Synthesis of [11C]/(13C)amines via carbonylation followed by reductive animation

Article abstract of DOI:10.1039/b403481c

Twelve ¹¹C-labelled amines were prepared via ¹¹C-carbonylation followed by reductive amination. The ¹¹C-carbonylation was performed in the presence of tetrakis(triphenylphosphine)palladium using aryl iodides or aryl trifla

Full text of DOI:10.1039/b403481c

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Synthesis of [11C]/(13C)amines via carbonylation followed by
reductive amination
Obaidur Rahman,a Tor Kihlbergb and Bengt Långström*a,b
a Department of Organic Chemistry, Institute of Chemistry, BMC, Uppsala University,
Box 599, S-751 24 Uppsala, Sweden
b Uppsala Imanet AB, P. O. Box 967, SE-751 09 Uppsala, Sweden.
E-mail: bengt.langstrom@uppsala.imanet.se
Received 8th March 2004, Accepted 27th April 2004
First published as an Advance Article on the web 11th May 2004
Twelve 11C-labelled amines were prepared via 11C-carbonylation followed by reductive amination. The
11C-carbonylation was performed in the presence of tetrakis(triphenylphosphine)palladium using aryl iodides or
aryl triflates, [11C]carbon monoxide and phenyl-/methylboronic acid. The [11C]ketones formed in this step were
then transformed directly into amines by reductive amination using different amines in the presence of TiCl4 and
NaBH3CN. The 11C-labelled amines were obtained with decay-corrected radiochemical yields in the range 2–78%.
The radiochemical purity of the isolated products exceeded 98%. (13C)Benzhydryl-phenyl-amine was synthesised and
analysed by NMR spectroscopy for confirmation of the labelling position. Specific radioactivity was determined for
the same compound. The reference compounds were prepared by reductive amination of ketones using conventional
reaction conditions and three of the compounds were novel. The presented approach is a new method for the
synthesis of [11C]/(13C)amines.
Introduction
Results and discussion
The non-invasive imaging technique, positron emission tomo-
graphy (PET) has become the tool of choice for many
diagnostic medical applications. Moreover, it has recently been
indicated that PET could be a potential tool in drug develop-
ment.1 The demand for new methods for the labelling of
biologically interesting compounds with short-lived positron
emitting radionuclides is increasing with the expanding use of
PET in biomedical research. The most commonly used radio-
nuclides for PET studies are 18F, 11C, 76Br, 68Ga and 15O. Among
these, 11C is particularly interesting since most biologically
important compounds are organic molecules and 11C can be
introduced into these molecules by substitution of a carbon
atom. Moreover its half-life (t = 20 min) allows both repeated
½
PET studies in the same object within a relatively short time
frame, and multi-step tracer syntheses. Another important con-
sequence of the short half-life and the production methods of
11C, is that high levels of specific radioactivity can be achieved.
The methods so far most commonly used for the synthesis of
11C-labelled compounds are S-, O- and N-methylations using
[11C]methyl iodide or [11C]methyl triflate.2 Other methods
like the Grignard reaction using [11C]carbon dioxide3 or C–C
coupling reactions using [11C]methyl iodide and organometallic
reagents4 are also used but less frequently. Carbonylation
using [11C]carbon monoxide has recently become an increas-
ingly employed 11C-labelling strategy and methods have been
developed for the synthesis of a wide range of 11C-labelled
carbonyl compounds such as ketones,5 amides,6 imides,7
hydrazides,8 etc. Recently, the synthesis of 11C-labelled ketones
by the Suzuki coupling reaction was reported.9 The successful
synthesis of [11C]ketones stimulated us to investigate the
possibility of converting the [11C]ketones to [11C]amines since
the amine group is a key functional group in many pharm-
aceutical agents. Reductive amination of carboxylic acids
and [11C]magnesium halide carboxylates was applied several
years ago for the preparation of [11C]amines3b and recently
[11C]acetone was used in a reductive amination with 1-phenyl-
piperazine.10 In this work, we have explored the scope and
limitations of transformations of various [11C]ketones prepared
by carbonylation using [11C]carbon monoxide to different
[11C]amines.
Fig. 1 Target molecules. * = 11C.
The 11C-labelled amines were synthesised by a route based on
[11C]carbonylation followed by reductive amination (Scheme 1).
