions such as solvent and reaction temperature ,

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The hydroxides, alkoxides and amides of the alkali metals and alkaline earth metals and of aluminum are preferably used. Particularly preferred alkali metals and alkaline earth metals here are sodium, potassium, lithium, magnesium, calcium, barium. Examples of alkoxides which may be mentioned are the methylate, ethylate, isopropylate, sec, butylate, tert-butylate and the salt of tetraethylene glycol. The amides may be, for example, unsubstituted amide, ethylamide, diethylamide, diisopropylamide, dibutylamide, etc. Among the bases mentioned, hydroxides and alcoholates are preferred, with sodium hydroxide, potassium hydroxide, sodium methylate, sodium ethylate and potassium tert-butylate being particularly preferred. Preferred bases are also quaternary ammonium hydroxide, for example, tetramethylammonium hydroxide and strongly basic ion exchangers e.g. those with quaternary ammonium hydroxide as a functional group. The base may optionally also be used in combination with a crown ether, e.g. 18-Crown-6 are used.

The base is used in an amount of 1-15 equivalents per mole of the 5-hydroxy-tetrahydropyrimidine (IV) or (IVa), preferably 1-10 equivalents, more preferably 2-7 equivalents.

Advantageously, but not absolutely necessary, the reaction mixture in the process according to the invention for the preparation of compounds of the formula (V) by oxidation of compounds of the formula (IV) or compounds of the formula (IVa) with oxygen in process step (c) are heavy metal salts, preferably transition metal compounds, added as catalysts. Effective are those transition metals which are known to catalyze oxidations, autoxidations and dehydrogenations, e.g. Vanadium, chromium, manganese, iron,

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Cobalt, nickel, copper, silver, niobium, ruthenium, molybdenum, palladium, tungsten, platinum. Among them, preferred are copper, manganese, cobalt, nickel, iron and ruthenium, more preferably copper, cobalt and manganese, and most preferably the copper. These metals may be added individually or in any combination and in any of the individually possible oxidation states become.

Possible forms of use of such metal compounds are the metal salts of inorganic acids, for example the halides such as fluorides, chlorides, bromides or iodides, the sulfates, nitrates, carbonates, phosphates, borates, sulfites, cyanides or the salts of organic acids, such as the acetates, stearates, oxalates or Ion exchangers containing such metals bound. It is also possible to use metal complexes or complex salts, e.g. Amine complexes, halogen complexes and metal chelate complexes, e.g. Metallacetylacetonate, Metallglyoximate, metal phthalocyanines, metalloporphyrins or metal complexes with the ligand bis-salicylaldehyde-ethylenediamine can be used. However, the metals can also be added in elemental form to the reaction mixture.

Preferably, the metal compounds in the form of the salts of inorganic or organic acids (particularly preferably inorganic acids) are used, in particular as chlorides, sulfates, nitrates, oxides, hydroxides, acetates, etc. in hydrated or dehydrated form. In a particularly preferred manner, inorganic and organic salts of copper are used, for example, CuO, CuCl ₂ '2 H ₂ O, CuSO ₄ , Cu (OAc) ₂ . CuCl etc.

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The amount of use of the metal catalyst is not specifically limited. Any amount, as far as it does not fall below O ₁ OOOl molar equivalents, based on the compounds of formula (IV) or, (IVa), is effective. The range is preferably from 0.0005 to 0.10, more preferably from 0.001 to 0.05 mol equivalents, based on the compounds of the formula (IV) or (IVa).

As oxygen for the process according to the invention for the preparation of compounds of the formula (V) by oxygen oxidation of compounds of the formula (IV) or (IVa) in process step (c), pure oxygen or oxygen in dilute form, for example in the form of oxygen-containing gases, preferably air or oxygen-nitrogen mixtures are used. The economically most favorable form of the oxygen which can be used according to the invention is the atmospheric air. The pressure of the oxygen or the oxygen-containing gas is not subject to any particular restriction and may be between 1-100 bar, preferably at 1-10 bar. The oxygen content is also not subject to restriction when using oxygen-containing gases. It is preferably based on operational aspects, such as operational safety and the speed of implementation.

The supply of oxygen to the reaction medium can be carried out, for example, using frits; However, it can also be drawn into the reaction mixture by vigorous stirring.

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The reaction temperature can vary within wide limits and is preferably 0-300 ⁰ C, particularly preferably 2 (1-200 ⁰ C and most preferably at 40 to 120 ⁰ C.

The oxidation of compounds of formula (IV) or (IVa) to compounds of formula (V) with oxygen by the process of the invention is preferably carried out in the liquid phase one or more components, eg the base and / or the compounds of the formulas (IV) or (IVa) are optionally metered in during the reaction with the aid of a solvent 6.

