Synthesis of 3-aminomethyl-4-hydroxycoumarins and their retro-Mannich reaction in dimethyl sulfoxide

Article abstract of DOI:10.1007/s11172-015-0879-5

Hydrogenation of 3-formyl-4-hydroxycoumarin aliphatic imines leads to 3-aminomethyl-4-hydroxycoumarins, which undergo a retro-Mannich reaction in dimethyl sulfoxide containing even traces of water.

Full text of DOI:10.1007/s11172-015-0879-5

Russian Chemical Bulletin, International Edition, Vol. 64, No. 2, pp. 423—428, February, 2015
423
Synthesis of 3ꢀaminomethylꢀ4ꢀhydroxycoumarins
and their retroꢀMannich reaction in dimethyl sulfoxide
B. G. Milevskii,a T. A. Chibisova,a N. P. Solov´eva,a A. Yu. Sukhorukov,b and V. F. Travena
aD. I. Mendeleev University of Chemical Technology of Russia,
9 Miusskaya pl., 125047 Moscow, Russian Federation.
Fax: +7 (495) 609 2964. Eꢀmail: traven@muctr.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation
Hydrogenation of 3ꢀformylꢀ4ꢀhydroxycoumarin aliphatic imines leads to 3ꢀaminomethylꢀ
4ꢀhydroxycoumarins, which undergo a retroꢀMannich reaction in dimethyl sulfoxide containꢀ
ing even traces of water.
Key words: 4ꢀhydroxycoumarin derivatives, imines, enamines, hydrogenation, aminoꢀ
methylcoumarins, retroꢀMannich reaction, dicoumarol.
4ꢀHydroxycoumarins substituted at position 3 are of
significant interest because of their high biological activiꢀ
ty.1—3 Among them are many known biologically active
agents possessing antiinflammatory, antituberculosis, or
anticoagulation properties (dicoumarol, sincoumar, phenꢀ
procoumon, warfarin). A number of 3ꢀsubstituted 4ꢀhyꢀ
droxycoumarins are used in agriculture as deraticides.
The aminomethyl fragment is also an efficient pharmaꢀ
cophore. In order to synthesize new coumarin derivatives
promising for the evaluation of their pharmacological
properties, we carried out the reduction reaction of aroꢀ
matic and aliphatic imines of 3ꢀformylꢀ4ꢀhydroxycouꢀ
marin. The analysis performed using the PASS Online
program4 showed the high levels of predicted biological
1: R = Bu (a), Bn (b), CH2CH2OH (c), 4ꢀMeC6H4 (d)
2: X = 1,2ꢀC6H4 (a), CH2CH2 (b)
activity for the reduction products, the coumarin alkylꢀ
(aryl)aminomethyl derivatives, no less than to 30 biologiꢀ
cal targets. During identification of obtained 3ꢀaminomeꢀ
thylcoumarins, we studied their hydrolytic transformaꢀ
tions in dimethyl sulfoxide.
acetic acid was used for the reduction of compound 2d,
the starting imine was recovered.
The structures of imines 1a—d and 2a,b, which were
subjected to reduction, are given below.
The failure of the reducing agents mentioned above
can be possibly explained by the increased tendency of
3ꢀformylꢀ4ꢀhydroxycoumarin imines to tautomeric transꢀ
formations. Earlier, we found that both in crystals and in
solutions these imines virtually completely exist as a mixꢀ
ture of Eꢀ and Zꢀisomers of the ketoenamine tautomeric
form (Scheme 1).5—7
As it turned out, the reduction of compounds 1 and 2
can be accomplished under hydrogenation conditions of
the C=C double bond. The hydrogenation was carried out
with gaseous hydrogen in the presence of heterogeneous
catalysts, Raney nickel and palladium on charcoal (Pd/C,
10% of Pd), at temperatures from 20 to 60 C and hydroꢀ
gen pressure from 2 to 10 atm.
