IL28858A - Process for the preparation of 2-benzimidazole carbamic acid esters - Google Patents

Description

28858/2 Process for the preparation of 2- benzimidazole carbamic acid esters E. I. DU PONT m NEMOURS AND COMPANY Briof Summary of tho Invontion This invention relates to novel processes for the manufacture of alkyl esters of certain benzimidazolecarbamic acids. More particularly, this invention relates to processes for the manufacture of such esters from cyanamide or cyanamide salts.

Alkyl esters of 2-benzimidazolecarbamic acids represented by the formula: where R is alkyl of 1 through carbon atoms; and X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; are useful as fungicides. The compounds when X is hydrogen and R is alkyl of 1 to carbon atoms are particularly useful. The above compounds are also useful as Intermediates in the preparation of dialkyl esters of l-carboxy-2-benzimidazolecarbamic acids represented by the formula: COO^ where X is as defined in formula (I) above and R and R1 are the same or different and are alkyl of 1 through 4 carbon atoms.

These. compounds are disclosed in U.S. Patent , 935, 50 and are very useful as fungicides.

U.S. Patent 3* 010, 968 describes a process for making the 2-benzimidazolecarbamic acid esters of formula (I) by reacting thiourea with dimethyl sulfate to produce 2-methyl-thiopseudourea sulfate. This reaction product is then reacted with an alkyl chloroformate and a base to produce an acylated 2-methylthiopseudourea, which is then reacted further with an o-phenylenediamine in the presence of a protonic acid to produce the desired product.

The process of this invention has several advantages over the process set forth in the above patent. One particular advantage is that commercially available, inexpensive, technical-grade cyanamide salts or cyanamide solutions can be used instead of the relatively more expensive thiourea materials. Further, the process of this invention do^s not require the handling or disposal of obnoxious methyl mercaptan materials which are by-products of the art process. Addition a batch or continuous manner with normal reaction vessels.

The process of this invention can be summarized by the following equations: (Step 1) o CN (a) mM2/mNCN + mCl-C-OR + M(N-C02R)m cyanamide alkyl alkyl salt chloro- cyanocarbamate formate salt CN M(HNCN) + m(R0)2C mROH + M(B-C02R) m H20 cyanamide alkyl alkyl salt carbocyanocarbamate nate salt HaO alkyl o-phenylene- cyanodiamine carbamate salt alkyl ester of 2-benzimidazolecarbamic acid where R is alkyl of 1 through carbon atoms; and X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; M is an alkali metal or an alkaline earth metal; and m is the valence of M and H+ may be derived from any acid.

In Step 1 above, since a cyanamide salt is employed, the cyanamide is present in the aqueous solution in anion form. This ionization usually is of itself sufficient to produce the desired pH. However, cyanamide as an aqueous solution can also be used in Step 1 if a base is added to the solution to maintain the desired pH. Step 1 in this embodiment is illustrated by the following equation: ( cyanamide alkyl base chloro- formate CN M(N-COaR) + MCI + 2α_Η20 m m alkyl cyanocarbamate salt In this reaction, any basic alkali metal or alkaline earth compound can be used as the base. Alkali metal and alkaline earth hydroxides are preferred, although oxides and carbonates can be used.

The 2-benzimidazolecarbamic alkyl esters produced formula II. This conversion reaction is summarized by the following equation: wherein R and R are as defined previously.

In another aspect this invention is related to the novel compounds methyl cyanocarbamate and the salts of alkyl cyanocarbamates with o-phenylenediamine .

Detailed Docoription of the Invention In the first step of the process of the invention, the appropriate alkyl chloroformate or alkyl carbonate is reacted with either cyanamide or a salt of cyanamide in essentially neutral to basic aqueous media to form a salt of an alkyl cyanocarbamate. Readily available technical-grade salts are -suitable for this process. Suitable starting materials are cyanamide alkaline earth or alkali metal salts, particularly the salts with magnesium, potassium, sodium and calcium. Commercially available calcium cyanamide is the preferred starting material. Cyanamide itself in a water solution is also a preferred starting material.

In the first step, when the alkyl chloroformate or 8ingle salt, i.e., M(HNCN)m or a double salt, i.e., M^ CN can be used; however, the double cyanamide salt is preferred for the reaction with the alkyl chloroformate.

The first step is conducted in water.

The concentrations of the starting materials in the reaction mixture are not critical; however, for economic reasons, high concentrations will usually be chosen. The concentration of the cyanamide in the water solution can range from 5 to 50 and since cyanamide is presently com-mercially available in a 5 aqueous solution, such solutions are preferred. With respect to the slurry or solution of the cyanamide salts, the concentration is only limited by the handling characteristics of the slurry.

