The Vilsmeier-Haack formylation of 2,3-dihydro-4H-1,3-benzoxazin-4-ones and isomeric 1,2-dihydro-4H-3,1-benzoxazin-4-ones: An effective approach to functionalized 2H-/4H-chromenes and tetrahydroacridines

Article abstract of DOI:10.1016/j.tet.2015.06.069

We found that 1,3- and isomeric 3,1-benzoxazin-4-ones react with the Vilsmeier reagent in vastly different ways. Thus, either 2H- or 4H-chromenes were obtained in good yields when 1,3-benzoxazin-4-ones were reacted at 75-80 °C, while the formylation of 3,1-benzoxazines at ambient temperature leads to acridine-9-one or 9-chloroacridine derivatives, depending on the amount of Vilsmeier reagent and the nature of substrate.

Full text of DOI:10.1016/j.tet.2015.06.069

Accepted Manuscript
The Vilsmeier-Haack formylation of 2,3-dihydro-4H-1,3-benzoxazin-4-ones
and isomeric 1,2-dihydro-4H-3,1-benzoxazin-4-ones: an effective approach to
functionalized 2H-/4H-Chromenes and Tetrahydroacridines
Oleg К. Farat, Victor I. Markov, Svetlana А. Varenichenko, Victor V. Dotsenko,
Alexander V. Mazepa
PII:
S0040-4020(15)00966-7
10.1016/j.tet.2015.06.069
TET 26905
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 April 2015
Revised Date: 3 June 2015
Accepted Date: 16 June 2015
Please cite this article as: Farat OК, Markov VI, Varenichenko SА, Dotsenko VV, Mazepa AV,
The Vilsmeier-Haack formylation of 2,3-dihydro-4H-1,3-benzoxazin-4-ones and isomeric 1,2-
dihydro-4H-3,1-benzoxazin-4-ones: an effective approach to functionalized 2H-/4H-Chromenes and
Tetrahydroacridines, Tetrahedron (2015), doi: 10.1016/j.tet.2015.06.069.
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ACCEPTED MANUSCRIPT
Graphical Abstract
The Vilsmeier-Haack formylation of 2,3-
dihydro-4H-1,3-benzoxazin-4-ones and
isomeric 1,2-dihydro-4H-3,1-benzoxazin-4-
ones: an effective approach to functionalized
2H-/4H-Chromenes and Tetrahydroacridines
Leave this area blank for abstract info.
Oleg К. Farat , Victor I. Markov, Svetlana А. Varenichenko, Victor V. Dotsenko and Alexander V. Mazepa
-
ClO4
CH3
H2
N+
R
R
R
CHO
( C
)
n
CH3
H2O, NaOH
O
O
O
O
1. POCl3, DMF
2. H2O, NaClO4
NH
(
(
)n
C
H2
)
H2
n
C
R
R
R
N
N
NMe2
NMe2

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
The Vilsmeier-Haack formylation of 2,3-dihydro-4H-1,3-benzoxazin-4-ones and
isomeric 1,2-dihydro-4H-3,1-benzoxazin-4-ones: an effective approach to
functionalized 2H-/4H-Chromenes and Tetrahydroacridines
Oleg К. Farata,b , Victor I. Markova, Svetlana А. Varenichenkoa, Victor V. Dotsenkoc and Alexander V.
Mazepad
aUkrainian State University of Chemical Technology, 49005 Dnepropetrovsk, Ukraine
bDepartment of Chemistry, M. V. Lomonosov Moscow State University, 119991Moscow, Russian Federation
cKuban State University, 350040 Krasnodar, Russian Federation
dA. V. Bogatsky Physico-Chemical Institute, 65080 Odessa, Ukraine
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We found that 1,3- and isomeric 3,1-benzoxazin-4-ones react with the Vilsmeier reagent in
vastly different ways. Thus, either 2H- or 4H-chromenes were obtained in good yields when 1,3-
benzoxazin-4-ones were reacted at 75–80 ˚С, while the formylation of 3,1-benzoxazines at
ambient temperature leads to acridine-9-one or 9-chloroacridine derivatives, depending on the
amount of Vilsmeier reagent and the nature of substrate.
Available online
2015 Elsevier Ltd. All rights reserved
.
Keywords:
Vilsmeier reagent
Rearrangement
Chromene derivatives
Tetrahydroacridine
1. Introduction
These results prompted us to examine the behavior of other
heminal 1,3-diheteroatomic systems under the same conditions.
Here we wish to report the results of the formylation of
benzoxazine derivatives.
The Vilsmeier-Haack reaction is a powerful tool in modern
synthesis and is widely used not only to introduce the CHO
group into activated aromatic and heteroaromatic substrates, but
also as an approach for various condensations and cyclizations
(for reviews on the Vilsmeier-Haack reaction see1–6).
2. Results and discussion
The Vilsmeier reagent was obtained by the classical method
with a molar ratio DMF : POCl3 3:1, then 0.5 mol of the
corresponding benzoxazine was added and the mixture was
maintained at 75–80 °С for 1 h (for compounds 4a–d) or 4 h (for
4e,f). When the mixture was neutralized by addition of aqueous
NaOH immediately thereafter, as recommended by the classical
Vilsmeier-Haack conditions, the yields were very poor and the
isolation of products was very difficult due to tar formation.
Therefore we had to use another work up procedure and we
succeeded by using a sodium perchlorate solution. Thus, the
reaction mixture was left to cool and treated with an excess of
ice-cold aqueous NaClO4, whereupon the solids of 5a–f
precipitated. The compounds 5a–f could be easily hydrolyzed by
aqueous alkali in DMF to form xanthene-type compounds 6a–f.
It should be noted that products 5a–d were also obtained by
The chemistry of the Vilsmeier reagent has attracted
increasing interest during the past few decades: the great interest
in this chemistry is supported by the significant increase in the
number of publications (for recent examples see7–10).
Recently, we have reported the unexpected reaction of
spirocyclic pyrimidine 1 with the Vilsmeier reagent that was
accompanied by a deep-seated rearrangement of the carbon
skeleton to give substituted acridines 2 and 3 (Scheme 1).11
H
CN
N
POCl3, DMF
+
NH
room temp., 5 days
N
N
H
O
CN
CHO
CHO
1
2 (42%)
3 (10%)
Scheme 1. Synthesis of substituted acridines.
———
Corresponding author. Tel.: +380562-47-46-70; fax: +380562-47-33-16; e-mail: faratok@mail.ru

2
Tetrahedron
H15…O2i [i: 1-x,-y,-z] (H…O 2.29 Å, C-H…O 173°). These
maintaining the substrates 4a–d with the Vilsmeier reagent at
ACCEPTED MANUSCRIPT
dimers are additionally stabilized by hydrogen bonds C-H…π :
room temperature for 24 h (Scheme 2).
C9-H9b…C7i (H…C 2.85 Å, C-H…C 144°) and C11-
-
H11b…C14i (H…C 2.85 Å, C-H…C 147°).