The type of workup following the process according to the invention for the preparation of the compounds of the formula (V) by oxygen oxidation is carried out by the customary methods. It depends on the respective execution conditions. When working in the presence of a metal catalyst, substantial recovery of the metal is indicated for environmental reasons. Since the oxidation in the process according to the invention takes place in an alkaline medium, the metal compounds, if they have been used as oxides or salts, are present as hydrated oxides after the hydrolysis of the crude mixture. The metals can be filtered off, for example, directly from the reaction mixture in the form of their oxide hydrates, wherein this has been diluted sufficiently, if necessary, to feedstocks and products

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2 S 3 3 9 9

The filtrate can then be evaporated, the residue taken up in water and the 5-hydroxypyrimidine released by acidification.

In a work-up variant, the solvent can be evaporated from the reaction mixture. The residue is taken up in water. The insoluble metal oxide hydrate can be filtered off. This procedure is possible since both the product and the by-products formed are excellently soluble in aqueous alkaline solution the 5-hydroxypyrimidine is released by acidification.

In yet another work-up variant, the reaction mixture can be mixed directly with water and the insoluble hydrated oxide can be filtered off. The organic solvent is removed from the filtrate, for example by distillation or extraction, and the 5-hydroxypyrimidine is liberated from the aqueous alkaline solution by acidification.

If the solvent used in the process of the invention is insoluble in water, the reaction mixture can be mixed with water, the organic part separated and optionally recycled. "From the aqueous alkaline solution, the metal oxide is then removed by filtration and from the filtrate by acidification of the 5-hydroxypyriroidin released "

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Ί ö 3 3 9 9

Since "after acidification of the aqueous alkaline solution liberated 5-hydroxypyrimidine can be isolated by the known methods" for example by filtration and / or extraction and then purified, for example by distillation and / or crystal ·

1 isation , 10

As examples of the compounds of general formula (V) obtainable according to the invention are listed:

_1C Table 5

(V)

H is -OC ₂ H ₅

-CH ₃ -OC ₃ H ₇ -n

-C ₂ H ₅ -OC ₃ H ₇ -I

-C ₃ H ₇ -I-CH ₂ CH ₂ OCH ₃

H is -OC ₂ H ₅

-C ₄ H ₉ -n-CH ₂ OC ₂ H ₅

-C ₄ H ₉ -I-CH ₂ CH ₂ OC ₂ H ₅

-C ₄ H ₉ -B -CH ₂ SO ₂ CH ₃

-C ₄ H ₉ -t -CH ₂ CH ₂ SO ₂ CH ₃

" ^C 5 ^H 11" ⁿ " ^CH 2 ^CH 2 ^S0 2 ^C 2 ^H 5

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- 39 -

Table 5 - continued

-OCH ₃

10 CH 2 CH-

CH-

-N (CHg) ₂

-C

These compounds can be used, for example, in process step (dj).

In process step (d), the compounds of general formula (I) are obtained from the compounds of general formulas (VI) and (V).

Is used in process step (d), for example, 0-Et hy 1-O-isopropy 1 -th ionophosphor-d acid esterchlor id and 5-hydroxy-2-pheny1-pyrimidine as starting materials »so __ the corresponding reaction by the following Outlined formula scheme:

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- 4Γ -

There

OC ₃ H ₇ -I - HCl

The starting materials of the general formula (VI) to be used in the process stage (d) are known and can be prepared industrially readily by methods and methods known from the literature. Examples of these are:

0.0-dimethyl, 0.0-diethyl, OiO-di-n-propyl, 0.0-diisopropyl, 0.0-di-n-butyl, 0.0-di-iso butyl, 0,0-disec-butyl, O-methyl-0-ethyl, O-methyl-0-n-propyl, 0-

Methyl-O-hexypropyl, O-methyl-O-n-butyl, O-methyl-O-iso-butyl, O-methyl-O-sec-butyl, O-ethyl-O-n propyl, O-ethyl-0-iso-propyl, O-ethyl-0-n-butyl, O-ethyl-0-sec-butyl, O-ethyl-0-ieo-butyl, on- Propyl-0-butyl or ₄ O-iso-propyl-O-butyl phosphoric acid diester chloride and

__ the corresponding thiono analogues, furthermore O, S-dimethyl, O, S-diethyi, O ₁ S-di-n-propyl, 0, S-di-iso-propyl, 0, S-di-n- butyl, O, S-di-iso-butyl, O-ethyl-Sn-propyl, O-ethyl-S-iso-propyl, O-ethyl-Sn-butyl, O-ethyl-S-secbutyl , On-propyl-S-ethyl, on-propyl-S-ico-propyl,

_3Q on-butyl-Sn-propyl and O-sec-butyl-S-ethylthiol

phosphoric diester chloride and the corresponding thio-analogues, furthermore O-methyl-, O-ethyl-, on-propyl-, 0-hexypropyl- »on-butyl-, O-iso-butyl- or O-sec-butylmethane or -ethane, n-propane, -n-butane, iso-bu-tan-j-eec-butane or, -phenyl-phoephonsaureeeterchlorid

