31 P- 15 N
Coupling Constants and 15N/14N Isotope Effects
on 31P NMR Chemical Shifts of 2-Phenylamino-2-oxo(-thioxo, -selenoxo)4-methyl-l,3,2-dioxaphosphorinanes and Related Compounds
Willy Gombler*
Ruhr-Universität Bochum, Anorganische Chemie II,
P. F. 102148, D-4630 Bochum 1 (FRG)
Ryszard W . Kinas and W o j c i e c h J . Stec*
Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies,
90-362 Lodz, Boczna 5, Poland
Z. Naturforsch. 38b, 815-818 (1983); received March 21, 1983
31P-15N Coupling Constants,
1,3,2 -Dioxapho sphorinanes
15 N/ 14 N
Isotope Effect,
15 N
Chemical Shifts,
The strong influence of a chalcogen atom (O, S, Se) attached to phosphorus on the
spin-spin coupling constant 1 J ( P - 1 5 N ) in the family of diastereoisomeric 2-|15N| -phenyla m i n o - 2 X ( X = O, S, Se)-4-methyl-l,3,2-dioxaphosphorinanes
is demonstrated.
The
15 N/ 14 N isotope effect on the nuclear shielding of phosphorus-31 is larger for the shorter
equatorial than for the longer axial P - N bonds.
T h e successful use of isotope effects in
NMR
spectroscopy for the analysis o f an isotopomeric
composition o f m o n o - and dialkyl| 18 0|-phosphates
[ 1 - 4 ] as well as for the estimation of bond distances
o f directly bonded atoms in a series of closely related
c o m p o u n d s [5], and increasing interest in o n e - b o n d
spin-spin coupling constants for the conformational
analysis
of
prompts
us to
several
compounds
[6-9]
publish the results of our
classes of
NMR
spectroscopic studies on the selected | 15 N|-phosphor -
All N M R measurements were performed on a
Bruker W M 250 instrument operating at 101.26,
47.71 and 25.35 M H z f o r 3 1 P, 77 Se and " N , respectively. External standards: 8 5 %
H3PO4,
(CH 3 )2Se, N O 3 - (aq), respectively. T h e substances
were dissolved in pyridin, 1 0 % CeDß was added for
field/frequency
locking.
anilidates 1 - 5 .
W
la:
lb:
2a:
2b:
3a:
3b:
4a:
4b:
5a:
5b:
X = NHPh,
X=0,
X=NHPh,
X=S,
X = NHPh,
X = Se,
X = PhNH,
X = 0,
X = PhNH,
X = 0,
Y= 0
Y=NHPh
Y=S
Y=NHPh
Y = Se
Y = NHPh
Y= 0
Y=NHPh
Y= 0
Y=PhNH
2 - c h l o r o - 4 - m e t h y l - 1 , 3 , 2 - d i o x a p h o s p h o r i n a n e with
| 15 N|-aniline followed b y oxidation (f-BuOOH),
thioylation (Ss) and selenylation (Sea), respectively,
o f 2-| 1 5 N|-phenylamino-4-methyl-l,3,2-dioxaphosphorinane intermediates, and subsequent chromatographic separation o f diastereomeric mixtures into
eis- and trans-isomers
[10], The synthesis of diastereomeric N,N,0 2 -tribenzoyladenosine 3',5'-cyclic
| 15 N|-phosphoranilidates (4) and 2'-deoxyadenosine
3',5'-cyclic | 15 N|-phosphoranilidates (5) ( 2 5 % isotopic enrichment) has already been briefly described
in recent communications [11, 12].
Results and Discussion
T h e results are collected in Table I . I t should be
mentioned that
\
J
\
J
Z = N(COPh) 2
W=0-C0-Ph
Z = NH2
W=H
Experimental
T h e 115N|-labeled compounds 1 - 3 ( 5 0 % isotopic
enrichment) have been obtained via condensation of
* Reprint request to Priv.-Doz. Dr. W . Gombler or
Prof. Dr. W . J. Stec.
0340-5087/83/0700-0815/$ 01.00/0
XH
NMR
studies performed for
c o m p o u n d s l a and l b (Table I I ) clearly indicate,
that the 1,3,2-dioxaphosphorinanyl
ring in both
isomers adopts the chair conformation in solution.