ClO4
CH3
N+
H2
R
R
( C
)
n
We found that benzoxazine 7 reacts in the same way and
under Vilsmeier-Haack conditions undergoes the rearrangement
to form (after hydrolysis) benzopyran 9. The structure of the
intermediate salt 8 can be best described by several resonance
structures with an assumption that the pyrilium salt is probably
the most contributing one (Scheme 3).
CH3
H2O, NaOH
O
O
O
1. POCl3, DMF
2. H2O, NaClO4
NH
(
)
H2
n
C
R
R
N
4a-f
5a-f
NMe2
R
CHO
O
(
)
H2
n
CH3
NH
C
O
6a-f
R
O
O
1. POCl3, DMF
2. H2O, NaClO4
N
NMe2
N
-
N+
ClO4
CH3
7
Scheme 2. Synthesis of xanthene-type compounds.
H3C
Table 1. The yields of compounds 4, 5 and 6.
8 (67%)
Compound
R
n
2
1
2
1
2
1
2
1
2
Yield %
92*
69*
80
Compound
R
n
1
2
1
2
1
2
1
2
1
Yield %
87
O+
O
H2O, NaOH
4a
4b
4c
4d
4e
4f
H
5d
5e
5f
i-Pr
I
H
54**
57**
85
N
NH
9 (78%)
-
i-Pr
i-Pr
I
I
ClO4
N
H3C
CH3
73
6a
6b
6c
6d
6e
6f
H
H
i-Pr
i-Pr
I
Scheme 3. Synthesis of benzopyran derivatives.
66
83
I
68
90
As we suggested, 2,2-dimethylbenzoxazines 10a,b react
further with the Vilsmeier reagent to afford dialdehydes 12a,b
5a
5b
5c
H
96
85
(Scheme 4).
H
80
85
-
CH3
N+ CH3
ClO4
-
i-Pr
95
I
80
ClO4
H2O, NaOH
R
R
N+
CH3
CH3
CH3
CH3
*Ref.:16
O
O
O
1. POCl3, DMF
2. H2O, NaClO4
**crude product
NH
R
R
11a R=H (90%)
11b R=i-Pr (85%)
N
The compounds were characterized by FTIR and mass
spectrometry, multinuclear NMR spectroscopy, and elemental
analysis. Finally, the structure of the compound 6a was
confirmed by a single crystal X-ray diffraction analysis (Fig. 1).
10a R=H (80%)
NMe2
10b R=i-Pr (70%)
R
O
CHO
CHO
12a R=H (80%)
12b R=i-Pr (84%)
R
NH2
Scheme 4. Synthesis of substituted benzopyrans.
Compounds 12a and b were characterized by spectroscopic
data, the structure of the compound 12a was confirmed by a
single crystal X-ray diffraction analysis (Fig. 2). The compound
12a is the hydrate 2:1. The independent part of the unit cell of
12a contained two molecules (A and B) with very close
geometrical parameters and a molecule of water.
All the non-hydrogen atoms in the molecule of 12a lie in the
same plane with RMSD less than 0.03 Å. The aldehyde groups
oriented so to form the intramolecular hydrogen bonds С8-
Н8…О3 (H…O 2.26-2.27 Å, C-H…O 125°) and attractive
contacts С11-H11…O1 (H…O 2.31-2.33 Å). The latter cannot
be considered to be hydrogen bonds due to the small angle С-
Н…О of 103°. The analysis of the bond lengths shows a
significant redistribution of the electron density in the molecule
from the amino group to the =C(CHO)2 moiety through the
conjugated π bond system.
Thus, the C=O bonds are longer (1.226(3)-1.241(3) Å) than
standard C=O double bond distances in aldehydes (1.192 Å),
while С9-N1 bonds are slightly shortened to 1.316(3)-1.320(3) Å
in comparison with the average distance of C(sp2)-NH2 bond of
1.336 Å.13 In addition, the formal single bond С7-С8 (1.360(3)-
1.364(3) Å) is even shorter than formal double bonds С8-С9 of
1.397(3)-1.400(3) Å and С7-С10 of 1.426(3)-1.429(3) Å. Such a
Fig.1. X-ray structure of 6a (50% probability thermal ellipsoids).
The cyclohexene ring has a sofa conformation. The atom С10
deviates by 0.628(3) Å from the plane of the other ring atoms.
The latter, in turn, lie in the same plane as the dihydropyran and
benzene rings (root mean square deviation of the atoms from the
plane is 0.017 Å). The dimethylamidine substituent is heavily
twisted by 119.0(2)° (C15-N1-C13-C1) with respect to the plane,
while the formyl substituent is essentially in the plane to form a
dihedral angle C9-C8-C14-O2 of 1.1(3)°. The orientation of
CHO is additionally stabilized by intramolecular attractive
shortened interaction O1…H14 (2.36 Å, the van der Waals sum
is 2.46 Å).12 In the crystal structure, the molecules 6a are paired
into centrosymmetric dimers linked by hydrogen bonds С15-

3
redistribution of the electron density in the crystal is stabilized by
Scheme 7. Proposed mechanism of the new rearrangement.
ACCEPTED MANUSCRIPT
a network of intermolecular hydrogen bonds N1A-H1AA...O3Bi
[i: 1/2+x,1/2-y,-1/2+z] (H...O 2.01 Å, N-H...O 166°), N1A-
H1AB...O2Bii [ii: 3/2-x,1/2+y,1/2-z] (H...O 2.10 Å, N-H...O
160°), N1B-H1BA...O3Aiii [iii: 1/2+x,1/2-y,1/2+z] (H...O 2.01 Å,
N-H...O 159°), N1B-H1BB...O1Wiv [iv: 1/2-x,-1/2+y,1/2-z]
(H...O 2.15 Å, N-H...O 152°), O1W-H1WA...O2B (H...O 2.04 Å,
O-H...O 172°) и O1W-H1WB...O2Aiii [iii: 1/2+x,1/2-y,1/2+z]
(H...O 2.00 Å, O-H...O 166°). In the crystal structure, the
molecules 12a are linked through hydrogen bonds into tetramers;
the latter consist of two pairs of A & B molecules, and are
bonded together in a three-dimensional structure by hydrogen
bonds with molecules of water.
It was found that the reaction of benzoxazine 15 with a three-
fold excess of Vilsmeier reagent at room temperature for 1 h
leads to formation of 9-chloroacridine 16 in quantitative yield.
Meanwhile,
tetrahydroacridine-9-one
17
was
isolated
quantitatively when the same reaction was conducted with 1 eq.
of Vilsmeier reagent for 0.5 h. The compound 17 could be
quantitatively converted into chloride 16 by reaction with a two-
fold excess of Vilsmeier reagent for 0.5 h.
The physical data of the compounds 16 and 17 appeared to be
identical to that previously described in the literature.14,15
According to LC–MS data, the purity of compound 16 was
96.3% prior to recrystallization. It is noteworthy that in all cases
the isolation of products is very straightforward, and the isolation
of acridines 16 and 17 is easily accomplished by simple filtration
(Scheme 8).
H
N
O
3 fold excess of
POCl3, DMF
POCl3, DMF
r.t., 1/2 h
O
15
r.t., 1 h
H
N
2 fold excess of
POCl3, DMF
N
Fig. 2. X-ray structure of 12a (50% probability thermal ellipsoids).
r.t., 1/2 h
The structure of compounds 12 is best described by resonance
structures shown below, from X-ray and Н NMR data (Scheme
1
Cl
O
16 (~100%)
17 (~100%)
5).
