Document wqO20MRmYXJME9KM75wVRdz5E

Dr. I. Gubelmam Dr. H. W. Elley J ' ' Dr. E. K. Bolton (l) Dr. William Kirk (1) Mr, J* S. (Jroveg for I.C.I. E. I. duPont de Wemoura & Company Jackson Laboratory ,May 26 1942 Preparation of Intermediates for Azo Research N4Q782 JLR-30-155, No. 64 Serial Number 180J4 E. I. duPont de Nemours & Company Jackson, Laboratory New Producta Division 0. B. Holbrook Progress Report May 26, 1942 Preparation of Intermediates for Ago Research group Leader - C. W. Croco Work Done By - J. B. Schaffer Reported By - J, R, Schaffer i J. M. TINKER ASSISTANT DIRECTOR Work Started - 10-8-40 Completed - 2-12-41 W. S. CALCOTT DIRECTOR DUP050059042 Preparation of Intermediates for Azo Research (Project No. 599) J. R, Schaffer _________ JLR-30-155, No. 64 Serial Number 18034 Object of the Investigation? To prepare intermediates for Azo Colors research. Period Covered by the Report: October 8, 1940 to February 12, 1941. Historical Background: These intermediates were requested by the Azo Division for their research work. Summary and Conclusions? The following compounds have been prepared by the methods outlined: (1) Mono-N-beta-Sulfo-Propionyl-Piperazine; (308/3460) c h 2--c h 2 /\ HN ^ N-COCHg-CHg-SO-jH CH2--CHg Piperazine hexahydrate + sulfo propionic anhydride -> product. The yield was 80% based on either starting material. (2) 4-Nltro-Aniline-g-Ethyl Phenyl Sulfonamide: (208.6/1923) -1- DUP050059043 4-Nitro-chlorbenzene-2-potassium sulfonate + phosphorus pentachlorlde 4-nltro-chlorobenzene-2-sulfonchloride + ethyl aniline 4-nitro-chlorobenzene-2-ethyl phenyl sulfonamide + ammonia > product. The yield was 74#. (3) 4-Nltro-Anlllne-2-Sulfon-Hexamethylene 3mlde: (307/3040) 4-Nitro-chlorobenzene sulfonohlorlde + hexamethylene imlne *> 4-nitro-chlorobenzene sulfon hexamethylene lmlde + ammonia > product. The yield was 16#. (4) 4-Ureldo Anlllne-2-Ethyl-Phenyl Sulfonamide; (208.6/1923) H0 Pk ^3^ + 4-Nitro-anlllne-2*ethyl phenyl sulfonamide 4-phenylene diamine-2-ethyl phenyl sulfonamide + potassium cyanate * pro3uct. The yield was 70#. (5) 4-0arbethoxy Amino Anillne-2-Ethyl Phenyl Sulfonamide; (208.6/1.925) 4-Phenylene dlamlne-2-ethyl phenyl sulfonamide + ethyl chloroformate -> product. The yield was 74#. ~2- DUP050059044 (6) 4,41-Hydrazo-Toluene-3.3*-Dlsulfonlc Acid? (210/2082) 4-Nitrotoluene-2-sodium sulfonate + reduce product. The product could not be freed from dlazotizable amine. (7) para,para *-Hydrazo-Toluene: (210/1950) HH h 3c GH-3 4-Nitrotoluene + reduce ... product* The yield was 40#. (8) 4-(Toluene Sulfonamino) Aniline-2-Ethyl Phenyl Sulfonamide; looSwlW!>V~ ! 4-Phenylene diaoine-2-ethyl phenyl sulfonamide chloride product. The yield was 75$. (9) 2-Methyl Benzimidazoles (308/3474) 4-toluene sulfan- ortho-Nitro-aniline + acetic anhydride -* ortho-nitro-acetylaniline reduce} ortho-amino-acetyl aniline ring close product. The yield was 50.8#. The preparation of the following compounds was attempted by the methods of synthesis indicated. The products were tested without identification. No data was obtained for the calculation of yields on these products, -3- DUP050059045 (10) 2-Methyl Benzlmldazol-4-Sulfonic Acid: (308/3707) (1) 2-Nitro-aniline-4-sulfonic acid ortho-phenylene diamine papa-sulfonic acid + acetic anhydride ring close product;, (2) 2-Methyl benzimldazol + oleum > product. (ll) 2-Methyl Benzoxazol-4-Sulfonic Acid: (312/4333) 2-Aminophenol-4-sulfonic acid + acetic anhydride (12) Sulfonated Tetra Hydrocarbazole: (307/3378) H2 i product. Carbazole The following compounds were not obtained by the methods outlined: (13) Hydrogenated 2-Methyl Benzimidazole: (308/3474) H H 2-Methyl-benzimidazole hydrogenatet no reaction* did not take place under the conditions used, -4- Hydrogenation DUP050059046 (14) Hydrogenated 2-Methyl BenzOxazol: (5X2/4194) CH.CH- 2-Methyl benzoxazol > No Reaction* Hydrogenatloft did not take place under the conditions used. (15) 2-Amino-Naphthalene-1-Sulfonamide (208.6/1925) S02KH2 nh2 2-Acetylamino naphthalene-l-sulfonic acid + PCI5 * 2-acetyl amino-naphthalene-1-sulfonchloride + NH^OH -> 2-acetylaminonaphthalene-1-sulfonamide hydrolyze product. Attempts to hydrolyze the acetyl derivative resulted in hydrolysis of both the acetyl and amide group, Patent Situation: The following compounds are believed to be new: (1) Mono-N-beta-sulfopropionyl-piperazine. (2) 4-Nitroaniline-2-ethyl phenyl sulfonamide. (3) 4-Nitroaniline-2-sulfon-hexamethylene imide. (4) 4-Ureldo-aniline-2-ethyl phenyl sulfonamide. (5) 4-Carbethoxy amino-aniline -2-ethyl phenyl sulfonamide. (6) 4,4-Hydrazo toluene,3>3'-disulfonic acid. (8) 4-Toluene sulfon-amlho aniline-2-ethyl phenyl sulfonamide (10) 2-Methyl benzimidazol-4-sulfonic acid. (11) 2-Methyl benzoxazol-4-sulfonic acid. (12) Sulfonated tetrahydro carbazole. (13) Hydrogenated 2-methyl benzimidazol. (14) Hydrogenated 2-methyl benzoxazol. (15) 2-Amino-naphthalene-l-sulfonamide. -5- DUP050059047 EXPERIMENTAL PART (1) Mono-N-Beta-Sulfoprlolonyl-Plperazlne: (JLNB 3592-95) A solution of 34 g. of sulfopropionic anhydride in 150 cc. of dioxane was added over 45 minutes with rapid stirring at 50-55C, to a solution of 48.5 g. of piperazine hexahydrate in 150 cc. of dioxane. The mixture was stirred for 2 hours and filtered and washed product with 100 cc. of dioxane* The product was placed in 150 C. oven for 20 hours in order to complete the reaction. Yield: 80# "based on either starting material. Analysis: N * 11.94#; S 12.8?#* Calculated for c7Hl44 N2S: N - 12.6#; S * 14.4#. t (2) 4-Nitro-Aniline-2-Ethyl Phenyl Sulfonamide: (JLNB 3392-97* 101) About 4 lbs. of para-nltrochlorobenzene-ortho-magnesium sulfonate was dissolved in about 10 qts, of boiling water and added potassium chloride until the hot solution yielded no more precipitate. The product was filtered and dried at 50C. The yield was about 4 lbs. of the potassium salt of para-nitrochlorobenzene-ortho-sulfonic acid. A mixture of 827 g* of this material, 624 g. of phosphorus penta-chloride and 175 cc. of phosphorus oxychloride was heated * in a 5 liter flask fitted with a thermometer, reflux and agitator to 100C. When the mixture had become sufficiently liquid, it was stirred for 1.5 hours at 100C., cooled to 25-30C, and added slowly to an ice-water mixture at 0-15C. The mixture was filtered and the cake washed with 2 liters of ice water, and sucked dry as possible. A mixture of about 85# of this wet material was refluxed for 5 hours with agitation in 1500 cc. of toluene, 363 g. of ethyl aniline and 375 g. of sodium acetate. The mixture was cooled and filtered. The toluene was distilled from filtrate with steam and the residue added to filter cake. The combined mass was slurried in water and made alkaline to Brilliant Yellow by adding 30# sodium hydroxide. The crude product was filtered and washed with 1 liter of 3# hydrochloric acid. The yield of crude product was approxl-. mately 800 g. or 87# based on para-nitro-chlorobenzene -orthopotassium sulfonate. 