Initially, for the reduction of imines 1a—d and 2a,b we
applied the reagents commonly used in the reduction of
a C=N bond: sodium borohydride, sodium cyanoboroꢀ
hydride, and triethylsilane. However, the use of these reꢀ
ducing agents did not lead to the preparation of the target
aminomethyl derivatives. In particular, the reaction of
compound 1a with sodium borohydride gives an unsepaꢀ
rable mixture of products, in which only traces of the exꢀ
pected aminomethyl derivative were found by thinꢀlayer
chromatography. A similar result was obtained upon atꢀ
tempted reduction of imine 2a with sodium cyanoboroꢀ
hydride in acetic acid. When triethylsilane in trifluoroꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0423—0428, February, 2015.
1066ꢀ5285/15/6402ꢀ0423 © 2015 Springer Science+Business Media, Inc.

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Milevskii et al.
points and 1H NMR spectra showed that the products
obtained by two alternative pathways are identical. At the
same time, the yield of compound 3a in the Mannich
reaction was considerably lower (58%) than in the hydroꢀ
genation of ketoenamine 1a (91%), that leads, apart from
anything else, to certain difficulties in the isolation of the
target product in the pure form.
Scheme 1
At the same time, the hydrogenation of ketoenamines
1d and 2a derived from aromatic amines is more compliꢀ
cated. The 1H NMR spectroscopic (CDCl3—DMSOꢀd6)
and mass spectrometric data showed that the hydroꢀ
genation of 3ꢀ((4ꢀmethylphenylamino)methylidene)ꢀ2Hꢀ
chromeneꢀ2,4(3H)ꢀdione (1d) using palladium on charꢀ
coal (hydrogen pressure of 10 atm., 60 C) did not lead to
the expected hydrogenation product 5. The reaction mixꢀ
ture obtained by hydrogenation of ketoenamine 1d conꢀ
tains 4ꢀhydroxyꢀ3ꢀmethylcoumarin 6 and pꢀtoluidine 7,
that indicates that the hydrogenolysis of the carbon—nitroꢀ
gen bond takes place in the course of the reaction (Scheme 3).
Besides, the products of hydrogenation of the benzene
ring of pꢀtoluidine were identified in the reaction mixture.
Hydrogenation of 1d on Raney nickel under milder condiꢀ
tions (hydrogen pressure of 2 atm., 20 C) is also accomꢀ
panied by hydrogenolysis, however, no products of hydroꢀ
genation of pꢀtoluidine were found in this case.
Hydroxy aimine
(E)ꢀKetoenamine
(Z)ꢀKetoenamine
The hydrogenation of ketoenamines 1a—c derived from
aliphatic and aliphatic aryl amines in the presence of Raney
nickel (Scheme 2) proceeds smoothly and the yields of the
target products 3a—c reach 76—91%. The 1H NMR specꢀ
tra of the hydrogenation products 3a—c exhibit singlets
for the protons C(9)H2 in the region from  3.97 to 4.07 as
characteristic signals. The chemical shift values for the
carbon atoms in the 13C NMR spectra of compounds 3a—c
also confirm the structure suggested for the hydrogenation
products. For example, if for the predominant in solution
(CDCl3) Eꢀisomer of ketoenamine 1b the chemical shifts
for the carbon atoms C(2), C(4), C(3), C(9) are  163.7,
181.2, 97.1, 154.7, for amine 3b (CDCl3—DMSOꢀd6) their
values are  174.3, 164.2, 87.6, 49.2, respectively. It should
be noted that the chemical shift for carbon atom C(4)
in 4ꢀhydroxycoumarin (CDCl3—DMSOꢀd6) is  160.5,
whereas for atom C(2) it is at  163.9.
Scheme 3
Scheme 2
1, 3: R =
(a),
(b),
(c)
Reagents and conditions: Raney Ni, H2 (2 atm.), MeOH, 20 C.
Reagents and conditions: Pd/C, H2 (10 atm.), MeOH, 60 C.
