Y U C L E A R JIAGNETIC
RESOKANCE SPECTRA O F 1,4-DIHETEROCYCLOHEXANES
579
The Nuclear Magnetic Resonance Spectra of Some 1,P-Diheterocyclohexanes
by William B. Smith and Ben A. Shoulders Department of Chemistry, Texas Christian University, Fort Worth, Texas
(Received September 16, 1964)
The n.m.r. spectra of inorpholine, N-methylmorpholine, N-phenylmorpholine, and thioxane have been analyzed, and the pertinent chemical shifts and coupling constants have been determined. The spectra are all of the A2B2type. The CI3-H spectruiii of dioxane has also been re-examined.
Introduction The utility of the Karplus equation for determining the relationship between the dihedral angle of C-H bonds on adjacent carbons and vicinal proton coupling constants is now well established.lV2 However, it is well known that factors other than the dihedral angle inay play a role, as well, in determining the exact values of vicinal coupling constants. l b Perhaps the iiiost significant other effect is that of the electronegativity of substituent groups. A nuinber of studies have established that for certain specific, systems there is a linear decrease in vicinal coupling constants with increasing substituent electronegativity. Among these, mention should be made of iiieasureiiients on rigid systeiiis made by Williamson3 and by Laszlo arid S ~ h l e y e r . ~Recently, Abraham and Pachlerj have made deterininations 011 a nuiiiber of disubstituted ethanes. On the basis of the average coupling constants in 103 differently substituted ethanes, they derived the relation, J,, = 17.97 - 0.796 E, where E is the Huggins electronegativity for the six atoms joined to the C-C fragment. Recently, Huitric, et al. ,6 have determined the axialaxial and axial-equatorial coupling constants for a series of partially deuterated cis- and trans-l-substituted-2-arylcyclohexanes. In contrast to the results above, they found no siiiiple correlation between the electronegativity of the substituents arid the various vicinal coupling constants. The lJ4-diheterocyclohexariesoffer an interesting systeiil related to the studies of both Abrahaiii and Pachler5 arid Huitric, et aL6 We have determined the cheiniral shifts and coupling coristarits for a series of these coiiipounds, and the results are reported below.
Experimental The compounds, with one exception, used in this study were all commercially available substances. Their n.11i.r. spectra were those of pure compounds and were consistent with the expected structures. Diiiiethylmorpholinium iodide was prepared by treating a saiiiple of inorpholine in benzene with an excess of methyl iodide. An exotherniic reaction occurred, and the precipitated salt was collected and recrystallized from absolute ethanol, ni.p. 244-246'; reported' i1i.p. 246 O. The spectra were deterinined on a Varian A-60 spectrometer equipped with a variable temperature probe assembly. The frequency was calibrated against rhloroforin, arid cheiiiical shifts mere read directly from the charts. The operating teinperature of the probe was around 43'. Resolution checks 011 the instrument indicated 0.3 c.p.s. or slightly better. Solutions of niorpholine, N-n~ethylmorpholine, Nphenylmorpholine, arid thioxane in both carbon tetrachloride and benzene were outgassed before each determination. Tetrainethylsilane was used as an internal standard. The only effect of the solvent change was a ~
~
~
~
(1) (a) .\I. Karplus, J . Chem. Phys., 30, 11 (1959); (b) J . Am. Chem. SOC.,8 5 , 2870 (1963). (2) For a general discussion and some applications see L. M. Jackman, "Applications of Nuclear hfagnetic Resonance Spectroscopy in Organic Chemistry," I'ergamon Press, New York, N. Y., 1959, Chapter 6; also, C. N. Banwell and N. Shepyard, Discitssions Faraday Soc., 34, 115 (1962). (3) K. L. Williamson, J . Am. Chem. Soc., 8 5 , 516 (1963). (4) P. Laszlo and P. yon 11. Schleyer, ibid., 8 5 , 2709 (1963). (5) It. J. Abraham and K . G . 11. I'achler, Mol. Phys., 7, 165 (19631964). (6) A . C . Huitric, J. B. Carr, W .F. Trager, and B. J . Nist, Tetrahedron, 19, 2145 (1963). (7) L. Knorr, Ann., 301, 13 (1898).
