- Email: [email protected]
NMR studies of pyridazine-N-oxide. Determination of spectroscopic parameters from the [15N]- and parent species
JOURNALOF
MAGNETIC
RESONANCE43,387-398(1981)
NMR Studies of Pyridazine-N-Oxide. Determination of Spectroscopic Parameters from the [15N]- and Parent Species TORBEN WAMSLER,JORGEN TORMOD NIELSEN,ERIK AMD KJELD SCHAUMBURG
JONAS PEDERSEN,
Uni\sersity of Copenhagen, Chemical Laboratory V, The H. C. @wed Institute, DK-2100 Copenhagen 0., Denmark Received August 20, 1980; revised November
18, 1980
Pyridazine-N-oxide and [15N]pyridazine-N-oxide have been investigated by NMR spectroscopy. ‘H and 13C spectra have been obtained and analyzed, in terms of chemical shifts and spin-spin coupling constants. Relaxation times have been measured for 13C and have been used to determine the correlation time 7c under the assumption of isotropic molecular diffusion. From rH, 15N INDOR experiments the lineshape of N(2) is determined; analysis of the lineshape yields ?I,, and 7 4Nuj. On the basis of experimental data and observed linewidth variations, the N(1) nitrogen quadrupole coupling constant has been evaluated. The experimental data are correlated with semiempirical calculations within the azine series. INTRODUCTION
Earlier we reported spectroscopic studies of pyridazine (I ), pyrazole (I), thiazoie (2), and 1,2,3,4-thiatriazole (3), all enriched in 15N in order to facilitate the NMR investigations. We also studied [15N]- and 12H]-enriched species of pyridine-N-oxide (4). One realson for the latter investigation was the large changes in spin-spin coupling constants between nitrogen and carbon or protons introduced by N oxidation. Theoretically we tried to reproduce this behavior by calculations using the CNDOI2 SOS method (5). Another reason was the large differences in lineshapes observed in both carbon and proton spectra brought about by scalar coupling toI nitrogen (6). The spectrum of pyridine-N-oxide indicated a rather small value of the nuclear quadrupole coupling constant (NQCC) of 1.3 MHz. In the investigation of pyridazine-iv-oxide (I) we wanted to pursue the same information as that in the case of pyridine-N-oxide. Several authors have reported data for pyridazine (1,7-l I). Pyridazine-N-oxide (I) was first investigated by Tori and Nakagawa (9) by ‘H NMR. Later Moritz and Paul (12) determined the relative signs and more accurate values of the proton-proton coupling constants. No data concerning the analysis of the proton-coupled carbon spectra of I, or relating to the 15N species I,, and I, have previously appeared.
387 0022-2364/81/060387-12$02.00/O Copyright 0 1981 by Academic Press, Inc. All rights of reproduction in any form reserved.
388
WAMSLER
ET AL.
EXPERIMENTAL
Pyridazine-N-oxide was prepared according to the method of Itai and Natsume (13) with the modifications enforced by the smaller quantities involved. Pyridazine (100 ~1) was added to a mixture of 1 ml acetic acid and 1.5 mol eq (with respect to pyridazine) of aqueous H,O, (30% w/w). The mixture was kept at 85°C for 12 hr. Unreacted material and solvents were distilled off leaving a residue consisting of pyridazine-N-oxide (colorless) and polymerization products. The appropriate NMR solvent was added and the solution filtered to remove the strongly colored polymerization products. 15N pyridazine 33% enriched in 15N was synthesized as described by Jacobsen ej al. (1). The synthesis of the N-oxide was as above. The resulting pyridazine-N-oxide consists of three isotopic species I,, Ib, and I, in the ratio 4: 1: 1. Samples of I, were prepared by dissolving it in CDCl, or (CD&CO, typically at 1.0 to 1.6 M, and adding TMS as internal reference. After several freeze-pump-thaw cycles the samples were sealed. The 15N-enriched sample was 0.8 M in (CD&CO. 13C spectra were obtained in the FT mode using a Varian XL-100 spectrometer operating at 25.12 MHz at 32°C. Proton-coupled spectra were recorded with 14N decoupling, 8K data points, and a spectral range of 250 Hz. The repetition time was 6.7 set and the pulse width 75 psec corresponding to 70”. Similar conditions were used for linewidth measurements in ‘Hdecoupled 13C spectra. 13C T, measurements by the inversion-recovery method were performed on a Varian XL-100 and a Bruker WH 90 spectrometer. Relaxation data were fitted using a nonlinear three-parameter regression analysis. ‘H spectra were recorded on a Varian HA-100 operating at 32°C modified for digital sweep under control of a Varian 620/i computer. In hetero-INDOR experiments a Schlumberger FSD 120 synthesizer was phase locked to the proton frequency and swept through the region of interest under control of a Varian 620/i computer storing the spectrum in 2K points. The ‘H signal monitored was derived from a Rockland 5 100 synthesizer used as sideband oscillator in the analytical channel. In heterodecoupling experiments an Electronic Navigation Instruments power amplifier Model 310L was used to boost the output of the FSD 120. The V 4330 probe was modified for heterodecoupling according to the method of McFarlane (14). lH spectra were also obtained using a Bruker HX 60 spectrometer coupled to a Varian C 1024 CAT. This instrument was used for homotickling and homoINDOR experiments. The lH spectra used in determination of coupling constants were recorded with a sweep expansion of 0.2 Hz/cm and with sweep rates not exceeding 6 x 10e3 Hz/set. Analysis of the spectra was performed using the program LAOCOON III (15). CND0/2 and INDO calculations were of the sum-over-state method (SOS). The parameterization has been discussed by Tow1 and Schaumburg (5). In the determination of nitrogen chemical shifts we have chosen to refer the nitrogen signals to the lH resonance of internal TMS. The usual nitrogen standard MeNO* then appears as a secondary standard. From Witanowski and Webb (16, Chap. 3), we have chosen the data for 0.1 M MeNO, in CDCI:, + TMS. They quote a v(15N) in MeN@ of 22,300,783 Hz for the ‘H in TMS resonating at 220,000,OOO Hz. In our modified Varian HA-100 spectrometer the TMS frequency was 100,002,500.00 Hz referenced to a rubidium standard. The magnetic field
389
PYRIDAZINE-N-OXIDE TABLE CHEMICAL
SHIFT
1
6, (ppnn) RELATIVE TO TMS AND ‘II H(A)H(B) (Hz) IN PYRIDAZINE-N-OXIDE
COUPLING
CONSTANTS
Compound
63 64 & f& n
A
B
3 4 5 3 4 3
3 3 3 4 4 5
4 5 6 5 6 6
Solvent Concentration
(M)
8.5271 7.2269 7.8705 8.2316
-c f ? c
0.0001 0.0001 0.0001 0.0001
5.40 2.53 0.99 7.73 0.91 6.47
k ? c k 2 ”
0.02 0.02 0.02 0.02 0.02 0.02
8.5265 7.2270 7.8707 8.2301
+ ? ” k
0.0001 0.0001 0.0001 0.0001
5.39 2.54 0.99 7.73 0.92 6.48
-c k k +k +
0.01 0.01 0.01 0.01 0.01 0.01
(CD, WO 0.54c
(CD,),CO 0.13c
8.5266 7.2270 7.8712 8.2315
5.40 2.56 1.00 7.76 0.90 6.51
k r 2 t
0.0002 0.0003 0.0003 0.0002
2 0.03 k 0.02 f 0.03 2 0.03 -c 0.05 + 0.02
(CQ),CO 0.13c
8.54 7.22 7.83 8.26
8.49 7.17 7.78 8.22
5.3 2.5 1.0 8.0 1.0 6.5
5.39 2.54 0.99 7.76 0.92 6.49 CDCI,
Note. I,, Ib, I, refer to the three isotopic species studied. a Reference (II). * Reference (12). c Total concentration (I, + Ib + I,) = 0.8 M.
corresponds to a MeNO, frequency 7,226,463 Hz for the 14N species.
