[ C O ~ B U T I O NNO. 31 FROM THE DEPARTMENT OF CHEMISTRY, UNIVERSITY TENNESSEE]
OF
T H E ACTION OF FORMALDEHYDE ON meta-NITROPHENOL C. A. BUEHLER, GEO. F. DEEBEL,
AND
ROBERT EVANS
Received October 18, 19.40
Although the literature contains many references to the reaction of formaldehyde with 0- and p-nitrophenols, a study of the m-isomer has received little attention. A German patent (1) describes the preparation of 2 ,2'-dinitro-4,4'dihydroxydiphenylmethane from m-nitrophenol, although we were unable to duplicate this claim. More recently, Mehta and Ayyar (2) obtained 5-nitro-1 ,3-benzodioxane from the msubstituted phenol. Under mild conditions the first product of the phenol-formaldehyde condensation is often a hydroxybenzyl alcohol or, if the reaction is carried out in hydrochloric acid medium, a hydroxybenzyl chloride. In some cases, such as p-nitrophenol (3) or salicylic acid (4),the benzyl chloride may be isolated in substantial yield. It was of interest not only to repeat these experiments using m-nitrophenol, but also to add to our limited knowledge of the position taken by a third substituent in this m-isomer, since the two substituents present oppose each other in their directing ability. + o C H s CHzCl NOz
1
CHzCl NOz
I
(JCHs COOH NO2
I1
at" 0
I11
1
NO2 CHa
V
IV
In our studies two products were obtained from m-nitrophenol. The first, 2-hydroxy-6-nitrobenzyl chloride, I, resulted from the action of 216
FORMALDEHYDE AND WNITROPHENOL
217
methylal and hydrochloric acid a t 37-38", Since this compound resinifies very easily, it was stabilized by methylation with diazomethane t,o give 2-methoxy-6-nitrobenzyl chloride, 11, which on oxidation with potassium permanganate gave 2-methoxy-6-nitrobenzoic acid, 111. Reduction of the latter produced 2-methoxy-6-aminobenzoic acid, IV. As a further method of structural proof, I was converted into 5-nitro-1 ,3-benzodioxane1 V, by a method similar to that employed by Mehta and Ayyar (2) in producing the same compound from m-nitrophenol. The second product obtained from m-nitrophenol, by the action of formaldehyde and sulfuric acid a t 40°,was 7-nitro-1 ,3-benzodioxane1VI. This compound, on oxidation with potassium permanganate in acetic acid solution, gave the known 2-hydroxy-4-nitrobenzoic acid, VII. As an additional proof of structure, VI1 was converted into the ethyl ester which agreed in melting point with that of ethyl 2-hydroxy-4-nitrobenzoate.
VI
VI1 EXPERIMENTAL
Preparation of .%hydroxy-6-nitrobenzyl chloride. A mixture of 50 g. of m-nitrophenol, 400 cc. of concentrated hydrochloric acid and 150 g. of methylal (b.p. 4246') in a three-necked, round-bottomed flask was heated under reflux with stirring at 37-38' while hydrogen chloride gas was continually passed through the reaction-mixture. After 24 hours some solid began t o separate and the amount increased u p t o 120 hours, at which point the reaction was stopped. The reddish-yellow solid was separated by decantation or by filtration through sharkskin filter paper. After washing several times with water and then stirring in several portions of benzene, there remained 17-25 g. of the crude, yellow benzyl chloride, m.p. 130-140' with decomposition. For additional purification, this solid was taken up in a large quantity of benzene heated t o not over 38", and recrystallized by evaporation of the solvent with a n electric fan. The yield of this purer, light yellow product, m.p. 142-143" with decomposition, was from 3 t o 10 g. (5 to 15%). Anal. Calc'd for CTH&lNOs: C1, 18.93; mol. wt., 187.5. Found: C1, 18.93, 18.75; mol. wt. (cryoscopic, acetic acid), 194, 201, 198. B-Methozy-6-nitrobenzyl chloride. Diaxomethane, 6.6 g., was generated from nitrosomethylurea (5) and dissolved in about 200 cc. of ether at 0". This ethereal solution, kept a t O", was mixed with another ethereal solution, about 100 cc. a t 0', containing 20 g. of the crude benzyl chloride. After 15 minutes the temperature was allowed to rise t o that of the room, under which conditions the reaction-mixture was kept for 2 hours. The solid which had formed was then filtered off, and crude 2methoxy-6-nitrobenxyl chloride was recovered as oily crystals upon evaporating the filtrate to dryness. After being washed with four or five 15-cc. portions of 95%
218
BUEHLER, DEEBEL, AND EVANS
