Reaction of 3-chloro-1-(2,4,6-trimethylphenyl)propan-2-one with amines

Full text of DOI:10.1134/S1070428009120185

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 12, pp. 1856–1858. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © R.R. Yadigarov, A.N. Khalilov, I.G. Mamedov, F.N. Nagiev, A.M. Magerramov, M.A. Allakhverdiev, 2009, published in Zhurnal
Organicheskoi Khimii, 2009, Vol. 45, No. 12, pp. 1857–1859.
SHORT
COMMUNICATIONS
Reaction of 3-Chloro-1-(2,4,6-trimethylphenyl)propan-2-one
with Amines
R. R. Yadigarov, A. N. Khalilov, I. G. Mamedov, F. N. Nagiev,
A. M. Magerramov, and M. A. Allakhverdiev
Baku State University, ul. Z. Khalilova 23, Baku, Az-1148 Azerbaidjan
e-mail: mirze_a@mail.ru
Received March 2, 2009
DOI: 10.1134/S1070428009120185
While continuing our studies in the fields of syn-
thesis and transformations of 1,2-chlorohydrins [1] ob-
tained by reaction of arenes with 3-chloro-1,2-epoxy-
propane in the presence of aluminum chloride, we
performed oxidation of 3-chloro-1-(2,4,6-trimethyl-
phenyl)propan-2-ol (I) with chromium(VI) oxide and
isolated 3-chloro-1-(2,4,6-trimethylphenyl)propan-2-
one (II). α-Chloro ketone II was brought into reaction
with various primary amines in aqueous potassium
hydroxide at room temperature. The reaction time was
20–45 min. Regardless of the amine nature, in all cases
the products were the corresponding N-substituted
3-(2,4,6-trimethylphenyl)propionamides III–IX which
were isolated in 50–97% yield as colorless crystalline
substances and were recrystallized from ethanol.
ing vibrations of aromatic C=C bonds. Asymmetric
and symmetric stretching vibrations of N–H bonds in
the primary amide group of III (involved in hydrogen
bond) were characterized by absorption bands at 3360
and 3175 cm–1, respectively. Stretching vibrations of
the amide carbonyl group had a frequency of 1645 cm–1
(amide I band), and bending vibrations of the NH
group appeared at 1545 cm–1 (amide II band). Absorp-
tion bands at 1430 and 710–600 cm–1 belong to stretch-
ing vibrations of the C–N bond and out-of-plane bend-
ing vibrations of the NH group, respectively.
1
Compounds I and II displayed in the H NMR
spectra two singlets with appropriate intensity ratio
from three methyl groups in the benzene ring (δ 2.1
and 2.2 ppm). Protons in the ArCH2 and CH2Cl meth-
ylene groups in compound I resonated as two doublets
at δ 2.70 and 3.25 ppm. The CHOH signal in the spec-
trum of I appeared as a quintet at δ 3.70 ppm. The
CH2CO and CH2Cl protons in ketone II gave signals in
a weaker field (δ 3.90 and 4.65 ppm, s) relative to
those of alcohol I. Two protons in the aromatic rings of
I and II resonated as singlets at δ 6.90 and 6.80 ppm,
respectively.
Obviously, the chlorine atom in α-chloro ketone
molecule II is not replaced directly by amino group,
but the reaction involves Favorskii rearrangement [2].
The structure of amides III–IX was proved by their IR
1
13
and H and C NMR spectra and elemental analyses,
and their purity was checked by TLC.
In the IR spectra of III–IX, stretching vibrations of
aromatic C–H bonds were observed at 3005–3010 cm–1,
aliphatic C–H bonds (methyl groups) gave rise to
absorption bands at 2926–2875 cm–1, and absorption
bands at 1615 and 1470 cm–1 were assigned to stretch-
1
The H NMR spectrum of amide V contained
a strong upfield singlet at δ 1.25 ppm from the tert-
butyl group. The N-methyl group in IV gave a signal at
Me
Me
Me
O
CrO3, H2SO4
RNH2
Cl
Cl
NHR
OH
O
Me
Me
Me
Me
Me
Me
I
II
III–IX
III, R = H; IV, R = Me; V, R = t-Bu; VI, R = Ph; VII, R = furfuryl; VIII, R = pyridin-3-yl; IX, R = HOCH2CH2.
1856

REACTION OF 3-CHLORO-1-(2,4,6-TRIMETHYLPHENYL)PROPAN-2-ONE WITH AMINES
1857
13C NMR spectrum, δC, ppm: 19 (2CH3), 21 (CH3), 23
(CH2CO), 25 [C(CH3)3], 37 (CH2), 50 (Ci), 129
(CHarom), 136, 137 (Ci ), 162 (CO). Found, %: C 77.83;
H 10.02; N 5.47. C16H25NO. Calculated, %: C 77.68;
H 10.19; N 5.66.
δ 2.60 ppm. Amides III–IX displayed a singlet at
δ 2.10–2.20 ppm from protons in the α-methylene
group, and methyl protons at the benzene ring were
characterized by chemical shifts in the region δ 2.15–
1
2.35 ppm. Aromatic protons resonated in the H NMR
spectra of III–IX in the region δ 6.75–6.85 ppm, while
the most downfield signal was that belonging to the
NH proton.
