42 GIBSON : NITRO-DERIVATIVES OF 0-CRESOL.

V11.-Nitro-derivatives of o-Cresol. By GEORGE PHILIP GIBSON.

THE direct nitration of o-cresol has been studied by many chemists ; the chief products are 3-nitro-o-cresol and 5-nitro-o-cresol, although Spiegel, Munblit, and Kaufmann (Ber., 1906, 39, 3240) record the formation of a little 3 : 5-dinitro-o-cresol (compare Hofmann and Millar, Ber., 1881,14,568 ; Rapp, Annulen, 1884,224, 175 ; Schultz, Ber., 1907, 40, 4319; Wieland, Bernheim, and Bohm, Ber., 1921, 54, 1776) ; all workers have given the melting point 70" for 3-nitro- o-cresol, but the recorded melting point of 5-nitro-o-cresol ranges from 79" to 95".

The author has attempted to elucidate these discordant results, although his main object has been the investigation of certain derivatives of 3-nitro-o-cresol, which were required for another research.

The greater part of the material used was prepared by Hofmann and Millar's method, although Schultz's procedure proved to be the best for mononitration owing to the ease with which the temperature and concentration can be regulated. Using the first method, if 3- and 5-nitro-o-cresols are the desired products, the conditions of nitration must be carefully adhered to, Otherwise 3 : 5-dinifro-o- cresol may be the main product of the reaction.

The fact that pure 5-nitro-o-cresol is dimorphous and the presence of 3 : 5-dinitro-o-cresol and of tarry materials in the residue after the removal of the 3-nitro-o-cresol render the isolation of 5-nitro- 0-cresol somewhat troublesome ; although these difficulties have been overcome, the yield is poor.

5-Nitro-o-cresol forms a monohydrate melting a t 3 0 4 0 " (Neville and Winther, Ber., 1582, 15, 2975), which possesses properties very different from those of otherwise similar nitrocresols, which are anhydrous ; crystallisation from aqueous solvents is therefore an excellent method for removing 3 : 5-dinitro-o-cresol from 5-nitro-o- cresol. Anhydrous 5-nitro-o-cresol crystallises in two forms which are interconvertible. One, the pale yellow, unstable form, which separates first, passes when i t is left in the presence of solvents, crushed or rubbed, into the more stable, colourless variety.

Previous workers have usually obtained derivatives of the above- named nitro-o-cresols by the nitration of the tolyl ethers and esters (Hofmann and Rlillar, Zoc. c i t . ; Borsche, Ber., 1923, 56, 1488; Stadel, ,4nnalen, 1883, 217, 155; Reverdin, Ber., 1902, 35, 1444; 1912, 45, 1450). In all cases, the orientation of the nitro-group is not certain and the structures of a number of these derivatives have

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GIBSOX : RITRO-DERIVATIVES O F 0-CRESOL. 43

therefore been established by preparinS the compounds directly from pure 3- and 5-nitro-o-cresols, and from 3 : 5-dinitro-o-cresol (compare Ullmann and Sank, Ber., 1911, 44, 3730 ; Cain and Simon- sen, J., 1914, 105, 156; Spiegel, Munblit, and Kaufmann, Zoc. cit. ; Hofmann and Millar, Zoc. cit .) .

I n the case of derivatives of 5-nitro-0-cresol, ordinary methods give excellent yields, but with 3-nitro- and 3 : 5-dinitro-o-cresol, probably owing to the presence of two groups ortho to the reacting hydroxyl group, poor results are obtained even when the temper- ntnre is raised and the time prolonged.

For the preparation of derivatives other than the acetates (Smit!] and Orton, J., 1908, 93, 1250), the dry sodium salts of 3-nitro- and 3 : Sdinitro-o-cresol were heated at high temperatures with benzoyl chloride, toluene-p-sulphonyl chloride, methyl sulphate, and methyl toluene-p-sulphonate, respectively (compare Hofmann aiid Millar, Zoc. cit.; Cain and Simonsen, J., 1914, 105, 156). The yields were satisfactory and the reactions took place in two directions, the proportions of the products depending on the nature of the reagent.

