Synthesis and thermal reactions of N-(2,3-epoxypropyl)diphenylamine

Article abstract of DOI:10.1007/s10593-007-0117-7

The synthesis of N-(2,3-epoxypropyl)diphenylamine is reported. It was found that thermal opening of the oxirane ring of N-(2,3-epoxypropyl)diphenylamine occurred both at the secondary and the tertiary carbon atoms but the basic reaction product is 3-hydro

Full text of DOI:10.1007/s10593-007-0117-7

Chemistry of Heterocyclic Compounds, Vol. 43, No. 6, 2007
SYNTHESIS AND THERMAL REACTIONS
OF N-(2,3-EPOXYPROPYL)DIPHENYLAMINE
B. Barvainiene1,2, A. Stanisauskaite1, and V. Getautis1
The synthesis of N-(2,3-epoxypropyl)diphenylamine is reported. It was found that thermal opening of the
oxirane ring of N-(2,3-epoxypropyl)diphenylamine occurred both at the secondary and the tertiary
carbon atoms but the basic reaction product is 3-hydroxy-1-phenyl-1,2,3,4-tetrahydroquinoline.
Keywords:
3-hydroxymethyl-1-phenylindoline,
3-hydroxy-1-phenyl-1,2,3,4-tetrahydroquinoline,
N-(2,3-epoxypropyl)diphenylamine, cyclization.
Heating diphenylamine 1 with epichlorohydrin (EPCH) under pressure [1] or with the addition of
sodium iodide at high temperatures [2] gives 3-hydroxy-1-phenyl-1,2,3,4-tetrahydroquinoline (2). In study [3]
compound 2 was obtained by heating diphenylamine 1 with excess EPCH at atmospheric pressure without a
catalyst. The same authors showed that formation of compound 2 occurs via N-(2-hydroxy-3-chloro-
propyl)diphenylamine [4]. We have found [5] that the tetrahydroquinoline 2 can also be prepared from the
epoxypropyl derivative of diphenylamine, i.e. N-(2,3-epoxypropyl)diphenylamine (3) which cyclizes upon
heating with opening of the oxirane ring at the secondary carbon atom in compound 2. The aim of this work is
the synthesis of compound 3 and a study of it cyclization processes.
Compound 3 is prepared by heating diphenylamine 1 with EPCH at 60-63ºC for 50 h in the presence of
glacial acetic acid with subsequent work up of the intermediate N-(2-hydroxy-3-chloropropyl)diphenylamine
with sodium hydroxide [4]. The drawback of this method is the long reaction time. The method we propose for
preparing compound 3 from diphenylamine 1 with EPCH in the presence of alkali differs in that the reaction is
carried out at room temperature in the presence of a 13 fold excess of KOH (with respect to the starting amine)
in order to shorten this time. Hence the synthesis of compound 3 can be carried out in a single step and the
reaction time is shortened to 7 h.
Many experiments have shown that the optimum temperature for the cyclization of compound 3 to
heterocycle 2 is 220-225ºC. Under these conditions the yield of compound 2 reaches 53%. At lower
temperatures the formation of compound 2 is very slow.
A study of the thermal reactions of compound 3 has shown that the 1,3-di(diphenylamino)-2-propanol
(4) and 3-hydroxymethyl-1-phenylindoline (5) are formed in addition to compound 2. With increase in the
cyclization temperature to 245-250ºC the amount of compound 5 increases but in this case the basic cyclization
reaction product is compound 2. Column chromatography of the reaction mass gave compounds 4 and 5 and also
the 1-phenyl-1,2,3,4-tetrahydroquinoline (6) and N-(2,3-dihydroxypropyl)diphenylamine (7). Formation of
__________________________________________________________________________________________
1Department of Organic Chemistry, Kaunas University of Technology, Kaunas LT-50270, Lithuania;
e-mail: brone.barvainiene@ktu.lt, albina.stanisauskaite@ktu.lt, and vytautas.getautis@ktu.lt. 2Faculty of
Technology, Kaunas College, Kaunas LT-50468. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.
6, pp. 852-855, June, 2007. Original article submitted March 22, 2006.
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0009-3122/07/4306-718©2007 Springer Science+Business Media, Inc.

