Isomerization of (het)aryl-benzoins in basic media

Article abstract of DOI:10.1023/B:COHC.0000027885.61368.a7

The α→β isomerization of the hetaryl analogs of unsymmetrical benzoins on heating in basic media is a convenient preparative method for the production of α-hydroxyacyl derivatives of π-excessive heterocycles. The motivating force here for the isomerizatio

Full text of DOI:10.1023/B:COHC.0000027885.61368.a7

Chemistry of Heterocyclic Compounds, Vol. 40, No. 2, 2004
ISOMERIZATION OF (HET)ARYL-
BENZOINS IN BASIC MEDIA
S. P. Ivonin, A. V. Lapandin, and V. G. Shtamburg
The α→β isomerization of the hetaryl analogs of unsymmetrical benzoins on heating in basic media is a
convenient preparative method for the production of α-hydroxyacyl derivatives of π-excessive
heterocycles. The motivating force here for the isomerization is the formation of a thermodynamically
more stable product. It was established that α→β isomerization is promoted by increase in the
difference between the electron-donating characteristics of the (het)aryl residues.
Keywords: benzoins, π-excessive heterocycles, isomerization.
The benzoin condensation is a convenient method for the synthesis of benzoins both with symmetrical
and with unsymmetrical structures [1]. With thiazolium salts as catalysts it was possible not only to increase the
overall yield and optical purity of the benzoins but also to use the reaction as a model to study the formation of
the C–C bond in natural systems, catalyzed by enzymes (thiamine diphosphate) [2-11]. Study of the mechanism
of the benzoin condensation and determination of the role of the acyl carbanion as intermediate made it possible
to obtain the less stable unsymmetrical α-benzoins as a result of a two-stage reaction [12-17], which is
impossible under the conditions of the classical benzoin condensation [1]. However, the α-benzoins are formed
here with low yields, while only the furan and pyridine derivatives are obtained from the hetaryl analogs [17].
The aldehydes of π-excessive heterocycles are inactive under the conditions of the benzoin condensation [18].
Therefore, for example, electrophilic acylation, requiring a few more stages for the production of the benzoins,
was used in the case of the synthesis of α-hydroxyacylindoles, which have pharmacological activity [19, 20].
4'-Dimethylaminobenzoin (the α-isomer) can be isomerized to the corresponding β-isomer in basic
media [1], and it was interesting to use α→β isomerization for the production of the more stable
hetarylbenzoins.
The starting compounds were the hetaryl analogs of α-benzoins, which can be easily obtained by
hydroxymethylation of the respective π-excessive heterocycles with arylglyoxals [21].
We found that the isomerization of α-benzoins 1-13 takes place smoothly in the presence of
triethylamine as base in boiling alcohol. As a result high yields of the corresponding hetaryl analogs of
β-benzoins 14-26 were obtained (Scheme 1).
In our opinion α→β isomerization of benzoins takes place as intramolecular migration of a hydrogen
atom between the oxygen atoms in the anion A, formed as a result of removal of a proton by the base from the
carbon atom of the hydroxymethyl group. In fact, use of the O-deuterated α-benzoin 27 in isomerization under
the indicated conditions gave the β-benzoin 28, in which the deuterium atom was preserved to the extent of
1
100%. The H NMR spectrum of the β-benzoin 28 does not contain the signals in the region of 5.70 and
11.88 ppm that in the spectrum of the β-benzoin 20 correspond to the OH and NH protons, while the signals of
__________________________________________________________________________________________
Dnepropetrovsk National University, Dnepropetrovsk 49050, Ukraine; e-mail: ivonin@dp.ukrtel.net.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 187-194, February, 2004. Original article
submitted November 14, 2003.
