3390
F. Hammerschmidt et al.
PAPER
1H and 13C NMR spectra (J modulated) were measured in CDCl3 at
300 K on a Bruker Avance DRX 400 spectrometer at 400.13 MHz
and 100.63 MHz, respectively. Chemical shifts were referenced to
residual CHCl3 (δH = 7.24) and CDCl3 (δC = 77.00). IR spectra were
run on a PerkinElmer 1600 FT-IR spectrometer; liquid samples
were measured as films on a silicon disc.29 Crystal structures were
analyzed using a Bruker AXS APEX CCD diffractometer. TLC was
carried out on 0.25 mm thick Merck plates, silica gel 60 F254. Flash
(column) chromatography was performed with Macherey-Nagel
silica gel 60M (230–400 mesh). Spots were visualized by UV
and/or dipping the plate into a solution of (NH4)6Mo7O24·4H2O
(23.0 g) and of Ce(SO4)2·4H2O (1.0 g) in 10% aq H2SO4 (500 mL),
followed by heating with a heat gun. S-Methylisothiuronium hemi-
sulfate was obtained from Aldrich. Melting points were determined
on a Reichert Thermovar instrument and are uncorrected.
stirred for 3 days at r.t. The layers were separated, and the aqueous
phase was extracted with CH2Cl2 (3 × 20 mL). The combined or-
ganic layers were dried (Na2SO4) and concentrated under reduced
pressure. The crude product was a mixture of N-(tert-butoxycarbon-
yl)-S-methylisothiourea (8) (Rf = 0.06, hexanes–CHCl3, 1:6) and 7
(Rf = 0.31, hexanes–CHCl3, 1:6). Flash chromatography (hexanes–
EtOAc, 7:1; TLC: hexanes–EtOAc, 5:1, Rf = 0.81) yielded 7 (2.643
g, 91%) as colorless needles; mp 120–121 °C (hexanes) (Lit.24 mp
122–123 °C).
IR (Si, film): 2982, 1741, 1645, 1575, 1363, 1285, 1139 cm–1.
1H NMR (CDCl3): δ = 11.57 (s, 1 H), 2.37 (s, 3 H), 1.49 (s, 18 H).
13C NMR (CDCl3): δ = 171.40 (2 C), 28.00 (6 C), 14.79.
The 1H NMR spectrum was identical to the one reported in the lit-
erature;24 no 13C NMR spectrum was given.
Radiosynthesis
N,N′-Bis(tert-butoxycarbonyl)guanidine (9a)
No-carrier-added [131I]NaI in 0.1 M NaOH was obtained from
PerkinElmer (Boston, MA, USA). The radioactivity was measured
in a Capintec CRC-15 dose calibrator (Ramsey, NJ, USA). Analyt-
ical high-performance liquid chromatography (HPLC) analyses
were performed on an Agilent 1200 system (Böblingen, Germany)
equipped with a quaternary pump, autosampler, and a variable
wavelength spectrophotometer, which was connected in series with
a Raytest radioactivity detector (Straubenhardt, Germany). Data
were collected by Raytest radio chromatography software. Radio-
TLCs were evaluated using an electronic autoradiograph (Canberra-
Packard, Watford, UK).
A solution of NH3 in MeOH (18 mL, 11.7 g NH3 in 70 mL of anhyd
MeOH) was added to N,N′-bis(tert-butoxycarbonyl)-S-methyliso-
thiourea (7; 0.935 g, 3.22 mmol). The mixture was stirred for 18 h
at r.t. The solvent was evaporated under reduced pressure and the
residue was purified by flash chromatography (hexanes–EtOAc,
2:1; Rf = 0.27, hexanes–EtOAc, 5:1) to give guanidine 9a (0.793 g,
95%) as colorless crystals; mp 143–144 °C (hexanes) (Lit.22 mp
144 °C; Lit.21 mp 144–145 °C).
IR (Si, film): 3411, 2980, 1732, 1667, 1578, 1369, 1305, 1153 cm–1.
1H NMR (DMSO-d6): δ = 10.28 (br s, 1 H), 8.51 (br s, 2 H), 1.41 (s,
18 H).
3-(Trimethylstannyl)benzyl Alcohol (2)
n-BuLi (5.75 mL, 9.2 mmol, 2.3 equiv, 1.6 M solution in hexanes)
was added dropwise to a stirred solution of 3-bromobenzyl alcohol
(1b; 0.748 g, 0.48 mL, 4.0 mmol) in anhyd THF (18 mL) at –78 °C
under argon. After stirring for 90 min at –78 °C, Me3SnCl (1.674 g,
8.4 mmol, 2.1 equiv) dissolved in anhyd THF (7.5 mL) was added,
and the reaction mixture was stirred for 18 h at r.t. (TLC: hexanes–
EtOAc, 5:1). The reaction was quenched with aq 5% NH4Cl (20
mL). The organic phase was separated and the aqueous layer was
extracted with CH2Cl2 (3 × 20 mL). The combined organic layers
were dried (Na2SO4) and concentrated under reduced pressure. The
crude product was purified by flash chromatography (hexanes–
EtOAc, 5:1, Rf = 0.29) to give stannyl alcohol 2 (1.013 g, 93%) as a
colorless oil.
13C NMR (DMSO-d6): δ = 158.5 (2 C), 158.2 (br s), 79.5 (2 C), 27.8
(6 C).
