Preparation of(dichloromethyl)pyridines by reductive dechlorination

PREPARATION OF (DICHLOROMETHYL) PYRIDINES BY REDUCTIVE DECHLORINATION (Dichloromethyl) substituted pyridines are known compounds which find utility as pesticides for the control of plant, insect and fungal pests, among others, and as intermediates for preparing compounds having the above utilities.

The present invention provides a process for preparing (dichloromethyl) substituted pyridines corresponding to the formula

<img file="IL61386A_D0001.tif" />

(CHC1₂)_p wherein X represents chloro, bromo, fluoro, phenoxy or phenoxy substituted by halogen or methoxy alkoxy of 1 to 4 carbon atoms, alkenyloxy of 2 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or carboxy; n represents an integer of from 0 to 4 and p is 1 or 2 which comprises reacting the corresponding (trichloromethyl) substituted pyridine compound under reductive dechlorination conditions, with metallic iron or a ferrous iron compound and an acid at temperatures between 80° and 120°C.

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Representative ferrous iron compounds useful in carrying out the present invention include ferrous chloride and ferrous sulfate. It is preferred to use ferrous chloride or metallic iron.

Solvents which can be employed in the practice of the present invention include, for example, acetone and the lower alkanols (C!־(^) or mixtures thereof. While the reaction can be carried out in the absence of a solvent, it is preferable that one be used.

The acid employed in the practice of the present invention can be organic or inorganic. Preferred acids include hydrochloric acid or acetic acid and mixtures of the acids can also be employed.

Representative (trichloromethyl) pyridines which can be employed in the practice of the present invention include, for example, 2-chloro-6-(trichloromethyl)pyridine, 2-chloro-4-methoxy-6~(trichloromethyl)pyridine, 2-chloro-6-methoxy-4-(trichloromethyl)pyridine, 2-chloro6־־-ethoxy-4- (trichloromethyl )pyridine, 2-chloro-6-phenoxy-4-(trichloromethyl)pyridine, 3,5-dichloro-6-(trichloromethyl)pyridine, 2-chloro-4,6-di(trichloromethyl)pyridine, 2-phenoxy-6-(trichloromethyl)pyridine,

-32-(4-chlorophenoxy)-6-( trichloromethyl)pyridine, 2-(3-fluorophenoxy)-6-(trichloromethyl)pyridine, 2-(4-fluorophenoxy)-6-( trichloromethyl)pyridine, and 2-(4-methoxyphenoxy)-6-(trichloromethyl)pyridine.

The reaction is initiated by contacting the reactants together in any order. They may all be mixed together and then heated or the pyridine compound, solvent and metallic iron or ferrous iron compound mixed together and the acid added slowly thereto.

The reaction is conveniently carried out at the reflux temperature of the mixture. Depending upon the reactants, this can be between 80° and 120°C. Temperatures below 75°C are not usually employed since the reaction rate at these temperatures is reduced and such reduced reaction rates are not practical. Temperatures above reflux, i.e. carried out at higher than atmospheric temperature, offer little or no advantage and only increase the cost of the operation.

The molar equivalent of the metallic iron or iron compound to the pyridine reactant varies depending on whether metallic iron or a ferrous iron compound is employed and whether there is one or two trichloromethyl groups on the pyridine reactant. The molar equivalent is usually between 0.50 and 3.0 moles of the metallic iron or ferrous iron compound per trichloromethyl group on the pyridine compound. In the case of metallic iron, an optimum molar equivalent of 0.50 to 1.0 mole of iron per trichloromethyl group on the pyridine compound is employed. With ferrous chloride or sulfate, an optimum molar equivalent of from 1.0 to 3.0 moles of the ferrous iron compound per trichloromethyl group on the pyridine

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-4compound has been found to be useful. The use of amounts less than the optimum amount leads to incomplete reduction, while an amount in excess of the above gives over reduction, i.e. formation of monochloromethyl or further reduction to the methyl group itself.

After the completion of the reaction, the reaction product is cooled and extracted throughly with a solvent such as chloroform, methylene chloride, toluene or tetrachloroethylene. Additionally, the reaction mixture is washed with water or dilute hydrochloric acid and dried. The reaction mixture can also be filtered to remove any insolubles. The crude product can be employed as such without further treatment, or if desired, the product can be purified by recrystallization from a solvent such as heptane, methanol, aqueous acetone or by distillation under reduced pressure.

The following examples further illustrate the present invention.