154
0009-3122/04/4002-0154©2004 Plenum Publishing Corporation

Scheme 1
HO
O
NEt3
O OH
Het
R
EtOH, 78 oC
Het
R
14–26
1–13
,
,
,
,
Het =
Me
Me
N
N
N
N
Me
Me
C6H4Me-p
3, 16
C6H4OEt-p
2, 15
4, 17
1, 14
R1
,
,
,
Me
Me
Me
Me
N
N
N
R2
C6H4Br-p
C6H4Me-p
7–12, 20–25
5, 18
6, 19
Me
O
13, 26
R = Ph (1–11, 13–24, 26), 2-thienyl (12, 25)
1
R = H (7, 12, 20, 25), Me (8, 9, 21, 22), Ph (10, 23), t-Bu (11, 24)
2
R = Me (9, 22), H (all other cases)
CHOD and H(2) Ind are in the form of singlets, in contrast to the doublets in the 1H NMR spectrum of 20. In the
IR spectrum of compound 28 the vibrations of the N–D and O–D bonds appear in the region of 2580-2490 cm-1
respectively. The presence of the deuterium at the oxygen atom and not at the carbon atom in the β-benzoin 28
Scheme 2
+
D
_
O
_
O
O
DO
Ph
Ph
NEt3
EtOH, 78 oC
N
N
D
D
A
27
OD
OMe
Ph
O
O
Ph
Me2SO4
DMSO, NaOH
N
D
N
Me
28
29
155

TABLE 1. The Duration of the Isomerization of α-Benzoins
Compound
Duration, h*
Compound
Duration, h*
Compound
Duration, h*
1.5
3.5
4
12
3
9
5
1
2
3
4
5
6
7
11
12
13
27
5
6.5
3
8
11.5
12
5
9
9
10
_______
* The duration was determined from the disappearance of the spot for the
initial compound in TLC (every 30 min).
1
was also proved by the alkylation of 28 with dimethyl sulfate in DMSO. In fact, the H NMR spectrum of the
1
isolated bis-O,N-alkylated product 29 contains a singlet at 5.32 ppm as also in the H NMR spectrum of the
β-benzoin 28, indicating the presence of a proton at the carbon atom.
The formation of the thermodynamically more stable β-isomer, determined by the electronic nature of
the hetaryl residue, is in our opinion the motivating force of the isomerization, and an increase in the duration of
the isomerization is therefore observed with decrease of the electron-donating power in the following order (for
R = Ph):
<<
<
Me
N
O
N
H
Me
The substantial decrease in the electron-donating power of the furan ring compared with the pyrrole
rings leads to the result that the α-benzoin 13 is less active than the α-benzoins 1 and 7. In the case of the pyrrole
derivatives it was established that the decrease in the electron-donating power of the position of the heterocycle
reduces the duration of isomerization in the following order (for R = Ph):
<<
<<
<
N
N
N
Me
OEt
Me
Me
~
~
Me
Me
Me
<<
Me
Me
N
N
N
Me
Br
Me
156

The most active is the α-benzoin 1, in which the reaction center is attached to the most electron-
donating group. Replacement of the alkyl group at the nitrogen atom by a less electron-donating aryl group
increases the duration of isomerization, and the reaction center here is sensitive to the electronic effect of the
substituent in the aryl ring. The pyrrole 2 is therefore somewhat more active than 3. In the case of the pyrroles 4-
6 the hydroxy ketone group is attached to the less electron-donating β-position of the heterocycle. The
duration of isomerization is therefore increased, while the influence of the electronic effect of the substituent at
the nitrogen atom is levelled out. The opposite effect from the electron-donating characteristics is observed for
(het)aryl groups in the righthand part of the benzoin molecule. Thus, the isomerization rate decreases with
increase in the donating power (for Het = Ind), i.e., the greater the difference in the electron-donating
characteristics of the (het)aryl substituents in the benzoin molecule, the more readily the isomerization takes
place.
Ph <
S
The increase in the size of the substituent at the o-position to the α-hydroxy ketone group in the hetaryl
moiety in the series of 2-alkylindole derivatives (for R = Ph) leads to a reduction in the rate of α→β
isomerization, due to steric hindrances to removal of the proton at the carbon atom by the base. In our opinion
the increase in the duration of the isomerization of the 2-phenylindole derivative is due in addition to the
electron-accepting effect of the phenyl ring.