Scheme 8. Synthesis of acridines derivatives.
O
R
CHO
CHO
R
In contrast to benzo analog 4, hexahydro-4H-1,3-benzoxazin-
4-one 18 failed to give xanthene derivatives. The perchlorate 19
was instead prepared in 67% yield by addition of the Vilsmeier
reagent to compound 18 (room temperature, 0.5 h) followed by
treatment with an aqueous NaClO4 solution. The salt 19 has been
found to be easily hydrolyzed by alkaline solution to form stable
enamine 20 (Scheme 9).
O
O
CHO
R
12a R=H
12b R=i-Pr
R
NH+2
NH2
Scheme 5. Resonance structures of substituted benzopyrans.
CH3
-
Next, we found that compound 13 does not undergo
recyclization even if maintained with Vilsmeier reagent at 75–80
°С for a couple of hours. Instead, the N-formylation occurs and
imide 14 was isolated as the sole product. Under mild conditions,
it could be easily hydrolyzed to form the starting benzoxazine 13
(Scheme 6).
N+
ClO4
H3C
1. POCl3, DMF
O
O
O
H2O, NaOH
NH
19 (67%)
NH
18
2. H2O, NaClO4
Cl
CH3
N
H3C
O
CH3
O
CH3
POCl3, DMF
O
N
NH
CHO
20 (87%)
N
O
O
H2O
Cl
14 (90%)
13 (95%)
Scheme 9. Synthesis of functionalized enamine.
Scheme 6. Synthesis of imide and his hydrolyze.
The structures of the synthesized compounds were confirmed
by means of spectroscopic data, and the compound 19 was
studied by single crystal X-ray diffraction analysis (Fig. 3).
Compound 19 is the salt consisting of an organic cation and
perchlorate anion. The independent part of the unit cell of 19
contained two cations (molecules A and B) with very close
Based on these data, we suggest the following mechanism of
the new rearrangement (Scheme 7).
O
O
+
O
POCl3
NH+
Cl2PO2
NH
4a
Cl
-
-
Cl2PO2
–
Cl
O
O
NH
geometrical parameters and three ClO4 ions, two of which are
located on a second-order axis. Tetrahydrooxazine ring has a
distorted sofa conformation with a flattened N1-C1-C2-C3-O1
fragment (root mean square deviation of the atoms from the plane
is 0.048 and 0.054 Å for molecules А & В, respectively) with С4
atom deviation of 0.610(5) Å (molecule А) and 0.594(5) Å
(molecule В) from the plane.
O
O+
-HCl
-HOPOCl2
Cl
Cl
-
Cl2PO2
NH
POCl3, DMF
NH
NH
O+
O
O
The cyclohexene ring has a sofa conformation with С8 atom
deviation of 0.688(5) Å (molecule А), or 0.691(5) Å (molecule
В) from the plane of other ring atoms. The positive charge is
localized on the nitrogen N2 atom, as indicated by N2-C14 bond
lengths of 1.306(5) Å (molecule A) and 1.303(5) Å (molecule B),
-HCl
Me2N+
Me2N
N
N
Cl
Me2N
1. POCl3, DMF
NaClO , H O
N
Cl
NaOH, H2O
2.
4
2
6a
5a

4
Tetrahedron
ACCEPTED MANUSCRIPT
which values are close to the average N=C double bond
3.1 Synthesis of Spirans 4a-f (General method). A mixture of
distance of 1.28 Å.13 The cis-orientation of the С14-N2 bond with
respect to С8-С7 leads to a steric repulsion between the methyl
С16 group and the methylene С7 fragment. It is evidenced by the
shortened intramolecular contact H7B…C16 2.67 Å (molecule
A) and 2.69 Å (molecule B) (the van der Waals sum is 2.87 Å),12
the increase of the valence angles C16-N2-C14 126.4(4)° (A),
126.2(3)° (B) and C14-C8-C7 124.6(4)° (A), 123.8(4)° (B) in
comparison with С15-N2-C14 120.1(4)° (A), 121.2(3)° (B) and
C14-C8-C3 116.6(4)° (A), 117.3(4)° (В), respectively. A small
twist along the С8-С14 bond (the dihedral torsion angles С7-С8-
С14-N2 are of 19.8(7)° (А) and -18.6(7)° (В)) also lends support
to the view of a steric repulsion. In the crystal structure, the
the corresponding salicylamide (0.10 mol), ketone (0.12 mol) and
p-TsOH × H2O (0.05 mol) in toluene (70 mL) was refluxed for 8
h with continuous removal of water with a Dean–Stark trap. In
the case of spirans 4a,b, the mixture was cooled to 10 °C and
stirred for 1 h at the same temperature. The resulting crystals
were collected, washed with toluene (10 mL) and i-PrOH (10
mL) and dried at 50 °C. In all other cases, a solvent was
evaporated to dryness under reduced pressure, the solid residue
was washed with 5% aq. NaOH solution and filtered off.
3.1.1. 6,8-Diisopropylspiro[1,3-benzoxazine-2,1'-cyclohexan]-
4(3H)-one (4c). 80%, white powder, mp 165–167 °C (aq.
MeOH); [Found: C, 75.86; H, 9.15; N, 4.69. C19H27NO2 requires
C, 75.71; H, 9.03; N, 4.65%]; νmax(KBr) 3184 (N–H), 3066
(aromatic C–H), 2965–2862 (aliphatic C–H), 1674 (C=O) cm-1;
δH (400 MHz, DMSO-d6/CCl4) 8.43 (1Н, s, NH), 7.41 (1Н, s, Н-
5 Ar), 7.17 (1Н, s, Н-7 Ar), 3.22–3.31 (1Н, m, CH(CH3)2), 2.79–
2.88 (1Н, m, CH(CH3)2), 1.95–2.07 (2Н, m, spiro-ring), 1.50–
1.70 (7Н, m, spiro-ring), 1.25–1.32 (1Н, m, spiro-ring), 1.21
(12H, d, J 6.1 Hz, 2CH(CH3)2); δC (100 MHz, DMSO-d6/CCl4)
161.4 (С=О), 140.6, 149.9, 128.6 (СH-7), 135.5, 121.4 (СH-5),
117.1, 86.9 (С-2), 35.4 (2СН2), 32.9 (CH(CH3)2), 25.8
(CH(CH3)2), 23.9 (2СН2), 23.8 (CH(CH3)2), 22.6 (CH(CH3)2),
21.6 (СН2); δC DEPT-135 (100 MHz, DMSO-d6/CCl4) 128.3
(СH-7), 121.1 (СH-5), 35.1* (2СН2), 32.5 (CH(CH3)2), 25.5
(CH(CH3)2), 23.9* (2СН2), 23.5 (CH(CH3)2), 22.3 (CH(CH3)2),
21.3* (СН2), *signals in antiphase; m/z (EI) 301 (9 M+), 205 (20),
189 (5), 176 (7), 161 (5), 97 (100), 41 (7%).
