多核NMR①：測定しやすい核としにくい核

多核NMR①：測定しやすい核としにくい核
有機分析化学特論＋有機化学４
第８回(2015/06/05)
多核NMR：
(核の種類による)検出感度(同じ濃度の時)
S = I(I+1)ν03N
※6/27,7/4の1限に
補講@6210号室
[6/19(金)休講]
I : 核スピン
Q : 核四極子モーメント
線幅因子 (line width factor)
I : 核スピン
ν0 : 共鳴周波数
N : 核スピン濃度
LW =
(2I + 3)Q2
I2(2I – 1)
相対感度(13C核を基準)
R’ =
I ( I + 1)
ν0
×
1 1
ν13C
( + 1)
2 2
よく利用されるI=1/2の核
3
15N
総合相対感度
(天然存在比も考慮して 13C核を基準)
R’ =
I ( I + 1)
1 1
( + 1)
2 2
×
ν0
ν13C
3
×
α0
α13C
(0.37%), 19F (100%), 29Si (4.7%), 31P (100%)
77Se (7.58%), 111Cd (12.75%), 119Sn (8.58%)
125Te (6.99%), 195Pt (33.8%), 207Pb (22.6%)
よく利用されるI=1/2以外の核
2H
(I = 1, 0.015%), 7Li (I = 3/2, 92.6%)
11B (I = 3/2, 81.2%), 14N (I = 1, 99.6%)
17O (I = 5/2, 0.037%)
他の核とのカップリングがよく利用される核
103Rh
(I = –1/2, 100%)
107Ag (I = –1/2, 51.82%), 109Ag (I = –1/2, 48.18%)
三共出版「多核種の溶液および固体NMR」
北川進, 水野元博, 前川雅彦著、竹内敬人・西川実希訳
ISBN: 9784782705681
核スピンや感度、それぞれの核の基準物質などのデータが多数掲載
1
多核NMR②：それぞれの核の共鳴周波数と化学シフト
共鳴周波数は核ごとに決まっている
電磁波のエネルギーΔE = h νとすると
γ ·B0
ν=
2π
化学シフト幅は核ごとに異なる
1H
~ 15 ppm
13 C ~ 200 ppm
11 B ~
測定前に行うオートチューニングは
この共鳴周波数を調整する作業
それぞれの核における共鳴周波数(1Hを100 MHzとしたとき)
http://www.chem.wisc.edu/areas/reich/nmr/notes-7-multi.pdf
210 ppm
31 P ~ 450 ppm
77 Se ~ 3000 ppm
195 Pt ~ 6700 ppm
59 Co ~ 18000 ppm
通常は高周波数の核を1Hに固定して測定
低周波数側をいろいろ設定することが多い
(=19F測定の後はチューニングを1Hに戻す)
共鳴周波数の高い核
＝ high frequency核
共鳴周波数の低い核
＝ low frequency核
2
多核NMR各論：2H NMRスペクトル
2 H,
核スピンI = 1, 天然存在比0.015%, 磁気回転比γ = 4.1066
四極子モーメント = 2.8×10–3, 相対総合感度 = 1.45×10–6
例：部分重水素化された化合物8のスペクトル
1H
NMR spectrum (C6D6)
2H
NMR spectrum (C6D6)
化学シフト基準はSi(CD3)4 = 0
応用例：styrene-d 8のMeReO3を用いた
触媒的ジヒドロキシ化反応速度測定
J. Mol. Cat. B: Enzymatic 2011, 73, 17.
Chem. Commun. 2002, 66.
3
多核NMR各論：7Li, 6Li NMRスペクトル
7 Li,
核スピンI = 3/2, 天然存在比92.6%, 磁気回転比γ = 10.396
四極子モーメント = –4×10–2, 相対総合感度 = 1.54×103
化学シフト基準はLiCl/D2O = 0
範囲は約–10~5 ppm
6 Li,
核スピンI = 1, 天然存在比7.4%, 磁気回転比γ = 3.937
四極子モーメント = –8×10–4, 相対総合感度 = 3.58
7Li応用例：Me
3Siアセチレンの脱プロトン化を
RI(rapid injection)NMR法で迅速モニター
6Li応用例：(Ph 6Li)
2と(Ph
6Li)
4の
6
O溶媒中低温の Liおよび
平衡をEt2
13C NMRスペクトルで観測
Prof. Hans J. Reich@U Wisconsin
J. Am. Chem. Soc. 2007, 129, 3492.
J. Am. Chem. Soc. 1998, 120, 7201.
4
single
togetherresonance
just prior to experimental
measurements.
