[CONTRIBUTIONFROM THE DEPARTMENT OF CHEMISTRY OF TEE UNIVERSITY O F ROCHESTER]
THE PROPERTIES OF SOME PHENOXYACETONES D. STANLEY TARBELL
Received December $1, 1941
The atomic coniiguration CH2=CHCH20C=C is the group involved in the Claisen rearrangement of aryl allyl ethers, the two carbon atoms on the right being part of an aromatic nucleus (1). The analogous systems which have been shown to give rearrangement are CH2==CHCH20CH=NR (2), CH2=CHCH2SC=C (3), CH2=CHCH2SC=N (4), and CHFCHCH~CC=C (5). In these examples, the CH2=CHCH2 group has not been altered, but it has been found that the systems N=CCH20C=C (6) and HC=CCH20C=C (7) do not give rearrangement of the Claisen type on pyrolysis. The work described in this paper had its inception in an examination of the behavior of 4-methylphenoxyacetone (I) and related compounds upon pyrolysis, since they contain the group O=C(CHs)CH20C=C.
I The resulli indicate that this group does not allow a rearrangement to take place, and that it should be classified with the last two systems mentioned in the first paragraph.' The preparation of 4-methylphenoxyacetone, first made by Stoermer (8), was tried under a variety of conditions, using both chloroacetone and bromoacetone. In every case, even with an excess of haloacetone, much of the phenol was recovered unchanged and the yields were poor. The best method tried was that o:f Calaway and Henze (9, lo), according to which the sodium salt of the phenol in benzene is treated with bromoacetone, but even here the yields were below 50%. In reaction with p-cresol, the contrast between the reactions of the haloacetones and allyl bromide is striking; the former give a poor yield of a mixture of products, with acetone and potassium carbonate as the reaction medium, while allyl bromide gives excellent yields of the allyl phenyl ethers under the 'Since this article was submitted for publication, Hurd and Perletz have described the synthesis of phenoxyacetone and its behavior on heating to 650" (Abstracts of papers presented before the Organic Division, Memphis Meeting of the American Chemical Society).
251
252
D. STANLEY TARBELL
same conditions (11). Furthermore, treatment of the sodium salt of a phenol with allyl bromide in benzene yields a large proportion of the C-a,lkylated product such as 11, in addition to the ether (12). Bromoacetone under the same
OH
OH
I1
I11
conditions gave a poor yield of the 0-alkylated compound I but nothing corresponding to the C-alkylation product I11 could be isolated by careful distillation of the alkali-soluble fraction. The difference in behavior of the allyl and acetonyl compounds is probably due to the fact that the carbonyl group is electron-attracting and tends to make the halogen more "positive" than is the allyl halogen. It was observed that the compound believed to be 4-methylphenoxyacetone showed some solubility in Claisen's alkali, and it seemed possible that this was because the product was actually the C-alkylated compound, 2-acetonyl-4methylphenol (111). The insolubility of I11 in aqueous alkali might be due to formation of a stable hemiacetal. To prove the structure of the product, it was synthesized by another method which ruled out the possibility of C-alkylation. @-Methylally14-methylphenyl ether (IV) was ozonized, and the semicarbazone OH OCH2CCHS '\CH2CCH3 A /\ II 0 'I1 AH, CH1 // CH2 % I CH3 V IV
()
-II
of the product shown to be identical with that of the product from p-cresol and bromoacetone. The ether IV was also rearranged to V, from which the acetonyl compound I11 was prepared in impure form by ozonization. Compound I11 was characterized by preparation of the semicarbazone. When 4-methylphenoxyacetonewhich had been purified through the bisulfite compound was heated at 250" for two and one-half hours, most of it was recovered unchanged, but a small amount of p-cresol was recovered and identified. The purified 4-methylphenoxyacetone decomposes on long standing a t room temperature and an alkali-soluble material is formed, presumably p-cresol. 2,6-Dimethylphenoxyacetonebehaved similarly when it was heated a t 200" for one hour; there was some formation of an alkali-soluble substance, presumably 2,6-dimethylphenoll and much of the starting material was recovered unchanged. Pure 2,6-dimethylphenoxyacetone also decomposed slowly a t room temperature, and 2,6-&methylphenol was isolated from a sample which had stood for five weeks.