of 10,136,973 Hz for the 15N species and RESULTS
The lH spectrum of I consists of the superimposed spectra of I,, I,,, and I, (see Experimental). It is observed that the presence of nitrogen broadens the lines excessively, and that 14N decoupling must be applied to obtain suitable spectra for analysis. In order to perforlm 14N decoupling or 15N tickling the nitrogen chemical shifts must be determined. There have previously been no report of the 6, for oxides of diazines in the literature. For a TMS resonance frequency of 100,002,500 Hz we found the following frequencies: 10,136,484 and 10,136,696 Hz for 15N(1) and 15N(2), respectively. These values correspond to -48 and -28 ppm referred to MeNO, (see Experimental). The values were obtained as well by heterotickling as by hetero-INDOR using data accumulation over several hours. In Table 1 proton chemical shifts and proton-proton coupling constants are reported. For comparison the data previously published are included (I I, 12). The experimental and calculated nitrogen-proton coupling constants are given in Table 2.l In some cases lines from I,, superimposed on stronger lines from the more abundant I,, were identified by triple resonance. With decoupling of ‘N, 1 Throughout the paper coupling constants between nitrogen and other nuclei refer to 15N unless explicitly stated. Where comparison to literature data has made it necessary l*N data have been converted to the proper value using the factor 1.40275710 2 7 x lOm8(14).
390
WAMSLER
ET AL.
TABLE ‘jN-‘H
COUPLING
(Hz)
CONSTANTS
2 IN PYRIDAZINE-N-OXIDE
(nJL5Nca,HcB,)
Calculated n
A
B
Experimental
3
1
3
-8.30
4
1
4
3
1
5
2
1
2
a
CNDO/Z@
INDO*
i 0.02c
-3.40 -3.95
-4.70 -5.46
f 0.02”
-0.26 -0.31
-0.22 -0.27
-5.04
CL 0.02c
-1.72 -2.01
-1.93 -2.27
6
-0.81
iz 0.02”
-1.92 -2.30
-2.34 -2.83
2
3
-14.46
2 0.03d
-6.63 -6.71
-9.70 -9.46
3
2
4
-1.85
” 0.09
-0.72 -0.74
-0.27 -0.27
4
2
5
3
2
6
0.81
0.58
-0.33
+ 0.03d
* 0.05d
’ The top value refers to fixed and electron density. For details of calculation b Calculation scheme. c Measured on I,,. d Measured on I,.
0.16 0.17
0.83 0.82
-0.25 -0.26 the bottom value see Ref. (5).
0.50 0.51 to
variable
‘H spectra were recorded with and without 15N decoupling. By appropriate sign reversal in the accumulation the signals from I, were found. The signs of the JNH are determined by heterotickling and homotickling on the basis of the conclusion (12) that all JHH are positive. The experimental and calculated carbon- hydrogen coupling constants are reported in Table 3. For some of the smaller coupling constants it was not possible to determine the sign. The more likely sign is given without parentheses. The values were obtained using a 1.6 M sample of I, dissolved in (CD&CO. The carbon chemical shifts are reported in Table 4. The position is relative to TMS for CDCl, whereas only chemical shift differences have been determined in (CD&CO. The calculations of the coupling constants (Tables 2, 3 and 5, 6) are CND0/2 and INDO (5). Because of the size of the system no configuration interaction was used. The geometry used in the calculations was not experimentally determined.* 2 Bond distances: N(l)N(2), 1.355 A; N(2)C(3), 1.330 A; C(3)C(4), 1.403 A; C(4)C(5), 1.378 A; C(5)C(6), 1.395 A; CH, 1.084 A; N(l)O, 1.299 A. Bond angles: LC(~)N(~)N(~), 122.3”; iN(l)N(2)C(3), 116.3”; LN(~)C(~)C(~), 125.8”; LC(~)C(~)C(~), 116.1”; LC(~)C(~)C(~), 119.0”; LC(~)C(~)N(~), 120.6”; LN(2)C(3)H(3), 114.3”; LC(3)C(4)H(4), 121.8”; LH(5)C(S)C(6), 119.2”; i~(6)N(i)0, 118.9”; LH(6)C(6)N(l), 113.7”.
391
PYRIDAZINE-N-OXIDE TABLE W-IH
COUPLING
CONSTANTS
(Hz)
3 IN PYRIDAZINE-N-OXIDE
(“J13ccAjHcBj)
Calculated
Fixed Variable
n
A
B
Experimental
Additivity rule”
1
3
3
184.7
186.2
2
3
4
3.6
3.5
1.81 1.99
2.48 2.74
3
3
5
8.1
8.2
4.04 4.42
4.06 4.44
4
3
6
< IO.3 /
2
4
5
5.2
7.0
1.49 1.52
2.40 2.40
1
4
4
175.3
174.0
77.54 80.19
75.15 76.91
2
4
5
-0.4
-0.7
3
4
6
5.4
3
5
3
2
5
1
CNDOI2 73.05 79.35
-0.5
0.16 0.18
INDO 74.07 80.22
-4.04 -0.04
0.34 0.35
1.11 1.13
5.7
2.61 2.76
2.81 2.94
7.3
7.6
3.56 3.79
4.37 4.59
4
(‘jO.4
1.1
0.53 0.57
1.34 1.43
5
5
170.76
171.0
70.19 75.22
68.85 73.05
2
5
6
4.1
3.8
4
6
3
‘+‘l . 5
3
6
4
7.5
2
6
5
1
6
6
1.45 1.59
1.85 2.02
0.13 0.13
1.05 1.06
7.1
3.01 3.14
3.91 4.02
4.4
4.0
3.03 3.14
3.53 3.60
193.2b
191.9
85.79 91.38
84.13 88.63
a The calculated values are based on an additivity * kO.2 Hz; all other values, kO.1 Hz.
-1.9
rule described
under
Discussion.
392
WAMSLER
ET AL.
TABLE CHEMICAL
SHIFTS
4
SlaC FOR PYRIDAZINE-N-OXIDE si (wm)
Concentration Solvent
A(% - 8,) (wm) 34.4 0.0 18.1 18.1 -1 CDCl,
150.6 116.2 134.3 134.3 -1 CDCl,
83 64 85 K3 (M)
35.13 0.00 19.17 18.69 -1.6 (C&)X0
It is based on our knowledge of bond angles and lengths in pyridine-hi-oxide (4) and assumptions consistent with available data on other aromatic ring compounds. Table 7 collects the data obtained for 13C relaxation times using the inversionrecovery method. In the same table the contributions to the observed linewidths resulting from scalar relaxation due to r4N are listed for 13Cand lH. On the basis of these data and the coupling constants given in Tables 2 and 6 the quadrupolar relaxation time TqN for N(1) has been calculated in various ways. Combination of these data with a molecular rotational correlation time of 0.35 x lo-” set (see below) yields the estimated nuclear quadrupole coupling constants (NQCC) presented. DISCUSSION
The proton spectrum of I is almost a first-order case, and the assignments are straightforward. The present results for proton chemical shifts and protonTABLE CALCULATED
SPIN-SPIN
5
COUPLING
Calculated
CONSTANTS
IIJHcAIHfB,
yz$le I
n
A
B
CNDOi2
INDO
Experimental
3
3
4
5.18 5.30
4.66 4.60
5.39
4
3
5
2.83 2.89
3.68 3.61
2.54
5
3
6
1.47 1.53
2.01 2.03
0.99
3
4
5
6.57 6.77
5.46 5.45
7.73
4
4
6
1.10 1.16
2.26 2.33
0.92
3
5
6
4.12 4.34
3.05 3.12
6.48
393
PYRIDAZINE-N-OXIDE TABLE CALCULATEDCOUPLINGCONSTANTS NONHYDROGEN
6
IN THE CNDOR AND INDO NUCLEI IN PYRIDAZINE-N-OXIDE Calculated
SOS APPROXIMATION iiJN(ijX(BI
BETWEEN
~~r~$e I
X
nA
B
Contact
Dipole-dipole
Spin-orbit
2
1
3
T
3
1
4
‘T
2
1
5
‘T
1
1
6
-7.29 -8.62
13c
1
2
3
-3.75 -4.07
‘T
2
2
4
-0.37 -0.37
-0.36 -0.36
-0.21 -0.20
-0.25 -0.23
T
3
2
5
-0.73 -0.78
-0.66 -0.70
-0.13 -0.13
-0.13 -0.12
-0.21 -0.21
‘T
2
2
6
-0.08 -0.08
-0.06 -0.06
-0.01 -0.01
‘jN
1
1
2
-1.23 -1.30
-1.25 - 1.33
Note. The first (1 Calculated from b Measured in the c Determined from
0.07 0.09
term
‘T
-1.87 -2.20 0.24 0.30
0.17 0.17 -2.98 -3.46
0.43 0.56 -1.89 -2.28 0.19 0.24 -5.84 -7.07 0.24 0.26
0.26 0.26 -5.96 -6.91
-0.05 -0.05
-0.04 PO.05
0.00 0.00
-0.25 -0.27
-0.25 -0.27
-0.25 -0.27
--0.18 -0.20
-0.16 -0.19
-0.01 -0.01
Total
0.00 0.00 -0.26 -0.29 0.00 0.00
0.02 0.03 -2.37 ~2.73
1.48 1.64
-0.09 -0.10
-0.10 -0.11
-5.85 -7.06
1.86 1.87
1.83 1.85
-0.10 -0.11
-0.11 -0.11
-1.99 -2.31
0.04 0.04
0.05 0.05 -0.22 -0.21 0.00 0.00 0.03 0.03
0.39 0.51 -2.41 -2.84
0.06 0.09
1.53 1.66
0.04 0.04
Experimental
-0”
~4.46 -5.54
(C)iSb
1.96 2.00 -0.56 -0.55
-1.08 -1.12
-1.00 -1.03
-4.17 -4.72
(2)9.4”
0.02 0.05
-0.53 -0.53
0.08 0.09
“‘6 _ 3”
0.21 0.20 -7.17 -8.27
(?)14.0C
column is calculated by CNDOI2 and the second by INDO. line broadening and T,4N,l) = 25 msec (Table 7). 13C spectrum. line broadening in INDOR experiments, as described under Discussion.
