174 COHEN AND MILLER: OXIDATION OF THE XXl.-The InJuence o f Substitution iqa the Nucleus o n the Rate of Oxidatioiz OJ’ the Side-chain. I. Oxidation of the Mono- mid Di-chlorotolTcenes. By JULIUS BEREND COHEN and JAMES MILLER ISOLATED observations on the effect of different oxidising agents, and on the influence OF certain groups in accelerating or retarding oxidation of the side-chain, have been made by different observers, but the subject has never been systematically investigated. Wroblewsky (Ber., 1882, 15, lO?l), without giving experimental details, states that if benzene with hydrocarbon side-chains in which hydrogen is re- placed by a halogen or a nitro-group is submitted to oxidation by chromic acid mixture, those side-chains pass into carboxyl which are farthest from the halogen.” Lellmann’s Organische Xynthese, p.196, contains the following statement : ‘‘ Negative atomic groups in the ortho-position protect the alkyl group from the action of oxidising agents, whereas alkaline oxidising agents attack this group.’’ The exact reference is not given, but the statement is apparently based on that of Wroblewsky and also on certain observations of W. A. Noyes (Amer. Chern. J., 1885, 7, 145; 1886, 8, 185; 1889, 11, 161). The latter investigator found that o-bromotoluene is oxidised with difficulty to o-bromobenzoic acid by means of potassium ferricyanide ; also that m-nitrotoluene is less readily oxidised by this reagent than its isomer- ides. Schopff (Bey., 1891, 24, 3778) concludes from the results of his attempts t o oxidise o-brorno-na-xylene that “ the oxidation of a methyl group in the ortho-position (to bromine) with acid oxidising agents is effected slowly and with difficulty.” Rupp ( B e y ., 18\12, 25, 347) ex- perienced t h e game difficulty with tetrachloro- and tetritbromo-p-xylenes, and only succeeded with a mixture of nitric acid and permanganate. It is clear that no satisfactory generalisation can be drawn from these isolated facts, Certain points which were noticed in the courseMONO- AND DI-CHLOROTOLUENES. 175 of the researches in which one of us has been engaged in collaboration with H. D. Dakin (Trans., 1901, 79, 1111) and with S . H. C. Briggs (Trans., 1903, 83, 1213) on the oxidation of the halogen derivatives of toluene suggested the present inquiry. The method which we have adopted is to heat about a gram of the substance with dilute nitric acid in a sealed tube for a length of time insufficient for complete oxidation, and to estimate the proportion of acidic product and unchanged substance.In our first experiments, the substance was weighed in small specimen tubes which were slipped into the tube containing the acid. The sealed tubes were heated in a cylindrical, jacketed, tin-plate air-bath which was fixed horizontally, the required temperature being attained by boiling turpentine con- tained in the outer jacket. The results of the experiments with this apparatus were not con- cordant. We attributed this partly to the specimen tubes, which to some extent pro- tected the substance from the action of the acid.These tubes were therefore discarded and the substance introduced directly into the acid. We found, moreover, that the inner compartment of the air-bath was about 5' hotter at the bottom than at the top, SO that the lower tubes were at a higher temperature than the upper ones. The horizontal, air-bath was therefore replaced by a vertical one, jacketed as before, and covered with flannel as shown in the figure. The liquid in the jacket was coal-tar naphtha boiling at 140-150'. Although there was still a difference of about 3' between the temperature of the top and bottom of the inner compartment, yet as the tubes, which / f were approximately of equal length, were placed vertically, they were consequently exposed t o the same conditions of temperature. Care was taken t o prevent direct contact between the tubes and the metal of the bath by fixing a cork pad a t the bottom and covering the tubes with flannel.Under