253
PHENOXYACETONES
The retiults of the experiments at high temperatures indicate that the system O=C(CHa)CH20C=C does not undergo a rearrangement analogous to the Claisen rearrangement. The observation that 4-methylphenoxyacetone (I) can be partially extracted from petroleum ether and benzene solutions by Claisen's alkali [prepared from potassiuni hydroxide and dilute methanol (13)] was rather unexpected, and a number of substituted phenoxyacetones were prepared to determine the effect of substituents on the acidic character of the compound. The extraction is not due to a physical solubility effect. Blanks carried out on several compounds showed that extraction of the benzene solution with a mixture of water and meth.ano1, richer in methanol than Claisen's alkali, did not remove as much of the ketone as Claisen's alkali. The ketones were changed to some extent by being dissolved in Claisen's alkali, since they were recovered as viscous oils. The semicarbazones could be obtained from the oil, however, showing that the condensation or resinification of the ketones was only partial. OCHzCOCHS
""0
b H 3
OCH2 COCH, b H 3
0 CH3
VI
VI1
The substituted phenoxyacetones prepared were of two types. Several phenoxyacetones were prepared with groups which increase the acidity of phenols (nitro and bromo) to find whether they would also increase the acidity of the acid hydrogen in the phenoxyacetones. This is presumably the hydrogen on the carban adjacent to the ether oxygen. The phenoxy1 group has an electronattracting inductive effect; phenoxyacetic acid has a dissociation constant 42 times greater than acetic acid (14). The second class of compounds prepared included 2,&dimethylphenoxyacetone 171, the 2,4-dimethyl compound VI1 and the nitro derivative of each, in order to see whether the phenomenon of damped resonance (15) would affect the behavior of the compounds greatly. The resonance forms contributing to the structure of aromatic ethers include three in which the oxygen is attached to the ring by a double bond, with a positive charge on the oxygen and a negative charge in the ortho or para positions, as in VIII, in which the group attached to the oxygen lies in the plane of the (+)
0-CH2 C OCH,
0 (->
VI11
(+)
O-CH2COCH3
cH30cH3 (-)
IX
254
D. STANLEY TARBELL
ring. Two methyl groups in the ortho position should prevent the occurrence of a similar planar structure such as IX, Le., the resonance is damped or inhibited by steric factors. Such steric effects have been observed recently (16) in several instances involving amino and nitro groups as the resonating groups, and have also been used to explain the unusual reactions of di-ortho substituted benzoic acids (17). The acidity of the phenoxyacetones was studied by extracting them from benzene with Claisen’s alkali under uniform conditions and determining the amount extracted. This, of course, is a qualitative method only, because the relative solubilities as well as the intrinsic acid strength enter in. It was found that, while the methyl- and bromo-phenoxyacetones could be recovered unchanged from Claisen’s alkali, a t least in part, 4-nitrophenoxyacetone was cleaved very rapidly at room temperature by Claisen’s alkali, yielding p-nitrophenol. The side chain was apparently polymerized after cleavage. There was no evidence that 4-nitrophenoxyacetone could dissolve in Claisen’s alkali without cleavage. The statement by Stoermer and Brockerhof (18) that 4nitrophenoxyacetone dissolves in aqueous alkali to give a yellow solution from which it can be recovered unchanged could not be confirmed, as the compound is insoluble in aqueous alkali. 2-Ntrophenoxyacetone was decomposed very rapidly by Claisen’s alkali, but nothing could be isolated, not even o-nitrophenol. The same results were obtained with 2,6-dimethyl-4-nitrophenoxyacetone and 2,4-dimethyl-6-nitrophenoxyacetone. The former was cleaved by Claisen’s alkali giving 2,6-dimethyl-4-nitrophenol,while the latter was decomposed completely and nothing could be identified. 