IL46306A - Preparation of beta-haloethylphosphonic acid - Google Patents

Description

PREPARATION OF fW-HALOETIIYLPHOSPHONIC ACID The present invention is a patent of addition to Patent Number 29,622. .

This invention relates to the production of the half ester and no more than 5% of Dehydrohalogena ed impurities and still more particularly to the production of B-chloroethylphosphoni acid and half esters thereof.

B-haloethylphosphonic acids are known in the art as being valuable as plant growth stimulants in the agricultural field. Thus, these compounds, particularly the chloro compound, have been used extensively as plant growth hormones for increasing crop yields of, for example, pineapples, soy beans and the like. The usefulness of these compounds is illustrated for example in the publication, Nature, Vol. 218, page 974, (1968) by Cook and Randall.

In preparation of these products, however, the process i known heretofore have not been satisfactory as they have not been able to provide a product of sufficient purity as to obviate all the toxicity effects of impurities normally contained therein. One of the most suitable procedures for the preparation of such compounds is by hydrolysis of the corresponding diester with aqueous HC1. The aqueous hydrochloric acid hydrolysis is a procedure known in the art as illustrated for example in the textbook by Kosolapoff, titled, Organophosphours Compounds, John Wiley & Sons Inc., New York (1950) page 139, which indicates that esters of phosphonic acid are readily hydrolyzed by hot hydrolysis of the diester to the desired B-haloethylphosphonic acid has been suitable to provide the highly pure products desired.

An object of this invention is to provide a new and improved process for producing B-haloethylphosphonic acids and half esters thereof.

Another object of this invention is to provide a process for producing such acids and half esters in good yields at low cost.

Still another object of the invention is to provide a new and improved provess that is particularly suitable for producing B-chloroethylphosphonic acid and its half esters.

Attainment of the above objects is made possible by the present invention which includes a controlled anhydrous proces containing' for producing B-haloethylphosphonic acid 2-407o of the half ester and no more than 5% of dehydrohalogenated impurities comprising introducing anhydrous HC1 or HBr from an outside source into a diester stable at a temperature of about 140°C to 175°C the products having the formula wherein is B-haloethyl and and represent the same or different alkyls or haloalkyls each containing no more than 6 car atoms, at a temperature of about 140°C to 165° C until a product is obtained containing about 2 to 40% of the corresponding mono- ester of the formula o II ' no more than 57. of dehydrohalogenated impurities, no more than about 57o of other impurities, and the balance β-haloethylphos-phonic acid or anhydride.

As only representative examples of diesters which may be cleaved in accordance with the process of the invention there may be mentioned: bis (2-chloroethyl) B-chloroethylphosphonate ; demethyl B-bromoethylphosphonate ; diethyl B-chloroethylphosphonate; ethyl isopropyl B-bromethylphosphonate ; gamma-bromopropyl n-hexyl B-chloroethylphosphonate; and the like. The chloro and bromo substituents may instead be iodo and/or fluoro. These diesters, and methods for their production, are generally known. They may be prepated for example by isomerization of the corresponding tris(alkyl and/or haloalkyl) phosphite containing at least one B-haloethyl group by heating, preferably in the presence of an inert organic diluent such as o-dichlorobenzene , cumene, xylene or the like at an elevated temperature such as about 160°C.

The claimed process involves a clevage or displacement as distinguished from the hydrolysis reaction disclosed in the prior art, and proceeds in two steps, the first step being more readily accomplished and involving clevage of one of the ester groups in the starting diester to produce the corresponding mono-ester according to the equation (using HC1 in the process) Equation III The second step of the reaction, represented by the following equation Equation IV is more difficult, but always results in a product substantially devoid of the precursor diester. The product usually contains small amounts of the dianhydride of the free B-ha loethylphosphonic acid which is actually equivalent to the free acid since it is readily hydrolyzed thereto when the product is applied to plants from an aqueous solution, and/or by the plant itself, The reaction could be carried to completion to produce a product devoid of the monoester precursor in Equation IV, but for reasons more fully explained below, it is essential that the reaction be allowed to proceed only until a minimum of about 2% of the monoester up to a maximum of about 40% remains in the product.