ethanol, the crystals were almost white. Recrystallization from a water-ethanol mixture gave 5.8 g. of white crystals melting a t 65-66". Anal. Calc'd for CsH8ClNOs: C1, 17.61; mol. wt., 201.5. Found: C1, 17.53, 17.41; mol. wt. (cryoscopic, acetic acid), 207, 204. 2-Methoxy-6-nitrobenzoicacid. The methoxy chloride, 2 g., and 6 g. of potassium hydroxide were dissolved in 60 cc. of water. This solution was heated on a steambath while 6-10 g. of potassium permanganate was added gradually over a period of 30 minutes. After an additional hour of heating, the manganese hydroxide was filtered off and the filtrate was acidified with hydrochloric acid. Upon cooling, a white solid separated. After one crystallization from water, 0.9 g. of an almost white product, melting a t 180-181", was obtained [Roberts, Wiles, and Kent (6) give J8Oo]. Anal. Calc'd for C8H7iY06: N, 7.11; neut. equiv., 197. Found: X, 6.91, 7.00; neut. equiv., 202, 207. 2-Methoxy-6-aminobenzoicacid.' Reduction of the nitro acid was accomplished catalytically in absolute alcohol using Raney catalyst and hydrogen a t 35 lbs. (2.4 atmos.) pressure. From 1g., there was obtained about 1 g. of a crude product which after crystallization from water four times melted a t 85" [Roberts and co-workers (6) give 877. Anal. Calc'd for CsHpNOs: N, 8.38. Found: N, 8.37, 8.46. 6-Nitro-f ,S-benzodioxane.' A solution of 1 g. of 2-hydroxy-6-nitrobenzyl chloride in 3 cc. of U. S. P. 40% formaldehyde and 15 cc. of concentrated hydrochloric acid was heated under reflux slowly to 100" for about 1 hour. The temperature was then raised to 140" where i t was held for another hour. After cooling, the supernatant liquid was decanted from the reddish-brown viscous mass. This product was washed with a little water, and then extracted with ether. Upon evaporation, about 0.04 g. of a yellow solid was obtained. Crystallization from an ethanol-water mixture gave colorless needles, m.p. 77". Anal. Calc'd for CsH7XO4: N, 7.73. Found: N, 7.70, 7.65. A mixed melting point with a sample of 5-nitro-1,3-benzodioxaneprepared by Mehta and Ayyar's method (2) gave no appreciable depression. Preparation of 7-nitro-f ,S-benzodioxane. A solution of 20 g. of m-nitrophenol in 25 cc. of 40% formaldehyde, prepared by gentle warming, was cooled to 10". In a round-bottomed flask equipped with a stirrer, 60 cc. of a 3:l sulfuric acid-water mixture was cooled to 10". The formaldehyde solution was then added gradually over a period of 5 minutes to the stirred sulfuric acid so that the temperature did not rise above 42'. Some solid, which formed during this period, remained during three hours more agitation a t 38-42". The reaction-mixture was then poured into water, and an oil separated. This oil was washed with a saturated solution of sodium carbonate until the aqueous solution no longer became red in color. After remaining in the carbonate solution overnight, the oil became semi-solid. This produdt was washed with a small amount of water, and then crystallized from water in the form of long, white, glistening needles, melting a t 90.5"; yield, 2.3 g. (9%). Anal. Calc'd for CsH7iYOl: C, 53.03; H , 3.87; S , 7.73; mol. wt., 181. Found: C, 53.26, 52.88; H I 3.98, 4.03; K , 7.61, 7.57, 7.63; mol. wt. (cryoscopic, benzene), 183, 182, 181. 8-Hydroxy-4-nitrobenzoicacid. 7-Nitro-lJ3-benzodioxane,1 g., was dissolved in 35 cc. of glacial acetic acid, and 5 g. of potassium permanganate and 55 cc. of water 1
We are indebted to Mr. Geo. W. Parker for this synthesis.
FORMALDEHYDE AND 112-NITROPHENOL
219
were added. This mixture was refluxed for about 4 hours, a t the end of which time clarification was accomplished by bubbling sulfur dioxide through the mixture. The solution thus obtained was evaporated almost to dryness in a current of air, diluted with about 100 cc. of water, and 7 cc. of concentrated hydrochloric acid was added. The solid, which now completely precipitated, was filtered off, dissolved in hot water and treated with boneblack to remove the color. After filtration, the acid wasagain precipitated with hydrochloric acid and finally recrystallized from water as fine, slightly yellow needles; yield, 0.2 g. The pure product darkened a t 225" and melted a t 235' with decomposition [Borsche (7) gives 235" with decomposition]. Anal. Calc'd for CrHsNO,: N, 7.65; neut. equiv., 183. Found: N, 7.73, 7.84; neut. equiv., 185, 184. The acid, 0.7 g., was esterified as recommended by Borsche (7) to give 0.5 g. of the ethyl ester, m.p. 86-87" (Borsche gives 87"). SUMMARY
On condensing mnitrophenol with methylal and with formaldehyde, each in acid medium, the directing influence of the hydroxyl group predominates, since moderate yields of 2-hydroxy-6-nitrobenzyl chloride and 7-nitro-1 ,3-benzodioxane, respectively, were obtained. KNOXVILLE,TENN. REFERENCES (1) German Patent 73,951 (to Meister Lucius & BrUning). (2) MEHTAAND AYYAR,J . Univ. Bombay, 8 , Pt. 3, 176 (1939); Chem. Abstr., 54,2814 (1940). (3) Org. Syntheses, 20, 59 (1940). (4) Unpublished work of this Laboratory. (5) Org. Syntheses, 16, 3 (1935). (6) ROBERTS,WILES,AND KENT,J . Chem. Soc., 1932,1795. (7) BORSCHE,Ann., 390, 18 (1912).