these modified conditions, concordant results were obtained. The substances employed were the three monochlorotoluenes and the six dichlorotoluenes, all of which were carefully purified by fractional distillation, and in the case of 3 : 5-di- chlorotoluene by crystallisation. T h e monochlorotoluenes were ob- tained quite colourless by distillation under diminished pressure, but this treatment was not found necessary in the case of the dichloro- toluenes. N 2176 COHEN AND MILLER: OXIDATION OF 'I'HE The following are the boiling points of the substances employed : b. p. mm. b. p. b. p. Monochlorotoluenes.Dichlorotoluencs. Ortho- looo 129 2 : 3 - 200-20Z0 2 : 6- 192-154' Meta- 102 130 2 :4- 194.5-195.5 3 : 4 - 203-204 Para- 85 61 2 : 5 - 195-157 3 : 5- m. p. 26-27 A weighed quantity of the substance (about 1 gram) was intro- duced into tho tube, and about six times this amoiint of dilute acid (1 vol. nitric acid of sp. gr. 1.4 to 2 vols. water) was added and the tube sealed. I n order to ascertain the effect of the length of the tube on the rate of oxidation, equal quantities of 3 : 5-dichlorotoluene were heated in two tubes, oce of which was about half the length of the other. It was found that the acid formed in the shorter tube was less pure and rather larger in amount, but the difference was insignificant and would be inappreciable in tubes so nearly of the same length as those which we employed.The air-bath was closed loosely by a cork holding a thermometer and heated until the temperature was constant. The tubes were then introduced, and when the temperature of the inner compartment reached 138-140' the tubes were left for 14 hours, during which the temperature of the interior did not exceed 145O. The bath was then allowed to cool and the tubes removed and opened. The method of analysis was as follows: the contents of each tube were in turn rinsed into a separating funnel with ether, the contents being then vigorously shaken, whereby the ether dissolved out the whole of the organic compounds. The acid layer was then drawn off and sodium carbonate solution added in excess to the ether and well shaken to extract the organic acid.The alkaline layer was removed and the ethereal extract washed with a small quantity of water, the washings being added to the alkaline liquid. The ethereal solution, which con- tained the unaltered substance (possibly also a little aldehyde), was dehydrated over calcium chloride, decanted into a tared flask, the ether removed, and the residue weighed. The alkaline liquid was acidified with hydrochloric acid, extracted with ether, the ethereal solution dehydrated over calcium chloride and treated as described above. The purity of the acid was in each case ascertained from the melting point. This and the total quantity of products obtained when com- pared with the substance taken was a satisfactory check on the result, although, of course, the method lacks the precision of an exact analytical process.I n the following experiments, all the tubes were heated together under precisely the same conditions,MONO- AND DI-CHLOROTOLUENES. 0'932 1'089 177 146-149 235-236 Chloro- toluene. Ortho. Meta- Yara- 2 :3- 2 : 4 - 2 : 5 - 2 : 6 - 3 : 4- 3:5- 3 : 5- I (short tube) Actual amount taken. _____- 1.005 0.989 0-964 1 *a32 1.035 1 -065 1.036 1 -024 1.046 0.988 1st series. Calculated to 1 gram. E:kzi 1 Unchanged acid. substance. 1*011 1.092 1 *G58 0.942 1,073 0.864 0.825 1 -060 0.726 0.759 ' 0.040 ~ 0.029 0.019 0.135 , 0.051 0.157 0 -236 0.047 0.297 0.228 .____ Total. 1.051 1'121 1.077 1.077 1'124 1.021 1'061 1.107 1 '023 0.987 m. p. of acid. 135-1 36' 145-148 233-234 159-162 160- 161 139-142 123-132 200-201 183-1 84 18 4-205 Correct m.p. of acid. 137" 153 236 163 ? 