Methods and devices for the trituration of mixtures

The present invention relates to new phosphoric acid amidohalides of the formula I, r₂-n ^R1

<img file="IL34419A_D0001.tif" />

wherein R^

R and R,

3

Y ¹

F ^Xo /X ^xc=c ' ^xC00R, ch₅ נ is hydrogen or lower alkyl of 1 to 3 carbon atoms, are lower alkyl of 1 to 5 carbon atoms, is hydrogen or chlorine, is oxygen or sulphur, and is chlorine on bromine!

The compounds of formula I are useful as intermediates in the production of biocidally active phosphoric acid esters. Processes for the production of the compounds also form part of the present invention.

In accordance with the processes of the invention a compound of the formula I may be obtained by:

a) reacting a phosphoric acid halide of formula II, ^YA

II/ p-o-c-c.

’ ^XCOOR lil-jZ

<img file="IL34419A_D0002.tif" />

II

150-5063 wherein Ry X, Y and Z have the above significance, with an equivalent amount of an amine of formula III,

R R₂NH III wherein and R^ have the above significance, in the presence of an acid acceptor, or

b) reacting a compound of formula IV,

Y

R -N— p-z

C I I . »1 ^z

IV wherein Ry Ry Y and

Z have the above significance, with a compound of formula V,

0

I II

CH -C-CH-C-OR, V ⁵ I ³

X wherein R^ and X have the above significance, in the presence of an acid acceptor.

The production may be effected as follows:

In accordance with process a) an equivalent amount of an amine of formula III in the presence of an acid acceptor, e.g. triethylamine, trimethylamine, dimethyl aniline, diethyl aniline or sodium carbonate, is added at a temperature of -20* to +50’C, preferably at -10’ to room temperature, to a compound of

150-5063 formula II in a solvent which is inert under the reaction conditions, e.g. an aromatic hydrocarbon such as toluene or xylene, a halogenated hydrocarbon, e.g. chlorobenzene or chloroform, or dioxane, during the course of 1/2 to 2 hours. The precipitate which generally results is filtered off and the filtrate is washed with water. The solvent is subsequently removed in a vacuum at a bath temperature of approximately 20° to 50°C. The residue is subsequently distilled in a high vacuum or, in the case of compounds which cannot be distilled, is crystallized.

In accordance with an embodiment of process a) it is possible to employ a second equivalent of an amine of formula III as acid acceptor. In this reaction an aqueous solution of the amine of formula III may be employed, and this is added to the compound of formula II.

Process a) may likewise be effected by reacting phosphorus oxychloride,,phosphorus oxyhrnmide-, phosphorus thioehloride.or phosphoric nhrnm-Mc with an acetoacetic ester of formula V, in which Τζ. and X have the above significance, in the presence of an acid acceptor and, without isolating the resulting compound of general formula II, adding an equivalent amount of the compound of general formula III, in the presence of an acid acceptor, to the reaction mixture. ..

In accordance with process b) a compound of formula

V is added, generally at -10 to +50°C, to a compound of formula IV, in an inert solvent, e.g. toluene or chlorobenzene, or optionally

130-3065 without solvent, and an acid acceptor, e.g. triethylamine, is added dropwise to the mixutre. After working up in the usual manner, the described compounds are obtained.

The compounds of formula I may be characterized in the usual manner by their physical constants.

Most of the compound of formula I obtained in accordance with the processes of the invention has a cis configuration in the crotonic acid radical, and only a small amount of the compound I has a trans configuration. The composition of the stereoisomeric forms of the compounds of formula I may be determined in known manner employing an NMR spectrum.

The production of compounds of formula II may be effected by reaction of a phosphorus, oxychloride w oxybromMe, or phosphorus‘ thiochloride -er thiobromldo, with an acetoacetic ester of the above formula V, in which signifies a lower alkyl radical containing 1 to ל carbon atoms and X signifies a hydrogen or chlorine atom, in the presence of an acid acceptor.

The compounds of formula I obtained in accordance with the processes of the invention may be used as intermediates for the production of valuable biocides, e.g. insecticides. The processes of the invention open the possibility of producing the new compounds which may be used as intermediates in an economical and practical process. ........ _ .. . .............

The new compounds of formula I react, for example, with alcohols, thioalcohols, phenols, thiophenols or amines in - . the presence of an acid acceptor with the exchange of the chlorine atom on the phosphorus atom for alkoxy, alkylthio, phenoxy, thiophenyl, or amino radicals.