–
cations and СlO4 anions are linked by intermolecular hydrogen
bonds N1A-H1A…O3i [i: 1/2-x,1/2+y,1/2-z] (H…O 2.06 Å, N-
H…O 156°) and N1B-H1B…O2i (H…O 2.03 Å, N-H…O 169°).
3.1.2. 6,8-Diisopropylspiro[1,3-benzoxazine-2,1'-cyclopentan]-
4(3H)-one (4d). 73%, white powder, mp 137–140 °C (aq.
MeOH); [Found: C, 75.37; H, 8.83; N, 4.91. C18H25NO2 requires
C, 75.22; H, 8.77; N, 4.87%]; νmax(KBr) 3183 (N–H), 3066
(aromatic C–H), 2958–2871 (aliphatic C–H), 1669 (C=O) cm-1;
δH (400 MHz, DMSO-d6/CCl4) 8.54 (1Н, s, NH), 7.41 (1Н, s, Н-
5 Ar), 7.13 (1Н, s, Н-7 Ar), 3.11–3.23 (1Н, m, CH(CH3)2), 2.77–
2.91 (1Н, m, CH(CH3)2), 2.03–2.13 (2Н, m, spiro-ring), 1.72–
1.88 (6Н, m, spiro-ring), 1.22 (6H, d, J 6.1 Hz, CH(CH3)2), 1.19
(6H, d, J 6.1 Hz, CH(CH3)2); δC (100 MHz, DMSO-d6/CCl4)
161.9 (С=О), 150.9, 140.6, 135.6, 128.4 (СH-7), 121.5 (СH-5),
117.4, 96.7 (С-2), 37.9 (2СН2), 32.9 (CH(CH3)2), 26.4
(CH(CH3)2), 23.8 (CH(CH3)2), 22.3 (CH(CH3)2), 22.2 (2СН2); δC
DEPT-135 (100 MHz, DMSO-d6/CCl4) 128.0 (СH-7), 121.1
(СH-5), 36.9* (2СН2), 32.4 (CH(CH3)2), 26.0 (CH(CH3)2), 23.3
(CH(CH3)2), 21.9 (CH(CH3)2), 21.8* (2СН2), *signals in
antiphase; m/z (EI) 287 (8 M+), 205 (29), 189 (6), 176 (10), 161
(9), 83 (100), 41 (10%).
Fig. 3. X-ray structure of 19 (50% probability thermal ellipsoids).
In the summary, we have found that 1,3-benzoxazin-4-ones
react with Vilsmeier reagent to form chromene derivatives, while
the Vilsmeier-Haack reaction with isomeric 3,1-benzoxazin-4-
ones leads to partially hydrogenated acridines in quantitative
yields. The obtained compounds are highly functionalized and
could serve as low-molecular-weight building blocks for organic
synthesis.
3. Experimental section
1
The H NMR and 13C NMR spectra were performed on a
Bruker Avance II 400 instrument (400,13 MHz and 100,62 MHz
for H and 13C respectively) in DMSO-d6, DMSO-d6/CCl4 or
1
DMSO-d6/CF3CO2D with Me4Si as internal standard. The FTIR
spectra were recorded in KBr pellets using a Spectrum one
(PerkinElmer) FT-IR Spectrometer. The mass spectra of
compounds 4c–f, 10b, 6a,c–f, 12b, 14 and 20 were recorded on a
MX1321 instrument with direct injection of the sample at an
ionization chamber temperature of 200 °C and with 70 eV
ionizing electrons. The FAB spectra of compounds were recorded
on a VG7070 spectrometer. Desorption of the ions from the
solution of the samples in meta-nitrobenzyl alcohol was realized
with a beam of argon atoms with energy 8 keV. Chromatographic
analysis of compound 16 was realized on an Agilent 1100 liquid
chromatograph with DAD and ELSD Sedex 75 detectors in
conjunction with an LC-MS VL spectrometer with electrospray
ionization. Elemental analysis was performed on a LECO CHNS-
900 instrument. The reactions and the purity of the obtained
compounds were monitored by TLC on Merck Silicagel 60 F-254
plates with 10:1 CHCl3–i-PrOH as eluent.
3.1.3. 6,8-Diiodospiro[1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-
one (4e). 66%, white powder, mp 235–237 °C (aq. DMF);
[Found: C, 33.40; H, 2.84; N, 3.06. C13H13I2NO2 requires C,
33.29; H, 2.79; N, 2.99%]; νmax(KBr) 3153 (N–H), 3070
(aromatic C–H), 2936–2850 (aliphatic C–H), 1689 (C=O) cm-1;
δH (400 MHz, DMSO-d6) 8.90 (1Н, s, NH), 8.19 (1Н, s, Н-5 Ar),
7.92 (1Н, s, Н-7 Ar), 1.79–2.08 (2Н, m, spiro-ring), 1.42–1.75
(7Н, m, spiro-ring), 1.12–1.28 (1Н, m, spiro-ring); δC (100 MHz,
DMSO-d6) 159.0 (С=О), 154.1, 149.4, 135.2, 119.8, 89.1 (С-2),
87.6 (C-I), 85.5 (C-I), 35.4 (2СН2), 24.1 (2СН2), 21.5 (СН2); m/z
(EI) 469 (55 M+), 373 (24), 245 (14), 97 (100%).
3.1.4. 6,8-Diiodospiro[1,3-benzoxazine-2,1'-cyclopentan]-4(3H)-
one (4f). 68%, white powder, mp 195–198 °C (aq. DMF);
[Found: C, 31.79; H, 2.49; N, 3.14. C13H13I2NO2 requires C,
31.67; H, 2.44; N, 3.08%]; νmax(KBr) 3177 (N–H), 3062
(aromatic C–H), 2971–2878 (aliphatic C–H), 1668 (C=O) cm-1;
δH (400 MHz, DMSO-d6) 9.02 (1Н, s, NH), 8.20 (1Н, s, Н-5 Ar),
Compounds 4a–f were synthesized by the method described
in literature.16 Compounds 7,17 1518 and 1819 were obtained by the
known procedures.

5
7.93 (1Н, s, Н-7 Ar), 1.95–2.10 (2Н, m, spiro-ring), 1.65–1.88
20.6; m/z (FAB) 310 (100 M+), 265 (6), 218 (11), 149 (33), 136
(35), 121 (12), 107 (24), 89 (19), 76 (27), 68 (21), 52 (29%).
ACCEPTED MANUSCRIPT
(6Н, m, spiro-ring); δC (100 MHz, DMSO-d6) 159.6 (С=О),
154.8, 149.3, 135.3, 119.9, 94.4 (С-2), 87.9 (C-I), 85.8 (C-I),
37.1 (2СН2), 22.1 (2СН2); m/z (EI) 455 (29 M+), 373 (17), 245
(5), 83 (100%).
