The Correlation of Multinuclear Spectral Data for Selectively Fluorinated Organic Compounds T. Stephen Everett' The Johns Hopkins University, Baltimore, MD 21205 Nuclear magnetic resonance is the workhorse of organic analysis and structure elucidation. Improved instrumentation now allows the detection of many nuclei and manipulation of data for stroneer structural evidence. Although fluorine NMR is not a n& development (1-4), current interest in oreanofluorine chemistrv accentuates the need to identifv thesecompounds correctly, taking advantage of all the spec"tral evidence available. A great wealth of structural information can he gleaned from proton and carbon NMR. With selectively fluorinated organic molecules even more spectral data are available through the acquisition of fluorine NMR. Correctly interpreted the combined data from 'H, '3C, and 19F spectra should fit together like pieces in a puzzle. Yet there are few sources which correlate data for all three nuclei (5.6). . . This article i h d r l .;rr\.r 8s a nmwnient introduction. After n renerd discussion of fluorine- 19 I\'\1R. s ~ e c t r adata l fur two series of selectively fluorinated compo;;ds2 will be presented. alona with the detailed correlation of multinuclear data for one specific compound. An lntroductlon to Fluorlne-19 NMR Fluorine NMR data can be readily collected on most spectrometers, requiring only minor adjustments to instrumentation used to run proton samples. The fluorine-19 nucleus is easily detected, with a relative abundance of 100%(the only naturally occurring isotope of fluorine) and a spin of %. Many of the guidelines given for the interpretation of proton NMR hold true for fluorine NMR. Regardless of the nucleus in question, knowledge of approximate chemical shifts is required to establish a basis for NMR comparisons. This foundation is often provided by a general correlation diagram (see below) and memorization of data for a few reference compounds. Fluorine NMR signals have a wide range of chemical shifts. The majority of signals when fluorine is hound to carbon are detected upfield from C F C h the most common reference? Most organic fluorides fall in a 300 ppm range, shown in the correlation diagram (Fig. 1).
422
Journal of Chemical Education
c WE6
E-C=O+CFf
I
I
-CF-
1
I
2
-CF-
I
I
I
Figure 1. Correlation diagram showing approximate ranges of chemical shlfls lor fivefluorinated subunits. In addition to chemical shift interpretation, a knowledge of the magnitude and multiulicitv of snin-snin counline . interactions is necessary in the ev&ation. In 'the multinnclear NMR of fluorinated com~ounds.the coupline . .. con;it8nrsJ11~, JCF,and J ~ ~ aimportant r e evidence in deciphering spectra. U M H spectra of fluorinnted molrrules are often quite fascinating d i e to the distinctive geminal ( V , twobond coupling - constant) and vicinal (3J). couplings - - of fluorine to proton and fluorine to fluorine. Long-range, throughbond or through-space coupling interactions are often seen in fluorinated comoounds. Fluorinated aromatics show complex splitting patterns due to proton-fluorine coupling throuahout the rine svstem. ~ e t e r o a t o m sdistinctively alter proton and carbon spectra, giving indirect evidence of their presence. The extreme electronegativity of fluorine and large spin-spin coupling Presented in part at the 20th Middle Atlantic Regional Meeting of the American Chemical Societv. SeDtember 1986. ' Current adaress Department of Chem~stry.Towson State Jn versty. Towson, MD21204 Empnas~swail be placea on the spectral Interpretat on of se ect,vely fluor nated compo~ndsthat requnre proton and I -orme hMR in combination rather than highly fluorinated or perfluorinated compounds that predominate earlier lgF NMR compilations.
TaMe 1. Mvltlnuclear Spectral Data lor Phenyllluoropropanes bp'
'H-NMR"
@CH&HSH2F42 (1.0) 4.44 (dt) BCH2CHFCHs 36 (1.0) 4.85 (dm) BCHFCH&H3 32 (1.0) 5.35 (dl)
'OC-NMRE 83 (d) 91 (6) 96 (d)
'A,. Hz
*AF. Hz
220 (ti)
165
171 (dddq) 176 (ddd)
169 171
47 48 48
'$F-NMRd
'Boiling paint at reduced prstoure. OC (mm Hg). bchemical shin in ppm lor proton[.) geminai to flwrine. 'Chemical Shin in ppm far mrbm bound to fluwine, fluorine mupledlproton decou-
initially splits the signal into a triplet arises from geminal coupling of two protons to fluorine, therefore CH2F is indicated. Further solittine of the sienal into a triolet of trinlets " is due to vicinal coupling from two more protons to indicate CHzCH2F as the most plausible subunit based on information to this point. Proton NMR supports this conclusion. Protons on the fluorinated methylene unit are shifted downfield (to 4.446) by deshielding due to the electronegative fluorine atom. This proton signal is split into a doublet of
-
PW. Qlnppm upfieid from CFCis.
