Catalyst-Free Synthesis of Chromane-Type N,O-Acetals via Intramolecular Addition of Phenols to Enamines

SYNTHESIS

0

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©

Georg Thieme Verlag Stuttgart · New York

2020, 52, A–R

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Synthesis

V. A. Osyanin et al.

Paper

Catalyst-Free Synthesis of Chromane-Type N,O-Acetals via

Intramolecular Addition of Phenols to Enamines

Vitaly A. Osyanin*

Dmitry V. Osipov

Irina V. Melnikova

Kirill S. Korzhenko

Irina A. Semenova

Yuri N. Klimochkin

R²

intramolecular

addition of

R²

R2NH (2 equiv)

R2N COX

0

0-0

0

1-

9

2

1

7-0

7

9

2

COX

phenol to enamine

R¹

Michael/1,2-AdN /E2

sequence

6-exo-trig

O

OH NR2

O

NR2

COCF3 or CHO

48 examples

one-pot operation

mild conditions

broad substrate scope

good reagent availability

yields up to 94%

gram-scale

Department of Organic Chemistry, Chemical Technological

Faculty, Samara State Technical University, 244 Molodogvar-

deyskaya St., Samara 443100, Russian Federation

VOsyanin@mail.ru

8

Received: 17.01.2020

Accepted after revision: 19.06.2020

Published online: 27.07.2020

2-aminochromanes. This approach was used in the synthe-

sis of the drug tolterodine and its analogues, which are an-

tagonists of muscarinic receptors and are used in the treat-

ment of urological diseases (Figure 1).⁹

DOI: 10.1055/s-0040-1707209; Art ID: ss-2020-c0037-op

Abstract A new strategy to 2-aminochromanes through catalyst-free

cascade reaction of 3-trifluoroacetyl-4H-chromenes and 4H-chromene-

R

O

NH

3-carbaldehydes with cyclic secondary amines is presented. The reac-

N

O

N

tion proceeds through subsequent 1,4- and 1,2-additions of amine, bi-

molecular elimination of trifluoroacetamide or formamide, and 6-exo-

trig cyclization. The latter stage is a very rare example of addition of

phenols to enamines. The obtained semicyclic N,O-acetals were applied

as useful precursors for the synthesis of other chromanes.

O

N

O2N

Ph

LY294002

anticancer activity

O

X

N

O

NC3327

glucocorticoid

receptor antagonist

X = O, R = N(CH2)5 or

X = CH2, R = SMe

Key words chromanes, 4H-chromenes, cascade reactions, enamines,

cyclic secondary amines, N,O-acetals

O

H

antiplatelet activity

Ph

H

O

HO

N

N,O-Acetals, also called N,O-aminals, represent an inter-

esting class of organic compounds, which is a common

structural element in various pharmaceuticals and biologi-

H

4

CO2H

O

OH N(i-Pr)2

perinadine A

from Penicillium citrinum

tolterodine

1

cally active natural products, for example, alkaloids. Be-

Figure 1 Selection of relevant 2-aminochromane derivatives

sides, N,O-acetals are useful reagents and building blocks

since they are relatively stable, but readily generate unsta-

ble N-imines, which are attacked by nucleophiles to pro-

Unlike acyclic N,O-acetals, there are significantly fewer

methods for the preparation of chromane-type N,O-acetals,

such as the reaction of chroman-2-ols with secondary

amines,⁴three-component condensation of 2-naphthol, 3-

hydroxy-2,2-dialkylpropanal and secondary amines in the

2

duce complex highly functionalized molecules. For exam-

ple, they have been well recognized as key intermediates for

the iminium ion-mediated carbon–carbon bond-formation

reaction, particularly under protonic or Lewis acid condi-

,9

3

10

tions.

presence of p-TSA, the Diels–Alder reaction of o-quinone

methide precursors with substituted enamines,⁵

a,11

as well

One of the type of semicyclic N,O-acetals with an exocy-

clic N-atom are 2-aminochromanes. Among 2-aminochro-

manes and their areno- and heterocondensed analogues,

compounds with antiplatelet, anticancer activity and

non-steroidal glucocorticoid receptor antagonists⁶were

identified. Tetracyclic alkaloid, perinadine A, isolated from

the cultured broth of the fungus Penicillium citrinum, also

contains an aminochromane fragment. In addition, com-

pounds of this type are effective precursors of 2-(3-amino-

propyl)phenols, which can be obtained by hydrogenation of

as the reaction of enamines with o-hydroxy--nitrosty-

renes¹²or 2-hydroxybenzaldehydes, and a three-compo-

nent condensation of phenols or 2-naphthol, ,-unsaturat-

13

4

5

14

ed aldehydes and amines. In these cases, the obtained

chromane-type N,O-acetals, as a rule, contain various sub-

stituents at the C-3 and/or C-4 carbons of the dihydropyran

ring. For this reason, to access 2-aminochromanes unsubsti-

tuted at mentioned positions remains difficult. One of the

obvious approaches to their preparation could be [4+2]

7

©

Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B

Synthesis

V. A. Osyanin et al.

Paper

cycloaddition between N-vinylamines and precursors of

o-quinone methides.¹⁵However, most N-vinylamines are

not commercially available, their synthesis is fraught with a

Table 1 (continued)

_P_r_o_d_u_c_tb

G

HNR

2

16

4-AcC

6

H

4

(5s)

11s, 90%

11t, 85%

number of difficulties, or they are not known. In addition,

enamines of this type are often thermally unstable and un-

pyrimidin-2-yl (5t)

16b

dergo polymerization.

H (1a)

HN

(6)

12, 74%

13, 71%

Table 1 Synthesized Benzo[f]chroman-3-amines^a

OMe

G

H (1a)

(7)

N

COCF3

H

MeOH, rt, 1 h

HNR2

2.0 equiv)

+

a

(

– R2NCOCF3

Reaction conditions: 1a–d (1 mmol) and amine (2 mmol) in MeOH (3 mL)

O

NR2

at rt for 1 h.

b

Isolated yields.

G

HNR

2

Product^b

H (1a)

8a, 79%

8b, 83%

8c, 87%

8d, 93%

9a, 89%

9b, 91%

The trifluoroacetyl group has the property of unusually

greatly increasing the reactivity of electrophilic substrates

and affecting the regiodirection of reactions involving nuc-

leophiles. Its introduction into a molecule often makes pos-

sible to easily proceed reactions that do not occur even un-

der the most severe conditions in the absence of this sub-

stituent. The presence of a trifluoroacetyl group in the -

position of the pyran ring increases its susceptibility to var-

ious nucleophiles and makes these compounds valuable

building blocks for the synthesis of a wide variety of hetero-

cyclic compounds. 3-Trifluoroacetyl-4H-chromenes and

their benzofused analogues can be easily obtained via reac-

tion of o-quinone methide precursors and 1,1,1-trifluoro-4-

morpholinobut-3-en-2-one.¹⁷In continuation of our inter-

Br (1b)

t-Bu (1c)

Ad (1d)

H (1a)

HN

O

(2)

(3)

Br (1b)

CX

2

:

H (1a)

CH

2

(4a)

10a, 79%

10b, 84%

10c, 80%

10d, 81%

10e, 70%

10f, 70%

10g, 71%

CHMe (4b)

CHBn (4c)

CHPh (4d)

HN

CX2

C(OH)Ph (4e)

C(OH)H (4f)

C=O (4g)

Y:

18

est in the chemistry of 3-trifluoroacetyl-4H-chromenes,

we have studied their reaction with cyclic secondary

amines.

We have shown that the reaction of 2-trifluoroacetyl-

H-benzo[f]chromenes 1a–d with 2.0 equivalents of cyclic

H (1a)

HN

NY

Me (5a)

11a, 73%

1

CH

2

CH

2

OH (5b)

11b, 69%

11c, 83%

11d, 74%

11e, 89%

11f, 90%

11g, 94%

11h, 75%

11i, 80%

11j, 82%

11k, 94%

11l, 71%

11m, 83%

11n, 80%

11o, 82%

11p, 78%

11q, 82%

11r, 80%

secondary amines 2–7 in a methanol solution at room tem-

perature leads to 3-amino-substituted 2,3-dihydro-1H-

benzo[f]chromenes 8–13 (Table 1). We initially studied the

effect of the nature of the solvent on the yield of the prod-

uct 8a in the reaction of chromene 1a (G = H) with morpho-

line. We have found that the yield of chromane 8a was 58%

in acetonitrile, 65% in THF, 67% in ethyl acetate, 75% in ben-

zene, and 79% in methanol. Thus, we have chosen methanol

as a solvent for further studying the scope and generality of

the reaction. The synthesis of chromane 8a was repeated on

several different scales (up to 20 mmol), all with compara-

ble yields. A variety of cyclic secondary amines, such as pyr-

rolidine (3), piperidines 4a–f, 4-piperidone (4g), pipera-

zines 5, homopiperidine (6), and 6-methoxy-2,3,4,9-tetra-

hydro-1H-pyrido[3,4-b]indole (7) were examined, and the

results are summarized in Table 1. The target products pre-

cipitate directly from the reaction mixture and, as a rule, do

not require additional purification. A full conversion was

usually obtained after only 1 hour or less to give 3-amino-

benzochromanes 8–13 in high yields. The second isolated

cinnamyl (5c)

Bn (5d)

CH(4-FC

6 4 2

H ) (5e)

CO Et (5f)

2

Boc (5g)

Ph (5h)

2

3

4

2

4

2

4

-MeC

6

H

4

(5i)

(5j)

(5k)

(5l)

,6-Me

2

C

6

H

3

-ClC

6

H

4

(5m)

(5n)

6

-O

-MeOC

-EtOC

-HOC

2

NC

6

H

4

(5o)

(5p)

(5q)

(5r)

6

H

4

6

H

4

6

H

4

C

Synthesis

V. A. Osyanin et al.

Paper

product in the reaction is N-trifluoroacetylmorpholine or

morpholin-4-ium trifluoroacetate as a result of the hydro-

lysis of amide. This reaction works extremely well under

mild conditions, which allows the use of various functional-

ly substituted amines and chromenes. The reaction of

chromene 1a and tetrahydrocarboline derivative 7 proceeds

selectively at the more nucleophilic nitrogen atom of the

six-membered ring (product 13). A characteristic feature of

due to ability of these cyclic N,O-acetals to epimerize at C-3

via phenoxyimmonium zwitterion¹²and, even if cis-iso-

mers were initially formed, only the less soluble trans-1,3-

disubstituted products were obtained.

Table 3 Synthesized 1-(Het)arylbenzo[f]chroman-3-amines^a

Ar

O

Ar

COCF3

13

Δ, 30 min

C NMR spectra of aminobenzochromanes indicated in Ta-

ble 1 is the presence of a strongly unshielded signal of the

HNR2

excess)

+

(

– R2NCOCF3

O

NR₂

trans/cis >9:1



-carbon atom of the dihydropyran ring in the range of

1

91.8–94.4 ppm. In the H NMR spectra, a semiaminal hy-

Ar

HNR

2

Product^b^,^c

drogen atom is usually detected in the form of a doublet of

doublets or a multiplet in the range of 4.54–4.86 ppm.

Acyclic secondary amines were also introduced in the

reaction. Unfortunately, we were not able to isolate the cor-

responding aminochromanes in the reaction of chromene

Ph (1i)

-O NC

8h, 84%

8i, 59%

8j, 81%

3

2

6

H

4

(1j)

HN

O

(2)

2-thienyl (1k)

1a with such amines as diethylamine, dibenzylamine, diiso-

Ph (1i)

HN

(4а)

10h, 85%

propylamine, and methylcyclohexylamine. We observed

rapid conversion of starting materials into a complex mix-

a

Reaction conditions: 1i–k (1 mmol), and amine (3 mL) under reflux for 30

min.

Diastereomeric ratio were determined by H NMR analysis of the unpuri-

19

ture of unidentified products. Apparently, the presence of

a nitrogen atom in the composition of the cycle is a key re-

quirement for the formation of aminochromanes. Besides,

less nucleophilic 1H-azoles (imidazole, pyrazole) do not re-

act with trifluoroacetylchromenes.

When using 3-trifluoroacetyl-4H-chromenes 1e–h in

the reaction with cyclic secondary amines, a number of

chroman-2-amines was produced under similar conditions

b

1

fied material.

c

Isolated yields.

The reaction between 3-phenyl-substituted 2-trifluoro-

acetyl-1H-benzo[f]chromene 1l and an excess of morpho-

line under reflux leads to the expected N,O-acetal 8k

(Scheme 1).

(Table 2).

COCF3

Table 2 _S_y_n_t_h_e_s_i_z_e_d_C_h_r_o_m_a_n_-₂_-_a_m_i_n_e_sa

morpholine (2, excess), Δ, 2 h

Mor = morpholino

Mor

Ph

O

1l

Ph

O

_R1

_R2

_R1

_R2

8k (81%)

COCF3

MeOH, rt, 1 h

– R2NCOCF3

HNR2

(2.0 equiv)

+

Scheme 1 Reaction of chromene 1l and morpholine

O

NR2

R³

A mechanistic rationale portraying the probable se-

quence of events is given in Scheme 2. We suppose that the

mechanism includes the conjugate addition of a secondary

amine to trifluoroacetylchromene 1 to form chroman A,

which may be in equilibrium with enaminoketone B. Next,

a second molecule of amine is attached at the carbonyl car-

bon atom to give intermediate C, which undergoes decom-

position into enamine D and N,N-disubstituted trifluoroac-

etamide. Since the O-atom in chromane C is a better (phe-

nolic) leaving group than the N-atom, the formation of

chromene E is not observed. The mechanism of cyclization

of enamine D into aminochromane, probably, includes its

isomerization into phenoxyimmonium zwitterion F, which

collapses via 6-exo-trig cyclization to give semicyclic N,O-

acetals 8–13. The initiator protons are generated in the me-

dium of methanol by the dissociation of the phenol. It

should be noted that very few examples of inter- and intra-

molecular addition of phenols to enamines are described in

the literature.²⁰

1

2

3

Product^b

R , R , R

HNR

2

Cl, H, H (1e)

8e, 70%

8f, 73%

Me, Me, H (1f)

Me, H, Ad (1g)

Br, H, Br (1h)

HN

O

(2)

8g, 82%

11u, 87%

11v, 77%

Y = cinnamyl (5c)

Y = 4-FC (5u)

HN

NY

Me, Me, H (1f)

6 4

H

a

Reaction conditions: 1e–h (1 mmol) and amine (2 mmol) in MeOH (3 mL)

at rt for 1 h.

b

Isolated yields.

This reaction was also extended to 1,3-disubstituted 2-

trifluoroacetyl-1H-benzo[f]chromenes. The corresponding

aminochromanes 8h–j and 10h were obtained in good

yields when carrying out the reaction in an excess of sec-

ondary amine without any additional solvent under reflux

Table 3). In spite of the presence of two asymmetric cen-

ters, only trans-isomers of 8h–j and 10h were isolated from

(

the reaction mixture in crystalline form. This is, probably,

©

D

Synthesis

V. A. Osyanin et al.

Paper

COCF3

1-Aryl-

and

1-hetaryl-substituted

1H-ben-

zo[f]chromene-2-carbaldehydes also react with cyclic sec-

ondary amines but under more severe conditions. For ex-

ample, the yield of 8j after boiling for 25 hours in methanol

even with excess of morpholine (5.0 equiv) was 41%, and

the yield of 8l after 40 hours was 48%. Higher yields of 1,3-

disubstituted 3-aminobenzochromanes were achieved by

prolonged heating of aldehydes 1n–p in an excess of sec-

ondary amine without any additional solvent under reflux.

The relative trans configurations of the C-1 and C-3 sub-

stituents of compounds 8h–j,l,m and 10h,i were assigned

O

8–13

NR2

1

HNR2

aza-Michael

COCF3

OH NR2

O

NR2

O

NR2

B

A

F

HNR2

,2-AdN

1

~H

1

on the basis of H NMR spectra. They were deduced from

H

O

the chemical shift values and coupling constants of the pro-

tons attached to C-1 and C-3 of the dihydropyran ring that

exists in a half-chair conformation. The protons attached to

C-1 give rise to a doublet of doublets with two small cou-

CF3

NR2

E2

–

R2NCOCF3

OH NR2

O

E

C

D

not formed

3

pling constants J = 1.8 and 5.3–5.4 Hz at  = 4.73–5.03.

Scheme 2 Proposed mechanism

Thus, H-1 is pseudo-equatorial and the aryl moiety occupies

the pseudo-axial position. The proton H-3 resonates at  =

4.51–4.80 as a doublet of doublets with two coupling con-

Attempts to extend the reaction of trifluoroacetyl-

chromenes 1 with cyclic secondary amines to 3-aroyl-4H-

chromenes, however, failed to furnish the expected N,O-ac-

etals. Nevertheless, it turned out that the presence of formyl

group in the -position to the O-atom of the pyran ring is

sufficient for the reaction to proceed. For example, chro-

mane 8a was obtained in 70% yield from 1H-ben-

zo[f]chromene-2-carbaldehyde 1m and morpholine (2.0

equiv) (Scheme 3) but the reaction was completed in 2 days

at room temperature, although usually no more than 1 hour

was required in the case of trifluoroacetyl derivatives. This

fact can be explained by a lower electrophilicity of alde-

hydes. It is interesting to note that when using only 1.0

equivalent of a cyclic secondary amine in the reaction with

aldehyde 1m, enaminals 14a,b were isolated as individual

E-isomers. The preparation of enaminals supports the

mechanism presented in Scheme 1. It should be noted that

attempts to prepare enaminoketones B (Scheme 2) from 3-

trifluoroacetylchromenes and 1.0 equivalent of a secondary

amine did not succeed, only half of starting chromene got

converted into aminochroman, while the other half re-

mained unchanged.

3

stants J = 1.8 and 11.0–11.4 Hz. Thus, H-3 is in the pseudo-

axial position and the amine moiety occupies the pseudo-

equatorial position.²¹In the NOESY spectra of 10i and 8m,

there are cross peaks corresponding to the interaction be-

tween the H-1 proton and the H -2 and H -2 protons (see

ax

eq

the Supporting Information). The proton H-3 has a cross

peak only with H -2. As shown in Figure 2, in the cis-iso-

eq

mers H-1 and H-3 protons must be spatially close in the I

conformer (showing an appreciable NOE), whereas in the

trans-isomers a weak or non-existent NOE effect is to be ex-

pected.