To confirm a possibility of the preparation of comꢀ
pounds 3a—c by the hydrogenation reꢀ
action of the corresponding imines, we
obtained compound 3a by the Manꢀ
nich condensation of 4ꢀhydroxycouꢀ
marin 4 with nꢀbutylamine and formꢀ
aldehyde.8,9 A comparison of melting
Similar results were obtained in the hydrogenation of
compound 2a using Raney nickel and palladium on charꢀ
coal (hydrogen pressure of 2 or 10 atm., temperature of 20
or 60 C) and compound 2b on Raney nickel (hydrogen
pressure of 2 atm., 20 oC). The 1H NMR spectra and mass
spectra of the reaction mixture obtained by hydrogenation

3ꢀAminomethylꢀ4ꢀhydroxycoumarins
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
425
of compounds 2a and 2b showed that it contains signals of
4ꢀhydroxyꢀ3ꢀmethylcoumarin 6 and oꢀphenylenediamine
or 1,2ꢀdiaminoethane, respectively. The formation of
4ꢀhydroxyꢀ3ꢀmethylcoumarin 6 in the course of hydroꢀ
genation of imines of 3ꢀformylꢀ4ꢀhydroxycoumarin and
compound 2a is not a surprise, since there are literature10
examples of the carbon—nitrogen bond cleavage during
hydrogenation of aminomethylarenes.
CH2 (9)
CH2 (benzylamine)
CH2 (8)
С(11)H2
С(9)H2
(3b)
(3b)
During synthesis and studies of hydrogenation prodꢀ
ucts of ketoenamines 1a—c, we noticed their hydrolytic
instability. It turned out that the 1H NMR spectra of comꢀ
pounds 3a—c recorded in DMSOꢀd6 containing even inꢀ
significant amount of water clearly exhibit signals of the
products of their hydrolysis, first of all, of dicoumarol 8
and the corresponding amines.* We studied in greater deꢀ
tails hydrolytic transformations of aminomethyl comꢀ
pound 3b. It was found that when compound 3b was alꢀ
lowed to stand in solution in DMSOꢀd6 at room temperaꢀ
ture for several days, a new strong singlet appears in the
spectrum at  4.02, as well as signals of dicoumarol 8
4.6 4.4 4.2 4.0 3.8 3.6 3.4 3.2 3.0

Fig. 1. Signals of dicoumarol 8, 4ꢀhydroxyꢀ3ꢀhydroxymethylꢀ
coumarin (9), and benzylamine in the 1H NMR spectrum
(DMSOꢀd6) of compound 3b.
(CH 3.65) and benzylamine (CH2 3.61) (Fig. 1).
2
The LC/MS of compound 3b in DMSO containing
water added on purpose makes it possible using ionꢀdetecꢀ
tion method to identify the following compounds: benzylꢀ
aminomethylcoumarin 3b (m/z 282), dicoumarol 8
(m/z 337), free benzylamine (m/z 108), and 4ꢀhydroxyꢀ3ꢀ
(hydroxymethyl)coumarin 9 (m/z 193). A peak with
m/z 456 should be also noted, which can be assigned to the
tertiary amine 11, the condensation product of secondary
amine 3b with compound 9. Thus, it can be suggested that
the transformation of compound 3b to dicoumarol 8 proꢀ
ceeds through the formation of 4ꢀhydroxyꢀ3ꢀ(hydroxyꢀ
methyl)coumarin 9, which gives rise to both quinoneꢀmeꢀ
thide 10 and 4ꢀhydroxycoumarin 4 (Scheme 4).
To confirm the presence of compound 8 in the prodꢀ
ucts of transformation of 3b in DMSOꢀd6, dicoumarol 8
was synthesized by an alternative method: by the reaction
of 4ꢀhydroxycoumarin with formaldehyde. The following
signals in the NMR spectra (DMSOꢀd6) are characteristic
of dicoumarol 8: a singlet for the CH2 group at  3.65 and
the signal for the carbon atom of the methylene group at
 19.79.**
Among the products of the hydrolytic transformation
of aminomethyl derivatives 3, other compounds were also
found. In particular, we assign the signal at  4.02 with the
1
hetero spinꢀspin coupling constant JC,H = 148.2 Hz to
the protons of the methylene group of 4ꢀhydroxyꢀ3ꢀhydrꢀ
oxymethylcoumarin 9. Besides, a weak singlet is observed
in the 1H NMR spectrum at  5.25, which corresponds to
proton H(3) of 4ꢀhydroxycoumarin 4. This was confirmed
by the 1H NMR spectrum of a mixed probe with the
authentic sample of 4ꢀhydroxycoumarin 4. Another weak
broad signal is observed at  6.83, which can be assigned to
the protons of the methylene group of 3ꢀmethylideneꢀ2Hꢀ
chromeneꢀ2,4(3H)ꢀdione (quinoneꢀmethide, 10).
