References and Notes
1
Isidro-Llobet A.
Álvarez M.
Albericio F.
Chem.
Rev.
2009,
109:
2455
2
Pothukanuri S.
Winssinger N.
Org. Lett.
2007,
9:
2223
3
Pothukanuri S.
Pianowski Z.
Winssinger N.
Eur.
J. Org. Chem.
2008,
3141
4
Loren JC.
Krasinski A.
Fokin VV.
Sharpless KB.
Synlett
2005,
2847
5a
Smith PAS.
Open-Chain Nitrogen Compounds
Vol. 2:
Benjamin;
New
York:
1966.
p.211-256
5b Bräse, S.; Gil, C.;
Knepper, K.; Zimmermann, V. Angew. Chem. Int.
Ed. 2005, 44,
5188
5c
Bräse S.
Bannert K.
Organic Azides: Syntheses and Applications
Vol.
1:
Wiley;
Chichester:
2010.
p.3-27
See, for example:
6a
Gangwar S.
Pauletti GM.
Siahaan TJ.
Stella VJ.
Borchardt RT.
J. Org. Chem.
1997,
62:
1356
6b Goebel T, Humbert-Droz E, and Schwarzenbach M. inventors; WO 200029378.
; Chem. Abstr. 2000, 132, 347496
6c
Gediya LK.
Khandelwal A.
Patel J.
Belosay A.
Sabnis G.
Mehta J.
Purushottamachar P.
Njar VCO.
J.
Med. Chem.
2008,
51:
3895
6d Gallop MA, Cundy
KC, Zhou CX, Yao F, Xiang J.-N, Ollman IR, and Qiu FG. inventors; US 20060229361 A1.
; Chem. Abstr. 2006, 145, 418708
7
CAUTION: Silver
azide is an explosive. Safety equipment such as leather gloves,
face shield, protective shield, and ear plugs is recommended. Further
safety notes for work with metal and organic azides can be found
in ref. 5c.
8 Remaining silver azide may be quenched
through oxidation with aq KI3 solution under sulfide
catalysis (iodine-azide reaction): Silver azide containing
salts and contaminated filters were added to a stirred aq solution
of KI3 (500 mL, 0.2 M) and Na2S (50 mg) resulting
in immediate development of N2. This slurry was stirred
overnight.
9 Calculated from signals in ¹H
NMR spectrum of crude.
10
Azidomethyl 4-Nitrophenyl
Carbonate (1)
AgNO3 (4.60 g, 27.1 mmol,
1.25 equiv) was dissolved in H2O (20 mL) and added to
a stirred solution of NaN3 (1.76 g, 27.1 mmol, 1.25 equiv)
in H2O (20 mL). AgN3 (4.06 g, 27.1 mmol, 1.25
equiv) immediately formed as a white microcrystalline precipitate.
The supernatant was aspired with a syringe, and the precipitate
was washed with H2O (3 × 30 mL),
acetone (3 × 30 mL), and toluene
(3 × 30 mL). The AgN3 was
suspended in toluene (50 mL), MS 4 Å (6.0 g) were added,
and the resulting slurry was stirred 15 min under argon. Iodomethyl
4-nitrophenyl carbonate6b (4,
7.00 g, 21.67 mmol, 1.0 equiv) was added in one portion. Complete
conversion was detected by TLC [R
f
= 0.52 (CH2Cl2-PE = 3:2)] after
3 h of stirring in the dark. Silver salts (compare ref. 8) were
filtered off, and the filtrate was diluted with CH2Cl2 (200
mL) and washed with H2O (50 mL), Na2CO3 solution
(2 × 50 mL, 2 M), H2O
(50 mL), and sat. NaCl solution (50 mL). The organic phase was dried over
Na2SO4, filtered, and evaporated under reduced pressure.
The resulting yellow oil was purified by flash column chromatography,
eluting with CH2Cl2-PE (3:4) → CH2Cl2-PE
(1:1). The title compound was obtained as a slight yellowish oil
that slowly crystallized (3 d) at -18 ˚C, but
rapidly crystallized after addition of a seed crystal (3.72 g, 15.6
mmol, 72%). Yellowish powder, mp 35 ˚C.