The reaction between of homopiperazine and 2-formyl-

1H-benzo[f]chromenes 1p–r proceeds in an unusual way

and leads to benzo[f]chroman-3-ol derivatives 15a–c con-

taining 1,5-diazabicyclo[3.2.1]octane core (Scheme 4). This

cascade reaction is a rare example of synthesis of 1,5-diaz-

abicyclo[3.2.1]octane core via double aza-Michael addi-

tion²²and includes the following main steps: aza-Michael

addition of homopiperazine to chromenes, opening of the

dihydropyran ring in the intermediate K with formation of

the enaminone L, repeated aza-Michael addition and he-

X

N

2

(2.0 equiv)

2 or 5g (1.0 equiv)

MeOH, Δ, 30 min

CHO

MeOH, Δ, 30 min

–

MorCHO

O

Mor

O

CHO

OH

8

a (70%)

1m

1

4a (X = O, 74%)

4b (X = NBoc, 81%)

R

O

CHO 2 or 5a (excess)

Δ, 10 h

8j (R = 2-thienyl, X = O, 57%)

l (R = pyridin-3-yl, X = O, 60%)

m (R = 4-MeOC6H4, X = O, 52%)

8

O

N

–

X

NCHO

10i (R = 2-thienyl, X = NMe, 53%)

R = 2-thienyl (1n)

X

R = pyridin-3-yl (1o)

R = 4-MeOC6H4 (1p)

trans/cis >9:1

Scheme 3 Reactions of 1H-benzo[f]chromene-2-carbaldehyde with cyclic secondary amines

©

E

Synthesis

V. A. Osyanin et al.

Paper

NR2

Hax

3

Ar

1

2

H

O

cis

Heq

4

Ar

O

4

H

1

H

Heq

Hax

R2N

2

3

S

G

H

Hax

Heq

H

NR2

3

Hax

H

1

2

O

H

O

trans

H_e_q

H

Mor

4_O

R2N

4

Ar

1

8j

Heq

Hax

2

Ar

3

H

I

J

(

preferred conformation)

1

Figure 2 Possible conformations of cis- and trans-isomers of 8h–j,l,m and 10h,i and selected NOESY H– H correlations of compound 8j

miketalization. In the additional experiment for the reac-

tion of chromene 1q and homopiperazine in deuterated

methanol as a reaction media in the presence of deuterium

oxide (10:1 CD OD/D O), a product 15b-d containing deu-

terium atom at the -position of the pyran ring and OD-

group instead of hydroxyl was obtained. This fact confirms

the formation of the intermediate L, which is further deu-

terated by a solvent as a result of the aza-Michael reaction.

At the same time, the experimental data do not completely

exclude another mechanism in which homopiperazine con-

denses on the exocyclic formyl carbon to form the aminal

without ring-opening, while subsequent enol hydration

leads to the products 15.

the basis of a new method of synthesis of 2-chromanols

widely used in organic synthesis.²³The usefulness of this

approach was demonstrated on the example of the synthe-

sis of hybrid heterocycle 18 containing benzochromane and

indole fragments.²⁴The reaction of compound 8a with ani-

line and 1,2,3,4-tetrahydroquinoline hydrochlorides pro-

ceeds with the substitution of morpholine moiety and for-

mation of aminochromanes 19a,b. It should be noted that

the attempt to the direct synthesis of 19a from trifluoro-

acetylchromene 1a and aniline leads to ring-opening prod-

uct 20.

3

2

LiAlH4

H2O, AcOH

THF, rt, 2 h

Δ, 30 min

Ar

homopiperazine

1.0 equiv)

MeOH, Δ, 30 min

Ar

H

OH Mor

6 (83%)

O

Mor

O

OH

(

CHO

N

8a

1

17 (81%)

Ar = 4-MeOC6H4 (1p)

Ar = 3-O2NC6H4 (1q)

Ar = Ph (1r)

PhNH ·HCl (1.0 equiv)

MeOH, Δ, 10 min

indole (1.0 equiv)

BF ·OEt

CH Cl , rt, 6 h

2 2

O

2

NH

3

2

1

p–r

K

Ar

H ·HCl

N

Ar

CHO

N

MeOH

Δ, 10 min

N

O

NHPh

O

OH

CHO

19a (85%)

OH

(

1.0 equiv)

18 (31%)

NH

L

PhNH2

Ar

O

N

HNPh

Ar

O

N

PhNH2

1.0 equiv)

N

COCF3

(

N

D

OD

O

9b (89%)

N

COCF3

OH

MeOH, Δ, 10 min

O

OH

20 (83%)

1

5a (4-MeOC6H4, 64%)

5b (3-O2NC6H4, 73%)

1

1a

15b-d2

5c (Ph, 69%, CCDC1838635) from CD3OD−D2O (10:1), Δ, 50 min

Scheme 5 Synthetic transformations of 4-(2,3-dihydro-1H-ben-

zo[f]chromen-3-yl)morpholine 8a

Scheme 4 Synthesis of benzochromanols 15 and plausible mechanism

The synthetic applicability of aminochromanes as valu-

able precursors for further transformations was studied.

The chromane-type N,O-acetals can be transformed in a

number of different ways (Scheme 5). For instance, treat-

In conclusion, we have offered an alternative approach

to 2-substituted chromanes, a class of privileged structures

with a broad range of interesting biological activities. The

developed transformation proceeds through subsequent

Michael and 1,2-nucleophilic additions of amine to 4H-

chromene, bimolecular elimination of trifluoroacetamide

or formamide and very rare intramolecular addition of phe-

nol to enamine as the key step of this cascade reaction. The

advantages of our method include 1) the use of readily pre-

pared starting materials, 2) simple operation and workup

ment of compound 8a with LiAlH in THF resulted in C–O

4

bond cleavage and the formation of 1-(3-morpholinopro-

pyl)naphthalen-2-ol 16 in 83% yield. In aqueous acetic acid,

the morpholinyl product 8a was hydrolyzed to a ben-

zochromanol 17. The proposed sequence of transforma-

tions starting from trifluoroacetylchromenes can become

©

F

Synthesis

V. A. Osyanin et al.

Paper

1

3

1

procedures, 3) generally good yields, and 4) scalability and

good functional group tolerance due to in general mild re-

action conditions.

C NMR (CDCl , 100 MHz):  = 21.6 (CH ), 109.9 (СН), 116.4 (q, J

=

3

2

C,F

2

1

91.4 Hz, CF ), 118.3 (С), 120.9 (СН), 128.5 (С), 129.4 (СН), 130.8 (С),

47.5 (С), 156.4 (q, J = 4.8 Hz, CH), 178.9 (q, J = 36.4 Hz, C).

3

2

C,F

19

F NMR (CDCl , 376 MHz):  = –70.4 (3 F, CF ).

3

HRMS (EI): m/z [M + H]⁺calcd for C₁₁H₇³⁵ClF O : 263.0087; found:

3

2

63.0075.

Melting points were determined by capillary method on a SRS Opti-

Melt MPA100 apparatus and are uncorrected. FTIR-spectra were tak-

en on a Shimadzu IR Affinity-1 spectrophotometer with single-reflec-

. H, F, and C NMR

spectra (including DEPT-135, HMBC, HMQC, and NOESY experiments)

were recorded on a JEOL JNM-ECX 400 spectrometer (400, 376, and

1-[(Dimethylamino)(pyridin-3-yl)methyl]naphthalen-2-ol (21)

tion ATR accessory and are reported in cm^–¹

1

19

13

Dimethylamine (11 mL of a 33% aq solution, 0.073 mol) and nicotinal-

dehyde (7.73 g, 0.069 mol) were added to a solution of naphthalen-2-

ol (10 g, 0.069 mol) in MeOH (35 mL) at rt. The solvent was distilled

off, the residue was dissolved in MeOH by heating, and the solution

was kept for 2 days at rt and then 1 day at –30 °C. The precipitate was

collected by filtration, washed with ice-cold MeOH, and purified by

recrystallization from cyclohexane; yield: 11.8 g (61%); colorless sol-

id; mp 117–118 °C.

1⁰⁰^M^H^z^,^r^e^s^p^e^c^tⁱ^v^e^l^y⁾ⁱⁿ^D^M^S^O^-^d6 ^o^r^C^D^C^l3 solutions at ambient

temperature, unless otherwise noted, relative to residual solvent sig-

1

13

1

nal [CHCl  = 7.26 ( H), CDCl  = 77.0 ( C); DMSO-d  = 2.50 ( H), 

=

3

6

1

19

39.5 (^C⁾^]^o^f^C^F^C^l3 ( F) as internal standard. Chemical shifts and

coupling constants were recorded in units of parts per million and

hertz (Hz), respectively. Mass spectra were recorded on a Finnigan

Trace DSQ chromato mass spectrometer (EI, 70 eV, mass-selective de-

tector). Elemental analyses were carried out on a Euro Vector EA-

IR (ATR): 3200–2400, 1622, 1599, 1578, 1522, 1474, 1460, 1427,

1

7

1

329, 1269, 1242, 1179, 1142, 1032, 997, 953, 943, 833, 816, 806,

45, 714 cm

–1

.

3000 automatic CHNS analyzer. High-resolution mass spectra (HRMS)

H NMR (DMSO-d , 400 MHz):  = 2.26 (s, 6 H), 5.27 (s, 2 H), 7.08 (d,

were recorded on an Agilent 6230 TOF using an electrospray (ESI) ion-

ization source. The reaction progress was monitored by TLC on alumi-

num foil-backed silica gel plates (Merck, Kiesgel 60 F254), visualiza-

tion under UV light and in I₂vapor, eluent CH Cl . Organic solutions

6

J = 8.9 Hz, 1 H), 7.19−7.23 (m, 1 H), 7.27 (dd, J = 7.8, 4.8 Hz, 1 H),

7.36−7.40 (m, 1 H), 7.68−7.73 (m, 2 H), 7.93 (d, J = 8.0 Hz, 1 H), 8.03 (d,

J = 8.7 Hz, 1 H), 8.39 (d, J = 4.8 Hz, 1 H), 8.84 (s, 1 H), 13.43 (br s, 1 H).

13C NMR (DMSO-d , 100 MHz):  = 44.0 (2 × CH ), 68.7 (CH), 116.5 (C),

120.1 (CH), 121.7 (CH), 123.1 (CH), 124.5 (CH), 127.2 (CH), 128.6 (C),

129.2 (CH), 130.1 (CH), 132.1 (C), 136.0 (CH), 137.0 (C), 149.7 (CH),

150.1 (CH), 155.5 (C).

2

were concentrated under reduced pressure on a rotary evaporator. All

commercial solvents and reagents were used without additional puri-

fication. The reported trifluoroacetylchromenes and 1H-ben-

zo[f]chromene-2-carbaldehydes were prepared according to litera-

ture procedures or Scheme 6.¹⁷^,²⁵

6

3

HRMS (EI): m/z [M + H]⁺calcd for C₁₈H₁₉N O: 279.1497; found:

2

79.1490.

Cl

+

Cl

COCF3

NMe3I

AcOH, Δ, 5 h

Mor

+

COCF3

OH

O

1-(Pyridin-3-yl)-1H-benzo[f]chromene-2-carbaldehyde (1o)

1

e (68%)

A solution of 21 (417 mg, 1.5 mmol) and 3-(diethylamino)acrolein

(190 mg, 1.5 mmol) in AcOH (5 mL) was heated under reflux for 30

N

min. The solvent was distilled off and the residue was purified by re-

crystallization from EtOH; yield: 271 mg (63%); colorless solid; mp

202–203 °С.

AcOH, Δ, 30 min

CHO

NMe2

2

Et N

+

CHO

OH

O

IR (ATR): 2854, 2754, 1665, 1647, 1616, 1589, 1576, 1510, 1477, 1462,

21

1o (63%)

1

8

1

422, 1383, 1300, 1260, 1229, 1213, 1198, 1061, 1026, 989, 957, 895,

–1

37, 808, 779, 750, 714, 704, 681 cm

.

COCF3

Ph

H NMR (CDCl , 400 MHz):  = 5.67 (s, 1 H), 7.11 (dd, J = 7.8, 4.8 Hz, 1

3

NMe2

Mor

AcOH, Δ, 1 h

COCF3

H), 7.35 (d, J = 9.0 Hz, 1 H), 7.37–7.46 (m, 2 H), 7.55 (s, 1 H), 7.60 (dt,

J = 7.8, 1.8 Hz, 1 H), 7.77–7.82 (m, 3 H), 8.34 (dd, J = 4.8, 1.6 Hz, 1 H),

+

OH

Ph

O

1

l (58%)

8.59 (d, J = 2.1 Hz, 1 H), 9.43 (s, 1 H).

Scheme 6 Synthesis of unknown 4H-chromenes

13

C NMR (CDCl , 100 MHz):  = 32.8 (CH), 115.0 (C), 117.2 (CH), 122.1

3

(

C), 123.4 (CH), 123.5 (CH), 125.5 (CH), 127.6 (CH), 128.8 (CH), 130.0

CH), 131.0 (C), 132.0 (C), 135.9 (CH), 139.4 (C), 148.1 (CH), 148.3 (C),

1-(6-Chloro-4H-chromen-3-yl)-2,2,2-trifluoroethan-1-one (1e)

A solution of 1-(5-chloro-2-hydroxyphenyl)-N,N,N-trimethylmethan-

aminium iodide (4.00 g, 12.2 mmol) and (E)-1,1,1-trifluoro-4-mor-

pholinobut-3-en-2-one (2.55 g, 12.2 mmol) in AcOH (15 mL) was

heated under reflux for 5 h. The reaction mixture was cooled to rt,

and the formed precipitate was collected. The crude product was pu-

rified by recrystallization from MeOH; yield: 2.18 g (68%); colorless

solid; mp 94–95 °С.

150.0 (CH), 157.9 (CH), 189.0 (CH).

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₁₉H₁₄NO : 288.1025; found:

2

288.1015.

2,2,2-Trifluoro-1-(3-phenyl-1H-benzo[f]chromen-2-yl)ethan-1-

one (1l)

A mixture of 1,1,1-trifluoro-4-morpholino-4-phenylbut-3-en-2-one

IR (ATR): 1684, 1630, 1614, 1574, 1508, 1481, 1425, 1412, 1360, 1315,

(

2.00 g, 7 mmol) and 1-[(dimethylamino)methyl]naphthalen-2-ol

1.41 g, 7 mmol) in AcOH (30 mL) was heated under reflux for 1 h. The

1

8

1

259, 1238, 1184, 1175, 1149, 1109, 1084, 933, 912, 903, 870, 856,

–1

29, 754 cm

.

solvent was distilled off, the residue was purified by column chroma-

H NMR (CDCl , 400 MHz):  = 3.57 (s, 2 H), 6.96 (d, J = 8.2 Hz, 1 H),

tography (silica gel, CCl ), and recrystallized from EtOH; yield: 1.44 g

3

4

7.14–7.18 (m, 2 H), 7.80 (s, 1 H).

(58%); colorless solid; mp 105–106 °C.

©

G

Synthesis

V. A. Osyanin et al.

Paper

1

IR (ATR): 1703, 1583, 1568, 1526, 1468, 1402, 1234, 1196, 1177, 1148,

H NMR (CDCl , 400 MHz):  = 2.14–2.25 (m, 2 H), 2.78–2.83 (m, 2 H),

3

1

121, 1074, 1011, 930, 879, 862, 773, 762, 741, 710, 694, 625 cm^–¹

.

3.01–3.10 (m, 3 H), 3.14–3.19 (m, 1 H), 3.72–3.81 (m, 4 H), 4.65 (dd,

1

J = 8.7, 3.4 Hz, 1 H), 7.05 (d, J = 8.9 Hz, 1 H), 7.50–7.53 (m, 2 H), 7.62

H NMR (DMSO-d , 400 MHz):  = 4.09 (s, 2 H), 7.33 (d, J = 8.7 Hz, 1

6

(d, J = 8.9 Hz, 1 H), 7.88 (d, J = 2.1 Hz, 1 H).

H), 7.47−7.59 (m, 6 H), 7.61–7.66 (m, 1 H), 7.85 (d, J = 8.5 Hz, 1 H),

7

13

.88 (d, J = 9.1 Hz, 1 H), 7.95 (d, J = 8.0 Hz, 1 H).

C NMR (CDCl , 100 MHz):  = 22.6 (CH ), 24.9 (CH ), 47.8 (2 × CH ),

3

2

1

3

67.3 (2 × CH ), 92.1 (CH), 113.6 (C), 116.9 (C), 120.4 (CH), 123.8 (CH),

127.0 (CH), 129.6 (CH), 130.1 (C), 130.4 (CH), 131.5 (C), 153.0 (C).

2

C NMR (CDCl , 100 MHz):  = 23.1 (CH ), 105.3 (C), 111.9 (C), 116.8

3

2

1

(q, J = 290.8 Hz, C), 117.0 (CH), 122.7 (CH), 125.4 (CH), 127.4 (CH),

C,F

1

28.6 (CH), 128.7 (2 × CH), 129.0 (CH), 129.1 (2 × CH), 131.1 (CH),

31.2 (C), 131.3 (C), 134.0 (C), 147.3 (C), 163.3 (C) 183.7 (q, J = 35.3

HRMS (EI): m/z [M + H]⁺calcd for C₁₇H₁₉⁷⁹BrNO : 348.0599; found:

2

348.0603.

C,F

Hz, C=O).

HRMS (EI): m/z [M + H]⁺calcd for C₂₁H₁₄F O : 355.0946; found:

4-[8-(tert-Butyl)-2,3-dihydro-1H-benzo[f]chromen-3-yl]morpho-

3

2

355.0952.

line (8c)

Yield: 283 mg (87%); colorless solid; mp 177–178 °C (EtOH).

4

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)morpholine (8a)

IR (ATR): 2961, 1597, 1474, 1462, 1450, 1416, 1393, 1373, 1360, 1263,

To

a

suspension of 1-(1H-benzo[f]chromen-2-yl)-2,2,2-trifluo-

1234, 1196, 1169, 1113, 1069, 1020, 966, 920, 887, 843, 820, 808 cm^–¹

.

roethan-1-one (1a; 278 mg, 1 mmol) in a solvent (MeCN, THF, EtOAc,

benzene, or MeOH; 4 mL) was added morpholine (0.172 mL, 174 mg,

1

H NMR (CDCl , 400 MHz):  = 1.40 (s, 9 H), 2.12–2.26 (m, 2 H), 2.78–

.84 (m, 2 H), 3.02–3.11 (m, 3 H), 3.18–3.24 (m, 1 H), 3.71–3.81 (m, 4

3

2

mmol) at rt. The resulting mixture was kept at rt for 1 h and then

H), 4.64 (dd, J = 8.8, 3.1 Hz, 1 H), 7.02 (d, J = 9.0 Hz, 1 H), 7.55–7.60 (m,

2

evaporated to dryness in vacuo. The residue was recrystallized from

MeOH (3 mL); yield: 156 mg (58%) in MeCN; 175 mg (65%) in THF;

H), 7.68 (d, J = 1.4 Hz, 1 H), 7.72 (d, J = 8.7 Hz, 1 H).