Earlier X - r a y examinations have shown that in the
solid state 2-phenylamino-2-oxo-5,5-dimethyl-1,3,2dioxaphosphorinane [13] and b o t h eis- and transdiastereoisomers
of
2-f-butyl-2-seleno-4-methyl-
1,3,2-dioxaphosphorinane
[14] exist in the chair
conformation. T h e same conformation
has
been
reported for the dioxaphosphorinanyl part of 2'-
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816
W. Gombler et al. • 3ip_i5jf Coupling Constants and
15 N/ 14 N
Isotope Effects
Tab. I. NMR data of compounds 1-5.
Compound
la
lb
2a
2b
3a
3b
4a
4b
5a
5b:
m.p.
m.p.
m.p.
m.p.
m.p.
m.p.
m.p.
<5(3ip)
ppm
<$(i5N)
ppm
154-156°,
173-175°,
171-172°,
91- 92°,
166-167°,
92- 93°,
155-157°,
i?/0.2 a — 4.0
—303.2
Ä/0.3a
0.9
—301.1
i?/0.25 b
61.0
—290.4
Rf 0.7 b
63.8
—286.4
RfO.3*
61.5
—286.1
Rf 0.7 b
63.3
—282.7
iü/0.14 c — 3.22 —303.7
Rf0.llc
0.81 —305.2
m.p. 161° with decomp.
Rf 0.27d — 3.21 —301.3
Rf 0.370
—304.0
0 .74
<5(77Se)
ppm
—209.5
—285.2
1 J ( P - « N ) !J( 7 7 Se-P) 1 /J 31 P( 15 / 14 N)
Hz
Hz
ppm
35.4
49.6
10.8
24.5
0.8
12.6
37.6
49.5
949.4
908.0
—0.0086
—0.0096
—0.0135
—0.0154
—0.0121
—0.0136
2j77Se(i5/i4N)
ppm
—0.070
—0.098
37.0
48.0
Accuracy of the values: M ± 0.0003, 2A ± 0.004, iJ(P- 1 5 N) ± 0.05 for 1-3, ± 1.5 for 4 and 5, iJ( 7 7 Se-P) ± 0.2.
Mobility on TLC silica gel (E. Merck) plates using aceton-chloroform (1:3) as developing system; b as above,
benzene as developing solvent; c as above, chloroform-ethanol (98:2) as developing system; d as above, chloroform-methanol (3:2) as developing system.
a
Tab. II. X H NMR parameters of compounds 1 a and 1 b.
Compound
Ha
Hb
He
Hd
HE
HA-HB
HA-HC
HA-HD
HA-HE
Ha-P
HB-HC
HB—HD
HB—HE
Hb-P
HC-HD
HC-HE
Hc-P
HD-HE
Hd-P
HE-P
la
<5 (ppm)
lb
Ö (ppm)
4.62
4.38
4.21
1.81
1.51
J (Hz)
0
0
11.1
2.4
2
11.5
11.5
2.6
2.5
4.75
1.95
22.4
14.6
1.3
2
4.92
4.75
4.23
1.92
1.56
J (Hz)
0
0
11.2
2.4
2.4
11.6
12.6
2.2
2.2
4.7
1.8
23.9
14.6
1.5
2
Computer-simulated spectra are identical with those
measured for original samples at 250.13 MHz.
deoxyadenosine 3',5'-cyclic phosphoranilidate [12].
W e assume that all compounds 1 - 5 have in common the same spatial architecture of the dioxophosphorinanyl ring system.
The following conclusions can be drawn from the
inspection of the data collected in Table I.
1. The criterion of 31 P N M R chemical shift can be
safely used for assignment of spatial orientation of
the phenylamino moiety with respect to the dioxaphosphirinanyl ring system if both diastereomers
are available. All compounds with an equatorially
disposed PhNH-group absorb at lower field than
those with an axially oriented PhNH- substituent
[15].