R1
N
R2
R1 = H < Me< Ph ~ t-Bu
In the 1H NMR spectra of the obtained β-benzoins it is possible to detect the following relationship: the
doublets of the o-protons of the unsubstituted phenyl ring are shifted upfield by 0.5-0.6 ppm compared with
those in the spectra of the initial α-benzoins [21]. This relationship can be used to determine the structure of
isomeric benzoins, since the position and form of the signals of these protons are similar for isomers of the same
series [22].
EXPERIMENTAL
1
The H NMR spectra were obtained in DMSO-d6 on a Varian VXR-300 instrument (300 MHz) with
TMS as internal standard. The reaction was monitored by TLC on Silufol UV-254 plates in the 5:1 benzene–
acetone system with development in iodine vapor.
We described the α-benzoins 1-10, 12, and 13 in [21].
The α-benzoins 11 and 27 were obtained by the general procedure in [21].
2-(2-tert-Butyl-1H-indol-3-yl)-2-hydroxy-1-phenylethanone (11). A solution of 2-tert-butylindole
(5.00 mmol) in benzene (4 ml) was added to a solution of phenylglyoxal (5.00 mmol) in benzene (4 ml). The
obtained solution was kept at room temperature for 24 h. The precipitate was filtered off and crystallized from
benzene. Yield 66.3%, colorless crystals; mp 142-144°C. 1H NMR spectrum, δ, ppm, J (Hz): 1.49 (s, 9H, t-Bu);
157

5.29 (d, 1H, CHOH, J = 5.4); 6.41 (d, 1H, CHOH, J = 5.4); 6.76 (t, 1H, H(6) Ind, J = 8.4); 6.92 (t, 1H, H(5) Ind,
J = 8.4); 7.19 (d, 1H, H(7) Ind, J = 8.4); 7.25 (d, 1H, H(4) Ind, J = 8.4); 7.34 (t, 1H, H(3) and H(5) Ar, J = 6.9);
7.46 (d, 1H, H(4) Ar, J = 6.9); 7.82 (d, 2H, H(2) and H(6) Ar, J = 6.9); 10.72 (s, 1H, NH). Found, %: С 78.11;
Н 6.87. C20H21NO2. Calculated, %: C 78.15; H 6.89.
O,N-Dideutero-2-hydroxy-2-(1H-indol-3-yl)-1-Phenylethanone (27). A solution of phenylglyoxal
deuteroxide (5.00 mmol), indole (5.00 mmol), and deuterium oxide (0.1 ml) in benzene (8 ml) was boiled for 2 h
and cooled. The precipitate was filtered off and crystallized from toluene. Yield 58.0%, colorless crystals;
mp 180-182°C. 1H NMR spectrum, δ, ppm, J (Hz): 6.39 (s, 1H, CHOD); 7.00 (t, 1H, H(6) Ind, J = 8.1); 7.08 (t,
1H, H(5) Ind, J = 8.1); 7.32 (d, 1H, H(7) Ind, J = 8.1); 7.35 (s, 1H, H(2) Ind); 7.40 (d, 1H, H(7) Ind, J = 8.1);
7.51 (t, 2H, H(3) and H(5) Ph, J = 7.8); 7.67 (d, 1H, H(4) Ph, J = 7.8); 8.02 (d, 2H, H(2) and H(6) Ph, J = 7.8).
Found, %: С 75.73; N 5.52. C16H11D2NO2. Calculated, %: C 75.87; N 5.53.
General Procedure for the Isomerization of α-Benzoins 1-13 and 27 (Table 1, Schemes 1 and 2). A
solution of the α-benzoin (1.50 mmol) and triethylamine (0.21 ml, 1.80 mmol) in ethanol (6 ml) was boiled for
the time indicated in the table. The obtained solution was evaporated under vacuum, and the residue was
crystallized. The following compounds were obtained in this way.
