3,804,844 United States Patent 0 ”"Ice Patented Apr. 16, 1974 1 2 are reacted with alkali metal cyanates in the presence 3,804,844 of a high dielectric-aprotic solvent. PROCESS FOR PREPARING The process of the present invention is generally ap PYRIDYLCARBAMATES Richard Garth Pews and Lennon H. McKendry, Mid plicable to carbocyclic or heterocyclic aromatic com land, Mich., and Ralph M. Rodia, Salem, Oreg., as pounds (hereinafter “aromatic ‘compounds’? ring-substi ls‘ilgngrs to The Dow Chemical Company, Midland, tuted with at least one substituent subject to nucleophilic displacement by a cyanate nucleophile. Such aromatic No Drawing. Continuation-impart of abandoned applica compounds can be ring-substituted with more than one tion Ser. No. 94,622, Dec. 2, 1970. This application identical or diiferent displaceable substituents which can Aug. 31, 1972, Ser. No. 285,503 10 be of the same or of varying degrees of nucleophilic Int. Cl. C07d 31/44 reactivity with a cyanate ion nucleophile. Furthermore, US. Cl. 260-295 AM 9 Claims the aromatic compounds can contain one or more non displaceable .substituents, i.e., not displaceable by a cyanate ABSTRACT OF THE DISCLOSURE ion nucleophile, as long as at least one ring-substituted There is disclosed herein a process for the preparation 15 ‘displaceable substituent is present. Such -based of aromatic and by reacting certain ‘derivatives have established utility in a variety of applica carbocyclic and heterocyelie aromatic compounds, ring tions such as, for example, bonding agents, , substituted with at least one displaceable substituent, additives or modi?ers in polymers to increase ?re retard with alkali metal cyanates and water or an alikanol in ancy and water repellancy, and the like. Other uses will the presence of a high dielectric-aprotic solvent. 20 be evident to those skilled in the art. DETAILED DESCRIPTION OF THE INVENTION CROSS-REFERENCE TO RELATED APPLICATION Examples of speci?c aromatic compounds which, when ring-substituted with at least one displaceable sub The present application is a continuation-in-part of 25 stituent, are useful in the present process include, for our co-pending application, Ser. No. 94,622, ?led Dec. example, , , pyrimidine, pyrazine, pyran, 2, 1970, now abandoned. quinoxaline, indazole, furan, pyrrole, thiophene, imid BACKGROUND OF THE INVENTION azole, oxazole, isoxazole and the like. Of these, benzene, pyridine, pyrimidine, pyrazine, pyran, quinoxaline, and The present invention pertains to a new method for 30 indazole constitute a preferred class. A preferred sub preparing aromatic amines and carbamates by reacting class of compounds within this invention are benzene, certain ring-substituted aromatic carbocyclic and hetero pyridine, pyrimidine and pyrazine. Within this preferred cyclie compounds with alkali metal cyanates and water sub-class especially preferred are benzene and pyridine. or an alkanol. Substituents which are subject to nucleophilic displace Various methods for preparing certain organic iso 35 ment by a cyanate ion nucleophile and which can be ring— cyanate-based derivatives are disclosed in the art. It is substituted on the above aromatic compounds include generally known that certain organic isocyanate inter mediates are prepared by the reaction of phosgene with —-SR2+, wherein each R independently represents hydro amines, or by the rearrangement of appropriate acyl 40 gen, phenyl or a loweral'kyl radical of from 1 to about azides. The preparation of organic by the 4 atoms, inclusive. reaction of aralkyl and aralkenyl halides, such as benzyl The following de?nitions will aid in the understand chloride and xylylene dichloride, with alkali metal ing of the disclosed invention. The term “aprotic solvent” cyanates in the presence of quaternary ammonium halides means a solvent which does not yield a proton to the or tertiary amines is also known. See US. Letters Patent 45 solute(s) under reaction conditions. For purposes of Nos. 2,866,802 and 2,866,803. The reaction of similar this invention, “high dielectric” refers to compounds hav organic halides with alkali cyanates to form isocyanates ing a dielectric constant equal to or higher than diglyme, is also known in the art. Generally, the reactive halide otherwise known as “diethyleneglycol