2. 15 N nuclei located in the axial position of compounds 1 - 3 are more shielded by the dioxaphosphorinanyl ring than those in the equatorial position. However, in nucleoside phosphoranilidates 4
and 5 a reverse relationship for the d( 15 N) values is
observed. This probably results from a deshielding
influence of the adenine-9-yl moiety on the axially
oriented 35 N nuclei. Thus, the chemical shift
criterion in 15 N N M R can be applied to distinguish
between diastereomeric cyclic phosphoranilidates
but cannot be applied in general for configurational
assignments.
3. The spin-spin coupling constant ^«/(P—^N)!, as
pointed out in our earlier papers [11, 12, 16], can
be fairly safely applied for configurational assignment at phosphorus incorporated in the diastereoisomeric dioxaphosphorinanyl ring system if both
isomers are available. There is a difference of
10-15 Hz between spin-spin interactions in axially
and equatorially displaced 15 N nuclei, and the lower
value of | 1 J(P- 1 5 N)| indicates an axial position of
the phenylamino group. As we reported earlier, the
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817 W . Gombler et al. • 3ip_i5jf Coupling Constants and
same relationship |ij(P- 1 5 N) a x < | 1 J(P- 1 5 N)| e q has
been found for the pair of diastereoisomeric t h y midine cyclic S'jö'-I^NI-dimethylphosphoramidates
[16], independent on the non-chair conformation o f
the dioxaphosphorinanyl part of the cis-isomer [17].
The difference in this coupling constant can be explained b y different P - N bond lengths (axial P - N
bonds are longer than equatorial ones [7, 10, 14, 18])
and the more strongly emphasized sp 3 hybridization
of the nitrogen atom in the axial position. The contribution o f a chalcogen atom attached t o phosphorus t o the absolute value of the 3iP—'5N coupling
constant can be understood in terms o f the different
electronegativities of 0 , S and Se. T h e more electronegative oxygen prefers more p-character in the
phosphorus hybrid orbital which forms the P - 0
bond and diverts more s-character into the other
orbitals [19, 20]. A higher s-character in the P - N
<7-bond causes a higher magnitude o f the coupling
constant, because this parameter is in general
governed b y the Fermi-contact-term if no multiple
b o n d character is involved.
T h e data indicate that the empirical rule
|iJ(P-X)|ax < ] 1 J(P-X)|eq is not effective for the
diastereoisomers of 2-fluoro-2-oxo-4-methyl-1,3,2dioxaphosphorinanes [21, 22], T h e values recently
reported b y Gerlt et al. [23], as well as those obtained b y Bruzik and Tsai [24] on b o t h isomers o f
2-phenylamino-2-|170|-oxo-4-methyl-l,3,2-dioxaphosphorinanes ( l a : X = P h N H - , Y = 1 7 0 ,
i J ( P - i 7 0 ) = 136 H z ; l b : X = * 7 0 , Y = P h N H - ,
! J ( P - 1 7 0 ) = 146 Hz, CDCls), indicate that the criterion of spin-spin coupling constants for configuration assignment within the pairs o f diastereoisomeric 1,3,2-dioxaphosphorinanes cannot be applied
for 1 J ( P - 1 7 0 ) . This finding is not yet completely
understood, a possible explanation being the difference in the ?r-bond strength between axially and
equatorially positioned oxygen atoms. Since the
multiple b o n d character of the P - 0 b o n d is m u c h
larger than that of the P - S and P - S e b o n d , the t w o
contributions of the a- and Ti-bond t o the coupling
constant have to be considered. T h e longer axial
P - 0 b o n d could consist of a weaker a- and a
stronger rc-bond relative to the equatorial P - 0
bond. Oxygen is a g o o d cr-acceptor and tz:-donor.
The higher p-character of the axial phosphorus
orbital favours the polarization o f the cr-bond, and
this leads to an increased jr-back bonding ability o f
oxygen. I f the difference in n-character between
15 N/ 14 N
Isotope Effects
axial and equatorial P - 0 bonds dominates that in
the o - b o n d s in determining the 3 1 P - 1 7 0 coupling
constant, then the contradiction between the observed 3 1 P - 7 7 S e and 3 1 P - 1 7 0 spin-spin interactions
can be understood.