Amides III, IV, and VI–IX were synthesized in
a similar way.
3-(2,4,6-Trimethylphenyl)propanamide (III).
Yield 93%, mp 171°C, Rf 0.81. IR spectrum, ν, cm–1:
3360, 3175, 3005, 2926, 2875, 1645, 1615, 1470,
It is known that reactions of α-bromo ketones with
secondary amines give the corresponding amino
ketones together with carboxamides [3, 4]. In the ex-
amined reaction, the only products were 3-(2,4,6-tri-
methylphenyl)propanamides.
1
1430, 710, 600. H NMR spectrum, δ, ppm: 2.10 s
(2H, CH2CO), 2.25 s (9H, CH3), 2.75 d (2H, CH2),
13
6.75 s (2H, Harom), 7.25 s (2H, NH2). C NMR spec-
trum, δC, ppm: 19 (2CH3), 21 (CH3), 27 (CH2CO), 36
(CH2), 129 (CHarom), 137 (Ci), 175 (CO). Found, %:
C 75.61; H 3.97; N 7.47. C12H17NO. Calculated, %:
C 75.35; H 3.96; N 7.32.
3-Chloro-1-(2,4,6-trimethylphenyl)propan-2-ol (I)
was synthesized as described in [5].
3-Chloro-1-(2,4,6-trimethylphenyl)propan-2-one
(II). A mixture of 20 ml of water, 6 ml of concentrated
sulfuric acid, and 0.2 g (2 mmol) of chromium an-
hydride was added dropwise to a solution of 4.25 g
(2 mmol) of alcohol I in 30 ml of acetone. The mixture
was vigorously stirred over a period of 2 h at 0–10°C
(the reaction was accompanied by heat evolution).
When the reaction was complete, the mixture was
extracted with several portions of benzene, the extracts
were combined, washed with water until neutral
reaction, and dried over calcined sodium sulfate. The
solvent was distilled off, the viscous residue was
dissolved in hexane, the solution was kept for 24 h at
0–10°C, and the colorless crystals were filtered off.
Yield 2.7 g (65%), mp 69–70°C. IR spectrum, ν, cm–1:
N-Methyl-3-(2,4,6-trimethylphenyl)propanamide
(IV). Yield 97%, mp 120–121°C, Rf 0.62. IR spectrum,
ν, cm–1: 3355, 3170, 3005, 2923, 2875, 1645, 1615,
1
1465, 1425, 715, 605. H NMR spectrum, δ, ppm:
2.15 s (2H, CH2CO), 2.20 s (9H, CH3), 2.60 s (3H,
CH3N), 2.70 t (2H, CH2), 6.25 s (2H, Harom), 7.80 s
13
(1H, NH). C NMR spectrum, δC, ppm: 20 (CH3), 21
(CH3), 26 (CH2CO), 35 (CH2), 129 (CHarom), 137, 136,
135 (Ci), 172 (CO). Found, %: C 75.96; H 9.16;
N 6.59. C13H19NO. Calculated, %: C 76.06; H 9.33;
N 6.82.
N-Phenyl-3-(2,4,6-trimethylphenyl)propanamide
(VI). Yield 50%, mp 149°C, Rf- 0.73. IR spectrum, ν,
cm–1: 3355, 3170, 3000, 2925, 2870, 1645, 1610, 1475,
1
3005, 2915, 1725, 1435, 1430, 710, 605. H NMR
1
spectrum, δ, ppm: 2.10 s (6H, CH3), 2.20 s (3H, CH3),
3.90 s (2H, COCH2), 4.65 s (2H, CH2Cl), 6.80 s (2H,
Harom). 13C NMR spectrum, δC, ppm: 19 (2CH3), 21
(CH3), 40 (CH2), 49 (CH2), 129 (Carom), 137 (Ci), 200
(CO). Found, %: C 68.19; H 7.43; Cl 16.68.
C12H15ClO. Calculated, %: C 68.41; H 7.32; Cl 16.83.
1435, 700, 600. H NMR spectrum, δ, ppm: 2.17 s
(3H, CH3), 2.25 s (6H, CH3), 2.41 s (2H, CH2CO),
2.84 s (2H, CH2), 7.61 s and 6.88 s (7H, Harom), 9.90 s
(1H, NH). 13C NMR spectrum, δC, ppm: 19 (2CH3), 21
(CH3), 23 (CH2CO), 37 (CH2), 120 (CHarom), 139, 138,
135, 129, 123 (Ci ), 171 (CO). Found, %: C 80.94;
H 7.86; N 5.51. C18H21NO. Calculated, %: C 80.75;
H 7.92; N 5.21.
N-tert-Butyl-3-(2,4,6-trimethylphenyl)propan-
amide (V). Ketone II, 2 g (0.01 mol), was added in
portions at room temperature to a solution of 0.7 g
(0.01 mol) of tert-butylamine in a mixture of 15 ml of
water and 0.7 g (0.01 mol) of potassium hydroxide.