Carbonylation was performed in a micro autoclave of 200 µL
volume using aryl iodide or triflate, tetrakis(triphenyl-
phosphine)palladium(), phenyl or methylboronic acids and a
low concentration (typically ca. 10 to 100 µM) of [11C]carbon
monoxide. In this study a standardised procedure based on a
5 min carbonylation was used. However, this time may not be
Scheme 1 X = I, OTf, Ar = phenyl, 4-nitrophenyl; R = phenyl, methyl;
RЈ = allyl, isopropyl, methylene, phenyl; RЉ = H, allyl. * = 11C. a: used in
the case where X = OTf.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 6 1 2 – 1 6 1 6
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4
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Table 1 Trapping efficiency and radiochemical yields for the 11C-amines shown in Fig. 1
Entry
Amine
Ketone
Product
TE (%)a
RYC b, %, (n)c
LC-MS [ESIϩ], m/z (M ϩ 1)
1
2
3
4
5
6
7
8
9
16
16
16
17
17
17
18
18
18
19
19
19
13
14
15
13
14
15
13
14
15
13
14
15
1
2
94
57
90
93
55
92
95
54
92
96
57
95
66 (34)
35 (18)
44 (20)
53 (28)
37 (17)
45 (18)
5
224
269
162
226
271
164
—
3
4
5
6
7
8
2
—
9
39 (15)
78 (49)
36 (17)
49 (26)
202
260
305
198
10
11
12
10
11
12
a TE = Trapping Efficiency, decay-corrected, the fraction of radioactivity left in the crude product after purge with nitrogen. b RCY = radiochemical
yield; decay-corrected and determined by analytical LC on the basis of radioactivity in the crude product before nitrogen purging and the purity of
crude product. The value is the mean value of at least 3 experiments. c Values in parentheses are the isolated yields.
optimal for all cases. The [11C]ketones obtained in this step were
reductively aminated using TiCl4, amines and NaBH3CN.
Three [11C]ketones (Fig. 2) and four amines (Fig. 3) were
selected in this investigation and all of the amines were reacted
with all of the ketones. The [11C]ketones were prepared by
11C-carbonylation of aryl iodide or triflate and phenyl-/methyl-
boronic acids. [11C]4-Nitro-benzophenone was prepared from
4-nitro-phenyl triflate using the same reaction conditions
described in our previous report,9 but [11C]benzophenone and
[11C]acetophenone were prepared from iodobenzene since
iodobenzene gave higher radiochemical yields in these cases.
using radio HPLC and LC-MS. Compounds 7 and 8 could
not be analysed by LC-MS owing to the low concentrations.
They were characterised by radio HPLC with co-injection of
non-radioactive reference compounds and comparing the
retention times for the UV and radioactivity peaks. Compound
10 was labelled in parallel with 11C and 13C, and the 13C-labelled
product was analysed by 13C NMR for confirmation of the
labelling position. The 13C spectrum displayed only one peak at
63.19 ppm (Fig. 4) which corresponded to the –CH– carbon
and matched with the same peak observed for the reference
compound. The specific radioactivity was determined for
compound 10 and the obtained value was 213 GBq µmolϪ1
,
50 min after a 10 µA bombardment. We expect that this
procedure will increase the possibility of producing compounds
with high specific radioactivity, although it was not the focus of
this research.
Fig. 2 Ketones used in the syntheses. * = 11C.
Fig. 3 Amines used in the syntheses.
The decay-corrected radiochemical yields (determined by
analytical HPLC) of the [11C]amines, calculated from [11C]-
carbon monoxide, were in the range of 2 to 78% (Table 1). The
radiochemical yield was lowest (2%) (entry 8 in Table 1) when
the secondary amine, diallylamine (18) was reacted with
[11C]4-nitro-benzophenone and a low radiochemical yield (5%)
(entry 7 in Table 1) also was obtained when the same amine was
reacted with [11C]benzophenone. The reason for these low
radiochemical yields may be steric hindrance, since the same
amine gave a higher radiochemical yield (39%) (entry 9 in Table
1) when reacted with [11C]acetophenone where steric hindrance
is less. The steric factor is less important when a longer reaction
time was used e.g. in the synthesis of reference compounds. The
radiochemical yields for amines 2, 5, 8 and 11 (entries 2, 5, 8
and 11 respectively in Table 1) prepared from [11C]4-nitro-
benzophenone were lower as the formation of [11C]4-nitro-
benzophenone itself was low. In all cases the isolated
radiochemical yields for [11C]amines were lower (as low as 50%)
than the analytical yields (Table 1) i.e. a substantial amount
of product was lost during the isolation and purification. After
the reductive amination, a precipitate was obtained and a lot
of radioactivity was trapped in the precipitate and could not be
removed. Further technological development is needed to
improve the recovery of the radioactive product.
