Graphic Representation of Proton Chemical Shifts General Consideration and Methyl and Methylene Groups KENKlCHl NUKADA', OSAMU YAMAMOTO, and TERUO SUZUKI Government Chemical lndustrial Research Institute, Tokyo, Shibuya-ku, Tokyo, Japan MAKOTO TAKEUCHI and MASAKO OHNlSHl Japan Electron Optics laboratory, ltd., Nakagarni-cho, Akishima, Tokyo, Japan
b To obtain a schematic representation of proton chemical shifts which could be used for rapid analysis of organic substances, a classification system for the protons is proposed. The system comprises the main classification groups in which some subdivisions are included. The main classification is by differences in the bond type of the carbon atom to which the proton is bonded, and 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 to the proton. Similarly, the second subdivision is made by species and bond type of the substituent at the /3position to the proton, and so on. By use of this classification system, the schematic representations of methyl and methylene proton shifts are given, Some trends of the proton shifts are observed from the results.
I
RECENT YEARS, high resolution nuclear magnetic resonance (NMR) spectroscopy has been developed to the point where it is successfully employed as a powerful analytical tool for a wide variety of hydrogen-containing organic substances. For analytical purposes, i t is most convenient to use chemical shifts to identify the various functional groups in the molecules. This method is based on the fact that a proton signal appears in a certain definite range, depending upon the species of the functional group or groups directly or indirectly bonded to the proton. The effects of substituents on the proton chemical shifts were studied with a variety of compounds by many authors. Among these, Shoolery (6) developed the method for estimating the proton chemical shifts of various compounds on the basis of the additivity of the effective shielding constants. Although this method is now
N
Present address, Basic Research Laboratories, Toyo Rayon Co., Ltd., Kamakura, Japan. 1892
0
ANALYTICAL CHEMISTRY
widely used by many investigators as a useful guide for identification of organic groups, it has some inconveniences in that i t cannot tell us the definite range of the chemical shifts shown by the proton in question. It is extremely desirable, therefore, that the proton chemical shifts are provided in a form classified by the nature of the proton, and, more preferably, that they are represented in some suitable scheme which provides the definite ranges of the proton chemical shifts arranged according to neighboring substituents. Several studies along these lines have been published. The first extensive work was carried out by Meyer, Saika, and Gutowsky (4) in 1953. Later Bother-by ( I ) , Tiers (6), Chamberlain (d), and Heathcock (3) also reported useful graphic presentations or tabulations of the proton chemical shifts according to their own systems. However, because of steady improvement of the equipment, and increased information about spectral measurements and standardization, such works need periodic revision. Furthermore, the elassification systems of previous works are not always satisfactory, for reasons which will be discussed. These considerations lead us to the necessity of developing a novel schematic representation of the proton chemical shifts which is more detailed and more systematic than the previous ones, and yet is more conveniently used for rapid analysis of functional groups in hydrogen-containing organic
substances. The principles on which the present work is based are as follows. The conditions for measurement are based chiefly upon those employed by Tiers (6), and the proton shifts are represented in 7-values. Classification of the functional groups was made as systematic as possible, but practical convenience was also taken into account. Homologue compounds in a classified group were selected so as to present a wide range of substituents in the groups. CLASSIFICATION SYSTEM
Proton signals in NMR spectra show characteristic chemical shifts due to the proton types or proton groupings in the molecules, where the proton type or grouping means a type of one or more protons which are contained in a certain radical or functional group. But in the literature, the proton types are arbitrarily chosen by many authors from various standpoints. For example, in the representation of Meyer, Saika, and Gutowsky (4),the characteristic chemical shifts due to proton types,
/
I
such as CHFC-, CHBN-, CHe, \ CHsO-, CHF, etc., are shown together in one graphic presentation. However, C H r also is often considered as a proton type in NMR spectroscopy, so that CH-Cy,
/
I
CH.,-N-,
and the
6
CH,Si t CH C ( 3
CH,C: CHC , = C H3SCH3Q CH,N( CH@CH8 \
, \
CH,-e- C f CH,-$- N( CH3-C- & = O CH,-$- Q
Figure 1. Schematic representa~ ~ 3 - c - o - tion of classification CH 3- Ssystem
C-
CH3- $- X \
like should be treated as finer subdivision of the CHa-- proton type. The group CH= or CHF should be treated on the same classification level with proton type CHa- rather than
I
CH8-Oor C H p N - . While the system used by Meyer, Saika, and Gutowsky may be s,Ltisfactory with a small number of clasrsification groups, with a large number of samples the proton group classific,ttion should be carried out step by stop in a more detailed system. Chamberlain (2), in his excellent representation, adopted a classification system obtained by se ecting a type of compound, such as alcohol, olefin, aromatic, etc., taking a suitable group as a reference--e.g., OH in alcohol-and classifying the proton as cy, 8, y, . . by its position with respect to the reference. This system is preferable in that the long range effects of one or more substituents can be expressed. But i t has some disadvantages because the types of cornpounds to be initially selected are necessarily increased in number as the classification system becomes more and more detailed. In other words, if chlorophenol, for example, is selected as E , particular type of compound, it is nat iral that bromophenol should also be selected in order to classify the bromophenol derivatives in his representation. In fact, both types are selected iri Chamberlain’s