4
054 J . Org. Chem., Vol. 66, No. 11, 2001
Notes
Huffman Laboratories (Golden, CO). All commercially obtained
reagents were used without further purification.
The yellow product crystals were filtered and rinsed with cold
methanol. The product was recrystallized twice from methanol
and again rinsed with cold methanol.
Gen er a l P r oced u r e for Syn th esis. Compounds 1a -g were
prepared and isolated using the following general procedure. The
procedure is illustrated using 1a as an example. Modifications
to the purification step for the oil phase 1b-d and to the reaction
and purification steps for synthesis and isolation of the longer
chain (crystalline) 1f,g are given in parentheses and in the
following sections.
N,N-Dip r op yl-p-n itr oa n ilin e (1a ): yield 8.51 g (98%); mp
1
55-56 °C; H NMR (CDCl ) δ 0.93 (t 6H, CH ), 1.64 (h 4H, CH ),
3
3
2
3.32 (t 4H, CH ), 6.80 (d 2H, Ar), 8.22 (d 2H, Ar); GCMS m/z
2
222, calcd m/z for C12H18N O 222. Anal. Calcd for C12H18N O :
2
2
2
2
C, 64.82; H, 8.17; N, 12.60; O, 14.41. Found: C, 64.83; H, 8.35;
N, 12.52; O, 14.30.
An excess of di-n-propylamine, 8.035 g (0.0796 mol), was
mixed with 5.5081 g (0.0391 mol) of 4-fluoronitrobenzene and
heated at a gentle boil for 1-3 days (longer reaction times are
required for the longer alkyl chain amines). These reactions
could be carried out using ground glass reaction vessels.
However, we found that the yield was not much changed when
the reactions occurred in open glassware, such as in a 100 mL
Erlenmeyer flask. The completion of the reactions was monitored
by TLC.
N,N-Dibu tyl-p-n itr oa n ilin e (1b). An 11.05 g (0.0857 mol)
portion of dibutylamine was mixed with 6.02 g (0.0427 mol) of
1
4-fluoronitrobenzene: yield 7.48 g (70%);
3
H NMR (CDCl ) δ 0.95
(t, 6H, CH ), 1.6 (m, 8H, CH ), 3.34 (t, 4H, CH ), 6.53 (d, 2H,
3
2
2
ArH), 8.07 (d, 2H, ArH); GCMS m/z 250, calcd. m/z for C H N O
2
1
4
22
2
250; TLC R 0.7 (toluene). Anal. Calcd for C14H22N O : C, 67.15;
f
2
2
H, 8.86; N, 11.9; O, 12.79. Found: C, 67.18; H, 9.25; N, 11.00;
O, 12.57.
N,N-Dip en tyl-p-n itr oa n ilin e (1c). A 7.331 g (0.0467 mol)
After the mixture was cooled to room temperature, ap-
proximately 35 mL of diethyl ether (dry reagent) was added (50
mL for the synthesis of 1e, 1f, and 1g). The mixture was warmed
lightly until all the solid was dissolved. The flask was stoppered,
and the solution was left to allow slow crystallization. Fifteen
milliliters of hexane was added (40 mL for the synthesis of 1e,
portion of dipentylamine was mixed with 3.290 g (0.0234 mol)
1
of 4-fluoronitrobenzene: yield 6.49 g (56%); H NMR (CDCl
3
) δ
0
.89 (t, 6H, CH
to N), 3.32 (t, 4H, CH
ArH); GCMS m/z 278, calcd m/z for C16
toluene).
N,N-Dih exyl-p-n itr oa n ilin e (1d ). A 8.114 g (0.0438 mol)
portion of dihexylamine was mixed with 3.035 g (0.0215 mol) of
3
), 1.32 (m, 8H, CH
R to N), 6.51 (d, 2H, ArH), 8.02 (d, 2H,
278; TLC R 0.74
2 2
γ to N), 1.61 (p, 4H, CH â
2
H
26
N
2
O
2
f
(
1
f, and 1g), and the white crystals of N,N-dipropylamine
hydrofluoride precipitated. The amine hydrofluoride salts were
removed by vacuum filtration and rinsed with cold hexane, and
the wash was combined with the filtrate. The solvents were
removed (from the combined filtrate) under reduced pressure
and the residue taken up in hot methanol and transferred to a
crystallizing flask, stoppered, and cooled on ice. Scratching of
the flask wall was required to initiate crystallization of the
product. Crystals of the yellow N,N-dipropyl-p-nitroaniline were
rinsed in cold methanol and recrystallized once from methanol.
P r oced u r e for Isola tion of 1b-d . Following removal of the
di-n-alkylamine hydrofluoride (see general procedure), the re-
maining solution was cooled on ice in a stoppered flask and then
transferred to a separatory funnel. Initially, all solutions were
washed with 100 mL of 3 M HCl. The acid layer was washed
with 50 mL of diethyl ether. The combined ether extracts were
saved. The ether extract was then washed with 100 mL of a
1
4
0
4
8
-fluoronitrobenzene: yield 3.045 g (46%); H NMR (CDCl
.88 (t, 6H, CH ), 1.30 (m, 12 H, CH γ, δ and ꢀ to N), 1.58 (p,
H, CH â to N), 3.32 (t, 4H, CH R to N), 6.50 (d, 2H, ArH),
.05 (d, 2H, ArH); GCMS m/z 306, calcd m/z for C18 306;
0.76 (toluene); n 1.5939/23 °C.