(

150^5065

Thus, for example, compounds of formula I may be employed In the production of compounds of. formula VI,

<img file="IL34419A_D0003.tif" />

wherein R^, ^R2

R , X and Y have the above significance, and

R^ is an alkyl group of 1 to 4 carbon atoms.

The compounds VI are thus prepared by reaction with an equivalent amount of an alcohol of formula VII,

R₄0H VII wherein R^ has the above significance, in the presence of an acid acceptor, such as described above.

The compounds VI posses insecticidal,acaricidal and nematocldal properties, and may be used as such in conventional manner. Thus, for example, formulations containing between 2 and 90 % by weight of active agent, preferably between 5 and JO ¢, may 15 be employed in combatting insects and/or acarids and nematodes.

In the following non-limitative Examples all temperatures are indicated in degrees Centigrade.

_ ס130-5063

<td> Example 1:</td><td> Production of 0-(l-n1ethoxycarbony 1-1-propen- 2-yl)-N-methyl-phosphoramido-chloridate (process a)</td>

<td> Cl '</td><td> 0 ^Ρ-ΟΟ=ΟΗΟΟΟΟΗ, / י s</td>

<td> CH^HN ^/</td><td> CH_?</td>

58.5 g (Ο.25 mols) of O-(l-methoxycarbonyl) l-propen-2-yl)-phosphoro-dichloridate are dissolved in 300 co of.chlorobenzene. A mixture of 7.8 g (0.25 mols) of methylamine in 3θ S of chloroform and 25.5 g (θ.25 mols) of triethylamine as well as 100 cc of chlorobenzene are added dropwise to this solution at 20° during the course of 72 hour.

After the addition is completed, the mixture is stirred for a further hour, the precipitated triethylamine hydrochloride Is filtered off, the solvent is removed by evaporation and the resulting product is distilled at a pressure of 10 mm of Hg. Redistillation yields pure 0-(l-methoxycarbonyl-l-propen-2-yl)-N-methylphosphoramido-chloridate which has a boiling point of

95-97° at a pressure of 5.10 mm of Hg. It has a re20 fractive index of η _β = 1.482.

<td> Analysis:</td><td> c₆H</td><td> CINO^P</td><td> Molecular</td><td> weight : 227.6</td>

<td> Found</td><td> c</td><td> 31.9 %</td><td> H 5.2 % Cl</td><td> 16.0 % N 6.0 %</td>

<td> Calculated</td><td></td><td> 51-7 %</td><td> 4.9 %</td><td> 15.6 % 6.2 %</td>

<td></td><td> P</td><td> 13.1 £ 13.6 #</td><td></td><td></td>

150-3063

Example Production of 0-(l-methoxycarbonyl-l־propen-2yl)-Ν,Ν-diethyl-phosphoramido-chloridate (process a)

Cl 0

II ✓ P-OC=CHCOOCH (C₂H₅)₂N' CH^

76.7 g (0.5 mols) of POCl^ are dissolved in 200 cc of chlorobenzene. A mixture of 58•1 g (0.5 mols) of acetoacetic acid methyl ester and 51 g (0.5 mols) of triethylamine is added dropwise at -10° during the course of 15 minutes. After the addition is completed, the reaction mixture is stirred at 0° for 72 hour and at 20° for one hour. The reaction solution is subsequently diluted with 300 cc of chlorobenzene, is cooled to -5° and 73.I g (1 mol) of diethylamine are added to the solution at -5° during the course of 72 hour. The solution is subsequently stirred at 0° for 72 hour and at 20° for 2 hours. The resulting precipitate is subsequently filtered off, the solvent is evaporated arid the resulting product is distilled. The resulting 0-(1methoxycarbonyl-l-propen-2-yl)-N,N-diethyl-phosphoramido~ chloridate has a boiling point of 69-71° at a pressure of 5.10־^ mm of -Hg. It has a refractive index of n ²⁰ 1 ־־Λ73״

Analysis : C H^CINO^P Molecular weight: 269.7

130-3063

<td> Found</td><td> C 40.1%</td><td> H 6.7 %</td><td> Cl 12.8 %</td><td> N</td><td> 4.9 %</td>

<td> Calculated</td><td> 40.1 % P 11.1 % 11.5 %</td><td> 6.4 %</td><td> 15-1 %</td><td></td><td> 5-2 %</td>

<td> Example J_^:_</td><td> Production</td><td> of 0-(l-me</td><td colspan="2"> thoxycarbonyl-1</td><td> -propen-</td>

-y 1)-N,N-diethyl-phosphoramido-chlor!date (process b) g (0.5 mols)of triethylamine are added at +5⁰ to a mixture of 95 g (0.5 mols) of N,N-diethyl-phosphoramidochloride and 58 g (0.5 mols) of acetoacetic acid methyl ester during the course of Y2 hour. The reaction mixture is stirred at 5° for one hour and at 20° for 15 hours. 500 cc of toluene are subsequently added and the resulting precipitate is filtered off. The solvent is removed by evaporation and pure 0-(l-methoxycarbonyl-l-propen-2-yl)Ν,Ν-.diethyl-phosphoramido-chloridate is obtained by distillation in a high vacuum.