at "23ppm)
ppm duringshowed
decomposition at
P NMR
observed
for Heating
3 (d 48.6
a 80
!
experiments were conducted
propose
that the resonancebetween
observed here is one
in which AB and
C min using
suitable for x-ray 195
diffraction
studies,
whichat a ramp
ex-rate of 1 interatomic
distance
boron
and
oxygen
Pt–31P coupling
Hz,
higherLiNH
than
thosein aof
on metal c
a laboratory constant
oven in which theof
flask1,726
was attached
to stainless
are associated
new the
hybrid phaseligands
with 1 : 1 stoichisteel
gas
lines.
ometry.
hibited different crystallographic
space
groups
(122.6
pm)Further
are
in fullHz),
agreement
with of
thebond
for
)L]
complexes
(about
1,000–1,600
comparable
cis-[(Et
The composition
of evolved 2
gas
was monitored
using a quadevidence that the NMR
resonancehypothesis
is distinct from AB
3P)2Pt(BR
11
rupole mass spectrometer (Dycor Dymaxion) with a flow (10 mL
was obtained using a sample which had been mixed for less than
and in some casesbut
contained
co-crystallized
solmulation
of aandP)triple
Detailed
analyses of the
pbond.
-olefin)]
much lower
thegas.highly
comparable
cis-[(Et
linearity
min )than
1 min3
had
not yet
formed
the liquid phase.
The B chemicalof the C–
of Ar carrier
Quantification
of NH was carried out
2Pt(
by bubbling the gases through 0.1 M HCl solution and backshift ("25 ppm, Fig. 1(B)) was initially the same as the –BH
p-alkyne)]group
(3,160–3,443
Hz)
(3,460–3,663
Hz)
andparameters
cis-[(Et
164.2(8)8)
and bond
that t
vent molecules. However,
structural
orbitals
(MOs)
inter
revealed
3P)
2Pt(
titrating with standard
NaOH solution.
The
totalmolecular
quantity of gas
in pure AB. Reaction
between
AB and alia
LiNH took
place
Published on 30 March 2009. Downloaded on 04/06/2013 17:47
ng materials and initial formation of one
uct (32). Phosphorus (31P) NMR data [21.2
per million (ppm), 1JPt-P = 2777 Hz] are
ative of a platinum(II)
boryl complex fea11
!
"1
C (JBH ¼ 94 Hz). We
2
多核NMR各論： B NMRスペクトル
"1
11
3
3
B, 核スピンI = 3/2, 天然存在比80.42%, 磁気回転比
= 8.5847confirmation
化学シフト基準はBF
3 ·OEt2 =in0no way coplanar
by way of single-crystal
complexes36.γ Structural
diffraction2 (see the Supplementary
Information,ppm
Crystal which distinguishes
四極子モーメント = 4.1×10–2, 相対総合感度X-ray
= 7.52×10
範囲は約–120~90
2
evolved was determined in separate experiments without a carrier
gas by directing the outlet to a gas burette initially filled with
paraffin oil. Correction for temperature expansion in the reaction
flask was established with a blank run.
Solid state 11B NMR spectra were recorded at 11 T on a Bruker
Avance 500 spectrometer without proton decoupling and referenced to BF3$Et2O (0 ppm). Samples were packed in silicon
3 2
2
2
nitride rotors in the Ar glove box and spun at ca. 10 kHz or
greater at the magic angle in a Doty probe. Parameters from
spectra with anisotropic quadrupolar resonances were obtained
using the line shape analysis module of the Bruker TopSpin
software.
Powder X-ray diffraction utilised a Bruker D8 diffractometer
fitted with Co Ka radiation and parallel beam optics. Samples
were loaded into a custom atmosphere-protected cell inside the
Ar dry box.