13

C NMR (CDCl , 100 MHz):  = 22.6 (CH ), 25.1 (CH ), 31.4 (3 × CH ),

3

2

3

180 mg (67%) in EtOAc; 202 mg (75%) in benzene; 213 mg (79%) in

3

4.6 (C), 47.9 (2 × CH ), 67.4 (2 × CH ), 91.9 (CH), 113.1 (C), 119.0

2

MeOH; colorless solid; mp 151–152 °С (MeOH).

(

CH), 121.8 (CH), 123.6 (CH), 125.2 (CH), 127.9 (CH), 128.8 (C), 130.9

C), 145.8 (C), 152.2 (C).

IR (ATR): 2957, 2911, 2889, 2849, 1618, 1595, 1512, 1468, 1435, 1406,

1

391, 1377, 1296, 1265, 1240, 1207, 1186, 1159, 1115, 1066, 1037,

HRMS (EI): m/z [M + H]⁺calcd for C21

3

H28NO : 326.2120; found:

–1

2

022, 970, 920, 887, 841, 814, 802, 772, 754 cm

.

26.2115.

H NMR (CDCl , 400 MHz):  = 2.14–2.25 (m, 2 H), 2.80–2.84 (m, 2 H),

3

.05–3.13 (m, 3 H), 3.19–3.25 (m, 1 H), 3.73–3.82 (m, 4 H), 4.65 (dd,

4

-[8-(Adamantan-1-yl)-2,3-dihydro-1H-benzo[f]chromen-3-

J = 8.9, 3.2 Hz, 1 H), 7.06 (d, J = 8.9 Hz, 1 H), 7.34 (t, J = 8.0 Hz, 1 H),

yl]morpholine (8d)

7.48 (t, J = 8.0 Hz, 1 H), 7.62 (d, J = 8.9 Hz, 1 H), 7.74–7.79 (m, 2 H).

The synthesis was carried out in MeOH (15 mL); yield: 376 mg (93%);

colorless solid; mp 229–230 °С (DMF–MeOH).

13

C NMR (CDCl , 100 MHz):  = 22.6 (CH ), 25.0 (CH ), 47.9 (2 × CH ),

3

2

67.3 (2 × CH ), 92.0 (CH), 113.4 (C), 119.2 (CH), 122.0 (CH), 123.3 (CH),

2

IR (ATR): 2847, 1682, 1626, 1597, 1504, 1477, 1450, 1391, 1298, 1269,

126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9 (C), 132.9 (C), 152.7 (C).

1

240, 1192, 1169, 1117, 1069, 1024, 972, 918, 887, 847, 822, 800 cm^–¹

.

HRMS (EI): m/z [M + H]⁺calcd for C₁₇H₂₀NO : 270.1494; found:

2

1

H NMR (CDCl , 400 MHz):  = 1.76–1.85 (m, 6 H), 1.99–2.01 (m, 6 H),

270.1499.

3

2.12–2.24 (m, 5 H), 2.78–2.84 (m, 2 H), 3.03–3.11 (m, 3 H), 3.17–3.24

N-Trifluoroacetylmorpholine described in the literature was also iso-

lated from the mother liquor by column chromatography as a color-

less liquid.

(m, 1 H), 3.72–3.81 (m, 4 H), 4.63 (dd, J = 9.0, 3.2 Hz, 1 H), 7.01 (d, J =

8.9 Hz, 1 H), 7.55–7.60 (m, 2 H), 7.63 (d, J = 1.8 Hz, 1 H), 7.73 (d, J = 8.9

Hz, 1 H).

13

1

H NMR (CDCl , 400 MHz):  = 3.65–3.76 (m, 8 H).

3

C NMR (CDCl , 100 MHz):  = 22.5 (CH ), 25.1 (CH ), 29.1 (3 × CH),

3

2

13

C NMR (CDCl , 100 MHz):  = 43.6 (CH ), 46.4 (CH ), 66.6 (2 × CH ),

36.1 (C), 37.0 (3 × CH ), 43.3 (3 × CH ), 47.9 (2 × CH ), 67.3 (2 × CH ),

3

2

2 2 2 2

1

2

116.7 (q, J = 297.7 Hz, C), 155.8 (q, J = 35.3 Hz, C).

91.9 (CH), 113.1 (C), 118.9 (CH), 121.7 (CH), 123.6 (CH), 124.5 (CH),

28.0 (CH), 129.0 (C), 131.1 (C), 146.1 (C), 152.2 (C).

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₇H₃₄NO : 404.2590; found:

C,F

1

2

,3-Dihydro-1H-benzo[f]chromen-3-amines and Chroman-2-

2

amines; General Procedure

404.2598.

To a suspension of 3-trifluoroacetyl-4H-chromene or 2-trifluoroace-

tyl-1H-benzo[f]chromene (1 mmol) in MeOH (4 mL) was added cyclic

secondary amine (2 mmol) at rt. The resulting mixture was heated

under reflux for 1–2 min until the trifluoroacetylchromene was com-

pletely dissolved (in case of poor solubility) and then kept at rt for 1 h

and at –30 °C for 30 min. The precipitate formed was collected by fil-

tration, washed with ice-cold MeOH (1 mL), and purified by recrystal-

lization, if necessary.

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)pyrrolidine (9a)

Yield: 225 mg (89%); colorless solid; mp 86–87 °С (MeOH).

IR (ATR): 1620, 1595, 1514, 1468, 1435, 1404, 1389, 1260, 1231, 1215,

1177, 1155, 1146, 1126, 1059, 1033, 1024, 961, 843, 818, 770, 743

–1

cm

1

.

H NMR (CDCl , 400 MHz):  = 1.82–1.90 (m, 4 H), 2.10–2.20 (m, 1 H),

3

2

.25–2.31 (m, 1 H), 2.93–2.99 (m, 2 H), 3.04–3.12 (m, 3 H), 3.20 (ddd,

J = 16.5, 6.1, 2.6 Hz, 1 H), 4.89 (dd, J = 10.1, 1.8 Hz, 1 H), 7.04 (d, J = 8.7

Hz, 1 H), 7.32 (ddd, J = 8.0, 6.9, 1.1 Hz, 1 H), 7.47 (ddd, J = 8.5, 6.9, 1.4

Hz, 1 H), 7.61 (d, J = 9.0 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.77 (d, J = 8.5

Hz, 1 H).

4-(8-Bromo-2,3-dihydro-1H-benzo[f]chromen-3-yl)morpholine

(8b)

Yield: 289 mg (83%); colorless solid; mp 207–208 °С (DMF–MeOH).

IR (ATR): 2855, 1614, 1585, 1495, 1462, 1445, 1389, 1310, 1292, 1263,

1

3

C NMR (CDCl , 100 MHz):  = 22.6 (CH ), 24.5 (2 × CH ), 27.4 (CH ),

3

2

1

236, 1194, 1179, 1159, 1115, 1067, 1038, 1022, 966, 918, 883, 839,

–1

47.2 (2 × CH

1

2

), 89.0 (CH), 113.5 (C), 119.4 (CH), 122.0 (CH), 123.1 (CH),

827, 808, 777 cm

.

26.3 (CH), 127.8 (CH), 128.4 (CH), 128.8 (C), 133.0 (C), 153.0 (C).

©

H

Synthesis

V. A. Osyanin et al.

Paper

HRMS (EI): m/z [M + H]⁺calcd for C₁₇H₂₀NO: 254.1545; found:

4-Benzyl-1-(2,3-dihydro-1H-benzo[f]chromen-3-yl)piperidine

254.1549.

(10c)

Yield: 286 mg (80%); colorless solid; mp 135–137 °C (MeOH).

1

-(8-Bromo-2,3-dihydro-1H-benzo[f]chromen-3-yl)pyrrolidine

IR (ATR): 1624, 1595, 1514, 1495, 1466, 1447, 1410, 1387, 1261, 1232,

(9b)

1

209, 1174, 1153, 1138, 1070, 1039, 1028, 1022, 970, 943, 845, 808,

–1

Yield: 302 mg (91%); colorless solid; mp 149–150 °C (DMF–MeOH).

791, 762, 746, 700 cm .

1

IR (ATR): 2965, 2821, 1611, 1585, 1495, 1462, 1445, 1435, 1412, 1387,

H NMR (CDCl , 400 MHz):  = 1.25–1.41 (m, 2 H), 1.60–1.78 (m, 3 H),

3

1

9

1

356, 1342, 1310, 1258, 1206, 1190, 1173, 1159, 1128, 1063, 1034,

2.13–2.28 (m, 2 H), 2.53–2.62 (m, 3 H), 2.90–3.00 (m, 2 H), 3.03–3.25

(m, 3 H), 4.71 (dd, J = 10.1, 2.0 Hz, 1 H), 7.02 (d, J = 9.0 Hz, 1 H), 7.16–

7.22 (m, 3 H), 7.27–7.34 (m, 3 H), 7.46 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H),

68, 961, 883, 808 cm^–

1

.

H NMR (CDCl , 400 MHz):  = 1.82–1.90 (m, 4 H), 2.08–2.18 (m, 1 H),

3

7.60 (d, J = 9.0 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.76 (d, J = 8.5 Hz, 1 H).

2.23–2.29 (m, 1 H), 2.92–2.98 (m, 2 H), 3.00–3.16 (m, 4 H), 4.88 (dd,

13

J = 10.1, 1.8 Hz, 1 H), 7.04 (d, J = 8.9 Hz, 1 H), 7.48–7.52 (m, 2 H), 7.61

C NMR (CDCl , 100 MHz):  = 23.0 (CH ), 25.5 (CH ), 32.5 (CH ), 32.7

3

2

(d, J = 8.9 Hz, 1 H), 7.87 (d, J = 1.8 Hz, 1 H).

(CH ), 38.2 (CH ), 43.4 (CH ), 44.9 (CH ), 50.9 (CH ), 92.7 (CH), 113.4

2 3 2 2 2

1

3

(С), 119.3 (СH), 122.0 (CH), 123.1 (CH), 125.9 (CH), 126.4 (CH), 127.8

CH), 128.3 (2 × CH), 128.5 (CH), 128.8 (C), 129.3 (2 × CH), 133.0 (C),

40.8 (C), 153.1 (C).

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C25^H28NO: 358.2171; found:

C NMR (CDCl , 100 MHz):  = 22.5 (CH ), 24.5 (2 × CH ), 27.2 (CH ),

3

2

(

1

4

1

7.1 (2 × CH ), 89.1 (CH), 113.7 (C), 116.7 (C), 120.5 (CH), 123.9 (CH),

26.9 (CH), 129.4 (CH), 130.0 (C), 130.3 (CH), 131.6 (C), 153.4 (C).

2

HRMS (EI): m/z [M + H]⁺calcd for C₁₇H₁₉⁷⁹BrNO: 332.0650; found:

3

358.2168.

32.0646.

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-phenylpiperidine

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperidine (10a)

(10d)

Yield: 211 mg (79%); colorless solid; mp 113–114 °C (MeOH).

Yield: 278 mg (81%); colorless solid; mp 170–172 °C (MeOH).

IR (ATR): 2936, 2824, 1622, 1599, 1514, 1466, 1410, 1381, 1350, 1306,

IR (ATR): 2936, 2824, 1624, 1597, 1514, 1493, 1410, 1379, 1261, 1232,

1205, 1180, 1151, 1140, 1067, 1036, 1009, 968, 959, 849, 808, 756,

1

8

1

231, 1206, 1196, 1177, 1113, 1076, 1057, 1036, 1013, 970, 959, 910,

51, 804, 739 cm

–1

.

–1

741, 698 cm .

H NMR (CDCl , 400 MHz):  = 1.52–1.72 (m, 6 H), 2.14–2.29 (m, 2 H),

3

1

H NMR (CDCl , 400 MHz):  = 1.73–1.99 (m, 4 H), 2.18–2.33 (m, 2 H),

2

1

7

.74–2.80 (m, 2 H), 3.02–3.12 (m, 3 H), 3.21 (ddd, J = 16.5, 5.5, 2.0 Hz,

H), 4.69 (dd, J = 10.1, 1.8 Hz, 1 H), 7.05 (d, J = 8.9 Hz, 1 H), 7.32 (t, J =

.8 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 1 H), 7.61 (d, J = 8.7 Hz, 1 H), 7.73–7.79

3

2.64 (tt, J = 12.1, 3.7 Hz, 1 H), 2.77 (td, J = 12.1, 1.8 Hz, 1 H), 3.07–3.18

(m, 3 H), 3.23–3.32 (m, 2 H), 4.78 (dd, J = 9.8, 1.6 Hz, 1 H), 7.08 (d, J =

8

1

.7 Hz, 1 H), 7.20–7.35 (m, 6 H), 7.46–7.50 (m, 1 H), 7.63 (d, J = 8.9 Hz,

H), 7.76 (d, J = 8.0 Hz, 1 H), 7.79 (d, J = 8.5 Hz, 1 H).

(m, 2 H).

13

C NMR (CDCl , 100 MHz):  = 23.1 (CH ), 24.8 (CH ), 25.5 (CH ), 26.4

3

2

13

C NMR (CDCl , 100 MHz):  = 23.1 (CH ), 25.6 (CH ), 33.8 (CH ), 33.9

(2 × CH ), 48.6 (2 × CH ), 93.1 (CH), 113.5 (C), 119.3 (CH), 122.0 (CH),

3

2

(CH ), 43.0 (CH), 45.2 (CH ), 51.6 (CH ), 92.7 (CH), 113.5 (C), 119.3

1

23.1 (CH), 126.4 (CH), 127.8 (CH), 128.5 (CH), 128.8 (C), 133.0 (C),

53.2 (C).

2

(

1

(

CH), 122.0 (CH), 123.2 (CH), 126.3 (CH), 126.4 (CH), 127.0 (2 × CH),

27.9 (CH), 128.49 (CH), 128.54 (2 × CH), 128.9 (C), 133.0 (C), 146.5

C), 153.1 (C).

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₂₆NO: 344.2014; found:

HRMS (EI): m/z [M + H]⁺calcd for C₁₈H₂₂NO: 268.1701; found:

268.1698.

344.2018.

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-methylpiperidine

(

10b)

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-phenylpiperidin-4-ol

Yield: 236 mg (84%); colorless solid; mp 99–100 °C (MeOH).

(10e)

IR (ATR): 2947, 2922, 2868, 2830, 1624, 1597, 1514, 1466, 1447, 1408,

Yield: 251 mg (70%); colorless solid; mp 176–177 °C (MeOH).

1

9

1

394, 1379, 1231, 1206, 1190, 1167, 1128, 1117, 1070, 1032, 1020,

82, 968, 953, 849, 802, 739 cm

–

1

IR (ATR): 3300–3100, 2959, 2934, 2885, 1622, 1595, 1514, 1500,

.

1

491, 1464, 1448, 1435, 1402, 1387, 1306, 1261, 1267, 1205, 1176,

151, 1126, 1065, 1043, 1012, 978, 966, 943, 862, 814, 760 cm

H NMR (CDCl , 400 MHz):  = 0.97 (d, J = 6.4 Hz, 3 H), 1.17–1.34 (m, 2

3

–1

.

H), 1.42–1.54 (m, 1 H), 1.69–1.73 (m, 2 H), 2.13–2.29 (m, 2 H), 2.58

H NMR (CDCl , 400 MHz):  = 1.77 (br s, 1 H), 1.84 (d, J = 13.1 Hz, 2

(

td, J = 11.9, 2.5 Hz, 1 H), 2.94–2.98 (m, 2 H), 3.04–3.25 (m, 3 H), 4.71

dd, J = 10.1, 2.1 Hz, 1 H), 7.04 (d, J = 8.9 Hz, 1 H), 7.32 (ddd, J = 8.0, 6.9,

3

H), 2.15–2.34 (m, 4 H), 2.91–2.96 (m, 1 H), 3.06–3.16 (m, 3 H), 3.22–

3

.28 (m, 1 H), 3.46 (td, J = 12.4, 2.5 Hz, 1 H), 4.77 (dd, J = 10.1, 2.1 Hz, 1

H), 7.10 (d, J = 8.7 Hz, 1 H), 7.27–7.41 (m, 4 H), 7.48 (ddd, J = 8.2, 6.9,

.4 Hz, 1 H), 7.54–7.58 (m, 2 H), 7.63 (d, J = 9.0 Hz, 1 H), 7.76 (d, J = 7.8

Hz, 1 H), 7.79 (d, J = 8.5 Hz, 1 H).

1

7

.2 Hz, 1 H), 7.46 (ddd, J = 8.2, 6.9, 1.4 Hz, 1 H), 7.61 (d, J = 8.9 Hz, 1 H),

.74 (d, J = 8.0 Hz, 1 H), 7.77 (d, J = 8.5 Hz, 1 H).

1

3

C NMR (CDCl , 100 MHz):  = 22.2 (CH ), 23.1 (CH ), 25.6 (CH ), 31.2

3

2

(

CH), 34.6 (CH ), 34.9 (CH ), 44.9 (CH ), 51.0 (CH ), 92.8 (CH), 113.5

C), 119.3 (CH), 122.0 (CH), 123.1 (CH), 126.4 (CH), 127.8 (CH), 128.5

CH), 128.8 (C), 133.0 (C), 153.1 (C).

2 2 2 2

13

C NMR (CDCl , 100 MHz):  = 22.9 (CH ), 25.4 (CH ), 38.8 (CH ), 38.9

3

2

(CH ), 41.3 (CH ), 46.5 (CH ), 71.8 (C), 92.5 (CH), 113.4 (C), 119.4 (CH),

2 2 2

122.0 (CH), 123.2 (CH), 124.7 (2 × CH), 126.4 (CH), 127.1 (CH), 127.9

HRMS (EI): m/z [M + H]⁺calcd for C₁₉H₂₄NO: 282.1858; found:

82.1855.

(CH), 128.5 (3 × CH), 128.9 (C), 133.0 (C), 148.5 (C), 153.0 (C).

2

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₂₆NO : 360.1964; found:

2

360.1966.

©

I

Synthesis

V. A. Osyanin et al.

Paper

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperidin-4-ol (10f)

IR (ATR): 3500–2600, 1620, 1595, 1512, 1470, 1408, 1391, 1377,

1

9

1

335, 1294, 1261, 1234, 1182, 1165, 1130, 1065, 1042, 1016, 974,

Yield: 198 mg (70%); colorless solid; mp 180–181 °C (MeOH).

–1

45, 858, 831, 800, 768, 750 cm

.

IR (ATR): 3450–3300, 2943, 2830, 1624, 1599, 1514, 1466, 1406,

H NMR (CDCl , 400 MHz):  = 2.13–2.25 (m, 2 H), 2.60–2.73 (m, 6 H),

1

9

1

368, 1231, 1219, 1206, 1180, 1136, 1096, 1063, 1036, 1020, 988,

3

–1

2.86–2.91 (m, 2 H), 3.03–3.25 (m, 4 H), 3.50 (br s, 1 H), 3.66–3.69 (m,

68, 932, 849, 804, 724 cm

.