compound 5 (an indoline derivative) upon heating compound 3 is evidently because the oxirane ring opens at the
1
bond between tertiary carbon atom and oxygen atom. We have recorded the mass, IR, and H NMR spectra of
compound 5 in order to confirm its structure.
+
N
_
N
N
N
6
OH
+
+
8
_
H2O
OH
O
OH
H2O
∆
N
N
N
OH
7
3
2
_
Cl
OH
NH
OH
O
N
N
N
3
,
∆
OH
4
5
1
Comparing the IR spectra of compound 2 and 5 shows that both spectra show a broad, strong absorption
band at 3280 and 3300 cm-1 respectively, typical of hydroxyl group stretching vibrations. The vibration
associated with the C–OH group appears at 1065 and 1040 cm-1 respectively. In the first case the band is more
characteristic of a secondary and in the second a primary alcohol [6]. The mass spectrum of compound 5 shows a
rather low intensity (36%) molecular ion peak [M+ 225] together with a more stable fragment of even mass
[M-31]+ which can be formed by simple fission of a single bond from the molecular ion with odd mass [7]. In
addition disruption of the aromaticity of the pyrrole part of the indole molecule infers that the initial loss of the
substituent as a whole occurs from position 3 [8]. According to this the substance separated is compound 5 and
this structure is also confirmed by 1H NMR spectroscopy.
The formation of compound 4 by heating 3 can evidently be represented as the result of desalkylation of
the latter, forming diphenylamine 1 which reacts with the starting compound 3. The production of compounds 6
and 7 can be rationalized as a dehydration of the cyclization product 2 to give 1-phenyl-1,2- (or 1,4-)
dihydroxyquinoline which then disproportionates to 6 and the 1-phenylquinolinium base 8 as shown in [9].
However, we were unable to separate and identify compound 8. The water formed in the process of dehydration
of compound 2 takes part in a reaction with the epoxypropyl derivative 3 to form 7 which proved identical to
that obtained by treating compound 3 with diluted trifluoroacetic acid in dioxane.
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EXPERIMENTAL
1H NMR spectra were recorded on a Tesla BS-487C spectrometer (80 MHz) with HMDS (δ 0.05 ppm)
as internal standard. IR spectra were taken on an IR-20 spectrometer for KBr tablets. Mass spectra were recorded
on a Hitachi M-80A instrument with direct sample introduction into the ion chamber and a voltage of 80 eV.
Monitoring of the course of the reactions was carried out by TLC on Silufol UV-254 plates which were revealed
with a UV lamp with 254 filter or by iodine vapor. Chemapol L40/100 was used for the column
chromatography.
N-(2,3-Epoxypropyl)diphenylamine (3). A mixture of diphenylamine (50.7 g, 0.3 mol), EPCH (277.5,
3.0 mol), and powdered anhydrous potassium carbonate (58.5 g, 0.45 mol) was stirred for 20-30 min and
powdered potassium hydroxide (198 g, 3.0 mol) was added at such a rate that the reaction temperature did not
exceed 30ºC. The reaction was carried out for 7 h (TLC, ether–petroleum ether, 1:1) and then treated with cold
water and extracted with ether. After removal of ether and excess EPCH the residue was distilled in vacuo in a
nitrogen stream. The fraction with bp 158-159ºC was collected at 1-2 mm Hg (bp 161-163ºC at 2.5 mm Hg [4])
to give compound 3 (61.8 g, 91.5%).
1,3-Di(diphenylamino)-2-propanol (4). A mixture of compound 1 (12.7 g, 0.075 mol) and compound 3
(11.3 g, 0.05 mol) was heated at 150-155ºC to the disappearance of the starting materials (4 days, TLC, acetone-
hexane, 1:4) to give compound 4 (9.9 g, 50%); mp 92-93ºC (hexane). IR spectrum, ν, cm-1: 3540 (OH); 3065,
3090 (arom. CH); 2925 with sh. at 2935, 2875 (aliph. CH); 1595 (C=C); 1500 with sh. at 1460 (C=C, aliph.