We found that the addition of water to the solutions of
compounds 3a and 3c in DMSO or methanol even at low
temperatures also leads to a noticeable increase in the
amount of dicoumarol 8. The data obtained allows us to
suggest the following scheme of the hydrolytic transforꢀ
mation of aminomethyl derivatives 3a—c under condiꢀ
tions studied (see Scheme 4).
The scheme is based on the retroꢀMannich reaction.
This scheme differs from the explanation suggested earlier
for the hydrolytic transformations of 4ꢀhydroxyꢀ3ꢀpiperiꢀ
dinomethylcoumarin upon its heating in a dilute hydroꢀ
chloric acid,8 according to which piperidine and quinoneꢀ
methide 10 are formed in the first step (Scheme 5). The
latter undergoes the retroꢀaldol condensation to give
* 1H NMR spectra were recorded in DMSOꢀd6 (99.6%, from
Deutero GmbH).
** Synthesis of dicoumarol was described earlier in the work,11
the reported chemical shift values for carbon atoms in the
13C NMR spectrum agree with those obtained in this work.

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Milevskii et al.
Scheme 4
Scheme 5
4ꢀhydroxycoumarin 4, which is involved in the Michael
addition to quinoneꢀmethide 10 with the formation of
dicoumarol 8. It should be noted that the intermediate
quinoneꢀmethide 10 was not isolated,8 but a similar conꢀ
densation product of 4ꢀhydroxycoumarin 4 and salicylalꢀ
dehyde was characterized earlier.12
In conclusion, in the present work hydrogenation of
imines of 3ꢀformylꢀ4ꢀhydroxycoumarin was used to synꢀ
thesize the corresponding 4ꢀhydroxycoumarin 3ꢀaminoꢀ
methyl derivatives. Such an approach to the preparation
of aminomethyl derivatives can be useful for the developꢀ
ment of organic synthesis methodology, including that for
the preparation of compounds with an aminomethyl group,
the synthesis of which by the Mannich reaction is compliꢀ
cated or impossible.13 An ability of 4ꢀhydroxycoumarin
3ꢀaminomethyl derivatives to undergo a retroꢀMannich
reaction in dimethyl sulfoxide containing even insignifiꢀ
cant amount of water was also studied.
Experimental
1
H and 13C NMR spectra were recorded on Bruker WPꢀ200ꢀSY
(200 MHz), Varian Unity+ 400 (400 MHz), and Bruker AM 300
spectrometers (300 MHz) in CDCl3 (99.8%, from Deutero
GmbH), DMSOꢀd6 (99.6%, from Deutero GmbH), and their
mixtures. The signals of residual protons of the solvent were used
as a reference (CDCl3,  7.27; DMSOꢀd6 and a mixture of
H
CDCl3—DMSOꢀd6, H 2.5,  39.5). Mass spectra (EI, 70 eV)
C
was obtained on a Kratos MSꢀ30 (United Kingdom), temperaꢀ
ture of the source of ions was 200 C, direct injection of the
sample. LC/MS were performed on a PE SCIEX API 165 specꢀ

3ꢀAminomethylꢀ4ꢀhydroxycoumarins
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
427
trometer (ELSD and UV 254 nm detectors). Elemental analysis
was performed on a Euro Vector Instruments analyzer and the
Euro EA Software (Elemental Analyzer).
Reaction progress and individuality of compounds obtained
were monitored by TLC on Silufol UVꢀ254, ARMSORB plates.
3ꢀFormylꢀ4ꢀhydroxycoumarin and bisimines 2a,b were obꢀ
tained according to the published procedure.5 Imines 1b,d were
obtained according to the described procedure.6,7
Before use, Raney nickel was several times washed with anꢀ
hydrous methanol and dried in vacuo at 100 C, then added to
anhydrous methanol. The thus prepared catalyst was active for
10 days.14
3ꢀ{[(nꢀButyl)amino]methylidene}ꢀ2Hꢀchromeneꢀ2,4(3H)ꢀdiꢀ
one (1a). nꢀButylamine (0.05 mL, 0.5 mmol) was added to
a solution of 3ꢀformylꢀ4ꢀhydroxycoumarin (100 mg, 0.5 mmol)
in ethanol (5 mL). The mixture obtained was refluxed for 2 h.