3-Ntrophenoxyacetone did not cleave, but was extracted to a greater degree than any of the methyl or the bromine substituted compounds; this must be due to the increased acidity of the compound caused by the inductive effect of the nitro group. The results on the extraction experiments are given in Table I. The first column gives the percentage of the ketone remaining in benzene solution after three extractions with Claisen’s alkali, the second the percentage extracted by Claisen’s alkali but not cleaved by it, and the third the percentage of the ketone cleaved by Claisen’s alkali. The procedure followed is described in the experimental part. The results in the table show that the 4-bromo and the %nitro ketones are extracted by Claisen’s alkali to a greater extent than the dimethyl ketones, and the solubility factor referred to above would probably operate in the opposite direction. These results must be due to the greater acidity of the compounds caused by the electron-attracting inductive effect of the bromine and the nitro groups substituted in the phenoxy group. The cleavage reaction shown by the 4-nitro ketones and the decomposition of the %nitro compounds in the presence of Claisen’s alkali must be due to a resonance effect involving forms such as VI11 and IX. If nothing but an inductive effect was operating, the 4-nitro compound should behave like the 3-nitro compound, except that the effect would be smaller in the former. In order to study the cleavage reaction under more exactly defined conditions,
255
PHENOXYACETONES
some rough quantitative tests were made of the cleavage reaction using 5% sodium methoxide in methanol. The procedure followed is described in the experimenltal part. The po'or recovery of material from 2-nitrophenoxyacetone was due to the fact that it formed a black material insoluble in ether. The results show that the 2,6-dimethyl-4-nitrophenoxyacetoneis cleaved by sodium methoxide at a rate not much different from the unmethylated compound, while 2-nitrophenoxyTABLE I EXTI~ACTION OF PHENOXYACETONES FROM BENZENE BY CLAISEN'SALKALI COMPOUND
1
% REMAINING I N BENZENE
Phenoxyacetonea ......................... 4-Methylphenoxyacetone . . . . . . . . . . . . . . . . . . 2,4-Dimethylphenoxyacetone............. 2 6-Dimethylphenoxyacetone . . . . . . . . . . . . . 4-Bromophenoxyacetone . . . . . . . . . . . . . . . . . . 2-Nitrophenoxyacetone . . . . . . . . . . . . . . . . . . . 3-Nitrophenoxyacetone . . . . . . . . . . . . . . . . . . . 4-Nitrophenoxyacetone . . . . . . . . . . . . . . . . . . . 2-Nitro-4,6-dimethylphenoxyacetone. ..... 4-Nitro-2,6-dimethylphenoxyacetone. .....
77
86 86 90 86 5
1
% EXTRACTED WITHOUT CLEAVAGE
I
1
?% CLEAVAGE
19 9 2 3
14 Only decomposition products 34 4 1 5fib 16 42= 8d
60
29 16 84
TABLE I1 CLEAVAGE OF PHENOXYACETONES BY SODIUMMETHOXIDE C0M P0U ND
4-Nitrophenoxyacetone. ...................... 2,6-Dimethyl-4-nitrophenoxyacetone., ........ 2-Nitrophenoxyacetone, ...................... 4-Bromoplienoxyacetone. .....................
1
WEIGHT, G .
~
TIME G.
0.5 0.5 0.5 0.6
4.5 hrs.
4.66 hrs. 5 min. 19 hrs.
0.28 0.34 0.01 0.54
0.14 0.09 0.03 0.05
acetone is decomposed extremely rapidly under the same conditions. It is apparent that the steric inhibition of resonance which might be present in 2,6dimethyl-4-nitrophenoxyacetone does not affect its properties very markedly compared to the unmethylated compound. In this connection it would be of consideretble interest to compare the dissociation constants of 4-nitrophenoxyacetic acid and 2,6-dimethyl-4-nitrophenoxyaceticacid, because here the existence of damped resonance involving oxygen might be detected. Ingham and Hamp'son (19) found that the dipole moment of nitroethoxydurene was somewhak lower than that of p-nitroanisole, indicating damped resonance involving oxygen, but the effect was much smaller than with the nitroamino derivatives.