The 1H NMR spectrum is identical with that of literature;21 no 13
NMR and IR spectra were given.
C
Crystal Structure30
Crystal data: C11H21N3O4, FW = 259.31, colorless prism of
0.57 × 0.28 × 0.26 mm from hexanes, T = 100(2) K, triclinic, space
group P-1, a = 11.6836(5) Å, b = 16.1253(6) Å, c = 16.3857(6) Å,
α = 88.442(2)°, β = 84.200(2)°, γ = 70.064(2)°, V = 2887.15(19)
Å3, Z = 8 (Z′ = 4), Dc = 1.193 g·cm–3, μ = 0.091 mm–1,
λ(MoKα) = 0.71073 Å. Of 68471 reflections measured, 16711 were
unique. Refinement of F2 using the program SHELXTL31 conclud-
ed with R1 = 0.0664 and wR2 = 0.1229 for 689 parameters and all
data. The structure contains four chemically identical but crystallo-
graphically different molecules assembled in bis-NH···N hydrogen
bonded pairs.
IR (Si, film): 3332, 2980, 2914, 1411, 1203 cm–1.
1H NMR (CDCl3): δ = 7.54–7.28 (m, 4 H), 4.67 (s, 2 H), 1.76 (br s,
1 H, OH), 0.29 [s, J(117/119Sn,C) = 55.3, 52.8 Hz, 9 H].
13C NMR (CDCl3): δ = 142.7, 140.2, 135.2 [J(117/119Sn,C) = 36.0
Hz], 134.4 [J(117/119Sn,C) = 35.9 Hz], 128.2 [J(117/119Sn,C = 45.9
Hz], 127.0 [J(117/119Sn,C) = 10.7 Hz], 65.6, –9.6 [3 C,
J(117/119Sn,C) = 351.1, 335.8 Hz].
N,N′-Bis(tert-butoxycarbonyl)-N-(3-trimethylstannylben-
zyl)guanidine (10)
A solution of N,N′-bis(tert-butoxycarbonyl)guanidine (9a; 0.583 g,
2.252 mmol, 2 equiv) and Ph3P (0.443 g, 1.689 mmol, 1.5 equiv) in
anhyd toluene (10 mL) was cooled in an ice bath under argon. 3-
(Trimethylstannyl)benzyl alcohol (2; 0.305 g, 1.126 mmol) dis-
solved in anhyd toluene (2 mL) and DIAD (0.321 g, 0.31 mL, 1.689
mmol, 1.5 equiv) were added and the stirring was continued for 5 h
at r.t. (TLC: hexanes–EtOAc, 5:1, Rf = 0.85). The solvent was evap-
orated under reduced pressure and the residue was purified by flash
chromatography (CH2Cl2–hexanes, 3:1) to give precursor 10 (0.503
g, 87%) as colorless crystals; mp 89–90 °C (hexanes, r.t. to –18 °C).
Anal. Calcd for C10H16OSn: C, 44.33; H, 5.95. Found: C, 44.75; H,
5.86.
3-(Trimethylstannyl)benzyl Azide (3)
Diisopropyl azodicarboxylate (0.281 g, 1.16 mmol, 0.27 mL, 1.2
equiv) and HN3 (0.98 mL, 1.41 M in toluene, 1.39 mmol, 1.2 equiv)
were added dropwise to a solution of 3-(trimethylstannyl)benzyl al-
cohol (2; 0.313 g, 1.16 mmol) and Ph3P (0.359 g, 1.39 mmol, 1.2
equiv) in anhyd toluene (6.9 mL) at 0 °C under argon. After stirring
for 18 h at r.t., no alcohol could be detected by TLC (hexanes–
EtOAc, 5:1). The solvent was removed under reduced pressure and
the residue was flash chromatographed (hexanes, Rf = 0.25) to yield
azide 3 (0.283 g, 82%) as a colorless oil. The 1H NMR spectrum was
identical to that reported in the literature.17
IR (Si, film): 3383, 2979, 2930, 1716, 1612, 1296, 1240, 1149 cm–1.
1H NMR (CDCl3): δ = 9.43 and 9.30 (2 br s, 2 H, 2 × NH), 7.45–
7.18 (m, 4 H), 5.15 (s, 2 H), 1.47 and 1.33 (2 s, each 9 H), 0.25 [s,
J(117/119Sn,H) = 55.1, 52.8 Hz, 9 H].
13C NMR (CDCl3): δ = 163.8, 160.9, 155.1, 141.9, 138.3, 135.0
[J(117/119Sn,C) = 37.5 Hz], 134.3 [J(117/119Sn,C) = 36.0 Hz], 127.8
[J(117/119Sn,C) = 47.4 Hz], 127.1 [J(117/119Sn,C) = 10.0 Hz], 84.0,
78.8, 47.6, 28.3 (3 C), 27.8 (3 C), –9.4 (3 C).
N,N′-Bis(tert-butoxycarbonyl)-S-methylisothiourea (7)
A mixture of S-methylisothiuronium hemisulfate (5; 1.392 g, 10.0
mmol), di(tert-butyl) dicarbonate (4.36 g, 20 mmol, 2 equiv),
CH2Cl2 (25 mL), and sat. aq NaHCO3 (25 mL) was vigorously
Synthesis 2012, 44, 3387–3391
© Georg Thieme Verlag Stuttgart · New York