Chemistry Reference
In-Depth Information
acetophenone and trifluoroacetophenone. Acid hydrolysis of the intermediate 2-
oxazolines gives optically active a-hydroxy aldehydes. The best asymmetric induc-
tion of the isocyanides is seen with (
)-S-phenyl-N-tosylsulfonimidoylmethyl iso-
cyanide 1605.
O
2
S
NC
NC
S
O
O
O
2
SO
2
SO
2
1602
1603
NC
NC
TosMIC
1600
1601
O
NC
O
S
N
SO
2
O
SO
2
NC
1604
1605
Typical procedure. p-Toluenesulfonylmethyl
isocyanide (TosMIC) 1600 [1202]:
N-(p-
Tolylsulfonylmethyl)formamide 1609:
Tol-SO
2
Na
þ
CH
2
O
þ
H
2
NCHO
!
Tol-SO
2
NHCHO
þ
H
2
O
1606
1607
1608
1609
A 3-L, three-necked, round-bottomed flask, equipped with a mechanical stirrer, a
condenser, and a thermometer, was charged with sodium p-toluenesulfinate 1606
(267 g, 1.5 mol). After the addition of water (750 mL), a 34-37% solution of form-
aldehyde 1607 (350 mL, 378 g, ca. 4.4 mol), formamide 1608 (600 mL, 680 g, 15
mol), and formic acid (200 mL, 244 g, 5.3 mol), the stirred reaction mixture was
heated at 90
C. The sodium p-toluenesulfinate dissolved during the heating, and
the clear solution was kept at 90-95
C for 2 h. It was then cooled in an ice/salt
bath with continued stirring and further cooled overnight in a freezer at
20
C.
The white solid produced was collected by suction filtration. It was washed thor-
oughly in a beaker by stirring with three 250 mL portions of iced water. The
product was dried under reduced pressure over phosphorus pentoxide at 70
Cto
provide 134-150 g (42-47%) of crude N-(p-tolylsulfonylmethyl)formamide 1609;
mp 106-110
C. This product was su
ciently pure to be used directly in the fol-
lowing reaction.
p-Toluenesulfonylmethyl isocyanide (TosMIC) 1600:
Tol-SO
2
NHCHO
þ
POCl
3
!
Tol-SO
2
CH
2
N
b
C
þ
HPO
2
Cl
2
þ
HCl
1609
1600