2

H), 4.70 (dd, J = 9.2, 3.2 Hz, 1 H), 7.04 (d, J = 8.9 Hz, 1 H), 7.32 (ddd,

J = 8.0, 6.9, 1.1 Hz, 1 H), 7.47 (ddd, J = 8.0, 6.9, 1.4 Hz, 1 H), 7.61 (d, J =

.9 Hz, 1 H), 7.73–7.77 (m, 2 H).

H NMR (CDCl , 400 MHz):  = 1.55–1.68 (m, 2 H), 1.79 (br s, 1 H),

3

1.94–2.02 (m, 2 H), 2.14–2.26 (m, 2 H), 2.63–2.70 (m, 1 H), 2.98–3.01

8

(m, 2 H), 3.04–3.13 (m, 1 H), 3.17–3.26 (m, 2 H), 3.75–3.82 (m, 1 H),

13

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.3 (CH ), 47.1 (br, 2 ×

4.72 (dd, J = 9.6, 2.5 Hz, 1 H), 7.03 (d, J = 8.9 Hz, 1 H), 7.32 (ddd, J = 8.0,

6.9, 0.9 Hz, 1 H), 7.47 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.60 (d, J = 8.9 Hz,

1 H), 7.73–7.78 (m, 2 H).

3

2

CH ), 53.2 (2 × CH ), 57.7 (CH ), 59.5 (CH ), 91.8 (CH), 113.3 (C), 119.2

2

(

CH), 122.0 (CH), 123.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9

C), 132.9 (C), 152.7 (C).

13

C NMR (CDCl , 100 MHz):  = 23.0 (CH ), 25.7 (CH ), 34.8 (CH ), 35.1

3

2

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C19^H25N O : 313.1916; found:

(

CH ), 43.4 (CH ), 47.2 (CH ), 68.5 (CH), 92.3 (CH), 113.4 (C), 119.2

CH), 122.0 (CH), 123.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9

C), 133.0 (C), 153.0 (C).

2

313.1919.

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₁₈H₂₂NO : 284.1651; found:

1-Cinnamyl-4-(2,3-dihydro-1H-benzo[f]chromen-3-yl)piperazine

11c)

2

(

284.1648.

Yield: 319 mg (83%); colorless solid; mp 149–150 °C (EtOH).

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperidin-4-one (10g)

IR (ATR): 1620, 1595, 1514, 1503, 1495, 1468, 1452, 1433, 1410, 1393,

1

375, 1331, 1290, 1263, 1234, 1207, 1167, 1132, 1099, 1070, 1059,

Yield: 200 mg (71%); colorless solid; mp 117–119 °C (MeOH).

–1

026, 1005, 968, 918, 847, 812, 768, 745, 691 cm

.

IR (ATR): 2828, 1730, 1713, 1624, 1599, 1514, 1468, 1408, 1375, 1348,

H NMR (CDCl , 400 MHz):  = 2.14–2.26 (m, 2 H), 2.63 (br s, 4 H),

1

9

1

298, 1233, 1209, 1194, 1177, 1159, 1140, 1070, 1038, 1016, 997,

3

–1

2.88–2.93 (m, 2 H), 3.03–3.20 (m, 4 H), 3.23 (d, J = 5.7 Hz, 2 H), 4.71

74, 945, 860, 853, 806, 737 cm

.

(dd, J = 8.7, 3.2 Hz, 1 H), 6.34 (dt, J = 15.8, 6.9 Hz, 1 H), 6.56 (d, J = 15.8

H NMR (CDCl , 400 MHz):  = 2.21–2.27 (m, 2 H), 2.54 (t, J = 6.2 Hz, 4

3

Hz, 1 H), 7.03 (d, J = 8.9 Hz, 1 H), 7.22–7.27 (m, 1 H), 7.30–7.35 (m, 3

H), 7.39–7.42 (m, 2 H), 7.47 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H), 7.61 (d, J =

9

H), 3.08–3.19 (m, 3 H), 3.26 (dt, J = 16.5, 4.0 Hz, 1 H), 3.32–3.39 (m, 2

H), 4.86 (dd, J = 6.4, 6.0 Hz, 1 H), 7.01 (d, J = 9.0 Hz, 1 H), 7.34 (ddd, J =

.0 Hz, 1 H), 7.74–7.78 (m, 2 H).

8.0, 6.9, 1.2 Hz, 1 H), 7.48 (ddd, J = 8.3, 6.9, 1.4 Hz, 1 H), 7.62 (d, J = 8.7

13

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.2 (CH ), 47.2 (br, 2 ×

Hz, 1 H), 7.75 (d, J = 8.3 Hz, 1 H), 7.78 (d, J = 8.7 Hz, 1 H).

3

2

CH ), 53.5 (2 × CH ), 61.2 (CH ), 91.8 (CH), 113.3 (C), 119.3 (CH), 122.0

13

2

C NMR (CDCl , 100 MHz):  = 22.8 (CH ), 26.0 (CH ), 42.0 (2 × CH ),

3

2

(CH), 123.2 (CH), 126.4 (CH), 126.5 (3 × CH), 127.7 (CH), 127.9 (CH),

4

1

2

7.7 (2 × CH ), 92.1 (CH), 113.3 (C), 119.1 (CH), 122.0 (CH), 123.4 (CH),

26.5 (CH), 128.0 (CH), 128.5 (CH), 129.0 (C), 132.9 (C), 152.6 (C),

09.3 (C).

2

1

28.5 (CH), 128.7 (2 × CH), 128.9 (C), 133.0 (C), 133.4 (CH), 137.0 (C),

52.8 (C).

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C26^H29N O: 385.2280; found:

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₁₈H₂₀NO : 282.1494; found:

2

385.2278.

282.1495.

1

-Benzyl-4-(2,3-dihydro-1H-benzo[f]chromen-3-yl)piperazine

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-methylpiperazine

(11d)

(11a)

Yield: 265 mg (74%); colorless solid; mp 113–115 °C (MeOH).

Yield: 206 mg (73%); colorless solid; mp 138–140 °C (MeOH).

IR (ATR): 1620, 1595, 1514, 1493, 1470, 1454, 1433, 1414, 1391, 1379,

IR (ATR): 1620, 1595, 1514, 1470, 1445, 1433, 1410, 1391, 1373, 1360,

1

333, 1310, 1294, 1260, 1238, 1209, 1186, 1167, 1130, 1078, 1026,

007, 841, 822, 808, 748, 704 cm

1

290, 1260, 1236, 1211, 1200, 1182, 1169, 1144, 1134, 1080, 1063,

032, 1013, 970, 932, 847, 826, 810, 745 cm

–1

.

–1

.

H NMR (CDCl , 400 MHz):  = 2.15–2.22 (m, 2 H), 2.57 (br s, 4 H),

3

H NMR (CDCl , 400 MHz):  = 2.14–2.21 (m, 2 H), 2.36 (s, 3 H), 2.54

3

2

3

8

.84–2.90 (m, 2 H), 3.03–3.25 (m, 4 H), 3.59 (s, 2 H), 4.70 (dd, J = 8.9,

.4 Hz, 1 H), 7.04 (d, J = 9.0 Hz, 1 H), 7.26–7.40 (m, 6 H), 7.47 (ddd, J =

.0, 6.7, 1.4 Hz, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.74–7.78 (m, 2 H).

(br s, 4 H), 2.85–2.90 (m, 2 H), 3.02–3.23 (m, 4 H), 4.69 (dd, J = 8.9, 3.4

Hz, 1 H), 7.02 (d, J = 8.9 Hz, 1 H), 7.32 (ddd, J = 8.0, 6.9, 1.1 Hz, 1 H),

.46 (ddd, J = 8.2, 6.9, 1.4 Hz, 1 H), 7.59 (d, J = 8.9 Hz, 1 H), 7.73–7.77

7

13

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.3 (CH ), 47.3 (2 × CH ),

(m, 2 H).

3

2

53.4 (2 × CH ), 63.2 (CH ), 91.9 (CH), 113.4 (C), 119.3 (CH), 122.0 (CH),

13

2

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.2 (CH ), 46.2 (CH ), 47.3

3

2

3

123.2 (CH), 126.4 (CH), 127.2 (CH), 127.9 (CH), 128.4 (2 × CH), 128.5

(

br, 2 × CH ), 55.4 (2 × CH ), 91.8 (CH), 113.3 (C), 119.3 (CH), 122.0

CH), 123.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9 (C), 132.9

C), 152.8 (C).

2

(CH), 128.9 (C), 129.4 (2 × CH), 133.0 (C), 138.0 (C), 152.9 (C).

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C24^H27N O: 359.2123; found:

2

359.2120.

HRMS (EI): m/z [M + H]⁺calcd for C₁₈H₂₃N O: 283.1810; found:

2

283.1814.

1-[Bis(4-fluorophenyl)methyl]-4-(2,3-dihydro-1H-ben-

zo[f]chromen-3-yl)piperazine (11e)

2

-[4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperazin-1-

Yield: 419 mg (89%); colorless solid; mp 141–143 °C (EtOH).

yl]ethan-1-ol (11b)

IR (ATR): 1624, 1601, 1503, 1468, 1445, 1435, 1412, 1391, 1323, 1294,

After completion of the reaction, the solvent was distilled off, and the

residue was purified by recrystallization from MeOH; yield: 215 mg

1

279, 1219, 1192, 1153, 1136, 1094, 1036, 1024, 1009, 974, 957, 849,

–1

826, 810, 783, 743 cm

.

(69%); colorless solid; mp 148–150 °C (MeOH).

©

J

Synthesis

V. A. Osyanin et al.

Paper

1

H NMR (CDCl , 400 MHz):  = 2.12–2.24 (m, 2 H), 2.40–2.56 (m, 4 H),

H NMR (CDCl , 400 MHz):  = 2.21–2.31 (m, 2 H), 2.96–3.03 (m, 2 H),

3

2

.82–2.90 (m, 2 H), 3.03–3.24 (m, 4 H), 4.27 (s, 1 H), 4.69–4.72 (m, 1

3.07–3.17 (m, 1 H), 3.22–3.32 (m, 7 H), 4.77 (dd, J = 9.2, 3.0 Hz, 1 H),

6.89 (t, J = 7.4 Hz, 1 H), 6.98 (d, J = 8.0 Hz, 2 H), 7.05 (d, J = 8.9 Hz, 1 H),

7.27–7.36 (m, 3 H), 7.46–7.51 (m, 1 H), 7.63 (d, J = 8.9 Hz, 1 H), 7.76

(d, J = 8.0 Hz, 1 H), 7.79 (d, J = 8.5 Hz, 1 H).

H), 6.96–7.02 (m, 4 H), 7.08 (d, J = 8.9 Hz, 1 H), 7.31–7.42 (m, 5 H),

7.47 (ddd, J = 8.2, 7.1, 1.2 Hz, 1 H), 7.63 (d, J = 9.0 Hz, 1 H), 7.74–7.78

(m, 2 H).

1

3

13

C NMR (CDCl , 100 MHz):  = 22.8 (CH ), 25.3 (CH ), 47.5 (2 × CH ),

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.3 (CH ), 47.5 (2 × CH ),

3

2

3

2

5

2.0 (2 × CH ), 74.6 (CH), 91.8 (CH), 113.4 (C), 115.5 (d, J_o_-_C_,_F= 21.0

49.7 (2 × CH ), 91.9 (CH), 113.4 (C), 116.4 (2 × CH), 119.2 (CH), 119.9

2

Hz, 4 × CH), 119.2 (CH), 122.0 (CH), 123.2 (CH), 126.4 (CH), 127.9

(CH), 122.0 (CH), 123.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9

(C), 129.2 (2 × CH), 133.0 (C), 151.6 (C), 152.8 (C).

3

(

1

CH), 128.5 (CH), 128.9 (C), 129.4 (d, J

= 6.7 Hz, 4 × CH), 133.0 (C),

m-C,F

1

38.3 (2 C), 152.8 (C), 161.9 (d, J

= 244.1 Hz, 2 C).

HRMS (EI): m/z [M + H]⁺calcd for C₂₃H₂₅N O: 345.1967; found:

ipso-CF

2

HRMS (EI): m/z [M + H]⁺calcd for C₃₀H₂₉F N O: 471.2248; found:

345.1970.

2

471.2253.

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(o-tolyl)piperazine

Ethyl 4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperazine-1-car-

(11i)

boxylate (11f)

Yield: 287 mg (80%); colorless solid; mp 175–176 °C (MeOH).

Yield: 306 mg (90%); colorless solid; mp 129–130 °C (MeOH).

IR (ATR): 1620, 1595, 1574, 1512, 1463, 1464, 1445, 1408, 1393, 1375,

1306, 1263, 1227, 1206, 1184, 1159, 1140, 1020, 976, 949, 932, 845,

816, 806, 764, 745, 721 cm .

IR (ATR): 1695, 1622, 1601, 1431, 1412, 1389, 1325, 1310, 1248, 1231,

–1

1

8

1

217, 1209, 1198, 1179, 1144, 1121, 1094, 1036, 1020, 997, 974, 953,

54, 806, 768, 745 cm^–

1

.

1

H NMR (CDCl , 400 MHz):  = 2.20–2.33 (m, 2 H), 2.37 (s, 3 H), 2.97–

3

H NMR (CDCl , 400 MHz):  = 1.28 (t, J = 7.1 Hz, 3 H), 2.14–2.27 (m, 2

3.30 (m, 10 H), 4.78 (dd, J = 8.9, 3.0 Hz, 1 H), 7.00 (td, J = 7.5, 1.2 Hz, 1

H), 7.06 (d, J = 7.8 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.17–7.21 (m, 2 H),

7.34 (ddd, J = 8.0, 6.9, 0.9 Hz, 1 H), 7.48 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H),

7.63 (d, J = 8.9 Hz, 1 H), 7.76 (d, J = 7.8 Hz, 1 H), 7.79 (d, J = 8.5 Hz, 1 H).

3

H), 2.75–2.81 (m, 2 H), 3.02–3.14 (m, 3 H), 3.19–3.26 (m, 1 H), 3.50–

3

7

.58 (m, 4 H), 4.16 (q, J = 7.1 Hz, 2 H), 4.70 (dd, J = 9.2, 2.9 Hz, 1 H),

.01 (d, J = 9.0 Hz, 1 H), 7.33 (ddd, J = 8.0, 6.9, 0.9 Hz, 1 H), 7.47 (ddd,

J = 8.5, 6.9, 1.4 Hz, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.73–7.78 (m, 2 H).

13

C NMR (CDCl , 100 MHz):  = 18.0 (CH ), 22.9 (CH ), 25.4 (CH ), 47.9

3

2

13

C NMR (CDCl , 100 MHz):  = 14.8 (CH ), 22.7 (CH ), 25.3 (CH ), 44.0

(br, 2 × СH ), 52.1 (2 × CH ), 92.1 (CH), 113.4 (C), 119.1 (CH), 119.3

3

2

(

br, 2 × СH ), 47.4 (2 × CH ), 61.5 (CH ), 92.1 (CH), 113.3 (C), 119.1

CH), 122.0 (CH), 123.3 (CH), 126.5 (CH), 128.0 (CH), 128.5 (CH), 128.9

C), 132.9 (C), 152.6 (C), 155.6 (C).

(CH), 122.0 (CH), 123.22 (CH), 123.24 (CH), 126.4 (CH), 126.7 (CH),

127.9 (CH), 128.5 (CH), 128.9 (C), 131.2 (CH), 132.8 (C), 133.0 (C),

151.7 (C), 152.9 (C).

2

HRMS (EI): m/z [M + H]⁺calcd for C₂₀H₂₅N O : 341.1865; found:

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₂₇N O: 359.2123; found:

2

3

2

341.1861.

359.2121.

tert-Butyl 4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperazine-1-

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(m-tolyl)piperazine

carboxylate (11g)

(11j)

Yield: 346 mg (94%); colorless solid; mp 122–123 °C (EtOH).

Yield: 294 mg (82%); colorless solid; mp 189–191 °C (MeOH).

IR (ATR): 1690, 1622, 1595, 1418, 1408, 1366, 1281, 1231, 1163, 1123,

IR (ATR): 2955, 2837, 1620, 1599, 1582, 1514, 1493, 1466, 1452, 1433,

1410, 1381, 1354, 1342, 1323, 1307, 1273, 1229, 1207, 1188, 1142,

1096, 1074, 1037, 1024, 993, 974, 953, 853, 835, 810, 772, 745, 689

–1

1020, 1001, 972, 953, 862, 854, 808, 768, 739 cm .

1

H NMR (CDCl , 400 MHz):  = 1.48 (s, 9 H), 2.14–2.27 (m, 2 H), 2.73–

3

–1

cm

.

2.79 (m, 2 H), 3.00–3.13 (m, 3 H), 3.20–3.26 (m, 1 H), 3.45–3.54 (m, 4

1

H), 4.70 (dd, J = 9.2, 3.0 Hz, 1 H), 7.02 (d, J = 8.9 Hz, 1 H), 7.33 (ddd, J =

H NMR (CDCl , 400 MHz):  = 2.22–2.28 (m, 2 H), 2.37 (s, 3 H), 2.97–

3

8

.0, 6.9, 0.9 Hz, 1 H), 7.47 (ddd, J = 8.0, 6.9, 1.4 Hz, 1 H), 7.61 (d, J = 8.9

3.03 (m, 2 H), 3.08–3.16 (m, 1 H), 3.23–3.30 (m, 7 H), 4.77 (dd, J = 8.9,

3.4 Hz, 1 H), 6.73 (d, J = 7.6 Hz, 1 H), 6.79–6.82 (m, 2 H), 7.08 (d, J = 8.7

Hz, 1 H), 7.20 (t, J = 7.8 Hz, 1 H), 7.36 (ddd, J = 8.0, 6.8, J = 0.9 Hz, 1 H),

Hz, 1 H), 7.73–7.78 (m, 2 H).

13

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.3 (CH ), 28.6 (3 × CH ),

3

2

3

7.50 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H), 7.64 (d, J = 8.9 Hz, 1 H), 7.77–7.82

43.1 (br, CH ), 44.2 (br, CH ), 47.5 (2 × CH ), 79.8 (C), 92.1 (CH), 113.3

2 2 2

(m, 2 H).

(

C), 119.2 (CH), 122.0 (CH), 123.3 (CH), 126.4 (CH), 127.9 (CH), 128.5

CH), 128.9 (C), 132.9 (C), 152.7 (C), 154.8 (C).

13

C NMR (CDCl , 100 MHz):  = 21.9 (CH ), 22.8 (CH ), 25.3 (CH ), 47.5

3

2

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₂H₂₉N O : 369.2178; found:

(2 × CH

2

), 49.8 (2 × CH ), 91.9 (CH), 113.4 (C), 113.5 (CH), 117.2 (CH),

2

3

119.3 (CH), 120.8 (CH), 122.0 (CH), 123.3 (CH), 126.5 (CH), 128.0 (CH),

28.5 (CH), 129.0 (C), 129.1 (CH), 133.0 (C), 138.9 (C), 151.6 (C), 152.8

369.2181.

