Download structure and substitution. Thus, the culties associated with

?
-
INTRODUCTION:
The history of
I^C
nuclear magnetic resonance (cmr)
spectroscopy has mainly concerned the recognition and cor-
relation of regularities in carbon chemical shifts which are
associated viith structure and substitution.
Thus, the
greatest share of cmr studies have concerned the gathering
and interpretation of chemical-shift data for a series of
closely related organic compounds.
Because of the diffi-
culties associated with peak assignments, a number of quanti
tative correlations between structure and carbon chemical
shifts have been devised,
so that it is presently possible
to estimate the cmr spectra of many compounds for vihich the
structure is known.
1.
2.
1-4
Despite its
enormous potential In
H. Spiesecke and W.G. Schneider, J. Chem. Phy5. ,35.722
(1961)
D.K. Grant and E.G. Paul, J. Amer.
(1964)
,
ibid
.
Chem. Soc.
,
86,
2984
,92 ,1338 ( 1970)
3.
J.D. Roberts et al.
4.
D.E. Dorraan and J.D. Roberts, unpublished results.
structure elucidation, cmr spectroscopy has been used surprisingly little in this purpose.
In fact,
given
an unknown
compound, it is not at present a simple matter to elucidate
its structure using only cmr data.
,
The purpose of the present proposal Is to suggest
ways in which cmr spectroscopy can be more efficiently used
in structure elucidation.
Specifically,
we will concern
ourselves with the proposed incorporation of cnr spectroscopy
into the DEI DEAL program devised and developed at Stanford
University.
5-9
As did these earlier workers, we villi at
,
5.
J. Lederburg, et al.
6.
A.M. Duffield, et al.
7.
G. Schroll, et al.
8.
A. Buchs, et al.
9.
A. Buchs, et al.
J. Amer. Chen. Soc.
,
,
91, 2973 (1969)
ibid., 91, 2977 (1969)
, ibid. , 91. 74^0 (1969)
, ibid. , 92, 6831 (1970)
, Helv. Chira. Acta, 53. 139^
(1970)
present limit ourselves to saturated, acyclic, monofunc-
tional (SAH) compounds containing only carbon, hydrogen, and
nitrogen, oxygen, or sulfur.
We villi also include simple
hydrocarbons in the following discussions, even though these
compounds have apparently not yet been considered by the
Stanford group.
In the following discussions
vie
will assume that mass
and proton magnetic resonance (pmr) spectra are available
in addition to the cmr spectrum.
reasons for this assumption:
There are good practical
presumable, anyone who has a
cmr spectrometer available will also have access to a proton
magnetic
resonance machine!
There is a considerable advan-
tage in assuming the availability of all three spectra, as
these three spectrometric methods are complementary.
Thus,
mass and pmr spectra are very useful in elucidations of the
structure near a functional group.
dues are present, hoviever
,
When large alkyl resi-
these spectra become rather com-
3
plex and
difficult to Interpret.
The cmr spectra of alkyl
groups are quite well resolved under full proton decoupling,
however, and there is accordingly many more usable data
available for the elucidation of such structures.
In principle the simplest approach to the incorporation
oi
cmr data into DENDRAL is its use in elimination^possible
structures vihich
spectral
data.
are generated on the basis of mass and prnr
Such a method would allow us simply to apply
the extant correlations available for carbon chemical shifts. - 7
The writer has chosen, however, to attempt to show that carbon
chemical shift data is potentially of enormous aid in the
preliminary-inference-making
stage.
Unfortunately, data are
lacking for some critical compounds, such that in some cases
our contribution to this stage of the process will be rather
limited at present.
An important remaining question regards the cmr data
which will be generally considered available.
Single fre-
quency off-resonance (3FOR) decoupling data would, for example,
be of great use in some cases.
These data are not always
easily available, however, and for the moment will not be
considered.
Proton coupled spectra contain an order of mag-
nitude more data, but such spectra are rarely available.