The ratio cis : trans isomer (in the crotonic acid radical) amounts to 90 : 10 (determined by the NMR spectrum).

Example 4: Production of 0-(l-methoxycarbonyl-l-propen2-yl) thionate (process b)

Cl S

P-OC=CHCOOCH^ ^: (c_־h₅)₂n/ ch₃

150-3065 t

A mixture of 51*5 S (0.25 mols) of N,Ndiethyl-phosphoramldo-thioate-dlchloride and 29 g (0.25 mols) of acetoacetic acid methyl ester is added at 20° during the course of j hours to 25.5 8 (θ.25 mols) of triethylamine. The reaction mixture is subsequently stirred at 20° for 10 hours and at 40° for 90 hours. The resulting precipitate is subsequently filtered off, the filtrate is washed with water and dried with magnesium sulphate. After distillation in a high vacuum pure 0-(l-methoxycarbonyl-l-propen-2-yl)-N,N-diethylphosphoramldo-chlorido-thionate, having a boiling point of 78-81° (5.10’3 mm of Hg),is obtained. It has a re20 fractive index of n =1.511♦

Analysis C_QH,״C1NO_XPS Molecular weight: 285.7 7 .h ע

<td> Found</td><td> c 37.4 %</td><td> H 5-9 %</td><td> Cl 12.1 %</td><td> N 4.6 %</td>

<td> Calculated</td><td> 37-8 % .</td><td> 6.0 % .</td><td> 12.4 %</td><td> 4.8 %</td>

<td></td><td> P 11.2 %</td><td> s 10.7 %</td><td></td><td></td>

<td></td><td> 10.9 %</td><td> 11.2 %</td><td></td><td></td>

Example Production of 0-(l-methoxycarbonyl-l-chloro1-propen-2-yl) chlorido-thionate (process b)

Cl S

P“OC=CC1COOCH^ n-C Η NH / CH, >1. 5

150-5063

A mixture of 48 g (0.25 mols) of N-n-propylphosphoramido-thioate-dichloride and 57.8 g (0.25 mols) of a-chloro-acetoacetic acid methyl ester in 150 cc of toluene is added to 25.5 S ef triethylamine at -5° during the course of one hour. The reaction solution Is subsequently stirred at 0° for one hour and at 20° for hours. The precipitated triethylamine hydrochloride

Is subsequently filtered off, the filtrate is washed with water, dried with sodium sulphate, the solvent is removed by evaporation and the residue is distilled; The resuiting 0-(l-methoxycarbonyl-l-chloro-l-propen-2-yl)N-n-propyl-phosphoramido-chlorido-thionate has a boiling point of 108-110° at a pressure of 5.1θ~^ mm of Hg,

It has a refractive index of η _β = 1.522.

<td> 15</td><td> Analysis:</td><td colspan="2"> C_qH, j,Cl״N0,PS Molecular weight: 506.2 0 1*1. d y</td>

<td></td><td> Found Calculated</td><td> c 51.0 % 51.4 %</td><td> H 4.7 % Cl 25.4 % M 4.5 % 4.6 % 25.2 % 4.6 %</td>

<td></td><td></td><td> P 10.4 % 10.1 %</td><td> S 10.8 % 10.5 %</td>

<td> 20</td><td> • Example 6:</td><td colspan="2"> Production of 0-(l-ethoxycarbonyl-l-propen-</td>

<td></td><td></td><td> 2-yl)-N-n</td><td> .-propyl-phosphoramido-chlorido-</td>

<td></td><td></td><td> thionate (process</td><td> a)</td>

Cl. s

X ¹¹ ;P-OC=CHCOOC״H_c/ 1 25 n-.C,H״NH^z CH, כ 7 נ _ 11 130-3063

A solution of 1J1.5 g (θ.5 mols) of 0-(,1ethoxycarbonyl-l-propen-2-yl)-phosphoro-dichloridothionate in 500 cc of toluene is added at 0° ־during the course of one hour to a mixture of 29.6 g (0.5 mols) of n-propyl amine and 51 g (0.5 mols) of triethylamine.