2-Hydroxy-1-(1-methyl-1H-pyrrol-2-yl)-2-phenylethanone (14). Yield 50.5%, colorless prisms;
mp 107-108 (hexane). 1H NMR spectrum, δ, ppm, J (Hz): 3.84 (s, 3H, NMe); 5.58 (d, 1H, CHOH, J = 5.7); 5.70
(d, 1H, CHOH, J = 5.7); 6.05 (dd, 1H, H(4) Pyr, J = 3.9, J = 2.4); 7.05 (d, 1H, H(5) Pyr, J = 2.4); 7.20 (d, 1H,
H(4) Ph, J = 6.9); 7.21 (d, 1H, H(3) Pyr, J = 3.9); 7.27 (t, 2H, H(3) and H(5) Ph, J = 6.9); 7.42 (d, 2H, H(2) and
H(6) Ph, J = 6.9). Found, %: C 72.53; H 6.10. C13H13NO2. Calculated, %: C 72.54; H 6.09.
1-[1-(4-Ethoxyphenyl)-2-hydroxy-1H-pyrrol-2-yl]-2-phenylethanone (15). Yield 80.4%, light-yellow
powder; mp 78-79°C (80% ethanol). 1H NMR spectrum, δ, ppm, J (Hz): 1.40 (t, 3H, CH3CH2, J = 7.0); 4.10 (q,
2H, CH3CH2), J = 7.0); 5.60 (d, 1H, CHOH, J = 5.6); 5.64 (d, 1H, CHOH, J = 5.6); 5.88 (dd, 1H, H(4) Pyr,
J = 3.9, J = 2.4); 6.04 (d, 1H, H(5) Pyr, J = 2.4); 6.87 (d, 1H, H(3) Pyr, J = 3.9); 7.04 (d, 2H, H(2) and H(6) Ar,
J = 8.7); 7.36 (d, 1H, H(4) Ph, J = 7.8); 7.45 (d, 2H, H(3) and H(6) Ar, J = 8.7); 7.47 (t, 2H, H(3) and H(5) Ph,
J = 7.8); 7.58 (d, 2H, H(2) and H(6) Ph, J = 7.8). Found, %: C 74.79; H 5.99. C20H19NO3. Calculated, %:
C 74.75; H 5.96.
2-Hydroxy-1-(1-(p-tolyl)-1H-pyrrol-2-yl)-2-phenylethanone (16). Yield 70.3%, oil from hexane.
1H NMR spectrum, δ, ppm, J (Hz): 2.38 (s, 3H, 4-MeAr); 5.71 (d, 1H, CHOH, J = 6.3); 5.82 (d, 1H, CHOH,
J = 6.3); 6.30 (dd, 1H, H(4) Pyr, J = 3.9, J = 3.9); 6.93 (d, 2H, H(2) and H(6) Ar, J = 9.0); 7.17 (d, 2H, H(3) and
H(5) Ar, J = 9.0); 7.25 (d, 1H, H(5) Pyr, J = 3.9); 7.29 (d, 1H, H(3) Pyr, J = 3.9); 7.31 (d, 1H, H(4) Ph, J = 8.1);
7.34 (t, 2H, H(3) and H(5) Ph, J = 8.1); 7.44 (d, 2H, H(2) and H(6) Ph, J = 8.1). Found, %: C 78.27; H 5.59.
C19H17NO2. Calculated, %: C 78.33; H 5.88.
2-Hydroxy-1-(1,2,5-trimethyl-1H-pyrrol-3-yl)-2-phenylethanone (17). Yield 64.7%, colorless plates;
1
mp 135-136°C (benzene). H NMR spectrum, δ, ppm, J (Hz): 2.08 (s, 3H, 5-MePyr); 2.45 (s, 3H, 2-MePyr);
3.31 (s, 3H, 1-MePyr); 5.26 (d, 1H, CHOH, J = 5.7); 5.53 (d, 1H, CHOH, J = 5.7); 6.29 (s, 1H, H(4) Pyr); 7.18
(d, 1H, H(4) Ph, J = 6.9); 7.27 (t, 2H, H(3) and H(5) Ph, J = 6.9); 7.36 (d, 2H, H(2) and H(6) Ph, J = 6.9).