When a cyanamide salt is used, it is preferred to add, with mixing, the alkyl chloroformate or alkyl carbonate to the aqueous slurry or solution containing the cyanamide salt. Reduced alkyl chloroformate consumption results when the pH of the cyanamide salt slurry in water is first lowered from approximately pH 12 to pH 8 - 10 by the addition of mineral acid before the alkyl chloroformate is added. When a cyanamide water solution is used, the alkyl chloroformate and base can be added concurrently to the cyanamide solution. During this concurrent addition, preferably the molar quantity of base added at any point should be equivalent or slightly in excess of the molar quantity of chloroformate.

During the first step, the pH should be maintained under essentially neutral to basic conditions, i.e., within the range of 6 to 15· As previously mentioned, when free cyanamide is used, this pH range can be maintained by adding the preferred range of pH is from 7 to 9 · However, with cyanamide salts, it is preferred to maintain the pH range between 8 to 10.

The temperature of this first step of the reaction is not critical within the range of 0* to 105eC. Generally, the range of 25 ° to 6oeC. is preferable. If desired, this step can be conducted at higher temperatures under pressure.

The reaction is rapid and the product ie stable in the reaction medium; thus the time of reaction is not critical and the product can be used directly in the second step or held for a period of time, depending upon which is desirable from an equipment viewpoint. In general, the reaction time will depend upon heat transfer rate and can be from 5 minutes to 2 hours.

When technical grade cyanamide salts have been used in the first step, sometimes insoluble impurities and salts, e.g., calcium salts, are included in the reaction mixture.

It is preferred to filter these impurities out prior to going forward into step 2.

In the second step of the reaction, o-phenylene-diamine is added to the reaction product from step 1, or if cyanamide salts have been used, to the filtered reaction product, in an aqueous acidic media to produce the 2-benziraida-zolecarbamic acid, alkyl ester. The o-phenylenediamine can be added to the reaction product while the product is at the temperature it was during the first step, 0 " up to 105°C.

To carry out the condensation and ring closure involved, during the second reaction the pH should be maintained in the range of 1 to 5, preferably 2.5 to 4 .5 by the the desired pH by the addition of any acid, for example, formic acid, acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, hydroxyacetic acid, sulfamic acid, and the like. Optionally, the o-phenylenediamine can be in the form, of a mineral acid salt or can be added as a solution in water. When o-phenylenediamine salts are used, the amount of acid required to produce the desired pH will correspondingly be reduced.

The second reaction will occur at temperatures above 0eC; it is preferred to heat during this step to speed the reaction to completion. The addition of heat is important in that the reaction of the second step would be too slow at low temperatures. The reaction mixture should be maintained at 40°C. to reflux, preferably 6oe to 105°C. The second step reaction can also be conducted under pressure if this is desired. If this is done, the temperature can go up to 130eC.

During the heating step, the desired product will precipitate. Thus the completion of precipitation is an indication that the reaction mixture has been heated for a sufficient period of time such that the reaction is complete. The time is not critical, and depends upon the temperature and pH. Thus at a pH of 2.5 to 4.5 and a temperature between 70° and 10 °C, the reaction time can be 5 to 30 minutes.

When lower temperatures are used, the time will be longer, and if the pH is not maintained in the range of 1 - 5> the reaction will be very slow or not occur at all.

The desired product can then be recovered by any of the conventional means, for example, spray drying, another liquid medium by distillation of the water.

In the overall reaction, the reactants can be used in the mole equivalent ratios indicated in the following table: PREFERRED REACTANTS MOLE EQUIVALENTS MOLE EQUIVALENTS Cyanamide or cyanamide salts 1 to 5 . 1 to 2.2 alkyl chloroformate or alkyl carbonate 1 to 3 1 to 1.8 o-phenylenediamine or derivatives thereof 1 1 It should be understood that the molar concentrations are not critical at the upper limit; however, they will not be practical or economical at higher levels. It is obvious that the concentration in the second step will depend upon the concentration in the first.

It has also been found that the first step of this reaction has produced a novel compound, methyl cyanocarbamate.

This compound can be prepared by reacting methyl chloroformate or dimethyl carbonate with cyanamide salt and then acidifying the resulting solution, or reacting the methyl chloroformate with cyanamide in the presence of a base such as sodium hydroxide and then acidifying the resulting solution. This reaction is exemplified by the following equations: 0 (a) mMg/ NC + mCl-C-0CH3 + MClm NH(CN)C02CH3 or (b) M(HNCN)m + m(CH30)2 C»0 PH \ M^CNjCOsCHa/^ + m(CH3OH) H20 or 0 (c) raHaNCN + mCl-C-0CH3 ♦ 2M(0H)m + H(CN)C02CH3 The methyl cyanocarbamate thus produced can be Isolated by extraction with organic solvents if desired; however, the above solution containing the methyl cyanocarbamate can be used for the second ste in the process of the invention. The product, methyl cyanocarbamate, is therefore a useful compound in that it can be reacted with o-phenylene-diamine to form 2-benzimidazolecarbamic acid, methyl ester.