Fig. 4 13C NMR spectra of 13C-labelled and reference benzhydryl-
phenyl-amine.
Reductive aminations of aldehydes and ketones are fre-
quently used methods for the synthesis of amines.11 The
reducing agents used for this purpose are hydride donors,
usually sodium cyanoborohydride (NaBH3CN).12 Reductive
aminations of hindered or biaryl ketones were performed
using NaBH3CN together with titanium() chloride13 or
The radiochemical purity of the isolated product exceeded
98%. The identities of the labelled compounds were assessed
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 6 1 2 – 1 6 1 6
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titanium() isopropoxide.14 Although these methods required
several hours of reaction time (which is not appropriate in a
synthesis with the short half-lived 11C), we could successfully
use NaBH3CN in combination with TiCl4 and complete the
reaction within 6 min using our reaction conditions. In a con-
ventional synthesis, the reductive amination of ketones using
TiCl4 and NaBH3CN required 2 mol equivalent of amines. But
in the labelling synthesis, a large excess of cold reagents is used
in order to avoid side reactions and most importantly to obtain
a reasonable reaction rate. If equimolar amounts (compared
with the labelled ketones) were used, the reaction rate would
be ca. 10Ϫ4 times lower. Therefore the optimal concentration
of amines required was determined experimentally. The
optimisation was performed for compound 10 and the optimal
concentration of amine (97.5 mM) was then used for other
compounds.
After carbonylation, the product was collected in a 5 mL vial
and reductive amination was performed directly in that vial.
The reagents were added in two steps. Amine and TiCl4 were
added first and the mixture was allowed to stand for 3 min at
60 ЊC, then the second reagent, NaBH3CN, was added and the
same temperature maintained for another 3 min. In most cases
the reductive amination was completed after 6 min (checked by
radio HPLC). When allylamine, isopropylamine or aniline were
used the 11C-ketones were consumed completely. But when
diallylamine was reacted with ketones 13 and 14, about 50% of
the 11C-ketones remained unreacted in the standardised
experiment.
Liquid chromatographic analysis (LC) was performed with
a Beckman 126 gradient pump and a Beckman 166 variable
wavelength UV-detector in series with a βϩ-flow detector. The
following mobile phases were used: triethylamine (0.1% in
H2O), pH 9 (A1) and acetonitrile (B1), 0.01 M formic acid in
H2O (A2) and methanol (B2). The identity and radiochemical
purity of the labelled products were assessed by analytical LC:
solvent A1–B1 (70 : 30); linear gradient to 0 : 100 in 10 min,
flow 1.5 mL minϪ1, wavelength 254 nm. A Jones Chromato-
graphy Genesis C18, 5 µm, 250 × 4.6 mm (i.d.) column was used
for this analysis. For semi-preparative LC, a Beckman Ultra-
sphere ODS C18, 5 µm, 250 × 10 mm (i.d.), column was used
with a flow of 4 mL minϪ1. The mobile phases used were
A1–B1(70 : 30); linear gradient to 0 : 100 in 10 min.
Synthia, an automated synthesis system, was used for LC
injection and fraction collection.19 The Beckman System Gold
chromatography software package was used for data collection
and LC control. Radioactivity was measured in an ion chamber,
Veenstra Instrumenten bv, VDC-202. For coarse estimations of
radioactivity during production, a portable dose-rate meter
was used, Långenäs eltekniska AB. The non-radioactive
compounds were characterised by 1H and 13C NMR and
GC-MS. NMR spectra were recorded on a Varian Unity-400
NMR instrument. [D1]Chloroform was used as the internal
standard. LC-MS was performed using a Micromass VG
Quattro with electrospray ionisation (ESIϩ). A Beckman 126
pump, a CMA 240 autosampler and a Jones Chromatography
Genesis C18 (5 µm, 250 × 4.6 mm id) column were used. Mobile
phases were A2 and B2. GC-MS was performed with a
Finnigan GCQ mass spectrometer coupled to a Finnigan
Q-GC.