proton coupling constants are almost identical to those of Moritz and Paul (12). In general theoretical predictions of 3JHH are good. In Fig. 1 the correlation previously (1) established for 3JHH is reproduced and the values obtained in this work have been added to the figure. The agreement is seen to be good. The,nitrogen chemical shift in pyridazine is +20 ppm (17) and in pyridine -58 ppm (4). In pyridine-N-oxide the shielding is increased by 22 to -80 ppm (4). In pyridazine the N oxidation produces an increase in shielding for N( 1) of 68 ppm, three times larger than for pyridine. Even in the N(2) position the observed effect is 47 ppm, indicating that the electron distribution is strongly affected at both nitrogen positions in I. This is substantiated by CND0/2 calculations where the total atomic charge changes from +0.07 electrons in pyridazine to -0.41 at N(1) and +0.17 at N(2) in the N-oxide. The 2J,H value in pyridazine was found to be - 12.04 Hz (1). The value of - 14.46 Hz found in I, is similar, indicating that the N oxidation of the neighboring nitrogen does not interfere with the (T lone pair at N(2), which is influential in determining the magnitude of 2J,H. N oxidation increases the value of the 2J,H for the
394
WAMSLER
ET AL.
TABLE RELAXATION
Position
T T, (se4
DATA (A*
7
FOR PYRIDAZINE-N-OXIDE - A)” (‘“C) (Hz)
(A*
- A) (‘H) (Hz)
3
14 ” 4
4.2
-
4 5 6
14 2 2 15 + 4 -
9.5
0.06 2.2 0.08
” (A* b The c The
-0 -
(1.0 M IN (CDS)&O) TqNo, msec 22 20 29
(e”qQlh) NV (MHz) 0.94 0.98 0.82
- A) indicates scalar broadenings of lines. is equal to 25 x 10e3 sec. mean value for TQNo, of all measurements mean value for e*qQlh of all measurements is equal to 0.88 MHz.
oxidized nitrogen itself. In pyridine (4) an increase of 11.3 Hz is observed. A closely related change (11.2 Hz) is found here, resulting in a *JNH value of -0.81 Hz in It,. In pyridine 3J,H showed behavior opposite to that of 2JNH, decreasing by - 1.53 Hz by N oxidation (4). If we take for 3JNccH in pyridazine the value of - 1.2 Hz (I ) as a starting point, we find for the two inequivalent 3JNccH values in I, - 1.85 Hz for 3JNc23Hc41 and -5.04 Hz for 3JN~1~H~5~.Considering the N-oxidized atom the direction of the observed change is again quite analogous to the pyridine/pyridine N-oxide case. The 3J,N,-H corresponding to a path involving nitrogen displays rather large variations. Here the pyridazine value was -3.70 Hz (1). The N oxidation increases the value in I,,, where the intervening nitrogen has been oxidized to 3JNc1,Hc3, = -0.33 Hz whereas in I, where the intervening nitrogen still is pyridine-like, 3J~c2m-~ is decreased to -8.30 Hz. The latter seems to be numerically the largest 3JNHthat has been reported. We mentioned (4) that 3JxNcH when X = 13C (for pyridine/pyridine N-oxide) was greatly influenced by the type of the intervening nitrogen. In I when X = 15N that point is even more evident. The 4JNH values are both small and positive as found in pyridine and pyridine-N-oxide. The carbon chemical shifts given in Table 4 can be rationalized by the variation in total electronic charge qtotal described by Bloor and Breen (18), as we have shown previously (4). The variation in 6, in the series pyridazine, pyridazinium ion, pyridazine-N-oxide is a little surprising, since from the pyridazine and I, we would have expected C(3) to be unsensitive and C(6) to show a large sensitivity. The average behavior observed in pyridazinium ion (19, 20) would be characteristic of C(3) alone. We know, on the basis of I, that C(6) will be broadened to such an extent that its detection may have been difficult. The JCH coupling constants have been calculated using an empirical scheme of superposition, ‘J,,(pyridazine-N-oxide)
= “J,,(pyridine) + “J,,(pyridine-N-oxide)
- “J&benzene),
where the positions in pyridine and pyridine-N-oxide are chosen to give the same relative positions in pyridazine-N-oxide compared to N( 1) and N(2), respectively.
395
PYRIDAZINE-N-OXIDE
Theorekol
values
of coupling
constants
FIG. 1. Correlation diagram between experimental (ordinate) and CNDOR calculated (abscissa) 3J,, coupling constants. The curve is established in Ref. (I ), and the data from this work are given by + .
The equation would permit the prediction of one molecule on the basis of knowledge of the other three. We have used benzene values of Tarpley and Goldstein (2Z),‘J,, = 1.11,3.Zcn = 7.58,4J,, = - 1.20 Hz, and pyridine data from the work of Hansen and Jakobsen (22) combined with our previous results on pyridineN-oxide (4). The predictions based on this additivity rule are given in Table 3. The predictions are all within 2 Hz of the experimental values. These results are far superior to the CNDO/2 and INDO calculations. The accuracy in the case of a 1,2-diazine makes it likely that predictions can be made even better for the pyrazine and pyrimidine cases.3 In Table 6 the calculated values for the nonhydrogen coupling constants are reported. The experimental values of .ZNc1)cc3), JNo)C(4j, .ZN(ljC.jj, and JN(ljN(B)could not be observed, but have been obtained indirectly from the line-broadening effects. It is seen from the calculated values that the orbital contribution is significant, whereas the dipole term is unimportant. This is the same relative importance as that found earlier (5) for diazomethane. To relate coupling constants to line broadening we utilize the fact that the line broadening observed for a nucleus with spin Ii = l/2 from a quadrupolar nucleus with spin I, and scalar coupling Ji, is given by (6,23) -=
1
rT,(sc)
(2~JisY(zs
+
3rr
3 We have analyzed the 13C spectrum of pyrazine-N-oxide in this case.
llzs
T qs,
[II
and found the relation valid within 1 Hz
396
WAMSLER
where the quadrupole
ET AL.
