Hammett Correlations of Amide Proton Chemical Shifts An Organic or Spectroscopy Experiment F. L. Setliff, N. G. Soman, and A. D. Toland
University of Arkansas at Little Rock, Little Rock, AR 72204 Electronic effects of substit u e n t s a r e t a u g h t extensively throughout organic chemistry, and this knowledge is essential to the understanding of relative reaction rates, equilibrium constants, relative stability of reaction intermediates, and many other important concepts. Unfortunately, there are relatively few student-oriented experiments available t h a t demonstrate a q u a n t i t a t i v e relationship bet w e e n a n easily m e a s u r a b l e property and the electronic effect of a substituent. This experiment involves the construction and analysis of a Hammett plot that shows the substituent electronic effect of a variety of groups in the 4'-position upon the amide proton NMR chemical shifts in a ser i e s of Y-substituted benzanilides. The Hammett equation and re- Hammett plot of amide proton chemical shift vs. substituent constant for the @-substitutedbenzanilides finements thereof ( 1 ) have been used extensively through t h e presence of electron-withdrawing substituents, whereas a years to assess the electronic effects of a substituent R atnegative value denotes facilitation by electron-donating tached directly to an aryl system upon a reaction center groups. Avalue for p is obtained by plotting log k vs. o~ and meta or para to the the reaction site. Substituents in the determining the slope of the line. ortho position are not studied due to complication by steric Attempts to correlate properties other than reaction effects. The equation is given a s rates or equilibrium constants with Hammett o constants have met with limited success. Although correlations of ullog k = p o + ~ log k, traviolet, infrared, and polarographic data have been marginally successful, NMR data seem to correlate extremely well (3). We developed this experiment with this knowlwhere k is the rate constant of the reaction being studied edge, encouraged by the excellent work of Giffney and with a substituent R present; and ko is the corresponding O'Connor on acetanilides and phenylureas ( 4 ) . rate constant of the unsubstituted comoound (R = HI. The llalnlnett subetitucnt constan1 n~ is charactenst~c Results and Discussion ofthr nature and ~o.,~tion ot'thr suhatirurnt. It'R is h\,drogen, then OR is dehned as zero. ~lectron-withdrawingsubThe 'H NMR spectra of a series of 4'-substituted benstituents have positive o values, whereas negative values zanilides are determined in DMSO-ds with tetramethylsilane a s internal standard. The amide protons i n the series of o are characteristic of electron-donating groups.' The are strongly deshielded and appear as sharp singlets in the magnitude of o for a given substituent varies according to range 6 10-11 ppm, well set apart from the aromatic proits location in the meta or para position. The o constants ton resonances. The group of benzanilides includes comused in this experiment are the standard Hammett values, pounds with both electron-donating and electron-withas opposed to any of the refined values developed to account for individualized inductive or mesomeric effects (2). drawing groups i n the li'-position. After obtaining the NMR spectra of all compounds, the student will plot the The reaction constant p is characteristic of a given reaction and denotes the sensitivitv of the reaction to the electronic amide proton chemical shift against the appropriate substituent constant. The table summarizes the amide proton effects of the various substituent groups studied. Apositive chemical shifts for each compound a s well a s the value of p indicates that the reaction is enhanced by the standard Hammett substituent constants (OR)for a para substituent (5). h he organic student will recognize electron-withdrawing substiA plot of SNHVS. (TR is depicted in the graph, and the lintuents as deactivators toward eiectrophilic aromatic substitution and electron-donating groups as activators. ear relationship is defined by the equation 362
Journal of Chemical Education
h, = 0
+
. 6 4 ~ 10.29 ~
Data on the 4'-Substituted Benzanilides
correlation coefficient = 0.99
C-N
In the Hammett context, the slope of the line (0.64) corresponds to the reaction constant p. The positive value of p indicates that the amide proton's chemical shift is very sensitive to electron-withdrawing influence. More specifically, a s the suhstituents in the Y-position become more n~ values hecome more positivr,, SSII (!l(,ctn,n-:~ttr;~ct~ng is dtsplxed farther downlirld ihighvr ppm . Thls 13 cxolninrd in terms (lf thr incnmcd ariditv m o a n e d to the amide proton by electron-withdrawing substituents in the 4'-position, which in turn facilitates the already present hydrogen bonding of the NH to the DMSO solvent. As the efficiencv of hvdroaen . .. bondine.. increases. the depree of drshirldinfi is mh:lnct,d ifi . I'hc electron-donntlng substituents methvl and methoxv, oroduce SW'S I(% dt:ihit.ldt:d than henzanikde itself (R =HI. "
R
A
-
Experimental Format This experiment is flexible and may be used as a n exercise in the sophomore organic lab or in a more advanced instrumental or spectroscopy laboratory. Two suggested approaches are descrihed. Organic Exercise As a n organic exercise, the experiment is carried out a s a group project in two lab periods, preferably a s one of the latter exercises i n the second semester. The subjects of snbstitnent effects, amide synthesis, and NMR spectrosc o.~ vshould have been covered ~reviouslvin the lecture component of the course. Aprelab lecture on Hammett correlations. not to exceed the scooe of that oresented herein, will be sifficient. A class of 20124 students is divided into groups of two or three, and each group prepares a different benzanilide.' In the second lab period each group obtains the NMR spectrum of its product.3 The class pools the &H data, and each student constructs a plot by hand and generates the correlation equation by the slope-intercept method. Spectroscopic Experiment As a spectroscopic experiment in an advanced lab (ten or less students) the henzanilides (either purchased or prepared previously by the organic class) are provided for each student. Students then obtain their own set of spectra. These students would be required to generate the&relation equation using a computerized linear-regression analysis. Experimental Procedures Caution: Benzoyl chloride is a lachrymator and skin irritant.