All reference compounds except N-allyl-α-methylbenzyl-
amine were prepared with good to excellent yields by reductive
amination of different ketones with different amines in the
presence of TiCl4 and NaBH3CN (Scheme 2) under the
conventional reaction conditions.12 Three of these compounds,
21e, 21f and 21g were new. Both 1H and 13C NMR data for the
known compounds 21a,15 21c,15 21d16 and 21k17 are available in
the literature and our data were compared with these for the
identification. NMR data for the other compounds and MS
data for all of the prepared reference amines are presented in
this report.
Synthesis of 11C-amines (1–12)
The 11C-Carbonylation was performed as described previously9
using tetrakis(triphenylphosphine)palladium() (5.0 mg, 4.3
µmol), aryl iodide/triflate (30.8 µmol) and phenyl- or methyl-
boronic acid (49.2 µmol). The crude product was transferred to
a pre-evacuated, septum-fitted vial (5 mL) and the radioactivity
was measured. The vial was purged with nitrogen to remove the
unreacted [11C]carbon monoxide and the radioactivity was
measured again to determine the trapping efficiency. Titanium
tetrachloride (500 µL of 1 M solution in CH2Cl2, 0.5 mmol) and
an amine (87.8 µmol) were added and the mixture was heated
for 3 min at 60 ЊC. Sodium cyanoborohydride (500 µL of 1 M
solution in MeOH, 0.5 mmol) was added and the mixture was
heated for an additional 3 min at the same temperature. The
reaction was quenched with slow addition of aqueous sodium
hydroxide (500 µL of 2 M aqueous solution) and filtered. The
crude product was analysed with HPLC together with a small
amount of the reference compound for identification of the
product. The non-isolated radiochemical yield was determined
by multiplying the purity of the crude product by the trapping
efficiency. The volume of the filtrate was reduced to 1 mL by
heating at 60 ЊC and purging with nitrogen. Methanol (1 mL)
and water (0.5 mL) were added and the resulting mixture was
injected onto the semi-preparative LC. The collected fractions
were analysed by analytical HPLC to determine the radio-
chemical purity and also analysed by LC-MS using electrospray
ionisation (ESIϩ) for final characterisation of the product.
Scheme 2 Ar = R = Ph, RЈ = allyl, RЉ = H (21a), Ar = R = Ph, RЈ =
isopropyl, RЉ = H (21b), Ar = R = Ph, RЈ = RЉ = allyl (21c), Ar = R = Ph,
RЈ = phenyl, RЉ = H (21d), Ar = Ph, R = 4-nitro-phenyl, RЈ = allyl, RЉ =
H (21e), Ar = Ph, R = 4-nitro-phenyl, RЈ = isopropyl, RЉ = H (21f ), Ar =
Ph, R = 4-nitro-phenyl, RЈ = RЉ = allyl (21g), Ar = Ph, R = 4-nitro-
phenyl, RЈ = phenyl, RЉ = H (21h), Ar = Ph, R = methyl, RЈ = isopropyl,
RЉ = H (21i), Ar = Ph, R = methyl, RЈ = RЉ = allyl (21j), Ar = Ph, R =
methyl, RЈ = phenyl, RЉ = H (21k),
Experimental
General
The reference compound, N-allyl-α-methylbenzylamine and all
of the reagents except tetrakis(triphenylphosphine)palladium
and boronic acids, were obtained from Aldrich. Tetrakis-
(triphenylphosphine)palladium and phenyl-and methylboronic
acids were obtained from Lancaster. Freshly distilled THF
(distilled from sodium/benzophenone under nitrogen) was used
in the labelling reactions.
Synthesis of 13C-benzhydryl-phenyl-amine
Tetrakis(triphenylphosphine)palladium() (6.0 mg, 10.6 µmol)
and iodobenzene (10 µL, 18.2 mg, 89.3µmol) were placed in a
vial (1 mL), flushed with nitrogen and dissolved in THF (200
µL). Phenylboronic acid (10 mg, 82.0 µmol) was dissolved
in THF (200 µL) and added to the previous solution. The result-
ing mixture was loaded into the injection loop. The reagent
mixture and (13C)carbon monoxide were transferred under
pressure (35 MPa) into the micro-autoclave (200 µL). The
[11C]Carbon dioxide was produced by the Scanditronix
MC-17 cyclotron at Uppsala Imanet AB using the 14N(p,α)11C
reaction with 17 MeV protons in a gas target containing
nitrogen (AGA, Nitrogen 6.0) and 0.1% oxygen (AGA. Oxygen
4.8). [11C]Carbon monoxide was produced by reducing
[11C]carbon dioxide in a zinc furnace at 400 ЊC using a remote
controlled work station.18
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micro-autoclave was heated (150 ЊC) for 10 min. The crude
product was transferred to a pre-evacuated, septum-fitted vial
(5 mL). Titanium tetrachloride (1 mL of 1 M solution in
CH2Cl2, 1.0 mmol) and aniline (20 µL, 20.4 mg, 219 µmol) were
added and the mixture was heated for 5 min at 60 ЊC. Sodium
cyanoborohydride (1 mL of 1 M solution in MeOH, 1.0 mmol)
was added and the mixture heated for an additional 5 min at the
same temperature. The reaction mixture was quenched by slow
addition of aqueous sodium hydroxide (1 mL of 2 M aqueous
solution) and filtered. The volume of the filtrate was reduced
to 1 mL by heating at 60 ЊC and purging with nitrogen.