Volume 69, .\-umber
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February 1966
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WILLIAMB. SMITHA N D BEN A. SHOULDERS
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slight variation in the chemical shift of the ring methylene groups. Since the amines slowly reacted with carbon tetrachloride, the coupling constants were determined only for the benzene solutions. All deterniinations are reported on the average values taken from five or six spectral determinations. The spectrum of N-phenylmorpholine was determined in carbon disulfide a t 0 and -70’ and on the pure liquid melt up to 180’. The only observed change in the spectruin was a slight broadening of lines a t -70”. Since the tetramethylsilane line was also broadened a t this temperature, it was assumed that this was a n instrumental effect.
Mo;pholmea N-Meth ylmorpholine N-Phen ylmorpholine Thioxane Dioxane
OCHz
XCHa
45
7 27 7 68 7 03 7 43
6 6 6 6 6
38 28 12 30
11 The spectrum of morpholine is given in the “Parian Spectra Catalog,” Varian Associates, Palo Alto, Calif, No. 83.
The structure of the niorpholine methylene bands remain the same for the pure liquid, in carbon tetrachloride, in benzene, and in deuterium oxide. The usual upfield shift of the N-H is observed on dilution with the nonaqueous solvents indicating that morpholine is hydrogen bonded. Addition of hydrochloric acid in portions to niorpholine in DZO first causes the upfield multiplet l o be badly washed out and to reduce slightly the cheiiiical shift between the inethylene groups. In concentrated acid, the upfield band was broad, but seven perceptible humps appeared on the envelope. The downfield multiplet was broadened. However, the major structural features remained intact. The value of N (as defined below) was readily ascertained from the downfield multiplet. The internal cheniical shift was estimated from the midpoints of each multiplet. The solution of di~~iethylmorpholiriiu~~i iodide in D,O also gave two multiplets for the ring methylenes. In this case, the downfield multiplet was badly washed The J O U T Wof~Physical Chemietry
1 1
I
20
-H+
I
30
Figure 1. T h e ‘N-methylene multiplet of morpholine determined in benzene solution a t 60 hlc. This is the upfield half of a n AzBzspectrum. Frequencies are in C.P.S. from the band center. The line assignments from left to right are 4, 3, 13, 11, 8, 5, 10, 9, 2, and 1.
out with eight peaks on the envelope. While the upfield niultiplet was slightly broadened, the features of the morpholine structure were quite evident again allowing an evaluation of N . The chemical shift difference was estimated as above. The methylene multiplet structures for iS-phenylmorpholine, N-methylmorpholine, and thioxane were all very siniilar to that of niorpholine (Figure 1). The major alteration in the first two cases was due to lines 9-10 and 11-12 which merged into two somewhat broadened bands. The positions of these lines were estimated from the amount of broadening. I n thioxane, line 12 appeared as a distinct shoulder on band 3 4 , arid line 9 appeared siniilarly on the downfield edge of band 1-2. Neither was resolved to the base line, and this was taken into account in estimating their frequencies. The CI3-H spectrum of dioxane has been determined previously.8 The deterinination was repeated here on (8) A. D. Cohen, N. Sheppard, and J. J. Turner, PTOC. Chem. Soe., 118 (1958).
NUCLEAR
JIAGNETIC
RESONANCE SPECTRA
the pure liquid. The results are reported in Table 11, where it may be seen that a slight difference from the reported coupling constants was found.
Results and Discussion 1,4-~)iheterocyclohexanes,such as those encountered in this study, most reasonably consist of rapidly equilibrating chair forms, for certainly the nuniber of nonbonding hydrogen interactions are less than for cyclohexane itself. Given this statement, the following forms for niorpholine may b,e considered.