relaxation time T,, is given by
The carbon relaxation times in I, in acetone solution Assuming isotropic rotational diffusion, only dipole-dipole cording to
are all about 14 sec. carbon relaxation ac-
131
and using a vibrationally averaged CH bond length of 1.10 A (24, 25), the correlation time T, was determined to be 0.35 x lo-l1 sec. The line broadening observed in the lH spectra can now be related to the quadrupolar relaxation time TqN(lj by relation [ 11, yielding the values of TqNcl)in Table 7. Those values, together with the line broadenings in the 13C spectra, give the experimental values of J,, reported in Table 6. The quadrupolar relaxation time is related to the NQCC by relation [2]. By introducing the rotational correlation time T, as found above and r) = 0 (23), NQCC values are calculated as shown in Table 7. The values for NQCC obtained are approximately 1 MHz. This value is somewhat smaller than the number found in pyridine-N-oxide, and both numbers are much smaller than the 4 MHz typical for azines where nitrogen has a free lone pair. The 15N INDOR spectra showed two very different lineshapes for 15N(1) and 15N(2). 15N(1) was very sharp, whereas 15N(2) was a broadened triplet band. The appearance of the two signals can be interpreted by reference to the work of Lehn and Kintzinger (23). They suggested an approximate formula for the steady-state lineshape Z(X) of a spin-l/2 particle coupled to a quadrupolar nucleus of spin 1. 45 + E2(5X2 + 1) 2E Z(x) = mJNN 225x’ + 8(34x4 - 2x’ + 4) + •~(9 - 2x4 + x2) ’
[41
E = 107~TqN.JNN,
[51
x = Au/J,,.
[61
Fitting of the lineshape to Eq. [4] gave E = 9. Insertion of this value in the expression for dZ(x)/dv yields x = 0.86 between the outer peaks. The separation is measured as 8.6 Hz; therefore 1JIjNIdN1 is equal to 10 Hz. From [5], TqNcl,is determined to be 29 2 1 msec, in good agreement with the values obtained from proton measurement (Table 7). Taking the NQCC for N(2) to be approximately 4 MHz as for pyridine (23) we calculate the contribution to the linewidth from N(2) to be less than the experimental linewidth for protons, carbon, and nitrogen. The value obtained for the nitrogen-nitrogen coupling constant cannot be compared to many experimental data. Bulusu et al. (26) measured some ?I,, coupling constants. Some examples where two sp*-hybridized nitrogen atoms, one of
397
PYRIDAZINE-N-OXIDE
which has a free lone pair, are found (27): dibenzyl nitrosamine tuans-azoxybenzene dinitrogen
lJ,swNI = 19.0 Hz,
[(I#LH,),NNOI,
IJ,aN,sNI = 13.7 Hz,
[+NN($)O],
JmN,sN= -9.3 Hz.
oxide [NNO],
Only in dinitrogen oxide has the sign been determined, and it was found to be negative (28). It would be reasonable to expect that the remaining compounds also have negative ‘J,,. Further evidence for this negative sign comes from the theoretical calculations of ?I,,. In clinitrogen oxide where the geometry is known (29), ?I,, is calculated to be CNDO/2 (- 1.78, -2.31 Hz), INDO (-9.53, - 11.86 Hz); the first value refers to fixed, the second to variable electron density (5). The calculated values for I are given in Table 6. Both calculated values are negative and they deviate similarly from the experimental values. CONCLUSION
Within the series of azines and their N oxides it seems that chemical shifts 6, and Sc and coupling constants can be rationalized by a superposition scheme allowing reliable predictions of parameters. The N oxidation results in very different NQCC for the two nitrogens in I. This in turn influences the carbon and proton spectra in a characteristic way since only N( 1) introduces scalar broadening. The NQCC is determined by 15N and ‘H lineshapes to a consistent value of 0.9 ? 0.2 MHz. Theoretical values of coupling constants are found to correlate lJ,” and 3J,, values for azines and their N oxides well, and they have been used to support the negative sign suggested for the lJ,, determined in I. ACKNOWLEDGMENTS The authors are grateful to NEUCC (Northern Europe University for free computation time. 13C spectra were obtained in part the cooperation of Dr. H. K. Bildsoe. Finally, we acknowledge Research Council placing a Bruker WH 90 at our disposal.
Computing Centre), Copenhagen, at the University of Aarhus with the support of the Danish Scientific
REFERENCES I.
J. P. JACOBSEN,
0.
E. J. PEDERSEN,
SNERLING,
10, 130 (1973). 2. I. N. BOJESEN, J. H. Hoc, Stand. 25, 2739 (1971).
J. T. NIELSEN,
AND
K. SCHAUMBURG,J.
Mugn.
Reson.
3.
A.
HOLM,
Chem. 4.
K.
J. T. NIELSEN,
SCHAUMBURG,
N.
DAHLBERG,
I. B. PEDERSEN,
AND
C. CHRISTOPHERSEN,
K.
SCHAUMBURG, AND
Acta
J. P. SNYDER,
Chem. J.
Org.
40, 431 (1975).
T. WAMSLER,
J. T.
NIELSEN,
E.
J. PEDERSEN,
AND
K.
SCHAUMBURG,
J. Mugn.
Reson.
31,
177 (1978). 5.
A. D.
C. TOWL
6.
T.
C.
FARRAR
AND
AND
New
York,
1971.
K.
SCHAUMBURG,
E.
D.
BECKER,
Mol. “Pulse
Phys. 22, 49 (1971). and Fourier Transform
7. V. M. S. GIL AND A. J. L. PINTO, Mol. Phys. 19, 573 (1970). 8. P. C. LAUTERBUR, J. Chem. Phys. 43, 360 (1965). 9. K. TORI AND T. NAKAGAWA, J. Phys. Chem. 68, 3163 (1964).
NMR,”
Academic
Press,
398 10. II. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29.
V. K. A. T. A. 0. M. M. J. A. R. A. M. J. N. P. S. G. P. J.
WAMSLER
ET AL.
M. S. GIL, Mol. Phys. 9, 443 (1965). TORI, M. OGATA, AND H. KANO, Chem. Pharm. Bull. (Tokyo) 11, 235 (1963). G. MORITZ AND D. B. PAUL, Aust. J. Chem. 22, 1305 (1969). ITAI AND S. NATSUME, Chem. Pharm. Bull. (Tokyo) 11, 83 (1963). CHARLES AND W. MCFARLANE, Mol. Phys. 14, 299 (1968). H. MANSCHER, M.Sc. thesis, University of Copenhagen, 1971. WITANOWSKI AND G. A. WEBB (Eds.), “Nitrogen NMR,” Plenum, New York, 1973. WITANOWSKI, L. STEFANIAK, H. JANUSZEWSKI, ANDG. A. WEBB, Tetrahedron 27,3129(1971). E. BLOOR AND D. L. BREEN, J. Am. Chem. Sot. 89, 6835 (1967). MATHIAS AND V. M. S. GIL, Tetrahedron Lett., 3163 (1965). J. PUGMIRE AND D. M. GRANT, J. Am. Chem. Sot. 90, 697 (1968). R. TARPLEY, JR., AND J. H. GOLDSTEIN, J. Phys. Chem. 76, 515 (1972). HANSEN AND H. J. JAKOBSEN, J. Magn. Reson. 10, 74 (1973). M. LEHN AND J. P. KINTZINGER, Ref. (16), Chap. 3. M. SZCEVERENYI, R. R. VOLD, AND R. L. VOLD, Chem. Phys. 18, 23 (1976). DIEHL AND W. NIEDERBERGER, J. Magn. Reson. 9, 495 (1973). BULUSU, J. R. AUTERA, AND T. AXENROD, J. Chem. Sot. Chem. Commun., 602 (1973). BINCH, J. B. LAMBERT, B. W. ROBERTS, AND J. D. ROBERTS,J. Am. Chem. Sot. 86,5564(1964). K.‘BHATTACHARYYA AND B. P. DAILEY, J. Chem. Phys. 59, 5820 (1973). K. G. WATSON, J. Mol. Spectrosc. 48, 479 (1973).