3.3.2.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-1,2-
dihydrocyclopenta[b]chromen-3-yl)methylene]-N-
methylmethanaminium perchlorate (5b). 80%, red needles, mp
262–265 °C (DMF); νmax(KBr) 2964–2862 (aliphatic C–H),
1674, 1623 cm-1; δH (400 MHz, DMSO-d6) 8.45 (1Н, s, N=CH–
N(CH3)2), 8.01–8.11 (1Н, m, H Ar), 7.97 (1Н, s, СН=N+(CH3)2),
7.61–7.71 (1Н, m, H Ar), 7.39–7.56 (2Н, m, H Ar), 3.35 (6Н, s,
СН=N+(CH3)2), 3.23 (3Н, s, N=CH–N(CH3)CH3), 3.21 (3Н, s,
N=CH–N(CH3)CH3), 3.07 (4Н, s, 2СН2); δC (100 MHz, DMSO-
d6) 172.8, 157.2, 153.1, 150.6, 144.0, 132.0, 125.6, 125.0, 121.4,
116.5, 114.1, 102.6, 41.0, 34.8, 25.1, 24.9; m/z (FAB) 296 (100
M+), 137 (14), 107 (7), 91 (10), 80 (7), 53 (10%).
3.2. Synthesis of oxazines 10a,b and 13 (General method).
Concentrated H2SO4 (1 mL) was added to glacial acetic acid (3
mL), and the solution formed was cooled on ice. A solution of
corresponding salicylamide (0.01 mol), acetone or acetaldehyde
(0.01 mol), and Ac2O (1 mL) in glacial acetic acid (3 mL) was
prepared separately. To the mixture obtained, the above ice-cold
solution of H2SO4 and AcOH was added gradually with stirring
on an ice bath. The resulted mixture was stirred for 40 min and
left to stay overnight at room temperature, then pH was adjusted
to ~7.0 with aq. Na2CO3 solution. The precipitate formed was
filtered off and recrystallized from aqueous MeOH.
3.3.3.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-
Yield of compound 10a was 80%, mp 137–138 °C (Ref.16: 136–
138 °C).
diisopropyl-2,3-dihydro-1H-xanthen-4-yl)methylene]-N-
methylmethanaminium perchlorate (5c). 95%, orange-red
powder, mp 215–217 °C. νmax(KBr) 2927 (aliphatic C–H), 1702,
1611 cm-1; δH (400 MHz, DMSO-d6) 8.17 (1Н, s, N=CH–
N(CH3)2), 8.13 (1Н, s, СН=N+(CH3)2), 7.47 (2Н, s, H-5,7 Ar),
3.53–3.59 (1Н, m, CH(CH3)2), 3.46 (6Н, s, СН=N+(CH3)2),
3.22 (3Н, s, N=CH–N(CH3)CH3), 3.19 (3Н, s, N=CH–
N(CH3)CH3), 2.95–3.05 (1Н, m, CH(CH3)2), 2.77–2.82 (2Н, m,
3-СН2 or 1-СН2), 2.63–2.68 (2Н, m, 1-СН2 or 3-СН2), 1.65–1.75
(2Н, m, 2-СН2), 1.30 (6H, d, J 6.8 Hz, CH(CH3)2), 1.23 (6H, d, J
6.8, CH(CH3)2); δC (100 MHz, DMSO-d6) 172.2, 165.8, 156.0,
148.3, 148.1, 145.2, 135.5, 130.5, 127.8, 119.5, 110.7, 101.2,
41.5, 35.4, 33.2, 26.4, 24.6, 24.1, 24.0, 22.3, 21.0; m/z (FAB) 394
(100 M+), 378 (5), 349 (6%).
Yield of compound 13 was 98%, mp 150–152 °C (Ref.20: 143–
147 °C).
3.2.1.
6,8-Diisopropyl-2,2-dimethyl-2,3-dihydro-4H-1,3-
benzoxazin-4-one (10b). 70%, white powder, mp 145–147 °C
(aq. MeOH); [Found: C, 73.42; H, 8.82; N, 5.30. C16H23NO2
requires C, 73.53; H, 8.87; N, 5.36%]; νmax(KBr) 3183 (N–H),
3066 (aromatic C–H), 2962–2871 (aliphatic C–H), 1674 (C=O)
cm-1; δH (400 MHz, DMSO-d6) 8.57 (1Н, s, NH), 7.45 (1Н, s, Н-
5 Ar), 7.24 (1Н, s, Н-7 Ar), 3.01–3.15 (1Н, m, CH(CH3)2), 2.78–
2.89 (1Н, m, CH(CH3)2), 1.49 (6Н, s, 2CH3), 1.13–1.19 (12H, m,
2CH(CH3)2); δC (100 MHz, DMSO-d6) 161.5 (С=О), 150.7,
140.9, 135.7, 129.2, 121.3, 116.7, 86.7 (С-2), 32.8, 27.2, 27.1,
23.9, 22.3; m/z (EI) 261 (74 M+), 246 (12), 205 (96), 189 (43),
176 (100), 161 (75), 91 (10), 58 (26), 41 (11%).
3.3.4.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-
diisopropyl-1,2-dihydrocyclopenta[b]chromen-3-yl)methylene]-
N-methylmethanaminium perchlorate (5d). 87%, red powder, mp
258–260 °C; νmax(KBr) 2960–2925 (aliphatic C–H), 1624 cm-1;
δH (400 MHz, DMSO-d6) 8.42 (1Н, s, N=CH–N(CH3)2), 7.78
(1Н, s, СН=N+(CH3)2), 7.75 (1Н, s, H Ar), 7.45 (s, 1Н, H Ar),
3.65–3.75 (m, 1Н, CH(CH3)2), 3.33 (6Н, s, СН=N+(CH3)2), 3.21
(3Н, s, N=CH–N(CH3)CH3), 3.16 (3Н, s, N=CH–N(CH3)CH3),
3.04–3.13 (4Н, m, 2СН2), 2.95–3.03 (1Н, m, CH(CH3)2), 1.29
(6H, d, J 6.8 Hz, CH(CH3)2), 1.22 (6H, d, J 6.8 Hz, CH(CH3)2);
δC (100 MHz, DMSO-d6) 172.5, 157.3, 152.9, 149.1, 148.6,
145.4, 136.0, 127.4, 121.3, 119.4, 116.0, 101.9, 40.8, 34.5, 33.2,
26.0, 25.1, 24.9, 23.8, 22.8; m/z (FAB) 380 (100 M+), 364 (9%).
3.3 Synthesis of perchlorates 5a–f (General method). Method A
(with heating).
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01
mol) and DMF (2.3 mL, 0.03 mol) with ice cooling. The
compound 4a (1.1 g, 0.005 mol) was added to the Vilsmeier
reagent. The reaction mixture was heated on a water bath at 75–
85 °C for 1 h (an orange solid was separated within 0.5 h). Then
the reaction mixture was cooled to 10 °C and treated with an ice-
cold 15% aq. solution of NaClO4 (10 mL). The precipitate of the
salt 5a was filtered off, dried and purified by refluxing with
toluene. In the case of salts 5b–d, the reaction mixture was
cooled to 10 °C and treated with an ice-cold 15% aq. solution
of NaClO4 (10 mL); then pH was adjusted to 8.0–9.0 with aq.
NaOH. The solid products were filtered off, washed and dried to
give pure salts 5b–d. For salts 5e,f, the reaction time was 4 h.