H-N
eo
u
o& *
I11
58 1
O F 1,4-DIHETEROCYCLOHEXANES
the rapid nitrogen inversion process. I t follows also that thioxane and dioxane are rapidly interconverting chairs a t room temperature. The spectra of the preceding conipounds were analyzed as exainples of typical A2Bz~ y s t e r n s . ~The ~ ~ ’per~ tinent relations for interpreting the spectra are
where the numbers are for the hydrogens given in the preceding structures for niorpholine. For rapidly equilibrating chair structures J14 = (J,, J , , ) / 2 , 513 = J,,, and J12 and 5 34 are the appropriate geminal coupling constants. The usual sum and difference relations for line frequencies may be used to determine N , L , M , and the internal chemical shift, A A B . ~ ~ , ~ ~ Assuming that J,, equals J,,, one may then calculate J,,, J,,, and the difference between the geminal coupling constants. Initially, the line assignments for niorpholine were made with the aid of reasonable values of AAB, the appropriate J values, and the assumption that the spectrum approximated an A2X2 situation. Subsequent calculations of the exact AzB2 spectrum were made with the aid of the Freqint A 1620 computer program. Under the conditioiis encountered here, the value of K cannot be approximated from the experiniental spectrum which, in fact, is quite insensitive to the exact value of K.j,14 For the purposes of the calculation, it was assumed that JI2was -13.2 C.P.S.~The values for the coupling constants and AAB for the compounds studied here are given in Table JI.
+
IV IV
In addition t o the chair-chair interconversion, one must also take into account the rapid inversion of the nitrogen and the exchange of the mobile hydrogen on the nitrogen. This latter factor must also be rapid; otherwise, coupling of the N-H with the nitrogen methylenes would have been observed. Reeves and Stroiiinieg have concluded from the n.ni.r. spectrum of S,N’-dimethylpiperazine that chair-chair interconversion is rapid at room temperature. From a consideration of the change in the spectrum a s the teniperature is lowered, they concluded that the interconversion is relatively slow a t -40’ and that the two methyl groups most likely remain in equatorial positions owing to the rapid nitrogen inversion prlocess. The syninietrical spectrum of inorpholine could arise either through a rapid equilibrium of I with I V or I1 with 111, or through a rapid equilibrium among I , 11, 111, and IV. Aroney and LeFevrelO have concluded on the basis of dipole inonient nieasureiiients that the hydrogeri on the niorpholine nitrogen remains in an axial pOSitiOti ( i . e . , 1 e I\r).ll,llaIt iS evident frOn1 the resu]ts r,3ported here that, the I1.lli.r. spect,rulil of morpholine offers 110 opportunity for a decision 011 this mat,ter and that, as far as 11.m.r. is concerned, all that caIi be said is that l,lorp~o~irle is a rapid equilibriuni of which the respective irlterconvertirig chair forms methylene hydrogens experience the same cheniical shift. Reasonably, ~-niethylmorpholirie and Xphenyliiiorpholine are rapidly interconverting chairs in whlch the IT-substituent is always equatorial owing to
(9) L. W. Reeves and K. D. Stromme, J . Chem. P h y s . , 34, 1711
.
.
(10) h i . Aroney and R. J.
w.LeFevre, J . Chem. soc.. 3002 (195s).
(11) A referee has pointed out that N. Allinger hRs receiitl?. pre-
sented evidence against this postulation (144th National hfeeting of the American Chemical Society, Los Angeles, Calif.. April 1963). Unfortunately, the abstract does not present this evidence. ( I l a ) NOTEADDEDI N I-’ROOF. For the evidence on this point. see N. L. Allinger, J. G. D. Carpenter, and F. A i . Karkowski. Tetrahedron Ltlttrs, 45, 3345 (1964). (12) . . (a) . J, A, Po&, w,G, Schneider, and H . J. Bernstein, cap^. J . Chem., 35, 1060 ‘(1957); (b) “High Resolution Nuclear hlagnetic I~esonance,”h\lcGraw-HillBook Co., Inc., New York, N . Y . , 1959. (13) D. X I . Grant, It, C. Hirst, and H. S.Gutowsky, J . Chem. P h y s . , 38, 470 (1963).
(14) 11 C. Hirst and D AI, Grant, abid, 40, io90 (1964)
Volume 69, .\Turnhcr 2
Febrziary 1985
582
WILLIAMB. SMITHA K D BEN A. SHOULDERS
Table 11 : C‘oupling Constants and Chemical Shifts of Some 1,4-Diheterocyclohexane~~
Thioxane Morpholine ~-~lethylmcirpholirie N-Phenylmurpholine Morpholinium ion N,N-Dimethylmorpholinium iodide Ilioxane Karplns values
10 0 12 05 2 65 83 9 7 10 28 3 04 54 9 7 10 25 3 05 87 9 9 9 66 3 38 48 9 9 39
9 7 9 3 102 72 9 2
60 1 97 24 1 45 57 0 16 50 0 60 5
33
28 17
0 00
a All determinations were made in benzene solution, except the two ionic coinpounds, which were run in D,O. All values are in
C.P.S.