MAGNETIC
RESONANCE43,387-398(1981)
NMR Studies of Pyridazine-N-Oxide. Determination of Spectroscopic Parameters from the [15N]- and Parent Species TORBEN WAMSLER,JORGEN TORMOD NIELSEN,ERIK AMD KJELD SCHAUMBURG
JONAS PEDERSEN,
Uni\sersity of Copenhagen, Chemical Laboratory V, The H. C. @wed Institute, DK-2100 Copenhagen 0., Denmark Received August 20, 1980; revised November
18, 1980
Pyridazine-N-oxide and [15N]pyridazine-N-oxide have been investigated by NMR spectroscopy. ‘H and 13C spectra have been obtained and analyzed, in terms of chemical shifts and spin-spin coupling constants. Relaxation times have been measured for 13C and have been used to determine the correlation time 7c under the assumption of isotropic molecular diffusion. From rH, 15N INDOR experiments the lineshape of N(2) is determined; analysis of the lineshape yields ?I,, and 7 4Nuj. On the basis of experimental data and observed linewidth variations, the N(1) nitrogen quadrupole coupling constant has been evaluated. The experimental data are correlated with semiempirical calculations within the azine series. INTRODUCTION
Earlier we reported spectroscopic studies of pyridazine (I ), pyrazole (I), thiazoie (2), and 1,2,3,4-thiatriazole (3), all enriched in 15N in order to facilitate the NMR investigations. We also studied [15N]- and 12H]-enriched species of pyridine-N-oxide (4). One realson for the latter investigation was the large changes in spin-spin coupling constants between nitrogen and carbon or protons introduced by N oxidation. Theoretically we tried to reproduce this behavior by calculations using the CNDOI2 SOS method (5). Another reason was the large differences in lineshapes observed in both carbon and proton spectra brought about by scalar coupling toI nitrogen (6). The spectrum of pyridine-N-oxide indicated a rather small value of the nuclear quadrupole coupling constant (NQCC) of 1.3 MHz. In the investigation of pyridazine-iv-oxide (I) we wanted to pursue the same information as that in the case of pyridine-N-oxide. Several authors have reported data for pyridazine (1,7-l I). Pyridazine-N-oxide (I) was first investigated by Tori and Nakagawa (9) by ‘H NMR. Later Moritz and Paul (12) determined the relative signs and more accurate values of the proton-proton coupling constants. No data concerning the analysis of the proton-coupled carbon spectra of I, or relating to the 15N species I,, and I, have previously appeared.
387 0022-2364/81/060387-12$02.00/O Copyright 0 1981 by Academic Press, Inc. All rights of reproduction in any form reserved.
388
WAMSLER
ET AL.
EXPERIMENTAL
Pyridazine-N-oxide was prepared according to the method of Itai and Natsume (13) with the modifications enforced by the smaller quantities involved. Pyridazine (100 ~1) was added to a mixture of 1 ml acetic acid and 1.5 mol eq (with respect to pyridazine) of aqueous H,O, (30% w/w). The mixture was kept at 85°C for 12 hr. Unreacted material and solvents were distilled off leaving a residue consisting of pyridazine-N-oxide (colorless) and polymerization products. The appropriate NMR solvent was added and the solution filtered to remove the strongly colored polymerization products. 15N pyridazine 33% enriched in 15N was synthesized as described by Jacobsen ej al. (1). The synthesis of the N-oxide was as above. The resulting pyridazine-N-oxide consists of three isotopic species I,, Ib, and I, in the ratio 4: 1: 1. Samples of I, were prepared by dissolving it in CDCl, or (CD&CO, typically at 1.0 to 1.6 M, and adding TMS as internal reference. After several freeze-pump-thaw cycles the samples were sealed. The 15N-enriched sample was 0.8 M in (CD&CO. 13C spectra were obtained in the FT mode using a Varian XL-100 spectrometer operating at 25.12 MHz at 32°C. Proton-coupled spectra were recorded with 14N decoupling, 8K data points, and a spectral range of 250 Hz. The repetition time was 6.7 set and the pulse width 75 psec corresponding to 70”. Similar conditions were used for linewidth measurements in ‘Hdecoupled 13C spectra. 13C T, measurements by the inversion-recovery method were performed on a Varian XL-100 and a Bruker WH 90 spectrometer. Relaxation data were fitted using a nonlinear three-parameter regression analysis. ‘H spectra were recorded on a Varian HA-100 operating at 32°C modified for digital sweep under control of a Varian 620/i computer. In hetero-INDOR experiments a Schlumberger FSD 120 synthesizer was phase locked to the proton frequency and swept through the region of interest under control of a Varian 620/i computer storing the spectrum in 2K points. The ‘H signal monitored was derived from a Rockland 5 100 synthesizer used as sideband oscillator in the analytical channel. In heterodecoupling experiments an Electronic Navigation Instruments power amplifier Model 310L was used to boost the output of the FSD 120. The V 4330 probe was modified for heterodecoupling according to the method of McFarlane (14). lH spectra were also obtained using a Bruker HX 60 spectrometer coupled to a Varian C 1024 CAT. This instrument was used for homotickling and homoINDOR experiments. The lH spectra used in determination of coupling constants were recorded with a sweep expansion of 0.2 Hz/cm and with sweep rates not exceeding 6 x 10e3 Hz/set. Analysis of the spectra was performed using the program LAOCOON III (15). CND0/2 and INDO calculations were of the sum-over-state method (SOS). The parameterization has been discussed by Tow1 and Schaumburg (5). In the determination of nitrogen chemical shifts we have chosen to refer the nitrogen signals to the lH resonance of internal TMS. The usual nitrogen standard MeNO* then appears as a secondary standard. From Witanowski and Webb (16, Chap. 3), we have chosen the data for 0.1 M MeNO, in CDCI:, + TMS. They quote a v(15N) in MeN@ of 22,300,783 Hz for the ‘H in TMS resonating at 220,000,OOO Hz. In our modified Varian HA-100 spectrometer the TMS frequency was 100,002,500.00 Hz referenced to a rubidium standard. The magnetic field
389
PYRIDAZINE-N-OXIDE TABLE CHEMICAL
SHIFT
1
6, (ppnn) RELATIVE TO TMS AND ‘II H(A)H(B) (Hz) IN PYRIDAZINE-N-OXIDE
COUPLING
CONSTANTS
Compound
63 64 & f& n
A
B
3 4 5 3 4 3
3 3 3 4 4 5
4 5 6 5 6 6
Solvent Concentration
(M)
8.5271 7.2269 7.8705 8.2316
-c f ? c
0.0001 0.0001 0.0001 0.0001
5.40 2.53 0.99 7.73 0.91 6.47
k ? c k 2 ”
0.02 0.02 0.02 0.02 0.02 0.02
8.5265 7.2270 7.8707 8.2301
+ ? ” k
0.0001 0.0001 0.0001 0.0001
5.39 2.54 0.99 7.73 0.92 6.48
-c k k +k +
0.01 0.01 0.01 0.01 0.01 0.01
(CD, WO 0.54c
(CD,),CO 0.13c
8.5266 7.2270 7.8712 8.2315
5.40 2.56 1.00 7.76 0.90 6.51
k r 2 t
0.0002 0.0003 0.0003 0.0002
2 0.03 k 0.02 f 0.03 2 0.03 -c 0.05 + 0.02
(CQ),CO 0.13c
8.54 7.22 7.83 8.26
8.49 7.17 7.78 8.22
5.3 2.5 1.0 8.0 1.0 6.5
5.39 2.54 0.99 7.76 0.92 6.49 CDCI,
Note. I,, Ib, I, refer to the three isotopic species studied. a Reference (II). * Reference (12). c Total concentration (I, + Ib + I,) = 0.8 M.
corresponds to a MeNO, frequency 7,226,463 Hz for the 14N species.
of 10,136,973 Hz for the 15N species and RESULTS
The lH spectrum of I consists of the superimposed spectra of I,, I,,, and I, (see Experimental). It is observed that the presence of nitrogen broadens the lines excessively, and that 14N decoupling must be applied to obtain suitable spectra for analysis. In order to perforlm 14N decoupling or 15N tickling the nitrogen chemical shifts must be determined. There have previously been no report of the 6, for oxides of diazines in the literature. For a TMS resonance frequency of 100,002,500 Hz we found the following frequencies: 10,136,484 and 10,136,696 Hz for 15N(1) and 15N(2), respectively. These values correspond to -48 and -28 ppm referred to MeNO, (see Experimental). The values were obtained as well by heterotickling as by hetero-INDOR using data accumulation over several hours. In Table 1 proton chemical shifts and proton-proton coupling constants are reported. For comparison the data previously published are included (I I, 12). The experimental and calculated nitrogen-proton coupling constants are given in Table 2.l In some cases lines from I,, superimposed on stronger lines from the more abundant I,, were identified by triple resonance. With decoupling of ‘N, 1 Throughout the paper coupling constants between nitrogen and other nuclei refer to 15N unless explicitly stated. Where comparison to literature data has made it necessary l*N data have been converted to the proper value using the factor 1.40275710 2 7 x lOm8(14).