In order that the above aspects of the invention can be better understood, the following Examples are offered: Example 1 - Preparation of 2-benzimidazolecarbamic acid, methyl ester Methyl chlorofonnate (75.6 parts) is added with good stirring to a slurry of 80 parts of technical grade calcium cyanamide and 300 parts of water. The temperature is maintained at 40° to 50eC. by ice-bath cooling. After stirring the reaction mixture for 1 hour, the mixture is filtered and the insolubles washed in portions with 100 parts of water.

To the combined wash and filtrate is added 3.2 parts of o-phenylenediamine . The pH of the mixture is adjusted to 3.5 with the addition of concentrated hydrochloric acid. The solution is then heated rapidly to 90eC. and the temperature maintained in the range of 90° to 98*C. for thirty minutes. During this time, the pH is maintained at 2.5 to 3.1 The reaction mixture is then filtered and the solid washed with water and acetone, and then dried in a vacuum oven at 120°C. This results in a yield of 64 parts of 2-benzlmlda-zolecarbamic acid, methyl ester, or a yield of 83.3# based on the o-phenylenediamine .

Example 2 - Preparation of 2-benzimidazolecarbamic acid, methyl ester To a suitable reaction vessel air added 5 .4 parts of a 50# cyanamide solution and 250 parts of water. Then 56.8 parts of methyl chloroformate and 88 parts of 50# sodium hydroxifle are added simultaneously. The pH of this mixture is controlled at 8.0 to 8.5 by the rate of sodium hydroxide addition, and the temperature is maintained near 40°C. by ice-bath cooling.

The resulting solution is further reacted by addition of 54 parts of o-phenylenediamine. The mixture is brought to pH 3.5 with concentrated hydrochloric acid. The mixture is then heated rapidly to 90°C. and for thirty minutes the temperature is controlled at 91 ° to 97"C During this time, the pH is maintained at 3.0 to 3.6 by the addition of concentrated hydrochloric acid. The resulting mixture is then cooled to 6oeC. and filtered. The product is washed with water and acetone and dried in a vacuum oven at 130 eC. This results in 78.9 parts of 2-benzimidazolecarbamic acid, methyl ester, or a yield of 82.6$ based on the o-phenylenediamine.

Example 3 - Preparation of methyl cyanocarbamate Into a suitable vessel fitted with a stirrer and thermometer are placed 50.4 parts of 0$ cyanamide solution alon with 2 0 arts of water. To this stirr t are gradually and simultaneously added 57 parte of methyl chloroformate and 88.2 parte of 50% sodiua hydroxide solution. The temperature is maintained at approximately 40eC. during the addition, and the mixture is stirred for an additional half hour.

The resulting solution is acidified to pH 1 with hydrochloric acid and cooled to 20*C. It is then extracted six times with 75 portions of methylene chloride.

The combined methylene chloride solutions are dried over 20 parts of anhydrous sodium sulfate and concentrated. The resulting light yellow oil consists essentially of methyl cyanocarbamate .

Example - Preparation of 2-benzimidazolecarbamic acid, methyl ester To a jacketed reactor equipped with feed ports stirrer, reflux condenser, and pH probe are added 32 parts of 50% cyanamide solution and 100 parts of water.

Methyl chloroformate (41.1 parts) and 67 parte of 50 sodium hydroxide solution are chargtd concurrently so as to maintain the pH of the solution at 7 - 7 ·5 and the reaction temperature at 40 - 50*C. The solution is held at 50 eC. for 45 minutes and then 36 parts of o-phenylenediamine is added. The pH of the solution is held at 3 - 9 to 4 . 1 by the gradual addition of 65 parts of 37# HC1. The solution is heated to 10 eC. and held at this temperature for 30 minutes. During this hold time, the product starts to crystallize. The reaction mass is cooled to 25-30 eC. and the solid product is filtered, washed with water and acetone, and dried in the vacuum oven at 8oeC. to give 59.6 parts of 2-benzimidazolecarbamic acid, methyl ester. This represents a product yield of 93.5 based on o-phenylenediamine .

Example 5 The following products are prepared by the procedure of Example 1. The starting materials used and the products obtained in this Example are listed in the following table. The amounts of starting materials are equivalent on a molecular basis to those of Example 1.

TABLE STARJING MATERIALS PRODUCT Cyanamide | Alkyl Chloroformate o-phenylenediamine sodium methyl 3-methyl- -methy1- cyanamide chloroformate o-phenylene- 2-benzimida- cTiamine zolecarbamic acid, methyl ester potassium propyl 3- chloro- -chloro- cyanamide chloroformate o-phenylene- 2-benzimida- d'iamine zolecarbamic acid, propyl ester calcium isopropyl o-phenylene- 2-benzimida- cyanamide chloroformate liamine zolecarbamic acid, isopropyl ester calcium ethyl 4-bromo- 5-bromo-2- cyanamide chloroformate o-phenylene- benzimida- cTiamine zolecarbamic acid, ethyl ester magnesium isobutyl 3-nitro- 4-nitro-2- cyanamide chloroformate o-phenylene- benzimida- liamine zolecarbamic Example 6 Preparation of 2-benzimidazolecarbamic acid, ethyl ester . ■ To a jacketed reactor fitted wit feed ports, stirrer, reflux condenser, bleed off and injector pumps, and pH probe are added 52 parts of 0# cyanamlde solution and 100 parts of water. To this stirred solution are con-r currently added 47.5 parts of ethyl chloroformate and 67 parts of 50 sodium hydroxide solution. The pH is maintained at 7 - 7.5, and the reaction temperature at 40 - 50°C. The solution is stirred for an additional 45 minutes at 50*C.