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D. STANLEY TARBELL
EXPERIMENTAL^ Q-Methylphenoxyacetone ( I ) . With chloroacetone and p-cresol in alcoholic sodium ethoxide and in aqueous sodium hydroxide, poor results were obtained (9), as was also the case with chloroacetone, sodium cresolate, and sodium iodide in acetone. Bromoacetone gave poor results in aqueous sodium hydroxide solution, and the most satisfactory method was found to be that of Calaway and Henze (10). Thirty grams of bromoacetone in 25 cc. of benzene was added dropwise with stirring a t room temperature to the sodium salt from 24 g. of p-cresol in 150 cc. of benzene. After refluxing for an hour on the steam-bath, the mixture was cooled, washed with water, with 10% sodium hydroxide solution, and the benzene solution concentrated on the steam-bath. The acidic material recovered from the sodium hydroxide washings amounted to 13.8 g. and was probably starting material. (In other runs, even with an excess of chloro- or bromo-acetone, considerable amounts of p-cresol were recovered. Fractionation failed t o reveal any carbon alkylation product in the acidic portions and no haloacetone was recovered from the reaction mixture.) The benzene solution was shaken with saturated sodium bisulfite solution and allowed to stand several hours to complete the formation of the bisulfite addition product; this was isolated by filtration, washed with methanol, and the ketone recovered by heating the addition product with 15% sulfuric acid on the steambath for an hour. The yield of recovered ketone, b.p. 107-109" (5 mm.), nz 1.5168, was 10 g . (27%). A forerun of 1 g . additional showed nf 1.5160. I n another preparation carried out in essentially the same manner but omitting the formation of the bisulfite addition compound, 122 g. of p-cresol and 155 g. of bromoacetone yielded 69 g. (37%) of product, n: 1.5162. The p-cresol recovered by distillation amounted to 55 g. (45%). Preparation by ozonization. &Methylally1 4-methylphenyl ether (20) (10 g.) in 70 cc. of chloroform was ozonized for one hour, using a 40% excess of ozone. Saturated sodium bisulfite solution was added, the chloroform was evaporated off, and the bisulfite addition compound which formed on standing several hours was collected by filtration and washed several times with ether. The bisulfite addition compound was decomposed as above, yielding 2.7 g. of 4-methylphenoxyacetoneP Mixed melting point determinations showed that the semicarbazone of 4-methylphenoxyacetone prepared by ozonization was identical with that prepared by the method described above. The semicarbazone of 4-methylphenoxyacetone crystallizes from methanol in shining white plates, m.p. 179-180". Calc'd for CllH16N302: C, 59.7; H, 6.8. Found: C, 59.6; H, 6.7. Action of heat on 4-methylphenozyacetone. 4-Methylpheno~yacetone~ prepared from chloro- or bromo-acetone and not purified through the bisulfite compound, gave a vigorous decomposition reaction when heated at 200" for a few minutes. The liquid turned black, water was evolved, and p-cresol, identified as the phenylurethan, could be isolated from the reaction mixture by washing with sodium hydroxide solution. 4-Methylphenoxyacetone (1.21 g.), which had been purified through the bisulfite compound and freshly washed with sodium hydroxide solution, was heated for two and one-half hours a t 250-260". The dark product was cooled, taken up in ether, and extracted several times with 10% sodium hydroxide solution; the ether solution yielded 0.89 g. of neutral material which was shown to be starting material by preparation of the semicarbazone, identified by a mixed melting All melting points corrected. Experiments of M. Insalacco indicate that better than 50% yields can be obtained in the ozonization by using ethyl acetate as solvent, and decomposing the ozon'de with zinc and hydrochloric acid. 4 Stoermer (21) reported that the b.p. of 4-methylphenoxyacetone was 255" and the m.p. of the semicarbazone was 187") but gave no analyses. e
