7
18
M. F. Mackay, D. J. Gale and J. F. K. Wilshire
Melbourne, or the Analytical Unit, Research School of Chemistry,
Australian National University. Ultraviolet spectra were recorded either
on a Beckman DK2 or on a Varian 235 spectrophotometer in ethanol,
1-Azetidinyl-2,4-dinitrobenzene (DNP azetidine) (1b) was prepared
as follows. A diglyme solution (11.4 ml) containing approximately 20
1
4
mmol azetidine (cf. ) was stirred with a solution of 1-fluoro-2,4-dini-
trobenzene (20 mmol) and triethylamine (0.28 ml, 2 equiv.) in dimethyl
sulfoxide (10 ml) for 16 h at room temperature. The mixture was then
poured into water, and extracted with ether to give a semisolid product
which was purified by silica gel chromatography; elution with
benzene/light petroleum (60–80°) (1 :1) gave DNP azetidine (1b), m.p.
carbon tetrachloride (Merck Uvasol grade) and trifluoroacetic acid
1
(
Fluka grade) solutions. H n.m.r. spectra were obtained in (D)chloro-
form and trifluoracetic acid with 0.4 M solutions either on a Varian
A60D spectrometer or on a JEOL FX90 spectrometer. In order to avoid
using large volumes of trifluoroacetic acid, solutions in this solvent
were prepared directly by weighing out the sample (0.7–1.5 mg) in the
cell (1 cm) and adding the solvent (3 ml). This procedure renders these
logꢃmax values less accurate than those obtained with ethanol as solvent.
With the exception of N-ethoxycarbonylpiperazine and azetidine,
the secondary amines used in this investigation were obtained from
commercial sources. N-Ethoxycarbonylpiperazine, b.p. 102–104°C/5
mm, was prepared in 34% yield on the basis of starting piperazine hex-
9 19 3 4
115–117°C, in 56% yield (Found: N, 18.7. C H N O requires N,
18.8%).
1-Azetidinyl-4-nitrobenzene (4b) was prepared by a similar method,
but with anhydrous potassium carbonate (2 equiv.) as the supporting
base. Reaction (40 mmol scale; steam bath; 5 h) gave a yellow semisolid
which was purified by chromatography on silica gel (30 g); elution with
benzene/light petroleum (2:1) gave 1-azetidinyl-4-nitrobenzene (4b),
1
3
15
1
ahydrate by the literature procedure. Azetidine was prepared as its
m.p. 118–120°C (lit. 119°C), in 29% yield. H n.m.r. (CDCl
quintet, CH ; 4.05, t, NCH ; 6.25, d (J c. 9 Hz), H 2/H6; 8.05, d (J c. 9
Hz), H 3/H5.
3
): ꢆ 2.45,
1
4
solution in diglyme (cf. ) by the reaction of sodium naphthalenide with
N-tosylazetidine; the azetidine content (33%) was determined by acidi-
metric titration with perchloric acid.
2
2
(b) Preparation of the N-2,4-Dinitrophenyl Derivatives
(c) The Reaction of DNP Azetidine (1b) with Trifluoroacetic Acid
1
All derivatives were crystallized from methylene chloride/light
Changes in the H n.m.r spectrum occurred almost immediately
petroleum (60–80°). New compounds gave satisfactory microanalyses
for nitrogen; their identities and purities were confirmed by their H
after dissolution of the sample in trifluoroacetic acid. In addition to all
the signals expected for DNP azetidine, other signals were also present.
Significantly, the original two multiplets due to the azetidine ring
protons had been joined by a third multiplet (upfield). After 30 min, all
the original signals had been replaced by new signals. The original
1
n.m.r. spectra in (D)chloroform solution. The chemical shift data for
their DNP ring protons (H3, H 5 and H6) are presented in Table 2, and
the chemical shifts, integration and appearance of the poly-
methyleneimino ring proton signals (not shown) were as expected.
Their preparation is exemplified by the following preparation. Thus, a
mixture of thiomorpholine (1.03 g, 10 mmol), 1-fluoro-2,4-dinitroben-
zene (1.86 g, 10 mmol) and triethylamine (2.8 ml, 20 mmol) in dimethyl
sulfoxide solution (20 ml) was stirred on a steam bath for 2 h before
being poured into water to give 1-(thiomorpholin-4Ј-yl)-2,4-dinitro-
benzene (1i) (DNP thiomorpholine), m.p. 106–108°C, in 72% yield
signals were located at ꢆ 3.77, m, CH
8.67, dd, H5; 9.13, d, H3. The new signals were located at ꢆ 2.35,
quintet, CH CH CH ; 3.77, t, NCH ; 4.67, t, OCH ; 7.13, d, H6; 8.67,
2 2
; 4.82, m, NCH ; 7.83, d, H6;
2
2
2
2
2
dd, H 5; 9.25, d, H3. The nature of the reaction which had occurred was
further revealed by removing the trifluoroacetic acid (by azeotropic
treatment to dryness with benzene), and then recording the spectrum of
the low-melting product in (D)chloroform solution. This spectrum
(
Found: N, 15.9. C10
-(2Ј,5Ј-Dimethylpyrrolidin-1Ј-yl)-2,4-dinitrobenzene (1d) (DNP
,5-dimethylpyrrolidine) had m.p. 126–128°C (yield 74%) (Found: N,
5.8. C12 requires N, 15.8%).
-(4Ј-Ethoxycarbonylpiperazin-1Ј-yl)-2,4-dinitrobenzene (1j) (DNP
N-ethoxycarbonylpiperazine) had m.p. 119–121°C (yield 90%) (Found:
N, 17.5. C13 requires N, 17.3%).