1

(C).

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-phenylpiperazine

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C24^H27N O: 359.2123; found:

(

11h)

2

359.2125.

Yield: 258 mg (75%); colorless solid; mp 212–213 °C (MeOH).

IR (ATR): 2882, 2833, 1620, 1593, 1503, 1466, 1449, 1408, 1387, 1323,

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(p-tolyl)piperazine

1

313, 1279, 1263, 1230, 1209, 1190, 1146, 1072, 1038, 1020, 959,

(11k)

–1

922, 845, 812, 748, 685 cm

.

Yield: 337 mg (94%); colorless solid; mp 233–235 °C (EtOH–DMF).

IR (ATR): 2824, 1620, 1595, 1562, 1514, 1466, 1450, 1435, 1414, 1383,

–1

1

319, 1269, 1207, 1198, 1188, 1018, 924, 843, 810, 746 cm .

©

K

Synthesis

V. A. Osyanin et al.

Paper

1

13

H NMR (CDCl , 400 MHz):  = 2.20–2.31 (m, 5 H), 2.94–3.02 (m, 2 H),

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.3 (CH ), 47.3 (2 × CH ),

3

2

3.07–3.28 (m, 8 H), 4.76 (dd, J = 9.0, 2.9 Hz, 1 H), 6.89 (d, J = 8.2 Hz, 2

49.7 (2 × CH ), 91.8 (CH), 113.3 (C), 117.5 (2 × CH), 119.2 (CH), 122.0

2

H), 7.04 (d, J = 8.9 Hz, 1 H), 7.09 (d, J = 8.2 Hz, 2 H), 7.31–7.35 (m, 1 H),

(CH), 123.3 (CH), 124.7 (C), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9

(C), 129.1 (2 × CH), 132.9 (C), 150.1 (C), 152.7 (C).

7

.46–7.50 (m, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H),

.79 (d, J = 8.5 Hz, 1 H).

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₃H₂₄³⁵ClN O: 379.1577; found:

2

13

C NMR (CDCl , 100 MHz):  = 20.5 (CH ), 22.7 (CH ), 25.3 (CH ), 47.5

379.1575.

3

2

(

2 × CH ), 50.2 (2 × CH ), 91.9 (CH), 113.4 (C), 116.7 (2 × CH), 119.2

CH), 122.0 (CH), 123.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9

C), 129.4 (C), 129.7 (2 × CH), 133.0 (C), 149.5 (C), 152.8 (C).

2

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(4-nitrophenyl)pip-

erazine (11o)

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₂₇N O: 359.2123; found:

2

Yield: 319 mg (82%); yellow solid; mp 222–223 °C (DMF).

359.2122.

IR (ATR): 1618, 1595, 1504, 1491, 1466, 1449, 1412, 1389, 1323, 1279,

1

7

1

244, 1227, 1207, 1190, 1165, 1146, 1115, 1092, 1018, 959, 922, 818,

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(2,6-dimethylphe-

–1

54 cm

.

nyl)piperazine (11l)

H NMR (DMSO-d , 400 MHz, 120 °С):  = 2.11–2.25 (m, 2 H), 2.86–

6

Yield: 264 mg (71%); colorless solid; mp 147–148 °C (MeOH).

2

.95 (m, 3 H), 3.01–3.18 (m, 3 H), 3.48–3.52 (m, 4 H), 4.80 (d, J = 9.4

Hz, 1 H), 6.95–7.00 (m, 3 H), 7.30 (t, J = 7.5 Hz, 1 H), 7.45 (t, J = 7.5 Hz,

1 H), 7.61 (d, J = 9.0 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.79 (d, J = 8.5 Hz,

1 H), 8.02 (d, J = 8.9 Hz, 2 H).

IR (ATR): 3061, 2934, 2837, 1620, 1597, 1516, 1466, 1408, 1395, 1375,

1

8

1

306, 1271, 1261, 1236, 1206, 1173, 1165, 1138, 1067, 1025, 972,

45, 808, 764, 745 cm^–

1

.

13

H NMR (CDCl , 400 MHz):  = 2.24–2.27 (m, 2 H), 2.40 (s, 6 H), 2.90–

C NMR (DMSO-d , 100 MHz, 120 °С):  = 22.1 (CH ), 25.3 (CH ), 47.2

3

6

2

2.96 (m, 2 H), 3.10–3.25 (m, 8 H), 4.76–4.80 (m, 1 H), 6.96–7.04 (m, 3

(2 × CH ), 47.6 (2 CH ), 92.1 (CH), 113.3 (2 × CH), 114.1 (C), 119.3 (CH),

2

H), 7.13 (d, J = 9.0 Hz, 1 H), 7.33–7.37 (m, 1 H), 7.47–7.51 (m, 1 H),

122.4 (CH), 123.5 (CH), 126.1 (2 × CH), 126.8 (CH), 128.0 (CH), 128.6

(CH), 129.2 (C), 133.2 (C), 138.1 (C), 152.8 (C), 155.4 (C).

7.65 (d, J = 9.0 Hz, 1 H), 7.77 (d, J = 8.2 Hz, 1 H), 7.80 (d, J = 8.5 Hz, 1 H).

13

HRMS (EI): m/z [M + H]⁺calcd for C₂₃H₂₄N O : 390.1818; found:

C NMR (CDCl , 100 MHz):  = 19.9 (2 × CH ), 22.9 (CH ), 25.4 (CH ),

3

2

3

4

8.9 (2 × CH ), 50.1 (2 × CH ), 92.6 (CH), 113.5 (C), 119.3 (CH), 122.0

390.1819.

2

(

CH), 123.2 (CH), 125.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9

C), 129.1 (2 × CH), 133.0 (C), 137.1 (2 C), 148.5 (C), 153.0 (C).

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(2-methoxyphe-

HRMS (EI): m/z [M + H]⁺calcd for C₂₅H₂₉N O: 373.2280; found:

nyl)piperazine (11p)

2

373.2284.

Yield: 292 mg (78%); colorless solid; mp 172–173 °C (MeOH).

IR (ATR): 1620, 1595, 1503, 1466, 1445, 1412, 1391, 1379, 1335, 1317,

1

-(2-Chlorophenyl)-4-(2,3-dihydro-1H-benzo[f]chromen-3-

1

8

1

306, 1250, 1207, 1190, 1140, 1119, 1070, 1059, 1020, 974, 953, 924,

yl)piperazine (11m)

–1

45, 822, 806, 752, 739 cm

.

Yield: 314 mg (83%); colorless solid; mp 169–170 °C (MeOH).

H NMR (CDCl , 400 MHz):  = 2.22–2.32 (m, 2 H), 3.00–3.36 (m, 10

3

IR (ATR): 1620, 1589, 1514, 1479, 1466, 1449, 1412, 1396, 1377, 1261,

H), 3.90 (s, 3 H), 4.77 (dd, J = 8.4, 3.7 Hz, 1 H), 6.89 (d, J = 8.0 Hz, 1 H),

6.93–7.08 (m, 4 H), 7.32–7.36 (m, 1 H), 7.48 (ddd, J = 8.0, 6.6, 1.2 Hz, 1

H), 7.62 (d, J = 8.9 Hz, 1 H), 7.76 (d, J = 8.2 Hz, 1 H), 7.79 (d, J = 8.7 Hz,

1 H).

1

8

1

229, 1207, 1188, 1153, 1138, 1123, 1069, 1018, 970, 955, 928, 847,

–1

12, 766, 745 cm

.

H NMR (CDCl , 400 MHz):  = 2.20–2.32 (m, 2 H), 3.00–3.33 (m, 10

3

13

H), 4.76 (dd, J = 9.2, 3.0 Hz, 1 H), 7.00 (td, J = 7.8, 1.4 Hz, 1 H), 7.07 (m,

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.2 (CH ), 47.7 (2 × CH ),

3 2 2 2

2

H), 7.22–7.27 (m, 1 H), 7.32–7.37 (m, 1 H), 7.39 (dd, J = 8.0, 1.4 Hz, 1

51.0 (2 × CH ), 55.5 (CH ), 92.0 (CH), 111.3 (CH), 113.3 (C), 118.4 (CH),

2

3

H), 7.49 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.64 (d, J = 8.9 Hz, 1 H), 7.76–

119.3 (CH), 121.1 (CH), 122.0 (CH), 123.1 (CH), 123.2 (CH), 126.4 (CH),

7

.80 (m, 2 H).

127.9 (CH), 128.5 (CH), 128.9 (C), 133.0 (C), 141.5 (C), 152.4 (C), 152.9

(C).

13

C NMR (CDCl , 100 MHz):  = 22.8 (CH ), 25.3 (CH ), 47.7 (2 × CH ),

3

2

5

1

1.6 (2 × CH ), 92.0 (CH), 113.4 (C), 119.3 (CH), 120.5 (CH), 122.0 (CH),

23.2 (CH), 123.8 (CH), 126.4 (CH), 127.7 (CH), 127.9 (CH), 128.5 (CH),

29.0 (2C), 130.8 (CH), 133.0 (C), 149.5 (C), 152.9 (C).

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₂₇N O : 375.2073; found:

2

375.2070.

HRMS (EI): m/z [M + H]⁺calcd for C₂₃H₂₄³⁵ClN O: 379.1577; found:

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-4-(2-ethoxyphe-

2

379.1580.

nyl)piperazine (11q)

Yield: 318 mg (82%); colorless solid; mp 153–154 °C (MeOH).

1

-(4-Chlorophenyl)-4-(2,3-dihydro-1H-benzo[f]chromen-3-

IR (ATR): 1620, 1595, 1503, 1488, 1451, 1406, 1385, 1337, 1308, 1236,

yl)piperazine (11n)

1

207, 1188, 1155, 1140, 1123, 1040, 1022, 974, 949, 937, 912, 843,

–1

Yield: 303 mg (80%); colorless solid; mp 256–257 °C (EtOH–DMF).

816, 762, 741 cm .

1

IR (ATR): 2833, 1620, 1593, 1466, 1447, 1410, 1385, 1358, 1344, 1312,

H NMR (CDCl , 400 MHz):  = 1.50 (t, J = 6.9 Hz, 3 H), 2.18–2.32 (m, 2

3

–1

1234, 1207, 1146, 1018, 957, 847, 810, 750 cm

.

H), 3.02–3.34 (m, 10 H), 4.10 (q, J = 6.9 Hz, 2 H), 4.77 (dd, J = 8.0, 3.9

Hz, 1 H), 6.86–6.89 (m, 1 H), 6.91–7.02 (m, 3 H), 7.07 (d, J = 8.7 Hz, 1

H), 7.34 (ddd, J = 8.0, 6.9, 0.9 Hz, 1 H), 7.49 (ddd, J = 8.3, 6.9, 1.2 Hz, 1

H), 7.63 (d, J = 8.9 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.79 (d, J = 8.5 Hz,

1

H NMR (CDCl , 400 MHz):  = 2.18–2.31 (m, 2 H), 2.94–3.01 (m, 2 H),

3

3.07–3.28 (m, 8 H), 4.76 (dd, J = 9.2, 3.0 Hz, 1 H), 6.87 (d, J = 9.0 Hz, 2

H), 7.03 (d, J = 8.9 Hz, 1 H), 7.21 (d, J = 9.0 Hz, 2 H), 7.31–7.35 (m, 1 H),

1

H).

7

.45–7.50 (m, 1 H), 7.61 (d, J = 9.0 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H),

.78 (d, J = 8.5 Hz, 1 H).

©

L

Synthesis

V. A. Osyanin et al.

Paper

13

C NMR (CDCl , 100 MHz):  = 15.1 (CH ), 22.7 (CH ), 25.3 (CH ), 47.7

C NMR (CDCl , 100 MHz):  = 22.8 (CH ), 25.3 (CH ), 44.0 (2 × CH ),

3

2

3

2

(

2 × CH ), 50.9 (2 × CH ), 63.7 (CH ), 92.0 (CH), 112.6 (CH), 113.4 (C),

47.5 (2 × CH ), 92.1 (CH), 109.9 (CH), 113.4 (C), 119.2 (CH), 122.0 (CH),

2

1

18.3 (CH), 119.3 (CH), 121.1 (CH), 122.0 (CH), 122.9 (CH), 123.2 (CH),

26.4 (CH), 127.9 (CH), 128.5 (CH), 128.9 (C), 133.0 (C), 141.6 (C),

51.7 (C), 152.9 (C).

123.2 (CH), 126.4 (CH), 127.9 (CH), 128.5 (CH), 128.9 (C), 132.9 (C),

152.7 (C), 157.8 (2 × CH), 161.8 (C).

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₁H₂₃N O: 347.1872; found:

4

HRMS (EI): m/z [M + H]⁺calcd for C₂₅H₂₉N O : 389.2229; found:

347.1876.

2

389.2232.

1-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)azepane (12)

4

-[4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperazin-1-yl]phe-

Yield: 208 mg (74%); colorless solid; mp 78–79 °C (MeOH).

nol (11r)

IR (ATR): 2926, 2847, 1622, 1597, 1514, 1468, 1449, 1431, 1416, 1383,

Yield: 288 mg (80%); colorless solid; mp 193–195 °C (DMF).

–1

1229, 1207, 1186, 1163, 1140, 968, 947, 818, 745 cm

.

IR (ATR): 3500–2500, 1620, 1593, 1514, 1466, 1452, 1433, 1410,

1

H NMR (CDCl , 400 MHz):  = 1.63–1.75 (m, 8 H), 2.17–2.23 (m, 2 H),

.90–2.97 (m, 2 H), 3.04–3.23 (m, 4 H), 4.80–4.83 (m, 1 H), 7.05 (d, J =

.9 Hz, 1 H), 7.32 (ddd, J = 8.0, 6.8, 1.1 Hz, 1 H), 7.47 (ddd, J = 8.2, 6.8,

3

1

9

1

391, 1306, 1261, 1229, 1206, 1188, 1157, 1144, 1099, 1072, 1020,

2

8

–1

74, 959, 922, 851, 827, 808, 772, 750 cm

.

H NMR (DMSO-d , 400 MHz, 120 °С):  = 2.10–2.23 (m, 2 H), 2.72–

1.4 Hz, 1 H), 7.60 (d, J = 9.0 Hz, 1 H), 7.74 (d, J = 8.5 Hz, 1 H), 7.77 (d, J =

6

3.20 (m, 10 H), 4.74 (d, J = 8.2 Hz, 1 H), 6.66 (d, J = 7.3 Hz, 2 H), 6.77 (d,

8.5 Hz, 1 H).

J = 7.3 Hz, 2 H), 6.99 (d, J = 8.7 Hz, 1 H), 7.27–7.31 (m, 1 H), 7.42–7.47

13

C NMR (CDCl , 100 MHz):  = 23.4 (CH ), 26.7 (CH ), 27.5 (2 × CH ),

3

2

(m, 1 H), 7.61 (d, J = 8.5 Hz, 1 H), 7.73–7.79 (m, 2 H), 8.31 (br s, 1 H).

29.9 (2 × CH ), 50.2 (2 × CH ), 94.4 (CH), 113.2 (C), 119.6 (CH), 122.0

2

13

C NMR (DMSO-d , 100 MHz, 120 °С):  = 22.2 (CH ), 25.4 (CH ), 47.7

(CH), 123.0 (CH), 126.3 (CH), 127.7 (CH), 128.4 (CH), 128.8 (C), 133.1

(C), 153.7 (C).

6

2

(

2 × CH ), 51.1 (2 × CH ), 92.3 (CH), 114.1 (C), 116.3 (2 × CH), 118.6 (2

2

×

1

CH), 119.4 (CH), 122.4 (CH), 123.4 (CH), 126.8 (CH), 128.0 (CH),

28.6 (CH), 129.1 (C), 133.3 (C), 145.2 (C), 151.7 (C), 153.0 (C).

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₁₉H₂₄NO: 282.1858; found:

282.1861.

HRMS (EI): m/z [M + H]⁺calcd for C₂₃H₂₅N O : 361.1916; found:

2

361.1919.

2-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-6-methoxy-2,3,4,9-tet-

rahydro-1H-pyrido[3,4-b]indole (13)

1

-{4-[4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperazin-1-

To a suspension of 2-trifluoroacetyl-1H-benzo[f]chromene (1a; 278

mg, 1 mmol) in MeOH (8 mL) was added 6-methoxy-2,3,4,9-tetrahy-

dro-1H-pyrido[3,4-b]indole (404 mg, 2 mmol) at rt. The resulting

mixture was heated under reflux for 15 min and then kept at rt for 1 h

and at –30 °C for 30 min. The precipitate formed was collected by fil-

tration, washed with ice-cold MeOH (1 mL) and purified by recrystal-

lization; yield: 273 mg (71%); colorless solid; mp 211–213 °C (DMF–

MeOH).

yl]phenyl}ethan-1-one (11s)

Yield: 348 mg (90%); light-yellow solid; mp 239–240 °С (DMF–

MeOH).

IR (ATR): 2841, 1659, 1618, 1595, 1510, 1389, 1360, 1277, 1227, 1188,

–1

1144, 1018, 955, 924, 847, 812, 770, 754 cm .

1

H NMR (CDCl , 400 MHz):  = 2.21–2.28 (m, 2 H), 2.53 (s, 3 H), 2.94–

3

.00 (m, 2 H), 3.07–3.16 (m, 1 H), 3.20–3.29 (m, 3 H), 3.38–3.46 (m, 4

H), 4.76 (dd, J = 9.1, 3.1 Hz, 1 H), 6.90 (d, J = 8.9 Hz, 2 H), 7.02 (d, J = 8.9

Hz, 1 H), 7.34 (ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.48 (ddd, J = 8.2, 6.9, 1.2

Hz, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.5

Hz, 1 H), 7.89 (d, J = 8.9 Hz, 2 H).

IR (ATR): 3381, 1620, 1595, 1512, 1483, 1466, 1454, 1433, 1401, 1389,

1

8

1

304, 1219, 1209, 1179, 1155, 1126, 1113, 1067, 1032, 966, 916, 835,

–1

10, 800, 770, 752 cm

.

H NMR (DMSO-d , 400 MHz):  = 2.18–2.32 (m, 2 H), 2.64–2.75 (m, 2

6

1

3

H), 3.02–3.20 (m, 3 H), 3.26–3.32 (m, 1 H), 3.72 (s, 3 H), 3.97 (d, J =

C NMR (CDCl , 100 MHz):  = 22.7 (CH ), 25.3 (CH ), 26.2 (CH ), 47.2

3

2

3

1

4.9 Hz, 1 H), 4.12 (d, J = 14.9 Hz, 1 H), 4.99 (d, J = 9.6 Hz, 1 H), 6.62

dd, J = 8.7, 2.1 Hz, 1 H), 6.86 (d, J = 2.1 Hz, 1 H), 7.00 (d, J = 9.0 Hz, 1

H), 7.14 (d, J = 8.5 Hz, 1 H), 7.29–7.33 (m, 1 H), 7.45–7.49 (m, 1 H),

.64 (d, J = 9.0 Hz, 1 H), 7.77–7.80 (m, 2 H), 10.54 (s, 1 H).