/
Every fully proton-decoupled spectrum, however, makes avail-
able both carbon chemical shifts and relative peak inten-
sities, and these data will therefore be utilized in the
following discussions.
The importance of peak intensities
is in their ability to detect symmetry in the molecule
and /or its parts.
Thus, peak Intensities could easily be
used to distinguish between tertiary- and iso-butyl groups.
The survey of carbon chemical shifts used in the discussions below does not represent a complete literature
search, but was derived from a compilation of the cmr
spectra of approximately
700
compounds.
Ihis compilation
,
vihich was collected by the author, includes several hundred
compounds which are cyclic
and/or
polyfunctional ,
so that
the following discussion is based upon the cmr spectra of
less than 200 compounds.
The reader must be warned, there-
fore, that many of the writer's conclusion are based upon
rather few data, and may therefore be unreliable.
Efforts
to extend this compilation, and the associated data retrieval
program, are presently under study.
PREIIFIGAFY-II
T
t?
t-ft
rr
Carton chemical shifts in SAM compounds span approximately 200 parts per million (ppm).
As shown in Figure 1,
2
sp -hybridized carbons resonate at lowest field, and
indeed
any resonance vihich occurs at lower field than approximately
85 ppm relative
to carbon
to such a carbon.
disulfide can immediately be assigned
Within the chemical-shift reange of 90 to
125 ppm are found the
simple alkyne carbon
resonances.
This latter range overlaps with that of sp -hybridized car-
bons, vihich extends to nearly 200 ppm.
Within these broad spans of chemical shifts are found
smaller ranges vihich are associated with similarly substituted carbons.
Tor first-row elements at least, the
5
electronegativity of a substituent is qualitatively related
to carbon chemical shifts.
Thus, carbons bearing hydroxy l
groups resonate at lower field than do carbons attached to
nitrogen
or carbon.
Within these more limited ranges of chemical shifts
shown in Figure 1 there are smaller but
variations.
equally important
One of the most important effects is the
dependence of carbon chemical shifts upon chain branching.
In Figure 2 is defined a molecular fragment which will
be used in simplifying the following discussion.
In all
cases we will be considering the dependence of the chemical
shift of
C°
proximity.
upon the number of carbons (C a ,C
a
c
and C ) in its
If the hydrocarbon chain branches at
example, there is necessarily
C
,
carbons.
C°,
an increase in the number of
In general, each carbon C
o
is associated with
a 2 to 10 ppm downfield shift in the resonance of C
the chemical shift of carbon 2 in 2-methylpentane is
ppm lower field that the C-2
for
resonance of pentane.
downfield shifts are associated with the number of C
.
Thus
5.2
Similar
carbons,
such that branching at C will also lead to downfield shifts
o
in the C resonance. Unfortunately, these generalizations
fail in cases of extensive branching, such that the resonances
of quaternary carbons
analogs.
of C
c
are frequently upfield from tertiary
Branching at C b (i.e.
,
an increase in the number
carbons) generally is associated with smaller upfield
shifts, while branching at C
only a very small effect.
or more distant centers has
6
C
o
C
a
C
cc
b
Figure 2:
A definition of the symbolism used in the
panying discussion.
accom-
Finally, it will be helpful to note the effects of
replacing C
a,
C
b
,
or G
c
with heteroatoms.
noted that replacement of C
a
We have already
with a more electronegative
atom leads to significant downfield shifts, Somewhat surb
pri singly, the replacement of C with a heteroatom has a
much smaller effect
on the chemical shift of the G
resonance.
Thus the chemical shift of the methyl carbon of ethanol is
only about
ment of C
c
ing the C
2.5 ppm downfield from that of propane.
Keplace-
with a heteroatom has the opposite effect, shift-
resonance slightly upfield, so that the methyl
resonance of 1-propanol is about 2 ppm higher field than
that of butane,
i'iore remote substitution by a heteroatom
has little effect.