Rehydrogenation of the material heated to 250 ! C was
attempted in a stainless steel pressure vessel. After23
pressurising
with hydrogen gas, the vessel was closed and heated to 400 ! C in
a tube furnace with a 1/1600 stainless tube leading to a pressure
transducer in the laboratory.
in this partially-mixed sample when the temperature was raised,
zerovalent platinum
line with the calcul
complexes 1a and 1
the HOMO of be
predominantly a fill
point above and belo
Structure Determination) confirmed the connectivity of 3 as the
p-diborene complex [(Et P) Pt(B Dur )] (Figs 4 and 5). Several
novel geometrical attributes exist in the structure of 3 (see
Table 1). The B–B distance of 3 (1.510(14) Å) is one of the shortest
例：BBr3: 38.5 ppm, BBr3·pyridine: –7.1 ppm
such bonds ever observed, and sits between those of the reported
他の核とのカップリングは３配位＞４配位 base-stabilized diborenes prepared by Robinson and co-workers
(IDip ! B(H)¼B(H) " IDip, IDip ¼ 1,3-bis(2,6-diisopropylphe11
nyl)imidazol-2-ylidene, 1.561(18) Å) and ourselves (IDip !
ホウ素クラスターでは二次元 B NMRが有用
B(Br)¼B(Br) " IDip, 1.546(6) Å), and the B–B distance in the
11 B NMRで
固体
triply bonded
diboryne
IDip ! B;B " IDip (1.449(3) Å)37. Also,
Results and
the B–B distance
ofdiscussion
3 is identical to that calculated for the free
水素吸蔵合金の
Initial mixing
diborene PhB¼BPh (1.520 Å) within experimental error (discorUpon mixing, the two solid components combined in an
反応を追跡
dant with the
significant
lengthening
observed for p-alkyne
apparently
exothermic bond
reaction, forming
a liquid phase.
Conclusions
Our computational a
thought possible, tha
can be emptied of el
with boron atoms) a
a new form of p-bac
Depending on the ambient temperature, the mixing time needed
a metal donates elect
to form the liquid varied from a few minutes to about half an
Fig.
1 Solid-state
NMR706.
Spectra of 1 : 1 LiNH : AB samples.
Energy
Sci.
2009,B 2,
hour. The air-sensitivity of the materials
and speedEnviron.
of reaction
Spectrum (A) was measured at room temperature from a sample mixed
which
strengthens no
prevented us from measuring the reaction enthalpy in a calountil the formation of a liquid phase. Spectra (B) to (E) were measured
[(Et3P)(Br
Durfor
rimeter. The liquid began evolving hydrogen slowly at room
2B2mixed
2)]<1 min and held at 60 C for 0 min, 15 min, 30
from a sample
11 B核を含む化合物
Given its out-of-plan
min, and 60 min respectively.
temperature,
eventually transforming into an amorphous solid.
特殊な環境の
+
for
this | interaction.
This journal is ª The Royal Society of Chemistry 2009
2, 706–710
707
Dur Energy Environ. Sci., 2009,
Pt(PEt
)
11
2
!
3 3
Pentane, r.t.
+
Et3P
2Br2B2Dur2
B
Methods
Computational details. T
Br
Br Pt
B
1. X-ray molecular structure of trans-[(Cy3P)2BrPt(BO)] (2) (left) and p-MOs of the model complex
(at the OLYP/TZP level38
38,44
structure
of
trans-[(Cy
-[(Me3P)2BrPt(BO)] (2′) (right). The bond lengths and angles of 2 are not fully reliable because of Fig. 2. Molecular
, as ba
analysis3P)
(EDA)
2(PhS)Pt(BO)
PEt3 Dur
(at are
the B3LYP/TZP
levela4
represented
isorder indicated by the white ellipsoids. Thermal ellipsoids are represented at the 50% probability (3) 2 CH2Cl2.2Thermal ellipsoids
δ 39
δB 47
zeroth-order relativistic ap
B 12.5
the 50% probability δlevel.
Hydrogen
atoms, solven
Hydrogen atoms and ellipsoids of the carbon atoms of 2 are omitted forB clarity.
Pt
the core electrons were
Science 2012, 336, 1420. Science 2006,
314,
113.
