[CONTRIBUTION FROM TEE LABORATORY OF OR(IANIC CHEMISTRY OF TEE STATB UNIVEWITY OF IOWA] THE ACTION OF NITROUS ACID ON THE BROMINE SUB- STITUTION PRODUCTS OF SOME PHENOLS L. CHAS. RAIFORD AND JOHN HOWE SCOTT Received May 17, 1957 By oxidation of tetrachloro-p-cresol with nitric acid Schneiderl ob- tained a tetrachloro cyclic ketone without loss of halogen. Following the same method, Auwers2 prepared from 2,6-dibromo-p-cresol a product of composition C ,H aBrzNOa, while Zincke3obtained a similar product from the corresponding chlorine compound. The last two substances were represented as shown below: 0 Meanwhile, in attempts to prepare the analogous nitroso compounds Zincke and students4tested a number of the bromine substitution products of the cresols toward nitrous acid. In all cases they obtained nitro com- pounds which were formed by the replacement of hydrogen or bromine by the nitro radical. Zincke6 summarized the results as follows: “In the meta series this reaction gives products in which the halogen atom para to hydroxyl is replaced by the nitro group, while in the ortho and para series the ortho halogen is replaced”. Raiford and others6 found that in most cases with this method of nitration the ortho and meta series give iso- meric inononitro compounds, and that the method is selective to the ex- tent that chlorine is not replaced.’ 1 SCHNEIDER, Dissertation, Marburg (1896), p. 29. AuwERs, Ber., 36,457 (1902). 3 ZINCKE, Ann., 328,289 (1903). 4 FOSTER, Dissertation, Marburg (1898); WAGNER, ibid., (1899). 5 ZINCKE, J. prakt. Chem., [2], 61,565 (1900). 6 RAIFORD, J. Am. Chem. SOC., 44,158 (1922). 7 RAIFORD AND MILLER, ibid., 66,2131 (1933). 213
Transcript
[CONTRIBUTION FROM TEE LABORATORY OF OR(IANIC CHEMISTRY OF TEE STATB UNIVEWITY OF IOWA]
THE ACTION OF NITROUS ACID ON THE BROMINE SUB- STITUTION PRODUCTS OF SOME PHENOLS
L. CHAS. RAIFORD AND JOHN HOWE SCOTT
Received May 17, 1957
By oxidation of tetrachloro-p-cresol with nitric acid Schneiderl ob- tained a tetrachloro cyclic ketone without loss of halogen. Following the same method, Auwers2 prepared from 2,6-dibromo-p-cresol a product of composition C ,H aBrzNOa, while Zincke3 obtained a similar product from the corresponding chlorine compound. The last two substances were represented as shown below:
0
Meanwhile, in attempts to prepare the analogous nitroso compounds Zincke and students4 tested a number of the bromine substitution products of the cresols toward nitrous acid. In all cases they obtained nitro com- pounds which were formed by the replacement of hydrogen or bromine by the nitro radical. Zincke6 summarized the results as follows: “In the meta series this reaction gives products in which the halogen atom para to hydroxyl is replaced by the nitro group, while in the ortho and para series the ortho halogen is replaced”. Raiford and others6 found that in most cases with this method of nitration the ortho and meta series give iso- meric inononitro compounds, and that the method is selective to the ex- tent that chlorine is not replaced.’
In the present work this study has been extended. It has been found that when an acetic acid solution of 2,4,6-tribromo-sym-xyleno18 was treated with sodium nitrite, as previously explained,g there was obtained a product that decomposed at about 147". By fractional crystallization this material was separated into two substances, (1) and (2), that melted a t 172-173" and 172" respectively. When a mixture of these products was heated it liquefied between 130" and 145" and underwent a t least partial decomposi- tion.
At first it was thought that these compounds might be the expected isomeric mononitrodibromoxylenols neither of which was found on record. Analysis of product (1) gave figures that agree with such a composition, and further study of it showed that the nitro radical was in position 4 (OH = 1). The substance was reduced to the corresponding amino compound, and this was converted into the mixed acetyl-benzoyl derivatives by introduction of the radicals in both possible orders. Isomeric mixed diacyl derivatives were obtained, and no rearrangement was observed, which shows that the nitro radical in compound (1) is not in the ortho position as respects hydroxyl.* This view is supported also by the behavior of the compound when oxidized. When it was treated with fuming nitric acid as directed by Kohn and Fhbinowitschlo it gave the corresponding dibromo-m xyloquinone previously obtained by Jacobsenll by oxidation of dibromo- mesitol. These relations are indicated on the following page.
Qualitative tests of compound (2) indicated the absence of nitrogen, and a mixture of it and the xyloquinone specified above melted without de- pression. It was further identified by a study of its derivatives. Reduc- tion of it gave a compound which, though not entirely colorless, was proved to be the required hydroquinone. The latter was easily converted into diacyl derivatives that were colorless and readily crystallized.