IR (neat): 3119, 2962, 2559, 2369, 2105, 1967, 1766, 1617, 1594,
1523, 1491, 1347, 1198 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 5.32
(s, 2 H, CH2N3), 7.40-7.46 (m, 2
H, ArH), 8.28-8.34 (m, 2 H, ArH). ¹³C
NMR (75 MHz, CDCl3): δ = 78.96
(CH2), 121.74 (CH), 125.45 (CH), 145.72, 152.29, 155.04.
MS (EI, 70 eV): m/z (%) = 238
(2) [M]+, 196 (12), 166 (36),
139 (40), 122 (42), 56 (100), 28 (71). HRMS (EI): m/z calcd
for C8H6N4O5: 238.0338 [M]+;
found: 238.0319 [M]+. Anal.
Calcd for C8H6N4O5:
C, 40.35; H, 2.54; N, 23.53. Found: C, 40.25; H, 2.69; N, 23.26.
11
General Procedure
for Azoc Protection with Azidomethyl 4-Nitrophenyl Carbonate (1)
and Analytical Data of Compounds 6b,d,g
Azidomethyl
4-nitrophenyl carbonate (1, 300 mg, 1.26 mmol,
1.0 equiv) was dissolved in anhyd DMF (3 mL) and cooled to 0 ˚C.
Either of compounds 5a-g (1.26 mmol) was dissolved in anhyd DMF
(2 mL) in an separate flask and treated with DIPEA (1.39 mmol, 236 µL,
1.1 equiv). The resulting solution was added dropwise, within 2
min, to the solution of 1. The reaction
was monitored via TLC (CH2Cl2-PE = 3:2).
After complete conversion, the reaction mixture was diluted with
EtOAc (200 mL) and washed with Na2CO3 solution
(8 × 50 mL, 2 M). The combined
aqueous solutions were re-extracted with EtOAc (30 mL). The extract
was washed once with H2O (10 mL). The combined organic phases
were washed with sat. NaCl solution (2 × 50 mL), dried
over Na2SO4, filtered, concentrated in vacuo
and dried at <10-³ mbar for
at least 3 h. Analytical data of compounds 6a and 6f were found to be identical to those
in ref. 2.
Azidomethyl 4-Aminobenzylcarbamate
(6b)
Orange oil which slowly crystallized at -18 ˚C
(2 weeks) to give an orange solid with mp 26-28 ˚C.
IR (neat): 3423, 3328, 2154, 2098, 1723, 1697, 1617, 1539, 1512
cm-¹. ¹H NMR (300
MHz, CDCl3): δ = 3.68
(s, 2 H, NH2), 4.27 (d, ³
J = 5.9 Hz,
2 H, CH2Ar), 5.05-5.20 (m, 3 H, CH2N3,
NH), 6.62-6.68 (m, 2 H, ArH), 7.08 (d, ³
J = 8.3 Hz,
2 H, ArH). ¹³C NMR (75 MHz, CDCl3): δ = 44.89
(ArCH2), 75.32 (CH2N3), 115.25,
127.59, 128.72, 129.04, 146.08, 155.18. ESI-HRMS: m/z calcd
for C9H11N5O2Na: 244.0805 [M + Na]+; found:
244.0802 [M + Na]+.
Azidomethyl 5-Hydroxypentylcarbamate (6d)
Colorless
oil. IR (neat): 3329, 2937, 2864, 2140, 2100, 1705, 1532 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 1.36-1.48
(m, 2 H, H-3), 1.51-1.65 (m, 5 H, H-2, H-4, OH), 3.24 (q, ³
J = 6.7 Hz,
2 H, CH2NH), 3.65 (t, ³
J = 6.4 Hz,
2 H, CH2OH), 5.02 (s, 1 H, NH), 5.13 (s, 2 H, CH2N3). ¹³C
NMR (75 MHz, CDCl3): δ = 22.87
(C-3), 29.51, 32.13, 41.02 (C-1), 62.55 (C-5), 75.22 (CH2N3),
155.36 (C=O). ESI-HRMS: m/z calcd
for C7H14N4O3Na: 225.0958 [M + Na]+;
found: 225.0964 [M + Na]+.
Methyl 4-[(Azidomethoxy)carbonylamino]-
N
-methyl-pyrrole-2-carboxylate
(6g)
Compound 6g was purified
via flash column chromatography using a gradient of CH2Cl2 → CH2Cl2-MeOH
(99:1).