To the resulting solution containing the intermediate ethyl cyanocarbamate, sodium salt is added J>6 parts of o- phenylenediamine . The vessel is sealed to withstand . pressure of the order of 2 - 3 atmospheres. A total of 65 parts of y hydrochloric acid is gradually pumped in to maintain the pH at 3.9 to 4 .1 while the solution is heated and then held at 120°C. for 20 jninutea. The reaction mixture ie copied to ambient temperature, filtered, and the solid washed first with water, then with acetone. The filter cake is dried in a vacuum oven at 80eC. and represents an excellent yield of 2-benzimidazolecarbamic acid, ethyl ester.

A second type of novel compound, the salt of an alkyl cyanocarbamate with a substituted or unsubstituted o-phenylenediamine, is formed during the operation of step 2 of the process of the invention. A convenient way to begin the operation of step 2 is to add the substituted or unsubstituted o-phenylenediamine to the aqueous solution of the alkali metal or alkaline earth metal salt of alkyl cyanocarbamate which is produced in step 1. The resulting mixture is then acidified to the proper pH with a suitable acid. At this point the novel salts are formed. These reactions are represented by the following equation: where n R is alkyl of 1 through 4 carbon atoms; X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; M is an alkali or alkaline earth metal; m is the valence of M; and is derived from any acid.

The novel salts of this aspect of the invention can be recovered by conventional methods such as filtration, centrifugation, or spray drying. However, if it is desirable to prepare substituted and unsubstituted esters of 2-benzimid zolecarbamic acid, then it is ordinarily more convenient to proceed with step 2 without isolating the salts. When the novel salts are heated in an acidic aqueous medium, as is the case during step 2, they are converted to substituted and unsubstituted esters of 2-benzimidazolecarbamic acid. This reaction is represented by the following equation: wherein R, X and H are as previously set forth.

Their ability to eliminate H3 and form benzimida-zolecarbamic acid esters is characteristic of these novel salts, and this property can manifest itself under other conditions than those ordinarily employed in the operation of step 2.

For example, although higher yields are obtained when the NH3 is neutralized by added acid, the reaction will proceed in the absence of any additional acid. Also, although the reaction is much more rapid at an elevated temperature, it will occur to an appreciable extent at room temperature.

Thus, an aqueous solution of the salt of methyl cyanocarbamate with o-phenylenediamine will deposit solid 2-benzimidazole-carbamic acid, methyl ester, after standing overnight at room temperature. These co.nvereions will also occur in other solvents, such as acetone and the lower alcohols, in which the salts are soluble.

It is not necessary to have the salts in solution, simple dry heating is all that is required to effect this characteristic reaction. For example, when a small sample of the salt of methyl cyanocarbamate and o-phenylenediamine is placed in a melting point bath which is at 125°C, the sample immediately melts with NH3 evolution and then rapidly resolidi- fies. This dry conversion can be controlled on a larger scale by having the salt suspended in an inert solvent and heating the slurry until the conversion is complete.

Besides their formation during step 2 of the process, these salts can be prepared by other methods. Essentially, the salts are formed whenever an alkyl cyanocarbamate and substituted or unsubstltuted o-phenylenediamine are brought together. If they are brought together in a solvent in which the salt is Insoluble or only partially soluble, then the salt can be recovered by conventional methods such as filtration, centrifugation, or spray drying.

Thus the solution of the alkali or alkaline earth metal salt of the alkyl cyanocarbamate which is produced in step 1 can be acidified. The alkyl cyanocarbamate can then be extracted by a water-immiscible solvent such as ether, methylene chloride, chloroform, or any of several others. The addition of the substituted or unsubstltuted o-phenylenediamine to the extract results in salt formation.

Alternatively, the alkyl cyanocarbamate could be obtained in an undiluted form by evaporation of the extract, and then added to a mixture of the substituted or unsubstltuted o-phenylenediamine and the appropriate solvent.

Another method of obtaining these salts involves one of the previously mentioned optional variations of step 2. In this case, a mineral acid salt of the substituted or unsubstltuted o-phenylenediamine is added to the product solution of step 1 which contains the alkali metal or alkaline earth metal salt of the alkyl cyanocarbamate. A metathetic with the substituted or unsubstituted o-phenylenediamine will precipitate as a result.