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and the corresponding Thionoanalogen, and O-methyl-N-methyl-, O-methyl-N-ethyl-, O-methyl-Nn-propyl-, O-methyl-N-iso-propyl _(O-ethyl-N- methyl, O-ethyl-N-ethyl, O-ethyl-Nn-propyl, O-ethyl-N-isopropyl, on-propyl-N-methyl, on-propyl-N-ethyl , On-propyl-Nn-propyl, on-propyl-N-isopropyl, O-iso-propyl-N-methyl, O-iso-propyl-N-ethyl, O-iso-propyl-Nn propyl, O-iso-propyl-N-isopropyl, on-butyl-N-methyl, on-butyl-N-ethyl, on-butyl-Nn-propyl, on-butyl-N- iso-propyl, 0-iso-butyl-N-methyl, O-iso-butyl-N-ethyl, 0-iso-butyl-N-propyl, 0-iso-butyl-N-iso-propyl , O-e-Butyl-N-methyl, O-sec-butyl-N-ethyl, O-sec-butyl-Nn-propyl, and O-sec-eutyl-N-hexypropyl-phosphoric acid monoester amide chloride and the corresponding thiono analogues.

The process step (d) for the preparation of the compounds

of the general formula (I) is preferably carried out with the concomitant use of suitable solvents and diluents. As such, virtually all inert organic solvents come into question. These include in particular aliphatic and aromatic, optionally chlorinated

Hydrocarbons, such as benzene, toluene, xylene, gasoline,

Methylene chloride, chloroform, carbon tetrachloride, chlorobenzene or ethers, such as diethyl and dibutyl ether, dioxane, furthermore ketones, for example acetone, methylethyl, methylisoprppyl and methyl isobutyl ketone, and also nitriles, such as acetonitrile and propionitrile,

As acid acceptors, all common acid binders can be used »have proven themselves special

Alkali carbonates and alcoholates, such as sodium and 35

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Potassium carbonate, potassium tert-butoxide, and also aliphatic aromatic or heterocyclic amines, for example triethylamine, trimethylamine, dimethylaniline, dimethylbenzylamine and pyridine. «

The reaction temperature can be varied within a wide range. In general, one operates zv / iechen O ⁰ C and 100 ⁰ C, preferably at 20 ° C to 60 ⁰ C,

The reaction is allowed to proceed generally at atmospheric pressure,

To carry out process variant (d), the starting materials are usually employed in an equivalent ratio. An excess of one or the other component brings no significant advantages. The reactants are usually combined in one of the abovementioned solvents in the presence of an acid binder and stirred at elevated temperature to complete the reaction for one or more hours. Thereafter, the mixture is treated with an organic solvent, e.g.

Toluene, and the organic phase works in a conventional manner by washing, drying and distilling off the solvent.

The compounds of general formula (I) are usually in the form of oils, which often can not be distilled without undecomposed, but by so-called "Andestillieren", i. freed by prolonged heating under reduced pressure to moderately elevated temperature of the last volatile fractions and thus purified

«The refractive index is used for their characterization ·

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As already mentioned several times, the compounds of the general formula (I) obtainable according to the invention are distinguished by an outstanding insecticidal, acaricidal and nematocidal action. They have an effect on plant, hygiene and storage pests and on the veterinary sector "They have a good action against sucking as well as eating insects and mites with low phytotoxicity"

For this reason, the compounds of the general formula (I) obtainable according to the invention can be successfully used as pesticides in crop protection and in the hygiene, storage and veterinary sectors.

Many of the compounds obtainable according to the invention and

their use is known and described e.g. in DE-OS 26 43 262, US-PS 4 127 652, EP-A 0 009 566, ÜS-PS 4 325 948 »ÜS-PS 4 444 764 and US-PS 4 429 125.

As already explained above, according to the invention

According to the process according to the process steps (a) to (d), it is possible to easily prepare the valuable compounds of the general formula (I) in smooth reactions, giving excellent overall yields

The process (a) to (d) according to the invention will be described

opens in a surprising way by the special combination of process steps and by the partial use of this emerging new compounds a way that allows a previously unattainable cost-effective production of the compounds of general formula (I).

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Since the individual intermediates are stable and can be stored for a long time, especially in the case of their isolation, the inventive method also allows an extraordinary flexibility in production, so that when the need for the end products rapidly demand-oriented production is possible, which in particular the climatic strong seasonal variations in the plant protection area can be very important.

embodiments

In the following, the processes (or process stages) and compounds according to the invention are to be explained by the following preparation examples:

All percentages are by weight unless otherwise specified.