Science
2011,
333,
610.
molecules and ellipsoids
of theorders
cyclohexyl
carbon
between boron
ato
Dur
Mes
Mes
determined
according
to
H
me 2. Preparation of transatoms are omitted for clarity. Selected Bond lengths
N
N
2
B
the
s
and
p
interactions
b
Et
P
P)2(PhS)Pt(BO)] (3).
(pm) and3 angles
(°): B–O 121.0(3),
Pt–B
198.3(3)
Pt
Mg Mg
techniques
based
on the E
Benzene, r.t.
Et3P
B
were
performed87.75(8)
by constr
Pt–S 241.06(6);
Pt–B–O
177.3(2),
B–Pt–P1
N
N
reference
axis
to
zero. Us
Dur 171.3(2), Pt–S–C 111.33(8)
3 B–Pt–S
Mes
Mes
B–Pt–P2 86.80(8),
the interaction between th
δB 17
δB 130deviations areinto
Estimated standard
given
incomponents,
parenthesesE
three
∙
http://u-of-o-nmr-facility.blogspot.jp/2008/04/11-b-cosy.htmlFigure 4 | Synthetic results presented herein. Oxidative addition of
Scienceto2010,
Nat.
2013,
Br2B2Dur2 to platinum
form 328,
2 and345.
the reduction
ofChem.
2 to form
3. 5, 115.
http://u-of-o-nmr-facility.blogspot.jp/2008/04/1-h-11-b-hmqc.html
16 APRIL 2010
r.t. ¼ room temperature.
VOL 328
SCIENCE
www.sciencemag.org
5
corresponds to the classica
distributions of the fragm
fragment densities). The s
多核NMR各論：15N NMRスペクトル
15 N,
核スピンI = –1/2, 天然存在比0.37%, 磁気回転比γ = –2.716
四極子モーメント = なし, 相対総合感度 = 2.19×10–2
化学シフト基準はCH3NO2 = 0
範囲は約–600~600 ppm
最近の応用例：窒素分子錯体の同定
Cl
P
N Mo Cl + N2 + Na!Hg
1H-15N HSQC
THF
(6
equiv)
(1
atm)
P Cl
room temp.
12 h
t
P = P Bu2
31P{1H}
N
N
N
P
N
P
N Mo N N Mo N
P Nα
Nβ
N
NP
P = PiPr2
δN –29.0
2J
yield Hz, terminal Nα)
(dt, 1JNN&63%
PN = 6.1&2.4
δN –16.5
(d, 1JNN = 6.1 Hz, terminal Nβ)
δN 8.5
1H),
(s, bridging N)
NMR (THF-d8): " 94.6 (s).
1H NMR (THF-d ): " 7.07 (t, J = 7.3 Hz, ArH,
8
Nat. Chem. 2011, 3, 120.
6.93 (d, J = 7.3 Hz, ArH, 2H),
3.37 (br, CH2PtBu2, 4H),
1.28 (pseudo t, CH2PtBu2, 36H).
IR (KBr, cm!1): 1936 (#NN). Raman (THF, cm!1): 1890 (#NN).
6
多核NMR各論：19F
19 N,
only i.tu. application but also the systemic delivery of the enzyme/
prodrug system. Intratumoural production of 5-FU following i.v.
injection of TAPET-CD and i.p. injection of 5-FC (300 mg/kg) was
measured in vivo in the HCT116 colon tumour (Figure 3A). The 5FC concentration in the tumours following i.p. injection was
comparable to the i.tu. administration (3-4 mM). A clear conversion of 5-FC to 5-FU was seen with this systemic application of
TAPET-CD/5-FC, although the 5-FU signals were less than3with the
i.tu. delivery route (compare Figure 1 and Figure 3A).
Because of the reduced 5-FU signal, the conversion quality was
further analysed and confirmed with in vitro high resolution 19F
MRS (8.4 Tesla) of extract preparations from these tumours.
Intratumoural concentrations of 5-FU were about 0.570.2 mM
(n ¼ 6) for the i.tu. and 0.1570.07 mM (n ¼ 7) for the systemically
TAPET-CD plus 5-FC treated tumours respectively. A representative example of this analysis (Figure 3B) illustrates the efficacy of
the TAPET-CD/5-FC conversion to 5-FU in this i.v./i.p. administration modality.