300 Grams of this crude material and 80 g, of ammonia dis solved in 1200 cc. of 2B alcohol was heated in a 2 liter autoclave for 6 hours at 135-140 *0. The mixture was filtered and the alcoho."1 -6- DUP050059048 distilled from the filtrate under reduced pressure. The residue was combined With filter cake. Another amination run was made using 450 g. of crude material by the same procedure as described above. Yield: 650 g. or 74# based on 4 -nitre-chlorobenzene - 2potassium sulfonate. Analysis: S = 8.97#; N m 14,01#; W02 * 13.27#. Calculated for 0x4*11504^8: S * 9*97#; N 13.09#; N02 * 14.34#, (3) 4-Nltroanillne-2-Sulfon-Hexamethylene 3mide: (JLNB 3392-115) 276 Grams of 4-nltrochlorobenzene-2-potassium sulfonate was treated with 208 g. of phosphorus pentachloride by the procedure described in Exp. 2, page 6, One-half of the wet 4-nltroehlorobenzeae-2-sulfon chloride and 130 g, of sodium acetate in 300 cc. of benzene was stirred in a 3 liter flask and 100 g of 50# hexamethylene imine added over 30 minutes at 20-40*C. The mixture was stirred for 45 minutes at 20-30*0. and 500 cc. of water added. The mixture was stirred for 30 minutes and filtered. The filter cake was crystallized from alcohol. Yield: 26 g, of product melting at 126#C. 17 Grams addition product melting at 120*0. was obtained from the benzene layer of the filtrate by evaporating the benzene to low volume under reduced pressure. The combined yield of product was aminated with 50 g. of ammonia in 750 cc. of 2B alcohol by heating the mixture for 6 hrs. at 135-140*0. in a 1 liter autoclave. The buff colored product was filtered from alcohol. The product melted at 118-120*0. Yield: 25 g. or 16# based on 4-nitroehlorobenzene-2-potassium sulfonate. Analysis: HO2 * 14.79#; 3 m 10,22#; N 10.81#. Calculated for 0x^1764838 * NOg * 15.38#; S 10.70#; K * 14.05#. (4) 4-Ureldo-Anlllne-2-Ethyl Phenyl Sulfonamide: (JLNB 3392-108) 14 Grams of potassium cyanate was added to a solution of 50 g. of para-phenylene diamlne-2-ethyl phenyl sulfonamide in dilute hydrochloric acid solution at 30*0. with rapid agitation. The product separated out as oil. The water solution was decanted off and the product slurried in dilute hydrochloric acid solution. The product was dried on steam bath. Yield: 45 g. or 70# based on para-phenylene diamine-2-ethyl phenyl sulfonamide. Analysis: N = 14.82#; 8 9.34#. Calc'd. for C15H18N4SO3: N = 16.76#; 3 = 9.59^ (5) 4 -Carbethoxy-Amino-Aniline -2-Ethyl Phenyl Sulfonamide; / '(JLNB 3392-110) 550 Grams of 4-nitro-aniline-2-ethyl phenyl sulfonamide was hydrogenated in an autoclave at 100*0, and 500 Ibs./sq.in. hydrogen -7- DUP050059049 pressure. The mixture was nucharred, filtered, and methanol distilled from the filtrate under reduced pressure* The residue was dissolved in dilute hydrochloric acid solution, nucharred, and the hrownish-gray product precipitated with ammonia* Yield: 343 g. or approximately 66# based on 4-nitro-aniline-2ethyl phenyl sulfonamide* Analysis: N 14.04#$ S* 10*77#; NO2 = 0.10#, Nitrite Value - 51.4#. Calculated for Cx^HiyOgNjS; N * 14,43#; S = 10.99#. , 50 Grams of this product was dissolved in 300 cc. of toluene and 20.6 g. of ethyl chloroformate was added dropwise at 20-300, The product was precipitated from the solution. The filter cake was filtered and slurried in cold dilute hydrochloric acid solu tion* Additional product was obtained by distilling off