A) Process for the preparation of the compounds of the general formula (IV)

Process variant al):

Example A 1:

_0H X HCl

- 44a -

13.6 g (0.1 mol) of pivalamidine hydrochloride are added in portions to a solution of 9 g (0.1 mol) of 1,3-diamino-2-propanol in 30 ml of ethanol. The mixture is refluxed for 90 minutes, cooled to room temperature and treated with 70 ml of diethyl ether. The precipitated product is filtered off with suction.

- 45 -

This gives 19 g (99 Y. of theory) of 2-tert-butyl-5-hydroxy-S ^ Sio-tetrahydropyriraidin hydrochloride in the form of colorless, highly hygroscopic crystals,

Example A2 i

To a solution of 13.5 g (0.15 mol) of 1,3-diamino-2-propanol in 30 ml of ethanol are added in portions 22.8 g (0.15 mol) of pivalyliminoethyl ether hydrochloride and the mixture is boiled for 2 hours reflux. Analogously to the work-up described under Example 1, 28.5 g (99 % of theory / 2-tert-butyl-5-hydroxy-3,4,5,6-tetrahydropyrimidine hydrochloride are obtained.

Analogously to Examples A1 and A2 and taking into account the details in the description of the process variant (a) according to the invention, the compounds of the formula (IV) listed below are obtained:

Table 6: R ^ v ^ N * ^!

H ^ N ^ v ^^ oH ^{x HC1 (IV)} Ex, -Nr, R

A 3 -C ₃ H ₇ -n

A4 H

A 5 -CH ₃

A 6 -N (CH ₃ ) ₂

^{A 7} " ^C 2 ^H 5

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^'46 "2 8 3 3

Expl R Fp [ ⁰ C]

A

Process variant a2):

Example AIP 15

N (CH ₃ ) ₃ C- < f

/ \ (CH ₃ ) ₃ C-CO ₂ ^e

306 g (3 mol) of pivalic acid and 135 g (1.5 mol) of 1,3-diamino-2-propanol are boiled in 3 1 xylene for 22 hours on Wasserabscheider «Thereafter, ca, 55 ml

Water is separated, allowed to cool, drained and

dries.

This gives 325 g (84 % of theory) of white crystals of melting point 154 ⁰ C.

Analogously to Example AlO, the following new compounds of formula IV are obtained:

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/ 83399

R - <) - OH Ζ ^θ

example

A12

A13 A14 yield phys, Y, the data theory

All (C ₂ Hg) ₂ CH-

benzyl

CM ₃ OCH ₂

A15 CH ₃ - (C ₂ Hg) ₂ CHCO ₂ 77.4 yellow

oil

Benzyl-CO ₂

CH ₃ OCH ₂ CO ₂ *

CH ₃ CO ₂ ⁶

60.3 red oil 91.2 Mp, 152 ⁰ C 78.4 Mp, 92 ^° C 83.3 yellow hydroscope crystals

Variant a2): Example A16

441 (3 MoJ) di-pivalic acid salt of 1,3-diamino-propanol-2

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e H ₃ N-CH ₂ X

(CHg) ₃ C-CO ₂ J CH-OH mp. 158 ⁰ C

" ^J 2 HqN-CH ₂ -

are cooked in 3 1 xylene for 22 hours on a water. The work-up is carried out as in Example AlO.

B) Process for the preparation of the compounds of the general formula (IVa)

Example Bl

(CH ₃ )

57.7 g (0.3 mol) of 2-tert-butyl-5-hydroxy-3,4,5,6-tetrahydropyrimidine hydrochloride are dissolved in 100 ml of water and mixed with 20 ml of 45 percent sodium hydroxide solution. The precipitated product is sucked off. Men thus obtained 32.7 g (70 X of theory) of 2-tert-butyl-5-hydroxy-3,4,5,6-tetrahydropyrimidine in the form of colorless crystals with a melting point of 210 ⁰ C.

Analogously to Example Bl and taking into account the information in the description of the process stage (b) according to the invention, the compounds of the formula (IVa) listed below are obtained

Table 7t

N \

(IVa)

N ν

u - ^f

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Table 7 Example no. R

B2 - ^C 3 ^H 7 ~ ⁿ

B3 H

B4 _-CH3

B5 -N _(CH3 J ₂ B6

Example B9

(CH _{3) 3} C

Dissolve 12.9 g (0.05 mol) of pivalic acid salt of 5-hydroxy-2-tert-butyl-tetrahydropyrimidine in 60 ml of water and is a strong base ion exchanger (MP 500 mp, Lewatit = W) is added. The mixture is stirred for about 5 minutes, filtered off and concentrated, the aqueous mother liquor in vacuo (steam jet) at 30 ⁰ C a. There remain 7.4 g of 5-hydroxy-2-tert-butyltetrahydropyrimidine (free base) in the form of white crystals. This corresponds to a yield of 94.9 % of theory.