¹³C NMR (DMSO-d

, 100 MHz):  = 22.5 (CH ), 22.7 (CH ), 25.7 (CH

4.0 (CH ), 47.4 (CH ), 55.8 (CH ), 92.5 (CH), 100.3 (CH), 107.2 (C),

(

2 × CH ), 47.8 (2 × CH ), 91.8 (CH), 113.3 (C), 113.6 (2 × CH), 119.1

CH), 122.0 (CH), 123.3 (CH), 126.5 (CH), 127.7 (C), 128.0 (CH), 128.5

CH), 128.9 (C), 130.5 (2 × CH), 132.9 (C), 152.6 (C), 154.3 (C), 196.6

C).

2

(

7

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₅H₂₇N O : 387.2073; found:

3

6

2

),

2

4

1

87.2073.

2

3

10.4 (CH), 112.0 (CH), 114.0 (C), 119.5 (CH), 122.5 (CH), 123.6 (CH),

27.0 (CH), 127.6 (C), 128.1 (CH), 128.7 (CH), 128.9 (C), 131.6 (C),

33.1 (C), 133.9 (C), 153.0 (C), 153.5 (C).

2

-[4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)piperazin-1-yl]py-

rimidine (11t)

HRMS (EI): m/z [M + H]⁺calcd for C₂₅H₂₅N O : 385.1916; found:

2

Yield: 294 mg (85%); colorless solid; mp 142–143 °C (MeOH).

385.1912.

IR (ATR): 1622, 1585, 1545, 1514, 1466, 1449, 1408, 1389, 1362, 1310,

1

8

1

260, 1231, 1207, 1192, 1179, 1153, 1138, 1020, 980, 970, 955, 939,

4

-(6-Chlorochroman-2-yl)morpholine (8e)

–1

37, 814, 783, 768, 743 cm

.

Yield: 178 mg (70%); colorless solid; mp 100–101 °C (MeOH).

H NMR (CDCl , 400 MHz):  = 2.19–2.31 (m, 2 H), 2.85–2.92 (m, 2 H),

3

IR (ATR): 2940, 2864, 2843, 1574, 1479, 1449, 1408, 1263, 1238, 1213,

3.06–3.17 (m, 3 H), 3.20–3.27 (m, 1 H), 3.86–3.96 (m, 4 H), 4.76 (dd,

1190, 1177, 1115, 1082, 1072, 1015, 968, 920, 914, 872, 831, 820,

J = 9.2, 3.0 Hz, 1 H), 6.49 (t, J = 4.8 Hz, 1 H), 7.01 (d, J = 8.9 Hz, 1 H),

–1

797, 770, 642 cm

.

7

8

4

.33 (t, J = 8.0 Hz, 1 H), 7.47 (ddd, J = 8.3, 7.1, 1.4 Hz, 1 H), 7.60 (d, J =

.7 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.4 Hz, 1 H), 8.32 (d, J =

.8 Hz, 2 H).

©

M

Synthesis

V. A. Osyanin et al.

Paper

1

H NMR (CDCl , 400 MHz):  = 1.93–2.09 (m, 2 H), 2.70–2.79 (m, 3 H),

1-(6,7-Dimethylchroman-2-yl)-4-(4-fluorophenyl)piperazine

3

2.84–2.92 (m, 1 H), 2.95–3.01 (m, 2 H), 3.68–3.77 (m, 4 H), 4.57 (dd,

(11v)

J = 9.8, 2.3 Hz, 1 H), 6.71 (d, J = 8.5 Hz, 1 H), 6.99 (d, J = 2.5 Hz, 1 H),

Yield: 262 mg (77%); colorless solid; mp 147–148 °C (MeOH).

7.01 (dd, J = 8.5, 2.5 Hz, 1 H).

IR (ATR): 2853, 1622, 1574, 1518, 1501, 1449, 1406, 1387, 1310, 1294,

1263, 1246, 1233, 1202, 1165, 1142, 1078, 1045, 1007, 951, 920, 868,

13

C NMR (CDCl , 100 MHz):  = 24.8 (CH ), 25.6 (CH ), 47.8 (2 × CH ),

3

2

6

7.2 (2 × CH ), 92.3 (CH), 118.1 (CH), 123.4 (C), 124.7 (C), 127.3 (CH),

–1

2

860, 818, 787, 750, 716, 702 cm .

128.7 (CH), 153.8 (C).

1

H NMR (CDCl , 400 MHz):  = 1.97–2.13 (m, 2 H), 2.17 (s, 3 H), 2.19

3

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C¹3^H17³⁵ClNO : 254.0948; found:

2

(s, 3 H), 2.73–2.79 (m, 1 H), 2.85–2.97 (m, 3 H), 3.12–3.20 (m, 6 H),

254.0951.

4.65 (d, J = 9.2 Hz, 1 H), 6.63 (s, 1 H), 6.82 (s, 1 H), 6.88–6.92 (m, 2 H),

6.95–7.00 (m, 2 H).

4

-(6,7-Dimethylchroman-2-yl)morpholine (8f)

13

C NMR (CDCl , 100 MHz):  = 18.9 (CH ), 19.6 (CH ), 25.5 (CH ), 25.7

3

2

Yield: 180 mg (73%); colorless solid; mp 94–95 °C (MeOH).

(CH ), 47.4 (2 × CH ), 50.6 (2 × CH ), 91.9 (CH), 115.6 (d, J = 21.9 Hz,

2

2 2 2 C,F

3

× CH), 117.7 (CH), 118.0 (d, ^JC,F = 7.6 Hz, 2 × CH), 118.9 (C), 128.1

IR (ATR): 2967, 2930, 2866, 2828, 1622, 1572, 1503, 1454, 1402, 1294,

1

(C), 130.0 (CH), 135.8 (C), 148.3 (C), 153.1 (C), 157.3 (d, ^JC,F = 237.4

1

9

1

273, 1260, 1218, 1200, 1165, 1111, 1092, 1069, 1043, 1020, 1006,

57, 918, 908, 885, 853, 785 cm

–1

Hz, C).

.

HRMS (EI): m/z [M + H]⁺calcd for C₂₁H₂₆FN O: 341.2029; found:

H NMR (CDCl , 400 MHz):  = 1.92–2.09 (m, 2 H), 2.15 (s, 3 H), 2.18

2

3

341.2033.

(s, 3 H), 2.70–2.77 (m, 3 H), 2.81–2.90 (m, 1 H), 2.96–3.02 (m, 2 H),

3.69–3.78 (m, 4 H), 4.54 (dd, J = 10.1, 2.0 Hz, 1 H), 6.62 (s, 1 H), 6.79 (s,

1

H).

1-Aryl(hetaryl)-2,3-dihydro-1H-benzo[f]chromen-3-amines; Gen-

13

eral Procedure

C NMR (CDCl , 100 MHz):  = 18.8 (CH ), 19.5 (CH ), 25.3 (CH ), 25.4

3

2

(

CH ), 47.8 (2 × CH ), 67.3 (2 × CH ), 92.0 (CH), 117.6 (CH), 118.9 (C),

A

solution of the corresponding 2-trifluoroacetyl-1H-ben-

2

1

28.1 (C), 130.0 (CH), 135.7 (C), 153.0 (C).

zo[f]chromene or 1H-benzo[f]chromene-2-carbaldehyde (1 mmol) in

cyclic secondary amine (morpholine, N-methylpiperazine, or piperi-

dine) (3 mL) was heated under reflux for 30 min (for 2-trifluoroace-

tyl-1H-benzo[f]chromenes) or 10 h (for 1H-benzo[f]chromene-2-car-

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₁₅H₂₂NO : 248.1651; found:

2

248.1647.

baldehydes). The reaction mixture was poured into H O (10 mL) to

yield a solid product, which was collected by filtration, washed with

2

4

-[8-(Adamantan-1-yl)-6-methylchroman-2-yl]morpholine (8g)

Yield: 301 mg (82%); colorless solid; mp 174–176 °C (MeOH).

H O, dried, and purified by recrystallization.

2

IR (ATR): 2901, 2849, 1462, 1447, 1408, 1373, 1342, 1315, 1298, 1261,

1

8

1

211, 1202, 1179, 1157, 1113, 1092, 1078, 1040, 995, 976, 943, 918,

4-(trans-1-Phenyl-2,3-dihydro-1H-benzo[f]chromen-3-yl)mor-

pholine (8h)

–1

89, 847, 816, 783 cm

.

H NMR (DMSO-d , 400 MHz):  = 1.71 (br s, 6 H), 1.80 (dd, J = 12.8,

Yield: 289 mg (84%) (from 2-trifluoroacetyl-1H-benzo[f]chromene);

6

6.1 Hz, 1 H), 1.92 (dd, J = 12.8, 5.6 Hz, 1 H), 2.01 (br s, 9 H), 2.12 (s, 3

colorless solid; mp 184–185 °C (MeOH–DMF).

H), 2.63–2.70 (m, 3 H), 2.82–2.91 (m, 1 H), 2.96–3.02 (m, 2 H), 3.55–

IR (ATR): 2855, 1620, 1595, 1508, 1491, 1454, 1302, 1236, 1211, 1192,

3.64 (m, 4 H), 4.55 (d, J = 9.6 Hz, 1 H), 6.65 (s, 1 H), 6.69 (s, 1 H).

–1

1113, 1059, 1024, 1011, 982, 920, 862, 849, 822, 746, 700 cm

.

13

C NMR (DMSO-d , 100 MHz):  = 21.0 (CH ), 25.2 (CH ), 26.5 (CH ),

1

6

3

2

H NMR (DMSO-d , 400 MHz):  = 2.16 (dt, J = 13.3, 1.8 Hz, 1 H), 2.55

6

2

6

1

9.0 (3 × CH), 36.9 (CH), 37.2 (3 × CH ), 40.7 (3 × CH ), 48.6 (2 × CH ),

2 2 2

(ddd, J = 13.3, 11.3, 5.4 Hz, 1 H), 2.73–2.79 (m, 2 H), 3.00–3.06 (m, 2

H), 3.65–3.71 (m, 4 H), 4.65 (dd, J = 11.3, 1.8 Hz, 1 H), 4.77 (dd, J = 5.4,

7.1 (2 × CH ), 92.3 (CH), 121.9 (C), 125.1 (CH), 127.8 (CH), 128.0 (C),

2

37.5 (C), 152.1 (C).

1.8 Hz, 1 H), 7.11–7.30 (m, 8 H), 7.43–7.46 (m, 1 H), 7.70–7.75 (m, 2

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₃₄NO : 368.2590; found:

H).

2

368.2592.

13

C NMR (DMSO-d , 100 MHz):  = 33.3 (CH ), 38.7 (CH), 47.7 (2 ×

6

2

CH ), 67.3 (2 × CH ), 87.6 (CH), 113.6 (C), 119.1 (CH), 123.1 (CH),

123.2 (CH), 126.5 (CH), 126.6 (CH), 128.50 (CH), 128.54 (2 × CH),

128.6 (2 × CH), 129.2 (CH), 132.8 (C), 145.3 (C), 153.7 (C).

2

1

-Cinnamyl-4-(6,8-dibromochroman-2-yl)piperazine (11u)

Yield: 428 mg (87%); colorless solid; mp 131–132 °C (MeOH).

HRMS (EI): m/z [M + H]⁺calcd for C23

H24NO : 346.1807; found:

IR (ATR): 2943, 2810, 1554, 1454, 1419, 1348, 1313, 1278, 1251, 1230,

2

1

7

1

197, 1180, 1134, 1085, 1058, 1039, 1006, 964, 927, 910, 858, 837,

346.1795.

–1

90, 775, 736, 717, 688, 659 cm

.

4-[trans-1-(3-Nitrophenyl)-2,3-dihydro-1H-benzo[f]chromen-3-

yl]morpholine (8i)

H NMR (CDCl , 400 MHz):  = 1.97–2.13 (m, 2 H), 2.57 (br s, 4 H),

3

2.74–2.96 (m, 4 H), 3.10–3.15 (m, 2 H), 3.19 (d, J = 6.9 Hz, 2 H), 4.74

(dd, J = 9.9, 2.1 Hz, 1 H), 6.30 (dt, J = 15.8, 6.9 Hz, 1 H), 6.53 (d, J = 15.8

Yield: 230 mg (59%) (from 2-trifluoroacetyl-1H-benzo[f]chromene);

Hz, 1 H), 7.09 (d, J = 2.1 Hz, 1 H), 7.22 (t, J = 7.3 Hz, 1 H), 7.28–7.32 (m,

colorless solid; mp 169–170 °C (MeOH).

2

H), 7.37 (d, J = 7.4 Hz, 2 H), 7.44 (d, J = 2.1 Hz, 1 H).

IR (ATR): 1618, 1528, 1341, 1265, 1260, 1236, 1203, 1192, 1119, 1059,

13

–1

C NMR (CDCl , 100 MHz):  = 25.1 (CH ), 26.1 (CH ), 47.4 (br, 2 ×

1036, 1022, 1013, 984, 918, 878, 849, 826, 781, 754, 733, 698 cm

.

3

2

СН ), 53.4 (2 × CH ), 61.2 (CH ), 93.6 (CH), 111.6 (C), 112.2 (C), 125.2

1

2

H NMR (DMSO-d , 400 MHz):  = 2.19 (dt, J = 13.0, 1.8 Hz, 1 H), 2.65

6

(C), 126.4 (2 × CH), 126.6 (CH), 127.6 (CH), 128.6 (2 × CH), 130.7 (CH),

(ddd, J = 13.0, 11.2, 5.4 Hz, 1 H), 2.74–2.79 (m, 2 H), 3.01–3.07 (m, 2

133.1 (CH), 133.2 (CH), 137.0 (C), 151.1 (C).

H), 3.65–3.75 (m, 4 H), 4.56 (dd, J = 11.2, 1.8 Hz, 1 H), 4.87 (dd, J = 5.4,

1.8 Hz, 1 H), 7.16 (d, J = 8.9 Hz, 1 H), 7.25–7.42 (m, 5 H), 7.75–7.78 (m,

2 H), 8.05–8.09 (m, 2 H).

HRMS (EI): m/z [M + H]⁺calcd for C₂₂H₂₅Br N O: 491.0334; found:

2

491.0335.

©

N

Synthesis

V. A. Osyanin et al.

Paper

13

1

C NMR (DMSO-d , 100 MHz):  = 33.3 (CH ), 38.5 (CH), 47.7 (2 ×

H NMR (DMSO-d , 400 MHz):  = 2.02 (dt, J = 13.3, 1.8 Hz, 1 H, H_e_q-2),

6

2

6

CH ), 67.2 (2 × CH ), 87.3 (CH), 111.9 (C), 119.3 (CH), 121.9 (CH),

2.12 (s, 3 H, CH ), 2.28 (br s, 4 H, 2 × CH₂_p_i_p-2,6), 2.51 (ddd, J = 13.3,

2

3

1

22.5 (CH), 123.3 (CH), 123.4 (CH), 126.9 (CH), 128.8 (CH), 129.4 (C),

29.6 (CH), 130.0 (CH), 132.3 (C), 134.8 (CH), 147.6 (C), 148.7 (C),

53.9 (C).

11.3, 5.4 Hz, 1 H, H -2), 2.61–2.66 (m, 2 H, CH₂_p_i_p-3,5), 2.92–2.97 (m,

ax

2 H, CH₂_p_i_p-3,5), 4.72 (dd, J = 11.3, 1.8 Hz, 1 H, H-3), 5.03 (dd, J = 5.4,

1.8 Hz, 1 H, H-1), 6.65 (d, J = 3.4 Hz, 1 H, H_t_h_i-3), 6.86 (dd, J = 5.0, 3.5

Hz, 1 H, Hthi-4), 7.05 (d, J = 8.9 Hz, 1 H, H-5), 7.22–7.26 (m, 1 H, H-8),

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₃H₂₃N O : 391.1658; found:

2

4

7^.²⁹^–⁷^.³⁴⁽^m^,²^H^,^Hthi-5, H-9), 7.56 (d, J = 8.5 Hz, 1 H, H-10), 7.74 (d,

391.1650.

J = 8.9 Hz, 1 H, H-6), 7.77 (d, J = 8.0 Hz, 1 H, H-7).

1

3

C NMR (DMSO-d , 100 MHz):  = 33.8 (CH-1), 34.2 (CH -2), 46.4

4

-[trans-1-(Thiophen-2-yl)-2,3-dihydro-1H-benzo[f]chromen-3-

6

2

(CH ), 47.2 (br, 2 × CH2pip^-³^,⁵⁾^,⁵⁵^.⁴⁽²^×^C^H2pip^-²^,⁶⁾^,⁸⁸^.⁴⁽^C^H^-³⁾^,¹¹⁴^.⁷

yl]morpholine (8j)

3

(C-10b), 119.5 (CH-5), 123.2 (CH-10), 123.5 (CH-8), 125.1 (CH_t_h_i-5),

Yield: 200 mg (57%) (from 1H-benzo[f]chromene-2-carbaldehyde);

1

6

26.0 (CH_t_h_i-3), 127.1 (CH-9), 127.6 (CH_t_h_i-4), 128.9 (CH-7), 129.1 (C-

a), 129.8 (CH-6), 132.8 (C-10a), 150.1 (C_t_h_i-2), 153.1 (C-4a).

284 mg (81%) (from 2-trifluoroacetyl-1H-benzo[f]chromene); color-

less solid; mp 158–159 °C (EtOH).

HRMS (EI): m/z [M + H]⁺calcd for C₂₂H₂₅N OS: 365.1688; found:

3

2

IR (ATR): 2855, 1622, 1595, 1508, 1468, 1454, 1435, 1416, 1393, 1302,

65.1689.

1

9

1

263, 1236, 1211, 1200, 1188, 1153, 1144, 1113, 1059, 1032, 1024,

99, 982, 918, 976, 860, 849, 822, 746, 708, 692 cm

–1

.

4

-[trans-1-(Pyridin-3-yl)-2,3-dihydro-1H-benzo[f]chromen-3-

H NMR (CDCl , 400 MHz):  = 2.25 (dt, J = 13.1, 1.8 Hz, 1 H), 2.51

3

yl]morpholine (8l)

(ddd, J = 13.1, 11.4, 5.3 Hz, 1 H), 2.76–2.82 (m, 2 H), 3.01–3.06 (m, 2

Yield: 208 mg (60%) (from 1H-benzo[f]chromene-2-carbaldehyde);

^c^o^l^o^r^l^e^s^s^s^o^lⁱ^d^;^m^p²⁰²^–²⁰³^°^C⁽^M^e^O^H^–^С^H^C^l3⁾^.