Caution! Organic perchlorates are potentially explosive. The
microanalysis were not performed in order to prevent an
explosion.
3.3.5.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-
diiodo-2,3-dihydro-1H-xanthen-4-yl)methylene]-N-
methylmethanaminium perchlorate (5e). Yellow powder, yield
~54% (calculated for proposed structure), mp 245–252 °C. This
intermediate perchlorate was used on the next step without
further purification.
3.3.6.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-
3.3.1.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-2,3-
diiodo-1,2-dihydrocyclopenta[b]chromen-3-yl)methylene]-N-
methylmethanaminium perchlorate (5f). Pink powder, yield
~57% (calculated for proposed structure), mp 225–233 °C. This
intermediate perchlorate was used on the next step without
further purification.
dihydro-1H-xanthen-4-yl)methylene]-N-methylmethanaminium
perchlorate (5a). 96%, orange powder, mp 300 °C; νmax(KBr)
2939 (aliphatic C–H), 1708, 1600 cm-1; δH (400 MHz, DMSO-
d6/CCl4) 8.56 (1Н, s, N=CH–N(CH3)2), 8.20 (1Н, s,
СН=N+(CH3)2), 7.76 (1H, d, J 7.6 Hz, H Ar), 7.60–7.68 (2Н, m,
H Ar), 7.34–7.42 (1Н, m, H Ar), 3.52 (6Н, s, СН=N+(CH3)2),
3.27 (3Н, s, N=CH–N(CH3)CH3), 3.25 (3Н, s, N=CH–
N(CH3)CH3), 2.74–2.81 (2Н, m, 3-СН2 or 1-СН2), 2.59–2.74
(2Н, m, 1-СН2 or 3-СН2), 1.61–1.78 (2Н, m, 2-СН2); δC (100
MHz, DMSO-d6/CCl4) 172.0, 165.2, 158.3, 155.8, 152.1, 132.3,
125.0, 124.7, 121.5, 119.2, 116.5, 101.9, 42.0, 40.0, 24.6, 24.0,
3.4. Synthesis of perchlorates 5a–d. Method B (at room
temperature).
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01
mol) and DMF (2.3 mL, 0.03 mol) with ice cooling. The
compound 4a (1.1 g, 0.005 mol) was added to the Vilsmeier
reagent. The reaction mixture was stirred vigorously at room

6
Tetrahedron
temperature for 24 h and maintained as in the method A. The
3.5.4. N'-(3-Formyl-5,7-diisopropyl-1,2-dihydrocyclopenta[b]-
ACCEPTED MANUSCRIPT
salts 5b–d were obtained in the same way.
Yield of compound 5a was 88 %.
Yield of compound 5b was 75%.
Yield of compound 5c was 85%.
Yield of compound 5d was 80%.
chromen-9-yl)-N,N-dimethylimidoformamide (6d). 85%, yellow
powder, mp 133–136 °C (aq. МеОН); [Found: C, 75.11; H, 8.08;
N, 7.99. C22H28N2O2 requires C, 74.97; H, 8.01; N, 7.95%];
νmax(KBr) 2925 (aliphatic C–H), 1630 (СНО) cm-1; δH (400 MHz,
DMSO-d6) 9.79 (1Н, s, СНО), 8.07 (1Н, s, N=CH–N(CH3)2),
7.48 (1Н, s, H Ar), 7.17 (1Н, s, H Ar), 3.33 (1H, m, CH,
overlapped with a peak of water), 3.07 (3Н, s, N=CH–
N(CH3)CH3), 3.03 (3Н, s, N=CH–N(CH3)CH3), 2.89–2.99 (1Н,
m, CH(CH3)2), 2.79–2.89 (2Н, m, СН2), 2.51–2.60 (2Н, m, СН2),
1.22 (12H, d, J 6.8 Hz, 2CH(CH3)2); δC (100 MHz, DMSO-d6)
180.0 (CHO), 166.5, 158.4, 147.6, 144.2, 143.6, 134.2, 125.1,
121.6, 118.8, 118.0, 111.6, 33.9, 33.1, 27.2, 24.0, 23.3, 23.2,
22.4; m/z (EI) 352 (100 M+), 337 (6), 323 (21), 308 (16), 280
(14), 44 (7%).
3.5. Synthesis of benzopyrans 6a–f (General method).
The corresponding salt 5a-f (1.0 g, 0.002 mol) was dissolved in
hot DMF (5 mL). To the obtained solution, an aqueous 15 %
NaOH solution (1.5 mL) was added and the mixture was stirred
vigorously at 60–75 °C for 5 min. The precipitated solid of
corresponding compound 6a–f was filtered off. If no solid
precipitated, the solution cooled to the room temperature and
water was added.
3.5.1.
N'-(4-Formyl-2,3-dihydro-1H-xanthen-9-yl)-N,N-
3.5.5.
N'-(4-Formyl-5,7-diiodo-2,3-dihydro-1H-xanthen-9-yl)-
dimethylimidoformamide (6a). 85%, yellow-green needles, mp
175–177 °C (aq. МеОН); [Found: C, 72.41; H, 6.49; N, 9.98.
C17H18N2O2 requires C, 72.32; H, 6.43; N, 9.92%]; νmax(KBr)
2932–2852 (aliphatic C–H), 1632 (СНО) cm-1; δH (400 MHz,
DMSO-d6) 10.13 (1Н, s, СНО), 7.70 (1Н, s, N=CH–N(CH3)2),
7.49–7.56 (1Н, m, H Ar), 7.33–7.42 (1Н, m, H Ar), 7.19–7.26
(1Н, m, H Ar), 7.10–7.18 (1Н, m, H Ar), 3.03 (3Н, s, СН3), 3.01
(3Н, s, СН3), 2.50 (2H, 3-СН2 or 1-СН2, overlapped with DMSO
signals), 2.25–2.29 (2Н, m, 1-СН2 or 3-СН2), 1.52–1.56 (2Н, m,
2-СН2); δH (400 MHz, DMSO-d6/CF3CO2D) 10.00 (1Н, s, СНО),
8.41 (1Н, s, N=CH–N(CH3)2), 7.58 (1Н, d, J 7.6 Hz, H-5 Ar),
7.50 (1Н, t, J 7.6 Hz, H-6 Ar), 7.34 (1Н, d, J 8.1 Hz, H-8 Ar),
7.25 (1Н, t, J 7.4 Hz, H-7 Ar), 3.27 (3Н, s, СН3), 3.31 (3Н, s,
СН3), 2.58–2.70 (2Н, m, 3-СН2 or 1-СН2), 2.28–2.40 (2Н, m, 1-
СН2 or 3-СН2), 1.55–1.75 (2Н, m, 2-СН2); δC (100 MHz,
DMSO-d6) 184.2 (СНО), 162.5, 154.6, 151.6, 146.9, 130.2,
124.0, 123.3, 120.8, 115.2, 110.9, 109.0, 33.8, 24.7, 27.0, 20.1;
m/z (EI) 282 (100 M+), 265 (16), 253 (60), 239 (13), 210 (10),
196 (6), 181 (11), 152 (5), 127 (7), 77 (8), 58 (6), 43 (17%).
