Graphic Representation of Nuclear Magnetic Resolnance Proton Chemical Shifts for the Acyclic Methine Group Osamu Yamamoto, Teruo Suzuki, Masaru Yanagisawa, and Kikuko Hayamizu Government Chemical Industrial Research Institute, Shibuya-ku, Toyko, Japan
Masako Oknishi National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
A graphic fepresentation of NMR chemical shifts for the acyclic methine protons was presented. *pproximately 250 7-values were compiled and used. The correlationcharts presented here provide definite ranges of the methine proton shifts arranged according to the neighboring substituents, and make it easier to deduce the chemical structures from NMR spectra.
Spectrometry has been extensively used for analysis or identification of a wide variety of compounds, especially in organic chemistry. For this purpose the proton chemical shift can be used as a principal guide for solving the problem, and in this respect many efforts have been devoted to collecting and compiling the proton shift values for compounds with selected functional groups (1-7). In a previous paper we presented a graphic representation of proton chemical shifts for methyl and methylene groups arranged according to neighboring substituents. Now, as a continuation of the work, we present a similar representation for methine groups. The methine group seems PROTON MAGNETIC RESONANCE
(a,
1 Present address, Japan Electron Optics Laboratory, Ltd., Nakagami-cho, Akishima, Tokyo, Japan.
(1) K. W. Bartz, and N. F. Chamberlain, ANAL.CHEM., 36, 2151 (1964). (2) N. F. Chamberlain, Zbid.,31, 56 (1959). (3) M. W. Dietrich and R. E. Keller, Zbid.,36, 259 (1964). (4) C. Heathcock, Can. J . Chem., 40, 1865 (1962). (5) L. H. Meyer, A. Saika, and H. S . Gutowsky, J . Am. Clzern. Soc., 75,4567 (1953). (6) K. Nukada, 0. Yamamoto, T. Suzuki, M. Takeuchi, and M. Ohnishi, ANAL.CHEM., 35, 1892 (1963). (7) F. C. Stehling and K. W. Bartz, ANAL.CHEM., 38,1467 (1966).
b Figure 1. First subdivision chart for the shifts of methine protons of the type
X
I
3 C-CH-C
f
(a) acylated. (b) C13CCHC1CCl8. (c) (CH& CHOCH = CHZ. (d) [(CH3)KH0],P. (e) (CH~)ZCHCOC~H~.(f) (C2HsOOC)zCHCH(COOCZ~~~)CHZCOOCZH~.
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ANALYTICAL CHEMISTRY
to be most favorably identified by NMR spectrometry, because in other analytical techniques (for example, infrared spectrometry) information regarding such groups is obscured. However, methine chemical shifts have not yet been presented in a systematic manner. Thus, in the famous table of Tiers (8) there are relatively few chemical shift values of methine protons. The most extensive work so far presented is that of Dietrich and Keller (3), in which 124 methine shifts are given in a graphic representation, but the classification of the proton groups is not very detailed, so that the use of the chart is considerably restricted. In the previous paper (6),we proposed a classification system that is reasonable and convenient for compiling proton chemical shifts for analytical purposes, and it was successfully used for methyl and methylene protons. This system is comprised of main classification groups in which some subdivisions are included. The main classification is based on differences in the bond type of the carbon atom to which the proton is bonded, and on differences in the number of protons attached to that carbon atom. The first subdivision is made by both species and bond type of the atoms which are substituted at the a-position. Similarly, the second subdivision is made by species and bond type of the substituent at the @position, and so on. This classification system may be used for methine protons. But, as stated in the previous paper, the methine group may have three different substituents at the a-position, where the first subdivisions are made. Thus, the number of first sub(8) G. V. D. Tiers, “Characteristic Nuclear Magnetic Resonance Shielding Values for Hydrogen in Organic Structures,” Part I: Tables of 7-Values for a Variety of Organic Compounds, Minnesota Mining and Manufacturing Co., St. Paul, Minn., 1958.