The reaction mixture is subsequently stirred at 0° for 2/נ hour and at 20° for one hour. The precipitated triethylamine hydrochloride is subsequently filtered off, the filtrate is washed with water, dried with Na₂S0^ and distilled. The resulting 0-(l-ethoxycarbonyl-l-propen-:.

2-yl)-N-n-propyl-phosphoramido-chlorido-thionate has a boiling point of 92° at a pressure of 5.10^ mm of Hg.

It has a refractive index of n = 1.514.

Analysis: C H,₇C1NO,PS Molecular weight: 285.7 y 1 i כ

<td> 15</td><td> Found</td><td> C 37-9 %</td><td> H 5.8 %</td><td> Cl 12.6 %</td><td> N 5.2 %</td>

<td></td><td> Calculated</td><td> 37-8 $</td><td> 6.0 %</td><td> 12.4 %</td><td> 4.9 %</td>

P 10.2 $ S 11.2 %

10.8 % 11.2 %

130-5063^

Example Production of 0-(l-iso-propoxycarbonyll-propen-2-yl)-N-ethyl-phosphoramidochlorido-thionate (process a, in the presence of water)

S ^C1-J

P-O-C=CHCOO-iC,H״ / 1 > 1

C_?HN^Z CH, ^d⁵׳h נ

12.8 g of a 70% solution of ethylamine in water (0.2 mols) are added dropwise at -3° to 277י g (0.1 mol) of 0-(iso-propoxycarbonyl-l-propen-2-yl)phosphoro-dichloridate during the course of 15 minutes while stirring. The mixture is stirred for a further 15 minutes, the oily product is separated, the residue is digested with water, dried and distilled in a high vacuum. 0-(l-iso-propoxycarbonyl-l-propen-2-yl)-Nethyl-phosphoramido- chlorido-thionate has a boiling point of 89°/5 . 10“^ mm of Hg. It has a refractive 20 index of nJ = I.5IOO.

<td> Analysis:</td><td> C_nH^ClNO_xPS ע u כ</td><td> Molecular</td><td> weight</td><td> ,: 285.7</td>

<td> Found</td><td> C 37.7 %</td><td> H 5-9 %'</td><td> Cl</td><td> 12.7 %</td>

<td> Calculated</td><td> 37.8 %</td><td> 6.0 %</td><td></td><td> 12.4 %</td>

<td></td><td> N 5.1 %</td><td> p 10.8 %</td><td> s</td><td> 11.2 %</td>

<td></td><td> 4.9 %</td><td> 10.85 %</td><td></td><td> 11.2 %</td>

The compounds of general formula I indicated in the Table are obtained in a manner analogous to that described in Examples 1 to 6. In Examples 8 to 17 the symbol Z signifies a chlorine atom.

<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td> B.P./</td><td></td><td> Analysis $</td><td></td>

<td> Exam-</td><td></td><td></td><td></td><td></td><td></td><td> Empirical ,</td><td> Mole-</td><td> mm of Hg</td><td>²⁰ת</td><td> Found</td><td></td>

<td> 1 A ת</td><td> Η,</td><td> Ηη</td><td></td><td> X</td><td> Y</td><td> formula</td><td> 2ular</td><td> °C</td><td>ⁿD</td><td> Calculated </td><td></td>

<td> |J1C</td><td> 1</td><td> 2</td><td> נ</td><td></td><td></td><td> 1 1</td><td> *eight</td><td></td><td></td><td> C H Cl N P '</td><td></td>

<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td rowspan="2"> 241,6</td><td> 4 _ Z M * * I</td><td></td><td> 54,8 5,4 14,8 6,0 12,1</td><td> 1</td>

<td> 8</td><td> Η</td><td rowspan="2"> y₅</td><td> CH,</td><td> H</td><td> 0</td><td rowspan="2"> C^jClNO^</td><td> .10675.10</td><td> *</td><td> ׳ 12,8 5,8 177 5,4 54,8</td><td></td>

<td></td><td></td><td></td><td></td><td></td><td rowspan="2"> 255,6</td><td> 4-., ״ .</td><td rowspan="2"> 1,476</td><td> 57,5 5,8 14,5 5,7 11,5</td><td></td>