PHENOXYACETONES
257
point, in practically quantitative yield. Acidification and extraction of the alkaline solution gave 0.11 g. of viscous oil, which, on treatment with phenyl isocyanate and a drop of pyridine, gave 0.06 g. of crude phenylurethan of p-cresol. This product was recrystallized from petroleum ether, melting a t 107-log", mixed m.p. with a known sample, 107-111". The ketone decomposes slowly on standing a t room temperature, yielding alkali-soluble materials and giving a marked change in odor. Preparation of 2-acetonyl-4-methylphenol. Five grams (0.031 mole) of 2-(p-methylallyl)4-methylphenol (m.p. of p-nitrobenzoate 65-66') (20) in 50 cc. of chloroform was ozonized for 25 minutes, using approximately 0.04 mole of ozone, and the ozonide decomposed with nTater. The semicarbazone of the product melted a t 187-188" with decomposition after three recrystdlizations from alcohol, and gave a depression when mixed with the semicarbazone of Gmethylphenoxyacetone. Anal. Calc'd for CllHI5N3O2:C, 59.7; H, 6.8. Foiind: C, 59.7; H, 6.9. 2,6-Dimethylphenozyacetone. Using the method described above, 30 g. of 2,6-dimethylphenol (0.25 mole), 5.64 g. of sodium (0.24 mole), and 48 g. (0.35 mole) of bromoacetone yielded 13.1 e:. of crystalline starting material, and 5.5 g . of 2,6-dimethylphenoxyacetone. The product has the b.p. 110-113" (4 mm.), nf 1.5097, and forms a semicarbazone, m.p. 163-165". A sample which had stood for five weeks yielded crystalline 2,6-dimethylphenol when washed with sodium hydroxide solution. A sample (0.81 g.) of the purified ketone which had belen heated a t 200-205" for an hour yielded 0.15 g. of alkali-soluble material and 0.61 g. of starting material when worked up in the usual way. Anal. (semicarbazone) Calc'd for C12H11N802: C, 61.3; H, 7.3. Found: C , 60.8; H , 7.5. 2,4-DimetliyZphenozyacetone. 2,4-Dimethylphenol (30.5 g., 0.25 mole), 8 g. of sodium (0.35 mole), and 48 g. of bromoacetone (0.35 mole) yielded, following the usual procedure, 9.6 g . of the starting phenol, and 15.3 g. of 2.4-dimethylphenoxyacetone,b.p. 113-120' (5 mm.). When purified through the bisulfite compound, i t had the following properties: b.p. 120" (6 xnm.), n$ 1.5110, and formed a semicarbazone melting a t 143-144.5' after recrystallization from dilute methanol.5 Anal. (semicarbazone) Calc'd for C12H11~802:C, 61.3; H, 7.3. Found: C, 61.4; H, 7.3. 4-Bromoplienoxyacetone. p-Bromophenol (34.6 g., 0.2 mole), 6.9 g. of sodium (0.3 mole), and 41 g. of bromoacetone (0.3 mole) yielded 17.3 g. of the starting phenol and 16.4 g. of 4-bromophenoxyacetone, b.p. 130-140" (6 mm.). The product crystallized on cooling, and when recrysl allized from low-boiling petroleum ether, formed transparent rectangular plates, m.p. 42.544'. Anal. Calc'd for C9HgBrOz: C, 47.2; H I 4.0. Found: C, 47.1; H, 4.0. The semicurbazone was prepared and recrystallized from alcohol, melting a t temperatures varying from 196" to 205" depending on the rate of heating. Anal. Calc'd for CloH~?BrNaOz: C, 42.0; H , 4.2. Found: C, 42.0; H , 3.9. 2-.~itrophr,nozyacetone. Potassium 2-nitrophenolate (17.7 g.), 9.3 g. of chloracetone, and 1.5 g. of sodium iodide were refluxed in 200 cc. of acetone for five hours. The solvent was evaporated, water was added, and the product taken up in ether. The ether solution was washed three times with 10% sodium hydroxide solution, which turned dark but yielded no solid on avidification. Ether extraction of this acid solution yielded a few grams of black tar. Evaporation of the ether yielded 11.7 g. of crystalline product, m.p. 65-66"; recrystallization from methanol-water gave 9.8 g., m.p. 67-69'. Stoermer (18) gave the m.p. as 69". S-~~itrophPnoryacetone. The sodium salt from 10 g. of 3-nitrophenol was prepared with 6 Stoermer (ref. 21, p. 301) gave the b.p. of 2,4-dimethylphenoxyacetone as 263", and the m.p. of the semicarbazone as 145', but no analyses were reported.