390
WAMSLER
ET AL.
TABLE ‘jN-‘H
COUPLING
(Hz)
CONSTANTS
2 IN PYRIDAZINE-N-OXIDE
(nJL5Nca,HcB,)
Calculated n
A
B
Experimental
3
1
3
-8.30
4
1
4
3
1
5
2
1
2
a
CNDO/Z@
INDO*
i 0.02c
-3.40 -3.95
-4.70 -5.46
f 0.02”
-0.26 -0.31
-0.22 -0.27
-5.04
CL 0.02c
-1.72 -2.01
-1.93 -2.27
6
-0.81
iz 0.02”
-1.92 -2.30
-2.34 -2.83
2
3
-14.46
2 0.03d
-6.63 -6.71
-9.70 -9.46
3
2
4
-1.85
” 0.09
-0.72 -0.74
-0.27 -0.27
4
2
5
3
2
6
0.81
0.58
-0.33
+ 0.03d
* 0.05d
’ The top value refers to fixed and electron density. For details of calculation b Calculation scheme. c Measured on I,,. d Measured on I,.
0.16 0.17
0.83 0.82
-0.25 -0.26 the bottom value see Ref. (5).
0.50 0.51 to
variable
‘H spectra were recorded with and without 15N decoupling. By appropriate sign reversal in the accumulation the signals from I, were found. The signs of the JNH are determined by heterotickling and homotickling on the basis of the conclusion (12) that all JHH are positive. The experimental and calculated carbon- hydrogen coupling constants are reported in Table 3. For some of the smaller coupling constants it was not possible to determine the sign. The more likely sign is given without parentheses. The values were obtained using a 1.6 M sample of I, dissolved in (CD&CO. The carbon chemical shifts are reported in Table 4. The position is relative to TMS for CDCl, whereas only chemical shift differences have been determined in (CD&CO. The calculations of the coupling constants (Tables 2, 3 and 5, 6) are CND0/2 and INDO (5). Because of the size of the system no configuration interaction was used. The geometry used in the calculations was not experimentally determined.* 2 Bond distances: N(l)N(2), 1.355 A; N(2)C(3), 1.330 A; C(3)C(4), 1.403 A; C(4)C(5), 1.378 A; C(5)C(6), 1.395 A; CH, 1.084 A; N(l)O, 1.299 A. Bond angles: LC(~)N(~)N(~), 122.3”; iN(l)N(2)C(3), 116.3”; LN(~)C(~)C(~), 125.8”; LC(~)C(~)C(~), 116.1”; LC(~)C(~)C(~), 119.0”; LC(~)C(~)N(~), 120.6”; LN(2)C(3)H(3), 114.3”; LC(3)C(4)H(4), 121.8”; LH(5)C(S)C(6), 119.2”; i~(6)N(i)0, 118.9”; LH(6)C(6)N(l), 113.7”.
391
PYRIDAZINE-N-OXIDE TABLE W-IH
COUPLING
CONSTANTS
(Hz)
3 IN PYRIDAZINE-N-OXIDE
(“J13ccAjHcBj)
Calculated
Fixed Variable
n
A
B
Experimental
Additivity rule”
1
3
3
184.7
186.2
2
3
4
3.6
3.5
1.81 1.99
2.48 2.74
3
3
5
8.1
8.2
4.04 4.42
4.06 4.44
4
3
6
< IO.3 /
2
4
5
5.2
7.0
1.49 1.52
2.40 2.40
1
4
4
175.3
174.0
77.54 80.19
75.15 76.91
2
4
5
-0.4
-0.7
3
4
6
5.4
3
5
3
2
5
1
CNDOI2 73.05 79.35
-0.5
0.16 0.18
INDO 74.07 80.22
-4.04 -0.04
0.34 0.35
1.11 1.13
5.7
2.61 2.76
2.81 2.94
7.3
7.6
3.56 3.79
4.37 4.59
4
(‘jO.4
1.1
0.53 0.57
1.34 1.43
5
5
170.76
171.0
70.19 75.22
68.85 73.05
2
5
6
4.1
3.8
4
6
3
‘+‘l . 5
3
6
4
7.5
2
6
5
1
6
6
1.45 1.59
1.85 2.02
0.13 0.13
1.05 1.06
7.1
3.01 3.14
3.91 4.02
4.4
4.0
3.03 3.14
3.53 3.60
193.2b
191.9
85.79 91.38
84.13 88.63
a The calculated values are based on an additivity * kO.2 Hz; all other values, kO.1 Hz.
-1.9
rule described
under
Discussion.
392
WAMSLER
ET AL.
TABLE CHEMICAL
SHIFTS
4
SlaC FOR PYRIDAZINE-N-OXIDE si (wm)
Concentration Solvent
A(% - 8,) (wm) 34.4 0.0 18.1 18.1 -1 CDCl,
150.6 116.2 134.3 134.3 -1 CDCl,
83 64 85 K3 (M)
35.13 0.00 19.17 18.69 -1.6 (C&)X0
It is based on our knowledge of bond angles and lengths in pyridine-hi-oxide (4) and assumptions consistent with available data on other aromatic ring compounds. Table 7 collects the data obtained for 13C relaxation times using the inversionrecovery method. In the same table the contributions to the observed linewidths resulting from scalar relaxation due to r4N are listed for 13Cand lH. On the basis of these data and the coupling constants given in Tables 2 and 6 the quadrupolar relaxation time TqN for N(1) has been calculated in various ways. Combination of these data with a molecular rotational correlation time of 0.35 x lo-” set (see below) yields the estimated nuclear quadrupole coupling constants (NQCC) presented. DISCUSSION
The proton spectrum of I is almost a first-order case, and the assignments are straightforward. The present results for proton chemical shifts and protonTABLE CALCULATED
SPIN-SPIN
5
COUPLING
Calculated
CONSTANTS
IIJHcAIHfB,
yz$le I
n
A
B
CNDOi2
INDO
Experimental
3
3
4
5.18 5.30
4.66 4.60
5.39
4
3
5
2.83 2.89
3.68 3.61
2.54
5
3
6
1.47 1.53
2.01 2.03
0.99
3
4
5
6.57 6.77
5.46 5.45
7.73
4
4
6
1.10 1.16
2.26 2.33
0.92
3
5
6
4.12 4.34
3.05 3.12
6.48
393
PYRIDAZINE-N-OXIDE TABLE CALCULATEDCOUPLINGCONSTANTS NONHYDROGEN
6
IN THE CNDOR AND INDO NUCLEI IN PYRIDAZINE-N-OXIDE Calculated
SOS APPROXIMATION iiJN(ijX(BI
BETWEEN
~~r~$e I
X
nA
B
Contact
Dipole-dipole
Spin-orbit
2
1
3
T
3
1
4
‘T
2
1
5
‘T
1
1
6
-7.29 -8.62
13c
1
2
3
-3.75 -4.07
‘T
2
2
4
-0.37 -0.37
-0.36 -0.36
-0.21 -0.20
-0.25 -0.23
T
3
2
5
-0.73 -0.78
-0.66 -0.70
-0.13 -0.13
-0.13 -0.12
-0.21 -0.21
‘T
2
2
6
-0.08 -0.08
-0.06 -0.06
-0.01 -0.01
‘jN
1
1
2
-1.23 -1.30
-1.25 - 1.33
Note. The first (1 Calculated from b Measured in the c Determined from
0.07 0.09
term
‘T
-1.87 -2.20 0.24 0.30
0.17 0.17 -2.98 -3.46
0.43 0.56 -1.89 -2.28 0.19 0.24 -5.84 -7.07 0.24 0.26
0.26 0.26 -5.96 -6.91
-0.05 -0.05
-0.04 PO.05
0.00 0.00
-0.25 -0.27
-0.25 -0.27
-0.25 -0.27
--0.18 -0.20
-0.16 -0.19
-0.01 -0.01
Total
0.00 0.00 -0.26 -0.29 0.00 0.00
0.02 0.03 -2.37 ~2.73
1.48 1.64
-0.09 -0.10
-0.10 -0.11
-5.85 -7.06
1.86 1.87
1.83 1.85
-0.10 -0.11
-0.11 -0.11
-1.99 -2.31
0.04 0.04
0.05 0.05 -0.22 -0.21 0.00 0.00 0.03 0.03
0.39 0.51 -2.41 -2.84
0.06 0.09
1.53 1.66
0.04 0.04
Experimental
-0”
~4.46 -5.54
(C)iSb
1.96 2.00 -0.56 -0.55
-1.08 -1.12
-1.00 -1.03
-4.17 -4.72
(2)9.4”
0.02 0.05
-0.53 -0.53
0.08 0.09
“‘6 _ 3”
0.21 0.20 -7.17 -8.27
(?)14.0C
column is calculated by CNDOI2 and the second by INDO. line broadening and T,4N,l) = 25 msec (Table 7). 13C spectrum. line broadening in INDOR experiments, as described under Discussion.
