Chemistry Reference
In-Depth Information
Ga
2
O
3
, CaO
4
13/14
NH
3
+5O
2
4
13/14
NO +6H
2
O (1)
2
13/14
NO+O
2
2
13/14
NO
2
(2)
13/14
NO +
13/14
NO
2
+H
2
O
2 [
13/14
N]HNO
2
(3)
NO
N
N
N
N
Cl
Cl
+
[
13
N]HNO
2
(4)
O
O
*
NO
N
N
N
13
NO
-
, Cu dust
AcOH
room temperature
N
Cl
Cl
Cl
Cl
O
O
scheme 4.30
synthesis of [
13
N]nitrous acid and the
13
N-nitrosation of ureas.
HO[
13
N](SO
3
)
2-
+H
2
O (1)
13
NO
-
+ 2HSO
-
+ H
+
HO[
13
N](SO
3
)
2-
+2H
2
O
13
NH
3
OH
+
+ 2SO
2-
+H
+
(2)
scheme 4.31
Preparation of [
13
N]hydroxamine via reaction of [
13
N]nitrite with sulphurous acid.
reaction with water resulted in the formation of [
13
N]nitrous acid; however, reactions with ureas via nitrosation resulted
in total synthesis times that were unacceptably long (60-65 min.) and in low specific radioactivities. An improved method
was later reported, as mentioned above, using the in-target
16
O(p,α)
13
N nuclear reaction that yielded a mixture of [
13
N]nitrite
and [
13
N]nitrate. The reduction of this mixture using Cu dust gave high radiochemical purity [
13
N]nitrite and resulted in an
improved yield of the nitrosation reaction of bis-(2-chloroethyl)-urea to give bis-(2-chloroethyl)-[
13
N]nitrosourea, which
was used in cancer chemotherapy programmes (scheme 4.30) [158]. Although the synthesis time was reduced to 15-20 min.,
the method was carrier-added, which resulted in low specific radioactivities. Additionally, the removal of insoluble material
was found to be tedious work under radiolabelling reaction conditions. recently, Llop et al. [159] reported an improved
online preparation of [
13
N]nitrite where the reduction of [
13
N]nitrate was effectively achieved by simply passing the mixture
through a column containing cadmium on sand. The only radiochemical impurity was found to be [
13
N]ammonia, which did
not affect subsequent reactions.
4.3.5.2 Synthesis of Hydroxyl[
13
N]amine
Hydroxylamine forms a variety of characteristic derivatives such as hydroxamic
acids, oximes, and amidoximes. such derivatives have proven useful in understanding the structure and function of many
biologically active molecules. [
13
N]hydroxylamine has been prepared from [
13
N]nitrite [160] via with sulphurous acid
(scheme 4.31), although low specific activities were obtained and [
13
N]nitrate was a major radiolabelling impurity in the
reaction from the initial nuclear reaction.
4.3.5.3 Synthesis of Nitrosothiols, Nitrosamines, and Diazo Compounds
S
-nitrosoglutathione is a known platelet
aggregation inhibitor and a potentially useful vascular imaging agent. [
13
N]
S
-nitrosoglutathione has recently been efficiently
prepared via the no-carrier added reaction of [
13
N]nitrite with a free thiol group under acidic conditions (scheme 4.32) [159].
A fully automated method has been developed for the radiosynthesis of [
13
N]
S
-nitrosothiols using a trapping [
13
N]nitrite and
nitrosation reaction on anion exchange resin [161]. A similar anion exchange resin technique has also proven useful for the
preparation of a range of [
13
N]nitrosoamines (scheme 4.32) [162].
The aromatic diazo moiety is a structural component of the Congo red dye, a widely used marker to identify beta-amyloid
(Aβ) aggregation in the brains of people who have suffered from Alzheimer's disease. C-11 and F-18 labelled Aβ marker ana-
logues have received considerable attention over the past decade as a diagnostic tool for Alzheimer's disease. N-13 labelling
of the diazo groups in Congo red derivatives also presents as a viable route for the preparation of PET tracers for amyloid
imaging. One route to labelling such diazo compounds recently developed by Llop et al. [163] reports the reaction of primary
aromatic amines with [
13
N]nitrite to give a [
13
N]diazonium salt followed by reaction with an aromatic amine or phenol to gen-
erate diazo compounds in good radiochemical yields (scheme 4.32).