interactions make its nresence easilv recoenized. Proton and carbon signals are sh;fted downfielb from their positions in analoeous nonfluorinated com~oundsand additional s d i t ting seen. Spin-spin coupling constants readily reveal those carbon and hydrogen atoms which are within three ~ ~ of approximately 50 Hz are bonds of fluorine. 2 Jvalues common and these signals tend to be prominent in the pro~ ~ ton NMR due to the magnitude of splitting. 3 Jcouplings are smaller, with values of greater than 10 Hz being common. ~ of hundreds of hertz for a In carbon-13 NMR, J Cvalues one-bond coupling quickly fall off to tens of hertz for a twobond counline constant. Anoreciable carbon-fluorine couplings of ireaim than 1 Hz &ay be seen for nuclei separated bv four or five bonds. The s~ecificexam~lesthat follow show hbw this spectral information is brought together for structure determination. Identificatlon of Selecllvely Fluorlnated Phenylpropanes Three phenylfluoropropanes were prepared by the reaction of commercially available phenylprupnnols with dierhyl. aminosulfur trifluoride (DASTJ according to the literature (71:
NMR analysis4 of the fluorinated products allows a comparison of proton-fluorine coupling interactions arising from a single fluorine attached to three different sites within the same molecule. The most prominent 'H, I3C, 19F chemical shifts and counline . " constants are given in Table 1. Many of these values are quite similar for the three isomers, but in combination with the distinct snlitting patterns (arising from JHF),each structure can be ciearly distinguished. Data on 3-phenyl-1-fluoropropane will be used to show how proton and fluorine spectra can work together in structure elucidation5. The spectra shown in Figure 2 should be deciphered by first evaluating the fluorine NMRto establish the identity of the basic fluorinated unit, then applying that information to assist in the internretation of the Droton NMR. The fluorine chemical shift' for this compound apnears far unfield at 2206. indicatine a single fluorine atS is split into a tached to a iaturated (sp3jcarbon. T ~ signal nine-peak symmetrical pattern, recognized as a triplet of triplets (tt). The largest coupling interaction (47 Hz) that These chemical shifts are given positive values, opposiie the sign convention for proton and carbon NMR. 'SDectral data for com~oundsreDoned in this study were obtained on an IBM NR180 FT NMR spectroketer using 16K memory, run at RO NMR. and 75.39 MHz for 'F - - 07 - MHz for 'H NMR. 20 14 MHzfor NMR Chem~caishlfls are reponed n ppm relatwe to mternai TMS for 'H and I3C NMR data and Internal CFCi, for '9F IUMR, uslnq CDCi3 as the solvent in all cases. This could be presented in the classroom as an N W problem after a discussion of fluorine NMR chemical shifts and coupling constants. I"An unknown fluorinated compound gave an elemental analysis of c,H,,F. . . .")The molecular foimulasuggestsa benzene ring and three saturated carbon units. The fluorine NMR chemical shift would narrow the possible sites of fluorine anachment and protonfluorinesplitting would pinpoint the placement.
Figure 2.Segments of the proton and fluorine specha of 3-phenyi-I-fluoroprapane. showing ChamCteriJtiC proton-fluorine coupling.