It is obvious, therefore, that generali-
zations based upon the extensive cmr dsita for the acyclic
alkanes villi be useful in elucidating the structures of
alkyl chains in SAM compounds.
Before progressing to a detailed description of the
ways in which the writer proposes to use these generalizations
in the identification of unknowns, it is necessary to mention
another simple and convenient use to which cmr data may
be applied.
Proton-decoupled cmr spectra of even compli-
cated molecules are generally completely resolved.
Coin-
cidental overlapping of carbon resonances is infrequent,
particularly so for SAI. compounds.
This leads to two useful
First, any overlapping of resonances
data.
shown by rela-
tive peak intensities suggests that an element of symmetry
exists within the molecule.
This symmetry may be due to
molecular symmetry or to chemical shift equivalence induced
by rapid rotation around single bonds.
Hence, tert-butyl
groups are characterized by the occurrence of two peaks of
3:1 relative Intensity in
158
to
165
ppm.
the region of chemical shifts
The recognition of such a group would
allow the DEFDRAL program to consider only those molecules
having such partial structures.
Secondly, the simple cmr data also give important
Information regarding the size of the molecule.
Hence,
the number and relative intensities of the carbon peaks
give a lower limit for the number of carbon nuclei in the
molecule.
An element of molecular symmetry can lead to the
occurrence of fewer peaks than carbon atoms, but in no case
villi there be more carbon resonances than nuclei.
This
fact allows the program to consider only a limited number
of possibilities while it is generating the empirical for-
9
-1
mula, which is required as input for the DS7DRAL algorithm.
We shall
now proceed to a detailed discussion of some
of the SAM compounds represented
in Figure 1.
At present
our discussion will be limited, to those classes of compound s
which have received prior study by the DENDRAL group, or
which have been extensively
Ketones and aldehydes:
studied in these laboratories.
Those compounds which have been
designated by the Beilstein system as "oxo-derivatives"
0
are readily Identified by the presence of a single carbon
resonance
downfield from the chemical shift of
occurring
carbon disulfide.
The carbonyl
ketone (acetone) occurs at
absorbtlons
value.
resonance of the simplest
-11.3 ppm, and
the analogous
of all other ketones are found downfield of this
This is an entirely reasonable result and could
have been predicted on the basis that the carbonyl carbons
of
more complicated ketones must by definition have a greater
number of C
carbons (Figure 2).
In fact, a breakdown of
the chemical shifts of ketone carbonyls shows that the positions of the resonances are related to the extent of branching at the
fl(-carbon.
The chemical shift of the butanone
carbonyl, for example, occurs at
-13.8
ppm,
while that of
3-pentanone is found at -16.2 ppm. In fact, ketones with
b
tvio C carbons (3-pentanone, 3-methyl butanone, etc.) display resonances in the range of -16 to -17 ppm, while ketones
involving more extensive branching are found to have lower
field
resonances.
The results are summarized in Table 1.
At present the chemical shift of only one aldehyde
(acetaldehyde.
<J C
_
0
6.0 ppm) seems to be available,
= -6.0
but we may expect similar trends to be observed for these
compounds.
Although the chemical shift ranges of aldehydes
and ketones villi probably be found to overlap to some degree,
they are very simply distinguished by the presence or ab-
sence of the low-field formyl proton resonance in the
pmr spectrum.
Thus,
vie
can expect that the cmr spectroscopy villi
be very useful in aiding in the identification of oxo-
TABLE 1:
Chemical Shifts of Carbonyl Carbons in Representative
Ketones.
Ketone:
#/C
b
C=o :
acetone
0
-11.3
butanone
1
-13. 8
3-pentanone, 3-methylbutanone
2
3 3-dimethylbutanone , 2-methyl-3-
3
-17.9 to -19.3
2,2-dimethyl-3-pentanone, 2,4-dimethyl-3-pentanone
4
-20.6
2,2, 4-tr imethyl-3-pentanone
5
-24.6
2,2,4,4-tetramethyl-3-pentanone
6
-22.6
.
pentanone
-16 to -1.7
to
-22.6
9
compounds.