the tol uene from the filtrate under reduced pressure. Yield: 42 g, or 74# based on 4-phenylene diamine-2-ethyl phenyl sulfonamide. Analysis: N = 11.59#$ 3 = 8.73#. Calculated for N * .11,3#{ 3 * 8.81#. (6) 4*41 -Hydrazo-Toluene-3.3' -Pisulfonic Acid: (JliNB 3392-12) A mixture of 2 mols. of para-nitrotoluene-2-sulfonic acid, 2 moles of barium hydroxide, and 2 liters of water in a 5-liter, 4-neck flask was heated with stirring to 90 "C. A total of 300 g. of zinc dust in 3 g. portions was added over 2.5 hours. The heat of reaction held the temperature at 90 + 5C . When all of the zinc had been added, the reaction mixture turned from a dark ` red to a yellow color. Carbon dioxide was passed into the mixture until it was Only slightly alkaline to BrilliantYellow. The mixture was filtered through a covered Bttchner through which was passed a stream of COg. On standing overnight in a stoppered flask, crystals of the barium salt of the sulfonic acid settled out. This product gave a positive test for diazotizable amine* The product was recrystallized from water but an amino-free product was not obtained. Since the Azo Division desired a product free of diazotizable amine, it was decided to attempt the preparation of 4,4,-hydrazotoluene which might be obtained free of amine and which would be satisfactory to the Azo Division* See Exp. 7, pages 8 and 9. (7) 4,4'-Hydrazo-Toluene; (JLNB 3392-14) A solution of 274 g. of 4-nitrotoluene was heated in 700 cc. of solvent naphtha in a 3-liter, 4-neck flask equipped with agitation, thermometer and a reflux condenser on a water bath to 80C . 100 cc. of 30# sodium hydroxide was added in 3-5 cc. portions and 350 grams of zinc dust in 3-5 gram portions -8- DUP050059050 was added over 2.5 hours at 80-90"G. At the end of the zinc and caustic additions, the solvent naphtha layer turned from a red to a greenish yellow color. The hot solvent naphtha layer was filtered immediately on a funnel through which was passed a stream of carton dioxide. The crystalline product which separated out of the cooled solvent naphtha filtrate was filtered off and the product crystallized three times from alcohol. The white product melted at 128-152C. (Lit. M.P. for 4,4'-hydrazo-toluene is 1540.) The product showed a negative test for free amino compound. Yields 40# based on 4-nitrotoluene. Analysis: Purity - 80.2# (Product was sent for analysis without drying.) The product was tested immediately on isolation by the Azo Division. On standing for two weeks, the product turned bright yellow in color, while the melting point of the material rose to 140C. (8) 4-Toluene Sulfonamino-Anilin* ~ ' " "onamide: A mixture of 29 g. of para-phenylene diamine-2-ethyl phenyl sulfonamide, 10 g, of para-toluene sulfonchloride and 15 g. of sodium acetate was stirred in 500 cc. of water for 1 hour at 25-30*0. The temperature was raised to 50C. and stirred for 15 minutes* The water was decanted off and the residue dissolved in 3# sodium hydroxide solution. The product was precipitated by making the solution slightly acid to Congo Bed with hydrochloric acid. The light brown product was filtered off and dried in air at room temperature, Yield: 35 g. or 75# based on para-phenylene diamine->2-ethy1 phenyl sulfonamide. Analysis: W 9.23#, S 13.65#. Calculated for 92iH224 N3s2: N 9-^l#i 3 = 14,55#* (9) 2-Methyl Benzlmidazol: (J1NB 3392-75) A mixture of 276 g. of 2-nitroaniline, 214 g. of acetic anhydride, and 250 cc. of acetic acid