This monoester need not be removed when the product is employed as a plant growth regulator since it is also hydrolyzed during application thereof or by the plant, though with more difficulty than the dianhydride. If desired, the monoester can be removed from the product by extraction with a C^_g halohydrocarbon such as chlorobenzene , dichlorobenzene , chloroform, tetrachloroethylene , by preferably methylene chloride or entylene dichloride.

The B-ha lcethylphosphonic acid containing products of the present invention, with or without purification, may be reacted with phosphorous pentachlor ide to produce B-ha loethylphosphonyl dichloride, a valuable intermediate. In addition, and more impor-tant, they act as plant hormones and aqueous solutions containing them may be applied to growing plants to regulate growth characteristics thereof, for example the control or inhibition of apical dominance. The B-ha loethylphosphonic acids are generally sprayed onto the plants in an amount to provide between about 0.1 lb. and about 16 lbs. of the acid per acre of plants. A variety of beneficial effects are obtained including substantially increased yields of fruits and vegetables. Other growth regulatin effects are described in the Nature publication referred to above and other publica ions.

In the above described use of these products in the a ricultural field and articularl with respect to food crops, it is essential that the product be devoid of undesirable impurities or adulterants.

In carrying out the process of this invention, an. entierly unexpected phenomenon has been found to occur, namely the tendency to product dehydroha logena ted products (containing ethylenic or vinyl linkages) ; it was entirely unsuspected that dehydroha logena tion could take place in the claimed process which is carried out in the presence of anhydrous hydrogen halide, e.g. HC1 or HBr , at 140-165°C. Indeed one would predict that dehydrohalogenation would be entirely suppressed in the presence of the hydrogen halide gas at elevated temperatures. Such dehydroha lognea ed products are for obvious reasons undesirable and the specified conditions of this process are accordingly essential for producing a product containing no more than 5% of such dehydrohalogenated materials.

It has been found in accordance with this invention that is is essential to keep the reaction temperature below about 165°C. to avoid excessive production of dehydrohalogenated materials. It has likewise been found that the proportion of dehydrohalogenated material in the product increases as the reaction approaches completion and the proportion of monoester in the product approaches a minumum of zero. It is accordingly also essential to allow the reaction to proceed only until a minimum of about 2% of monoester is present in the product.

There is a greater tendency to form dehydroha logena ted products when R2 and/or are haloalkyl, and in such cases, the reaction should be run only until a minimum of about 20% up to about 40%, of the monoester remains in the product, whereby the production of dehydrohalogenated products is held to no more than 5%. When and are alkyl, the reaction may be permitted to run until the monoester in the product amounts to about 2 to 20%.

It will be understood that a further feature of this invention is the provision of a process for producing the mono-ester of formula II by Equation III above. The proportion of monoester in the product is substantially increased by stopping the reaction before the second step of Equation IV has progressed to any substantial degree, but after substantially complete disappearance of the precursor diester. In this manner, products are obtained containing over 50% of the monoester which can if desired by separated out by extraction with a ha lohydrocarbon as described above.

Still another feature of the invention is the provision of a process for producing the free acid of formula V from said monoester by Equation IV above.

Control of the reaction steps and the production of the desired products in accordance with the processes of this invention may be maintained by any one or a combination of the following expedients: 1. Measure the amounts of R2 halide and halide evolved as the reaction proceeds according to Equations III and IV above. 2. React a sample of the product with an esterifying agent to convert the OH groups in the free acid (formula V above) and monoester (formula II above) to OR^, R^ being alkyl, e.g. methyl, different from R2 and R^ , and analyze by VPC (vapor phase chroma ography) for amounts of product containing two OR. 4 groups derived from the free acid, amounts of product containing one OR^ group derived from the said monoester, and amounts of product devoid of OR^ (unreacted precursor diester of formula I above) . 3. Titrate a sample of the product with NaOH for deter¬ mination of the free acid content and run a chlorine (or other halogen) analysis on a sample of the same product, effective for determining amounts of free acid and monoester wherein OR3 is chloroalkyl (or other haloalkyl). 4. Determine the relative disappearance from samples of the product of terminal methyl groups in the precursor diester or monoester by NMR (nuclear magnetic resonance) procedure.

Any one or a combination of the foregoing control or analytical procedures may be employed for determining the exact conditions of time and temperature and the like for producing the desired product from any particular precursor diester or monoester.

The following examples are only illustrative of various embodiments of this invention and are not to be regarded as limitative. All parts and proportions referred to herein and in the appended claims are by weight unless otherwise indicated.