Figure 3. ExpandedfiuorinsNMR signalsaf 1-phenyi-I-fluoropropane(ien)and 2-phenyl-I-Iiuoropropana (right). Volume 65 Number 5 May 1968
423
Table 2. Multlnuclear Spectral Data for Halomethylated Isopropylmalonate,
90 (0.7) 80 (0.7) 100 (0.4)
CHPI CHzF CHBrF CHCiF CHFI CBrF2
gO(0.5)
75 (0.7) 90 (0.3)
3.98 (s) 4.84 (d) 6.88 (d) 6.66 (d) 8.33 (t)
-
45 ( 5 ) 83 (d) 93 (d) 101 (6) 118 (1) 120 (1)
-
-
-
227 (t) 142 (d) 141 (6) 125 (d) 44 (s)
175 282 252
47 47
248
48 54
318
-
'80
trig pow! 1redxed vsrwre 'C (mm mgt cnem ca 9h h m ppm for ~rotonlrgem nal to I lor ns rCnemCB sh fi n m m lor C s r W l 110mW 10 Illor ne I .Or#"e M L P e d VOlO" OecO.. pled. ppm upfisld hornCFC18
triplets, clearly arising from geminal fluorine coupling of 47 Hz and vicinal proton coupling of 6 Hz. These vicinal protons appear as a douhlet of multiplets a t 2.06 and confirm the vicinal fluorine coupling of 25 Hz already established in the fluorine spectrum. Thus the general complementary nature of oroton and fluorine suectra has been shown, with proton-fluorine rvupliny~~ervinga:, the link. Sprcifically the CH -CH,F - s u h n i r is now rradily distinguished h \ romplementary dt/tt splitting patterns-in the proton and fluorine spectra. More complex '9F splitting patterns are predicted for 1phenyl-1-fluoropropane and 1-phenyl-2-fluoropropane. In both of these cases attachment of fluorine within the carbon chain creates a chiral center and generates diastereotopic (magnetically nonequivalent) protons vicinal to fluorine. The fluorine signal for 1-phenyl-1-fluoropropane(Fig. 3, left) appears as a doublet of doublet of doublets (ddd, eight peaks of approximately equal intensity; 2 J ~ = p 48 Hz, 3 J ~ ~ = 20 and 24 Hz) rather than a doublet of triplets due to slightly different coupling interactions of the fluorine with each diastereoto~icuroton. 1-Phenvl-2-fluoropropane (Fig. ( 2= 48~ ~ ~ 3, right) appearsas complicated 14-line Hz, 'JHF= 19, 24, and 24 Hz) a t 75 MHz. Here vicinal coupling constants one-half the value of the geminal coupling constant lead to considerable overlapping of peaks (theoretically a 32-line pattern might he seed6. ~~
~
~
ldentlficatlon of Fluoromethylated Malonic Esters Malonic ester synthesis is a basic synthetic methodology that creates new carbon-carbon bonds by alkylation of active methylene compounds. The generality of this reaction has been expanded to include the use of fluoromethanes (10) as alkylating agents to prepare fluoromethylated malonates (11).The general alkylation reaction7 and products prepared for this study are given below.
The chemical shifts and coupling constants for these three phenylfluoropropanescompare favorably (but not exactly) with NMR data given in the literature (see references Band 9). A detailed account for this synthetic procedure is available as Supplemental material from the author. 424
Journal of Chemical Education
Figure 4. Proton, carbon, and fluorinespectra of diethyi (fluoromethyl)isopropyimaionate. where CHxFyXz = CBrzFz, CHCIF2, CHBrzF, CHCIzF, CHzClF and R = CBrFz, CHF*, CHBrF, CHCIF, CH2F. Multinuclear NMR of these five fluoromethylated malonic esters provides data for the direct comparison of a variety of fluoromethyl moieties attached to a common parent comuound. The characteristic 'H.. 13C.. 19F chemical shifts and coupling constants of fluoromethyl moieties attached to diethvl isonronvlmalonate are eiven in Table 2. The compounds are-listed by increasing electronegativity of the fluoromethyl suhstituent. Clear correlations between carbon and fluorink chemical shifts and group electronegativity are indicated, although the proton shifts deviate from this expected trend. The widely split signals for the fluoromethyl moieties of these compounds are easily recognized in the proton and fluorine spectra. The large coupling is due solely to geminal proton-fluorine interactions (47-54 Hz) since these com-
Table
peak
3. Multlnuclear Spectral Data tor Dlethyl (Fluoromethyl)lsopropylmalonate P P ~
Hz
Table
1.01 1.10 1.18 1.27 1.36 2.58 4.10 4.18 4.27 4.36 4.54 5.13
Correlation
c4 Multlnuclear Spectral Data for
Dlethyl
(Fluor0methyl)isopropylmalonate
integral
intensity
39 41 20 39 21 4 9 19 17 6 13 13
11 12 8 77 9 1' 3 6 7 2 6 6
Interpretation 'KNMR
'H-NMR Data (CDCi3)
1 2 3 4 5 6 7 8 9 10 11 12
4.