Methanol (1 mL), water (1 mL) and a sufficient amount of the
previously synthesised corresponding 11C-labelled compound
were added. The product was purified by semi-preparative LC
using the same chromatographic method as described for
11C-labelled compound. The radioactive fraction was collected
and evaporated under reduced pressure to yield the title
compound. The residue was dissolved in CDCl3 and analysed
by NMR spectroscopy.
142.7, 136.3, 128.9, 128.1, 127.7, 127.3, 123.8, 116.3, 66.0, 50.4.
GC-MS (EI): m/z = 268 (M ϩ, 18%), 267 (85%), 251 (32%), 227
ؒ
(22%), 191 (69%), 180 (68%), 165 (100%), 146 (60%), 91 (19%),
77 (16%).
Isopropyl-[(4-nitro-phenyl)-phenyl-methyl]-amine (21f ). Yield
69%, yellow crystal, mp 78–79 ЊC. δH (400 MHz, CDCl3): 8.1
(d, 2H), 7.6 (d, 2H), 7.3 (m, 4H), 7.2 (m, 1H), 5.0 (s, 1H),
2.7–2.8 (m, 1H), 1.4 (bs, 1H), 1.1 (m, 6H). δC (100 MHz,
CDCl3): 152.3, 146.9, 143.3, 128.8, 128.1, 127.5, 127.3, 123.7,
64.1, 46.5, 23.3, 23.1. GC-MS (EI): m/z = 270 (M ϩ, 5%), 255
ؒ
(78%), 212 (100%), 193 (7%), 166 (43%), 153 (8%), 106 (5%).
Diallyl-[(4-nitro-phenyl)phenyl-methyl]-amine (21g). Yield
70%, yellow oil. δH (400 MHz, CDCl3): 8.1 (d, 2H), 7.6 (d, 2H),
7.3 (m, 4H), 7.2 (m, 1H), 5.9 (m, 2H), 5.1–5.2 (m, 4H), 5.0
(s, 1H), 3.1–3.2 (m, 4H). δC (100 MHz, CDCl3): 150.5, 146.8,
140.1, 134.9, 128.9, 128.7, 128.6, 127.6, 123.6, 117.8, 69.1, 52.5.
GC-MS (EI): m/z = 308 (M ϩ, 15%), 267 (10%), 231 (39%),
ؒ
212 (100%), 186 (39%), 166 (95%), 154 (19%), 96 (27%),
91 (10%).
δC (100 MHz, CDCl3): 63.19.
Preparation of reference compounds
[(4-Nitro-phenyl)-phenyl-methyl]-phenyl-amine (21h). Yield
75%, yellow crystal, mp 122 ЊC (lit.23 mp 120–121 ЊC). δH (400
MHz, CDCl3): 8.1 (d, 2H), 7.6 (d, 2H), 7.3–7.6 (m, 5H), 7.1–7.2
(m, 2H), 6.7 (m, 1H), 6.5 (m, 2H), 5.5 (s, 1H), 4.2 (bs, 1H).
δC (100 MHz, CDCl3): 150.3, 147.3, 146.7, 141.8, 129.3, 129.2,
128.3, 128.1, 127.7, 124.1, 118.5, 113.6, 62.9. GC-MS (EI): m/z
General method. The procedure is exemplified by the prepar-
ation of allyl-benzhydryl-amine (21a). Benzophenone (1.0 g,
5.5 mmol) was dissolved in dry CH2Cl2 (30 mL) and TiCl4
(6.0 mL of 1.0 M solution in CH2Cl2, 6.0 mmol) was added.