Example I: Preparation of 2-Chloro-6-(dichloromethyl)pyridine

Into a 250 milliliter (ml) flask fitted with a condenser, magnetic stirrer and dropping funnel were added 46.2 grams (g) (0.20 mole) of 2-chloro-6-(trichloromethyl)pyridine, 30 g of methanol and 9.1 g (0.16 mole) of 20 mesh iron filings (passed through sieve opening of 0.84 mm). The mixture was heated to 70°C and 30 g of concentrated hydrochloric acid was added thereto over a 5 minute period. A slight exotherm occurred and the mixture was heated and maintained

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-5under reflux (83°-86°C) for 1 hour. The reaction mixture was cooled to 45°C, and 50 ml of methylene chloride was added thereto. The mixture was filtered through diatomaceous earth and the filter cake washed thoroughly with water and then with methylene chloride. The filtrates were combined and the methylene chloride phase separated from the water phase. The product from a second run was combined with the above product mix and the mixture concentrated to a pot temperature of 95°C at 15 millimeters of mercury (mm Hg). This residue was present in an amount of 74.5 g and melted at 48^O°C. Analysis by gas-liquid chromatography (glc) showed a yield of 90.1 percent 2-chloro-6-(dichloromethyl)pyridine,

3.7 percent 2-chloro-6-(chloromethyl)pyridine and 1.7 percent 2-chloro-6-(trichloromethyl)pyridine. The 2-chloro-6-(dichloromethyl)pyridine was recovered by recrystallization from heptane and melted at 53.3°-54.0°C.

Example II: Preparation of 2-chloro-6-(dichloromethyl)pyridine

A mixture of 23.1 g (0.10 mole) of 2-chloro-

6-(trichloromethyl)pyridine, 10.0 g of methanol, 15.0 g of concentrated hydrochloric acid and 40.0 g (0.20 mole) of ferrous chloride as the tetrahydrate was stirred while heating to reflux. The mixture was a slurry which slowly became fluid and a two-phase liquid mixture resulted after 15 minutes. The mixture was maintained under reflux conditions (80°-90°C) for one and one-half hours and then cooled to 45°C. The mixture was extracted with 50 ml of methylene chloride and then 20 ml of water. The extracts were combined and the organic phase separated. Further dilution of the aqueous phase with water and extraction with 20 ml of methylene chloride gave an

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-6oil which was combined with the main extract and washed once with water. The crude product mixture was recovered in a yield of 88 g and after drying over anhydrous sodium sulfate, analyzed by glc. This analysis showed the mix to contain 82 percent 2-chloro-6-(dichloromethyl)pyridine, 4 percent 2-chloro-6-(trichloromethyl )pyridine and 14 ׳י percent unresolved impurities.

The combined product mixture of several runs carried out in a fashion similar to Example II was concentrated and distilled using a 10-plate Oldershaw column. A forecut containing the volatile impurities was separated and the main cut which boiled at 113°C at 9 mmHg was collected as a colorless liquid which solidified upon cooling. This product analyzed as 98.3 percent 2-chloro-6-(dichloromethyl)pyridine and melted at 50.0°-53.5°C.

Example III

A series of runs were conducted following the procedures of Example II employing 0.1 mole of 2-chloro-6-(trichloromethyl)pyridine and 0.2 mole of ferrous chloride as the tetrahydrate and employing different solvents, different amounts of concentrated hydrochloric acid (HC1), varied reaction times and varied reaction temperatures. The results of these runs are set forth below in Table I.

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Temperature w

TABLE I

ן*

Amount of

Run Amount of Concentrated

Number Solvent Solvent in grams HC1 in grams Time in Hours

<td></td><td> 1</td><td> None</td><td> mai</td><td> 20</td><td> 2</td>

<td></td><td> 2</td><td> Methanol</td><td> 10</td><td> 15</td><td> 1.5</td>

<td></td><td> 3</td><td> n-Butanol</td><td> 50</td><td> 10</td><td> 1.5</td>

<td> 1 sj ן</td><td> 4</td><td> Isopropanol</td><td> 20</td><td> 15</td><td> 3.6</td>

<td> 1</td><td> 5</td><td> Acetone</td><td> 11</td><td> 11</td><td> 4</td>

90-120

1 &lt;1 1

TABLE I (Continued)

<td rowspan="2"></td><td rowspan="2"> Run Number</td><td colspan="4"> ____________Product Analysis________</td>

<td> *RCHCl, Lt</td><td> *RCHjCl</td><td> *RCC1, w</td><td> Unknowns</td>

<td></td><td> 1</td><td> 95</td><td> *2</td><td> Trace</td><td> *3</td>

<td></td><td> 2</td><td> 86</td><td> Trace</td><td> *5.8</td><td> *8.2</td>

<td></td><td> 3</td><td> 82</td><td> *1.2</td><td> *1.3</td><td> *15,5</td>

<td> 1 00 I</td><td> 4</td><td> 69</td><td> MM</td><td> *31</td><td> nil</td>

<td></td><td> 5</td><td> 91</td><td></td><td> *1</td><td> N.D,</td>

00 I *R =

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N.D. = not determined

Example IV

A series of runs were conducted following the procedures of Example II employing 0.1 mole of 2-chloro-6-(trichloromethyl)pyridine and employing varying amounts of 20-mesh iron filings (passed through sieve opening of 0.84 mm), different solvents, different amounts of concentrated hydrochloric acid, varied reaction times and varied reaction temperatures. The results of these runs are set forth below in Table II.