258
D. STANLEY TARBELL
sodium in methanol, and the dry salt was refluxed in 75 cc. of acetone with 6.7 g. of chloroacetone and a trace of sodium iodide for 7.5 hours. The reaction was worked u p as described above, and 7 g. of crystalline product obtained, which, after washing with a little cold benzene and two recrystallizations from dilute methanol, melted at 79-81'. Anal. Calc'd for CgHgNOa: C, 55.4; H, 4.6. Found: C, 55.2; H, 4.8. Arnall (22) reported the melting point 83-84' but gave no analysis. 4-Nitrophenoxyacetone. Following the procedure described for 2-nitrophenoxyacetone, 16 g. of sodium 4-nitrophenolate, 9.3 g. of chloroacetone, and 1.5 g. of sodium iodide yielded It was found that chloroform was a better 19.5 g. of 4-nitrophenoxyacetone, m.p. 74-80'. solvent than ether for taking up the reaction product. The product was recrystallized from methanol, and 13.5 g. obtained, m.p. 79-81'. Stoermer (18) gives the m.p. as 81". Aqueous sodium hydroxide does not dissolve the nitrophenoxyacetone (contrary to Stoermer's statement); 0.5 g. of the ketone was heated on the steam-bath for fifteen minutes with 10 cc. of 10% sodium hydroxide, and the solid removed by filtration after cooling; acidification of the filtrate gave no precipitate. I n another experiment, 0.5 g. of the ketone dissolved in 10 cc. of ether was washed with three 10-cc. portions of 20% sodium hydroxide; acidification and extraction of the alkaline solution yielded only 0.02 g. of material. 2,4-Dimethyl-6-nitrophenol.To 3 g. of 2,4-dimethylphenol in 30 cc. of acetic acid kept in an ice-bath, a solution of 1.5 cc. of fuming nitric acid (sp. gr. 1.59) in 10 cc. of acetic acid was added dropwise. After the addition was complete, excess water was added t o precipitate the product, and the mixture extracted several times with chloroform. The chloroform solution was steam-distilled and 2.2 g. of crystalline 2,4-dimethyl-6-nitrophenolisolated from the distillate by chloroform extraction. The pure product melts at 72" (23). 2,4-Dimethyl-6-nitrophenoxyacetone.The sodium salt from 2.12 g. of 2,4-dimethyl-6nitrophenol was prepared with sodium in methanol and the dry salt treated with 1 cc. of chloroacetone and a trace of sodium iodide in acetone. The preparation was worked up as described above, and yielded 1.51 g. of crystalline 2,4-dimethyl-6-nitrophenoxyacetone; recrystallization from low-boiling petroleum ether yielded fine fiber-like crystals, m.p. 68-69'. Anal. Calc'd for C ~ I H I ~ NC, O ~59.2; : H, 5.9. Found: C, 59.4; H, 6.0. 2,6-Dimethyl-.&nitrophernl. Numerous variations of the procedure of Auwers and Markovits (24) were tried, of which the following was the most satisfactory. One gram of 2,6-dimethylphenol dissolved in 5 cc. of acetic acid was added to 5 cc. of a solution made up as follows: 1 cc. of water, 20 cc. of acetic acid, and 3 cc. of fuming nitric acid (sp. gr. 1.59). When half of the phenol had been added, a red precipitate of the diphenoquinone (24) appeared; if instead, the nitric acid was added to the phenol, the quinone was formed with the addition of the first portion of acid. The reaction mixture was poured into excess water, and solid sodium carbonate added until the solution was distinctly alkaline. It was then filtered to remove the quinone, the filtrate acidified and the 2,6-dimethyI-4-nitrophenol (0.60 g.) collected by filtration. When recrystallized from dilute methanol, the phenol forms leaf-shaped crystals, m.p. 170-171.5'. 2,6-Dimethyl-~-nitrophenoxyacetone. The sodium salt from 2.47 g. of 2,6-dimethyl-4nitrophenol was refluxed for two hours in 70 cc. of acetone with 1.37 g. of chloroacetone and 0.1 g. of sodium iodide. The reaction mixture was poured into excess water, and 1.63 g. of 2,6-dimethyl-4-nitrophenoxyacetonecollected by filtration. From the filtrate 0.48 g. of the starting phenol was obtained on acidification. The yield of the phenoxyacetone obtained after recrystallization from methanol was 1.31 g., and the product melted at 111.5-113". Anal. Calc'd for CllHI3NO4:C, 59.2; H, 5.9. Found: C, 59.4; H, 5.8. The semicarbazone was prepared and crystallized twice from chloroform (in which i t is only slightly soluble), m.p. 197-199" with decomposition.