It is of particular interest here to note the behavior of this quinone to- ward amino compounds. Attempts to prepare the oxime, the phenyl- hydrazone and the semicarbazone gave, in each case, the hydroquinone
The position was determined in the following way.
8 N~LTING AND FOREL, Ber., 18,2679 (1885). e RAIFORD, Am. Chem. J., 46,426 (1911). * It has been shown by RAIFORD AND OTHERS [ J . Am. Chem. Soc., 68,1586 (1934) I
that when two different acyl radicals derived from carboxylic acids are introduced into an ortho aminophenol, only one mixed diacyl derivative can usually be obtained, and in this product the heavier and more acidic radical is attached to nitrogen. To meet this requirement the migration of acyl from nitrogen to oxygen must occur in one of these reactions.
lo KOHN AND RABINOWITSCH, Monatsh., 48,380 (1927). l1 JACOBSEN, Ann., 196,273 (1879).
BROMINE SUBSTITUTION PRODUCTS OF PHENOLS 215
Proof of structure of 2,6-dibromo-4-nitro-sym-xylenol
in yields of 81, 83, and 94%, respectively, and nothing else was isolated from the reaction mixtures.t These relations are shown on page 216.
The second compound studied was the tribromo derivative of resorcinol monomethyl ether. When this product was nitratedI2 it gave a high yield of a mononitrodibromo compound that melted at 126-127'.$ Reduction of this product (111) (see accompanying diagram) gave an aminophenol (IV) which was readily converted into the corresponding diacyl derivatives (V) and (IX). Partial hydrolyses of these products gave the phenolic substances (VI) and (VIII), respectively, which must have had the re- maining acyl groups attached to nitrogen. When these products, in turn, were scylated with the required reagents they gave the acetyl-benzoyl derivatives (VII) and (X), which melted a t 186" and 170-171', respec-
t This behavior agrees with the observations of NEB [Ann., 257,12 (1887)l who was unable to obtain an oxime from duroquinonecarboxylic acid, and of KEHRXA" [Ber., 21, 3320 (1888)l who found that tetrasubstituted quinones, such as chloranil, give no oximes. These authors did not test their products toward phenylhydrazine and sernicarbazide, and the formation of a hydroquinone was noted in only one case.
I* RAIFORD AND GROSZ, J . Am. Chem. SOC., U, 3422 (1931). $ Ko'hn and Loff [Monatsh., 46,594 (1924)l recorded 122" for a product that should
have the structure of this one.
216 L. CHAS. IUIFORD AND JOHN HOWE SCOTT
Behavior of 2,4,&tribromo-sym-xyleno1 toward nitrous and nitric acids
OH
CH OH
tively, and which depressed each other's melting points profoundly. This showed that the positions of the acyl radicals could not have been the same in the two products (see page 217). But, inasmuch as the partial hydrolysis of these compounds gave the same benzoylaminophenol, product (VIII), it follows that in the latter reaction the benzoyl radical in product VI1 migrated from oxygen to nitrogen.$
Acknowledgment. We are indebted to Mr. Donald W. Kaiser of this Laboratory for assistance with certain portions of the experimental work.
EXPERIMENTAL PART
~,4,6-Tn'bromo-sym-zyZenoZ (OH = I).-ThW gave 162.5" as the melting point of a product which he regarded as having this structure, but he described no method of preparation and recorded no analytical data. In the present work, Anselmino's" method, modified in certain details, was used. To a solution of one molecular proportion (122 9.) of sym-m-xylenol in 800 cc. of acetic acid there was slowly added three molecular proportions of bromine dissolved in 150 cc. of acetic acid, with con- tinual stirring. The solution was a t room temperature when reaction was started; by the time all bromine was in it was near the boiling point of acetic acid. The pasty mass that formed as the mixture cooled was allowed to stand overnight and was then poured with stirring into ten volumes of dilute solution of sodium acid sulfite. The yield was nearly quantitative. Crystallization from carbon tetra-
$ This behavior has previously been noted by RAIFORD AND COUTURE [ J . Am.
Chem. Soc., 46,2307 (1924) ] in the study of other ortho aminophenols.