proton coupling constants are almost identical to those of Moritz and Paul (12). In general theoretical predictions of 3JHH are good. In Fig. 1 the correlation previously (1) established for 3JHH is reproduced and the values obtained in this work have been added to the figure. The agreement is seen to be good. The,nitrogen chemical shift in pyridazine is +20 ppm (17) and in pyridine -58 ppm (4). In pyridine-N-oxide the shielding is increased by 22 to -80 ppm (4). In pyridazine the N oxidation produces an increase in shielding for N( 1) of 68 ppm, three times larger than for pyridine. Even in the N(2) position the observed effect is 47 ppm, indicating that the electron distribution is strongly affected at both nitrogen positions in I. This is substantiated by CND0/2 calculations where the total atomic charge changes from +0.07 electrons in pyridazine to -0.41 at N(1) and +0.17 at N(2) in the N-oxide. The 2J,H value in pyridazine was found to be - 12.04 Hz (1). The value of - 14.46 Hz found in I, is similar, indicating that the N oxidation of the neighboring nitrogen does not interfere with the (T lone pair at N(2), which is influential in determining the magnitude of 2J,H. N oxidation increases the value of the 2J,H for the
394
WAMSLER
ET AL.
TABLE RELAXATION
Position
T T, (se4
DATA (A*
7
FOR PYRIDAZINE-N-OXIDE - A)” (‘“C) (Hz)
(A*
- A) (‘H) (Hz)
3
14 ” 4
4.2
-
4 5 6
14 2 2 15 + 4 -
9.5
0.06 2.2 0.08
” (A* b The c The
-0 -
(1.0 M IN (CDS)&O) TqNo, msec 22 20 29
(e”qQlh) NV (MHz) 0.94 0.98 0.82
- A) indicates scalar broadenings of lines. is equal to 25 x 10e3 sec. mean value for TQNo, of all measurements mean value for e*qQlh of all measurements is equal to 0.88 MHz.
oxidized nitrogen itself. In pyridine (4) an increase of 11.3 Hz is observed. A closely related change (11.2 Hz) is found here, resulting in a *JNH value of -0.81 Hz in It,. In pyridine 3J,H showed behavior opposite to that of 2JNH, decreasing by - 1.53 Hz by N oxidation (4). If we take for 3JNccH in pyridazine the value of - 1.2 Hz (I ) as a starting point, we find for the two inequivalent 3JNccH values in I, - 1.85 Hz for 3JNc23Hc41 and -5.04 Hz for 3JN~1~H~5~.Considering the N-oxidized atom the direction of the observed change is again quite analogous to the pyridine/pyridine N-oxide case. The 3J,N,-H corresponding to a path involving nitrogen displays rather large variations. Here the pyridazine value was -3.70 Hz (1). The N oxidation increases the value in I,,, where the intervening nitrogen has been oxidized to 3JNc1,Hc3, = -0.33 Hz whereas in I, where the intervening nitrogen still is pyridine-like, 3J~c2m-~ is decreased to -8.30 Hz. The latter seems to be numerically the largest 3JNHthat has been reported. We mentioned (4) that 3JxNcH when X = 13C (for pyridine/pyridine N-oxide) was greatly influenced by the type of the intervening nitrogen. In I when X = 15N that point is even more evident. The 4JNH values are both small and positive as found in pyridine and pyridine-N-oxide. The carbon chemical shifts given in Table 4 can be rationalized by the variation in total electronic charge qtotal described by Bloor and Breen (18), as we have shown previously (4). The variation in 6, in the series pyridazine, pyridazinium ion, pyridazine-N-oxide is a little surprising, since from the pyridazine and I, we would have expected C(3) to be unsensitive and C(6) to show a large sensitivity. The average behavior observed in pyridazinium ion (19, 20) would be characteristic of C(3) alone. We know, on the basis of I, that C(6) will be broadened to such an extent that its detection may have been difficult. The JCH coupling constants have been calculated using an empirical scheme of superposition, ‘J,,(pyridazine-N-oxide)
= “J,,(pyridine) + “J,,(pyridine-N-oxide)
- “J&benzene),
where the positions in pyridine and pyridine-N-oxide are chosen to give the same relative positions in pyridazine-N-oxide compared to N( 1) and N(2), respectively.
395
PYRIDAZINE-N-OXIDE
Theorekol
values
of coupling
constants
FIG. 1. Correlation diagram between experimental (ordinate) and CNDOR calculated (abscissa) 3J,, coupling constants. The curve is established in Ref. (I ), and the data from this work are given by + .
The equation would permit the prediction of one molecule on the basis of knowledge of the other three. We have used benzene values of Tarpley and Goldstein (2Z),‘J,, = 1.11,3.Zcn = 7.58,4J,, = - 1.20 Hz, and pyridine data from the work of Hansen and Jakobsen (22) combined with our previous results on pyridineN-oxide (4). The predictions based on this additivity rule are given in Table 3. The predictions are all within 2 Hz of the experimental values. These results are far superior to the CNDO/2 and INDO calculations. The accuracy in the case of a 1,2-diazine makes it likely that predictions can be made even better for the pyrazine and pyrimidine cases.3 In Table 6 the calculated values for the nonhydrogen coupling constants are reported. The experimental values of .ZNc1)cc3), JNo)C(4j, .ZN(ljC.jj, and JN(ljN(B)could not be observed, but have been obtained indirectly from the line-broadening effects. It is seen from the calculated values that the orbital contribution is significant, whereas the dipole term is unimportant. This is the same relative importance as that found earlier (5) for diazomethane. To relate coupling constants to line broadening we utilize the fact that the line broadening observed for a nucleus with spin Ii = l/2 from a quadrupolar nucleus with spin I, and scalar coupling Ji, is given by (6,23) -=
1
rT,(sc)
(2~JisY(zs
+
3rr
3 We have analyzed the 13C spectrum of pyrazine-N-oxide in this case.
llzs
T qs,
[II
and found the relation valid within 1 Hz
396
WAMSLER
where the quadrupole
ET AL.