80.6 87.6 94.6 101.7 106.8 207.0 328.0 335.0 342.1 349.2 363.9 410.7
(doublet. 6H.3&~ = 7.0 Hz) (triplet, 6H, a& = 7.1 Hz) (septet. lH. = 7.0 Hz) (quartet. 4H '& = 7.1 Hr) (doublet. 2H. 2&F = 46.8 Hz)
methyls of iropropyl methyls of ethyl esters methine in isapropyl methylenes of ethyl esters flu~romethyl
13.9 16.3 30.3 61.2 62.2 76.9 82.7 166.4
(singlet) (doubM,'& (doublet. 'JZF (singlet) (doublet. 2 J C ~ (hlplet. 'JCD (doublet, (doublet,3&
= 32.0 Hz) = 174.6 Hz) = 6.7 Hz)
methyls of ethyl esters methyls of isoprapyi methine of isopropyl methylenas of ethyl esters alpha-carbon CDCIJ solvent fluoromethyl ester carbonyls
0.0 227.4
(singlet) (triplet. *&
= 46.8 Hz)
CFCI. reference fluoromethyl
1.05 1.27 2.58 4.23 4.64 '3C-NMR
'&
=
=
1.8 Hz) 1.8Hr)
= 18.9 Hz)
data). Proton chemical shifts of 4.546 and 5.136 may easily be misinterpreted as two singlets rather than the widely split doublet for the fluoromethyl moiety. The carbon NMR was run fluorine coupled/proton decoupled; therefore, some of the signals are doublets arising from carhon-fluorine interactions. Note that some peaks are not resolved in the plotted spectrum. To interpret one must refer to the tabulated raw data and recognize which signals are generated through fluorine coupling. The number of peaks in the carbon NMR of fluorinated compounds is not a reliable indication of the number of carbon atoms in that molecule. Acknowledgment a C ~ ~ e~ a kronly given far this multiplet Flwrine wvpledlprMon dawupled. "Proton wuplsd.
pounds have no protons vicinal to fluorine. Instant NMR recognition of the methyl units is possible as their proton chemical shifts fall in a less populated region (4.5-7.06) of the proton spectrum. Thus when there are no vicinal coupling interactions to generate more complicated splitting patterns, fluoromethyl moieties are readily identified by these 'H and lgFcombinations:
Complete N.MR information on diethyl (fluoromethyl). isonrou\halonate is nresented in Firure 4 (actual suectra), ~abley(raw spectral 'data), and ~ a h 4g(correlated spectral
This work was supported by the Rohm and Haas Company, Spring House, PA. Technical assistance was provided by Howard Goldfarb. The author wishes to acknowledge Rohert C. Smoot, 111, of the McDonogh School, for his dedication t o teaching and his influence on the author's first inquiries in chemistry. Llterature Cited (11 Dungan.C. H.:van Wwer,J.R.CompilntionofReporledF-19NMR C h ~ m i c o l S h i f f s 1851-1951; Wiley: New York, 1970. (21 Mwney,E.F. Anlntmduerion taFluon'ne-ISNMR S p a e f m m p y : Heyden: London,
.".". ,OVA
(31 Emsiey, T.W.; Phillips, L. Pmgress in Nudeor Magnetic Resononce Sp~rlroscopy: Pergamon: Oxford. 1971: Vol. 7. ( 0 Hudiickv. M. Chemistry olFluotine Compounds; Ellis Horwoad: New York, 1976; pp 576584. ~~ (51 G0rdon.A. J.;Ford,R.A. TheChomialh Companion: Wiley: NeuYork, 1 9 7 2 :288293. (6) Everett, T. S. Mulfinudoar N M R Spectral IdenlMcation o f Orgonolluorina Compounds: in preparation. (71 Middleton, W . J.J. Org. Chem. 1975,40, 574. (81 Weigert. F J. J. 0%. Chem. 1980.45.3176. (9) Patrick,T.B.; Johri, K. K.:White. D. H. J. Or#. Chrm. 1983,48,4158. (101 Everett, T . S. J. Chem. Educ 1987.64.143. (111 Ererett,T.S.;Purrington.S.T.:Bumgardner,C.L.J. Org. Chem. 1984,49,3702.
Volume 65
Number 5
May 1988
425