Within the total in vivo experimental time, no metabolic activity
was observed in the tumours, ie, the concentrations of the
catabolites and anabolites of 5-FU were below the detection
threshold of the in vivo 19F MRS. Using the much more sensitive in
vitro MRS on tumour extracts, we observed a small catabolite
signal around !17 p.p.m. (i.tu. 0.170.1 mM (n ¼ 4), i.p.
0.02570.025 mM (n ¼ 5)) and in some cases also a very small
anabolite signal between 3.5 and 5.5 p.p.m. (B0.015 mM) (an
example is shown in Figure 4).
Those tumours, which were not further investigated with in vitro
MRS, were analysed for bacterial colonization. Levels of
5 # 10872 # 108 cfu per gram tissue were found.
http://www.cerij.or.jp/
二次元19F NMR：
化学シフト基準はCFCl = 0
範囲は約–300~900 ppm
5
2
tumours, also extracts
with in vitro 19F MRS
detected in the tumo
catabolite signals of a
!17.3 p.p.m. and a-flu
observed in the liver e
to 5-FU that was obser
5-FC application was
catabolite levels in th
(0.0570.04 mM (n ¼
(0.0970.02 mM (n ¼ 6
5-FU
3
2
1
0
-1
Chemical shift (ppm)
3
Figure 5 In vitro F M
16 decoupling) of the pe
liver of a mouse (Figure
injected i.tu. with 5-FC o
vivo evaluation (ie, about
a mouse treated i.v. with
snap-frozen immediately
5-FC administration).
5-FC
4
4
Ch
5-FU
5
×20
19
It is obviously important to evaluate normal tissue in parallel with
tumour tissue, as both ultimately determine the therapeutic
window of treatment. Besides the perchloric acid extracts of
5-FC
2
B
A
In vitro 19F MRS of liver PCA extracts of mice treated with
TAPET-CD/5-FC
A
3
5-FC
最近の応用例：ネズミの腫瘍に
F-cytosineを注射、そのままF-uracilを検出
B
4
Figure 4 In vitro 19F
WALTZ-16 decoupling)
shown in Figure 2, snaplarge conversion of 5-FC
between in vivo 19F M
(B4 p.p.m.) and cataboli
NMRスペクトル
核スピンI = 1/2, 天然存在比100%, 磁気回転比γ = 25.1815
四極子モーメント = なし, 相対総合感度 = 4.73×103
使用例：含フッ素ポリマーの構造解析
5
-2
DISCUSSION
10
http://www.toray-research.co.jp/new_bunseki/index.html
5
0
−5
−10
−15
Chemical shift (ppm)
−20
−25
Figure 3 (A) In vivo 19F MRS spectrum obtained after 2 weeks (20 min/
Brit.
J.¼Cancer
89, 1796.
spectrum; TR ¼ 0.75
s; NS
1536) of a 2004,
mouse treated
with an i.v. injection
of the TAPET-CD system (day 0) followed with an i.p. 5-FC injection
(300 mg/kg). Spectrum obtained 2.5 h after 5-FC inoculation. (B) In vitro 19F
MRS spectra of the perchloric acid extract of the whole tumour from the
7
In the present 19F MR
detection of the dyna
human HCT116 colo
cytosine deaminase(TAPET-CD). The resu
to 5-FU within 30 m
measurement time e
多核NMR各論：29Si NMRスペクトル
29 Si,
核スピンI = –1/2, 天然存在比4.7%, 磁気回転比γ = –5.3190
四極子モーメント = なし, 相対総合感度 = 4.95×10
化学シフト基準はSiMe = 0
範囲は約–200~100 ppm
使用例：固体29Si NMRによる
Al,Si含有ゼオライトの分析
最近の例：特殊な環境の Si核を含む化合物
Downloaded from www.sciencemag.org on Jun
compound with a Si"C double bond (10).