representation. Therefore, one must add new reference types to the representation whenever a different compound is to be classified. Furthermore, in his representation it is necessary that the reference type of the compounds be previously known, and this condition is not a1waj.s obtainable for some analytical purposes. The tabulations of t,he proton shifts values by Tiers (6) and Bothner-by (1) are very useful for Ending accurate values of particular compounds in the tables, and for obtaining by analogy the proton shifts of relsted compounds. But often it is desirade to know the proton shift range shonn by a particular proton type, rather lban the proton shift values of a particular compound, and to see the corre1,ttions of proton shifts among various types of protons. In this respect, the gr:tphic representation is preferred to the titbulation system. A representation of proton shifts, therefore, should be such that it provides easily-understandable correlation charts of the proton shil ts among various types of protons, which are classified according to a reasonallle system. The classification system .;hould be unaltered in principle by additim of finer subdivisions, even if new types of protons are added to the system. Considering these circumstances, we adopted the following classification
.
system which will be easily understood by referring to Figure 1. Main Classification. I n general, proton chemical shifts occur mainly as a result of electronic shielding effect and the neighboring magnetic anisotropy. Thus, the classification system t o be used here should be the system in which both effects will be properly reflected. I n the first classification step, therefore, we take the difference in bond type of carbon atom to which the proton is bonded, since the difference is considered to be an important factor in the above mentioned two effects. Thus, for example, protons attached to single- and doublebonded carbon atoms, respectively, are classified into separate groups. Furthermore, in the practice of NMR spectroscopy, methyl, methylene, and methine protons are distinguished from each other, the distinction being very convenient for the following reasons. In the first place, splitting of the signal by spin-spin interaction may often assist assignment of the signal or identification of the group. Multiplicity of the splitting depends upon the number of protons bound in neighboring equivalent sets in the first order approximation, Thus methyl, methylene, and methine groups give a quartet, triplet, and doublet, respectively, to the adjacent proton signals. This information is very useful in identifying the functional groups in the molecule. Secondly, it is well known that a proton signal is shifted by substitution of certain groups-e.g., halogensand the effect becomes more pronounced by increasing substitution of the groups, The distinction among methyl, methylene, and methine groups is again useful because the possible maximum numbers of substituents that the groups may have are different. From these points of view, the previous classifications, by difference in bond type of the carbon to which the proton is bonded, are further divided into some groups which differ in the number of protons contained therein. Thus, the proton group attached to singlebonded carbon atom is divided into methyl, methylene, and methine proton groups; the proton group attached to double-bonded carbon atom, into terminal and nonterminal olefinic groups -i.e., CH2= and -CH= groups. Thus, the main classification group consists of seven groups: methyl (CHs), methylene (-C&--), methine
1
(-CIX-), terminal olefinic (CI-IF), nontmminal olefinic (=CH-), acctylcnic (CH=), and aromatic proton groups. The bond type of an aromatic carbon atom is different from that of an ordinary double bond. The ring-currcnt contribution is appreciable in aromatic proton shifts, so that the aro-
matic proton group as a whole should be treated as a separate classification group. Distribution of proton shifts according to this system is illustrated in Figure 2. As will be seen from this figure, the distributions of proton shifts in one group extend over rather wide ranges, and the effect of substituents is also expected to be large. Further subdivision of each group is required for the practical use of such figure. Protons whose chemical shifts are seriously dependent on the concentration or the nature of solvente.g., -OH or -NH2 -are excluded from the present work. Thus, in our representation only proton shifts given by the protons directly bonded to carbon atoms are shown. Subdivision. The first subdivision is made by species and bond type of the substituent atom adjacent t o the carbon atom bonded to the proton of the main classification group-that is, in the a-position to the proton. Thus, the first subdivision is rather different from the ordinary functional group classification. For example, in I I
our I Isystem, CH8-C=0
and C I I r
d=d-
belong to the same group in the first subdivision and the effect due to the difference between them, if any, should be represented in a further subdivision. On this basis the following nine substituents are selected for the first subdivision :
\
-N-,
-S-,
-Si-
\
and X-,
where Ar represents aryl radical and X represents halogen and other electronegative substituents. If each group of X- is bonded to a methyl group, i t is convenient for these 7-values to be shown in a table rather than on the chart, because they often consist of only one sample, and their chemical shifts differ considerably from each other. A particular compound is classified as follows: acetone, CIT&OCHs, belongs to the methyl-group main classification,
I
and to CHJ-C= in the first subdivision. Similarly, diethyl ether belongs to the methyl and the methylene groups in the main classification, and further, \ belongs to C H r C -/ and -C--CH\ / 0- in the first subdivision of the methyl and the methylene group, respectively. In addition to tlic :hove fundarncntal substituents of the subdivision, some other substituents, such as -N=, are also adopted. The number of samples iii these groups were small, so that only the approximate position of the proton shifts is known. VOL 35, NO. 12, NOVEMBER 1963
1893
Figure 2.