The alkyl cyanocarbamate need not even be preformed; it may be produced in situ. This occurs when a dialkyl cyanolmlnodlcarboxylate is reacted with a substituted or unsubstituted o-phenylenediamine. The initial products of this reaction are an alkyl cyanocarbamate and the diester of a substituted or unsubstituted o-phenylenedicarbamic acid. The alkyl cyanocarbamate then reacts with additional diamine to form the salt. These reactions are represented by the following equations : In any of the methods for producing the novel salts, the molar proportions of the alkyl cyanocarbamate and substituted or unsubstituted o-phenylenediamine are not critical variables and either may be in excess when the two are brought together for salt formation. It is obviously uneconomical of material, however, to have one present in great excess over the .other.

Temperature is not a critical variable and the salts can be obtained at any temperature below that at which decomposition begins. This temperature will of course vary depending upon the particular salt but decomposition is slow below 50 °C. in all cases. A convenient working temperature range for the preparation of these salts is 0eC. to 50 °C.

Another characteristic of these salts is their acidity. For example, "an aqueous solution of the salt of methyl cyanocarbamate with o-phenylenediamine may be titrated to a sharp end point using 0.1 N NaOH and phenolphthaleln indicator.

Application of the novel salts of this aspect of the invention by the following methods surprisingly entirely pre- eludes or reduces damage to plants due to fungi. Fungus mycelia are killed or prevented from developing further by the presence of one or more of these salts, i.e. the compounds are fungicidal or fungistatic.

These salts provide protection from damage caused by fungi when applied to the proper locus at a sufficient rate to exert the desired fungicidal effect. They are especially suited for the protection of living plants such as fruit-bearing trees and vegetable crops.

Living plants may be protected from fungi by applying one or more of the salts to the soil in which they are growing or in which they may subsequently be seeded or planted at preferred ratesof 0.1 to 1000 parts per million by weight of the soil; or to seeds, tubers, bulbs or other plant reproductive parts prior to planting at preferred rates of 0.5 to kOOO grams active compound per 50 kilograms of plant parts treated; as well as to foliage, stems and fruit of the living plant at preferred rates of 0.1 to 100 kilograms of active ingredient per hectare. Living plants can also be protected by dipping the root system or physically injecting the chemical or chemicals into roots or stems. The preferred rates for this utility are 50 to 500 grams per 400 liters of water or other liquid carrier.

Applications are made from dusts, slurries or solutions.

Such treatments protect the treated parts themselves from damage due to fungi and, in addition, impart extended protection to the resulting new plants.

Plant parts such as fruits, tubers, bulbs, roots and the like, harvested for food or feed, are protected from decay and other deterioration caused by fungi during processing, distribution and storage by treatment with an active salt of this invention.

As was previously set forth, the salts are especially suited for use in living plants. Application to the foliage, stems and fruit of plants at the rate indicated above is generally accomplished by employing sprays, dusts or aerosols containing an effective amount of active ingredient. For the control of fungi which are regularly present, applica- tions often start prior to the time that the problem actually appears and continue on a pre-determined schedule.

The salts can be formulated into fungicidal compositions which contain in sufficient amount to exert fungicidal action, one or more salts in admixture with a carrier material or conditioning agent of the kind used and commonly referred to in the art as an adjuvant or modifier. The general classes of adjuvants applicable to the salts are inert solids, organic liquid solvents, organic liquid or aqueous diluents and surface-active agents. Formulations adapted for ready and efficient application using conventional applicator equipment are prepared by compounding the salts with suitable adjuvants by mixing, grinding, stirring or other conventional processes. Normally, the active ingredient composes 1 - 95$ by weight of the fungicidal composition* Practical compositions of the salts are wettable powders, dusts or granules. The salts of this invention are sufficiently water soluble to form solutions at normal spray concentrations. However, water solubility is no assurance of rapid wetting and dispersion into water prior to solution. In order that this take place rapidly, without slow-dissolving agglomerates, it is desirable to incorporate an inert diluent to prevent lumping and agglomeration, a wetting agent to prevent surface float and a dispersant to aid dispersion into individual particles so that solution is rapid.

Other compositions are concentrated solutions in water or in a water-miscible solvent such as methanol or acetone, which can be sprayed directly or diluted for application.

. Suitable wetting and dispersing agents may be anionic or nonionic. Cationic agents are undesirable since they usually produce low pH mixtures which accelerates product decomposition. A listing of wetting and dispersing agents may be found in "Detergents and Emulsifiers" by John W. McCutcheon, Inc. 1967· Most suitable wetting agents include alkyl naphthalene and alkyl benzene sulfonates, sodium salts of dialkyl sulfosuccinates , sodium lauryl sulfate, aliphatic, sulfonates, the oleyl ester of sodium isethionate and sodium-N-methyl-N-palmitoyl taurate. Liquid nonionic agents such as alkyl phenol polyethyleneoxide condensation products are effective wetting agents but may tend to promote caking or agglomeration in storage because of their physical form. They are best used when preextended upon a high surface area diluent. One commercial product offered in this form is "Triton" X120.