The mixture turned orange–brown. The precipitate was
filtered off and recrystallized from ethanol. Yield
2.16 g (86%), mp 143°C, Rf 0.72. IR spectrum, ν,
cm–1: 3360, 3170, 3005, 2928, 2878, 1645, 1615, 1470,
N-(Furan-2-ylmethyl)-3-(2,4,6-trimethylphenyl)-
propanamide (VII). Yield 79%, mp 135–136°C,
Rf 0.84. IR spectrum, ν, cm–1: 3365, 3170, 3100, 3000,
2925, 2870, 1645, 1610, 1620, 1 475, 1425, 1255, 955,
1
710, 605. H NMR spectrum, δ, ppm: 2.15 s (11H,
CH3, CH2CO), 2.75 s (2H, CH2), 4.25 s (2H, CH2N),
6.76 (2H, Harom); 6.17, 6.37, and 7.54 s (3H, furan);
8.30 (1H, NH). 13C NMR spectrum, δC, ppm: 19
(2CH3), 21 (CH3), 26 (CH2CO), 37 (CH2N), 38 (CH2),
107, 111 (furan), 129 (CHarom), 137, 144 (Ci), 172
1
1430, 715, 605. H NMR spectrum, δ, ppm: 1.25 s
(9H, t-Bu), 2.15 s (2H, CH2CO), 2.25 s (9H, CH3),
2.75 t (2H, CH2), 6.75 s (2H, Harom), 7.45 s (1H, NH).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

YADIGAROV et al.
1858
173 (CO). Found, %: C 71.18; H 8.77; N 5.82.
C14H21NO2. Calculated, %: C 71.46; H 8.99; N 5.95.
(CO). Found, %: C 74.61; H 7.76; N 5.65. C16H19NO2.
Calculated, %: C 76.68; H 7.44; N 5.44.
N-(Pyridin-3-yl)-3-(2,4,6-trimethylphenyl)pro-
panamide (VIII). Yield 66%, mp 127°C, Rf 0.78.
IR spectrum, ν, cm–1: 3360, 3170, 3005, 2930, 2875,
1645, 1610, 1475, 1430, 705, 600. H NMR spectrum,
δ, ppm: 2.10 s (2H, CH2CO), 2.35 s (9H, CH3), 2.85 s
The IR spectra were recorded in KBr on a Specord
75 IR spectrometer. The 1H and 13C NMR spectra were
measured on a Bruker AM-300 instrument at 300 MHz
1
1
(for H) using DMSO-d6 as solvent and tetramethyl-
silane as internal reference. The progress of reactions
was monitored, and the purity of products was
checked, by TLC on Silufol UV-254 plates using
hexane–propan-2-ol (3:2) as eluent.
(2H, CH2), 6.80 s (2H, Harom); 7.08 t, 7.77 t, 8.13 d,
13
and 8.21 d (4H, pyridine); 10.5 s (1H, NH). C NMR
spectrum, δC, ppm: 19 (2CH3), 21 (CH3), 25 (CH2CO),
37 (CH2), 128 (CHarom); 114, 120, 137, 147 (CH,
pyridine); 129, 136, 138, 139 (Ci), 149 (CH), 153 (Ci),
173 (CO). Found, %: C 76.22; H 7.67; N 10.26.
C17H20N2O. Calculated, %: C 76.09; H 7.51; N 10.44.
REFERENCES
1. Allakhverdiev, M.A., Mustafaev, K.N., and Farzali-
ev, V.M., Russ. J. Org. Chem., 2002, vol. 38, p. 1620.
N-(2-Hydroxyethyl)-3-(2,4,6-trimethylphenyl)-
propanamide (IX). Yield 43%, mp 110°C, Rf 0.65.
IR spectrum, ν, cm–1: 3450, 3360, 3170, 3005, 2430,
2385, 1645, 1615, 1620, 1470, 1420, 995, 700, 605.
1H NMR spectrum, δ, ppm: 2.15 s (2H, CH2CO),
2.20 s (9H, CH3), 2.75 t (2H, CH2), 3.15 t (2H, CH2N),
3.35 t (2H, CH2CO), 4.65 s (1H, OH), 6.75 s (2H,
2. Muldgaard, L., Thomsen, I.B., Hazell, R.G., and
Bols, M., J. Chem. Soc., Perkin Trans. 1, 2002, p. 1297.
3. Kirrmann, A. and Yoschek, H.I., Bull. Soc. Chim. Fr.,
1963, p. 2483.
4. Dodson, R., Morello, E., and Danben, W., J. Am. Chem.
Soc., 1954, vol. 76, p. 606.
13
Harom), 7.85 s (1H, NH). C NMR spectrum, δC, ppm:
5. Allakhverdiev, M.A., Khalilova, A.Z., Farzaliev, V.M.,
and Sultanov, Yu.M., Khim. Geterotsikl. Soedin., 1988,
p. 598.
19 (2CH3), 21 (CH3), 26 (CH2CO), 36 (CH2), 42
(CH2N), 61 (CH2O), 129 (CHarom), 138, 137, 136 (Ci),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009