-(Azacyclooctan-1Ј-yl)-2,4-dinitrobenzene (1n) (DNP azacyclooct-
H
11
N
3
O
4
S requires N, 15.6%).
showed signals located at ꢆ 2.25, quintet, CH
2 2
; 3.60, dt, NCH ; 4.53, dt,
1
OCH ; 6.95, d, H6; 8.33, dd, H5; 8.58 br, NH; 9.13, d, H3.
2
2
1
Significantly, the H5 signal showed fine splitting (J c. 0.7 Hz) which is
9
H
15
N
3
O
4
due to long-range NH,H 5 coupling (cf. ). The broad signal at ꢆ 8.58
1
was assigned to an aromatic NH group because it was absent in the tri-
fluoroacetic acid spectrum.
1
H
16
N
4
O
6
From the above H n.m.r. evidence, it seemed likely that the product
1
of the acidic reaction was the trifluoroacetate (5b). This deduction
was confirmed in the following way. 3-[(2Ј,4Ј-Dinitro-
phenyl)amino]propan-1-ol (5a), m.p. 73–75°C, was prepared in 80%
yield by the reaction of 3-aminopropan-1-ol with 1-fluoro-2,4-dini-
trobenzene in dimethyl sulfoxide solution in presence of triethylamine
ane) had m.p. 104–105°C (yield 70%) (Found: N, 15.0. C13
requires N, 14.9%).
The corresponding reaction with N-methylpiperazine gave 1-(4Ј-
methylpiperazin-1Ј-yl)-2,4-dinitrobenzene (1k) (DNP 4-methylpiper-
17 3 4
H N O
azine), m.p. 77–79°C, in 84% yield (Found: N, 21.2. C11
requires N, 21.1%) However, reaction (steam bath; 4 h) of N-
methylpiperazine (400 mg, 4 mmol) with 1-fluoro-2,4-dinitrobenzene
1.488 mg, 8 mmol) in a mixture of ethanol (32 ml) and water (8 ml) in
H
14
N
4
O
4
as described in section (b) (Found: N, 17.1. C
17.4%). H n.m.r. (CDCl ): ꢆ 2.07, quintet, CH CH CH
3 2 2 2
9
H
11
N
3
O
5
requires N,
; 2.12, s, OH
(removed by the addition of deuterium oxide); 3.62, dt, NCH ; 3.98, t,
OCH ; 6.98, d, H 6; 8.25, dd, H 5; 8.85, br, NH (removed by the addi-
1
.
2
(
2
the presence of sodium acetate (656 mg, 8 mmol) gave 1,4-bis(2,4-dini-
trophenyl)-1-methylpiperazin-1-ium hydroxide (3) as an orange solid
tion of deuterium oxide); 9.07, d, H 3. The H 5Ј signal showed long-
range NH,H 5 coupling (J c. 0.7 Hz). The trifluoroacetate (5b) was
prepared by stirring a solution of the parent alcohol (5a) (1.94 g) in
chloroform (20 ml) with trifluoroacetic anhydride at room temperature
for 1 h. The solvent was removed on a rotary evaporator to give a
yellow oil (2.67 g; 98% crude yield) which solidified in the fridge.
Crystallization from pentane cooled in dry ice gave 3-[(2Ј,4Ј-dinitro-
phenyl)amino]propyl trifluoroacetate (5b), m.p. 48–50°C (Found: C,
(
1.33 g; 74% yield) which crystallized from the mixture on cooling. The
analytical sample (from ethanol/acetonitrile) had m.p. 195–197.5°C
Found: C, 45.1; H, 4.1; N, 18.5). C17 requires C, 45.3; H, 4.0;
SO]: ꢆ 2.77, s, CH ; 3.17 and 3.47, m,
(not assigned); 5.53, br s, OH (removed by the addition of deu-
terium oxide); 6.58, d (J c. 9 Hz), H6 (ring A); 7.50, d (J c. 9 Hz), H 6
ring B); 7.93, dd (J c. 2 and c. 9 Hz), H5 (ring A); 8.33, dd (J c. 2 and
(
18 6 9
H N O
1
N, 18.7%). H n.m.r. [(CD
×NCH
3
)
2
3
2
2
(
10 3 3 5
39.0; H, 2.9; N, 12.6. C11H F N O requires C, 39.2; H, 3.0; N,
–
1
1
c. 9 Hz), H5 (ring B); 8.55 and 8.60, d (J c. 2 Hz), H3 (signals not
assigned).
The reaction (20 mmol scale; steam bath; 2 h) with 2,6-
dimethylpiperidine (4 equiv.) (a mixture of cis and trans isomers) in the
presence of triethylamine (4 equiv.) gave, after chromatography on
12.5%). ꢇmax (C=O) 1780 cm . The H n.m.r spectra of this compound
in both (D)chloroform and trifluoroacetic acid solutions were identical
with the corresponding spectra (see above) of the product obtained
from the reaction of DNP azetidine (1b) with trifluoroacetic acid.
The action of trifluoroacetic acid on 1-azetidinyl-4-nitrobenzene
1
silica gel, 1-(cis-2Ј,6Ј-dimethylpiperidin-1Ј-yl)-2,4-dinitrobenzene (1f)
(4b) was also briefly studied. The H n.m.r spectrum of a solution (0.4
8
(
DNP cis-2,6-dimethylpiperidine), m.p. 82–84°C (lit. 84–85°C), in 33%
M) of this compound in trifluoroacetic acid changed very slowly. After
3 days, partial ring opening was observed; complete reaction was not
achieved, however, because decomposition appeared to occur there-
after.
yield. The trans-2,6-dimethyl isomer (1g) could not be freed from unre-
acted 1-fluoro-2,4-dinitrobenzene; a small sample of this isomer was
donated by Professor F. Pietra (see Acknowledgments).
Mackay, Maureen F.