BROMINE SUBSTlTUTION PRODUCTS OF PHENOLS 217
Derivatives of 2,4-dibromo3-methoxy-6-nitrophenol OH OH OH
OCHa
Br Br
I \ I
m.p., 186'
Br m.p., 170-lo
218 L. CHAS. RAIFORD AND JOHN HOWE SCOTT
chloride gave colorless, silky needles that melted a t 166", which agrees with Ansel- mino's value.*
Nitration of Iribromo-sym-xyleno1.-A suspension of 100 g. of the tribromo com- pound in 700 cc. of acetic acid a t room temperature was stirred for one and one-half hours while 2.5 molecular proportions of sodium nitrite was added. No attempt was made to control the temperature. The mixture was allowed to stand overnight and was then poured with stirring into 10 volumes of water. A yield of 89% was obtained. One crystallization from carbon tetrachloride gave a mass of fine yellow crystals that seemed to decompose a t about 147", suggesting a mixture. Several repeated crystallizations finally gave pale lemon-colored clusters of tablets that decomposed a t 172-173". The yield of purified material was 58%. This compound, designated above as product (l), was identified as 2 ,6-dibromo-3,5-dimethyl-4-nitrophenol.
Anal. Calc'd for CsH,BrlNOa: Br, 49.23. Found: Br, 48.92.
9,6-Dibromo-3 ,b-dimethyl-4-aminophenol.-Twenty grams of the above nitro compound, dissolved in 125 cc. of boiling acetic acid, was reduced by means of stan- nous chloride and hydrochloric acid. The yield of purified amine hydrochloride16 was 69%.
Anal. Calc'd for CsHld3r&1NO: N, 4.22. Found: N, 4.26.
A portion of the hydrochloride was made into a paste with water and treated with ammonium carbonate solution to obtain the aminophenol, which was almost colorless when freshly prepared. Crystallization from benzene gave pale brown needles that melted with decomposition a t 207".
Anal. Calc'd for C8HoBr2NO: Br, 54.23. Found: Br, 53.94. 8,6-Dibromo-3,b-dimethyl-~-diacetylaminophenyl acetate.-When a portion of the
required aminophenol, mixed with anhydrous sodium acetate, was warmed with the theoretical amount of acetic anhydride the product obtained had a melting range of 120-135" and could not be purified by crystallization. By the use of excess of acetic anhydride a single compound was obtained. Crystallization from alcohol gave colorless plates that melted a t 153-154". The yield of purified material was 81%. Analysis indicated the presence of three acetyl radica1s.t
Anal. Calc'd for C I ~ H I ~ B ~ ~ N O ~ : Br, 38.00. Found: Br, 37.99.
Hydrolysis of this product with caustic alkali caused the loss of acyl from oxygen and one of these groups from nitrogen to give the corresponding acetylaminophenol. Analytical data and other properties for this and related acyl derivatives are given in Table I.
b,6-Dibromo-m-xyloquinone.-This .compound, designated above as product (2), melted a t 172", which is two degrees lower than that reported by Jacobsen. Analysis of the product here under consideration indicated that it was nearly pure.
* It is of interest here to note that attempts to alkylate this phenol were unsuccess-
16 RAIFORD, Am. Chem. J . , 48,419 (1911). t The formation of such triacetyl derivatives has previously been noted by PFOB
[Monatsh., 18, 475 (1897)] and by RAIFORD AND COUTURE: [ J . Am. Chem. Soe., 46, 2313 (1924)l.
ful. The failures may be due to steric hindrance.
BROMINE SUBSTITUTION PRODUCTS OF PHENOLS 219
POSITXON OF ACYL RADICAL
Aoetalyminophenol.. . . . .
N-Acetyl-0-benzoylc, . . .
N-Benzoyl-0-benzoyl.. . .
Anal. Calc'd for CsHeBr102: Br, 64.42. Found: Br, 54.33. ~,6-Dibromo-m-sylohydroquinone.-In the first attempt to obtain this product a
dilute alcoholic solution of the quinone was saturated with sulfur dioxide. A dark- colored product, probably a quinhydrone, was formed, but this was not changed by fifteen hours' further treatment with the gas. In a second experiment a solution of 10 g. of stannous chloride (30% excess) in 10 cc. of concentrated hydrochloric acid was added gradually through a return condenser to a boiling solution containing 10 g. of the quinone in 50 cc. of acetic acid. The mixture became dark colored at first but was nearly colorless after all stannous salt had been added. Heating was continued for fifteen minutes, and the liquid was allowed to cool, which caused a
TABLE I ACYL DERIVATIVES OF 2,6-DIBROMO-3,5-DIMBTHYL-4-AMINOPHENOL
YIELD' %
88"
69
82
Mc'd
47.47
36.28
31.80
40.10
36.28
Found -- 47.34
35.98
31.57
39.89
36.09
I I
Colorless rhombo- hedra
Colorless needles
Colorless amor- phous powder
COYPOBITION CRYETAL Ids;, 1 F O W b
243-244
252-253
d
Benzoglaminophenol. . . .
N-Benzoyl-0-acetyl.. . . .
ANALYLIES, HALOGEN
90
These figures refer to purified material. * These products were crystallized from a mixture of equal volumes of acetone and
The Schotten-Baumann method gave poor results here, but that described by toluene.