60 153 139-14 0 200-201 182-183 It will be seen from the above table that the monohalogen com- pounds are more rapidly attacked than the majority of the dihalogen derivatives, for the former are almost completely converted into acid, whilst only two of the latter are completely oxidised. The dihalogen compounds show well-marked differences ; the 3 : 5-compound is least attacked. The next in order being the 2 :5- and 2:6-isomerides, which are oxidised to approximately the same extent, although the 2 : 6-compound yields a very impure acid. The 2 : 3-compound comes next,, and finally the 2 : 4- and 3 : 4-derivatives, which may be bracketed together as being almost completely oxidised. As the rnonobalogen compounds were too far oxidised for any con- clusions to be drawn as to their relative rates of oxidation, a second experiment was made i n which the tubes were heated for only half an hour at 140-145O.I Calculated t o 1 gram, Ortho- Meta- Para- 1.015 0.687 0.307 1.011 0'384 0548 1.007 I 0.998 1 0.091 1 3 i " 153 236178 OXIDATION OF THE MONO- AND DI-CHLOROTOLUENES. It is therefore evident that the meta-compound is least affected, then follows the ortho-derivative, and finally the para-isomeride, which is almost entirely converted into the corresponding chlorobenzoic acid. Two other series of experiments which were made with the dihalogen compounds confirm the results of the first series. 2nd Series. Dichloro- toluene. 2 -3 2 *4 2.5 2.6 3'4 3 '5 Chloro- toluene. 2-3 2.4 2'5 2 '6 3 '4 3'5 Amount taken.__ 0.993 0 '974 0.989 1 '044 0.997 1 -000 Amount taken. ____ 1 *076 1 '030 1.165 1.093 1.165 1*000 Calculated to 1 gram. 0.762 I 0'290 0.949 0.119 0,614 0.381 0.546 1 0'4.51 1 '025 0.470 1 i::i 1.052 1.068 0'995 0.997 1.105 0.965 3rd Series. Calculated to 1 gram. Dichloro - benzoic acid. 0'773 1'017 0.631 0'640 1.060 0.357 J n changed substance. Total. 0.247 0496 0.373 0.342 0.055 0.581 1 -020 1-113 1.004 0'982 1'115 0.938 I j __ I 159-161" 163" 138-143 159-1 59.5' 1 , 8 ~ ~ 1 8 3 160 11 5-129 139-140 200-201 200-201 183-184 m. p. of acid. 162-163" 16 0-16 1 139-142 114-128 200-201 182-1 83 Correct m. p. of acid. - _ ~ .- 163" 160 153 139-140 200-201 182-183 So far as the special conditions of the above experiments are con- cerned, namely, the use of halogen compounds on the one hand and of nitric acid as oxidising agent on the other, the results are perfectly definite.The meta-compounds retard oxidation, and the para-compounds assist it, whilst the ortho-compounds occupy an inter- mediate position. Thus, rn-chlorotoluene and 3 : 6-dichlorot oluene are least attacked. p-Chlorotoluene and the two dichlorotoluenes sub- stituted in the para-position (2 : 4 and 3 : 4) are most readily oxidised. It is not clear why the 2 : 3-dichloro-compound should be more readilyDERIVATIVES OF HIGHLY SUBSTITUTED ANILINES. 179 oxidised than the 2 : 5-derivntice, for they are both substituted in the meta- as well as in the ortho-position with respect to the methyl group, nor is it evident why the 2 : 6- and 2 : 5-compounds should be oxidised to the same extent. It is interesting to note that, Noyes, when working with the nitrotoluenes and potassium ferricyanide, found that the meta-compound is less readily oxidised than the other two isomerides. On' the other hand, Wroblewsky's observation (vide ante) seems to be only true in part, unless, indeed, chromic acid has a very different action from that of the other two oxidising agents. It is difficult to account for the behaviour of the different isomerides. I t is clear that (contrary to the view which we were led to adopt as the result of our preliminary experiments) it is not a question of steric hindrance. The only process which seems to offer any analogy to the present one is that of substitution in the nucleus in which the formation of meta-compounds is sharply differentiated from that of the ortho- and para-compounds, yet it is difficult to see how any process of substitution in the nucleus can be applied t o explain the conversion of a side-chain into a carboxyl group. We have accumulated a number of facts in regard t o the oxidation of simple and mixed dihalogen derivatives and nitro-halogen compounds of toluene, which we hope shortly to publish. THE YORKSHIRE COLLEGE, LEEDS.