I n the case of benzoyl chloride and toluene-p-sulphonyl chloride, t h e products were chiefly the corresponding benzoates and toluene- psulphonates with very sniall proportions of the corresponding chloronitrotoluene or chlorodiiiitrotoluene (compare Ullmann and Ssn6, Zoc. cit.).

I n the experiments with methyl sulphate and sodium 3-nitro-o- tolyl oxide, the purity of the reagent seems to be the determining factor. Using pure niethyl sulphate, the yield of the methyl ether is nearly theorctical, but if methyl hydrogen sulphate is present very serious complications arise aiid the yield inay fall below 50% ; sulphonic derivatives of 3-nitro-o-cresol and its methyl ether are produced with appreciable charring, the small amount of impurity (10 yo in commercial methyl sulphate) acting as an intermediary according to the equation

n.here R is NO,*C,H,Me*OH (1) or NO,~C,H,Xe*OMe (11) (compare C. S. Gibson and Vining, J., 1923, 323, S40 ; Simon and FrGrejacque, Cornpt. w a d . , 1923, 176, 900).

In the casc of 3 : 5-dinitro-o-cresol, methylation takes place quantitatively in either of the above cases, because the 5-position is occupied, so that sulphnnic derivatives cannot readily be formed ; using methyl or ethyl toluene-p-sulphonate with the above dry sodium salts, good yields of the Corresponding ethers are easily obtained.

R*H + OPI*SO,~UMe -4 R*XO,*OJ4e + H,O,

c* 2

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44 GIBSON : NITRO-DERIVATIVES OF 0-CRESOL.

E X P E R I M E N T A L. Preparation of 3- and 5-Nitro-o-cresols.-A mixture of nitric acid

(107 c.c.; d 1.42) and glacial acetic acid (300 c.c.) was stirred in a freezing mixture a t - 15" while a mixture of o-cresol (100 g.) and glacial acetic acid (100 c.c.) was added in the course of 2 hours, when a thick magma of crystals separated. After standing 2 hours in the freezing mixture, the mass was poured into water (5000 c.c.), the crystals were separated, and submit'ted to steam distillation, when crude 3-nitro-o-cresol (yield 35%) containing a small pro- portion of 3 : 5-dinitro-o-cresol passed over ; 5-nitro-o-cresol mixed with a little (10%) 3 : 5-dinitro-n-cresol then remained in the flask as an oil, which solidified when cold.

The crude distillate, m. p. 55-65", was fractionally distilled in steam, and the various fractions were crystallised from petroleum (b. p. 80-looo). The first fractions gave deposits of deep yellow plates of nearly pure 3-nitro-o-cresol ; the last gave pure 3 : 5-dinitro- o-cresol in well-defined, colourless prisms. The 3-nitro-compound may also be isolated by the crystallisation of the crude sodium salt from water.

Pure 3 nitro-o-cresol has b. p. 102-103"/9 mm. and m. p. 70". The residue from the steam distillation was cryst'allised from a

large quantity of 50% alcohol, when crude 3 : 5-dinitro-o-cresol was deposited, the 5-nitro-o-cresol remaining in solution. The filtered solution was evaporated and the dark oily residue purified by dis- tillation (b . p. 186-1 90"/9 mm .), by distillation in superheated steam at 180°, or by crystallisation of the sodium salt from water; in the last two cases, the monohydrate was dried at 100" and the anhydrous compound crystallised from a dry solvent such as benzene.

Anhydrous 5-nitro-o-cresol is deposited from a hot benzene solu- tion in h e , yellow needles which, when left in the mother-liquor for a day or two, redissolve and crystallise again in large, colourless plates; the change takes place slowly from one or two centres of crystallisation, so that the line. of advance of the transformation is quite distinct throughout the process. On attempting to separate the needles by filtration, they immediately fall to powder when touched or pressed, and are transformed into the plates with the correct melting point. With great care, the needles may be isolated and they remain clear for a short time, but eventually become opaque. Similar phenomena to the above occur in other solutions with more or less rapidity, but are most characteristic in benzene.

