Chemistry Reference
In-Depth Information
(MgSO
4
) and concentrated under reduced pressure to give 5.8 g of crude (
)-cis-
isocyanide as a yellow solid. Column chromatography (SiO
2
; EtOAc/hexane, 2:1)
gave 4.52 g (17.0 mmol, 69%) of analytically pure (
G
)-cis-2-(isocyanomethyl)-5,5-
dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphorinane 1618 as transparent needles;
mp 145
C.
(2S,4S)-(
G
)-cis-2-(Isocyanomethyl)-5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphor-
inane was prepared as described above from (2S,4S)-(
)-cis-2-(formamidomethyl)-
5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphorinane (3.5 g, 12.4 mmol) in 31%
yield (1.0 g, 4.0 mmol); mp 133
C; [a]
20
578
þ
¼
46
:
4(c
¼
0
:
5, CHCl
3
) [1207].
Typical
)-trans-2-(Isocyanomethyl)-5,5-dimethyl-2-oxo-4-phenyl-
1,3,2-dioxaphosphorinane 1619 [1207]:
A solution of
procedure.
(2R,4S)-(
)-cis-2-(isocyano-
methyl)-5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphorinane (265 mg, 1.00 mol)
and KF (25 mg, 0.4 mmol) in DMSO (4 mL) was heated at 100
C for 4 h. After
cooling to room temperature, water (20 mL) was added and the mixture was cooled
in ice. The solid formed was collected and dried to give 250 mg (94%) of a solid
mixture of (2S,4S)-(
(2S,4S)-(
)-isomers (1:3). The mixture was sepa-
rated by column chromatography (SiO
2
; EtOAc/hexane, 2:1) and the first fraction
(R
f
)- and (2R,4S)-(
¼
0
:
6) gave, after three crystallizations from hexane/Et
2
O (2:1), solid (2R,4S)-
(
)-trans-2-(isocyanomethyl)-5,5-dimethyl-2-oxo-4-phenyl-1,3,2-dioxaphosphorinane
1619 (160 mg, 60%), mp 155
C, which was pure according to NMR; [a]
20
578
¼
5, CHCl
3
).
Formamidines are interesting and important compounds that feature in the bio-
syntheses of imidazoles and purines. For the preparation of unsymmetrical form-
amidines, benzotriazol-1-ylalkyl isocyanides are versatile synthons [1208]. They
are prepared from the corresponding formamides by dehydration with phosphoryl
chloride in yields of 64-77%.
A useful tool in the direct isocyanomethylation of nitroarenes 1620 at the ortho-
or para-positions to the nitro group, thereby yielding 1622-1624, is phenyl-
thiomethyl isocyanide 1621 [1209]. The isocyanomethyl group can be readily con-
verted into the aminomethyl group, which is otherwise not easily accessible in the
vicinity of a nitro group.
38
:
2(c
¼
0
:
NO
2
NO
2
NO
2
1) BuOK
DMF
0-3°C
15-30 min
NO
2
NC
CN
+
+
+
PhS
NC
Cl
Cl
Cl
1621
Cl
2) CO
2
AcOEt
1620
NC
16 %
1622
40 %
1623
16 %
1624
Typical procedure. Phenylthiomethyl isocyanide 1621 [1209]: To a stirred solution of
N-(phenylthiomethyl)formamide (10.9 g, 0.065 mol) and triethylamine (55 g, 0.54
mol) in dichloromethane (200 mL), POCl
3
(10.7 g, 0.07 mol) was slowly added
dropwise while the temperature was kept at 20-30
C. After the addition was