dimethyl .” is present on an aliphatic carbon atom having at least The term “loweralkyl” as used in the present speci?ca one hydrogen atom on the halogen-substituted atom. See, 50 tion and claims, means saturated, monovalent aliphatic for example, US. Letters Patent Nos. 2,536,849; radicals, including straight and branched-chain radicals 2,866,801; and 3,584,028. of from one to about 4 carbon atoms, as illustrated by, It has now been discovered that aromatic ring~substi but not limited to, methyl, ethyl, propyl, isopropyl, butyl tuted isocyanate-based derivatives can be prepared from see-butyl, and the like. > various ring-substituted aromatic carbocyclic and hetero 55 The alkali metal cyanates which can be employed in cyclic compounds; furthermore, the process can be car the present invention include those of lithium, sodium, ried out without prior or separate reduction to a cor potassium, and cesium; preferably sodium and potassium responding . cyanate are employed. Normally, it is advantageous to SUMMARY OF THE INVENTION employ from about 10 to about 50% equivalent excess 60 of alkali metal cyanate. According to the present invention, it has been dis The high dielectric-aprotic solvents useful in this covered that carbocyclic and heterocyclic aromatic invention include acetonitrile, dimethyl , di amines and carbamates, hereinafter termed “isocyanate methyl formamide, diglyme (otherwise known as di based compounds,” can be prepared by reacting certain ethyleneglycol dimethyl ether), monoglyme (other-wise carbocyclic and heterocyclic aromatic compounds, ring 65 known as 1,2-dimethoxyethane), acetone, methyl ethyl substituted with at least one displaceable substituent, , dioxane, tetrahydrofuran, N-methylpyrrolidone, with alkali metal cyanates and water or an alkanol in and the like. Of these solvents, acetonitrile and N-methyL the presence of a high dielectric-aprotic solvent. Other pyrrolidone are especially preferred. Representative isocyanate-based compounds, such as for example, aro alkanols suitable for use in the present invention are those matic isoeyanurates, are prepared in similar methods 70 containing from 1 to about 4 carbon atoms, including wherein aromatic carbocyclic or heterocyclic compounds, methanol, ethanol, propanol, iso-propanol, butanol, and ring-substituted with at least one displaceable substituent, the like. 3,804,844 3 4 In carrying out the process of the present invention, Cl, 48.9; N, 9.66. Found (percent): C, 29.1; H, 1.43; Cl, the aromatic ring-substituted compound and alkali metal 48.5; N, 9.82. cyanate contacted in the presence of a high dielectric EXAMPLE 3 aprotic solvent. Water or an alkanol is added and the re sulting reaction mixture is heated for a su?icient period 4-methylsulfonyl-2,3,5,6-tetrachloropyridine (5.0 grams; of time to allow for substantial completion of the reduc 0.017 mole), (2.0 grams; 0.03 mole), tion. The isocyanate-based compound obtained upon the 20.0 milliliters of acetonitrile and 2.0 mililiters of metha addition of water alone is the corresponding aromatic nol were mixed in a glass pressure cell. The glass cell amine, whereas the aromatic is obtained upon was placed in an oil bath and the reaction mixture was heated at a temperature of from about 100 to about 125° the addition of an alkanol only. Mixtures of the amine and 10 carbamate compounds are obtained upon the addition of C. for a period of one hour. Following the reaction pe both water and alkanol. In each instance, the aromatic riod, the reaction mixture was ?ltered while hot to re amine and carbamate products are derived from a com move solid by-products and the ?ltrate was cooled to about mon isocyanate intermediate. In alternative operations, the minus 10° C. The precipitate formed upon cooling of the ?ltrate was ?ltered off and treated as in Example 2. The water or alkanol can be added to the reaction mixture fol~ 15 lowing the initial heating of the aromatic compound and crystalline solid was identi?ed as methyl 2,3,5,6-tetra alkali metal cyanate reactant. Where it is desired to pro chloropyridine carbamate, melting at 181—18l.5° C. duce other isocyanate-based compounds, such as, for ex EXAMPLE 4 ample, aromatic isocyanurates, the addition of water or an alkanol is omitted. 