The reaction mixture was cooled to room temperature to obtain
compound 2a. The yield was 73.5 mg (60%), m.p. 128—130 C
(ethanol) (cf. Ref. 15: m.p. 131—132 C (chloroform—hexane)).
1H NMR (200 MHz, CDCl3), : 11.91 (br.s, 0.7 H, NH (Eꢀisoꢀ
mer)); 10.27 (br.s, 0.3 H, NH (Zꢀisomer)); 8.55 (d, 0.3 H, H(9)
(Zꢀisomer), 3J = 14.6 Hz); 8.39 (d, 0.7 H, H(9) (Eꢀisomer),
3J = 13.7 Hz); 8.06 (d, 1 H, H(5), 3J = 7.9 Hz); 7.57 (m, 1 H, H(7));
7.27 (m, 2 H, H(6), H(8)); 3.56 (m, 2 H, NHCH2); 1.61 (m, 4 H,
NHCH2CH2CH2Me); 0.99 (m, 3 H, CH3).
3ꢀ{[(2ꢀHydroxyethyl)amino]methylidene}ꢀ2Hꢀchromeneꢀ2,4ꢀ
(3H)ꢀdione (1c). 2ꢀAminoethanol (0.032 mL, 0.5 mmol) was
added to a solution of 3ꢀformylꢀ4ꢀhydroxycoumarin (100 mg,
0.5 mmol) in anhydrous toluene (5 mL). The reaction mixture
was refluxed for 1 h. The reaction mixture was cooled to room
temperature to obtain compound 1c. The yield was 107 mg (92%),
m.p. 176—178 C (dioxane—nꢀhexane). The 1H NMR spectrum
corresponds to that described in the literature.15 1H NMR
(200 MHz, CDCl3), : 11.65 (br.s, 0.6 H, NH (Eꢀisomer)); 10.36
(br.s, 0.4 H, NH (Zꢀisomer)); 8.47 (m, 1 H, H(9)); 7.93 (d, 1 H,
H(5), 3J = 7.9 Hz); 7.68—7.25 (m, 3 H, H(6), H(7), H(8)); 5.03
(br.s, 1 H, OH); 3.63 (br.s, 4 H, CH2CH2).
m.p. 159 C (decomp.)). 1H NMR (200 MHz, DMSOꢀd6),
: 7.82 (d, 1 H, H(5), J = 7.9 Hz); 7.33—7.62 (m, 6 H, H(7),
3
H(2´), H(3´), H(4´), H(5´), H(6´)); 7.09—7.23 (m, 2 H, H(6),
H(8)); 4.09 (br.s, 2 H, C(9)H2); 3.87 (br.s, 2 H, C(11)H2).
13C NMR (50 MHz, CDCl3—DMSOꢀd6), : 174.3 (C(2)); 164.2
(C(4)); 154.0 (C(8a)); 132.4 (C(1´)); 130.8 (C(7)); 130.1 (C(3´),
C(5´)); 128.8 (C(4´)); 128.7 (C(2´), C(6´)); 124.5 (C(5)); 121.3
(C(6)); 116.0 (C(8)); 115.5 (C(4a)); 87.6 (C(3)); 49.2 (C(9)H2);
42.8 (C(11)H2). MS (EI, 70 eV), m/z (Irel (%)): 174 [M –
–C7H9N]+ (4), 162 [M – C8H9N]+ (8), 121 [M – C8H9N –
–C2HO]+ (34), 106 [M – C10H7O3]+ (57), 91 [C7H7]+ (100).
4ꢀHydroxyꢀ3ꢀ{[(2ꢀhydroxyethyl)amino]methyl}ꢀ2Hꢀchromꢀ
enꢀ2ꢀone (3c). The yield was 153 mg (76%), m.p. 175—176 C
(decomp.) (cf. Ref. 8: m.p. 177 C (decomp.)). 1H NMR
(200 MHz, DMSOꢀd6), : 7.81 (d, 1 H, H(5), 3J = 7.9 Hz);
7.38—7.50 (m, 1 H, H(7)); 7.09—7.22 (m, 2 H, H(6), H(8));
5.19 (br.s, 1 H, CH2OH); 3.94 (s, 2 H, C(9)H2); 3.63 (m, 2 H,
C(12)H2); 2.92 (m, 2 H, C(11)H2). 13C NMR (50 MHz, CDCl3—
DMSOꢀd6), : 174.3 (C(2)); 164.3 (C(4)); 154.0 (C(8a)); 130.7
(C(7)); 124.4 (C(5)); 122.3 (C(6)); 116.0 (C(8)); 115.4 (C(4a));
87.5 (C(3)); 56.4 (C(12)H2); 47.7 (C(9)H2); 43.2 (C(11)H2).
