Preparing and Purifying 2,4=Dinitrophenylhydrazones Alternatives to the Brady Procedure Juan Zhang, Russell L. Hertzler, and E. J. Eisenbraun Oklahoma State University, Stillwater, OK 74078 The Brady Procedure Bradyintroduced sulfuric acid a s a catalyst for preparing the 2,4-dinitrophenylhydrazones(2,4-DNPH'sj of aldehydes and ketones ( I ) . Phosphoric acid (2)or acetic acid in diglyme (3) also have been used. The latter i s recommended for acid-sensitive materials. Bradv's for aualitativelv detecting . orocedure . - carbonvl compounds has remnined'essentiall~unchanged 14,. ~ 6 e following order is used: 2.4-dinitr~~phenylhsdr;lzine, sulfuric acid,water, ethanol, aldehyde or ketone. ~ u r r e n t l ythe , Brady procedure is probably the most widely used method for this preparation (4, 5 ) . Problems with the Brady Procedure However, with larger preparations, which are frequently required for purifying ketones through regeneration from the 2,4-DNPH derivative (6, 71, purifymg the derivative becomes time-consuming and troublesome. The derivative is isolated by filtering, which requires extensive washing of the filter cake with water1 or sodium bicarbonate solution (8)to remove residual sulfuric acid. Because water is used, the freshly prepared derivative is wet, usually sticky, and difficult to transfer from a filter funnel. The weight of the wet derivative greatly exceeds that of the theoretical quantity. Thus, the yield can not be determined gravimetrically. The wet filter cake may be dried2 or it may be recrystallized from ethanol (4,5),which is effective in removing water, but this requires large volumes of alcohol. An Alternative Procedure Amberlyst-15 Catalysis To minimize these difficulties and to improve the purification process, other approaches were investigated. A sulfonic acid ion-exchange resin, Amberlyst-15 (A-15) (Rohm and Haas), in refluxing toluene effectively catalyzes the formation of the derivative. The resin is easily and completely removed from the product by filtering through Dicalite or Celite. Soxhlet Extraction The workup and purification process is further improved by extracting the reaction mixture through acidic alumina3 using a modified Soxhlet extraction apparatus (9). This allows students to avoid the less convenient handling of the wet derivative obtained from the Brady procedure. I n this Soxhlet-extraction procedure, toluene (200 mL for 0.01 mol of ketone) is the solvent used i n all three phases of the preparation: reaction, extraction, and crystallization. Thus, the purified product is directly provided in a single operation. This procedure also gives the students experience in using a D e a n a t a r k apparatus4 to shift the equilibrium through the azeotropic removal of water and to minimize chemical waste disposal. Despite the need for setting up the Soxhlet apparatus, the overall time required to prepare and purify the dinitro-
phenylhydrazones (e.g., the 2,4-DNPH of acetophenone) is reduced, compared to the time required using the Brady procedure. A summary of the steps described in the procedure includes the following. setting up the Saxhlet apparatus measuring reagents and refluxing: 75 &in transferring the toluene solution to the Saxhlet apparatus 'eluting t h e dcnrutive wth toluene: 3 0 4 0 mm provided n fwr-fluwing frit i i w e d in cunstruning the Soxhlet apparatus) concentrating the toluene extract by distilling: 30 min coaling and filteringthe crystals: 20 min The total time required is about 3.5 h. Comparing the Two Methods Monitoring Reaction Progress I n comparing the time required for the two procedures, the reaction time for preparing a 2,4-DNPH using A-15 is longer than when using sulfuric acid. Thus, it may be of interest to monitor the reaction for completion. Periodic sampling for thin-layer chromatography using toluene (E. M. Science, Kieselgel 60fZs4)can be used to monitor the progress of the reaction by directly observing the change in the value of Rr for the develooine soots of reagent and der~valivc.If unreacted ketone is present, a U\.' light IS reauired to reveal its orcsence. Volatile ketones are difficult td detect by TLC.
. ~. .
