[CONTRIBUTION FROM THE CHleMICAL
LABORATORY OF MCGILLUNIVEReITT]
SOME LIMITATIONS OF 2,4-DINITROPHENYLHYDRAZINE AS A REAGENT FOR CARBONYL GROUPS C. F. H. ALLEN* AND J. H. RICHMOND Received M a y 81, 1957
Since the appearance of our earlier paper' the use of 2,4-dinitrophenylhydrazine as a reagent for identification of aldehydes, ketones and ketone derivatives has been generally adopted. In addition to the many isolated instances in which the derivatives have been prepared as reference compounds for new substances, there have been numerous papers dealing with carbonyl group reagentsa2 The many discrepancies in the melting points as recorded in various laboratories for the same substances are noteworthy; the variation is frequently too great to be explained on the ground of insufficient purification. The purpose of this paper is to describe certain observations made inthis laboratory over a period of years, which may be of assistance to others, as well as accounting for some of the discrepancies. There are two modifications of the general procedure for the preparation of the derivative-one employing hydrochloric and the other sulfuric acid. The latter is applicable in a few instances where the former has not been useful, but, in our opinion, the ease of purification of the derivative is greater when hydrochloric acid is the catalyst. Traces of sulfuric acid persist through several recrystallizations, and, if secondary reactions are possible, as is frequently the case, lead to increasing difficulty in purification. Brady'ss objection that the hydrochloride of the reagent is less soluble, is unimportant if one adds the acid before the carbonyl compound, though this is only necessary in a very few extreme instances. Acetaldehyde, as is well-known, gives dinitrophenylhydrazones that seem to exist in two modifications, one melting at 147" and the other at 164". In half a dozen comparable runs, the use of hydrochloric acid in every instance gave a crude product melting a t 157" or higher, whereas sulfuric acid gave the low-melting form each time. Whether these are true isomers or one an impure form of the other is under controversy. * Present address, Eastman Kodak Co., Rochester, N . Y. ALLEN,J . Am. Chem. SOC.,62,2955 (1930). STRAIN, ibid., 67,758 (1935); ( b ) COWLEYAND SCRUETTE, ibid., 3463 (1935); (e) CAMPBILL,Analyst, 61,391 (1936); ( d ) RODUTAAND QUIBILAN, Rev. Filipina med. a (a)
farm., 27, 123 (1936) [Chem. Abstr., 31,98 (1937)1. a BRADY, J . Chem. SOC.,133,756 (1931). 222
LIMITATIONS OF 2,4-DINITROPHENYLHYDRAZINE
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Bryant' assumes that the two are polymorphs, whereas in Campbell'szc experience it is a case of insufficient purification. An alternative explanation, rejected by both authors, is that of geometrical isomerism. Bredereck6 demonstrated the occurrence of this in the furan series, and it might be encountered with other aldehydes. The change of one form into the other is catalyzed by acidic reagents, and would be more probably encountered in the sulfuric acid procedure, in which the acid is less readily removed during purification. However, this explanation cannot. account for the discrepancies recorded for the melting points of dinitrophenylhydrazones of symmetrical ketones. The separation of the dinitrophenylhydrazones from the unused reagent is difficult. It is advisable always to use a slight excess of the carbon#ylcompound and thus avoid this complication. In our opinion, many of the discrepancies in melting points in the literature may be accounted for by contamination of the derivat.ive with the reagent. The nature of the solvent selected for purification may be of importance. When it can be used, alcohol is preferable to all others, but when the derivative is too sparingly soluble some substitute is necessary. Acetic acid and acetone must be avoided for obvious reasons; dioxane, aromatic hydrocarbons, or esters are usually suitable. In our experience, chloroform is usually to be avoided, since it does not give a good separation of mixtures; the melting point is often unchanged after successive crystallizations, yet subsequent use of another solvent a t once raises it. As a rule, the substances are too soluble in nitrobenzene, and it is not easily removed from the crystals owing to its high boiling point. I n every case the derivative should be recrystallized to the same constant melting point f r o m two diferent solventrr. Frequently the derivative obtained does not correspond to the substance started with. This is unimportant, provided the same procedurc always gives the same product. The most noticeable instances are the ketonic acids,20*which give esters so rapidly that alcohols, as mediR for the reaction, are to be avoided. I n the case of keto esters, the possibility of radical interchange on recrystallization from an alcohol should be kept in mind. The dinitrophenylhydrazine of benzoylformic acid, prepared in water solution, melts at 196O6and that of the methyl ester at 171",l but the ethyl ester gives a product, m.p. 158", that has lost alcohol; it is probably a pyridazine. BRYANT, J . Am. Chem. SQC., 68,2335 (1936). BREDERECK, Ber., 66, 1833 (1932); BREDERECK AND FRITZSCHE, ibid., 70, 802 (1937). 6 GORGON, SANBORN, AND VANEss, J . Am. Chem. SQC., 66,3463 (1935).