relaxation time T,, is given by
The carbon relaxation times in I, in acetone solution Assuming isotropic rotational diffusion, only dipole-dipole cording to
are all about 14 sec. carbon relaxation ac-
131
and using a vibrationally averaged CH bond length of 1.10 A (24, 25), the correlation time T, was determined to be 0.35 x lo-l1 sec. The line broadening observed in the lH spectra can now be related to the quadrupolar relaxation time TqN(lj by relation [ 11, yielding the values of TqNcl)in Table 7. Those values, together with the line broadenings in the 13C spectra, give the experimental values of J,, reported in Table 6. The quadrupolar relaxation time is related to the NQCC by relation [2]. By introducing the rotational correlation time T, as found above and r) = 0 (23), NQCC values are calculated as shown in Table 7. The values for NQCC obtained are approximately 1 MHz. This value is somewhat smaller than the number found in pyridine-N-oxide, and both numbers are much smaller than the 4 MHz typical for azines where nitrogen has a free lone pair. The 15N INDOR spectra showed two very different lineshapes for 15N(1) and 15N(2). 15N(1) was very sharp, whereas 15N(2) was a broadened triplet band. The appearance of the two signals can be interpreted by reference to the work of Lehn and Kintzinger (23). They suggested an approximate formula for the steady-state lineshape Z(X) of a spin-l/2 particle coupled to a quadrupolar nucleus of spin 1. 45 + E2(5X2 + 1) 2E Z(x) = mJNN 225x’ + 8(34x4 - 2x’ + 4) + •~(9 - 2x4 + x2) ’
[41
E = 107~TqN.JNN,
[51
x = Au/J,,.
[61
Fitting of the lineshape to Eq. [4] gave E = 9. Insertion of this value in the expression for dZ(x)/dv yields x = 0.86 between the outer peaks. The separation is measured as 8.6 Hz; therefore 1JIjNIdN1 is equal to 10 Hz. From [5], TqNcl,is determined to be 29 2 1 msec, in good agreement with the values obtained from proton measurement (Table 7). Taking the NQCC for N(2) to be approximately 4 MHz as for pyridine (23) we calculate the contribution to the linewidth from N(2) to be less than the experimental linewidth for protons, carbon, and nitrogen. The value obtained for the nitrogen-nitrogen coupling constant cannot be compared to many experimental data. Bulusu et al. (26) measured some ?I,, coupling constants. Some examples where two sp*-hybridized nitrogen atoms, one of
397
PYRIDAZINE-N-OXIDE
which has a free lone pair, are found (27): dibenzyl nitrosamine tuans-azoxybenzene dinitrogen
lJ,swNI = 19.0 Hz,
[(I#LH,),NNOI,
IJ,aN,sNI = 13.7 Hz,
[+NN($)O],
JmN,sN= -9.3 Hz.
oxide [NNO],
Only in dinitrogen oxide has the sign been determined, and it was found to be negative (28). It would be reasonable to expect that the remaining compounds also have negative ‘J,,. Further evidence for this negative sign comes from the theoretical calculations of ?I,,. In clinitrogen oxide where the geometry is known (29), ?I,, is calculated to be CNDO/2 (- 1.78, -2.31 Hz), INDO (-9.53, - 11.86 Hz); the first value refers to fixed, the second to variable electron density (5). The calculated values for I are given in Table 6. Both calculated values are negative and they deviate similarly from the experimental values. CONCLUSION
Within the series of azines and their N oxides it seems that chemical shifts 6, and Sc and coupling constants can be rationalized by a superposition scheme allowing reliable predictions of parameters. The N oxidation results in very different NQCC for the two nitrogens in I. This in turn influences the carbon and proton spectra in a characteristic way since only N( 1) introduces scalar broadening. The NQCC is determined by 15N and ‘H lineshapes to a consistent value of 0.9 ? 0.2 MHz. Theoretical values of coupling constants are found to correlate lJ,” and 3J,, values for azines and their N oxides well, and they have been used to support the negative sign suggested for the lJ,, determined in I. ACKNOWLEDGMENTS The authors are grateful to NEUCC (Northern Europe University for free computation time. 13C spectra were obtained in part the cooperation of Dr. H. K. Bildsoe. Finally, we acknowledge Research Council placing a Bruker WH 90 at our disposal.
Computing Centre), Copenhagen, at the University of Aarhus with the support of the Danish Scientific
REFERENCES I.
J. P. JACOBSEN,
0.
E. J. PEDERSEN,
SNERLING,
10, 130 (1973). 2. I. N. BOJESEN, J. H. Hoc, Stand. 25, 2739 (1971).
J. T. NIELSEN,
AND
K. SCHAUMBURG,J.
Mugn.
Reson.
3.
A.
HOLM,
Chem. 4.
K.
J. T. NIELSEN,
SCHAUMBURG,
N.
DAHLBERG,
I. B. PEDERSEN,
AND
C. CHRISTOPHERSEN,
K.
SCHAUMBURG, AND
Acta
J. P. SNYDER,
Chem. J.
Org.
40, 431 (1975).
T. WAMSLER,
J. T.
NIELSEN,
E.
J. PEDERSEN,
AND
K.
SCHAUMBURG,
J. Mugn.
Reson.
31,
177 (1978). 5.
A. D.
C. TOWL
6.
T.
C.
FARRAR
AND
AND
New
York,
1971.
K.
SCHAUMBURG,
E.
D.
BECKER,
Mol. “Pulse
Phys. 22, 49 (1971). and Fourier Transform
7. V. M. S. GIL AND A. J. L. PINTO, Mol. Phys. 19, 573 (1970). 8. P. C. LAUTERBUR, J. Chem. Phys. 43, 360 (1965). 9. K. TORI AND T. NAKAGAWA, J. Phys. Chem. 68, 3163 (1964).
NMR,”
Academic
Press,
398 10. II. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29.
V. K. A. T. A. 0. M. M. J. A. R. A. M. J. N. P. S. G. P. J.
WAMSLER
ET AL.
M. S. GIL, Mol. Phys. 9, 443 (1965). TORI, M. OGATA, AND H. KANO, Chem. Pharm. Bull. (Tokyo) 11, 235 (1963). G. MORITZ AND D. B. PAUL, Aust. J. Chem. 22, 1305 (1969). ITAI AND S. NATSUME, Chem. Pharm. Bull. (Tokyo) 11, 83 (1963). CHARLES AND W. MCFARLANE, Mol. Phys. 14, 299 (1968). H. MANSCHER, M.Sc. thesis, University of Copenhagen, 1971. WITANOWSKI AND G. A. WEBB (Eds.), “Nitrogen NMR,” Plenum, New York, 1973. WITANOWSKI, L. STEFANIAK, H. JANUSZEWSKI, ANDG. A. WEBB, Tetrahedron 27,3129(1971). E. BLOOR AND D. L. BREEN, J. Am. Chem. Sot. 89, 6835 (1967). MATHIAS AND V. M. S. GIL, Tetrahedron Lett., 3163 (1965). J. PUGMIRE AND D. M. GRANT, J. Am. Chem. Sot. 90, 697 (1968). R. TARPLEY, JR., AND J. H. GOLDSTEIN, J. Phys. Chem. 76, 515 (1972). HANSEN AND H. J. JAKOBSEN, J. Magn. Reson. 10, 74 (1973). M. LEHN AND J. P. KINTZINGER, Ref. (16), Chap. 3. M. SZCEVERENYI, R. R. VOLD, AND R. L. VOLD, Chem. Phys. 18, 23 (1976). DIEHL AND W. NIEDERBERGER, J. Magn. Reson. 9, 495 (1973). BULUSU, J. R. AUTERA, AND T. AXENROD, J. Chem. Sot. Chem. Commun., 602 (1973). BINCH, J. B. LAMBERT, B. W. ROBERTS, AND J. D. ROBERTS,J. Am. Chem. Sot. 86,5564(1964). K.‘BHATTACHARYYA AND B. P. DAILEY, J. Chem. Phys. 59, 5820 (1973). K. G. WATSON, J. Mol. Spectrosc. 48, 479 (1973).