The reaction of 2,2,3,3-tetrabromo-1,1,4,4-tetrakis[bis(trimethylsilyl)methyl]As for triple bonds, Power and co-workers
1,4-diisopropyltetrasilane with four equivalents of potassium graphite (KC8) in
recently prepared alkyne analogs of the
tetrahydrofuran produces 1,1,4,4-tetrakis[bis(trimethylsilyl)methyl]-1,4-diisoheavier group 14 elements: germanium, tin,
propyl-2-tetrasilyne, a stable compound with a silicon-silicon triple bond, which
and lead (11–13). However, despite bearing
can be isolated as emerald green crystals stable up to 100°C in the absence of
nominal triple bonds, these compounds acair. The Si!Si triple-bond length (and its estimated standard deviation) is
tually exhibited a highly
4 pronounced non2.0622(9) angstroms, which shows half the
magnitude
of
the
bond
shortening
bonding
electron
density
character at the
–1
of alkynes compared with that of alkenes. Unlike alkynes, the substituents at
central atoms, resulting in a decrease in the
the Si!Si group are not arranged in a linear fashion, but are trans-bent with
bond order on descending group 14 (14,
a bond angle of 137.44(4)°.
15). In light of these results, isolation of the
www.nature.com/scientificreports
silicon analog of alkynes has been a comwww.nature.com/scientificreports
Hydrocarbons containing C"C double
pelling goal. Although the theoretical analed the synthesis of the stable distannene
bonds (alkenes) and C!C triple bonds
ysis predicted the experimental accessibil[(Me 3 Si) 2 CH] 2 Sn"Sn[CH(SiMe 3 ) 2 ] 2 ,
where Me is methyl, which has a Sn"Sn29 ity of disilynes with a silicon-silicon triple
(alkynes) form an abundant and structurally
diverse class of organic compounds. However, the ability of heavier congeners of
carbon (where element E is Si, Ge, Sn, and
Pb) to form double bond of the type
http://www.ube-ind.co.jp/usal/
#E"E$ and triple bond of the type -E!Edocuments/o224_145.htm
was for a long time doubted (1–4). The first
attempts to generate such species were unSi 90
successful, resulting in the formation of Fig. 1. Schematic representations of molecular orbital diagrams of CBD. δ
(A) Square-shaped triplet. (B)
polymeric substances. This led to the often- Rectangular-shaped
Science
2004, 305,
1755.
Reaction 1.
singlet from covalent second-order Jahn-Teller
(J-T) distortion.
(C) Rhombic-shaped
cited “double-bond rule”: Those elements singlet from polar second-order J-T distortion.
Fig. 1. Molecular strucwww.nature.com/scientificreports
with a principal quantum number equal to
ture of 1,1,4,4-tetor greater than three are not capable of
rakis[bis(trimethylforming multiple bonds because of the consilyl)methyl]-1, 4-disiderable Pauli repulsion between the elecisopropyl-2-tetrasilyne
(2) (30% probability
trons of the inner shells (5–7). Such a
ellipsoids for Si and
viewpoint prevailed despite the accumulaC). Selected bond
tion of a vast amount of experimental data
lengths (Å): Si1–Si1’ "
supporting the existence of multiply bond2.0622(9), Si1–Si2 "
ed species as reactive intermediates (1–4).
2.3698(6), Si2–C1 "
This conflict was resolved nearly 30 years
1.9119(15), Si2–C8 "
1.9120(15), and Si2–
ago, when Lappert and Davidson report-
Fig. 2. Theoret
puckered D2d s
tetrasilatetrahed
energy minima
ture with two S
rhombic C2h s
point structures
the valence is
have been isol
isotropically bu
butyl) or dend
(where Me is m
(30, 31). A sq
diene has also b
transition metal
that bulky 1,1
s-hydrindacenmight have the
C15 " 1.9180(16).
nar tetrasilacyclo
Selected bond angles
Department of Chemistry, Graduate School of Pure
observations of
(°): Si1’–Si1–Si2 "
and Applied Sciences, University of Tsukuba, Tsukuba,
137.44(4), Si1–Si2–C1
frameworks com
Ibaraki 305– 8571, Japan.
" 108.97(5), Si1–Si2–
bonds (34, 35).
C8 " 108.38(5), Si1–Si2–C15 " 106.47(5), C1–Si2–C8 " 106.83(6), C8–Si2–C15 " 114.77(7), and
*To whom correspondence should be addressed. EWe now rep
C1–Si2–C15 " 111.30(7). Estimated
mail: [email protected]
Si standard deviations are in parentheses.
zation of the s
(1), stabilized by
Science 2011, 331, 1306.
www.sciencemag.org SCIENCE VOL 305 17 SEPTEMBER 2004
1755
1,1,7,7-tetraethyl
4-yl (EMind) g
1 has a planar r
pyramidal and
silicon atoms. C
groups on the si
29
rhombic four-m
Sci.andRep.
