Chemistry Reference
In-Depth Information
size and number of milling balls, and the material of milling balls and bea-
kers. The first two have been found to be the most important parameters.
1
Basically two types of ball mills have been frequently used to perform organic
transformations, i.e. mixer mill (MM) and planetary mill (PM) (for further
details the reader is referred to Chapter 10).
The present chapter covers reactions involving carbon-heteroatom (C-N,
C-O, C-S, C-Cl, C-Br, etc.) bond formation and synthesis of heterocycles
under ball milling.
1.2 Carbon-Heteroatom Bond Forming Reactions
under Ball Milling
1.2.1 C-N Bond Forming Reactions
Kaupp and co-workers have reported the quantitative formation of imines
by ball milling a stoichiometric mixture of aldehyde and amine in less than
30 min (Scheme 1.1).
2,3
All the reactions were carried out below 0 1C except for the condensations
of 4-nitroaniline with 4-hydroxybenzaldehyde and 4-nitrobenzaldehyde,
which were performed at 60 and 80 1C, respectively.
The same group also investigated the solid-state reactions of hydrazine-
hydroquinone (1 : 1 complex) and of hydrazine hydrochloride with solid
aldehyde, ketone, carboxylic acid, thiohydantoin and 4-nitrophenyl iso-
thiocyanate and found that only the hydrazine hydroquinone complex
provides quantitative addition, condensation, ring opening and ring closure
(Schemes 1.2 and 1.3).
4
1) MM (30 Hz)
-20 °C to 80 °C
0.5-12 h
2) drying under
vacuum at 80 °C
R
2
NH
2
CHO
N
+
R
1
R
2
R
1
100%
Scheme 1.1
Imine formation under mechanical milling.
OH
O
N
N
Ball-milling
-2H
2
O
R
1
R
1
2
+
NH
2
-NH
2
.
R
1
R
2
R
2
R
2
OH
100%
Some selected examples:
N
N
N
N
OH
Cl
HO
Cl
H
H
H
H
N
N
N
N
N(CH
3
)
2
NO
2
(H
3
C)
2
N
O
2
N
H
H
Scheme 1.2
Synthesis of azines from the solid state reaction between aldehyde or
ketone and hydrazine-hydroquinone complex in a ball mill.
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