Hydrogenation of imine 1d. According to the 1H NMR
spectroscopic (400 MHz, CDCl3—DMSOꢀd6) and mass specꢀ
trometric data, the mixture of hydrogenation products of imine
1d contains 4ꢀhydroxyꢀ3ꢀmethylcoumarin 6,16 pꢀtoluidine, and
products of hydrogenation of pꢀtoluidine benzene ring.
Hydrogenation of ketoenamine 2a. According to the 1H NMR
spectroscopic (400 MHz, CDCl3—DMSOꢀd6) and mass spectroꢀ
metric data, the mixture of hydrogenation products of ketoꢀ
enamine 2a contains 4ꢀhydroxyꢀ3ꢀmethylcoumarin 6 (see
Ref. 16) and oꢀphenylenediamine.
Hydrogenation of ketoenamine 2b. According to the 1H NMR
spectroscopic (400 MHz, CDCl3—DMSOꢀd6) and mass spectroꢀ
metric data, the reaction mixture obtained contains 4ꢀhydroxyꢀ
3ꢀmethylcoumarin 6 (see Ref. 16) and 1,2ꢀdiaminoethane.
Synthesis of compound 3a by Mannich condensation. A 40%
aqueous solution of formalin (0.41 mL, 0.006 mol calculated on
formaldehyde CH2O) was added to a solution of nꢀbutylamine
(0.6 mL, 0.006 mol) in anhydrous ethanol (10 mL), followed
by the addition of a solution of 4ꢀhydroxycoumarin 4 (1 g,
0.006 mmol) in anhydrous ethanol at room temperature. The
crystallization of the product was completed after cooling of the
mixture to 5 C and standing at this temperature for 1 h.
A precipitate of compound 3a was filtered off, washed with diꢀ
ethyl ether, and dried. The yield was 2.6 g (58%), m.p. 129—130 C
(EtOH, with decomp.).
Hydrogenation of imines 1 and 2 under hydrogen atmosphere
(general procedure). A suspension of the corresponding ketoꢀ
enamine (0.86 mmol) and Raney nickel (or palladium on charꢀ
coal) (about 50 mg) in anhydrous methanol (40 mL) was stirred
for 6 h under hydrogen (2 atm). After the starting ketoenamine
disappeared (TLC data, Silufol UVꢀ254 plates, eluent light petroꢀ
leum—ethyl acetate, 1 : 1), the catalyst was filtered off, the solꢀ
vent was evaporated. A precipitate obtained was washed with
ethyl acetate, the product was dried in vacuo.14
3ꢀ[(Butylamino)methyl]ꢀ4ꢀhydroxyꢀ2Hꢀchromenꢀ2ꢀone (3a).