Furthermore, the identlcatlon of an unknown as an
oxo-compound
,
in conjunction with the number of carbons in-
dicated by the cmr peaks, specifies the empirical formula of
the compound.
Finally, data regarding the extent of branching
at the 0(-carbon are inherent in the chemical shift of the carbonyl carbon.
graphs^.9
Hence, the number of possible structural sub-
necessarily considered by DEKDRAL and tested against
the mass spectral data are significantly reduced.
Alker.es :
these
Because the alkenes have been extensively studied in
laboratories,^
they villi be briefly discussed in this
The presence of a carbon-carbon double bond is
proposal.
signalled by the occurrence of a carbon resonance in the range
of
45
to
85
ppm.
If there is only one peak, then there exists
some form of two-fold symmetry passing through the midpoint
of the
pound
double bond,
and the possible structures for the
are significantly limited.
com-
Again, having specified the
unknown as an alkene, it is but a small step to the specification of the empirical
formula.
Alkenes which are not symmetrically substituted, however
,
have tvio alkene carbon resonances which are significantly
different in chemical shift.
Substitution of the alkene moiety
results in large downfield shifts in the resonance of the
directly substituted sp 2 -hybridized carbon, while the remaining
alkene carbon resonance is shifted upfield by smaller increments.
In Table 2 are summarized the
vir iter's
initial approaches to
the use of these data in the preliminary-inference-making
process.
It is noted that 1 ,2-di substituted alkenes in which
\eX\t
jL'ir
Cm^JcJ
2'
j/«t+*
_<J
■yia^..
G^r^i.
0
i.
TYMftS- G
ci :
I,\.
-
- 2 'rj
x«.-C
x->-.- c.
07
- 3-ocK^
z:
;
sj
J~
"'.
i's
"
i
- _. - /?/v\ v"'-"-A-C_
>
s.
I
-51
,'A \
I
i
I
/
0
XV-WW-j-p-nta
I
il I ■'_
v
eJ
""
.;
4/
]
*~
!
.?.
-_-
H
. .err. i-i"
y'
i
£.3
;c4.
«.*/#/.
o
/;-U
as las
o
izs.o
13,4-
\7$,D
al) M.I
o
wr.i
/ft. I
JU
nio
x
Vti/ftA
/fo
1X6.2
1
K^im JJo
\u.i
w/i/.l
4U
/*u
A.
22
0
A
/. U
I. | '' :
M.4/K4
4<s
3
i 20
A>
W3/^.O
'°
/*M
*?,3
.29-3
X
ftU
!Q
3
ISLI
M
I
310
T
i
.
s\
s^
r
-v
cKs-
fG
_
1
(""\
(,*N
*-^
""31)
AJ
*30
r.
'>/■/'
, *i f
.ui
1
1
o
!
i
.-.
.--
Uo
Mm\
f,4
/-;?,?
i-aetvi^^
??.?
■>',*
AT.*1
JA.. i
. .XW_,
62.4
\&A
4,J
(?xo
i
311
"T
70,0/6-.4
lb
1-0,4
3.
2\o
!^:
Ct%(bU
9-. 5
/3.,4
X
211
/ 1
A" h'i .-70
'
l
h.yax
a<|
/1
r
" p4«H*"*_
Cii-'H-.K
"-■'.: -A-
pi
_-
k:>7— ''"''".! 'l-p>h. U.z150.%
J±nJ~oJ^L
7
1
!■
-
M
y
fai/itf
G:i
)30.y
Ztflll.X
577'
130.1
W.r/4fl 3^.6
fS/,4-
sr.i/4.4
3J,r
i#.y
x
210
7yf/i/,o
?_r
/31.5"
X
210
cj>l->-J.l )-Ui~><~
liiiill
US
lilA
cji'l-r-J J
WlfsSA
%L4-
I3ZX
A-i
il
o
'
;
'
1
>~
'
J
ll i Ij I I
L -bi-^c
o
1
XII
rt
"
i
-J
'
i
2/1
\J
1 : ,_"
V
wl- >
u
"
-
A c r -r l
/-:c<.-l
" C
Vii l lvr
'*
_
_q
1
.
