Karen P. Long Diablo Valley College
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A More Convenient Method of Preparation - nide Derivatives of Carboxylic Acids
The prevalent textbook preparation of amide and substituted amide derivatives of carboxylic acids involves initial formation of the acid chloride by heating the carboxylic acid a t reflux in the fume hood with a laree excess of thionvl chloride for a specified 15-30 min. hep procedure has oft& been considered less than ideal in undereraduate laboratories. Problems include insufficient hood space with water lines, loneer times than desired. and oossible svatterine .. orocedure . with formation of unwanttd ammonlum salt f n m r~action(;f the excess thionyl chloride with the amine. In nddirion, s t n q acids such as polynitrwwwnaric and n-trihalucarlr~xylicacids or hindrred acids may nut n,nct sufiiciently in the specified time, while others may undergo side reactions during thereflux with thionyl chloride. These disadvantaees mav he overcome to a laree extent bv the use of dimethylformamide catalysis in the ;id chloridk formation. Acid chlorides of the less reactive acids have been made for some time hy refluxing with thionyl chloride containing a small amount of DMF.' That this reaeent can also he us& to form acid chlorides of a large varietyof acids, and works a t reaction temperatures below reflux has not been widely promoted. An adaptation of this method was devised for use in a qualitative organic analysis program. T o make the acid chloride of an unknown acid, the students are told to mix in the hood 1e of unknown acid. 1ml of thionvl chloride. and 5 drops of DGF.A calcium chloiide drying tude is then attached directly to the flask and the flask is clamped into a 55-65'C water bath in the hood. Bubbling and/or fuming usually begins shortly after addition of the DMF. When bubbling greatly slows down, the reaction is considered to be sufficiently complete and the acid chloride mixture is used for making the This paper was presented a t the 169th National American Cemical Society Meeting in Philadelphia, Pa., April 1975. Basshard, H. H., Mory, R., Schmid, M., and Zollinger, Hch., Helu. 42,1653 (1959). 1.00 ml of thionyl chloride is sufficient molar amount for complete reaction with 3 carbon or more monoearboxylic acids and 6 earhon or more dicarhoxylic acids with no other functional groups. a Dovbenchuk, E. M., Nikipanchuk, M. V., Pirig, Ya. M., Serendnitskii, Ya. A., and Tolopko, D. K., Vim L'Viu Politehh. Inst., 58, 36 (1971). [Chem. Ahstr., 77,113613K (1972)l. "ikugawa, K. and Kawashima,T., Chem. Pharm. Bull, IS, 2629 (1971). Vinogradova, S. V., Pankratov, V. A,, Korshak, V. V., and Kamarova, L. I., Izu. Akad. Nauk SSSR, Ser. Khim. 3,513 (1971). [Chem. Abstr., 75.4830m (1971)l. Willard Grant Press, 20 Newhury St., Boston, Mass. 02116. Ask for ANAL-173: "Amide, Anilide, and p-Toluidide Derivatives of Unknown Organic Acids" in their modular laboratory program in Chemistry. A Supplemental Instructor's Module is also available.
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420 1 Journal of Chemical Education
amide in the usual way. If bubbling starts a t room temperature, the acid may not require the heating (for example, 1naphthoic acid undergoes about 90% conversion in 5 min a t room temoerature). Ry using a trmperature belo% the rrflux temperature, evolution of rrtxlurt rases SO. and HCI is easily observable. This indicates k u g h l y i h e desired reaction time rather than necessitating unthinking reliance on a text-specified time which might be too short o r long for the particular acid. Warming a t 5545°C gives convenient reaction times, normally less-than 10 min andrarely longer than 30 min (about 25 m h for 3,5dinitrohenzoic acid).. The short reaction times and use of a laree communitv water bath in the hood allow limited hood facil~tiesto he used hy a large number of students. Since a great excess of thiunvl chloride i.; not used.' the subseoumt t~midepwparatiun is cleanw and less hazardous. The method also nllows derioatization of both acid crouoi in dicarboxylic acids, which is not possible with tlhionil chloride alone, and gives better yields of derivatives of unsaturated carboxylic acids. However, both methods produce primarily undesired products when used with hydroxy acids, N-acylamino acids, o-benzoylbenzoic acids, and acetylsalicylic, malonic, ethoxyacetic, and cyanoacetic acids. On the whole, the DMF catalyzed procedure was more reliable in student hands and far more convenient in the 350 student classes which used i t than was the usual procedure using thionyl chloride alone. DMF also worked better than vvridine as a catalvst in a few comoarison trials below reflux iemperature withcomparable amounts of thionyl chloride. More than 50 different acids have been successfully derivatized in student trials, including unsaturated acids, dicarhoxylic acids, and acids containing halogen, ether, thioether, or nitro groups. Amide, anilide, or p-toluidide derivatives were made. When the reaction is carried out below 70°C as it is here, the active intermediate has been shown to be the adduct LI.3
0
1I
I(CHs)zN=CHOSOCl]+CI- (CH3I2NC-CI I I1 [(CHd2N=CH-CI]+CI111
Above 70' the mechanism is believed to involve 11. Adduct I is formed first a t room temperature but is slowly converted to a mixture of I and 111 a t 40-50°C under vacuum. Heating under reflux converts I to a mixture of I1 and IIL" A complete student write-up using this method has been published as a n introductory experiment in identifying unknown acids. A list of 24 good acids is included. Interested instructors may ohtain a free copy from the p u b l i s h e ~ . ~