PHENOXYACETONES
259
The solubility of phenoxyacetones in Claisen’s alkali. The phenoxyacetones were treated by the following general procedure: about 1 g. of the ketone in 50 cc. of benzene was extracted with three 10-cc. portions of Claisen’s alkali, each portion of extract being run a t once into excess dilute sulfuric acid. I n some cases one-half of the above quantities of everything was used. [Claisen’s alkali is prepared by dissolving 350 g. of potassium hydroxide in 250 cc. of water and diluting to 1000 cc. with methanol (13).1 The acidified Claisen’s alkali solution was extracted with ether and the ether solution washed with sodium hydroxidt: solution; any product contained in this alkaline solution (which would be the cleavage product) was obtained by acidification and extraction. As example of a blank test: 1.00 g. of 4-bromophenoxyacetone in 50 cc. of benzene was extracted with three 10-cc. portions of a mixture of 2 volumes of methanol and one of water. From the extract 0.02 g. was obtained, while with Claisen’s alkali 0.14 g. was extracted (Table I). The nitrophenols formed by cleavage were identified by mixed melting points. The ketones extracted by Claisen’s alkali were transformed into the semicarbazones and mixed melting points were taken with the semicarbaaones of the original ketones. Action of sodium methoxide on phenoxyacetones. A given weight of the phenoxyacetone was dissolved in 30 cc. of 5% sodium methoxide in methanol and allowed to stand at room temperature for a definite time. The reaction mixture was then diluted with water, acidified with dilute sulfuric acid, extracted with ether and the ether extract washed with 10% sodium h,ydroxide to remove the phenol formed by cleavage. The phenol was recovered by the usual method. The ether solution was dried and evaporated to obtain the starting material; the identity of the nitrophenols formed by cleavage and of the neutral product tYas checked by melting point determinations. A small amount of o-nitrophenol seemed t o be present in the mixture from 2-nitrophenoxyacetone, but i t could not be characterized. SUMMARY
Pure 4-methylphenoxyacetone and 2,6-dimethylphenoxyacetone do not rearrange on heating, although they do form a small amount of the corresponding phenol. Bromoacetone gives no C-alkylation when treated with the sodium salt of ;p-cresol in benzene. 4-Methylphenoxyacetone has been prepared by ozonization of P-methylallyl 4methylphenyl ether, and Zacetonyl-4-methylphenol by ozonization of 2-(~-methylallyl)-4-methylphenol. The phenoxyacetones can be partially extracted from benzene or petroleum ether solution by Claisen’s alkali. A series of substituted phenoxyacetones has been prepared including the following new ones: 2 ,&dimethyl, 4-bromo, 2,6dimethyl-4-nitr0, and 2,4-dimethy1-6-nitro. The 4-nitro and 2,6-dimethyl-4nitro compounds are cleaved by Claisen’s alkali, giving the corresponding nitrophenols, while the 2-nitro and 2,4-dimethy1-6-nitro compounds are completely decomposed by Claisen’s alkali. 3-Nitrophenoxyacetone is extracted from benzene without cleavage by Claisen’s alkali, and its acidity is attributed to the increase of the electron-attracting effect of the phenoxy group by the nitro group, making the hydrogen on the carbon next to the ether oxygen more acidic. The 4-nitro and the Zf6-dimethy1-4-nitro compounds are cleaved by sodium methoxide in methanol at room temperature at about the same rate, while the %nitro (compound is decomposed very much more rapidly, and the 4-bromo compouiid is scarcely affected. ROCHESTER, IT.Y.
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D. STANLEY TARBELL
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