3
) δ
3
2
2
2
30 2 2
H N O
TLC R
f
D
N,N-Dioctyl-p-n itr oa n ilin e (1e). A 12.834 g (0.0532 mol)
portion of dioctylamine was mixed with 5.379 g (0.0532 mol) of
triethylamine and 7.500 g (0.0532 mol) of 4-fluoronitrobenzene:
1
yield 17.92 g (93%); mp 31 °C; H NMR (CDCl
3
) δ 0.875 (t, 6H,
), 3.332 (t, 4H, CH ),
.52 (d, 2H, ArH), 8.07 (d, 2H, ArH); GCMS m/z 362, calcd m/z
for C20 362; TLC R 0.84 (toluene). Anal. Calcd for
: C, 72.87; H, 10.57; N, 7.73; O, 8.83. Found: C,
CH
3
), 1.295 (m, 20H, CH
2
), 1.596 (p, 4H, CH
2
2
6
H
34
N
2
O
2
f
22 38 2 2
C H N O
7
3.15; H, 10.57; N, 7.60; O, 8.68.
N,N-Did ecyl-p-n itr oa n ilin e (1f). A 15.817 g (0.0532 mol)
portion of didecylamine was mixed with 5.379 g (0.0532 mol) of
second solution of H
NaHCO . The concentrations of acid in the second solution (for
successive syntheses) are given in Table 2. The ether extract
was dried over anhydrous CaCl and filtered. The ether was
removed under reduced pressure. The residue was taken up in
0 mL of hot methanol and transferred to a crystallizing flask.
2 4
SO (or HCl) and then again with 5%
3
triethylamine and 7.500 g (0.0532 mol) of 4-fluoronitrobenzene:
1
yield 21.820 g (98%); mp 48-50 °C; H NMR (CDCl
3
) δ 0.93 (t,
), 6.80 (d, 2H,
0.87 (toluene). Anal. Calcd for
: C, 74.58; H, 11.08; N, 6.69; O, 7.65. Found: C,
2
6
H, CH
3 2 2
), 1.64 (m, 32H, CH ) 3.32 (t, 4H), CH
ArH), 8.22 (d, 2H, ArH); TLC R
f
4
C
26
H
46
N
2
O
2
The flask was stoppered and placed on ice. The oil was allowed
to settle and coalesce, and the overlying solution was decanted
and drawn off. The oil was dissolved into another 40 mL of hot
methanol. The flask was stoppered and placed on ice. Again,
the orange oil was allowed to settle and the supernatant solution
was decanted and drawn off. This procedure was repeated one
7
4.57; H, 11.08; N, 6.70; O,7.65.
N,N-Did od ecyl-p-n itr oa n ilin e (1g). An 18.799 g (0.0532
mol) portion of didodecylamine was mixed with 5.379 g (0.0532
mol) of triethylamine and 7.500 g (0.0532 mol) of 4-fluoroni-
1
trobenzene: yield 23.99 g (95%); mp 56-57 °C; H NMR (CDCl
3
)
δ 0.93 (t, 6H, CH
d, 2H, ArH), 8.22 (d, 2H, ArH); TLC R
Calcd for C30 C, 76.20; H, 11.10; N, 5.93; O, 6.77.
3
), 1.64 (m, 40H, CH
2
), 3.32 (t, 4H, CH
2
), 6.80
more time. The orange oil was dried by heating under N
Afterward, the oil was purified by preparative normal-phase
SiO ) TLC using toluene as the mobile phase. Alternatively, we
were able to purify the compounds by preparative reversed-phase
2
.
(
f
0.90 (toluene). Anal.
52 2 2
H N O :
(
2
Found: C, 75.92; H, 11.12; N, 6.05; O,6.91.
(
(
C
18 on SiO
solvent A ) 0.1 M aqueous trifluoroacetic acid; solvent B ) 0.1
CN/H O). The fractions were
and extracted into chloroform. The
2
) HPLC using a gradient elution mobile phase
Ack n ow led gm en t. This work was supported by the
Petroleum Research Fund (ACS-PRF Grant No. 31890-
GB4) and the Research Corporation (Cottrell College
Science Award No. CC4338). Special thanks go to Mike
Zaworotko and Kumar Biradha for collecting X-ray data
on crystals of compounds 1a and 1f, to Edgar Civitello
for use of the preparative HPLC instrumentation, and
to the Department of Chemistry at Arizona State
University for providing access to their 500 MHz NMR
spectrometer.
M trifluoroacetic acid in 90/10 CH
neutralized with NaHCO
3
2
3
chloroform was removed under reduced pressure. Vacuum
distillation proved difficult for the higher molecular weight oils
and led to decomposition of a large amount of the product.
Mod ifica tion s for 1e-g. Synthesis of 1e-g followed the
general reaction for 1a . However, equal molar quantities of the
dialkylamine and 4-fluoronitrobenzene were mixed, along with
an additional molar quantity of triethylamine. For these reac-
tions, crystals of the triethylamine hydrofluoride were isolated
by addition of cold hexane (see general procedure for 1a ).
Following removal of the crystalline triethylamine hydrofluoride,
the solvent was removed under reduced pressure from the
remaining solution, and the residue was taken up in hot
methanol and transferred to a crystallizing flask. The super-
saturated solution required seed crystals and/or scratching of
the flask wall to initiate crystallization of the product. Crystal-
lization took place at a reduced ambient temperature of e19 °C.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data are given in Tables S1-S10 and in CIF files for
compounds 1a and 1f. ORTEP drawings showing the molec-
ular structures of 1a and 1f also are available. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O0014764