Distribution of proton chemical shifts among main classification system
!%E I
A
I
2 CH,k=
1
5~CH3N( 1 CH30-
I
732
A
__-___
Figure 3.
Z-Value-
--
First subdivision chart for CH3-
6
w
1
CHiC-CC
7 ~---8 7 - 7
I
I
1
9
4
...........
I
.
... .. ..........
i
CH,-N-Cf
'
Q'
31
6 0
1 11
CH;O-C~I Q
I
-c.o
I
Figure 4.
894
Min,Max No: 8901 9 2 1
51
I
l 877
905
877
896
4
868
880
E
14
856 902
33
___
!
812'851
/ I
7 8 6 841
25
7 3 2 8 0 5
31
7 8 9 8 0 3
8
7 5 9 8051
IO
7 6 9 794
3
7 32 7 5 5
5
EXPERIMENTAL
I
I
I
1 -
-
-- ~ _ _ _ _
A I
1
766
786
5
4
690
729
4
A
695
726
5
653
676
II
614
639
6
604
643
12
L
A
I
I
-~ --
Z-Value-+
IO
I
1
,
572 7 8 4
I
-Cf '
I
I
I
-CCCI Q l
33
847,877
CHjC 0 - O-
i
18
876
I
~
-x
690 788 598
--i
-0 -S-
20
proton shifts
Q
!j
3
I
'
~
-L
1
-N( 40
,
58
7 4 2 ' 798
7 - I
I
841
~ ~ _ _ _ 7_24 _ 1 7 86
CH,X
,. ..
I
I
CH,SCH,Q
46
L 7 8 8 817
L
I
923
812
The number of constituents in the first subdivision of a main classification group may be determined by the number of bonds through which nine or more types of the substituents mentioned above may be bonded to the carbon atom of the main classification group. Thus, the main classification group CH3- may have a substituent a t the a-position to the methyl proton, so the number of subdivisions in CH3- is nine or more. In the case of the main classification group, - C H r , there are two such substituents a t the cY-position to the methylene proton, so that if n substituents are used, n(n+1)/2 subgroup will be divisions in -CH2obtained, the number being very large. Further, in the case of a methine group, a great many members of the subdivision may be found. This brings the system into extremely troublesome conditions. From the practical point of view, however, formal combinations among each of the substituents are not always necessary, and uncommon combinations may be omitted for most of our purposes. This consideration leads to some reduction of the number of subdivision groups. Availability of samples also limits the subdivision number. The second and further subdivisions are made by substituents a t the b, y , . . . position to the proton of the main classification group. In principle, each of the first subdivision group can be further divided into nine or more in a similar way. But finer subdivisions do not always have practical importance because of the smaller differences in chemical shift ranges and the experimental errors which must be taken into account. The second and further subdivisions, therefore, were carried out only in the case where the distinction in proton shift ranges thereby obtained was clearly noted or the subdivision was considered t o be of some practical importance.