was heated in a 3-liter flask with stirring for 18 hours at 90-100C, The mixture was drowned in 3 liters of ice water, and the light yellow product filtered off. This product gave a negative test for diazottzable amine. The 2-nitro-acetyl aniline was reduced in a hydrogenation autoclave in methanol solution at 100*0, and 500 lbs./sq. in. hydrogen pressure. The nickel catalyst was filtered off and the methanol distilled off under reduced pressure. This material was heated with 450 cc. of glacial acetic acid on steam bath for 12 hours. The solution was neutralized with ammonium hydroxide and the buff colored product filtered off on crystallization from water; the M.R, was 166-170*0. A portion of this material was DUP050059051 crystallized three times from alcohol. The M.K. was 174-176"C. Literature M.P. of 2-methyl benzimidazol is 175C. Yields 155 g* or 50.8# based on 2-nitroaniline. (10) 2-Methyl-BenzimldaZQl-4-3ulfonic Acid: (JLRB 5592-64, 76) (1) 527 Grams of 2-nitroani1ine-4- sulfonic acid was reduced ^.with iron and acetic acid in 800 cc. of water. The mixture was ' made alkaline to Brilliant Yellow with soda ash, filtered hot and the filtrate cooled to 20C. 155 g. of acetic anhydride was added to the filtrate at 25 to 55C. with stirring and the mixture heated to 8oC . over 1 hour. This mixture was evaporated to dryness on the steam bath. An alkaline solution of this material was tested by the Azo Division for use as a Diagen stabilizer. (2) 15 Grams of 2-raethyl-benzimidazol was added to 100 cc. of 22# oleum at 10-25"C. over 1 hour in a 500 cc. flask equipped with agitation and cooled in an ice bath. The mixture was drowned In an ice-water mixture with stirring, and the gray colored pre cipitate filtered off. This material was readily soluble in soda ash solution. When tested by the Azo Division it was found not to take up diazc, indicating that sulfonatlon had taken place on the /N-h of the heterocyclic ring. ,, (ll) 2-Methyl-Benzoxazol-4-Sulfonic Acid: (JLNB 5592-68) A mixture of 1 mol of 2-aminophenol-4-sulfonie acid, 1.5 mols of acetic anhydride> and 200 cc. of acetic acid was stirred in a 2 liter flask at reflux for 6 hours. Two mols of sodium acetate was added and the mixture stirred for 20 hours. The reaction mixture was evaporated to dryness on the steam bath. An alkaline solution of this residue was sent to the Azo Division for testing as a Diagen stabilizer. (12) Sulfonated Tetra-Hydrocarbazole: (JLNB 5592-60) 245 Grams of sodium was added as rapidly as possible at reflux, to a mixture of 140 g. of carbazole and 5500 g, of iso-amyl alcohol in a 5-liter flask equipped with agitation* The mixture was stirred for 1 hour after all of the sodium was added, and then l.f3 liters of iso-amyl alcohol was distilled from the mixture. The ' solution remaining in the flask was drowned with more iso-amyl * alcohol. The alcohol layer was separated and the alcohol distilled off under reduced pressure. The crude hydrogenated carbazole crystallized on cooling from the residue* The crude product was treated with Nuchar and Norite A in hot alcohol and crystallized four times from alcohol. 52 Grams of white product was obtained, -10- DUP050059052 M.P. 110-114C. Literature M.P, for tetra-hydrocarbazole is ll4C. The alcohol filtrates were diluted with water, filtered and the filter cake crystallized twice from 75# 2B alcohol. 54 g. addi tional product which had a M.R. of 106-110*0. was obtained. 