Example I 1938 grams of crude bis (20chloroethyl) B-chloroethyl-phosphonate, prepared by the rearrangement of tr is (2-chloroethyl) phosphite in o-dichlorobenzene, were introduced into a 3 liter 3 neck flask, equipped with stirrer, glass inlet tube and a "Y" tube, containing a thermometer which extended below the liquid surface. The other arm of the "Y" tube was attached to a down dropping bulb condenser attached to a one liter one neck distillation flask, containing a side arm which was connected to a cascade water scrubbing tower for removal of excess hydrogen chloride.

The crude diester was heated, with stirring, to a temperature of 159-160°C, at which temperature anhydrous hydrogen chloride from a pressure cylinder was introduced beneath the surface of the liquid, resulting in vigorous evolution of 1 , 2-dichloroethane . The addition of hydrogen chloride was continued for 6.5 hours while maintaining the same temperature. The evolution of 1,2-dichloroethane was very rapid during the first four hours. The resulting product weighted 1039 grams, had a melting point of 35-55°C, and contained 34.6% of the mono 2-chloroethyl ester of B-chloroethylphosphonic acid, 48.4% of the free B-chloroethylphosphonic acid and 11% of its anhydride, 2.2% of dehydrochlor i-nated im urities and the balance other im urities. 100 grams of Che above product were extracted with 4 consecutive 100 gram portions of methylene chloride (Cl^Cl^ , in which the said free acid and its anhydride are substantially insoluble. About 65 grams of a white crystalline material remained composed of said free acid and anhydride with about 5% of said monoester and dehydrohalogenated material.

The solvent in the combined extracts from the above 4 extractions was distilled off leaving about 35 grams of a thick syrup composed of said monoester with about 5% of said free acid and dehydrohalogenated material.

Example II Following the procedure of Example I, anhydrous HCl was passed through 39.8 grams ^0.2 mole) of diethyl B-chloroethyl-phosphonate of 85-90% purity, prepared by reaction of vinyl chloride with diethylphosphite , at about 150°C. for about 16 hours and until about 70-85% of theory of ethyl chloride byproduct was collected in a trap cooled with dry ice-acetone.

The viscous liquid product was subjected to vacuum pumping to constant weight, 27 grams (theoretical yield of pure B-chloro-ethylphosphonic acid is 28.8 grams). Analysis of the product showed 12.9% B-chloroethylphosphonic acid 5.3% B-chloroethylphosphonic acid anhydride (bis) 5.0% mono(2-chloroethyl) ester of B-chloroethylphosphoni acid 4.0% dehydrochlorinated products

Claims (4)

■ν.ι WHAT WE CLAIM IS:

1. A controlled anhydrous process for producing β-halo- ethylphosphonic acid or anhydride and its monoester which comprises introducing anhydrous HC1 or HBr from an outside source into a diester stable at a temperature above 140°C. and having the formula wherein is haloethyl and and represent alkyl or haloalkyl containing no more than 6 carbon atoms, characterized by carrying out the reaction at a temperature of about 140°C. to lb5°C. until a product is obtained containing 2% or more of the corresponding monoester of the formula 0 no more than 5% of dehydrohalogenated impurities, no more than about 570 of other impurities, and the balance β-haloethylphos- phonic acid or anhydride.

2. A process according to Claim 1 wherein the product contains 2 to 40%, of the corresponding monoester.

3. A process according to Claims 1 or 2 wherein R^ is chloroethyl .

4. A process according to any of Claims 1 to 3 wherein at least one of and R^ is haloalkyl and the anhydrous HCl or HBr is introduced until the product contains about 20 to 40% of the corresponding monoester. A process according to any of Claims to wherein at least one of R.2 and R-j is chloroethyl. A process according to any of Claim to wherein R.2 and R^ are alkyl and the anhydrous HCl or HBr is introduced until the product contains about 2 to 20%, of the corresponding monoester. A process according to any of Claims to wherein a product is obtained substantially devoid of the diester and containing over 507» of onoester of the formula A process according to any of Claims to followed by the step of extracting said monoester from said product with a g halohydrocarbon. A controlled anhydrous process for producing -halo-ethyIphosphonic acid or anhydride and its monoester substantially as set forth and described hereinbefore. S,HOROWITZ § CO, AGENTS FOR APPLICANTS