Project for a Problem-Oriented Undergraduate Organic or Integrated Undergraduate Laboratory
Augustine Silveira, Jr. State University of New York College at Oswego Oswego, 13126
Although goals of chemists teaching the organic chemistry or integrated undergraduate laboratory vary, a general goal that most teachers attempt is to design a laboratory which will develop their students' creativity and independence and teach them a variety of experimental techniques. Project oriented experiments we believe are often successful in accomplishing these goals. Reported herein is an open-ended pruject which allows a great degree of flexibility in the laboratory. The project provided ahout a &week study for groups of 24 students each. These students were in their second semester of organic chemistry lecture. The elegant method developed by Carpino ( I ) in the preparation of n-phenylcinnamic and n-phenylcrotonic acids, which involved reaction of 4-halopyrazolones with aqueous alkali, was utilized and adapted in our group project starting with 0-keto esters. For purposes of clarity, the overall synthetic scheme will be presented before each reaction is discussed.
Table 1. Carbonyl IR Absorptions of Pyrazolones
F Cpd (Ill) (111)
(1111
(1'4 (Ivl (v)
Table 2.
= B& 0
Rl
R.
H
+ >c='
\
COOH R, COOH (VII (V) E isomer Z isomer The synthesis as it stands is exceedingly useful from a pedagogical point of view. It easily provides for student involvement and discussion in the following reactions or concepts: cycloaddition, chemical economics and patent rights (some final products were difficult to obtain by other methods and thus costlv). molecular orbital theories, elimination, electrophilic, nucleophilic addition and displacement reactions, orbital symmetry, thermodynamic and kinetic control and regiospecificity of reactions, tautomerism and steric inhihitiun of resonance. Student attendance a t optional evening discussion sessions was excellent and enthusiasm remained hieh throuehout the proiect. ~ e c h n i q u e that s sfudents utilized throughout the project were spectral methods of analysis in structure elucidation, H
vapor phase chromatography including fraction collection, thin layer chnmatography, and trapping experiments. All of the halopyrazolines(1V) previously investigated by Carpino hore aryl suhstituents a t either C-3 or C-4. Recently ( 2 ) work has been done where R, has been varied with alkyl (ethyl, sec-hutyl, and tert-hutyl) and phenyl groups.
CHj CHI CH1 CH9 CHJ CHI
CHa CHICH, CH3CH2CH2 CHJ
CHGHI CH3CH2CH2
R3
Position (cm-'1
H
1613 1616 1616 1733 1724 1725
H H CI CI CI
Stereochemistry of the Conversion of 3,4-Dlalkyl-4to a$-Unsaturated Acids RI
CHs CH3CH2
CH, CHs CHn
>-
oledwith stirring in a n ice hath and 0.015 mole ol'the :i,4-dialk.vl-4-chlor1~pyraz~~lin~5-~~ne was added. T h e solid dissolved giving the solution a yellow-orange color with gas evdution. After gas evolution had suhsided, the ice bath was removed and the stirring was continued for 2 additional hours a t nmm temperature. T h e solution wasacidified with :i N HCI and t h e acids were extracted with one-35 ml portion and five 1 5 ~ mportionsofether. l Thecomhined ether extracts were extracted 4 times with 1.0 N NaHCO:,. T h e NaHCO:, extracts were acidified with concentrated HCI and t h e organic acids reextracted with ethyl ether as hefore. T h e ether extracts were dried over MgS04, filtered, and the ether was removed. T h e average yields of(E1- and (Z)acids ( V ) (VI) are given in Table 1 and the mixtures were readily separated hy vapor phase chn,matography. No isomerizatim of the acids occurred under the conditions ol'gas chromatography as pnwed lhy the use of the pure acids. T h e products were collected in a fractim collector described previwsly ( I 1 ) . T h e proton magnetic resonance peaks, due t o the vinyl pnlton, appeared in all cases as qrtartels and the values are reported fur the center of each quartet and expressed in ppm. T h e vinyl proton value fin each acid (K,CH = CR2COOH1 is shown in'rahle 3. Typical gas chrc,matographic conditirms and relative retention times are given in TaMe 4. Some students detemined the dissociation constants and nentralizatim equivalents oftheir ( E l - and (Zl- acids, hy standard prwedurps.
Table 4. Isomer
z3 Eb Zr
ES Zd Ed
+
T h e method ol' Carpino, e t al. ( I ) in t h e 4,s-diphenyl case was idlawed. Cyelopentadiene and I,:$-hutadiene were used as the trapnine,. aeents and cave t h e same comnaund shown not t o be the expeeted adduct. The structure of the a m p o u n d formed in this reaction has not hpen established, h u t the d i m e is clearly not involved in its furmation. With respect t o the 4,s-diphenyl rase, the adduct was readily ohtnined hy t h e students in 75.0'Vn average yields.
.
RI
R2
15% FFAP
CH3 CHa CH3 CH3 CH3 CHJ
CH3 CHs CH3CH2 CH3CH2 CH3CH2CH2 CH3CH2CH2
1.16 1.28 1.55 1.73 1.37 1.46 1.00
RS-2-methylbutanoic acid
Time corrected tor gas hatd-up. * ~ y p i c a~l x p tconditionr: . lnln 275': column temp. program: 68'at 10°1min, to 188'. 2O/min l a 5 minstartingat 18S0, lO0/min to 218'; pressure 20.0 psi. amples size 20ul: menuation 2: detector femo. 238O: filament current 2 5 0 ~ Achart . speed 0.5 inlmin: flow rate 72.5 mllmin: air peak eluiion 4.75 mm; RS-2-methylbutanoic acid elution: 130.75 mm. 'TypicalExpt.Cond1tions: lnlet275°; colvmntemp.program: W a t 1S0imin1o 171'. 18.0 mi. samoIestze9u1, anen0.5°/minfrom 171.176'. 19.5°imin. f 0 2 1 5 ~ ~ressure : uation 10; detector temp. 238': filament curreni 250uA, char weed 0:5 inimin: flow rate 58.5 mt/min. air peak elution 5.80 mm: RSBmelhylbutanoic acid elution: 119.9 mm. dTypical Expt. CoMitions: Inlet 275': column temp. program: 68' at 18'1min to 183'. O k l m i n from 183-189'. 255'imin to 240°C: oressure 20.0 osi. samole sire 5ut. attenvation 5: detector temp. 238"; filament current 275uA, chan speed 0.5 inlmin: flow rate 120 ml/min.: air peak elution time 12 s: RS-2-methylbutanoic acid elution time. 13.8 mi". ~
Trapping of the Proposed 4.5-Diaikyl-2.3-DiazacycloPentadienone intermediate
Relatlve Retention Timese (RICH = CRFOOH)
~
..
Literature C i t e d
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t i 1 ('ram. 11. I. "Yundnmentnls . 01 rart~rninn~ h ~ m i r f r ) A