I
11. <"■
fc.l
f32.r
U< y>J4-l~.yJ-^- KA/tt,\
lIS
,33.7
fe-3-iiJU^U*u- 74.9/5?,-
IM
4-kJU? )-d**Lu
ffllss.l
u.l
I- a. It
V'
-?_4
1
w
|~W
,»
"'■"<:
l* V7 -."?..I- -p-^-^^
"'
KA "?
7M/5W
'
14
"
I
10
/
j
r
o/*- 1 1
yy
I
3!o
T
lil.T
I
ill
T
(3?. I
3
uj.
I-
1
iO r
M'tf.r X6fl
'y
1
1
?
" a" i'.'y- ■»-
31 !1
-_■
3 //
o7'T/6/"t
Cj}
y
1
111
A
iA
I is> i
3
110
i?4
<
3
111
1
I3U
3
111
A
v\
,\g-''
2,S^;,i>k
' / (W
H |-^
.-vi.fftHJ
":r
#.*/tf\<
'' - /
4,0
p. j*
mhis
10.3
|?C '
3
f.^7 - 7- G'Gv c , .'
o r- t // & i
0
WoA
2
■
V
1.35M
A
I
v
\7
Uo
—
-i
?_ O
'
0
4L
.
I) j - j ]
d\-ij7J
X- IMfVC
*V
,
J
I
«'?
!rl i
tililI lbi*l
ny
,5_
7c,4/-y4
o
140,2
u
/41-S
/
M'Y/V
I
/P.
I
I
-d ~ ri-*-'"'
-'U-S-.VftJ
I
<-^
!
f
y
-
«
r1
4
i
00 o
4.
*
1
Zoo
11
/
i
0
S u-*«n
'
T^-
p*V
n
—
7H.
H/a-wo-v
yci'^- , /.*<
«y
two
uTn-lt"-.
Cockf
pv©r*^
W'H
**.
/
-10-
the double bond is at least two carbons removed from the end
of the hydrocarbon chain possess the lowest £- values, which
represent the sum of the two alkene carbon chemical
shifts.
It is also apparent that the alkene chemical shifts for these
compounds do not differ greatly U3_-valt.es),
is branching at the allylic carbon
pentene).
(e.g.
except when there
, cls-^- methyl-2-
The monosubstltuted and 1 ,1-di substituted alkenes,
however, have typically large A-values and intermediate
values.
2-
Furthermore, the sp 2 -hybridized methylene groups of
these compounds typically have chemical shifts which exceed
77 ppm.
Though many details remain to be worked out, it is
hoped that these considerations, taken in conjunction with
the integrated intensity of the vinylic proton resonances of
the pmr spectrum, will allow the construction of specific
subgraphs.
Alkynes:
Acetylenic hydrocarbons have also been studied in
these laboratories, and many of the conclusions above
re-
garding the alkenes are applicable with minor variations to
these compounds.
Thus, substitution of an alkyne moiety
"polarizes" the chemical shifts of the sp-hybridized carbons
in the same sense as in the alkenes.
Unfortunately, our
analysis of the chemical shifts of alkyne carbon is incomplete,
and it is presently impossible to state whether cmr spectra
will be as useful in the detection of chain branching as is
the case for the alkenes.
Because the alkyne range of chemical shifts overlaps
those of the alkanols and aliphatic ethers,
"
it is necessary
1
to note that carbon chemical shifts alone are not
to differentiate these classes of compounds.
sufficient
Cmr data can,
however, narrow the number of possible classes to these three,
thereby allowing the program to choose which of the mass and
pmr spectral tests to apply.