<td> 9</td><td> Ή</td><td rowspan="2"> ,־,_־1</td><td> CH,</td><td> H</td><td> 0</td><td> ΟθΗ^Οϋψ</td><td> 102°/4.10</td><td> 57,6 5,9 15,9 5,5 12,1</td><td></td>

<td></td><td></td><td> ✓</td><td></td><td></td><td></td><td rowspan="2"> 269,7</td><td rowspan="2"> 11670,07</td><td rowspan="2"> 1,475</td><td> 59,9 6,5 15,6 5,5 10,8</td><td></td>

<td> 10</td><td> .Η</td><td> nCX</td><td>^c2^h5</td><td> H</td><td> 0</td><td> Ο^ϋΐΐψ</td><td> 40,1 6,4 15,1 5,2 11,5</td><td></td>

<td></td><td></td><td> ) 1</td><td></td><td></td><td></td><td></td><td rowspan="2"> 285,7</td><td></td><td rowspan="2"> 1,475</td><td> 41,7 7,0 15,2 4,8 9,9</td><td> 1 u</td>

<td rowspan="2"> 11</td><td rowspan="2"> . Η</td><td rowspan="2"> Λ</td><td rowspan="2"> iC₃H_?</td><td rowspan="2"> H</td><td rowspan="2"> 0</td><td rowspan="2"> C^H^CINO^P</td><td rowspan="3"> Sirup 9570,1</td><td rowspan="2"> 42,5 6,8 12,5 4,9 10,0 55,1 5,1 15,9 6,2 12,2'</td><td rowspan="2"> r* VI 1</td>

<td rowspan="2"> 241,6</td><td rowspan="2"> 1,474</td>

<td> 12 .</td><td> CB</td><td> CH, ר</td><td> CH,</td><td> K</td><td> 0</td><td> C״H״C1NOJ 7 1; ל</td><td> 54,8 5,4 14,7 5,8 12,8</td><td></td>

<td></td><td></td><td> &gt;</td><td> j</td><td></td><td></td><td></td><td></td><td rowspan="2"> 11470,04 5• , , ״</td><td rowspan="2"> 1,470</td><td> 45,0 7,1 12,7 75 10,5</td><td></td>

<td> 1)</td><td>^C2^K5</td><td>^C2^H5</td><td>^C2^H5</td><td> H</td><td> 0</td><td> y₁₉c1H,f «</td><td> 285,7</td><td> 42,5 6,8 12,5 4,9 10,9 56,0 5,6 25,2 4,8 9,8</td><td></td>

<td> 14</td><td> Η</td><td>^C2^H5</td><td rowspan="2"> nC,H. 5 7</td><td> Cl</td><td> 0</td><td> C₉H₁₆C1₂1^P</td><td> 504,1</td><td> 108-12%.10 ^J</td><td> 1,486</td><td> 55,5 5,5 25,5 4,6 10,2</td><td></td>

<td></td><td> •</td><td></td><td></td><td></td><td></td><td></td><td></td><td rowspan="2"> 1,489</td><td> 55,1 5,0 25,9 5,0 10,2</td><td></td>

<td rowspan="2"> 15</td><td rowspan="2"> Η</td><td rowspan="2">^C2^H5</td><td rowspan="2">^1C5^H7</td><td rowspan="2"> Cl</td><td rowspan="2"> 0</td><td rowspan="2"> V16^CW</td><td rowspan="2"> 504,1</td><td rowspan="3"> 11571.10 ^J 120-270,01</td><td rowspan="2"> 55,5 5,5 25,5 4,6 10,2 )7,2 5,4 22,1 4,7 9,4</td><td rowspan="2"> H</td>

<td rowspan="2"> 1,485</td>

<td> 16</td><td> Η</td><td> nCH</td><td> ״CH</td><td> Cl</td><td> . 0</td><td>^C1O^H18^C12^KO4^?</td><td> 518,1</td><td> 57,8 5,7 22,5 4,4 9,7</td><td> VI 0 I</td>

<td></td><td></td><td> &gt; 1</td><td> &gt; 1</td><td></td><td></td><td></td><td></td><td> (י-</td><td rowspan="2"> 1,525.</td><td> 55,8 5,1 22,5 4,0 9,9</td><td> 0</td>

<td> 17 ♦</td><td> Η</td><td> nC^</td><td> c₂B₅</td><td> Cl 1</td><td> . s,</td><td> c₉h₁₆c1₂no₃ps</td><td> 520,2</td><td> 96-775-10</td><td> 55,8 5,0 22,1 4,4 9,7</td><td> 01 VI</td>

<td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td colspan="2"></td>

.