The yield was 193 mg (91%), m.p. 132 C (decomp.) (cf. Ref. 8:
m.p. 133 C (decomp.)). 1H NMR (200 MHz, CDCl3—DMSOꢀd6),
Dicoumarol 8. A 40% aqueous solution of formalin (0.41 mL,
0.006 mol calculated on formaldehyde CH2O) was added to
a solution of 4ꢀhydroxycoumarin 4 (2 g, 0.012 mol) in 50% aqueꢀ
ous ethanol. After 1 h of stirring, a precipitate of dicoumarol 8
was filtered, washed on the filter with water and ethanol, and
dried. The yield was 1.9 g (94%), m.p. 287—288 C (cf. Ref. 17:
m.p. 288—289 C). 1H NMR (200 MHz, CDCl3), : 8.01 (d, 2 H,
H(5), 3J = 7.9 Hz); 7.54—7.66 (m, 2 H, H(7)); 7.30—7.44 (m, 4 H,
H(6), H(8)); 3.87 (s, 2 H, CH2). 13C NMR (50 MHz, CDCl3—
DMSOꢀd6), : 168.0 (C(2)); 163.7 (C(4)); 151.7 (C(8a)); 132.1
(C(7)); 124.3 (C(6)); 123.4 (C(5)); 121.3 (C(4a)); 116.1 (C(8));
3
: 7.83 (d, 1 H, H(5), J = 7.9 Hz); 7.35—7.47 (m, 1 H, H(7));
7.08—7.20 (m, 2 H, H(6), H(8)); 3.90 (s, 2 H, C(9)H2); 2.83 (t, 2 H,
C(11)H2, 3J = 7.4 Hz); 1.51—1.69 (m, 2 H, C(12)H2); 1.19—1.43
(m, 2 H, C(13)H2); 0.88 (m, 3 H, CH3). 13C NMR (50 MHz,
CDCl3—DMSOꢀd6), : 174.5 (C(2)); 164.7 (C(4)); 154.4
(C(8a)); 131.0 (C(7)); 124.2 (C(5)); 122.6 (C(6)); 116.0 (C(8));
115.9 (C(4a)); 88.1 (C(3)); 46.0 (C(9)H2); 43.4 (C(11)H2); 27.8
(C(12)H2); 19.8 (C(13)H2); 13.9 (CH3). Found (%): C, 61.64;
H, 7.00; N, 4.99. C14H17NO3. Calculated (%): C, 61.70; H, 6.90;
N, 5.14.
1
102.3 (C(3)); 19.3 (CH2). The H and 13C NMR spectra correꢀ
spond to those described in the work.11 MS (EI, 70 eV), m/z
(Irel (%)): 336 [M]+ (78), 215 [M – C7H5O2]+ (34), 187 [M –
– C7H5O2 – CO]+ (15), 174 [M – C9H6O3]+ (94), 162 [M –
3ꢀ[(Benzylamino)methyl]ꢀ4ꢀhydroxyꢀ2Hꢀchromenꢀ2ꢀone (3b).
The yield was 188 mg (78%), m.p. 157 C (decomp.) (cf. Ref. 8:

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Russ.Chem.Bull., Int.Ed., Vol. 64, No. 2, February, 2015
Milevskii et al.
– C10H6O3]+ (70), 121 [M – C12H7O4]+ (94), 120 [M – C12H8O4]+
(100), 92 [M – C13H8O5]+ (70).
Heterocycl. Compd. (Engl. Transl.), 2013, 48, 1781 [Khim.
Geterotsikl. Soedin., 2012, 1903].
Reduction of ketoenamine 1a with sodium borohydride. Sodiꢀ
um borohydride (0.86 mmol) was added to a solution of ketoꢀ
enamine 1a (0.86 mmol) in methanol in several portions. After
the reaction reached completion (TLC monitoring, Silufol UVꢀ254
plates, eluent nꢀhexane—ethyl acetate, 3 : 2), the reaction mixꢀ
ture was poured into water and extracted with ethyl acetate. The
extract was dried with freshly calcined magnesium sulfate, the
drying agent was filtered off, the solvent was evaporated on
a rotary evaporator to obtain an oily mixture of products, which
was difficult to separate. Thinꢀlayer chromatography showed
the presence of only traces of desired aminomethyl derivative 3a.
Reduction of ketoenamine 1a with triethylsilane. Triethylsilane
(1 mL, 0.74 mmol) was added to a solution of ketoenamine 1a
(103 mg, 0.37 mmol) in trifluoroacetic acid (4.5 mL). The soluꢀ
tion was refluxed for 5 h and allowed to stand at room temperaꢀ
ture for 16 h. The solvent was evaporated on a rotary evaporator.
A precipitate obtained was washed with ethanol and dried to
recover the starting ketoenamine 1a.
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B. G. Milevskii, N. P. Solov´eva, V. I. Polshakov, G. G.
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The authors are grateful to Ph.D. (chem.) O. S. Anisiꢀ
mova (D. I. Mendeleev University of Chemical Technolꢀ
ogy of Russia) for the discussion of mass spectra of obꢀ
tained compounds.
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Received July 18, 2014;
in revised form October 24, 2014