ˇ
P. S im u˚ nek, A. Ly cˇ ka, V. Mach a´ cˇ ek
FULL PAPER
the replacement of an amino group by a phenylamino 5,5-Dimethyl-3-(phenylamino)cyclohex-2-en-1-one (1a):
A
flask
equipped with an adapter for the azeotropic removal of water was
charged with dimedone (3.5 g, 25 mmol), toluene (50 mL), aniline
group causes a distinct shift in the tautomeric equilibrium
towards the hydrazone form of the neighbouring group in-
troduced by azo coupling.
(
2.33 g, 25 mmol), and glacial acetic acid (0.5 mL). The mixture
was heated in an oil bath until the distillate consisted of pure tolu-
ene only (ca. 7 h). The product precipitated by cooling was col-
lected by suction and dried in air. A second portion was obtained
by concentrating the mother liquor. The enaminone obtained was
The main difference lies in the fact that while 4-aminop-
ent-3-ene-2-one only reacts with one equivalent of di-
azonium salt at the 3-position,[ 3-amino-5,5-dimethyl-
cyclohex-2-ene-1-one derivatives undergo two azo coupling
1]
recrystallized from toluene. Yield 3.54 g (65%); m.p. 182Ϫ183 °C
reactions (at the 2- and 4-positions) even if the molar ratio (ref.[ m.p. 184Ϫ185 °C).
9]
of starting components is only 1:1. The formation of only
3
-Amino-5,5-dimethylcyclohex-2-en-1-one (1b): This compound was
traces of the 1:1 product (from one molecule of benzenedia-
zonium ion and one molecule of enaminone) was observed
in the preparation of compound 2e. The reason for the dif-
ferent behaviour of the two types of enaminones during azo
coupling reactions is not known at present. The azo coup-
ling reactions of 3-amino-5,5-dimethylcyclohex-2-ene-1-one
gave the respective 5,5-dimethylcyclohexane-1,2,3-trione 2-
prepared as above. Gaseous ammonia was introduced into the ap-
paratus, and the water formed in the reaction was again removed
by azeotropic distillation. The product was recrystallized from acet-
[10]
one; yield 56%, m.p. 160Ϫ162 °C (ref. m.p. 164Ϫ165 °C).
Preparation of Azo Coupling Products: A flask was charged with
the respective enaminone (1.08 g, 5 mmol) dissolved in 30 mL of
dichloromethane. This solution was treated with sodium acetate
(subst. phenyl) hydrazones as minor side products.
(
1.23 g, 15 mmol) and 10 mmol of the respective benzenediazonium
tetrafluoroborate. The mixture was stirred at room temperature
4 h. The solid portion was collected by suction on a sintered glass
2
filter and washed with dichloromethane. The dichloromethane ex-
tracts obtained were distilled until dry, and the evaporation residue
was submitted to column chromatography on silica gel with
Experimental Section
CH
2 2
Cl as eluent. The product obtained was recrystallized from
General Remarks: The NMR spectra were measured with Bruker
the solvent mixtures specified below.
AMX 360 or Avance 500 spectrometers in CDCl
3
at 25 °C. Measur-
1
ing frequencies were 360.14 MHz and 500.13 MHz for H, The following compounds were prepared in the above-described
0.57 MHz and 125.77 MHz for C, 36.50 MHz and 50.69 MHz way:
1
3
9
for 15N. The proton chemical shifts are referenced to hexamethyl-
5,5-Dimethyl-3-(phenylimino)cyclohexane-1,2,4-trione
2,4-Bis(4-
disiloxane (δ ϭ 0.05 ppm); the carbon chemical shifts are refer-
methylphenylhydrazone) (2a): After the above-mentioned chromato-
graphy, recrystallization from a chloroform/ethanol mixture gave
enced to the middle signal of the solvent triplet (δ ϭ 76.9 ppm).