4. One-bond 1 5 N-induced isotope effects on the
chemical shifts of the 3 1 P nuclei, M 3 1 P ( 1 5 ' 1 4 N ) (for
definition see Ref. [5]), were observed for the compounds 1 - 3 . These upheld isotope shifts are somewhat smaller than the recently reported XA 3ip(i8/ieo)
values for P - 0 single bonds [2, 25], but are, as expected, m u c h smaller than those measured for
2 H / ! H substitution in dialkyl phosphonates
[26].
All three pairs o f diastereomers 1 - 3 exert larger
isotope shifts for 1 5 N located in the equatorial
position:
l/|3ip(15/14N) ax < M3iP(15/14N)eq
As the equatorial P - N bond distances are shorter
than the axial ones, these values demonstrate once
more the dependence o f one-bond isotope shifts on
b o n d lengths. Such a correlation was recently
established for M 7 7 S e ( 1 3 ' i 2 Q values [5]. I n the meantime t w o further one-bond isotope effects were
found t o correlate with b o n d distances [27]. Hence,
it appears that the dependence of one-bond isotope
effects on the corresponding b o n d lengths is o f
general validity if closely related series of angular
compounds are considered (one series of linear compounds has been found to depend strongly on the
valence force constant while the bond length is
nearly constant [5]).
5. A s emphasized in earlier work [7], one-bond
spin-spin interactions between 3 1 P and 77 Se can be
safely utilized for the determination of spatial
orientation o f selenium nuclei in diastereoisomeric
2-selenono- and
2-selenolo-1,3,2-dioxaphosphorinanes. Compounds 3 a and 3 b constitute another
example [28] demonstrating the complementary
character o f the empirical rule
|lJ(P-X)|ax < |U(P-X)|eq.
Compound
1J(P-77Se)
compound
in 3 a and
3 a shows a lower 1 J ( P - 1 5 N ) and a higher
value relative t o those measured for
3 b. The coupling constants | 1 J(P- 7 7 Se)|
3 b indicate that the tautomeric form
n°t
|iJ(P-i5N)|eq
responsible
for the
in 3 b is larger than
in 3a. I f this would be the
CELS6,
fact
that
|iJ(P-i5N)| a x
Si much smaller
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818
W. Gombler et al. • 3ip_i5jf Coupling Constants and
15 N/ 14 N
Isotope Effects
77 Se
should be noticed, but further examples are
necessary for attempts of any generalization. The
two-bond isotope effect 2 Zl 77 Se( 1 5 /14 N) (Table I) is
the first observed value of this type. This parameter is also sensitive to the spatial orientation of
X and Y .
a x value should be observed due to the
well-demonstrated relationship between the P-Se
bond order and the corresponding coupling constant [7]. The empirical rule can theoretically be
interpreted in terms of a larger s-character in
equatorial phosphorus orbitals than in axial ones.
An easy access to phosphoroselenoates via P m
intermediates (as exemplified by the synthesis of 3,
vide supra) and stereospecific conversion of phosphoroselenoates into phosphates [29] simplifies the
procedure of assignment of spatial orientation of
exocyclic substituents at the phosphorus atom in
the family of diastereoisomeric 1,3,2-dioxaphosphorinanes. The pronounced difference in 77 Se
chemical shifts for equatorially and axially located
Accomplishment o f this work, initiated in the
Ph. D. Thesis (R. W . K . ) , was possible during a
three-month stay of one of us (W. J. S.) as Visiting
Professor at the University of Bochum. Words of
gratitude are expressed to Prof. A. Haas for his kind
interest in this work and to the Deutsche Forschungsgemeinschaft for financial assistance. Dr. K .
Bruzik and Dr. Tsai of Ohio State University, USA,
are acknowledged for the delivery of 1 7 0 N M R data
prior to publication.
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[2] S. L. Buchwald and J. R. Knowles, J. Am. Chem.
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[4] M. D. Tsai and K. Bruzik, in L. J. Berliner and
J. Reuben (eds.): Biological Magnetic Resonance,
Vol. 5, Plenum Press, 1983 in press.
[5] W. Gombler, J. Am. Chem. Soc. 104, 6616 (1982).
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references cited therein.
[7] W. J. Stec, Z. Naturforsch. 29b, 109 (1974); W . J.
Stec, R. W. Kinas, and A. Okruszek, ibid. 31b,
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ibid. 5, 21 (1976).
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Chem. 41, 233 (1976).
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