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TABLE II

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1 מי

<td> Run Number</td><td> Solvent</td><td> Amount of Solvent in grams</td><td> Amount of Iron filings in Moles</td><td> Amount of Concentrated HC1 in grams</td><td> Time in Hours</td><td> Temperature</td>

<td> 6</td><td> Methanol</td><td> 15</td><td> 0.082</td><td> 15</td><td> 1</td><td> 86</td>

<td> 7</td><td> Methanol</td><td> 15</td><td> 0.082</td><td> 15</td><td> 3</td><td> 86</td>

<td> 8</td><td> Methanol</td><td> 15</td><td> 0.068</td><td> 15</td><td> 1.5</td><td> 85</td>

<td>⁹ 0 1</td><td> Methanol</td><td> 15</td><td> 0.068 + 0.068 after one hour</td><td> 15</td><td> 7</td><td> 85</td>

<td> 10</td><td> Methanol</td><td> 30</td><td> 0.07</td><td> 12</td><td> 4</td><td> 85</td>

H 0

I

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TABLE II (Continued) *1

<td></td><td> Run</td><td></td><td colspan="2"> Product Analysis</td><td></td><td></td>

<td></td><td> Number</td><td rowspan="2"> RCHC1_; 94.6</td><td rowspan="2"> rch₂c1 rcc!₃ 3.6 1.2</td><td> Unknowns</td><td> Comments</td><td></td>

<td></td><td> 6</td><td> 0.6</td><td> HC1 added over 5 minute period.</td><td></td>

<td></td><td> 7</td><td> 96.6</td><td> 4.3 4.1</td><td> nil</td><td> HC1 added over 5 minute period. Iron added in two portions.</td><td></td>

<td> l P P 1</td><td> 8</td><td> 96</td><td> 1.6 2.4</td><td> nil</td><td> HC1 added over 30 minute period.</td><td> 1 P P 1</td>

<td></td><td> 9</td><td> 91</td><td>.7</td><td> 6.3</td><td> HC1 added dropwise over 25 minutes.</td><td></td>

<td></td><td> 10</td><td> 91.9</td><td> 1.2 1.8</td><td> 5.1</td><td> HC1 added dropwise over 30 minutes.</td><td></td>

<td rowspan="2"> Run Number</td><td rowspan="2"> Solvent</td><td rowspan="2"> Amount of Solvent in grams</td><td colspan="2"> TABLE II (Continued)</td><td rowspan="2"> Time in Hours</td><td rowspan="2"> Temperature</td>

<td> Amount of Iron filings in Moles</td><td> Amount of Concentrated HC1 in grams</td>

<td> 11</td><td> Methanol</td><td> 15</td><td> 0.068</td><td> 15</td><td> 1.5</td><td> 85</td>

<td> 12</td><td> Methanol</td><td> 15</td><td> 0.068</td><td> 15</td><td> 2</td><td> 75</td>

<td> 13</td><td> None</td><td> 1 </td><td> 0.068</td><td> 5 + 26 grams</td><td> 1.5</td><td> 125</td>

of Acetic Acid

ST

2~7,552

TABLE II (Continued)

I

מי

<td> Run</td><td> Product Analysis</td>

<td> Number</td><td> *RCHC1, *RCH.C1 *RCC1, Unknowns נ £ £</td>

<td> 11</td><td> 90.9 2.7 Trace 6.4</td>

<td> 12</td><td> 9.2 - 41.3 49.5</td>

Comments

1/4 of HCL added over 30 minutes, remainder in 5 minutes.

HC1 added dropwise over one hour.

I

Η ω

I

82.9 14.5 -- 2.9 HC1 added at once.

P u

I *R =

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Example V: Preparation of 2-(dichloromethyl)-6-phenoxypyridine

A mixture of 1.0 g (0.0035 mole) of 2-phenoxy-6-(trichloromethyl)pyridine, 2.0 g of methanol and 1.0 g of concentrated hydrochloric acid was heated to 70°C. To this mixture was added 0.16 g (0.0028 mole) of 20 mesh (passed through sieve opening of 0.84 mm), degreased iron filings, at once. Heating was conducted at mild reflux for 0.5 hour followed by the addition of more iron filing in the amount of 0.06 g (0.0011 mole). After being heated a total of 1.5 hours, the reaction mixture was cooled, diluted with 10.0 g of chloroform and 3 ml of water and filtered to remove insolubles. The filtrate was removed and allowed to separate into aqueous and organic phases with each phase being further extracted with chloroform. The organic layer (phase) was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 0.71 grams of an amber oil (ηβ = 1.5902) which was analyzed by glc to be 85.4 percent 2-(dichloromethyl)-6-phenoxypyridine, 11.9 percent 2-(chloromethyl)-6-phenoxypyridine and 2.7 percent unreacted 2-phenoxy-6-(trichloromethyl)pyridine.