20 A reaction mixture consisting of pentachloropyridine The temperature at which the reaction is carried out (20.0 grams; 0.079 mole), (20.0 grams; is dependent upon the raw material reactants and solvent 0.4 mole) and 250 milliliters of N-methylpyrrolidone employed. Generally, the reaction temperature ranges from Were heated at a temperature of about 135 ° for a period about 20 to about 200° C.; preferably, the reaction is of about 3 hours with agitation under the pressure of ni carried out at the boiling temperature of the reaction trogen. Following the reaction period, the N-methylpyr mixture under re?ux conditions. Similarly, the reaction rolidone was removed from the reaction mixture by distil time, which ranges from about one hour to 4 or 5 days, lation at 0.5 mm. of pressure at a temperature of 80° C. varies inversely with the reaction temperature. Ambient The reaction mixture was cooled and 25 milliliters of pressures are adequate at the reaction temperature em ethanol, followed by 200 milliliters of water, was added. ployed when the volatility of the aromatic reactant, al 30 The resultant suspension was extracted with methylene cohol, and solvent permit; many reactions of the invention chloride and dried; the solvent was removed from the can be carried out at atmospheric pressure. extract by evaporation under reduced pressure. Chroma To further illustrate the process of the present inven tography of the residue on silica gel gave 4-amino-tetra tion, the following examples are provided. It should be chloropyridine, identical with authentic samples, and eth understood that the details thereof are not to be regarded yl 2,3,5,6-tetrachloropyridine carbamate melting at 178 as limitations, as they may be varied as will be under 179° C. stood by one skilled in the art. EXAMPLE 5 EXAMPLE 1 Pentachloropyridine (20.0 grams; 0.07 mole) was dis A reaction mixture consisting of 2,4-dinitrochloroben 40 solved in 250 milliliters of N-methylpyrrolidone contain zene (25.0 grams; 123 mole), potassium cyanate (12.0 ing sodium cyanate (20 grams; 0.4 mole). The resulting grams; 0.184 mole), 7.5 milliliters of methanol and 50 reaction mixture was heated at 135-140° C. in an atmos milliliters of acetonitrile was heated with agitation at the phere of for a period of about 3 hours. Follow boiling point of the mixture under re?ux conditions for ing the reaction period, the N-methylpyrrolidone was re a period of about 5 days. Following the reaction period, moved by vacuum distillation over a period of about 2 the reacton mixture was ?ltered while hot to remove solid 45 hours. The dark brown residue thus obtained was treated by-products and the ?ltrate was cooled to about —10° C. with 200 milliliters of Water and the resultant suspension The red precipitate formed upon cooling of the ?ltrate was ?ltered to obtain a tan solid material which was crystal removed by ?ltrate was removed by ?ltration and dissolved lized and recrystallized from a CHCl3-hexane mixture. in chloroform to give a yellow solution containing a red As a result of these operations, the desired 4-amino-tetra solid. The solution was ?ltered and the ?ltrate concen 50 chloropyridine compound, identical with authentic sam trated to dryness by evaporation under reduced pressure. ples, was obtained as a yellow crystalline solid. The residue thus obtained was puri?ed by exposure to column chromatography using chloroform as the eluent EXAMPLE 6 and activated alumina as an adsorbent, and by subsequent A reaction mixture consisting of 4-methylsulfonyl-2,3,5, recrystallization from . As a result 55 6-tetrachloropyridine (25.0 grams; 0.085 mole), potas of these operations, the desired methyl 2,4-dinitrocarba sium cyanate (10.3 grams; 0.127 mole), and 60 milliliters nilate product was obtained as a crystalline solid melting of acetonitrile was heated with agitation at the boiling at 127 to 127.5° C. temperature under re?ux conditions for a period of about EXAMPLE 2 20 hours. Following the reaction period, the reaction mix A reaction mixture consisting of 4-methylsulfonyl-2,3, 60 ture was ?ltered while hot to remove a precipitate identi 5,6-tetrach1oropyridine (25.0 grams; 0.085 mole), sodium ?ed by infrared analysis to be a mixture of unreacted cyanate (7.0 grams; 0.14 mole), 8.0 milliliters of metha potassium cyanate and isocyanurate