N,N-dimethylimidoformamide (6e). 85%, yellow powder, mp
295–300 °C (aq. DMF); [Found: C, 38.31; H, 3.05; N, 5.29.
C17H16I2N2O2 requires C, 38.23; H, 3.02; N, 5.24%]; νmax(KBr)
2925 (aliphatic C–H), 1674 (СНО) cm-1; δH (400 MHz, DMSO-
d6) 10.29 (1Н, s, СНО), 8.05 (1Н, s, N=CH–N(CH3)2), 7.73 (1Н,
s, H Ar), 7.72 (1Н, s, H Ar), 3.04 (3Н, s, CH3), 3.01 (3Н, s, CH3),
2.50–2.55 (2Н, m, 3-СН2 or 1-СН2), 2.24–2.30 (2Н, m, 1-СН2 or
3-СН2), 1.51–1.57 (2Н, m, 2-СН2); δC (100 MHz, DMSO-d6)
185.1 (CHO), 166.0, 161.8, 155.1, 145.5, 144.8, 132.2, 123.6,
111.8, 110.2, 88.1 (C-I), 85.4 (C-I), 34.9, 33.9, 24.5, 20.8, 19.9;
m/z (EI) 534 (100 M+), 505 (19), 152 (7), 42 (34%).
3.5.6.
N'-(3-Formyl-5,7-diiodo-1,2-dihydrocyclopenta[b]-
chromen-9-yl)-N,N-dimethylimidoformamide (6f). 80%, pink
powder, mp 300 °C (aq. DMF); [Found: C, 37.09; H, 2.75; N,
5.44. C16H14I2N2O2 requires C, 36.95; H, 2.71; N, 5.39%];
νmax(KBr) 2924 (aliphatic C–H), 1615 (СНО) cm-1; δH (400 MHz,
DMSO-d6/CF3CO2D) 9.74 (1Н, s, СНО), 8.42 (1Н, s, N=CH–
N(CH3)2), 8.09 (1Н, s, H Ar), 7.81 (1Н, s, H Ar), 3.28 (3Н, s,
CH3), 3.21 (3Н, s, CH3), 2.84–2.88 (2Н, m, СН2), 2.52–2.60 (2Н,
m, СН2); m/z (EI) 520 (100 M+), 505 (7), 491 (13), 476 (7), 139
(9), 44 (40%).
3.5.2.
N'-(3-Formyl-1,2-dihydrocyclopenta[b]chromen-9-yl)-
N,N-dimethylimidoformamide (6b). 83%, yellow-green needles,
mp 196–198 °C (aq. МеОН); [Found: C, 71.51; H, 5.97; N,
10.40. C16H16N2O2 requires C, 71.62; H, 6.01; N, 10.44%];
νmax(KBr) 2924 (aliphatic C–H), 1630 (СНО) cm-1; δH (400 MHz,
DMSO-d6) 9.77 (1Н, s, СНО), 8.08 (1Н, s, N=CH–N(CH3)2),
7.71–7.77 (1Н, m, H Ar), 7.32–7.40 (1Н, m, H Ar), 7.15–7.24
(2Н, m, H Ar), 2.51–3.07 (3Н, s, СН3), 3.02 (3Н, s, СН3), 2.76–
2.85 (2Н, m, СН2), 2.55 (2Н, m, СН2); δC (100 MHz, DMSO-d6)
180.4 (CHO), 166.2, 155.5, 152.2, 143.2, 129.7, 124.0, 123.8,
122.2, 118.6, 155.5, 112.0, 33.8, 23.2; m/z (FAB) 269 (100
MH+), 239 (11%).
3.6. Synthesis of salts 8 and 11 a,b (General procedure).
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01
mol) and DMF (2.3 mL, 0.03 mol) with ice cooling. The
corresponding oxazine 7 or 10 (0.005 mol) was added to the
Vilsmeier reagent. The reaction mixture was left to stand at room
temperature for 24 h. Then the reaction mixture was cooled to 10
°C and treated with an ice-cold 15% aq. solution of NaClO4 (10
mL). The precipitate of the corresponding salt 8 or 11 was
filtered off, dried and purified by refluxing with toluene.
The microanalysis were not performed in order to prevent an
explosion.
3.5.3. N'-(4-Formyl-5,7-diisopropyl-2,3-dihydro-1H-xanthen-9-
yl)-N,N-dimethylimidoformamide (6c). 90%, yellow powder, mp
188–190 °C (aq. МеОН); [Found: C, 75.47; H, 8.32; N, 7.69.
C23H30N2O2 requires C, 75.38; H, 8.25; N, 7.64%]; νmax(KBr)
2927–2864 (aliphatic C–H), 1651 (СНО) cm-1; δH (400 MHz,
DMSO-d6) 10.19 (1Н, s, СНО), 7.66 (1Н, s, N=CH–N(CH3)2),
7.24 (1Н, s, H Ar), 7.19 (1Н, s, H Ar), 3.35–3.43 (1Н, m,
CH(CH3)2), 3.05 (6Н, m, N=CH–N(CH3)2), 2.86–2.91 (1Н, m,
CH(CH3)2), 2.49–2.53 (2Н, m, 3-СН2 or 1-СН2), 2.29–2.34 (2Н,
m, 1-СН2 or 3-СН2), 1.56–1.62 (2Н, m, 2-СН2), 1.29 (6H, d, J
6.8 Hz, CH(CH3)2), 1.21 (6H, d, J 6.8 Hz, CH(CH3)2); δC (100
MHz, DMSO-d6) 183.4 (CHO), 162.8, 154.6, 148.0, 147.0,
142.9, 134.1, 125.3, 120.3, 118.9, 110.4, 108.7, 33.8, 33.1, 26.8,
24.4, 23.9, 22.3, 21.2, 20.3; m/z (EI) 366 (100 M+), 349 (8), 337
(36), 322 (6), 59 (8), 43 (19%).
3.6.1.
N-Methyl-N-({[(4Z)-2-phenyl-4H-chromen-4-ylidene]-
amino}methylene)methanaminium perchlorate (8). 67%, yellow
powder, mp 210–213 °C (МеОН); νmax(KBr) 1630–1640 (C=N),
1614 (C=C), 1597 cm-1; δH (400 MHz, DMSO-d6) 9.23 (1Н, s,
N–CH=N+(CH3)2), 8.51–8.58 (1Н, m, H Ar), 8.29–8.35 (2Н, m,
H Ar), 8.07 (1Н, s, Н-3), 8.01–8.13 (2Н, m, H Ar), 7.62–7.82
(4Н, m, H Ar), 3.52 (3Н, s, CH3), 3.49 (3Н, s, CH3); δC (100
MHz, DMSO-d6) 166.4, 164.7, 161.6, 155.0, 136.4, 133.5, 130.2,
129.3, 127.3, 127.2, 125.7, 121.2, 118.6, 101.1, 42.9 (СН3), 36.7
(СН3); m/z (FAB) 277 (100 M+), 222 (6%).