2As an alternative some of the compounds may be purchased because most of the benzanilides are commercially available (Aldrich or TCI America Organic Chemicals). 3 ~ i t hinstructor assistance and a well-tuned spectrometer, the needed eight spectra may be obtained easily in a 3-h lab period. Alternatively, copies of predetermined spectra may be distributed or posted if time will not permit all spectra to be recorded. 4Because 4-nitoaniline is not soluble in chloroform, benzene is used as solvent in the preparation of 4'-nitrobenzaniiide(TCIAmerica Organic Chemicals).
Caution: Benzene is a reported carcinogen.
Samples are prepared in DMSO-d6 (Aldrich) containing 1% tetramethylsilane a t a concentration of 20 mg of benzanilide in 1.5 mL of solvent. Our NMR spectra were obtained on a Bruker 200-MHz instmment equipped with ASPECT 3000 computer control. The Hammett plot was produced by an Axum least-squares program (Tetramatrix, Seattle, WA). Although most of the benzanilides are available commercially, students may prepare all of them by the semimicroscale procedure described as follows. A solution of henzoyl chloride (0.25 mL, 0.0022 moll in dry chloroform (3 mL) is added to the a ~ o r o ~ r i a t e substituted lv 4-substituted aniline (0.0045 moil in dry c6lorofom4 (10 mL). The mixture is heated under gentle reflux for 45 min with maenetic stirring and cooledto room temperature. Then i t i s vacuum-filtered to remove the solid, which i s washed on the filter with 5 mL of dry chloroform. The solid, which is a mixture of the aniline hydrochloride and the henzanilide product, is transferred to a beaker and stirred magnetically with water (100 mL) for 15 min. The hydrochloride dissolves, leaving the product a s a residue. If there is little or no residue, the henzanilide is ohtained from the chloroform filtrate. The filtrate is transferred to a separatory funnel and washed first with 2 x 10 mL water and then with 2 x 10 mL 10% hydrochloric acid. The lower chloroform layer is separated and evaporated i n a n air stream. The crystalline residue from the evaporation is combined with any solid residue ohtained from the water washing of the original precipitated solid and is recrystallized from aqueous ethanol. Yields are in the range of 50-70%. Literature melting points (7)are given i n the table. Literature Cited 1. Johnson, C. D.The Hmrnmatf Equalinrr: Univerlity Pres-: Camh6dge. 1973. 2. Exner, 0. Cormlolion Analysis of Chernicol Dora: Plenum: New York. 1988; Chapter 1.
3. Ewing. D. F. In Correlalio,, Analysis in Ch~mislry:Chapman. N. B.; Shorter. J., Eds; Plmum: New Yark, 1978; Chspler 8. 4. Giflne). C. J.: K o n n o q C. J.J. M ~ g Rema n 1975.1X. 230-234. 5. Exner 0. Cormlolion Andysir ofCltliemirnlDaCo; Plenum: New York, 1988: p 61. 6. Kemp. W Organic Spedrorcopy. 3rd ed.; Freeman: New York,1991: p 132. 7. Rappoport, 2. In Hondbuok of lhbies for Orgnnic CompouzcdIderrlificn!ion. 3rd ed.: Weart. R..Ed.: Chemical Ruhhrr Co: Cleveland, 1967: Tahla XVIII, pp 303-318.
Volume 72 Number 4 April 1995
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