Alcohols and ethers:
Although the alcohols have been systemat
ically studied, 3 there are rather few data available for the
aliphatic ethers.
Most of the compounds which have been
studied have been methyl ethers, and for these compounds
at least there are indications that the ethers will show the
same trends as
observed, in the
of compounds have the
alcohols.
Because both classes
same general empirical formula, the cor-
rect empirical formula of an unknown alkanol or ether follows
immediately from the determination of n from cmr data.
The chemical shifts of alkanol carbons show the same
dependence upon branching as is observed for the alkanes. 3
Thus, the lowest field carbinol carbon resonances are assoc-
iated with tertiary alcohols, or with cases in which there is
extensive branching at the adjacent center.
The carbinol
resonances of linear, primary alkanols are found at approximately
ppm, varying from this value only when there is
b
a
branching at C or C
Secondary alcohols are generally found
130
.
near 125 ppm, though extensive branching at C a can lower this
value to less than 110 ppm.
It is seen, therefore, that
it is not possible to determine the extent of branching on
the basis of carbon chemical shifts alone.
Used in conjunc-
tion with the Integrated intensities of pmr signals near
,
12
however, it would be possible to limit to some degree the neces
sary OC-cleavage tests based upon mass spectral data.
Further
correlations of the chemical shifts of carbinol carbons are
presently being planned
.
Amines, thiols, and thioethers:
Unfortunately, there
are
presently extremely few data regarding these compounds, and
it is not possible at present to contribute to any signifi-
cant degree to the recognition of these classes.
Because
the ranges of the chemical shifts of these compounds overlap
with that of the alkyl groups, it is not likely that cmr
chemical shifts will be able to contribute any significant
information regarding the environment of the heteroatom,
unless the heteroatom has been previously identified.
Conclusion:
Obviously, above
125
ppm it is
more difficult
to use simple cmr data in preliminary-inference-making.
Further discussion of techniques in which cmr data might be
used in structural inferences must be based on the assumption
that the heteroatom, if any, has been identified.
section of this report is based on that
The final
assumption.
A schematic representation of the use of cmr data in
preliminary-inference-making is shown in Scheme 1.
FURTHER IGFFG'KI'-TIAI. USE OF CMR DATA:
We have found in the section above that it is difficult,
if not impossible, to distinguish between alkynes, alcohols,
ethers, thiols, thioether , amines, and even alkanes.
It must
Scheme 1:
IGHJT:
The Use of Cmr Spectra in Preliminary-inferencemaking.
<f(i),
-where
1(1), 1= 1,ffi
f(l)
= chemical shift of the i
external carbon disulfide.
resonance from
I(i) = an integer representing the relative
intensities of the peaks. All I(i) = 1
if all peaks are equally intense.
= number of peaks in the spectrum.
ffi
THE "UMBER OF CARBONS IN THE COKFOUFD
m
n «3El(i)
-where n
= the least possible number of carbon in
the molecule.
The actual number of carbons
can be any integral multiple of n.
CHEKICAL SHIFT TEST
In the test below, a "yes" answer results if there is
any
<T(i) in
the spectrum which satisfies the specified
specified
conditions:
1(1)
yes:
no:
I.
<
85?
go to I
go to II
J(i) (-.5?
yes:
no:
A.
go to A
go to B
1(1) (0?
yes:
no:
1.
go to 1
go to 2
Oxo-compound
a. Empirical formula = Cn Hg 0
b. Apply pnr data to distinguish between
aldehyde and ketone.
c. Use (i) to infer degree of branching
at oC-carbons.
Scheme 1: (continued)
2.
Carboxylic acid,
ester, or amide
sidered.
B.
Are there two
yes:
no:
Unsymmetrical alkene
a. Empirical formula =C H 2
b. Further tests to identify subgraphs.
2.