The 15N NMR spectra were standardised by referencing to external
red-brown needles. Yield 50%. M.p. 222Ϫ225 °C. C28
451.57): calcd. C 74.48, H 6.47, N 15.51; found C 74.22, H 6.49,
N 15.50.
29 5
H N O
neat nitromethane placed in a coaxial capillary (δ ϭ 0.00 ppm).
The individual signals were assigned on the basis of H,H-COSY,
HETCOR, gradient-selected (gs) HSQC, HMQC and HMBC tech-
niques. The 13C NMR spectra were measured in the standard way
and by pulse sequence APT.
(
5,5-Dimethyl-3-(phenylimino)cyclohexane-1,2,4-trione 2,4-Bis(4-me-
thoxyphenylhydrazone) (2b): Recrystallization from a chloroform/
ethanol mixture. Black-brown needles. Yield 34%. M.p. 197Ϫ202
The melting points were determined on a Kofler hot stage micro-
scope and were not corrected. The elemental analyses were carried
out on an automatic analyser FISONS EA 1108.
°
C. C28
29 5 3
H N O (483.56): calcd. C 69.55, H 6.04, N 14.48; found
C 69.80, H 6.16, N 14.50.
3
-Imino-5,5-dimethylcyclohexane-1,2,4-trione
phenylhydrazone) (2c): Recrystallization from ethanol. Black
needles. Yield 60%. M.p. 185Ϫ186 °C. C22 O (375.47): calcd.
C 70.38, H 6.71, N 18.65; found C 70.29, H 6.89, N 18.95.
2,4-Bis(4-methyl-
Dichloromethane was pre-dried by standing over calcium chloride
overnight. It was then filtered into a distilling flask and distilled
from over phosphorus pentoxide; the fraction boiling at 39Ϫ40 °C
was collected.
25 5
H N
5
,5-Dimethyl-3-(phenylimino)cyclohexane-1,2,4-trione 2,4-Bis(4-bro-
A commercial sample of anhydrous sodium acetate was remelted
on a porcelain dish and left to cool in a desiccator.
mophenylhydrazone) (2d): After the above-mentioned chromato-
graphy, recrystallization from ethanol gave black-green needles
with a metallic lustre. Yield 19%. M.p. 168Ϫ170 °C. C20
505.21): calcd. C 47.55, H 3.79, N 13.86; found C 47.30, H 3.70,
N 13.91.
2 5
H19Br N O
Tetrafluoroborates of Benzenediazonium Salts: The respective aro-
matic amine (0.05 mol) was dissolved in 22 mL of hot HCl (1:1).
The solution was then cooled with stirring to 5 °C, and an aqueous
solution of sodium nitrite (3.62 g, 0.053 mol) was added drop by
drop with cooling. The temperature of the reaction mixture was
(
3-Amino-4-(4-methoxyphenylazo)-5,5-dimethylcyclohex-3-ene-1,2-
dione 2-(4-Methoxyphenylhydrazone) (2e): Recrystallization from
ethanol gave black-violet needles. Yield 51%. M.p. 137Ϫ140 °C.
2
kept below 10 °C. The excess of HNO was monitored by drop
tests on KI-starch paper. The final excess nitrous acid was removed
by addition of amidosulfonic acid. The resulting solution of di-
azonium chloride was treated with a saturated aqueous solution
C
22
H
25
N
5
O
3
(407.47): calcd. C 64.85, H 6.18, N 17.19; found C
64.74, H 6.19, N 17.15.
of NaBF
4
(10 g, 0.09 mol) added with stirring. The precipitated Preparation of Selectively 15N-Labelled Azo Coupling Products: The
diazonium tetrafluoroborate was collected by suction, washed
with cold methanol and (several times) with ether and dried in a
desiccator.
respective aniline (2.8 mmol) was dissolved in 3 mL (ഠ30%) of
HBF . The solution obtained was treated with sodium nitrite
(210 mg, 3.04 mmol) (15% N) dissolved in a minimum amount of
4
1
5
2768
Eur. J. Org. Chem. 2002, 2764Ϫ2769