Orange brownish powder; mp 136-138 ˚C.
IR (neat): 3509, 3310, 2958, 2163, 2141, 2112, 1967, 1717, 1679,
1586, 1565 cm-¹. ¹H
NMR (500 MHz, DMSO-d
6): δ = 3.72
(s, 3 H, Me), 3.82 (s, 3 H, Me), 5.27 (s, 2 H, CH2N3),
6.69 (d, 4
J = 1.9
Hz, 1 H, ArH), 7.14 (d, 4
J = 1.9
Hz, 1 H, ArH), 9.80 (s, 1 H, NH). ¹³C
NMR (126 MHz, DMSO-d
6): δ = 36.09,
50.88, 74.88, 107.56, 118.99, 119.47, 121.92, 152.38, 160.54. ESI-HRMS: m/z calcd for C9H11N5O4Na:
276.0703 [M + Na]+; found:
276.0716 [M + Na]+.
12
Baird E.
Dervan PB.
J. Am. Chem. Soc.
1996,
118:
6141
13
Ammonium 2-[(Azidomethoxy)carbonylamino]ethyl Hydrogenphosphate
(6h)
Azidomethyl 4-nitrophenyl carbonate (1, 300 mg, 1.26 mmol, 1.0 equiv) and 2-aminoethyl
dihydrogen phosphate (177.7 mg, 1.26 mmol, 1.0 equiv) were added
to a flask and suspended in DMF (4 mL). DIPEA (4.16 mmol, 707 µL,
3.3 equiv) and H2O (3 mL) were added. The resulted suspension was
sonicated for 2 min and then stirred at 20 ˚C.
After 20 min, a clear solution formed. A complete conversion was detected
after 30 min via TLC (CH2Cl2-PE = 3:2).
The reaction mixture was diluted with H2O (200 mL) and
poured on a DEAE-cellulose column [100 g, 20 cm, HCO3
- form, Express-Ion
exchanger D, Whatman (Maidstone, UK)]. The column was washed
with H2O (200 mL) and 100 mM NH4HCO3 solution
(500 mL). The product-containing fractions were combined and the
resulting solution concentrated to 20 mL, followed by lyophilization
to dryness. The title compound 6h was obtained
as a colorless solid (321 mg, 1.25 mmol, 99%). IR (neat):
3210, 2889, 2103, 1705, 1532, 1455 cm-¹. ¹H
NMR (300 MHz, D2O): δ = 3.28
(t, ³
J = 5.3
Hz, 2 H), 3.75-3.83 (m, 2 H), 5.06 (s, 2 H, CH2N3). ¹³C
NMR (75 MHz, D2O): δ = 41.25
(d,
³
J
P-C2 = 7.8
Hz, C-2), 63.59 (d, ²
J
P-C1 = 5.2
Hz, C-1), 75.71 (CH2N3), 157.35 (C=O). ³¹P
NMR (121.5 MHz, D2O): δ = 1.10.
ESI-HRMS: m/z calcd for C4H8N4O6P:
239.0187 [M]-; found: 239.0175 [M]-.
14
Ammonium 3-[(Azidomethoxy)carbonylamino]-propanoate
(6i)
A sample of β-alanine (112.2 mg, 1.26
mmol) was treated as described in ref. 13 but in the presence of
a smaller amount of DIPEA (471 µL, 2.77 mmol, 2.2 equiv).
The column purification used a higher concentration of NH4HCO3 (250 mM)
for elution from the DEAE-cellulose. The title compound was obtained
as colorless oil (236.2 mg, 1.15 mmol, 91%). IR (neat):
3231, 2965, 2103, 1967, 1701, 1524, 1447, 1409, 1219 cm-¹. ¹H
NMR (300 MHz, D2O): δ = 2.44 (t, ³
J = 6.6 Hz,
2 H), 3.31 (t, ³
J = 6.6
Hz, 2 H), 5.06 (s, 2 H, CH2N3). ¹³C
NMR (75 MHz, D2O): δ = 34.95,
36.79, 75.62 (CH2N3), 157.14, 177.60. ESI-HRMS: m/z calcd for C5H7N4O4:
187.0473 [M]-; found: 187.0468 [M]-.
15
Bentley DR. et
al. Nature (London)
2008,
456:
53