C) Process for the preparation of the compounds of general formula (V) [Process (c)]

Example Cl ; 10

(CH ₃ ) ₃ C- <^ -O

To 15.8 g, 4,5,6-tetrahydro-2-tert-butyl-5-hydroxypyrimidine in 80 ml of water, 10.4 g (0.066 mol) of potassium permanganate are added dropwise in portions over about 20 minutes while cooling, so that the reaction temperature does not rise above 40 ° C. After the addition, the mixture is stirred for one hour in a water bath, then at 90 ° C. for 10 minutes and then filtered off with suction. The filtrate is adjusted to pH 4-5 at room temperature with concentrated hydrochloric acid for about one hour allowed to stand in an ice bath, the crystalline precipitate of 5-hydroxy-2-tert-butyl-pyrimidine is filtered off with suction and dried in air (mp: 132 ⁰ C),

Analogously to the example Cl and taking into account the information in the description of the process step (c) according to the invention, the compounds of the formula (V) listed below are obtained:

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Table 8!

C7 <H>

Example C9 25

(CH ₃ ) ₃ C- </ -OH

(V)

Example no. R Fp [ ⁰ C]

C2 ~ ^c 3 ^H 7 " ⁿ 117 C3 H 216 C4 -CH ₃ 173 C5 -N (CH ₃ ) ₂ 164 C6 -C H 149

C8 C ,)

A mixture of 5.0 g (0.032 mol) of 3,4,5,6-tetrahydro-2-tert-butyl-5-hydroxypyrimidine (99X), 11.8 g (O ₁ 10 mol) of potassium tert-butyl. -butcnolate (cat 95 X) and 25 g of i-butanol is at 60 ⁰ C in an oxygen atmosphere under

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Normal pressure stirred vigorously «The oxygen consumption is measured by a gas burette. After 30 minutes, the oxygen uptake comes to rest after a total intake of 0.038 mol of oxygen.

For working up, the reaction mixture is mixed with 5 ml of water. The t-butanol is distilled off under reduced pressure, the residue is taken up in 50 ml of water and acidified to pH = 4.5 with half-concentrated hydrochloric acid. Then, 3 × is extracted with diethyl ether, which is organic. dried over sodium sulfate and the solvent evaporated, leaving 1.98 g of crystalline residue containing 88.2 % of Z- tert -butyl-5-hydroxypyrimidine, corresponding to a yield of 35.9 X,

Example ClO

Procedure as Example C9 with the difference that 0.10 g of copper (II) oxide are added. After a reaction time of 20 minutes, 0.035 mole of oxygen is taken up.

To isolate the product, the Reaktionsgemiech is hydrolyzed with 5 al water, the solvent was distilled off under reduced pressure and the Rücketand taken up in 50 ml of water. After filtration to separate the Kupferoxidhydrats the aqueous solution is acidified with hslb concentrated hydrochloric acid to pH 4.5, extracted with diethyl ether, the ethereal phase over

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Dried sodium sulfate and evaporated, as a residue 3.71 g of crystalline product containing 89.4 V, 2-tert. Butyl-5-hydroxypyrimidine, corresponding to a yield of 68.1 '/ ,,

Example CIl 10

Procedure as in Example C9 with the difference that 0.10 g of CuO and additionally 0.10 g of MnO ₂ are added as a catalyst, working up as in Example ClO.

* 5 crude product 4.0 g with a content of 91.3 * /. 2-tert-butyl-5-hydroxypyrimidine, corresponding to a yield of 7 5.0 * / ..

Example C12 20

Procedure as Example C9 with the difference that 0.10 g of cobalt (11) chlorine id are added. Work-up as in example ClO. Yield 49.7 · / ,.

Example C13

A mixture of 6.50 g / 0.025 mol) of the salt of 3,4,5,6-tetrahydro-2-tert-butyl-5-hydroxypyrimidine and pivalinic acid, 14.5 g (0.123 mol) of potassium tert-butyl, butanolate (0.95 '/.) And 40 g of t-butanol and 0.08 g Kupf he (11) oxide is stirred vigorously at 60 ⁰ C in an oxygen atmosphere under atmospheric pressure. After 30 minutes reaction time, the oxygen uptake is at a total uptake

of 0.31 mole finished, 35

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" ⁵⁴ " 2 0 3 3 9 9

Work-up as in example ClO

 5

Crude product 5.70 g with a content of 45.5 V, 2-tert-butyl-5-hydroxypyrimidine, corresponding to a yield of 67.7 '/.,

Example C1 4

A mixture of 5.0 g (0.032 mole) 3,4,5,6-tetrahydro-2-tert-butyl-5-hydroxypyrimidine (99%), 4.0 g sodium hydroxide (0.10 mole) 25 g Dimethyl sulfoxide and 0.10 g of copper (11) oxide is stirred vigorously at 60 ^° C. in an oxygen atmosphere at atmospheric pressure. After 60 minutes, the oxygen uptake is complete with a total uptake of 0.039 mol.