Found, %: C 74.01; H 7.04. C15H17NO2. Calculated, %: C 74.05; H 7.04.
1-[1-(4-Bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-hydroxy-2-phenylethanone (18). Yield 92.6%,
1
light-yellow powder; mp 160-161°C (80% ethanol). H NMR spectrum, δ, ppm, J (Hz): 1.91 (s, 3H, 5-MePyr);
2.25 (s, 3H, 2-MePyr); 5.39 (d, 1H, CHOH, J = 5.7); 5.55 (d, 1H, CHOH, J = 5.7); 6.44 (s, 1H, H(4) Pyr); 7.22
(d, 1H, H(4) Ph, J = 7.5); 7.23 (d, 2H, H(2) and H(6) Ar, J = 8.4); 7.31 (t, 2H, H(3) and H(5) Ph, J = 7.5); 7.42
(d, 2H, H(2) and H(6) Ph, J = 7.5); 7.68 (d, 2H, H(3) and H(5) Ar, J = 8.4). Found, %: C 62.53; H 4.71.
C20H18BrNO2. Calculated, %: C 62.51; H 4.72.
2-Hydroxy-1-[2,5-dimethyl-1-(p-tolyl)-1H-pyrrol-3-yl]-2-phenylethanone (19). Yield 85.8%, light-
1
yellow powder; mp 126-127°C (80% ethanol). H NMR spectrum, δ, ppm, J (Hz): 1.89 (s, 3H, 5-MePyr); 2.24
(s, 3H, 4-MeAr); 2.40 (s, 3H, 2-MePyr); 5.29 (d, 1H, CHOH, J = 6.3); 5.52 (d, 1H, CHOH, J = 6.3); 6.37 (s,
158

1H, H(4) Pyr); 7.09 (d, 2H, H(2) and H(6) Ar, J = 8.1); 7.21 (d, 1H, H(4) Ph, J = 6.9); 7.28 (d, 2H, H(3) and
H(5) Ar, J = 8.1); 7.30 (t, 2H, H(3) and H(5) Ph, J = 6.9); 7.41 (d, 2H, H(2) and H(6) Ph, J = 6.9). Found, %:
C 78.98; H 6.65. C21H21NO2. Calculated, %: C 78.97; H 6.63.
2-Hydroxy-1-(1H-indol-3-yl)-2-phenylethanone (20). Yield 85.9%, colorless prisms; mp 194-196°C
(toluene). 1H NMR spectrum, δ, ppm, J (Hz): 5.70 (d, 1H, CHOH, J = 4.2); 5.77 (d, 1H, CHOH, J = 4.2); 7.12
(t, 1H, H(6) Ind, J = 8.1); 7.15 (t, 1H, H(5) Ind, J = 8.1); 7.20 (d, 1H, H(4) Ph, J = 7.3); 7.28 (t, 2H, H(3) and
H(5) Ph, J = 7.3); 7.40 (d, 1H, H(7) Ind, J = 8.1); 7.51 (d, 2H, H(2) and H(6) Ph, J = 7.3); 8.18 (d, 1H, H(4) Ind,
J = 8.1); 8.43 (d, 1H, H(2) Ind, J = 3.0); 11.88 (d, 1H, H(l) Ind, J = 3.0). Found, %: C 76.47; H 5.21.
C16H13NO2. Calculated, %: C 76.48; H 5.21.
2-Hydroxy-1-(2-methyl-1H-indol-3-yl)-2-phenylethanone (21). Yield 71.4%, colorless crystals;
1
mp 175-176°C (benzene). H NMR spectrum, δ, ppm, J (Hz): 2.41 (s, 3H, Me); 5.72 (d, 1H, CHOH, J = 6.0);
5.90 (d, 1H, CHOH, J = 6.0); 7.16 (t, 1H, H(6) Ind, J = 7.2); 7.22 (t, 1H, H(5) Ind, J = 7.2); 7.24 (d, 1H,
H(4) Ph, J = 7.8); 7.30 (t, 2H, H(3) and H(5) Ph, J = 7.8); 7.45 (d, 1H, H(7) Ind, J = 7.2); 7.54 (d, 2H, H(2) and
H(6) Ph, J = 7.8); 7.83 (d, 1H, H(4) Ind, J = 7.2); 11.88 (s, 1H, H(l) Ind). Found, %: C 76.87; H 5.73.