1
6
7
8
9
Second and further subdivision chart for CH3-
ANALYTICAL CHEMISTRY
proton shifts
The proton magnetic resonance spectra were obtained with a Varian Associates DP-60 spectrometer equipped with a V-4311 R-F unit a t 60 me. and a Japan Electron Optics Lab. JNN-3 spectrometer a t 40 me. Chemical shifts were measured with the usual side band technique. The mean error was within 10.02 p.p.m. If a signal consisted of unsymmetrical pairs of peaks, the center of gravity of the peaks was takrn as the true 7-value. Coiimercially - availablr, rragentgrade samples were used without further purification. Some of the samples were provided from various institutes or lnboratorieq in ,Japan. They were h u f f i ciently pur(' for N l I R spectroscopy. According t o the previously mentioned principles, the samples were
,
3 C -CH,-SI f I 3C-CH2-CC 2 SC-CH,-C= >C-CH,C 5 S C-C H,-S QCH,-CC
l
;::~ :::
69 25
17.20
7871
15
703
761'
9
66 6.40
7s381
6.80
693'
4
6.75
6981
3
I
I -_
1
3 SC-CHgN( SC-CH2- I I =C-CH,S 4 =(!-CHfL=
1
4
19 0 3 9 4 9
'
SC-CHfBr I = C - CH,N( >C-CH,-N = >C-CH,-CI :C-CH,-N( aCHfk=
-
QCH2-S I =C-CH,-Ci I =C -CH2- I 5 :C-CH,-OQCH2-Q I -CH2-I -C-CH,-Br 6 QCH,-N(
772
38
6 0 8 ~ 7 30
7
' 6 3 7 674
8
, I
9
707
621
6 I
6 39
6 66
II 6 31
665
6 I2
6.76
603 5.97
655 6 55
I
7 4
5
J5.92
1
2
6 I6
l
659 631
1552
664
604
6 19
4
2
1
2
4 2
5
I 1
__
~
-
1-
I
1
595
6 18
2
I
557
668
II
I
5.63
6 30'
6
I
=
C- CH,-Br CI-CH,- C-
2
I
=C-CH,N= I =C -CH,-CI CI-CH,- P= >C-CH,-N02 >C-CH,-F Q C H,- Br QCHiCI -0 - CHfO 7 1 rC-CH,-OI =C-CH,-03 QCHiO1 B r - C H,- Br CI-CH,-Br C I-C H,-C I 1 CI-CHiO-
I 5.87 5 . 9 1 ~
l
I
1 ~
I
-
--
542
1
IO
608
I
I
I 563
~
I
572)
2 I
I ~
4
5 . 5 7 , 5.6C
I 5.55
4
5.I8l 559
5
5. 04 5.99
I O
540
I '
4.93
5.83
8
4. 6 6
5.66
18 I I
I I
i
I
I
4.49
, 465'
I ' I
I
2
1
L...I
VOL. 35, NO. 12, NOVEMBER 1963
1895
measured in 1 to 10% CC14 solutions with tetramethyl silane as an internal standard. If the samples were insoluble in CC4, 1 to 10% chloroform solutions were used. About 0.5 to 0.7 ml. of tile solution was sealed in a cylindrical glass tube of 5-mm. 0.d. and measured with scan speeds of 1 to 3 C.P.S. per second. Needless to say, the homologue compounds were carefully selected. The extent of chemical shift ranges in a classification group is due to the variations of the substituents, which will be subdivided in the next classification
step. Thus, the homologue compounds in the classification group should be selected so that they include as many variations in the functional groups as possible. The large extent of the chemical shift ranges are sometimes due to a small number of the samples which show considerably different chemical shifts from the remainder of the samples in the same group. These samples should be listed in another table -e.g., Tiers' table (@--so that they are excluded from the correlation chart shown. As an example of one of these
samples, the compound in which two or more halogen atoms are substituted to on the same carbon atom, which is at the 8-position to the proton-e.g., CH&HClz for the methyl proton-can be mentioned. r-Values given by protons having more than one substituent at the pposition are excluded from the correlation charts without further specification. RESULTS A N D DISCUSSION
In this paper the graphic representation of the main classification groups
-C f
3C -CH;
-N(
I '
8.46' 9.02 8.38
~
7. 9 7
-X
i '
II
8.67
8.341
3
II
-c=o Ct
3CCHiN
voltammetric indicator electrode. The ions chosen are representative of a VOL. 35, NO. 12, NOVEMBER 1963
1867
ACKNOWLEDGMENT
The authors express their hearty thanks to G. Van Dyke Tiers who kindly permitted them to quote 7-values from his table. They are also indebted to Shueo Hattori of the Nagoya University and ToAimasa Seki of the Japan Electron Optics Laboratory, Ltd., for their valuable discussions, to Yoichiro Mashiko and Shinnosuke Saeki of the Government Chemical Industrial Research Institute, Tokyo, for their
kmd encouragement throughout this work, and to many institutes and laboratories which provided the valuable samples. LITERATURE CITED
(1) Bothner-hy, A. A., Glick,
R. E., “NMR Spectra and Structure Correlations, Vol. 1, Mellon Institute, Pittsburgh, Pa., unpublished notes, 1956; Bothner-by, A. A,, Naar-Colin, (2)C., chamberlam, Shapiro,B. L., N, Ibid., F., Vol. 2,CHEM, 1958. 31,56 (1959).