The mixture was cooled to 0 ЊC and allylamine (0.9 mL. 0.68 g,
11.9 mmol) was added. The resulting mixture was stirred for 3 h
at ambient temperature under argon. The reaction was
quenched with a methanolic solution of NaBH3CN (10 mL of
6.5 M solution, 6.5 mmol) and stirred for an additional 1 h at
the same temperature. The mixture was made basic (pH ∼10)
with 5 M aqueous solution of NaOH and filtered. The filtrate
was partitioned between ethyl acetate (100 mL) and water
(100 mL). The organic layer was separated, washed with water
(2 × 100 mL) and brine (100 mL), dried over MgSO4 and con-
centrated under reduced pressure. The crude product was
dissolved in ether, acidified (pH ∼2) with conc. HCl and
extracted with water. The water extract was made basic (pH
∼11) with aqueous ammonia (28%) and extracted with ether.
The ether extract was dried over MgSO4 and the solvent was
removed under reduced pressure to give the title compound as
a yellowish oil.
= 304 (M ϩ, 42%), 212 (100%), 166 (44%), 77 (40%).
ؒ
Isopropyl-(1-phenyl-ethyl)-amine (21i). Yield 83%, yellow oil
(lit.24 bp 176–177). δH (400 MHz, CDCl3): 7.3 (m, 4H), 7.2
(m, 1H), 3.9 (q, 1H), 2.6 (m, 1H), 1.3 (d, 3H), 1.2 (bs, 1H), 1.0
(m, 6H). δC (100 MHz, CDCl3): 146.2, 128.4, 126.7, 126.4, 55.1,
45.5, 24.9, 24.1, 22.3. GC-MS (EI): m/z = 163 (M ϩ, 25%), 148
ؒ
(100%), 106 (44%), 77 (12%).
Diallyl-(1-phenyl-ethyl)-amine (21j). Yield 86%, brown oil
(lit.25 bp 103–104). δH (400 MHz, CDCl3): 7.3 (m, 4H), 7.2
(m. 1H), 5.8 (m, 2H), 5.1–5.2 (m, 4H), 3.9 (q, 1H), 3.1 (m, 4H),
1.4 (d, 3H). δC (100 MHz, CDCl3): 144.2, 136.7, 128.1, 127.7,
126.7, 116.7, 58.4, 52.7, 17.2. GC-MS (EI): m/z = 201
(M ϩ, 5%), 186 (100%), 105 (26%), 11 (10%).
ؒ
Compounds 21d, 21h and 21k were purified by column
chromatography using pentane/ether (90 : 10) as the eluent.
Phenyl-(1-phenyl-ethyl)-amine (21k). Yield 91%, colourless
oil (lit.26 bp 132–134). GC-MS (EI): m/z = 197 (M ϩ, 10%),
ؒ
182 (39%), 165 (37%), 106 (100%), 77 (22%).
Allyl-benzhydryl-amine (21a). Yield 95%, yellow oil, (lit20 bp
105–110 ЊC). GC-MS (EI): m/z = 223 (M ϩ, 4%), 180 (26%), 167
ؒ
Acknowledgements
(51%), 146 (100%), 104 (28%), 91 (37%).
We thank Mr. Martin Lavén for support with the LC-MS
analysis. The Swedish Research Council is acknowledged for its
support by grant K3464 (B.L.).
Benzhydryl-isopropyl-amine (21b). Yield 90%, colourless oil
(lit21 bp 181.5–182.0 ЊC). δH (400 MHz, CDCl3): 7.5 (m, 4H),
7.3–7.4 (m, 4H), 7.3 (m, 1H), 5.1 (s, 1H), 2.8 (m, 1H), 1.5
(bs, 1H), 1.2 (m, 6H). δC (100 MHz, CDCl3): 144.6, 128.4,
127.4, 126.8, 64.3, 46.1, 23.28. GC-MS (EI): m/z = 225
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ؒ
(4%), 167 (100%), 104 (3%), 77 (14%).
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Allyl-[(4-nitro-phenyl)-phenyl-methyl]amine (21e). Yield 85%,
yellow oil. δH (400 MHz, CDCl3): 8.1 (d, 2H), 7.6 (d, 2H), 7.3
(m, 4H), 7.2 (m, 1H), 5.9 (m, 1H), 5.1–5.2 (m, 2H), 4.9 (s, 1H),
3.2 (d, 2H), 1.7 (bs, 1H). δC (100 MHz, CDCl3): 151.6, 147.1,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 6 1 2 – 1 6 1 6
1615

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O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 6 1 2 – 1 6 1 6
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