Owing to the readiness with which the unstable form is converted into the stable, both seem to melt a t 96"; if great care is taken to procure the needles unchanged, the melting point is sometimes as low as 75", but i t depends on the rapidity of the heating.

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GIBSOPJ NITRO-DERIVATIVES O F 0-CRESOL. 45

On crystallisation from aqaeous alcohol or acetone, 5-nitro-o- caresol is deposited in very fine needles of the mono-hydrate, I-. 13.

30-40" as stated by Neville and Winther (Ber., 1882, 15, 2973). Preparation of 3 : 5-Binitro-o-cresol.-A mixture of nitric acid

(150 c.c.; d 1-42) and glacial acetic acid (300 c.c.) was cooled in ice m d mechanically stirred while a solution of o-cresol(lO0 g.) in glacial acetic acid (100 c.c.) was gradually added. After standing at the ordinary temperature for 24 hours, the product was poured into water, the granular solid separated, and distilled in steam to remove a small amount of crude 3-nitro-o-cresol (~7ield 10:h). The residue in the flask was chiefly 3 : 5-&nitro-o-cresol with some 5-nitro-o- crcsol (loo/) and tarry materials. After crystallisation from 50y0 alcohol (p. 44), the (lark brown 3 : 5-dinitro-o-crcsol was converted into the sodium salt, when the colouring matter remained in the mother-liquor and the pure salt was obtained.

Pure 3 : 5-dinitro-o-cresol is slightly volatile in steam (3 g. per litre) and can be recrystallised from 50% aqueous alcohol or petrol- eum (b. I>. GO-SOo).

T h e Xodimz 8aZts.-As the sodium salts of the nitro-o-cresols are fairly readily solublc in water and appear t o hydrolyse during the process of drying a t 100°, they are best prepared in the pure state by treating a suspension of sodium ethoside in boiling benzene with a benzene solution oE a slight excess of the nitro-compound; the products are separated and washed with dry benzene.

Sodium 3-nitro-o-tolyl oxidc crystallisea froin water in deep red plates (+ 2H,O) ; at loo", i t sinters and then gives the anhydrous compound as a light brick-led powder (Prazer, i lmer . Chem. J . , 1903, 30, 309). Sarupk prepared with sodium ethoxide (Found : X a = 13.10. Calc. for C,H,O,NNa, ISa = 13.14%).

Sodium 3-nitro-o-to13Z oxide crystallises from water in yellow, hytirated needles, which, at 100", without sintering, give a beautiful cerise, anhydrous salt. Specimen prepared with sodium ethoxide

Sodium 3 : 5-dinitro-o-tolyl oxide forins a deep yellow solution and crxstallises in yellow, hydrated needles which, without softening at loo", give a deep brick-red powder. Specimen dried at 100" (Found : Na = 10.5,.

l'yricline 3 : 5-dinitro-o-toh~Z oxide, C1,H1105N,, separates in orange needles when a solution of 3 : 5-dinitro-o-cresol (2 g). in a hot mistilre of pyridinc (2 g.) and benzene (10 c.c.) is cooled. It melts at 96" 2nd gradually dissociates in the air and in solution, but i t can Lc recrystallised from dry solvents containing a little pyridine (Found : C == 52.2 ; H = 4-1. CI2H,,O5N3 requires C = 52.0 ;

(FOU~IC~ : Ka = 1 3 . 1 3 ~ ~ ) .

C7H5O5N2N% requires Na = 10-460/,).

11 = 4*Q(',LJ).

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46 GIBSON : NITRO-DERIVATIVES O F 0-CRESOL.