Most suitable dispersing agents are ligninsulfonates, polymerized alkyl naphthalene sulfonate condensates, and protective colloids such as methylcellulose or low viscosity polyvinyl alcohol. Suitable diluents for wettable powders include natural kaolin, attapulgite montmorillonite and diatomaceous silica. Since acidity is undesirable, acidic diluents such as kaolin should be buffered, i.e., with N 2HP04, if used. In addition to natural minerals, synthetic products such as calcium silicates and synthetic fine silicas are satisfactory. Diluents for dusts should be dense and rapid settling. Suitable dust diluents include micaceous talcs, pyrophillite, ground phosphate rock and tobacco stem dust. Granular diluents are preferably preformed, screened grades of attapulgite, vermiculite or ground corn cob.

Surface active agents may be added to wettable powders in concentrations of from 0.0$ to 2.5 when the objective is merely to attain rapid wetting, dispersion and solution of the active. However, some wetting agents, e.g. sodium lauryl sulfate, have also been found to aid the biological action when used at high levels. Such wetting agents can make up 50 to 90 of the dry composition when a single composition of maximum activity is desired. Dispersing agents do not display this effect and are used only at the lower levels of 0.0 - 2.5 .

Many liquid non-ionic wetters and emulsifiers also enhance biological activity when present at 100 - 1000 ppm in the final spray. Such agents are most conveniently added to the spray tank as a separate component.

In order that this aspect of the invention can be better understood, the following Examples are offered; the parts in all of the Examples are parts by weight unless otherwise indicated.

Example 7 - Preparation of the Salt of Methyl Cyanocarbamate , with o-Phenylenediamlne Separate solutions of 96 .0 parts of 50 sodium, hydroxide and 65.0 parts of 87 methyl chloroformate are added simultaneously to a solution of 25. 2 parts of cyanamide in so that the pH remains between 6.0 and 7.5. External cooling is used to keep the temperature below 55°C.

Water (100 parts) is added followed by enough concentrated 'HCl (29.4 parts) to give a pH of 3.0. The solution is cooled to 25eC. and 21.6 parts of o-phenylene-diamine are added. The resulting slurry is cooled to 10°C. and filtered. The product is washed with cold water and dried at room temperature. This procedure gives 33.8 parts (8l# yield) of the salt of methyl cyanocarbamate with o-phenylenediamine.

When placed in a 125eC. melting point bath, a small sample of this salt immediately melts with accompanying NH3 evolution and then rapidly resolidifies.

Example 8 - Preparation of the Salt of Methyl Cyanocarbamate with 4-Methyl-o-phenylenediamine Separate solutions of 96.0 parts of 50$ sodium hydroxide and 65.Ο parts of 87$ methyl chloroformate are added simultaneously to a solution of 25.2 parts of cyanamide in 250 parts of water. The separate addition rates are controlled so that the pH remains between 6.5 and 8.5. External cooling is used to keep the temperature under 50eC. The solution is cooled to 15°C. and acidified to pH 1.7 with concentrated HCl. The solution is then extracted with ether (6 x 36 parts) . Magnesium sulfate is used to dry the combi ed extract A portion (36 parts) of this extract is added to a solution of 12.0 parts of 4-methyl-o-phenylenediamine in 71 parts of ether. A second, oily appearing layer forms immediately. After standing several days the oil solidifies . -arid dried at room temperature. This procedure gives 15.^ parts ( 70 yield) of the salt of methyl cyanocarbamate with -methyl-o-phenylenediamine.

A small sample of this salt partially melts with accompanying NH3 evolution and then rapidly resolidifies when it is placed in a melting point bath which is at 155*C.

Example 9 - Preparation of the Salt of Methyl Cyanocarbamate with o-Phenylenediamine Dimethyl cyanoiminodicarboxylate (15.8 parte) and o-phenylenediamine ( 21 .6 parts) are added to 214 parts of ether. The resulting slurry is stirred for an hour at room temperature and is then filtered. The product is washed with ether and dried at room temperature. This procedure gives 18.7 parts (90# yield) of the salt of methyl cyanocarbamate with o-phenylenediamine.

A small sample of this salt immediately melts with accompanying H3 evolution when it is placed in a melting point bath which is at 125*C. Titration of a larger sample in aqueous solution using 0. 1 N NaOH and phenolphthalein indicator gives a neutral equivalent of 211 . The theoretical value for the named salt is 208.

The following novel salts can be prepared by any of the procedures described in Examples 8 through 10.

Salt of P with 3-Ch Salt of E with 4-Br Salt of I with 3-Ni tro-o-phenylenediamlne Salt of Isopropyl Cyanocarbamate with 4-Ethyl-o-phenylenediamine Salt of Butyl Cyanocarbamate with 4-Isopropyl-o-phenylenediamine Salt of Methyl Cyanocarbamate with 3-Butyl-o-phenylenediamine Salt of Methyl Cyanocarbamate with 3-Methyl-o-phenylenediamine Example 10 - Conversion of the Salt of Methyl Cyanocarbamate with o-Phenylenediamine to 2-Benzimidazolecarbamie Acld."Methyl Ester With Heat _ The salt of methyl cyanocarbamate with o-phenylene-diamine (1.0 parts) is heated at 1 5-50°C. for 10 minutes.