x
Y
z 2
5
3
6
n
7
T
Hal -Cf. -CC
15
Hal -C4 -& Hal - C f 0 Hal - C f - 0 -
13 4 1
0
Hal 0 Hal Hal -C( Hal Hal
10
-k=
4
Hal Hal 0 Hal Hal Hal
4 4
-0-
-ce
29 13
'-0-
-ce 0
1
-Ct
11 4
-*-c=
-0-0-
I
I -0--c=
-eI
T -Value
2
5 I
1
I
11
-0- - C f -0-o--cz ( J -o--& (-J
-0- 0 0 -0--0- 8
8
- 1
-ce - c a
3 e)
3 1 1
I
3
4
5
6
Y
I
Figure 2. First subdivision chart for the shifts of methine protons of the type X-CH-Z (a) acylated. (aa) diacylated. (b) CISCCHCICCIS. (c) (CH&CHOCH = CHI. (d) [(CH3)2CHO]3P. CBH~CH(OH)COOCZH~. (f) C&iiCH(OH)COC&.. (8> CHScE(ca5)2. (h) (;C&. CI)~CHCC13-Halrepresents CI or Br
(e)
divisions is considerably larger as compared with methyl and methylene groups, and the second subdivisions which are made by the substituent at the P-position, are greatly increased in number. Thus, the formal application of the classification system leads to a formidable difficulty in handling the data. In fact, for the methyl and the methylene groups this difficulty more or less occurred, and was avoided by omitting uncommon combinations of the substituents in the subdivisions. For the methine protons in the present work, this convenience is widely used. In particular, the second subdivision is omitted. The effect of the substituents at the P- and further remote positions is usually smaller than that of the substituents
at the a-position. Thus, the former effect will be reflected in the methine proton shifts only within a rather smaller range, and in a complex manner because of the plurality of substituents at such remote positions. Conversely, many of the subdivision groups may fall into a given smaller range of the chemical shift, which, from the practical point of view, results in no useful information about the functional groups at such remote positions. In practice the detailed subdivision is also limited by sample availability. In the present work the methine protons are restricted to those with acyclic structures. The methine protons in alicyclic frameworks give rise to chemical shifts in a rather differVOL. 40, NO. 3, MARCH 1968
* 569
ent way from those in acyclic compounds because in more or less rigid ring structures, the anisotropy effect of a particular substituent is often predominant. The anisotropy effect is strongly dependent on the particular type of ring structure and, hence, such methine protons should be classified on a different basis.
7-Value
I
'
-Hal
EXPERIMENTAL
NMR spectra were obtained with a Varian HA-100 spectrometer at 100 Mc. Most of the signals were easily assigned and the chemical shifts of the methine protons were read directly on the chart from an electronic counter. Some of the spectra were obtained with a Varian DP-60 spectrometer at 60 Mc., in which case the usual sideband technique was used. For signals whose chemical shifts could not be obtained by simple inspection, double or triple resonance techniques were used. For broad signals which could not be expected to be simplified by the decoupling technique, the center of gravity of the signals was taken as a true chemical shift. The overall precision of the measured shift values can be expected to be well within k0.02 ppm, even if the uncertainty resulting from the measuring conditions and the small variation in the concentration of the samples is taken into account. The concentration of the samples was about 10% in CC14, as long as the solubility of the samples permitted. When the solubility was not sufficiently large to form a 10% solution, a saturated solution was used, and when the sample was insoluble in CC14, deuterated chloroform was used as a solvent, Most of the samples were from commercial sources and of reagent grade, and were used as such without further purification, The chemical shifts were expressed in 7values. These sampling conditions are the same as in the previous paper (6). RESULTS
Results obtained are shown in chart form in Figures 1 and 2. Figure 1 shows the graphic representation of methine protons of the type in which two of the substituents at the a-positions are saturated carbon atoms. The compounds with this type of methine proton are relatively available and, hence we could obtain a relatively large number of the 7-values. Figure 2 shows the graphic representation of all other types of methine protons. In spite of the very large number of possible combinations of substituents, the number of available samples was small, and only the measured types of methine protons are presented in the chart. In the figures the range of the chemical shift for the methine group shown in the left-hand column is represented by a horizontal thick line, with the vertical short line expressing the mean of the 7-values of the samples measured for each classification group. The figures in the right-hand column are the numbers of samples in the groups. When a small number of the samples in a particular classification group unduly extends the chemical shift range, the 7values of such samples are given outside the range shown by the horizontal thick line. For methine protons, this is quite necessary because many possible different functional groups in the 0-or further remote positions can cause large shifts from the remainder of the samples in the same group. If all of the values obtained in a group were included in the range, the
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ANALYTICAL CHEMISTRY
-0-co-
L
13
Figure 3. Second subdivision chart for some methine proton snifts R represents hydrogen atom or - C f Hal represents C1 or Br
group, and
chart would be almost impractical because of a small number of such samples. It must be mentioned that in the classification system
I I
adopted here, -C=C-
I
and & 0
belong to the same
I group -e, and the effect due to the difference between them, if any, should be represented in a further subdivision.
I
Actually, however, the number of the samples with -CH-
I I
C==C- was very small, and thus most of the samples classified
I
I
I
under -C= group are those with - C H - e O . No significant differences were observed between these two groups. The acylation shift for methine protons is observed to be larger than those for methyl and methylene protons. For the latter two groups, the differences between the average of 7values in a group before and after acylation are below 1 ppm (6). On the other hand, for the methine protons the acylation shift is so large that the differences well exceed 1 ppm. Thus the ranges corresponding to acylated and unacylated groups are represented separately in the first subdivision charts. The second subdivision chart is presented in Figure 3 for only two classification groups. It will be seen from the figure that the effect of the substituents at the @-positionis relatively small for the classification groups shown. But Figures 1 and 2 show many exceptions, in which large shifts caused by particular types of the substituents at the 0-positions are observed. Thus, for the methine protons, it seems to be difficult to find any general rule about the effect of substituents at the 0-or more remote positions. ACKNOWLEDGMENT
The authors express their hearty thanks to Tokyo Kasei Kogyo Co. Ltd., from which a majority of the samples were obtained , RECEIVED for review August 8, 1967. Accepted November 7, 1967.