'Washing with sodium bicarbonate solution to remove residual acid,which lowers the melting point ofthe derivative through syn-anti isomerization, has been recommended (8).However, thorough washing with water of the acetophenone 2,4-DNPH filter cake from the Brady procedure gave a product having the same mp and the same TLC response. 'Dryin0 air orthrouah use of avacuum . can be done bv. exoosureto , des ccalor, ~ J these I techn qLes are slow A lernal veiy tne wet f iter cakeof acelopnenone 2 4.DNPh can oeo sso ,ed n chloroform(1 2 LI Tne re% t ng solAon s lnen washeo w th water and b caroonate solution. dried (MgSO,), filtered, and concentrated. This treatment gave a derivative with a melting point and TLC response that were similar to those obtained using ethanol. As afinal alternative,the wet filter cake may be wrapped in paper toweling, squeezed once by hand, and then squeezed again in a vise with dry toweling. This process is repeated with dry toweling until a satisfactory dryness is achieved. -- . .. 3 A d~c ~ al~m~na was used in tne Soxh el apparat-s oecadse t aoSorOS Jnreacteo reagenl Only traces of mater al were e Jteo oJr ng several hours of extraction in a separate experiment using only the Soxhlet apparatus, 1 g of the 2,4-DNPH reagent, and a fresh charge of acidic alumina. Thus.. 75 a" of alumina will retain anv unreacted reaaent. "6ean-slark apparau (Ace G ass, V neland. NJI however, commerc al traps do no1 nave a tofa retJrn oram conlro leo w lh a slopcocn Th s 1s an mporlant cons~deratonfor a vo at e kelone or aldehyde because some of the ketone could be carried to the trap and thus excluded from the reaction.
-
Volume 69 Number 12 December 1992
1037
Comparison Runs Comparison runs using both procedures were made for five comnounds: acetonhenone. benzaldehvde. " . cvclo. hexanone', 2-cyclohexen:l-one, and cyclopentanone. The vields and meltine ooint data are oresented in the tahle. While the ~radiprocedureusuaily gave the better yield, the Soxhlet ~rocedureis a good alternative due to the ease of manipul&ion and the purity of the derivative. If the yield is important, additional reagent can be added, and the reaction time can be increased. The ratio between the reactants and the volume of toluene were studied using acetophenone to optimize yields and reaction times.
-
Comparison of Melting Points and Yields: The Bradv Procedure versus Amberlyst-15 ~ a t a i ~ sand i s Soxhlet Extraction 2,CDNPH
Crude mp O C (%Yield)
Recryst. mp, C (%Yield)
Lit. mp
O C
Preparation and Purification
of ACetODhenOne 2.4-Dinitro~henvlhvdrazone . . Use of acetone to rinse the glassware should be strictly avoided unless it is thoroughly removed before use. Current Nonaqueous Soxhlet Procedure C a u t i o n : Toluene is toxic and flammable. All operations involving toluene should he carried out in the haad. Reaction Toluene (200 mL total) was added to a 500-mL, roundbottom, two-neck flask containing a magnetic stirbar, acetophenone (1.20 g, 0.01 moll, and 2,4-dinitrophenylhydrazine (1.98 g x 1.1= 2.18 g).5A-15 catalyst (2.0 g) was added last. The flask was attached to a D e a n a t a r k trap,4 which in turn was fitted with a foam trap and condenser. (The foam trap was placed between the flask and the condenser.) The reaction mixture was brought to rapid reflux and heated with stirring for 60 min. Small amounts of water were carried into the Dean-Stark trap as a finely divided azeotropic mixture. (ARer 20-30 min, the formation of water was no longer observed.) Extraction During the reflux period, the alumina column was re pared by slowly loading 75 g (80 mL) of acidic alumina (E.Merck; activity: 1) into a modified Soxhlet6 extractor (9) containing 70 mL of toluene. Adding alumina too rapidly causes formation of air Dockets. These mav be removed bv stirring the suspended alumina with a glass or stainless steel rod. Toluene should cover the alumina at this staee. The hot reaction mixture was poured into the Soxhlet apparatus through a spray funnel. To minimize disturbance of the alumina surface, this funnel should be constructed bv sealine the end of a lone-stem funnel and ~ i e r c ing the siies of t h l stem with s m a i holes near the bdttom. Thus. the emereina liauid can be directed as a sDrav " to all sides'for even d&gibukon. After the reaction mixture was rinsed into the Soxhlet apparatus, the stopcock draining the Soxhlet chamber was o~ened.Extraction was then carried out bv r a ~ i d"l vrecvcling boiling toluene (about 30-60 min) untii the major band of colored ~ r o d u c was t carried to the receiving flask. The stopcork leading to the receiving flask was closed, and toluene tabout id0 ~ Lwas I distilled Into the Soxhlet chamber.