CH); 750 with sh at 745, 700 (CH, monosubstitued benzene). 1H NMR spectrum (CDCl3), δ, ppm: 7.5-6.5 (20H,
m, Ar); 4.40-4.35 (5H, m, NCH2CHCH2N); 1.12 (1H, m, OH). Found, %: C 82.02; H 6.52; H 7.23. C27H26N2O.
Calculated, %: C 82.20; H 6.64; N 7.10.
N-(2,3-Dihydroxypropyl)diphenylamine (7). Compound 3 (5.6 g, 0.025 mol) was dissolved in dioxane
(25 ml) and 0.12 ml of a solution of trifluroacetic acid in water (0.8 g CF3COOH in 100 ml water) was added at
105ºC over 5 min. The mixture was refluxed to the absence of starting material (TLC, acetone-hexane, 1:4). The
mixture was then cooled and diluted with water (200 ml). The water was decanted and compound 7 (4.9 g) was
obtained as an oily substance crystallizing on standing. Yield 80.7%; mp 95.5-96.5ºC (from a mixture of toluene
and hexane, 1:1). IR spectrum, ν, cm-1: 3500-3100 (br, OH); 3070, 3045 (arom. CH); 2960, 2940, 2900, 2880
(aliph. CH); 1595 (C=C); 1500 with sh. at 1455, 1470 (C=C, aliph. CH); 1065 with sh. at 1040 (primary and
secondary OH); 750 with sh. at 780, 735, 700 (CH, monosubstituted benzene). 1H NMR spectrum (acetone-d6),
δ, ppm: 7.62-6.75 (10H, m, Ar); 4.15-3.00 (7H, CH2CH(OH)CH2OH). Found, %: C 73.99; H 6.87; N 5.64.
C15H17NO2. Calculated, %: C 74.05; H 7.04; N 5.76.
Cyclization of N-(2,3-epoxypropyl)diphenylamine (3). A. Compound 3 (11.3 g, 0.05 mol) was heated
at 220-225ºC in a nitrogen atmosphere for 30 h. The reaction product was chromatographed eluting with
acetone-hexane (1:4) to give compound 2 (6.0 g, 53.1%); mp 77-78ºC and compound 4 (1.5 g, 7.6%);
mp 92-93ºC. Compound 5 was also observed by chromatography in addition to 2 and 4. The spectroscopic data
for compound 2 has been published in [5].
B. Compound 3 (45 g, 0.2 mol) was heated at 245-250ºC for 8 h. The reaction product was separated
analogously to method A to give compound 4 (2.4 g) with mp 92.2-93ºC (mixed sample with compound 4
prepared as above did not give a melting point depression) as well as compound 6 [2.1 g, yield 5%, bp
142-145ºC, 2-3 mm Hg; bp 142.5-145, 2-3 mm Hg, [3]), compound 7 [1.7 g, yield 3.5%, mp 95.5-96.5ºC], and a
mixture of compounds 2 and 5 (20 g) which was dissolved in ethanol. Cooling to 0-2ºC gave crystals which were
filtered off and crystallized three times from ethanol to give compound 2 (16.2 g, 36.6%) with mp 79-80.5ºC.
After evaporation of the mother liquor the residue was purified by column chromatography eluting with
acetone–ether–hexane (1:1:3) to give compound 2 (5.5%) and compound 5 plus an admixture of compound 2
(0.8 g) which was separated by repeated column chromatography. Yield of compound 5 was 0.5 g;
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mp 81-83ºC (from ethanol). IR spectrum, ν, cm-1: 3300 (br, OH); 3050 with sh. at 3025 (arom. CH); 2920-2880
(aliph. CH); 1590 (C=C); 1040 (C–OH); 748 with sh. at 765, 752, 700 (CH mono and o-disubstituted benzene).
1H NMR spectrum (CDCl3), δ, ppm: 7.38-6.71 (9H, m, Ar); 4.15-3.76 (4H, m, CH2OH, N–CH2); 3.56 (1H, m,
CH); 1.6 (1H, m, OH). Mass spectrum, m/z (Irel, %): 225 [M]+ (24), 194 [M-CH2OH]+ (100). Found, %: C 79.81;
H 6.62; N 5.98. C15H15NO. Calculated, %: C 79.97; H 6.71; N 6.22.
C. Compound 3 (22.5 g, 0.1 mol) was heated at 260-265ºC in a nitrogen atmosphere for 2.5 h. The
reaction product was separated as indicated above to give compound 2 (6.2 g, 27.5%), compound 6 (2 g, 8.9%),
compound 7 (2.5 g, 12%), compound 5 (1.1 g, 0.5%), and compound 4 (2 g, 5%).
This work was carried out with the financial support of the Lithuanian fund for science and education
(project B-18/2006).
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