For the series, thioxane, morpholine, and dioxane, there is a ntarked decrease in N , a form of averaged J,, and J,,, wil h increasing electronegativity of the heteroatom substituent^.'^ The relation is not linear in the most exact sense. However, the fit would probably be no worse than that observed for several series of conipounds by Abraham and 1’achler.j These authors observed that as the percentage of trans rotonier increased in their series of 1,2-disubstituted ethanes, there was a departure from linearity with the electronegativity relationship. The factor responsible for this deviation has not yet been ascertained. One point of interest brought out by the data in Table I1 is the fact that the decrease in N in the preceding series is not due to a iiioriotoriic decrease in J,, and J,?. The linear relationship between the average vicinal couplirig constants and the electronegativity of the substituents is obviously influenced in sonie subtle fashion by effects other than the electronegativity of the substituents. The va1uc.s of N and A,B in Table I1 for the series niorpholinc, S-niethylniorpholine, N-phenylmorpholine, iiiorpholinium ion, and diniethylniorpholiniuni ion offer an interesting coninientary on the question of group electi.onegativities us. atom electronegativities in considerations of vicinal coupling constant effects. Presuniably, the value of AAB reflects the group electroncgativity of thc nitrogen moiety in the sense defilled by C:tvanaugh and Dailey. l e Wrillianison3 and Laszlo and Srhleyer4 have found a relation between J
Thc Journal of Physical Chemistrg
and ER (the substituent electronegativity). Abraham and Pachler5 relied only on the Huggins atom electronegativity feeling that the anisotropy effectsi6!” incorporated in the substituent electronegativities offered a fundanierital point of objection to their use. Certainly, here the latter point of view would seem to be the more justified. Thus, AAB varies over 160% between the diniethplniorpholiniun~ ion and K-methylniorpholine while the value of N is unchanged. The enhanced inductive deshielding of the S-methylene in the quaternary salts coinpared to the X-methyl group is hardly surprising, but the lack of variation in the value of N again points to our inexact knowledge of how substituents influence vicinal coupling constants. Finally, the spectra of the two quaternary nitrogen compounds deserve comnient. In concentrated hydrochloric acid the exchange of the hydrogens on the niorpholirie nitrogen has been slowed, allowing the coupling of the S-H with the nitrogen methylene hydrogens to be observed. The system has now beconie an A2BzX2 case, and the splittings of the 0-methylene are broadened. However, the essential features of the rnorpholine 0-methylene are still observable, and the value of N can be obtained. These observations parallel those of Grunwald, Loewenstein, and ,Ileiboo~ii’~ on the spectrum of methylamine in acid. In dimethylniorpholinium iodide, the coupling is between the N i 4 nucleus and the 0-Inethylene group. Since this splitting is imposed on the AzB2 niultiplet structure of this group, the effect is to wash out the features of the band. The N-methylene band is soiiiewhat broadened, but again a reliable value for N can be obtained. Similar couplings of XI4have been observed b e f ~ r e . ~ ~ ~ ~ ~
Acknowledgment. We wish to express our gratitude to the Robert A. Welch Foundation for their generous support of this work. (15) The sums of the heteroatom electronegativities: (0,s)5.65; ( 0 , N ) 6.55; ( 0 , O j 7.00 (M.L. Huggins, J . A m . Chem. Soc., 75, 4123 (1953)). (16) J. R. Cavanaugh and B. I’. Dailey, J . Chem. Phys., 34, 1099 (1961). (17) See ref. 3, footnote 28. (18) E. Grunwald, A. Loewenstein, and S. Meiboom, J. Chem. Phys., 27, 630 (1957). (19) J. M .Anderson, J. D. Baldeschwieler, D. C. Dittmer. and W. D. Phillips, ibid.. 38, 1260 (1963). (20) M. Franck-Newmann and J. M . Lehn, M o l . Phys., 7, 197 (1963-1 964).
