From Cyclohexanol to ZAlkylated Cyclopentanones An Open-Ended Set of Experiments for an Upper Level Organic Laboratory Claude E. Wintner Haverford College, Haverford, PA 19041 This communication outlines a sequence from cyclohexan01 to 2-alkylated cyclopentanones (figure) that has proved to be very successful over the past four years as the initial task for students in an integrated laboratory course at Haverford College. We use it to acquaint students with a numhar of techniques in synthetic organic chemistry as well as to introduce them hands-on to analysis using IR, 'HNMR, W N M R , and GC-MS. Specific procedures are not given out; instead, students are introduced to the use of library sources, after which they devise procedures based on their own searching. The needed sources are certainly not ohscure, but there are a number of available choices to he considered. Students are given 50 g cyclohexanol to start with and are asked to convert this to the maximum amount of adipic acid that they can. They are encouraged first to investigate a procedure on a small scale and then to run perhaps two larger scale reactions. Nitric acid oxidation (1-3) generally proves most efficacious. The resultant adipic acid is analyzed using only IR spectroscopy (KBr pellet), which is introduced concurrently. After the adipic acid has been isolated, the nitric acid mother liquors from the oxidation are allowed to evaporate slowly. In addition to adipic acid, the mother liquors contain suhstantial quantities of succinic and glutaric acids, due to overoxidation (2).This allows an interesting amplification of the subsequent esterification step, as described below. Recrystallization of a small portion of the adipic acid from water is generally necessary to obtain a pure sample; however, the losses in the recrystallization are substantial, and the hulkof the raw product may he used further as it is. Esterification to diethyl adipate (4.5) is a smooth reaction, with very high yield, and serves t o introduce vacuum distillation. The product is analyzed using both IR and NMR spectroscopy ('H and 13C), for which it provides a simple textbook case. Dieckmann cyclization of diethyl adipate to ethyl 2-0x0cyclopentanecarboxylate (6, 7) is readily carried out using sodium in toluene, with a small amount of added ethanol to help initiate the reaction. We have obtained excellent results with rather finely cut pieces of sodium (1 X 3 X 3 mm) in toluene, and efficient mechanical stirring (a magnetic stirrer will not develop sufficient torque to stir the pasty sodium salt of the cyclized product). For this product the analysis after workup is now extended to include GC-MS as well as IR and NMR. With GC-MS now in the arsenal, we take a side trip hack to the raw crystalline material from the evaporated nitric acid mother liquors. Esterification and subsequent vacuum distillation afford a mixture of diethyl succinate, diethyl glutarate, and diethyl adipate. This mixture provides an excellent vehicle for analysis by GC-MS as well as by 'H and WNMR. Presented in part at tha Symposium on the Impact of College Sclenm Instrumentation Programs on Middle Atlantic Institutlons. Division of Chemical Education. 23rd ACS Middle Atlantic Regional Meeting. 24 May 1989. 984
Journal of Chemical Educatlon
Alkylation (8-12) of ethyl 2-oxocyclopentanecarboxylate is efficiently accomplished using potassium carbonate in acetone (8). We have obtained good results using- iodomethm e , 1-bromopropane, and I-bromobutane. Hydrolysis and decarhoxylation of ethyl 2-oxocyclopentanecarboxylate may be carried out using standard methods (13-19). The procedure of Krapcho and Lovey (15), using dimethyl sulfoxide and chloride ion, is superior for the more hindered alkylated cases. In this series of reactions we find especially successful on the one hand the introduction of spectroscopy as a tool in the real world of svnthesis. and on the other the seouenced , and GC-MSas thestepnp&ress. introductionof i ~NMR, Resoectable overall vields of the final alkvlated ketones are within the reach of most students. Furthermore, in case of a "disaster"along the way, the intermediates are readily commercially available. Recently we have also worked out the two opening steps for use in a fint-year organic microscale laboratory (20). The stimulation and encouragement of my colleague Colin MacKav in manv ohases of this work are eratefullv acknowlchro&atographedged. he purehase of Haverford's mass spectrometer was funded by grants from the National Science Foundation (Grant #CSI-8551, the Keck Foundation, and the Du Pont Company.
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Literature Cned 1. ~ i e l d K. . w.;Shields, J. P.; Sfandard, J. M.: Ash. C. K.: Hmh. D.J.: Kdb. K. E. J . Chsm. Edur. 1985.62.637438. 2. Ellis. 8. A. In Orgonir Synfhaaoa, Coll. Vol. I, 2nded.r Blatt, A. H., Ed.: WileY: New York, 1941: pp 18-20. 3. G d t . H. C.;Quinn. J. F. J. Amer Chem. Soc. 1956,78,146-1464.
IO. A ~ ~ ~ ,K R . ~ ; R. M.~I" o ~ ~synthares, , ~ cell. ~ VOI. ~I, 2nd ed.; i ~ k~t tA. . H., ~d.: Wiley: New York. 1941;pp 2W251. organic .yyntheSea, toll. vol. Y; ~ ~ ~H.~ . ~. m . Wiley: ;~ New ~ ~ 11, Elsinger, F, York, 1973; pp 7680. 12, Thampron,D, L,.Reves,P. C,J, c ~ ~ ~1g85,62,907.g08, , E ~ ~ ~ , 13. nazzard, B. J.;Ongley, P. A.,Eds. Organicurn; Addison-Weday: Rosding,MA, 1973:p
433. 4. Mimuic,V.M.InOrgonicSynthesas,Coll.Vol.II:Hhtt.A.H..~.;W~l~Y:N~~Y~~k~ 14, ~ ~ h , , ~ J, ,,, ~ , . H ~ ~ ~ ~~, F ~, D ~, ~ ~ ~ ~ Vol.I,2nded.:Blatt,A. i ~ ~ ~ ~ f H..h ~ 1943: pp 264.235. Ed.: Wiley: New York, 1941: pp351-353. 5. man, M. S. ~n Aduoncad O m n i c Laboratory C o u w : Macmilh: New Yo% 15, K ~ ~ ~P . ;~L ~~, . ~ , AJ.A . ~ . ~ i ~ ~ h ~1913,957-950. d ~ ~ ~ L ~ f t . 1972:pp 7-42. 16. K r a ~ h oA. , P.: Jahngren. E. G. E.,Jr.:Lovey, A. J.: Short, F. W. T~lrahedronLdf. Ed.; Wiley: N& York. 5. Pinkney, P. S.In Organic Syntheses. Coll. Vol.Ik Blstf, A. H., 1914.1091-1094.
Volume 67
Number 11 November 1990
985
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