15 Grams of the product melting at 110-114*0. was added with stirring to 100 cc. of monohydrate at 20-55*0. and the mixture warmed to 150C. over 2 hours. The mixture was cooled and drowned in about 250 g. of ice with stirring. The precipitated material was filtered off and a portion dissolved in soda ash solution. This alkaline solution was tested by the Azo Division as a Diagen stabilizer. Further work on this preparation was abandoned on the advice of the Azo Division. (15) Hydrogenated 2-Methyl-Benzlmidazol: (JLNB 5592-77, 119) The hydrogenation of 25 g. of 2-methyl-benzimldazol was attempted in an autoclave at 200*0. and 1000 lbs, per square inch of hydrogen pressure in the presence of nickel catalyst and using cyclohexane as the solvent. The 2-methyl-benzimidazoi was re covered unchanged. Other attempts to hydrogenate this compound In which palladium catalyst and methyl alcohol were used at 100C. and 500 lbs. per sq, in. hydrogen pressure also produced no change in the material. It is suggested that other catalysts or higher temperatures and pressures be tried. (14) Hydrogenated 2-Methyl-Benzoxazole: (JLNB 5592-122) The hydrogenation of 25 g. of 2-methyl-benzoxazole was attempted in an autoclave at 200*0. and 500 lbs. per sq. in. hydrogen pressure using cyclohexane as the solvent . The nickel catalyst was filtered off and the cyclohexane distilled off under reduced pressure* The product was tested by the Azo Division for use as a Diagen stabilizer. (15) 2-Amino-Naphthalene-l-Sulfonamlde: (J1HB 5592-70) 265 Grams of acetyl Tobias Acid was added to a mixture of 218 g, of phosphorus pentachloride and 150 cc, of phosphorus oxy chloride at 50-57C. with stirring in a 5-liter, 4-neck flask. The mixture was stirred at 65-70*0. for 1 hour, cooled, and drowned in ice-water mixture at 0-5"C. with stirring. The water was decanted off and the semi-solid 2-acetyl-amino-naphthalene-1sulfonchloride was washed with ice water . The sulfonehloride was added with rapid stirring to 500 cc. of 28# ammonium hydroxide at DUP050059053 20-50C. and stirred at 20-50*0, for 3.8 hours. The buff colored sulfonamide was isolated by acidifying the mixture with hydro chloric acid. Analysis: N *7.65#? S 10.54#, Calculated for C10H125 N2S: N * ll*3#i S = 12.9#. The hydrolysis of 0.11 mol of this product was attempted by heating in 265 g. of dilute hydrochloric acid solution containing 0.15 mol of hydrogen chloride at reflux for 12 hours. The mixture' was filtered and the filtrate made alkaline to Brilliant fellow with ammonium hydroxide. The product was filtered off and dried at 50*0. Analysis: H * IO*55#J S = 0.04#. Calculated for c 10h 102 n 2S: w ' 12,6#; S 14.42#. The analysis indicates that the sulfonamide group was hydrolyzed along with the acetyl group. Another hydrolysis was attempted using the same materials and conditions as above except that 50# alcohol was used instead of water as the solvent. Analysis: N m 11.45#; S * 7.55#: Nitrite Value * 55.5#. This analysis indicates a partial hydrolysis of both the acetyl and the sulfonamide groups. The hydrolysis of 25 g. of the 2-aeetyl-amino-naphthalene-1sulfonamide in 5# sodium hydroxide solution by refluxing for 18 * hours was tried. Some beta-naphthylamine was isolated along with some tar and unhydrolyzed material from the reaction mixture. Further work on this preparation was stopped on the advice of Dr. C. W. Croco. Submitted for Typing May 27, 1942 Typed June 25, 1942 BSD & -12- DUP050059054