The Acetyl Derivatives.-5-Nitro-o-tolyZ acetate, N02*C,H3Me*OAc, was formed by the action of acetic anhydride on pure 5-nitro-0- cresol in dry pyridine at the ordinary temperature. After 12 hours, the solution was diluted with water, extracted with ether, and the extract shaken with dilute acid and then with dilute sodium hydroxide solution. The ether was evaporated and the solid residue crystallised from a mixture of petroleum (b. p. 80-100") and acetone (large prisms) or from alcohol (needles).

This ester, m. p. 88", is readily soluble in acetone, benzene, or chloroform, but sparingly soluble in alcohol, carbon tetrachloride, or light petroleum (Pound : C = 55-3; H = 4.6. C,H,O,N requires C = 554; H = 4.6%).

3-Nitro-o-toZyl acetate was prepared by treating pure 3-nitro-0- cresol (5 g.) at the ordinary temperature with acetic anhydride (15 c.c.) containing a trace of concentrated sulphuric acid (Smith and Orton, Zoc. cit.) until the yellow colour of the nitrocresol had disappeared ; water was added, the oily ester extracted with ether, the extract washed with dilute caustic soda and evaporated; the residue crystallised from alcohol in large tablets, m. p. 42". This acetate is readily soluble in the ordinary organic solvents and crystallises well from alcohol or petroleum (b. p. 60-80") (Found :

3 : 5-Dinitro-o-tolyl metate, C,H,Me(??O,),*OAc, prepared in a similar manner, melts a t 96" and crystallises readily from alcohol. It is fairly soluble in alcohol, acetone, benzene, or chloroform, but sparingly soluble in petroleum (b. p. 60-80") or carbon tetrachloride (Pound : C = 4443; M = 3.4. C,H,O,N, requires C = 45.0;

C = 55.4 ; H = 4-57:).

H = 3.3:/,). The Benxoyl Deri~atives.-5-~Yitro-o-tolyl benzoate,

N02*C6H3h~e*OBz , was prepared in the same way as the corresponding acetate (above), a slight excess of pure benzoyl chloride being used in place of acetic anhydride.

It melts at 128", is sparingly soluble in ether, alcohol, or light petroleum and fairly soluble in acetone, benzene, chloroform, or carbon tet,rachloride (Found : C = 65-3; H = 4-3. C,,H,,O,N requires C = 65.4; H = 4.28:/,).

3-Nitro-o-tolyl benzoate was obtained by heating anhydrous sodium 3-nitro-o-tolyl oxide (p. 45) with pure benzoyl chloride (2 mols.) for 1 hour at 120". The product was treated in the cold with a mixture of pyridine, water, and ether ; the ethereal solution was shaken successively with acid and with dilute alkali and finally evaporated ; the residue crystallised from alcohol or petroleum (b. p. SO-80") in needles, m. p. 42", b. p. 215--220"/9 mm. This

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GIBSON : NITRO-DERIVATIVES OF O-CRESOL. 47

ester is soluble in the usual organic solvents with the exception of petroleum (b. p. S0-8O0) (Pound : C = 65.4; I3 = 4.2%).

3 : 5-~initro-o-fdyl benzoate, C,H,Me(NO,),*O~z, m. p. 132", prepared in a similar manner from sodium 3 : 5-djnitro-o-tolyl oxide, crystallises readily from acetone, alcohol, or benzene ; it is sparingly soluble in alcohol, etcher, or light petroleum, but easily soluble in acetone, benzene, chloroform, or carbon tetrachloride (Found : c = 55-7 ; H = 3.4. = 3.3%).

The Toluene-p-sulphonyl Derivatives.-5-Nitro-o-tolyl tokuene-p- sulphomte, ~ 0 3 0 C 6 H 3 ~ ~ e * O * S o ~ * c 7 H 7 , obtained as in the case of the corresponding benzoate (p. Q6), using toluene-p-sulphonyl chloride, crystallises from alcohol, petroleum (b. p. 60--80°), or carbon tetrachloride in indefinite plates, m. p. 107". It is sparingly soluble in alcohol or light petroleum, but fairly soluble in acetone, benzene, chloroform, or carbon tetrachloride (Pound : S = 10-5. C14H130,NS requires S = 10.4:/,).