C17H15NO2. Calculated, %: C 76.96; H 5.70.
2-Hydroxy-1-(1,2-dimethyl-1H-indol-3-yl)-2-phenylethanone (22). Yield 73.9%, colorless crystals;
mp 185°C ethanol. 1H NMR spectrum, δ, ppm, J (Hz): 2.50 (s, 3H, 2-MeInd); 3.70 (s, 3H, l-MeInd); 5.69 (d, 1H,
CHOH, J = 5.9); 5.94 (d, 1H, CHOH, J = 5.9); 7.19 (t, 1H, H(6) Ind, J = 8.1); 7.22 (t, 1H, H(5) Ind, J = 8.1);
7.27 (d, 1H, H(4) Ph, J = 6.3); 7.37 (t, 2H, H(3) and H(5) Ph, J = 6.3); 7.43 (d, 1H, H(7) Ind, J = 8.1); 7.49 (d,
2H, H(2) and H(6) Ph, J = 6.3); 8.04 (d, 1H, H(4) Ind, J = 8.1). Found, %: C 77.35; H 6.06. C18H17NO2.
Calculated, %: C 77.40; H 6.13.
2-Hydroxy-2-phenyl-1-(2-phenyl-1H-indol-3-yl)ethanone (23). Yield 90.9%, white powder;
mp 151-152°C (benzene–hexane). 1H NMR spectrum, δ, ppm, J (Hz): 5.79 (d, 1H, CHOH, J = 6.0); 5.83 (d, 1H,
CHOH, J = 6.0); 7.17 (t, 1H, H(6) Ind, J = 6.9); 7.21 (t, 1H, H(5) Ind, J = 6.9); 7.23 (d, 1H, H(4) Ph, J = 7.9);
7.30 (t, 2H, H(3) and H(5) Ph, J = 7.9); 7.35-7.40 (m, 5H, 2-PhInd); 7.45 (d, 1H, H(7) Ind, J = 6.9); 7.53 (d, 2H,
H(2) and H(6) Ph, J = 7.9); 7.77 (d, 1H, H(4) Ind, J = 6.9); 11.51 (s, 1H, H(1) Ind). Found, %: C 80.59; H 5.18.
C22H17NO2. Calculated, %: C 80.71; H 5.23.
1-(2-tert-Butyl-1H-indol-3-yl)-2-hydroxy-2-phenylethanone (24). Yield 80.0%, colorless prisms;
1
mp 222-224°C (benzene). H NMR spectrum, δ, ppm, J (Hz): 1.61 (s, 9H, t-Bu); 5.97 (d, 1H, CHOH, J = 8.1);
6.22 (d, 1H, CHOH, J = 8.1); 7.17 (t, 1H, H(6) Ind, J = 7.2); 7.21 (t, 1H, H(5) Ind, J = 7.2); 7.24 (d, 1H,
H(4) Ph, J = 7.9); 7.30 (t, 2H, H(3) and H(5) Ph, J = 7.9); 7.45 (d, 1H, H(7) Ind, J = 7.2); 7.54 (d, 2H, H(2) and
H(6) Ph, J = 7.9); 7.83 (d, 1H, H(4) Ind, J = 7.2); 12.10 (s, 1H, H(1) Ind). Found, %: C 78.09; H 6.77.
C20H21NO2. Calculated, %: C 78.15; H 6.89.