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LIMITATIONS O F 2 , CDINITROPHENYLHYDRAZINE
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Benzalacetophenone might give isomeric dinitrophenylhydrazones or a pyrazoline derivative. Actually it gives mixtures of two substances the relative amounts depending on the time of contact with the acid. A high-:melting form, which decolorizes permanganate rapidly, is probably the open-chain derivative. The low-melting isomer reacts only slowly with the hot oxidizing agent and is presumably the pyrazoline; the latter results by simple recrystallization of the hydrazone in the presence of a trace of mineral acid. These results indicate that mixtures may be expected with unsaturated ketones. We have, so far, been unable to recrystttllize satisfactorily the derivative from methyl vinyl ketone. Diricetone alcohol loses water during the short time of preparation of the dinitrophenylhydrazone, so that the derivative is that of mesityl oxide ; hydroxycitronellal shows a similar behavior. Although chloral has been reported as giving a derivative,2din our hands the reactivity of the chlorine atoms has led to mixtures, so that the reaction cannot be considered convenient or easily reproducible. Finally, regeneration of the carbonyl compound from the dinitrophenylhydrazones cannot be said to be satisfactory. The procedure involving simple reversal of the reaction by which they are formed has been mccessful in a very few instance^.^ Replacement by a different carbonyl compound has not been as valuable a method as might be anticipated. Strain2" recommends the use of the relatively inaccessible glyoxals or diacetyl, while Rupe suggests a five-hour treatment with alcoholic mnitrobenzaldehyde. Picryl chloride has been used in a few instances.Q Collatz and Neuberg7 observed that heating in a pressure bottle with a large excess of acetaldehyde, acetone, or furfural enabled them to regenerate substances like glyceric aldehyde and dihydroxyacetone. Since 2,4-di:nitrophenylhydrazine is unstable to alkaline reagent^,^"^ lo the use of the latter has led to success in some instances." EXPERIMENTAL
The dinitrophenylhydrazones in the table were obtained by the general procedure using hydrochloric acid, unless otherwise noted, when sulfuric acid gave a better result. Neither modification gave useful products with chloral, bromal, methyl n-hept,yl ketone, methyl n-octyl ketone, methyl vinyl ketone, di-n-butyl ketone, vinyl phenyl ketone, phenacyl bromide, p-chloropropiophenone, or dimethyl pyrone. As examples of the failure of chloroform as a solvent for purification may be cited these instances: ( a ) p-tolualdehyde gave a product, m.p. 214215°C. unchanged by r
7
COLLATZ AND NEUBERG, Biochem. Z . , 266,27 (1932).
* R u m AND GASSMA", Helv. Chim. Acta, 19,574 (1936).
CUISA,Gazz. ital. chim., 97, [ii], 301 (1907). PRICE, J. Chem. SOC., 1934, 1637. '1 Private Communication, G. F. WRIGHT, McGill University. l o MACBEATH AND
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recrystallization from this solvent, but one treatment with dioxane raised it 12". In the preparation, the reagent is completely dissolved, so contamination of the product by the former seems unlikely. ( b ) The mixtures of dinitrophenylhydrazone and pyrazoline from benzalacetophenone are usually unchanged by recrystallization from chloroform, but a t once separated by the use of dioxane. These mixtures, secured under apparently identical conditions, melt anywhere from 204 to 240°C. One of them, m.p. 208°C. seems to behave like a single substance, and has been mistaken for the pure dinitrophenylhydrazone.1 The pure high-melting isomer, which is thought to be the hydrazone, when boiled 15-20 minutes in alcohol with a trace of sulfuric acid, gave this mixture. It is well known that pyrazolines are formed by the action of mineral acids on phenylhydrazones of a,@-unsaturated ketones. SUMMARY
Attention is called to limitations in the application of 2,4dinitrophenylhydrazine z ~ 9a reagent for identifying carbonyl compounds, and suitable precautions are suggested t o circumvent these. The avoidance of an excess of reagent is emphasized; a procedure and solvents are recommended; and the nature of certain secondary products is illustrated.