3-Nitro-o-tolyl toluene-p-sulphonate was prepared by treating sodium 3-nitro-o-tolyl oxide (1 mol.) with pure tolaxene-p-sulphonyl chloride (2 mols.) : * the conditions and method of isolation were the same as those described in the case of t h e benzoate (p. 46).

The compound melts at 66" and boils at 257"/11 mm. with decom- position, but distils unchanged a t 205-.210"/0~5 mm. ; it crystallises well from alcohol, in which it is sparingly soluble, and dissolves freely in acetone, benzene, chloroform, or carbon tetrachloride (Found : S = 10.2%).

The corresponding toluene-p-sulphonate from 3 : 5-dinitro-o- cresol, which has already been isolated by Ullmann and San6 (Ber., 1911, 44, 3730), can be prepared in a similar manner.

3-Nitro-o-chlorotoluene is formed in very small quantities by the action of benzoyl or toluene-p-sulphonyl chloride on sodium 3-nitro- o-tolyl oxide and can be isolat,ed by steam distillation of the crude reaction mixture, when a pale yellow, pleasant-smelling oil passes over (compare Holleman, Bee. trczv. chim., 1908, 27, 456).

I n a similar manner, sodium 3 5-dinitro-o-tolyl oxide yields the corresponding 3 : 5-dinitro-o-chlorotoluene (m. p. 63"), which was oxidised to 3 : 5-dinitro-o-chlorobenzoic acid (m. p. 238").

The Methyl Ethers.-5-Nitro-o-tolyl methyl ether, m. p. 64" (Cain and Simonsen, J., 1914,105,2390, give m. p. 62"), crystallises readily in needles from alcohol or petroleum, but is freely soluble in acetone, chloroform, carbon t'etrachloride, or benzene. On

~14Hl,06N, requires c = 55.6 ;

* The commercial compound was dried in a vacuum at 100' and dissolved in hot petroleum (b. p. 60-80°), the tarry material filtered of f , the solvent removed, and the residue distilled under reduced pressure; b. p. 138- 139"/9 mm.

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48 WHITE: LIMITS FOR THE PROPAGATION OF F U M E

oxidation with boiling dilute permanganate, 5-nitro-o-methoxy- benzoic acid (m. p. 150") was obtained in theoretical yield.

3-Nitro-o-tolyl methyl ether was obtained by heating sodium 3-nitro-o-tolyl oxide (I mol.) at 120" with pure methyl sulphate (2 mols.) for 2 hours. The dark-coloured reaction mixture was submitted to distillation in steam, the volatile oil extracted with ether, and the 3-nitro-o-cresol removed with dilute alkali. The ethereal solution was evaporated, the residue distilled under 10 mm., and the product (b. p. 121-122") dissolved in pet'roleum (b. p. 6O--SO0) ; a t - 15", the solution deposited 3-nitro-o-%olyl methyl ether in large needles, m. p. 30".

The residue from the steam distillation of the methyl ether, treated with calcium carbonate, gave a mixture of calcium nitro- cresolsulphonates (p. 43) together with sodium carbonate, but the acids could not be separated by the fractional crystallisation of various inorganic and organic sahs which were tried.

3 : 5-Dinitro-o-tolyl methyl ether (m. p. 72") can be prepared under the conditions just described; the yield is good. 3-Nitro-o- tolyl methyl and ethyl ethers and the corresponding methyl and ethyl derivatives of 3 : 5-dinitro-o-cresol were also prepared by heat- ing the requisite dry sodium salts with methyl or ethyl toluene-p- sulphonate * in a similar manner. The yields were good, and the products had the properties given in the literature.

I n conclusion, the author desires to express his thanks to the Department of Scientific and Industrial Research for a grant which enabled him to carry out the above work, and to Professor F. S. Kipping for his kindly supervision.

UNIVERSITY COLLEGE, NOTTINGHAM. [Received, August 29th, 1924.1 Publ

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