Symmetrical alkene
a. Empirical formula
= (cn
Further tests to identify subgraphs.
H2n^2
125?
go to A
go to 111
no:
A.
the prescribed range?
1.
1(1) <(
yes:
not yet con-
go to 1
go to 2
b.
11.
d(i) within
—
Are there two tf(i) within the prescribed range?
yes:
no:
1.
go to 1
go to 2
Unsymmetrical alkyne or unsymmetrical ether
a. Apply pmr and ins tests
b. Alkyne: empirical formula =C H
2 ?
c. Ether: empirical formula
c n H 2n+?°
-
2.
111.
—
or ether, unsymmetrical ether,
further tests necessary.
Symmetrical alkyne
alkanol
<f(i) /133?
yes:
no:
go to A
to E
p:o
A.
Probable alcohol, possible ammine.
3.
Amine, thiol, thioether.
13
be noted that most other spectroscopic methods would also
have difficulties in differentiating some of these classes
of compounds.
The point has therefore been reached past which
we cannot conveniently proceed without mass spectral data.
Current versions of DENDRAL make extensive use of fragmentations
induced by electron impact,
Q
and the present section is In-
tended to show that a judicious combination of mass spectral,
pmr, and cmr data can lead to a more efficient and discriminating program.
Reference to Scheme 1 shows that compounds with no cmr
resonance below 85 ppm cannot be unambiguously assigned to
a specific class of compounds using cmr data alone.
To pro-
ceed further,- we must deduce the empirical formula and identify the heteroatom, if any.
The latter problem is obviously
the first to be attacked, using the "plausibility score"
developed earlier.
9
These
scores might be calculated using
the following variation of the earlier method:
A
= Mass(X) + Valence(X) + Kass(CH)
"A" represents the mass of the lowest possible
peak in the
mass spectrum,
CH2=XHv _j_.
The symbol X repre-
sents the heteroatom (O,S, or IC), and vis its valence.
entire homologous series of ions
containing X, the
Mi
We
mass of the i
An
are possible for a compound
such ion being:
= A + ( lta )
now scan the mass spectrum, summing the intensities (J)
for this homologous series of ions:
n-1
Score = 22 J(IF )
I=o
*
where
n is the number of carbons in the molecule, as deduced
from the cmr spectrum.
If course the number of carbons could
,
if an element of molecular symme-
-
try exists in the molecule.
If peaks exist in the mass spec-
-,
trum at masses higher than:
actually be 2n or 3n, etc.
M
= A + l^(r--l)
then such a symmetry does exist and the empirical formula
should be adjusted accordingly.
The existance of such symmetry
has important consequences in further deductions, but this
matter will not be considered further in this report.
The scores determined in this way may be compared to
various empirical and theoretical tests, with the result
that the mo3t probable heteroatom is identified.
If the pro-
gram infers that no heteroatom is present, then cmr chemical
shift data may be used to identify the compound as either an
alkyne or an alkane, and the empirical formula follows immediately.
If the heteroatom is oxygen, then the compound is
either an ether or an alcohol; carbonyl derivatives would
already have been screened.
follow immediately.
Again the empirical formula would
Similar considerations would result in
the empirical formulae of sulfur- or nitrogen-containing
compounds.
The stage is now set for a series of mass spectral,
pmr, and
cmr tests to determine the superatom of the compound. 9
Hence, the
H-18
and
M-l?
peaks of the
be used to identify alkanols.
mass spectrum could
If the compound is by default
an ether, and if there exists in the cmr spectrum only one
peak below 130 ppm, it must be an C-methyl ether, a conclu-
15
sion which is easily checked via pmr data.
The choice of
these tests and the order in which they are applied will
require collaborative experiments
with the Stanford
group,
and will not be discussed further in this report.
But by definition SAM compounds consist mainly of
hydrocarbon residues, and these fragments are the ones which
are not easily elucidated using mass and. pmr spectra.
of the primary
One
concerns of our contribution will therefore be
the elucidation of the alkyl moieties.