H), 3.70–3.76 (m, 4 H), 4.80 (dd, J = 11.4, 1.8 Hz, 1 H), 4.98 (dd, J = 5.3,

.8 Hz, 1 H), 6.58 (d, J = 3.5 Hz, 1 H), 6.84 (dd, J = 5.0, 3.5 Hz, 1 H), 7.11

d, J = 8.9 Hz, 1 H), 7.15 (d, J = 5.0 Hz, 1 H), 7.25–7.29 (m, 1 H), 7.32–

.36 (m, 1 H), 7.63 (d, J = 8.2 Hz, 1 H), 7.70 (d, J = 8.9 Hz, 1 H), 7.74 (d,

J = 8.0 Hz, 1 H).

1

(

7

IR (ATR): 2859, 2839, 1620, 1597, 1572, 1481, 1466, 1414, 1391, 1337,

1300, 1294, 1261, 1231, 1200, 1167, 1153, 1144, 1109, 1069, 1061,

1024, 1011, 978, 972, 920, 872, 858, 843, 833, 820, 787, 745, 725, 712

–1

13

cm .

C NMR (CDCl , 100 MHz):  = 33.7 (CH ), 34.2 (CH), 47.8 (2 × CH ),

3

2

1

6

1

7.3 (2 × CH ), 88.0 (CH), 114.0 (C), 119.2 (CH), 122.9 (CH), 123.2 (CH),

24.2 (CH), 126.1 (CH), 126.7 (CH), 127.0 (CH), 128.5 (CH), 129.1 (C),

29.5 (CH), 132.7 (C), 149.3 (C), 153.1 (C).

H NMR (DMSO-d , 400 MHz):  = 2.03 (dt, J = 13.5, 1.8 Hz, 1 H), 2.55–

2

6

2.66 (m, 3 H), 2.88–2.94 (m, 2 H), 3.50–3.57 (m, 4 H), 4.51 (dd, J =

11.4, 1.8 Hz, 1 H), 4.89 (dd, J = 5.3, 1.8 Hz, 1 H), 7.13 (d, J = 8.9 Hz, 1 H),

7.21–7.28 (m, 3 H), 7.36–7.38 (m, 2 H), 7.76–7.80 (m, 2 H), 8.35–8.38

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₁H₂₂NO S: 352.1371; found:

2

(m, 2 H).

352.1369.

13

C NMR (DMSO-d , 100 MHz):  = 33.1 (CH ), 35.8 (CH), 47.7 (2 ×

6

2

CH ), 66.9 (2 × CH ), 87.8 (CH), 113.0 (C), 119.5 (CH), 123.2 (CH),

1

-(trans-1-Phenyl-2,3-dihydro-1H-benzo[f]chromen-3-yl)piperi-

2

1

23.6 (CH), 124.0 (CH), 127.2 (CH), 129.0 (CH), 129.3 (C), 129.8 (CH),

32.5 (C), 136.3 (CH), 141.2 (C), 148.1 (CH), 150.1 (CH), 153.9 (C).

dine (10h)

Yield: 292 mg (85%) (from 2-trifluoroacetyl-1H-benzo[f]chromene);

colorless solid; mp 193–195 °C (EtOH).

HRMS (EI): m/z [M + H]⁺calcd for C22

47.1757.

H N O : 347.1760; found:

23 2 2

3

IR (ATR): 2928, 1622, 1597, 1491, 1464, 1450, 1410, 1314, 1261, 1231,

1

7

1

209, 1190, 1165, 1126, 1117, 1053, 1020, 1011, 972, 839, 822, 812,

–1

4-[trans-1-(4-Methoxyphenyl)-2,3-dihydro-1H-benzo[f]chromen-

-yl]morpholine (8m)

45, 696 cm

.

3

H NMR (DMSO-d , 400 MHz):  = 1.48–1.65 (m, 6 H), 2.16 (dt, J =

6

Yield: 193 mg (52%) (from 1H-benzo[f]chromene-2-carbaldehyde);

colorless solid; mp 188–190 °C (MeOH).

1

2

5

3.0, 1.8 Hz, 1 H), 2.59 (ddd, J = 13.0, 11.0, 5.5 Hz, 1 H), 2.64–2.75 (m,

H), 2.94–3.05 (m, 2 H), 4.67 (dd, J = 11.0, 1.8 Hz, 1 H), 4.77 (dd, J =

.5, 1.8 Hz, 1 H), 7.10–7.28 (m, 8 H), 7.45 (d, J = 8.7 Hz, 1 H), 7.68–7.75

IR (ATR): 1620, 1611, 1597, 1582, 1506, 1466, 1435, 1414, 1395, 1317,

1298, 1285, 1261, 1234, 1202, 1186, 1144, 1115, 1061, 1022, 1007,

(m, 2 H).

–1

13

980, 918, 876, 862, 853, 837, 820, 812, 746 cm .

C NMR (DMSO-d , 100 MHz):  = 24.8 (CH ), 26.3 (2 × CH ), 33.6

6

2

1

(CH ), 38.9 (CH), 48.6 (2 × CH ), 88.5 (CH), 113.7 (C), 119.2 (CH), 122.9

H NMR (DMSO-d , 400 MHz):  = 1.95 (dt, J = 13.1, 1.8 Hz, 1 H, H_e_q-2),

2

6

(

1

CH), 123.2 (CH), 126.4 (CH), 126.5 (CH), 128.4 (CH), 128.5 (2 × CH),

28.6 (2 × CH), 129.0 (CH), 129.1 (C), 132.9 (C), 145.5 (C), 154.1 (C).

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₂₄H₂₆NO: 344.2014; found:

2.44–2.54 (m, 1 H, H_a_x-2), 2.59–2.65 (m, 2 H, CH N), 2.89–2.96 (m, 2

2

H, CH N), 3.52 (br s, 4 H, 2 × CH O), 3.64 (s, 3 H, CH O), 4.51 (dd, J =

2

3

11.0, 1.8 Hz, 1 H, H-3), 4.73 (dd, J = 5.4, 1.8 Hz, 1 H, H-1), 6.78 (d, J =

8^.⁷^H^z^,²^H^,^Ho-MeO⁾^,⁶^.⁹⁶⁽^d^,^J⁼⁸^.⁷^H^z^,²^H^,^Hm-MeO), 7.09 (d, J = 8.9 Hz,

1 H, H-5), 7.19–7.27 (m, 2 H, H-8,9), 7.39 (d, J = 8.0 Hz, 1 H, Ar), 7.72–

7.78 (m, 2 H).

3

44.2009.

1

-Methyl-4-[trans-1-(thiophen-2-yl)-2,3-dihydro-1H-ben-

13

C NMR (DMSO-d , 100 MHz):  = 33.7 (CH -2), 37.3 (CH-1), 47.8 (2 ×

zo[f]chromen-3-yl]piperazine (10i)

6

2

CH N), 55.5 (CH O), 66.9 (2 × CH O), 88.0 (CH-3), 114.4 (2 × CH_o_-_M_e_O),

2

3

2

Yield: 193 mg (53%) (from 1H-benzo[f]chromene-2-carbaldehyde);

colorless solid; mp 152–154 °C (MeOH). In the NMR assignments, pip

=

1

(

1

14.5 (C-10b), 119.4 (CH-5), 123.4 (2 × CH-8,10), 126.9 (CH-9), 128.9

CH-7), 129.2 (C-6a), 129.4 (CH-6), 129.7 (2 × CH_m_-_M_e_O), 132.8 (C-10a),

37.9 (C_p_-_M_e_O), 153.6 (C-4a), 158.2 (C–OMe).

piperazine and thi = thiophenyl.

IR (ATR): 1620, 1599, 1464, 1456, 1412, 1398, 1375, 1352, 1321, 1287,

1

9

HRMS (EI): m/z [M + H]⁺calcd for C₂₄H₂₆NO : 376.1913; found:

3

261, 1227, 1200, 1190, 1155, 1142, 1130, 1078, 1059, 1013, 997,

–1

376.1917.

78, 851, 833, 810, 785, 748, 710, 696 cm

.

©

O

Synthesis

V. A. Osyanin et al.

Paper

1

3

4

(

-(3-Phenyl-2,3-dihydro-1H-benzo[f]chromen-3-yl)morpholine

8k)

solution of 2,2,2-trifluoro-1-(3-phenyl-1H-benzo[f]chromen-2-

C NMR (DMSO-d , 100 MHz):  = 18.5 (CH ), 28.5 (3 × CH ), 43.9 (br,

6

2

3

CH NBoc), 44.2 (br, CH , CH NBoc), 50.4 (br, 2 × CH , CH N), 79.8

2 2 2 2 2

(

CMe ), 112.1 (C–CHO), 118.7 (CH-3), 119.6 (C-1), 122.9 (CH-6), 124.4

C-8), 126.0 (CH-7), 128.2 (CH-4), 128.8 (CH-5), 129.0 (C-4a), 133.9

C-8a), 152.2 (C-2), 154.0 (C=O), 159.7 (=CHN), 191.2 (HC=O).

A

3

yl)ethan-1-one (354 mg, 1 mmol) in morpholine (3 mL) was heated

under reflux for 2 h. The reaction mixture was poured into H O (10

mL) to yield a solid product, which was collected by filtration, washed

2

HRMS (EI): m/z [M + H]⁺calcd for C₂₃H₂₉N O : 397.2127; found:

2

4

with H O, dried, and purified by recrystallization; yield: 280 mg

397.2130.

2

(81%); light-yellow solid; mp 145–146 °C (DMF–MeOH).

IR (ATR): 2845, 1620, 1595, 1512, 1466, 1445, 1396, 1352, 1277, 1240,

(1R*,2R*,3R*)-1-Aryl-2-(1,5-diazabicyclo[3.2.1]octan-8-yl)-2,3-di-

hydro-1H-benzo[f]chromen-3-ols 15a–c; General Procedure

1

196, 1152, 1117, 1022, 972, 918, 885, 851, 818, 772, 756, 746, 700

–1

cm

1

.

To a suspension of 1-aryl-1H-benzo[f]chromene-2-carbaldehyde 1p–

r (1 mmol) in MeOH (4 mL for 15a, 7 mL for 15b,c) was added homo-

piperazine (200 mg, 2 mmol) at rt. The resulting mixture was heated

H NMR (CDCl , 400 MHz):  = 2.24–2.38 (m, 2 H), 2.54–2.71 (m, 3 H),

3

3.00–3.10 (m, 3 H), 3.64–3.74 (m, 4 H), 7.19–7.43 (m, 8 H), 7.64 (d, J =

8.2 Hz, 1 H), 7.70 (d, J = 8.9 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H).

under reflux for 30 min and then kept at rt for 24 h. H O (2 mL for

2

1

3

15a, 1 mL for 15b,c) was added, the precipitate formed was collected

by filtration, washed with 60% aq MeOH (1 mL) and purified by re-

crystallization.

C NMR (CDCl , 100 MHz):  = 20.2 (CH ), 29.3 (CH ), 46.1 (2 × CH ),

3

2

6

1

7.6 (2 × CH ), 94.8 (C), 113.9 (C), 118.7 (CH), 122.0 (CH), 123.1 (CH),

26.3 (CH), 126.9 (2 × CH), 127.5 (CH), 128.2 (3 × CH), 128.5 (CH),

28.8 (C), 132.8 (C), 141.2 (C), 152.6 (C).

2

(1R*,2R*,3R*)-2-(1,5-Diazabicyclo[3.2.1]octan-8-yl)-1-(4-me-

HRMS (EI): m/z [M + H]⁺calcd for C₂₃H₂₄NO : 346.1807; found:

3

2

thoxyphenyl)-2,3-dihydro-1H-benzo[f]chromen-3-ol (15a)

Yield: 266 mg (64%); colorless solid; mp 176–177 °C (MeOH).

IR (ATR): 3100–2900, 1622, 1599, 1508, 1464, 1244, 1231, 1177,

46.1803.

(E)-2-[(2-Hydroxynaphthalen-1-yl)methyl]-3-morpholinoacrylal-

1

138, 1111, 1074, 1059, 1049, 1030, 1005, 947, 893, 835, 812, 787,

dehyde (14a)

–1

758, 746, 725 cm

.

To a suspension of 1H-benzo[f]chromene-2-carbaldehyde (1m; 210

mg, 1 mmol) in MeOH (3 mL) was added a solution of morpholine (87

mg, 1 mmol) in MeOH (2 mL) dropwise with stirring at rt for 10 min.

The mixture was stirred additionally for 30 min, stored at –30 °C for 1

h, the formed product was collected by filtration, and recrystallized

from MeOH; yield: 220 mg (74%); colorless solid; mp 144–145 °C.

¹H NMR (CDCl

, 400 MHz):  = 1.09 (dt, J = 14.6, 4.3 Hz, 1 H), 1.82–

3

1.98 (m, 2 H), 2.82–2.94 (m, 3 H), 3.00–3.26 (m, 5 H), 3.72 (s, 3 H),

4.10 (d, J = 11.2 Hz, 1 H), 4.89 (s, 1 H), 5.38 (d, J = 2.1 Hz, 1 H), 6.74 (d,

J = 8.9 Hz, 1 H), 6.95 (d, J = 8.9 Hz, 2 H), 7.24–7.27 (m, 4 H), 7.49–7.52

(m, 1 H), 7.72–7.76 (m, 2 H) (hydroxyl proton does not appear in the

1

H NMR spectrum).

IR (ATR): 3300–2500, 1626, 1584, 1558, 1506, 1458, 1437, 1404,

¹³C NMR (CDCl

(CH ), 51.0 (CH

(CH), 112.7 (C), 114.1 (2 × CH), 119.2 (CH), 123.4 (CH), 124.1 (CH),

26.5 (CH), 128.4 (CH), 129.2 (CH), 129.3 (2 × CH), 129.8 (C), 133.0

C), 138.0 (C), 152.1 (C), 158.1 (C).

, 100 MHz):  = 18.5 (CH

), 39.7 (CH), 42.2 (CH), 49.7

), 87.4 (CH), 93.5

1

8

1

358, 1290, 1273, 1234, 1157, 1115, 1067, 1026, 982, 922, 889, 876,

12, 748 cm

3

2

–1

.

2

), 55.1 (CH ), 56.1 (CH ), 55.3 (CH

2

3

H NMR (DMSO-d , 400 MHz):  = 3.23–3.26 (m, 4 H), 3.37–3.40 (m, 4

6

1

(

H), 3.95 (s, 2 H), 6.86 (s, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.17–7.21 (m, 1

H), 7.24–7.28 (m, 1 H), 7.58 (d, J = 8.7 Hz, 1 H), 7.66–7.70 (m, 2 H),

8

HRMS (EI): m/z [M + H]⁺calcd for C26

H N O : 417.2178; found:

.87 (s, 1 H), 9.77 (br s, 1 H).

29 2 3

13

417.2182.

C NMR (DMSO-d , 100 MHz):  = 18.6 (CH ), 51.1 (2 × CH ), 66.8 (2 ×

6

2

CH ), 111.9 (C), 118.8 (CH), 119.7 (C), 122.9 (CH), 124.4 (CH), 126.0

2

(

1R*,2R*,3R*)-2-(1,5-Diazabicyclo[3.2.1]octan-8-yl)-1-(3-nitro-

(CH), 128.1 (CH), 128.7 (CH), 129.0 (C), 133.9 (C), 152.2 (C), 159.7

CH), 191.1 (CH).

phenyl)-2,3-dihydro-1H-benzo[f]chromen-3-ol (15b)

(

_H_R_M_S₍_E_I₎_:_m_/_z_[_M₊_H_]+ calcd for C₁₈H₂₀NO : 298.1443; found:

Yield: 315 mg (73%); light-yellow solid; mp 196–197 °C (DMF–

MeOH).

3

298.1439.

IR (ATR): 3088, 2951, 2895, 1624, 1601, 1523, 1464, 1391, 1344, 1323,

1

308, 1263, 1234, 1140, 1111, 1072, 1049, 1001, 949, 889, 829, 785,

tert-Butyl (E)-4-[2-Formyl-3-(2-hydroxynaphthalen-1-yl)prop-1-

en-1-yl]piperazine-1-carboxylate (14b)

−1

752, 698, 679 cm

.

¹H NMR (CDCl

, 400 MHz):  = 1.12 (dt, J = 14.6, 4.3 Hz, 1 H), 1.85–

The title compound was prepared similarly to compound 14a from

3

1

H-benzo[f]chromene-2-carbaldehyde (1m; 210 mg, 1 mmol) and

1.98 (m, 2 H), 2.84–2.95 (m, 3 H), 3.03–3.27 (m, 5 H), 4.13 (d, J = 11.2

Hz, 1 H), 5.07 (s, 1 H), 5.32 (d, J = 1.6 Hz, 1 H), 7.23–7.31 (m, 4 H),

7.34–7.38 (m, 2 H), 7.76–7.80 (m, 2 H), 8.01–8.04 (m, 2 H), 9.66 (br s,

1 H).

tert-butyl piperazine-1-carboxylate (186 mg, 1 mmol) in MeOH (3

mL); yield: 321 mg (81%); colorless solid; mp 171–172 °C (DMF–

MeOH).

¹³C NMR (CDCl

(CH ), 51.0 (CH

(C), 119.3 (CH), 121.8 (CH), 123.2 (CH), 123.4 (CH), 123.8 (CH), 126.9

, 100 MHz):  = 18.4 (CH

), 40.5 (CH), 41.9 (CH), 49.7

2

IR (ATR): 3329, 2903, 2849, 1647, 1593, 1560, 1454, 1369, 1342, 1317,

3

–1

1292, 1244, 1211, 1140, 1105, 1067, 980, 864, 791 cm

.

2

), 55.1 (CH ), 56.2 (CH ), 87.2 (CH), 93.1 (CH), 110.8

2

1

H NMR (DMSO-d , 400 MHz):  = 1.33 (s, 9 H, t-C H ), 2.98 (br s, 4 H,

6

4

9

(

CH), 128.8 (CH), 129.7 (CH), 130.0 (C), 130.1 (CH), 132.5 (C), 134.5

CH), 148.2 (C), 148.8 (C), 152.4 (C).

CH NBoc), 3.34 (br s, 4 H, CH N), 3.96 (s, 2 H, CH ), 6.88 (s, 1 H, =CHN),

2

7

.12 (d, J = 8.9 Hz, 1 H, H-3), 7.16–7.20 (m, 1 H, H-6), 7.23–7.27 (m, 1

H, H-7), 7.59 (d, J = 8.7 Hz, 1 H, H-4), 7.66 (d, J = 8.5 Hz, 1 H, H-5), 7.69

d, J = 7.6 Hz, 1 H, H-8), 8.88 (s, 1 H, CHO), 9.82 (s, 1 H, OH).