8
-
A
-
'The 2,4-DNPH reagent contained 10%water as a diluent, hence the correction factor. 6A~imilarSoxhlet apparatus has been described (9).The dimensions of the chamber used in the current version are 45-mm-0.d. and 41-mm-i.d. x 300 mm. The amaratus was fitted with a 55/50 outer 10 nt at me top and a 24 25 inner lomt at the ootton A coarse, slntered-gass plate ,40-mm d ameter, was Lseo n the construcuon. The coarse porosity s mponant oecaLse I shonens the extract on time. 1038
Journal of Chemical Education
q n e nonaqLeoLs Soxh et p r o m l r e a n g A-15 catalyst T n e y e d was oslermmea nd8reclly oy ComDn ng tne welghtafcrystas wnln that ot tne resoie from stnppmg tne to .em t ltrate
'Brady pmcedure with sulfuric acid catalyst d~umped at room ternperaturei0.t m m to canstant weight. T h e yield is essentially quantitative, but it is difticult to determine due to water retention in the sample. 'Pumped at room temperature tor48 h.
Crystallization Crystallization was observed in the receiving flask when about 150 mL of toluene had been removed. The flask was allowed to cool, and disconnected from the Soxhlet apparatus. The orange crystals were removed by filtration, weighed, and analyzed by TLC (toluene, Rf = 0.41, which showed a single well-defined spot. The toluene filtrate was stripped of solvent (rotary evaporator), and the residue was weighed and analyzed. TLC showed reagent a t the origin and an extra spot (R, = 0.36). Cleanup If additional extraction of the column is needed, the distilled toluene in the Soxhlet chamber can be used with a second receiver flask. Solvents of greater polarity (ether, dichloromethane, chloroform) can be used as eluents on the alumina column. The column was drained and inverted. The alumina was shaken out, spread on a pie plate in a hood to dry, and then bagged for disposal. To minimize disposal, the toluene was recovered by distilling. The Dean-Stark apparatus may be used for this.
The Brady Procedure
Acknowledgment
The widely used procedure described by Shriner e t al. ( 4 ) was closely followed, but the scale was increased &fold. The quantities used are given below.
An Oklahoma Statc University Presidential Fellowship to R. L. H. i s grstcfully acknowledged. We thank 0.C. Dermer for reading the manuscript aGd for his comments.
2,4-dinitmphenyhydrazine ( 1 . 9 8 g x 1.1 = 2 . 1 8 g; 0 . 0 1 rnol)' sulfuric acid (10 m L ) water (15 m L ) ethanol (50 mL of 9 5 % ) aldehyde or ketone ( 0 . 0 1 mal) ethanol (100 mL of 95 %)
The product was removed by filtration, and then the filter cake was thoroughly washed with water1 (4 x 250 mL) or saturated sodium bicarbonate solution (8)(4 x 200 mL) and water (300 mL). The wet filter cake may be dried2 or directly dissolved i n boiling 95% ethanol (about 1Wg) for recrystallization a s recommended(4).
Literature Cited 1. Brady 0. L. J. Ckm. Soc 1931,756. 2. Johnsan, G. D . J Am. C k m Soc 1951, 73,5888. 3. Shine. H.J. J. Olg Chem. 1969,24,1190. 4. Shriner,R.L.;Fuaon,R. c.;curtin. D. Y;Morrill,T. C. TkSysf4moticI&nti,hfion of Organic Compounds; 6th ed.: Wiley: New York, 1980: pp 179-180. 5. &krts,R.M.;G;lherZ J.C.;&dewdd,L.B.; W~ngmvgm,AS.MalemE~~~menfol Olgonie Chemistry; 4th ed.: Saunders: Philadelphia, 1985; pp 7W-701. 6. Harrison,H.R.;Els~braun,E.J J Olg Chem. 1966.32, 1294. 7. Vankar, P : Rathore, R.; Chandraseksran, S. J 0,s Chrm. 1986,5I, 3063. 8. Behfomuz, M.: Bola", J. L.;Flynt,M. S. J Org. Chem 1985,50,1186. 9. Browne. C. E.; Buchanan, W L.; Eiaenhraun,E. J. Cham. I d . 1917.35. 10. Hodbook of Tabla for Orgonic Compound I&nfificofion, 3rd 4.;Rappoport, Z., Ed.; CRC Press: Boea Raton,FL, 1976: p 169.
Volume 69 Number 12 December 1992
1039