(3) Heathcock, C., Can. J . Chem. 40, 1865 (1962).
(4) Meyer, L. H., Saika, A,, Gutowsky,
H. S., J . Am. Chem. SOC.75,4567 (1953). (5) Shoolery, J. N., Technical Information Bulletin 2, No. 3, Varian Assooiates, Pa10 Alto, Calif., 1959. ( 6 ) Tiers, G. V. D., “Characteristic
Nuclear Magnetic Resonance Shielding Values for Hydrogen m Organic Struetures,” Part I: Tables of T-Values for a Variety of Organic Compounds, Minnesota Minipg and Manufacturing CO.,St. Paul, Mmn., 1958. RECEIVED for review February 18, 1963. Accepted June 24, 1963.
Precipitation Chromatography Separation of Metals as Ferrocyanides on Filter Paper ADELE M. LllMATTA and JAMES D. SPAIN Department of Chemistry and Chemical Engineering, Michigan College of Mining and Technology, Houghton, Mich.
b
When a mixture of certain metal ions is allowed to flow from a capillary tube onto a piece of filter paper impregnated with a precipitating agent such as manganese ferrocyanide, concentric rings af metal precipitate develop. These rings form in the order of increasing solubility, since more soluble precipitates will form only after the metal ions of a less soluble one are exhausted b y the precipitation process. A procedure for separation and identification of 1 1 ions which farm insoluble ferrocyanides is described. If the precipitant is dispersed uniformly on the paper, then the area of the spot produced is proportional ta the total number of equivalents of metal ion applied. A quantitative procedure which is based on this principle is described and certain variables in the procedure are discussed.
Figure 1.
impregnated with precipitant and dried. The impregnation technique has been used by Velculescu and Cornea (6) for the separation of halide ions using silver nitrate. Nagai (4, 6) has puhlished several papers on the separation of metal ions using 8-quinolinol. Vyakhirev and Kulaev (7) carried out an extensive study of metd ion separation using papers impregnated with a variety of soluble precipitants. Using this technique, Kulaev in a later paper (3) related the size of the spot to the solubility product and the concentration. The diameter of the spot varied inversely with the solubility product constant and directly with the concentration. These relationships, which were derived with the use of soluble precipitants, did not bold true for the insoluble precipitants employed in the present investigations. The importance of using an insoluble precipitant was first appreciated by Clarke and Hermance ( 1 , $). These investigators separated various metalion pairs using papers impregnated with insoluble cadmium sulfide, zinc ferrocyanide, and barium carbonate. Another contribution of these investigators was the use of an elaborate capillary applicator so that the sample flowed from essentially a point source. The present investigation is intended
PRECIPITATION
CHROFTOQRAPHY is a differential migration procedure in which a distribution takes place between a nonmobde precipitate and mobile ions in solution. Separations result from differences in the well known solubility product equilibrium. Either gels or filter paper can be used as the supporting medium. Precipitation chromatography on paper can take place by simply placing a drop of precipitant on paper followed by a drop of solution containing the metal ions to be separated. Such a technique haa been employed by Zolotavin and associates (8, 9 ) for the separation of anions using silver nitrate, and for the separation of metallic cations using potassium iodide. A more elegant procedure is to employ a paper which has been previously
1898
ANALYTICAL CHEMISTRY
Apparatus
to provide the basis for both qualitative and quantitative application of the type of precipitation chromatography which employs papers impregnated with an insoluble precipitant. A type of capillary apparatus is introduced which greatly simplifies the technique, and makes it possible to run several samples simultaneously.
Method of Preparation of Manganese Ferrocyanide Papers. Strips of Whatman No. 1 filter paper, approximately 7 em. by 30 em., were dipped into a solution of 0.1M potassium ferrocyanide and blotted between two strips of the same paper to remove excess solution. The papers were then rolled loosely and placed on edge on a hot plate or in an oven until dry. Then they were submerged rapidly in a solution of manganese nitrate containing Mnt2 in a concentration of 0.2lM and allowed to stand in this solution for approximately 5 minutes. Next, the papers were blotted and‘placed in a water bath for a few minutes to remove excess reagents, blotted again, and dried in the same manner as before. The order in which the reagents were applied to the paper bad a distinct effect on the type of chromatograms obtained. If the manganese solution were applied first, followed by the potassium ferrocyanide solution, the spots obtained when the paper was used had quite irregnlar boundaries and a light ring always formed around the spot during the washing process. When the potassium ferrocyanide solution was applied first, followed by the manganese nitrate solution, the spots obtained bad more even boundaries and the halo effect previously produced by washing was completely absent.