This treatment gives 0.86 parts {Sk yield) of 2-benzimi-dazolecarbamic acid, methyl ester.

Example 11 - Conversion of the Salt of Methyl Cyanocarbamate •with o-phenylenediaioine to 2*Benzimldazolecarbamic Acid."Methyl Ester with Acid A solution of 5.0 parts of the salt of methyl cyanocarbamate Vitlv o-phenylenediamine and 1.5 parts of acetic acid in 25 parts of water ia refluxed for 30 minutes.. The solution is cooled to 50*C. and filtered. The product is washed with water and dried in vacuo at 95°C. This procedure gives 3.3 g. (7 $ yield) of 2-benzimidazolecarbamic acid, methyl ester.

Example 13 Salt of methyl cyanocarbamate with o- 80# phenylenediamine Oleyl ester of sodium isethionate VjS> Diatomaceous silica 19$ The above components are mixed and micropulverized. The resulting powder disperses readily when placed in water, followed by solution of the active component.

This formulation is added to water at a rate to provide 800 parts per million by weight of active ingredient in the total slurry and resulting solution. This solution is sprayed on selected apple trees in a commercial orchard.

Application procedure is such as to provide uniform Coverage of all foliage to the point of liquid run-off. Applications start at the time that the first spring foliage growth appears and continues at weekly intervals until one month prior to the normal harvest date for apples. At the time of harvest, trees that had been treated in this manner have healthy foliage of good color and provide a good yield of high quality fruit. Similar and adjacent trees left unsprayed, on the other hand, have foliage showing disease caused by the fungi Venturia lnsequalis (scab fungus) and Podosphaera leucotricha (powdery mildew fungus). The foliage on the unsprayed trees Is also of poor color. The unsprayed trees yield only a few small fruit with diseased spots caused by the fungus Venturia inaequalls . Thus, the compound of this invention applied by the method described here effectively prevents damage to crop plants caused by certain fungi.

Example 13 Salt of methyl cyanocarbamate with -methyl- 25$ ^-phenylene diamine Tech 92# sodium lauryl sulfate 1 The above components are mixed and micropulverized. When added to water at use concentrations, the product is completely soluble. The high surfactant level enhances the activity of the active compound.

This formulation is added to water at a rate to provide 1,000 parts per million by weight of active ingredient in the final solution. This solution is sprayed on alternate rows of grape vines in a vineyard at the rate of 800 liters per hectare. Such applications start with the earliest growth in the spring and continue at intervals of 12 to 14 days until harvest time.

At harvest time the foliage on the treated vines is healthy and dark green in color and the yield of marketable fruit is high. The alternate unsprayed grape rows have foliage heavily diseaeed with powdery mildew (caused by the fungus Uncinula mecator) . Thus, the compound of this invention applied by the method described effectively controls powdery mildew.

Example 14 Salt of methyl cyanocarbamate with 10% £-phenylenedlamine Micaceous talc 90% An equal weight mixture of active and talc is first micropulverized. This product is then blended with the balance of the talc in a ribbon blender to yield a fungicidal dust.

The above dust is applied with a hand duster to designated plots within a large cucumber field. Each application is at the rate of 10 kilograms of the formulation per hectare. The first application is made as the plants start to form runners and this is repeated at intervals of 10 to 14 days until the picking period.

At picking time the plants within the treated plots are healthy and yield well. The untreated areas outside the plots, on the other hand, contain only cucumber plants heavily diseased with powdery mildew (caused by the fungus Erysiphe clchorocearum) .

Example 15 Salt ofethyl cyanocarbamate with 4-bromo- 2 o-phenylenediamine The active component is first dissolved in acetone, then sprayed upon the attapulgite in a blender. The acetone is then evaporated from the* product.

Selected plots in a rice field are dusted with the formulation described above employing a hand dust applicator. Application is at the rate of 5 kilograms of the formulation per hectare. The first application is made when the rice plants are about 10 inches tall and it is repeated at intervals of two weeks until about 14 days prior to harvest.

The rice within the treated plots remains healthy and yields well. The untreated areas outside the test plots, however, are heavily infected with the rice blast fungus ( and provide only a negligible yield of low quality grain.