Einhorn and Hollandt [Ann., 301,101 (1898)l was quite satisfactory.
portion of the product to separate in pale brown needles. The mixture was filtered, and concentrated hydrochloric acid was added to the filtrate, which caused an addi- tional portion of hydroquinone to crystallize out. The total yield was 96%. In this condition the compound decomposed when heated to about 211'. Attempts to recrystallize i t were not successful. Its identity was established by a study of its derivat,ives. $
* Dbd not melt below 276'.
1 CLAWS AND RUNSCHKE [ J . prakt. Chem., [2], 42, 124 (lS90)] used stannous chloride to reduce the corresponding dichloroquinone and stated that they obtained a product that melted at 224'. The compound was not analyzed and is not listed in Richter's Lexikon, nor in Stelzner's Register. The authors assumed that the sub- stance was a hydroquinone, because they were able to oxidize i t into the quinone with which they started, and for which they obtained analytical data.
The diacetyl derivative.-A mixture of 10 g. of the hydroquinone, 3 g. of fused anhydrous sodium acetate and 15 cc. of acetic anhydride was gently warmed for three-fourths hour, and the cooled mixture was extracted with water. The residue was crystallized from alcohol, from which it separated in colorless needles that melted a t 215-216'. The yield of purified material was 86%.
Anal.
The dibenzoyl derivative was obtained by treatment of the hydroquinone with ben- zoyl chloride by the Schotten-Baumann method. Crystallization of the product from n-amyl alcohol gave h e colorless needles that melted a t 249-250'. A 76% yield of purified material was obtained.
Calc'd for C12HllBrz04: Br, 42.10. Found: Br, 41.76.
Anal. Calc'd for C24H16Br204: Br, 31.74. Found: Br, 31.70.
8,4,6-Tribromoresorcinol monomethyl ether (OH = l).-Benedikt'6 found 99" as the melting point for a product he obtained by the action of excess of bromine on an acetic acid solution of resorcinol monomethyl ether, and which he designated a~ a
TABLE I1 ACYL DERIVATIVES OF 2,4-DIBR0M0-3-METH0XY-6-~M1NOPHENOL
8 ,~-lh'bromo-S-methox~-6-nitrophenol.-To a solution of the above tribromo compound in acetic acid there was gradually added with stirring 2.5 molecular proportions of sodium nitrite, while the temperature was held between 12" and 16". After standing overnight the solution was poured into about 5 volumes of water, stirred well and allowed to remain until the precipitate had settled. The yield was 95%. Repeated crystallization from alcohol gave yellow needles that melted a t 126-127". Kohn and LOiP reported 122" for a product which probably has this composition, though their analytical data did not indicate a pure substance. Also, while the present work was in progress Hodgson and Nixon19 reported 128" for a compound obtained in an attempt to alkylate 2,4-dibromo-3-fluoro-6-nitrophenol, which they regarded as having thesame structure as the one here under consideration.
Anal.
9 ,~-L~ibromo-S-methox~-6-aminophenol.-When the nitro compound just described was reduced with a mixture of stannous chloride and hydrochloric acid20 the corre- sponding amine hydrochloride was obtained in nearly quantitative yield.
Calc'd for C,H6Br2NO4: Br, 48.92. Found: Br, 48.70.
Anal. Calc'd for C,HsBrzCINOa: Hal, 58.62. Found: Hal., 58.59.
A portion of this salt was mixed into a paste with water, the solution was treated with the calculated amount of ammonium carbonate, and filtered, and the residue was washed with several small portions of cold water. A yield of more than 90% was obtained. Crystallization from ligroin gave pale brown needles that melted a t 105-106.5".
Anal. Calc'd for CIH,Br2NO2: Br, 53.87. Found: Br, 53.99.
The diacyl derivatives.-The simple and mixed diacyl derivatives were obtained by standard methods. Analytical data and other properties of the products are given in Table 11.
SUMMARY
When sym-tribromo-m-xylenol was subjected to the action of nitrous acid as directed by Zincke there was obtained a mixture of 2,6-dibromo- 4-nitro,-m-xylenol and 2,6dibromo-m-xyloquinone. When 2,4,6tribromo- resorcinol monomethyl ether was treated in the same way, 2,sdibromo- 3-methoxy-6nitrophenol was formed. The relative positions of the hydroxyl and nitro radicals in these compounds were determined by reduc- tion to the corresponding aminophenols and study of the mixed acetyl- benzoyl derivatives of these products. From the aminoxylenol isomeric mixed diacyl derivatives were obtained and no rearrangement was ob- served, which showed that the amino and hydroxyl groups were not ortho to each other. The migration of acyl previously found to be characteris- tic of o-aminophenol derivatives was found to occur in the product ob- tained from resorcinol monomethyl ether.
