Sami A. S h a m a a n d Thuan L. Tran California State University. Fullerton Fullerton, California 92634
I Amides and Hydrazides from Amine I
and Hydrazine Hydrochlorides
T h e Schotten-Baumann procedure is extensively used for the n r e.~ a r a t i o nof carboxvlic acid derivatives in the undergraduate chemistry labo~atory.'.~ For example, the synthesis of N-substituted carhoxvlic acid amides, by the SchottenBaumann procedure, involves the addition ofan acid chloride to a mixture of the amine and aqueous sodium hydroxide solution. Amines, however, are corrosive and toxic substances and their use poses a hazard t o 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 t o report here, a slight modification of the Schotten-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 - a u b s t i t ~ ~ t r i l amiaes and hvdr:rzide~,and is applici11,lt to a varier). ol'iullstrates as shown in the accompanying table. T h e modification is also valuable when t h e amine or hydrazine is available, commercially or synthetically, in the form of the hydrochloride salt. T h e 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 t h e monoacylated or the N,N'-diacylated product deoendine on the steric interactions around the nitrogen atoms. 'rhus, ;heny]-hydrazine yields the dibenzoyl derivative while di~henvlhvdrazineand diisopropylhydrazine produce the m b n o h e n ~derivatives ~~l predominantly.
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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 containing 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.
Amldes and Hydrazides from Amine and Hydrarine Hydrochlorides Starting Material
- Reagent
Solvent
Reaction Time
%
Product
mp
yield
Comments ir. 1650 and 3400 cm-'
CsH5COCI Toluene CaHsCOCl Toluene CsHsCOCl None
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-'
CaHsCOCl None C.H.COCI Benzene C.H5COCI Benzene
Toluene Toluene C&COCI
Benzene
(CHJC0)20 Benzene
CeH&OCI
Benzene
BHS
i-prop NHNH &prop.
(CHsC0)20 Nane CsHSCOCI Benzene
HCI
(CH3CO)z0 Nane CsHSCOCI Benzene
Melt ng po nrs are ~ncarrected I spectra
were recoroeo for N u p mu Is
Nmr values are 6 relative to TMS. 816 / Journal of Chemical Education
CH&ON(CH3)N(CH3)COCHo56-60' &prop N(COCsHr)NH i-prop I-prop N(COCHs)NH I-prop
C
N-NHCDC,,HyHCi
nmr(CDC11) 2.00(s),2.10(s) torr
...
bp 89'11
...
bp
207-209-
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-'
52'11 torr, nmr(CDC11).1.30(1).2.05(s).4.20(m). 7.35(~)