For product isolation, the dimethyl sulfoxide is under

Heat in vacuum as completely evaporated, the solid residue was then taken up in 50 ml of water and the aqueous alkaline solution to separate the Kupferoxidhydrats filtered. The filtrate is acidified to pH = 4.5, extracted with diethyl ether, the ether phase dried over sodium sulfate and evaporated. 4.15 g of crystalline product containing 88.1 * /, 2-tert-butyl-5-hydroxypyrimidine, corresponding to a yield of 75.1%, remain as residue .

Example C15

A mixture of 5.0 g (0.032 mol) 3,4,5,6-tetrahydro-2-tert-butyl-5-hydroxypyrimidine (99:54), 6.6 g (0.10 mol) 35

LeA_25713 foreign

Potassium hydroxide (about 85 '/.), 40 g of V-picoline, 0.1 g of copper oxide and 0.1 g of manganese dioxide is stirred vigorously in an oxygen atmosphere at 90 ° C under atmospheric pressure. During 4 hours, 0.038 mole of oxygen is taken up,

Work-up as in example ClO,

Crude product 3.05 g containing 68.3 '/ 2-tert-butyl-5-hydroxypyrimidine, yield 42.0 54.

Example C16

A mixture of 5.0 g (0.032 mol) of 3, 4,5,6-tetrahydro-2-tert-butyl-5-hydroxypyrimidine (99:54), 11.8 g (0.10 mol) of potassium tert , butanolate (95 54), 40 g of dimethylformamide and 0.10 g of copper (11) oxide is stirred in an oxygen atmosphere at 60 ° C, After 15 minutes, the oxygen uptake is completed at a total uptake of 0.036 mol,

Work-up as in Example ClO, yield 55.9%

D) Process for the preparation of the compounds of

General formula (I) [Process variant (d)]

Example of the Dl

/ ^{N ==} \ _ "

ISO-C ₃ H ₇ -C // -O-P (OC ₂ H ₅ ) 2 Le A 25 713-foreign countries

A mixture of 300 ml of acetonitrile, 13.8 g (0.1 mol) of 2-iBO-propyl-5-hydroxy-pyrimidine, 20.7 g (0.15 mol) of potassium carbonate and 18.8 g (0.1 mol ) 0,0-Diethyl-thionophosphorsäurediesterchlorid is stirred for 2 hours at 45 ⁰ C then poured the reaction mixture into 400 ml of toluene and washed twice with 300 ml of water, the toluene solution is dried over sodium sulfate and evaporated in vacuo The residue distilled in a high vacuum.

This gives 17.4 g (62 % of theory) of O, O-diethyl-O- [2-iso-propyl-pyrimidin-5-yl] -thionophosphorsäureester in the form of a brown oil with a refractive index nS ¹ = 1.4970 ,

In an analogous manner, the following compounds of the formula (I)

II / 0R ²

getting produced:

LeA 25713-foreign countries

Table 9;

- 57 -

Example

No. F ²

Refractive X prey indox (X d.Th.)

D ₂ C ₃ H ₇ -I CH,

C ₃ H ₇ -I 74 ng ¹ S, 5102

D3 CH,

OCH,

C ₃ H ₇ -I 66 ng ⁴ S 1.5080

D4 C ₂ H ₅ SC ₃ H ₇ -n C ₃ H ₇ -IS

69

26 n _D : 1.5284

D5 C ₉ H

2 "5

C ₃ H ₇ -I 26 74 n _D J1.5570

^{D6 C} 2 ^H 5

C ₃ H ₇ -I 32 82 n _D : 1.4630

Ώ7 C ₂ H ₅ NH-C ₃ H ₇ -IC ₃ H ₇ -I 57

32 n _D S1,5057

D8 C ₃ H ₇ -n

D9 C ₂ H ₅ OC ₂ H ₅ CH ₃ 73

92

32 n _D s 1,4929

32 n _D S 1.4992

DlO C ₉ H

2 "5

CH _: 32 S 80 n _D : l, 5169

Le A 25 713-foreign countries

- 58 -

2 ö 3 3 9 9

Table 9 - Continued

Ex. No. Aue-refraction X prey index (X d.Th.)

