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Sami A. Shama and Thuan L. Tran I Amides and Hydrazides from Amine California State University. Fullerton Fullerton, California 92634 I and Hydrazine Hydrochlorides The Schotten-Baumann procedure is extensively used for the nre~aration of carboxvlic acid derivatives in the under- . . graduate chemistry labo~atory.'.~ For example, the synthesis of N-substituted carhoxvlic acid amides, by the Schotten- Baumann procedure, involves the addition ofan acid chloride to a mixture of the amine and aqueous sodium hydroxide so- lution. Amines, however, are corrosive and toxic substances and their use poses a hazard to the inexperienced student. In addition, aliphatic amines are highly volatile substances that may escape easily from the reaction mixture resulting in a low yield of the desired product. We wish to report here, a slight modification of the Schot- ten-Baumann orocedure in which the amine or hvdrazine is replaced hy thicorresponding hydrochloride salt, and the use of alkali is eliminated altoaether. This modification presents a siaf(, and eificient method for thesynthrsiiof S-aubstit~~tril amiaes and hvdr:rzide~, and is applici11,lt to a varier). ol'iull- strates as shown in the accompanying table. The modification is also valuable when the amine or hydrazine is available, commercially or synthetically, in the form of the hydrochloride salt. The direct use of the salt saves time and leads to better overall yields than those obtained by the traditional procedure which requires the extra step of liberating and separating the amine. This modification leads to the predominant formation of the monoacylated amines. Hydrazines, on the other hand, yield the monoacylated or the N,N'-diacylated product de- oendine on the steric interactions around the nitrogen atoms. 'rhus, ;heny]-hydrazine yields the dibenzoyl derivative while di~henvlhvdrazine and diisopropylhydrazine produce the mbnohen~~~l derivatives predominantly. Experimental Procedure A 100-mlround-bottom flask containing a l-cm magnetic stirring bar is charged with 100 mmole of the amine hydrochloride, 100 mmole of the acid chloride and enough toluene to produce a total volume of approximately50 ml. The flask is equipped with a water-cooled reflux condenser and the condenser is topped with a vacuum adapter con- taining anhydrous calcium chloride. The side arm of the adapter is connected to a water aspirator while the wide end is left open to the atmosphere. This arrangement serves as an efficient gas trapGnd insures that the hydrogen chloride gas that evolves during the reaction does not escape into the laboratory. The aspirator is turned on and the mixture is stirred and heated to a reflux by a heating mantle. If a heating mantle is not available, the mixture may be refluxed on the steam cone with occasional shaking of the apparatus to insure the thorough mixing of the reactants. Refluxing is continued until most of the hydrochloride salt disappears or until the evolution of hydrogen chloride gas subsides. The reflux condenser is then replaced by a still head and the solvent is removed by distillation under aspirator pressure. In the case of amines containingfour carbon atoms or less,_ the product is purified by distillation under reduced pressure. Amines with higher carbon content and all the hydrazines tested in thisstudy yield a solid residue after the evaporation of the solvent. The residue is recyrstallized from ethanol-water,and the product is identified by the usual analytical techniques (ir, nmr) as well as a mixture melting point with an authentic sample. Vogel, A. I., "A Text-Bookof Practical Organic Chemistry," 3rd ed., John Wiley and Sons, Inc., New York, 1962, p. 582. 2 Shriner, R. L., Fuson, R. C., and Curtin, D. Y., "The Systematic Identification of Organic Compounds," 4th ed., John Wiley and Sans, Inc., New York, 1959, p. 98. "oherts, R. M., Gilbert, J. C., Rodewald, L. B. and Wingrove, A. S., "An Introduction to Modern Experimental Organic Chemistry," 2nd ed., Holt, Rinehart and Winston, Inc., New York, 1974, p. 104. Starting Material Reaction % Reagent Solvent Time Product mp yield Comments Amldes and Hydrazides from Amine and Hydrarine Hydrochlorides - i-prop NHNH &prop. HCI CsH5COCI Toluene CaHsCOCl Toluene CsHsCOCl None CaHsCOCl None C.H.COCI Benzene C.H5COCI Benzene Toluene Toluene C&COCI Benzene (CHJC0)20 Benzene CeH&OCI Benzene (CHsC0)20 Nane CsHSCOCI Benzene (CH3CO)z0 Nane CsHSCOCI Benzene BHS CH&ON(CH3)N(CH3)COCHo 56-60' &prop N(COCsHr)NH . . . i-prop I-prop N(COCHs)NH . . . I-prop C N-NHCDC,,HyHCi 207-209- ir. 1650 and 3400 cm-' ir. 1650 and 3350 cm-' ir. 1654 and 3350 cm-' ir. 1650 and 3350 cm-' nmr, (CDCI,) 3.02(s). 7.40(s) ir. 1639, 1670 and 3250 cm-' nmr(CDC11) 2.00(s), 2.10(s) bp 89'11 torr bp 52'11 torr, nmr(CDC11).1.30(1). 2.05(s). 4.20(m). 7.35(~) Anal. Calculated for ClqHq5N20CI: C. 58.27; H, 6.67: N. 12.36 found: C, 58.56; H. 6.80 N, 12.42 ir. 3250 and 1640 cm-' Melt ng po nrs are ~ncarrected I spectra were recoroeo for Nup mu Is Nmr values are 6 relative to TMS. 816 / Journal of Chemical Education