2, 564.
Figure 3 | 29Si single pulse (SP)
Si-1H2012,
cross polarization
(CP) magic angle sample spinning (MAS) spectra of non-aminosilanised diamagnetic
which is in con
silica nanoparticles. (a); condensed/polymerised APTS (b); silica nanoparticles aminosilanised in water (c) and silica nanoparticles aminosilanised via
TPRE (d).
C2h structure th
(SiH)4.
使用例：ビーズ表面に形成した
シロキサンの状態分析
δ –52, –50, 300, 308
8
Published on 17 February 2010. Downloaded by CHUO-KENKYUJO LIB o
31 P,
多核NMR各論：31P NMRスペクトル
核スピンI = 1/2, 天然存在比100%, 磁気回転比γ = 10.8394
四極子モーメント = なし, 相対総合感度 = 1.44×102
利用例：
View Article Online
Ph
(a) 1 + xantphos (1 eq), 80 °C, 15 min, in C6D6, under H2/CO (1/1, 0.1 MPa)
Ph
Ph
Ph
O
Ph
P
Ru
P
CO
CO
10
δP 38.8
化学シフト基準は85%H3PO4 = 0
範囲は約–400~600 ppm
10
P
Ru
P
View Article Online
Ph
Ph
O
Ph
CO
CO
δP 22.2
Published on 17 February 2010. Downloaded by CHUO-KENKYUJO LIB on 05/06/2013 07:30:18.
Published on 17 February 2010. Downloaded by CHUO-KENKYUJO LIB on 05/06/2013 07:30:18.
(b) 1 + xantphos (1 eq), 120 °C, 15 min, in DMA, under H2/CO (1/1, 0.1 MPa)
View Article Online
(c) Rh(acac)(CO)2 + xantphos (1 eq) + 1 (2.5 eq), 120 °C, 15 min, in DMA, under H2/CO (1/1, 0.1 MPa)
Ph2P
H
P
PPh2
O
Rh
CO
P
1J
7
CO
δP 19.2
=
122
Hz
RhP
δP 17.7
free xantphos
asymmetric transformation (DYKAT) mechanism as a source of asymmetric induction during formation of
Fig. 1 Stereoselective condensation of ribonucleoside H-phosphonates (1) with nucleosides.
CO
ribonucleoside H-phosphonate diesters
O of type
CO5. (A) Reaction in the presence of a nucleophilic catalyst (pyridine); (B) direct esterification of the
two unidentified doublets
Rh
required to record the first 31P NMR spectrum) formation of
formation
of the DP diastereomery
of the H-phosphonate
mixed anhydride δ2;
(C) transesterification
of Paryl group,
nucleoside
H-phosphonate
4.
P 0.7, J = 148 Hz
O
P
δP 8.1, J = 135 Hz
diester was favoured (Fig. 1). The diastereoselectivity of
H-phosphonate diester, accompanied by the products of
12
= 4-nitrophenyl
this reaction under non-optimized conditions, expressed as a
decomposition of theAr
condensing
agent, i.e. hydrochlorides
diastereomeric excess (de) of the DP product, was estimated to
of amines, pivalic acid and/or pivalic anhydride. Despite the
(e) Rh(acac)(CO)2 + xantphos (1 eq), 120 °C, 15 min, in DMA, under CO (0.1 MPa)
p-nitrophenyl and p-chlorophenyl esters (hereinafter
apparent simplicity, the reaction is a multi-step process
be ca. 70%referred
for all nucleoside 3 0 -H-phosphonates, with an
involving reactive species whose structure was only deduced
exception
for
a cytidine derivative (B = CytBz, de ca.
to as dmtUPHPhNO2 (4a) and dmtUPHPhCl (4b), respectively)
39,41
indirectly. The reaction sequence starts with an attack of
40%).