DIl C ₂ H ₅ OC ₂ H ₅

32 S 80 n ₀ S1.5643

D12 C ₂ H ₅ C ₂ H ₅

32 n _D s 1,5827

D13 C ₂ H ₅ OC ₂ H ₅ H 32 n _D S 1.5028

20

D14 C ₂ H ₅ OC ₂ H ₅ "C ₂ H ₅ S 84 n _D : 1.5014

20 D15 C ₂ H ₅ OC ₂ H ₅ -C ₃ H ₇ -n S 60 n ^ S1, 4833

D16 C ₂ H ₅

OC ₂ H ₅ -C ₄ H ₉ -n S 94 n _D S1,4958

D17 C ₉ H

2 "5

OC ₂ H ₅ -C ₄ H ₉ -t 26 S 61 n _D : 1.4902

D18 C ₂ H ₅ OC ₂ H ₅

23 n _D : l, 5158

D19 C ₂ H ₅ -NHOC ₃ H ₇ -I- (H> S 51

23 n _D : 1.5246

D20 CH ₃ -OCH ₃

23 S 64 n _D S 1.5287

Le A 25 713-foreign countries

- 59 -

Table 9 continuation

Eg no,

physical data

[Refractive · off. index / X prey Schmolz- (V. d.Th.) point ⁰ C]

D21 C ₂ H ₅ OC ₂ H ₅ S 78 n _D ⁴ 5l, 514?

D22 C ₂ H ₅ NHC ₃ H ₇ -I 49

D23 CH ₃ OCH ₃ - t n 24 _D: 1.5390

D24 C ₃ H ₇ -n OC ₂ H ₅ n 25 _D 1.5128 ί

D25 C ₂ H ₅ NHC ₂ H ₅

S 74 n _D : l, 5310

026 C ₂ H ₅ OC ₂ H ₅

D27 C ₂ H ₅ OC ₂ H ₅ D 28 C ₂ H ₅ OC ₂ H ₅

23 n _D : l, 5164

D29 C ₂ H ₅ OC ₃ H ₇ -Ii - \ H Le A 35 713-foreign countries

- 60 -

2 8. ^ 399

Table 9 continuation

Item no.

physical, data

[Refractive index / X prey. Melting point (X of the least) point ⁰ C]

D30 C ₂ H ₅ CH 25 S 72 n _D ! 1.5428

D31 C ₂ H ₅ OC ₂ H ₅

D32 C ₂ H ₅ NHC ₃ H ₇ -I

D33 C ₂ H ₅

D34 C ₂ H ₅ SC ₃ H ₇ -n 25 n _D ! 1.5815

D35 C ₂ H ₅

D36 C ₂ H ₅ NHC ₂ H ₅

23 n _D s1,5329

037 C ₂ H ₅ SC ₃ H ₇

D38 C ₂ H ₅ C ₂ H ₅

Le A 25 713-AU3land

- 61 -

Table 9 continuation

Eg _r Nr, R '

physikal. dates

[Refraction off. index / X prey melting (X d.Th,) point ⁰ C]

D40 C ₃ H ₇ -I CH ₃ 26 n _D S1, 5233

D41 CH ₃ NHC ₃ H ₇ CH ₃ -I D42 NHCH ₃

S 66 n _D ~ S1,5460

043 C ₂ H ₅ NHCH ₃

D44 CH ₃ NHC ₂ H ₅ D45 C ₂ H ₅ NH-C ₃ H ₇ -I

23 n _D 5 1.5247

D46 C ₂ H ₅ OC ₂ H ₅ >

H ₃ C

D47 C ₂ H ₅ OC ₃ H ₇ -I -C ₃ H ₇ -I

23 S 92 n _D Jl, 4910

Le A 25 713 -Outland

- 62 -

Table 9 continuation

Ββρ

No. R ²

phyeikal. dates

CBref-Ausindex / X prey · melting (X d.Th.) point ⁰ C]

D48 C ₃ H ₇ -IC ₃ H ₇ -I -OC ₃ H ₇ -I

D53

^C 2 ^H 5

D49 C ₄ H ₉ -t C ₂ H ₅ -OC ₃ H ₇ -IS

D50 CgHj-i C ₂ H ₅ -OC ₄ H ₉ -SS

D51 C ₄ H ₉ -t C ₂ H ₅ -OC ₄ H ₉ -SS

D52 C ₄ H ₉ -t C ₃ H ₇ -J-OC ₃ H ₇ -IS

-OC ₃ H ₇ -IS

nS °: 1,4869 nS ° 11,4917 nS ° J1,4960 nS ² «1,4935 ng ⁸ : 1,4857

ng ² : l, 5516

D54 C ₄ H ₉ -t C ₂ H ₅ "NHC ₂ H ₅

D55

C ₂ H ₅ -OC ₄ H ₉ -SS

ng ¹ : 1.5100

D56

D57 C ₃ H ₇ -I

-n-OC ₃ H ₇ -HS

ng'i1,4915

Le A 25 713 abroad

Claims (5)