HRMS (EI): m/z [M + H]⁺calcd for C25

H N O : 432.1923; found:

26 3 4

(

432.1920.

©

P

Synthesis

V. A. Osyanin et al.

Paper

13

(1R*,2R*,3R*)-2-(1,5-Diazabicyclo[3.2.1]octan-8-yl)-1-(3-nitro-

C NMR (DMSO-d , 100 MHz):  = 22.1 (CH ), 23.8 (CH ), 51.4 (2 ×

6

2

phenyl)-2,3-dihydro-1H-benzo[f]chromen-2-d-3-ol-d (15b-d₂)

CH ), 56.4 (CH ), 63.7 (2 × CH ), 118.2 (C), 118.6 (CH), 122.7 (CH),

2 2 2

1

22.9 (CH), 126.7 (CH), 128.0 (CH), 128.7 (C), 129.0 (CH), 133.5 (C),

53.0 (C).

A suspension of 1-(3-nitrophenyl)-1H-benzo[f]chromene-2-carbal-

dehyde (150 mg, 0.45 mmol) and homopiperazine (75 mg, 0.75

mmol) in a mixture of CD OD (5 mL) and of D O (0.5 mL) was heated

3

2

Anal. Calcd for C₁₇H₂₁NO ·HCl: C, 66.33; H, 7.20; N, 4.55. Found: C,

2

under reflux for 50 min under argon atmosphere. After 40 min, the

solution became homogeneous. The precipitated light-yellow crystals

were collected by filtration and washed with ice-cold MeOH; yield:

66.28; H, 7.17; N, 4.46.

1-(3-Morpholinopropyl)naphthalen-2-ol (16)

0.115 g (59%).

1-(3-Morpholinopropyl)naphthalen-2-ol hydrochloride (200 mg,

1

H NMR (CDCl , 400 MHz):  = 1.09–1.14 (m, 1 H), 1.88–1.96 (m, 1 H),

3

0.65 mmol) was dissolved in MeOH (2 mL), treated with sat. aq NaH-

CO₃(5 mL), and the free base was extracted with CH Cl (3 × 5 mL).

The combined organic layers were washed with H O (5 mL) and brine

2

.84–2.96 (m, 3 H), 3.03–3.28 (m, 5 H), 4.12 (s, 1 H), 5.07 (s, 1 H), 5.31

d, J = 1.1 Hz, 1 H), 7.23–7.30 (m, 4 H), 7.34–7.38 (m, 2 H), 7.76–7.80

m, 2 H), 8.01–8.04 (m, 2 H).

2

(

1

2

(5 mL), dried (anhyd Na SO ), and concentrated; yield: 164 mg (93%);

2 4

3

C NMR (CDCl , 100 MHz):  = 18.4 (CH ), 40.4 (CH), 41.5 (t, J = 18.2

colorless solid; mp 87–88 °C.

3

2

Hz, CD), 49.7 (CH ), 51.0 (CH ), 55.1 (CH ), 56.1 (CH ), 87.1 (CH), 92.9

2

IR (ATR): 3462, 3410, 3287, 3065, 2949, 1558, 1452, 1425, 1352, 1248,

(CH), 110.8 (C), 119.3 (CH), 121.8 (CH), 123.1 (CH), 123.4 (CH), 123.8

(CH), 126.9 (CH), 128.8 (CH), 129.7 (CH), 130.0 (C), 130.1 (CH), 132.5

(C), 134.5 (CH), 148.1 (C), 148.8 (C), 152.4 (C).

1

cm

229, 1163, 1146, 1107, 1053, 1034, 984, 953, 895, 876, 856, 731, 710

–1

.

1

H NMR (CDCl , 400 MHz):  = 2.03–2.09 (m, 2 H), 2.26–2.30 (m, 2 H),

3

2

8

1

.54 (br s, 4 H), 3.12–3.15 (m, 2 H), 3.87 (t, J = 4.5 Hz, 4 H), 7.18 (d, J =

.7 Hz, 1 H), 7.29–7.33 (m, 1 H), 7.44–7.48 (m, 1 H), 7.65 (d, J = 8.7 Hz,

H), 7.77 (d, J = 8.0 Hz, 1 H), 7.85 (d, J = 8.5 Hz, 1 H), 11.18 (br s, 1 H).

(

1R*,2R*,3R*)-2-(1,5-Diazabicyclo[3.2.1]octan-8-yl)-1-phenyl-2,3-

26

dihydro-1H-benzo[f]chromen-3-ol (methanol solvate) (15c)

Yield: 289 mg (69%); colorless solid; mp 131–132 °C (MeOH).

13

C NMR (CDCl , 100 MHz):  = 21.3 (CH ), 24.3 (CH ), 52.8 (2 × CH ),

3

2

IR (ATR): 3400–2800, 1622, 1599, 1466, 1389, 1265, 1233, 1134,

54.5 (CH ), 66.4 (2 × CH ), 117.4 (C), 120.2 (CH), 122.5 (CH), 122.6

(CH), 126.2 (CH), 128.2 (CH), 128.8 (CH), 129.3 (C), 133.5 (C), 154.4

(C).

2

1

109, 1072, 1059, 1030, 1011, 949, 893, 814, 799, 698 cm^–¹

.

1

H NMR (CDCl , 400 MHz):  = 1.09 (dt, J = 14.7, 4.4 Hz, 1 H), 1.41 (br

3

HRMS (EI): m/z [M + H]⁺calcd for C₁₇H₂₂NO : 272.1651; found:

s, 1 H), 1.83–1.94 (m, 1 H), 1.97 (d, J = 11.2 Hz, 1 H), 2.83–2.94 (m, 3

H), 3.00–3.28 (m, 5 H), 3.46 (s, 3 H), 4.12 (d, J = 11.2 Hz, 1 H), 4.95 (s, 1

H), 5.40 (s, 1 H), 7.04 (d, J = 7.3 Hz, 2 H), 7.14 (t, J = 7.2 Hz, 1 H), 7.19–

2

272.1654.

7

.28 (m, 5 H), 7.49 (dd, J = 7.3, 1.8 Hz, 1 H), 7.75 (d, J = 8.2 Hz, 2 H),

2

,3-Dihydro-1H-benzo[f]chromen-3-ol (17)

9.67 (br s, 1 H).

4-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)morpholine (8a; 2.69 g, 10

13

C NMR (CDCl , 100 MHz):  = 18.5 (CH ), 40.7 (CH), 42.0 (CH), 49.7

3

2

mmol) was dissolved in AcOH (27 mL) and H O (13 mL) was added.

The resulting solution was heated under reflux for 30 min. The solu-

tion was cooled to rt, H O (40 mL) was added, and the resulting sus-

pension was kept at 5 °С for 1 h. The formed precipitate was collected

2

(

CH ), 50.88 (CH ), 50.95 (CH ), 55.1 (CH ), 56.1 (CH ), 87.4 (CH), 93.5

CH), 112.4 (C), 119.2 (CH), 123.5 (CH), 124.0 (CH), 126.5 (CH), 126.6

CH), 128.4 (3 × CH), 128.8 (2 × CH), 129.4 (CH), 129.8 (C), 132.9 (C),

2 3 2 2 2

2

145.9 (C), 152.2 (C).

by filtration, washed with H O, and recrystallized from MeOH; yield:

2

Anal. Calcd for C₂₅H₂₆N O ·CH OH: C, 74.61; H, 7.23; N, 6.69. Found: C,

1.62 g (81%); colorless solid; mp 90–92 °C.

2

3

74.55; H, 7.20; N, 6.61.

IR (ATR): 3400–3100, 2935, 1626, 1595, 1514, 1464, 1431, 1418,

1

400, 1350, 1307, 1296, 1263, 1234, 1225, 1174, 1122, 1053, 1024,

–1

1-(3-Morpholinopropyl)naphthalen-2-ol Hydrochloride (16·HCl)

980, 960, 881, 870, 806, 768, 737 cm .

1

To a solution of 4-(2,3-dihydro-1H-benzo[f]chromen-3-yl)morpho-

line (8a; 269 mg, 1 mmol) in anhyd THF (10 mL) was added LiAlH₄

H NMR (CDCl , 400 MHz):  = 2.09–2.24 (m, 2 H), 3.05–3.20 (m, 2 H),

3

3.34 (br s, 1 H), 5.66 (dd, J = 3.9, 2.5 Hz, 1 H), 7.06 (d, J = 8.9 Hz, 1 H),

7.37 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 1 H), 7.64 (d, J = 8.0 Hz, 1 H),

7.77 (d, J = 8.0 Hz, 1 H), 7.84 (d, J = 8.5 Hz, 1 H).

(115 mg, 3 mmol) in one portion. The resulting mixture was stirred at

rt for 2 h, and then quenched with sat. aq NH Cl. The solvent was re-

4

moved under reduced pressure. The residue was extracted with EtOAc

13

C NMR (CDCl , 100 MHz):  = 17.4 (CH ), 27.1 (CH ), 92.1 (CH), 113.9

3

2

(

3 × 10 mL), and the combined organic layers were washed with H O

2

(

C), 119.0 (CH), 122.1 (CH), 123.6 (CH), 126.5 (CH), 128.1 (CH), 128.5

CH), 129.3 (C), 132.8 (C), 149.3 (C).

(

10 mL) and brine (10 mL), and dried (anhyd Na SO ). The solvent was

2

4

again removed under reduced pressure, the residue was treated with

EtOAc (2 mL) saturated with gaseous HCl, and the product was isolat-

ed by filtration; yield: 274 mg (89%); colorless solid; mp 242–243 °C.

HRMS (EI): m/z [M + H]⁺^c^a^l^c^d^f^o^r^C13^H13O : 201.0916; found:

2

201.0918.

IR (ATR): 3163, 2926, 2668, 2558, 2471, 1626, 1605, 1582, 1514, 1477,

–1

3-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-1H-indole (18)

1439, 1358, 1267, 1119, 1094, 970, 818, 741 cm .

To a solution of 17 (269 mg, 1 mmol) and indole (117 mg, 1 mmol) in

1

H NMR (DMSO-d , 400 MHz):  = 1.92–2.02 (m, 2 H), 2.94–3.20 (m, 4

6

CH Cl (4 mL) was added boron trifluoride etherate (1 drop) and the

2

H), 3.15 (t, J = 7.9 Hz, 2 H), 3.28–3.35 (m, 2 H), 3.72–3.88 (m, 4 H),

solution was kept at rt for 6 h. The solvent was distilled off, the resi-

due was purified by column chromatography (silica gel, CH Cl ), and

7

(

1

.21–7.26 (m, 2 H), 7.39–7.43 (m, 1 H), 7.61 (d, J = 8.7 Hz, 1 H), 7.74

d, J = 7.8 Hz, 1 H), 7.88 (d, J = 8.5 Hz, 1 H), 9.81 (br s, 1 H), 11.14 (br s,

H).

2

recrystallized from MeOH; yield: 93 mg (31%); colorless solid; mp

43–145 °C.

IR (ATR): 3410, 3352, 1620, 1597, 1555, 1512, 1458, 1431, 1393, 1346,

1

–1

1

261, 1231, 1211, 1096, 1042, 972, 868, 806, 768, 739 cm .

©

Q

Synthesis

V. A. Osyanin et al.

Paper

1

H NMR (CDCl , 400 MHz):  = 2.41–2.48 (m, 2 H), 3.13–3.16 (m, 2 H),

(E)-1,1,1-Trifluoro-3-[(2-hydroxynaphthalen-1-yl)methyl]-4-

3

5

1

.42 (dd, J = 8.0, 3.7 Hz, 1 H), 6.99 (t, J = 7.6 Hz, 1 H), 7.02 (d, J = 9.0 Hz,

H), 7.08 (t, J = 7.6 Hz, 1 H), 7.33 (t, J = 7.4 Hz, 1 H), 7.37 (d, J = 8.3 Hz,

H), 7.42 (s, 1 H), 7.48 (t, J = 7.7 Hz, 1 H), 7.64–7.68 (m, 2 H), 7.79 (d,

(phenylamino)but-3-en-2-one (20)

A mixture of chromene 1a (278 mg, 1 mmol) and aniline (93 mg, 1

mmol) in MeOH (3 mL) was heated under reflux for 10 min, and kept

at rt for 30 min. The formed precipitate was collected by filtration and

recrystallized from EtOH; yield: 308 mg (83%); colorless solid; mp

175–176 °C.

J = 8.3 Hz, 1 H), 7.83 (d, J = 8.5 Hz, 1 H), 11.09 (s, 1 H).

13

C NMR (CDCl , 100 MHz):  = 21.9 (CH ), 27.8 (CH ), 72.3 (CH), 112.2

3

2

(CH), 114.1 (C), 115.4 (C), 119.3 (CH), 119.6 (CH), 119.8 (CH), 121.8

(CH), 122.5 (CH), 123.7 (CH), 123.8 (CH), 126.4 (C), 127.0 (CH), 128.0

(CH), 128.8 (CH), 129.0 (C), 133.3 (C), 136.9 (C), 153.1 (C).

IR (ATR): 3400–2800, 1655, 1628, 1601, 1558, 1512, 1493, 1450,

1

439, 1404, 1335, 1296, 1265, 1246, 1234, 1188, 1173, 1153, 1126,

HRMS (EI): m/z [M + H]⁺calcd for C₂₁H₁₈NO: 300.1388; found:

00.1390.

–1

1057, 995, 930, 907, 810, 748 cm

.

3

1

H NMR (DMSO-d , 400 MHz):  = 4.12 (s, 2 H, CH ), 7.09 (t, J = 7.6 Hz,

6

2

1

H, H_p_-_P_h), 7.14 (d, J = 7.8 Hz, 2 H, H_o_-_P_h), 7.23–7.27 (m, 2 H, H-3,6),

7.34–7.41 (m, 3 H, H-7, H_m_-_P_h), 7.68 (d, J = 8.9 Hz, 1 H, H-4), 7.74 (d, J =

.0 Hz, 1 H, H-5), 7.95 (d, J = 13.8 Hz, 1 H, =CHN), 7.99 (d, J = 8.9 Hz, 1

H, H-8), 9.99 (d, J = 13.8 Hz, 1 H, NH), 11.21 (s, 1 H, OH).

N-Phenyl-2,3-dihydro-1H-benzo[f]chromen-3-amine (19a)

8

A mixture of 8a (269 mg, 1 mmol) and aniline hydrochloride (130 mg,

1

mmol) in MeOH (5 mL) was stirred under reflux for 10 min and

13

cooled to rt. The formed precipitate was collected by filtration,

washed with MeOH, and recrystallized from EtOH–DMF; yield: 234

mg (85%); colorless solid; mp 151–153 °C.

C NMR (DMSO-d , 100 MHz):  = 19.1 (CH ), 108.8 (C–COCF ), 116.9

6 2 3

1

(2 × CH_o_-_P_h), 117.1 (C-1), 117.9 (CH-3), 118.6 (q, J = 290.8 Hz, CF₃),

C,F

123.5 (CH-6), 124.0 (CH-8), 124.9 (CH_p_-_P_h), 127.0 (CH-7), 128.97 (CH-

5

), 129.05 (CH-4), 129.4 (C-4a), 130.5 (2 × CH

), 133.9 (C-8a), 139.9

IR (ATR): 3393, 1620, 1595, 1510, 1466, 1433, 1391, 1304, 1261, 1221,

m-Ph

4

2

(^CPh), 146.7 (q, J = 3.8 Hz, CHN), 151.3 (C-2), 176.0 (q, J = 30.5 Hz,

1

209, 1179, 1157, 1140, 1117, 1069, 1042, 966, 858, 824, 743, 689

C,F

–1

C=O).

cm

1

.

HRMS (EI): m/z [M + H]⁺calcd for C₂₁H₁₇F NO : 372.1211; found:

H NMR (DMSO-d , 400 MHz):  = 2.10–2.18 (m, 1 H), 2.21–2.31 (m, 1

3

2

6

372.1201.

H), 3.06–3.28 (m, 2 H), 5.49–5.56 (m, 1 H), 6.63–6.63 (m, 1 H), 6.74 (d,

J = 8.7 Hz, 1 H), 6.83 (d, J = 8.0 Hz, 2 H), 6.94 (d, J = 8.9 Hz, 1 H), 7.12 (t,

J = 7.8 Hz, 2 H), 7.30–7.33 (m, 1 H), 7.46–7.50 (m, 1 H), 7.62 (d, J = 8.9

Hz, 1 H), 7.77 (d, J = 8.0 Hz, 1 H), 7.81 (d, J = 8.5 Hz, 1 H).

Funding Information

13

C NMR (DMSO-d , 100 MHz):  = 20.4 (CH ), 27.0 (CH ), 80.8 (CH),

6

2

The work was supported by Russian Science Foundation (Grant No.

1

(

1

13.9 (C), 114.0 (2 × CH), 118.1 (CH), 119.7 (CH), 122.5 (CH), 123.7

CH), 126.9 (CH), 128.1 (CH), 128.7 (CH), 129.0 (C), 129.5 (2 × CH),

33.1 (C), 146.8 (C), 151.5 (C).

HRMS (EI): m/z [M + H]⁺calcd for C₁₉H₁₈NO: 276.1388; found:

19-13-00421).

R

u

si

a

n

S

c

i

e

n

c

e

F

o

u

n

d

ati

o

n

(19-13-0

0

4

2

1)

Acknowledgment

276.1392.

We thank Dr. V. B. Rybakov (Moscow State University) for the X-ray

diffraction analysis, which was fulfilled using a STOE STADI VARI PIL-

ATUS-100K diffractometer purchased by MSU Development Program.

1

-(2,3-Dihydro-1H-benzo[f]chromen-3-yl)-1,2,3,4-tetrahydro-

quinoline (19b)

A mixture of 8a (269 mg, 1 mmol) and 1,2,3,4-tetrahydroquinoline

hydrochloride (170 mg, 1 mmol) in MeOH (5 mL) was stirred under

reflux for 10 min and cooled to rt. The formed precipitate was collect-

ed by filtration, washed with MeOH, and recrystallized from EtOAc;

yield: 280 mg (89%); colorless solid; mp 154–156 °C.

Supporting Information

Supporting information for this article is available online at

https://doi.org/10.1055/s-0040-1707209.

S

u

p

orti

n

g Inform ati

o

n

S

u

p

orti

n

g Inform ati

o

n

IR (ATR): 1620, 1597, 1574, 1497, 1464, 1395, 1344, 1302, 1288, 1258,

1

229, 1211, 1190, 1063, 1034, 1024, 968, 895, 856, 843, 818, 756, 745

–1

cm

1

.

References

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The

Cambridge

Crystallographic

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Centre

via

www.ccdc.cam.ac.uk/getstructures.

1

&

©

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Catalyst-Free Synthesis of Chromane-Type N,O-Acetals via Intramolecular Addition of Phenols to Enamines

DOI: 10.1055/s-0040-1707209

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Full text of DOI:10.1055/s-0040-1707209

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