product. The solvent nol and 100 milliliters of acetonitrile was heated with was removed from the ?ltrate by evaporation under re duced pressure and the oily residue thus obtained was so agitation, at the boiling temperature under re?ux condi 65 tions for a period of 3 days. Following the reaction period, lidi?ed by the addition of chloroform. The solid precipitate the reaction mixture was ?ltered While hot to remove formed upon addition of chloroform was obtained by ?ltra solid by-products, and the ?ltrate was cooled to about tion and suspended in ether. Subsequent acidi?cation of the —10° C. The yellow precipitate formed upon cooling suspension with concentrated hydrochloric acid gave a of the ?ltrate was removed by ?ltration and recrystallized solid precipitate which was ?ltered oil. The ?ltrate was from a solution of hot carbon tetrachloride. As a result evaporated in vacuo leaving a solid residue which was of these operations, the desired methyl-2,3,5,6-tetrachlo recrystallized from re?uxing acetonitrile. As a result of ro-4-pyridinecarbamate product was obtained as a crystal these operations, the di-(2,3,5,6-tetrachloro - 4 - pyridine) line solid melting at 181-18l.5° C. ‘Elemental analysis isocyanurate product was recovered as a crystalline solid calculated for C7H4Cl4N202 (percent): C, 28.9: H, 1.38; 75 melting at 338—339° C. 3,804,844 5 6 What is claimed is: acetonitrile and N-methylpyrrolidone, and wherein the 1. A process for the preparation of a pyridyl carbamate alkali metal cyanate is selected from the group consisting which comprises reacting a pyridine compound, ring-sub of sodium and potassium. stituted with at least one displaceable substituent selected 6. The process of claim 1 wherein the reaction is carried from the group consisting of chloro, bromo, ?uoro, iodo, out at a temperature of from about 20 to about 200° C. -—N2+, -—OSO2R, —SO2R, and -SR2+, wherein each R 7. The process of claim 1 wherein the reaction is car independently represents hydrogen, phenyl or a loweralkyl ried out at the boiling temperature of the reaction mix radical of from one to about 4 carbon atoms, inclusive, ture under re?ux conditions. with an alkali metal cyanate in the presence of a high 8. The process of claim 1 wherein the pyridine ring-sub dielectric-aprotic solvent and water or an alkanol. 10 2. The process of claim 1 wherein the pyridine com stituted compound is selected from the group consisting of pound is reacted with an alkali metal cyanate in the 4-methylsulfonyl - 2,3,5,6 - tetrachloropyridine and penta presence of a high dielectric-aprotic solvent and alkanol. chloropyridine. 3. The process of claim 1 wherein the high dielectric 9. The process of claim 2 wherein 4-methylsulfonyl 2,3,5,6-tetrachloropyridine is reacted with potassium cy aprotic solvent is selected from the group consisting of 15 acetonitrile, dimethyl sulfoxide, dimethyl formamide, di anate in the presence of acetonitrile and methanol. glyme, monoglyme acetone, methyl ethyl ketone, dioxane, tetrahydrofuran and N-methylpyrrolidone. References Cited 4. The process of claim 1 wherein the alkali metal Fieser & Fieser, Reagents for Organic Synthesis, Wiley cyanate is selected from the group consisting of sodium, Publishers, p. 1059 (1967). potassium, lithium, and cesium, and wherein the alkanol is selected from the group consisting of methanol, ethanol, ALAN L. ROTMAN, Primary Examiner propanol, isopropanol, and butanol. 5. The process of claim 1 wherein the high dielectric US. Cl. X.R. aprotic solvent is selected from the group consisting of 25 260—-248 CS, 294.8 F, 295.5 A, 296 R, 471 C; 71-94 mg? - - UNITED STATES PATENT oFmcE . CERTIFICATE @F .CORREC'HQN Patent; No. > 3,804,844 Dated April 16, 1974

Inve?tor(s) R.‘ G; Pews, L. H, McKendry and R. M. Rodia

It is certified. that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

(iolumn 3, lines 6 and 7, change "reduction" to m-P- reaction —-; Column 3, line 41,, change "123" to --»,0,123 w; "Column 3, lines’ 48 49,}delete "was removed by filtrate"; Column 3, line- iilioorreoit, s'pel-ling .‘frealction"; Column 5, ‘line l?pdelete "wateror";

Signed and {sealed} this 19th day of November 1974.,

(smw Atteast: v ‘McCoy M. GIBSON JR. 7 c. MARSHALL DANN Arresting Officer > Commissioner of Patents

c-16,162