2-Hydroxy-1-(1H-indol-3-yl)-2-(2-thienyl)ethanone (25). Yield 52.7%, colorless needles;
mp 162-163°C (ethanol). 1H NMR spectrum, δ, ppm, J (Hz): 6.06 (d, 1H, CHOH, J = 4.5); 6.13 (d, 1H, CHOH,
J = 4.5); 6.93 (t, 1H, H(4) Th, J = 4.8); 7.13 (d, 1H, H(3) Th, J = 4.8); 7.20 (t, 1H, H(6) Ind, J = 7.8); 7.22 (t,
1H, H(5) Ind, J = 7.8); 7.40 (d, 1H, H(5) Th, J = 4.8); 7.48 (d, 1H, H(7) Ind, J = 7.8); 8.19 (d, 1H, H(4) Ind,
J = 7.8); 8.57 (s, 1H, H(2) Ind); 12.05 (s, 1H, H(1) Ind). Found, %: С 65.34; Н 4.27. C14H11NO2S.
Calculated, %: C 65.35; H 4.31.
2-Hydroxy-1-(5-methyl-2-furyl)-2-phenylethanone (26). Yield 90.3%, colorless needles;
1
mp 150-151°C (ethanol). H NMR spectrum, δ, ppm, J (Hz): 2.33 (s, 3H, 5-MeFur); 5.63 (d, 1H, CHOH,
J = 3.9); 5.94 (d, 1H, CHOH, J = 3.9); 6.24 (d, 1H, H(4) Fur, J = 3.0); 7.21 (d, 1H, H(4) Ph, J = 7.5); 7.29 (t,
2H, H(3) and H(5) Ph, J = 7.5); 7.43 (d, 2H, H(2) and H(6) Ph, J = 7.5); 7.46 (d, 1H, H(3) Fur, J = 3.0).
Found, %: C 72.19; H 5.62. C13H12O3. Calculated, %: C 72.21; H 5.59.
O,N-Dideuterio-2-hydroxy-1-(1H-indol-3-yl)-2-phenylethanone (28). Yield 80.9%, colorless prisms;
1
mp 198-200°C (toluene). H NMR spectrum, δ, ppm, J (Hz): 5.80 (s, 1H, CHOD); 7.16 (t, 1H, H(6) Ind,
J = 9.6); 7.19 (t, 1H, H(5) Ind, J = 9.6); 7.23 (d, 1H, H(4) Ph, J = 8.1); 7.30 (t, 2H, H(3) and H(5) Ph, J = 8.1);
159

7.46 (d, 1H, H(7) Ind, J = 9.6); 7.54 (d, 2H, H(2) and H(6) Ph, J = 8.1); 8.21 (d, 1H, H(4) Ind, J = 9.6); 8.54 (s,
1H, H(2) Ind). Found, %: C 75.84; N 5.49. C16H11D2NO2. Calculated, %: C 75.87; N 5.53.
2-Methoxy-1-(1-methyl-1H-indol-3-yl)-2-phenylethanone (29). To a stirred solution of the α-benzoin
28 (380 mg, 1.50 mmol) in DMSO (5 ml) a 10% aqueous solution of sodium hydroxide (0.60 ml, 1.50 mmol)
and dimethyl sulfate (0.57 ml, 6.00 mmol) were added successively. The obtained mixture was stirred, 20 ml of
water was added, and the precipitate was filtered off and crystallized from 80% ethanol. Yield 51.8%, light-
yellow powder; mp 132-133°C. 1H NMR spectrum, δ, ppm, J (Hz): 3.40 (s, 3H, NMe); 3.88 (s, 3H, OMe); 5.33
(s, 1H, CHOMe); 7.18 (t, 1H, H(6) Ind, J = 8.4); 7.21 (t, 1H, H(5) Ind, J = 8.4); 7.25 (d, 1H, H(7) Ind, J = 8.4);
7.30 (t, 2H, H(3) and H(5) Ph, J = 7.5); 7.46 (d, 1H, H(4) Ph, J = 7.5); 7.51 (d, 2H, H(2) and H(6) Ph, J = 7.5);
8.19 (d, 1H, H(4) Ind, J = 8.4); 8.57 (s, 1H, H(2) Ind). Found, %: С 77.36; H 6.10; N 5.00. C18H17NO2.
Calculated, %: С 77.40; H 6.13; N 5.01.
The work was carried out with financial support from the Ministry of Education and Science of Ukraine
(No. 0101U00159).
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