- 63 - claims 1. Process for the preparation of the compounds of general formula (I) (I) in which R is hydrogen, alkoxy, alkylamino, dialkylamino or optionally substituted radicals from the series alkyl, cycloalkyl and aryl, R ^{1 represents} optionally substituted radicals from the series alkyl, alkoxy, alkylthio, mono- or dialkylamino and phenyl, R ^{2 is} optionally substituted alkyl and Y is oxygen or sulfur, thereby gsksnnzelehnet, dsl nan al) Compounds of the general formula (Ha) (Ha) Le A 25 713-foreign countries - 64 - in which
5 R has the meaning given above, ft R ^{3 is} amino or the group XR ⁴ , in which
10 X is oxygen or sulfur and R ^{4 is} methyl or ethyl, with 1,3-diamino-2-propanol of the formula (III) NH ₂ -CH ₂ \ CH-OH (III) or its acid addition salts, optionally in the presence of diluents at temperatures between ^{0 0} C and 120 ⁰ C.
25 a2) or when carboxylic acids of the formula (lib) R ⁵ -CO ₂ H (lib) in which R ^{5 has} the meaning given above for R except hydrogen, Le A 25 713-foreign countries with 1 | 3-diamino-2-propanol of the formula (III) H ₂ N-CH ₂ \ CH-OH (III) "2 2 optionally in the presence of diluents at temperatures between 120 ⁰ C and 250 ° C; or a3) if the carboxylic acid salts of the 1,3-diamino-2-propanol of the formula (lic) Γ ς ΘΊ H ₃ N-CH ₂ \ R ⁵ -CO ₂ CH-OH (lic) 2
20 in which R ^{5 has} the meaning given above on Temperati
heated, Temperatures between 120 ⁰ C and 25O ⁰ C. and the forming 5-hydroxy-3,4,5,6-tetrahydropyriraidine salts of the general Formula (IV) N-CH ₂ \ χΉ R- <c (IV) Le A 25 713-foreign countries - 66 - in which 5 Z is chlorine or R ⁵ -CO ₂ where R ^{5 has} the abovementioned meaning and R has the meaning given above has 10 optionally isolated and b) if appropriate from this with a base, the 5-hydroxy-3, 4,5,6-tetrahydropyrimidines of the general formula (IVa) N-CH ₂ / H RC C (IVa) ^ N) H in which R has the meaning given above, releases and then c) either the 5-hydroxy-3,4 _# 5,6-tetrahydropyrimidine Salts of the general formula (IV) N-CH ₂ / H RC C (IV) Le A 25 713-foreign countries "* ^r " 2 8 3 3 in which Z is chlorine or R ⁵ -CO ₂ , where R ^{5 has} the meaning given above and R has the meaning given above has 10 or the free S dine of general formula (IVa) N-CH ₂ \ / H RC C (IVa) N-CH ₂ ^ N) H in which R has the meaning given above « optionally after isolation to give the compounds of general formula (V) Ν "Λ R- <"^ -OH (V) in which the meaning given above has oxidized or dehydrated and then Le A 25 713-foreign countries - 68 - d) the compounds of the formula (V) ", if appropriate after their isolation, with compounds of the general formula (VI) Il .. OR ²
Hal - P (VI) ^ ¹ in which Shark stands for halogen and 1 2
Y, R and R have the abovementioned meaning, if appropriate in the presence of an acid binder and if appropriate in the presence of a solvent, and the compounds of the general formula (I) are isolated. 2. The method according to claim 1, characterized in that in formula (I) R is hydrogen, for alkoxy having 1 to 12 carbon atoms, for mono- or di-alkylamino having in each case 1 to 6 carbon atoms in the alkyl moiety, for alkyl optionally substituted by C ₁ -C ₄ -alkoxy or C ₁ -C ₄ -alkylsulfonyl with 1 to 12 carbon atoms, optionally substituted by C ₁ -C ₄ -alkyl-substituted cycloalkyl having 3 to 8 carbon atoms, and optionally substituted by C ₁ -C ₄ alkyl, C ₁ -C ₄ -alkoxy or C ^ C ^ alkylsulfonyl-substituted aryl with 6 to 10 carbon atoms. - 69 - j ι « 3. The method according to claim 1, characterized in that in formula (I) R is hydrogen, alkoxy having 1 to 6 carbon atoms, mono- or Oialkylamin each having 1 to 4 carbon atoms in the alkyl moiety or optionally substituted by methoxy, ethoxy, methylsulfonyl or ethylsulfonyl alkyl having 1 to 6 carbon atoms, optionally substituted by methyl or ethyl cycloalkyl with 3 to 6 carbon atoms ι and optionally substituted by methyl, ethyl, methoxy, ethoxy, methylsulfonyl or ethylsulfonyl phenyl. 4. The method according to claim 1, characterized in that in formula (I) R is methyl, isopropyl or tert-butyl. 5. Process according to claims 1 to 3, characterized in that in formula (I) R ¹ ethoxy, R ² for ethyl or s-butyl and Y stand for sulfur.