Claims (18)

HAVING NOW particularly described and ascertained the nature of our said invention and in what manner"the Same is to be performed, we declare that what we claim is

1. A process for making 2-benzimidazolecarbamic acid esters of the formula: wherein R is alkyl of 1 through carbon atoms; X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; comprising reacting cyanamide or a cyanamide salt with an alkyl chloroformate or an alkyl carbonate in an essentially neutral to basic aqueous medium at a temperature between 0e and 105* C. to form an alkyl cyanocarbamate salt, reacting said alkyl cyanocarbamate salt with an o-phenylenediamine of the following formula: wherein X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; in an acidic aqueous medium at a temperature of 40" to 130°C. until the precipitation of the desired 2-benzl- midazolecarbamic acid ester is complete, and recovering said 2-benzimidazolecarbamic acid ester from the reaction mixture .

2. A process for making 2-benzimidazolecarbamic acid esters of the formula: R is alkyl of 1 through 4 carbon atoms; X is hydrogen, halogen, nitro, or alkyl of 1 through 4 carbon atoms; comprising reacting cyanamide or a cyanamide salt with an alkyl chloroformate or an alkyl carbonate in the presence of water, at a pH of 6 to 13 and a temperature between 0° to 105°C. to form an alkyl cyanocarbamate salt, reacting said alkyl cyanocarbamate salt with an o-phenylene-diamine of the following formula: wherein X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; in the presence of water at a pH of from 1 to 5 and at a temperature from 40° to 130°C. until the precipitation of the desired 2-benzimidazolecarbamic acid ester is complete, and recovering said 2-benzimidazolecarbamic acid ester from the reaction mixture.

3. 5. The process of Claim 2 wherein the cyanamide salt is the salt with an alkali metal or an alkaline earth.

4. The process of Claim 2 wherein the reactants are present in the following mole equivalents : o-phenylenediamine 1 mole alkyl chloroformate or alkyl carbonate 1 - 3 moles cyanamide or cyanamide salt 1 - 3 moles

5. A process such as set forth in Claim 2 wherein the alkyl cyanocarbamate salt is separated from the reaction mixture prior to being reacted with the o_-phenylenedlamine. according to Claim 2

6. A process/for making 2-benzimidazolecarbamic acid, methyl ester comprising reacting cyanamide with methyl chloroformate in the presence of water and sodium hydroxide, at a pH from 7 to 9 at a temperature between 25° and 60eC. to form methyl cyanocarbamate sodium salt, reacting said methyl cyanocarbamate sodium salt with o_-phenylenediamine in the presence of water and hydrochloric acid, at a pH from 2.5 to 4.5 and at a temperature between 60° and 105eC, and recovering said 2-benzimidazolecarbamic acid, methyl ester from the reaction mixture. according to Claim 2

7. A process/ for making 2-benzimidazolecarbamic acid, methyl ester, comprising reacting calcium cyanamide with methyl chloroformate in the presence of water at a pH from 8 to 10 at a temperature between 25° and 60°C. to form methyl cyanocarbamate calcium salt, reacting said methyl cyanocarbamate calcium salt with o-phenylenediamine in the presence of water and hydrochloric acid, at a pH from 2.5 to 4.5 and at a temperature between 60° and 105°C, and recovering said 2-benzimidazolecarbamic acid, methyl ester from the reaction mixture. according to Claim 2

8. A process/ for making 2-benzimidazolecarbamic acid esters comprising reacting an alkyl cyanocarbamate salt of the following formula: CN M(N-C02R)m where M is an alkali metal or an alkaline earth metal; m is the valence of M; and R is alkyl of 1 through 4 carbon .atoms; with an o-phenylenediamine of the following formula: X where X is hydrogen, halogen, nitro or alkyl of 1 through carbon atoms; in an acidic aqueous medium at a temperature of 40° to 130°C. until the precipitation of a 2-benzimidazolecarbamic acid ester is complete, and recovering said 2-benzimidazolecarbamic acid ester from the reaction mixture. _9 _ afeh-yl-eyaHeeaj?feamate - 35 28858/2

9. Compounds of the formula HNfCNjCOgR] wherein R is alkyl of 1 through 4 carbon atoms; and X is hydrogen, halogen, nitro, or alkyl of 1 through 4 carbon atoms.

10. The salt of methyl cyanocarbamate with o-phenyl-enediamine.

11. A method for preventing injury due to fungi comprising applying to the locus to be protected a fungi-cidally effective amount of a compound according to Claim 9.

12. A method according to Claim 11 for preventing injury due to fungi comprising applying to the locus to be protected a fungicidally effective amount of the compound according to Claim 10.

13. A process for making 2-benzimidazolecarbainic acid esters of tlie formula I in Claim 1 comprising heating a compound according to Claim 9 or 10.

14. A process according to Claim 13 , wherein the reaction takes place in an acidic solvent system.

15. 2-Benzimidazolecarbamic acid esters of formula I in Claim 1 whenever prepared by the process of Claim 2 . - 36 - 28858/2

16. 2-Benaimidazolecarbamic acid esters of formula I in Claim 1, whenever prepared by the process of Claim 13.

17. 2-Bensimidazolecarbamic acid, methyl ester when prepared by the process of Claim 2.

18. 2-Benzimidazolecarbamic acid, methyl ester when prepared by the process of Claim 14. PC/rb