In principle there
are two ways of proceeding with this task.
If one is to depend
upon the previous cmr studies, 1-4 one must allow DEKDRAL to
generate all possible structures consistent with the inferences
made to this point, calculate a cmr spectrum for each possibility,
2-4
discarding those structures which have an empiri-
cal cmr spectrum significantly different from the calculated
one.
i-'or larger compounds, however, there
mous number of possible structures.'-5
preferable to
are often an enor-
It would therefore be
use the empirical cmr data to further limit the
number of possibilities before structure generation is begun.
Fortunately, there is a vast pool of data for alkyl
groups upon which we may base our conclusions.
.
At the present
time the author has stored in a form convenient for data
retrieval well over
range of
500 carbon chemical shifts within
150-185 ppm.
the
The difficulty lies in the fact that the
data are so numerous that detailed correlations have not yet
been concluded.
The reader is warned, therefore, that the
following discussion is preliminary and tentative.
16
The most convenient starting point would be the identification of the end of the alkyl chain.
Unfortunately, the
identification of methyl resonances is not necessarily a
hi
straightforward
matter.
We will base
our discussion on the
general "end-of -chain" shown in Figure
3.
Our
concern will
be the id.entif lcation of the methyl resonance, and the
use
of the methyl carbon chemical shift to infer the degree of
a
substitution at C , C b , and C C 10
.
10.
Smaller alkyl chains such as methyl, ethyl, and propyl
cannot be treated in the manner described here.
C°
Thus, if
is replaced, by a heteroatom, some of the criteria applied
in the accompanying
discussion fail.
There are, however,
only four possible ways to arrange three
or fewer carbons,
and each resulting structure has properties which are, easily
recognizable using a number of methods.
Such details can be
considered at a later date.
Though this hypothesis has not yet been adequately tested,
it is here postulated that the highest field resonance of the
cmr spectrum will generally be the end -of -chain methyl.
Ex-
ceptions can be readily imagined, but these cases can be
recognized using criteria other than carbon chemical shifts.
Thus, br aching at C
to
163
occur.
can reduce the chemical shift of the methyl
ppm, above which methylene carbon resonances frequently
Put it must be remembered that the branch at C
can
only be a methyl group; if it is an ethyl or larger group,
then the CHo of Figure 3 Is not the end -of -chain. Branching
a
at C can therefore lead only to iso-propyl or tert-butyl
groups, which should be recognizable on the basis of peak
(
a
n
CH t%
Figure
*
3:
k_
\J
mm
C
b
Ks
17
""
V_*
The "end-of-chain"
fragment.
intensities, and readily conflrmable through the use of pmr
data.
Thus, the end-of-chain resonance(s) should be identi-
fiable by consideration of a combination of the chemical
shift and peak intensity information available in the input
cmr data.
Once an end-of-chain methyl resonance has been identified, its chemical shift can be utilized to determine the
extent and location of substitution on the end-of-chain
fragment.
If there is no branching at a position closer to
,
the CH~ than C
the chemical shift of the methyl
villi be approximately 179.6 ppm.
will be a
2.5 ppm
Branching at C
c
upfield
resonance
For each branch at C
there
shift in the methyl resonance.
has already been considered.
It therefore seems
quite possible that cmr spectra villi be able to identify
end-of-chain superatoms, vihich, taken in conjunction with the
superatoms inferred previously, villi significantly limit the
number of possible structures, prior to the structure generation step.
The reader should not forget, however, the caveat
vihich began this
discussion:
these postulates are prelimi-
nary and tentative, and badly need further consideration.
Regardless of the many uncertainties involved in the
discussions included in this report, there
great promise in the application of
developments of DETDRAL.
certainly
seems
cmr data to further
If the reader (s) of this report/
18
proposal continue to show interest, the viriter villi seek,
develop, and evaluate further applications of cmr data to
problems in structure
!
<
t
elucidation.