The
fraction
of
each
diastereomer
could
be
convewith MeOH and EtOH, were chosen as the most suitable to
nucleoside 3 0 -H-phosphonate anion at the carbonyl carbon
niently assigned by integration of their 31P NMR signals. This
study the kinetics of transesterification.
technique was also applied to analysis of the reaction mixtures,
of PvCl, followed by an attack of the 5 0 -OH group of
Fig. 5 shows changes in diastereomeric ratio
ofthe
alkyluridine
since
signals of the substrates, the intermediates and the
nucleoside at the chiral phosphorus atom of an activated
(f) Rh(acac)(CO)2 + xantphos (1 eq), 80 °C, 15 min,
in C6D6, under H2/CO (1/1, 0.1 MPa)
3 0 -H-phosphonate
of type 5 formed during transesterification
products could be identified according to their chemical shifts
H-phosphonic moiety. Apart from H-phosphonic pivalic
of dmtUPHPhNO2 (4a) with alcohols ofanddiﬀerent
steric Additionally, for most ribonucleoside
coupling constants.
mixed anhydride, formation of several other intermediates is
3 0 -H-phosphonates,
possible. For instance, it is generally believed that in this
hindrance. For promptly-reacting primary alcohols,
a stepwise the signal located at the lower field
reaction pyridine acts not only as base but also as a nucleocorresponded
to
the
D
diastereomer,
while
the
signal
at
P
decrease of DP-5 fraction due to progressive accumulation of
philic catalyst,43 giving rise to extremely reactive pyridinium
higher field corresponded to the LP diastereomer. This rule
the LP isomer of the product is clearly seen. Those changes
of31thumb held for the vast majority of compounds in this class;
derivatives of H-phosphonates. These intermediates may
(g) Rh(acac)(CO)2 + xantphos (1 eq), 120 °C, 15 min, in DMA, under Ar (0.1 MPa)
coincided
disappearance
of thehowever,
P NMR
signal
O
CO
O
CO withO a rapid
CO
it should
be noted that the relative positions (higher
rapidly equilibrate before reacting with an alcohol or nucleoRh P
Rh
Rh
31
of the
diastereomer
e.g. in
theoffirst
vs.
field)
the signals
could
somefor
solvents
to of
form
an H-phosphonate
2, lower
Fig.
4 be
Pinverted
NMR in
traces
the time side
course
transesterification
of diester. Substitution at the
O minor
P
O
P
O of
P dmtUPHPhNO
(e.g.This
in toluene)
and for some
sequences uridine
of nucleobases
(e.g.
phosphorus
centre
in these
reactions is usually considered
minuteP of its the11'reaction with
EtOH (Fig. 4).
suggested
P
p-nitrophenyl
H-phosphonate
4a
with EtOH
(5 equiv.).
Note
11
11
for G inUthe
to be an SN2(P)
linkage).
such correlation
must
process,
although addition–elimination
the immediate
consumption
of Lbe
of the
reaction.
that the
DP isomer of dmtU
early Therefore,
P-4a in the first minute
PHEt (5b) was formedPH
PPM
treated with care and as a provisional guide only.42
(implying a possibility of pseudorotation) or SN1(P)
(via34,
metaphosphites)
In a typical condensation, a triethylammonium
salt of the
40.0
30.0
20.0
10.0
0.0
-10.0
-20.0
New J. Chem.
2010,
854. 44 mechanisms cannot be excluded in
!
c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2010
858 |ofNew
J. Chem.,
2010,
34,
854–869
This
journal
is
0
Figure S1. The 31P NMR spectra of admixtures
Rh(acac)(CO)
,
xantphos,
and
1.
2
nucleoside 3 -H-phosphonate of type 1 and a nucleoside
the sterically demanding environment of protected ribonucleoside
Angew. Chem. Int. Ed. 2010, 49, 4488.
derivatives. In pyridine none of these species could be
(both
appropriately protected) are dissolved in pyridine and
S5
detected; however, it was possible to generate uridine 3 0 -Hca. 3 equiv. of pivaloyl chloride (PvCl) as a condensing
agent is added. This causes a rapid (less than 1 min, the time
phosphonic–pivalic mixed anhydride 2 quantitatively using
10. Downloaded by CHUO-KENKYUJO LIB on 05/06/2013 07:30:18.
(d) Rh(acac)(CO)2 + xantphos (1 eq), 120 °C, 15
min, in
under
H2/CO (1/1,kinetic
0.1 MPa)
Fig.
3 DMA,
The
dynamic
9

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