3.6.2. N,N'-[2-(4-{[(1E)-(Dimethylamino)methylene]amino}-2H-
chromen-2-ylidene)propane-1,3-diylidene]bis(N-
methylmethanaminium) diperchlorate (11a). 90%, yellow

7
powder, mp 223–225 °C (МеОН); νmax(KBr) 2929 (aliphatic C–
H), 1622, 1526 cm-1; δH (400 MHz, DMSO-d6) 8.94 (1Н, s,
N=CH–N(CH3)2), 8.42–8.48 (3Н, m, H Ar and СН=N+(CH3)2),
7.89–8.05 (2Н, m, H Ar), 7.63–7.69 (1Н, m, H Ar), 7.12 (1Н, s,
Н-3), 3.61 (6Н, s, СН=N+(CH3)2), 3.46 (3Н, s, N=CH–
N(CH3)CH3), 3.42 (3Н, s, N=CH–N(CH3)CH3), 3.24 (6Н, s,
СН=N+(CH3)2); δC (100 MHz, DMSO-d6) 164.7, 162.4, 160.5,
154.3, 135.6, 127.0, 125.7, 120.4, 118.2, 101.4, 92.1, 48.5, 42.9,
42.6, 36.4; m/z (FAB) 427 (14 (M+37ClO4)+), 425 (42
(M+37ClO4)+), 326 (12), 311 (6), 280 (12), 270 (6), 225 (6), 165
(7%).
80 °C for 1 h. Then the reaction mixture was cooled to the room
ACCEPTED MANUSCRIPT
temperature, treated with water (10 mL) and left to stand at r.t.
The precipitate was filtered off to give the imide 14 (0.86 g,
90%) as white powder, mp 60–62 °C (aq. МеОН); [Found: C,
62.98; H, 4.82; N, 7.39. C10H9NO3 requires C C, 62.82; H, 4.74;
N, 7.33%]; νmax(KBr) 1714 (imide) cm-1; δH (400 MHz, DMSO-
d6) 9.27 (1Н, s, СНО), 7.93 (1Н, d, J 7.8 Hz, H-8 Ar), 7.69 (1Н,
t, J 7.7 Hz, H-7 or H-6 Ar), 7.23 (1Н, t, J 7.6 Hz, H-6 or H-7 Ar),
7.12 (1Н, d, J 8.3 Hz, H-5 Ar), 6.37–6.44 (1Н, q, J 6.2 Hz, Н-2),
1.42 (3Н, d, J 6.2 Hz, СН3); δC (100 MHz, DMSO-d6) 160.0
(CHO), 159.8 (CO), 155.4, 137.1, 128.1, 123.0, 117.9, 115.5,
78.8 (С-2), 18.8 (СН3); m/z (EI) 191 (6 M+),163 (24), 148 (11),
120 (100), 92 (47), 65 (12), 39 (10), 31 (27%).
3.6.3. N,N'-[2-(4-{[(1E)-(Dimethylamino)methylene]amino}-6,8-
diisopropyl-2H-chromen-2-ylidene)propane-1,3-diylidene]bis(N-
methylmethanaminium) diperchlorate (11b). Yellow powder,
yield 85% (calculated for proposed structure), mp 220–227 °C.
This intermediate diperchlorate was used on the next step
without further purification.
3.9. The hydrolysis of imide 14.
To a solution of compound 14 (1.91 g, 0.01 mol) in MeOH (10
mL), water (4 mL) was added and the mixture was left to stand at
the room temperature for 12 h. The colorless needles of oxazine
13 were filtered off, the yield was 1.55 g (95 %), mp 150–152 °C
(Ref.20: 143–147 °C).
3.7. Synthesis of benzopyrans 9 and 12a, b (General method).
The corresponding salt 8 or 11 (1.0 g) was dissolved in MeOH (5
mL) and treated with 15 % aq. NaOH solution (1.5 mL) the
mixture was slightly heated for a few minutes. After cooling to
the room temperature, water (3–4 mL) was added, the
precipitated solid was filtered off, washed with water to give
benzopyrans 9, 12.
3.10. 9-Chloro-1,2,3,4-tetrahydroacridine (16). Method A.
The compound 15 (2.17 g, 0.01 mol) was added to DMF (1 mL).
The suspension formed was treated with the ice-cold Vilsmeier
reagent obtained from DMF (6 mL) and POCl3 (2.75 mL, 0.03
mol) under ice-cooling. A yellow solid precipitated abundantly
within 10–15 min. After 0.5 h the reaction mixture was poured
on ice and treated with aqueous ammonia, the obtained solid was
filtered off and dried to give acridine 16 (2.17 g, ~100%), as
yellow powder, mp 68–70 °C (Ref.:14 mp 68–70 °C). Spectral
data for 16 (NMR) were identical to the reported data.14
3.7.1. 2-Рhenyl-4H-chromen-4-imine (9). 78%, white powder,
mp 68–70 °C (Ref.:21 66–67 °C) (МеОН); δH (400 MHz, DMSO-
d6) 9.00 (1Н, с, NH), 8.12–8.19 (1Н, m, H Ar), 7.83–8.01 (2Н,
m, H Ar), 7.45–7.66 (5Н, m, H Ph), 7.33–7.37 (1Н, m, H Ar),
6.87 (1Н, s, Н-3); δC (100 MHz, DMSO-d6) 178.1, 155.9, 152.2,
133.1, 130.9, 129.4, 127.8, 126.2, 125.1, 121.1, 118.2, 117.3,
94.0; m/z (FAB) 222 (100% MH+); m/z (FAB+NaI) 244 (36%
MNa+).
Method B.
The compound 17 (1.99 g, 0.01 mol) was added to DMF (1 mL).
The suspension formed was treated with the ice-cold Vilsmeier
reagent obtained from DMF (4 mL) and POCl3 (1.83 mL, 0.02
mol) under ice-cooling. A yellow solid precipitated abundantly
within 10–15 min. After 0.5 h the reaction mixture was poured
on ice and treated with aqueous ammonia, the obtained solid was
filtered off and dried to give acridine 16 (2.17 g, ~100%), as
yellow powder, mp 68–70 °C.
3.7.2. (4-Аmino-2H-chromen-2-ylidene)malonaldehyde (12a).
80%, pink powder, mp 300 °C (aq. DMF), mp of hydrate 220–
222 °C (aq. MeOH); [Found: C, 66.89; H, 4.18; N, 6.46.
C12H9NO3 requires C, 66.97; H, 4.22; N, 6.51%]; νmax(KBr)
3369, 3348 (NH2), 1615 (CHO) cm-1; δH (400 MHz, DMSO-d6)
9.86 (2Н, br. s, 2СНО), 9.14 (1Н, br. s) and 8.85 (1H, br. s,
NH2), 8.20 (1Н, d, J 8.1 Hz, H Ar), 7.79–7.86 (2Н, m, H Ar),
7.69 (1Н, d, J 8.1 Hz, H Ar), 7.53 (1Н, t, J 7.6 Hz, H Ar); δC (100
MHz, DMSO-d6) 185.8 (2CHO), 167.3, 156.5, 152.8, 134.4,
125.2, 123.2, 118.2, 114.5, 106.8, 91.4; m/z (FAB) 216 (83 MH+)
(83), 186 (26), 170 (11%); m/z (FAB+NaI) 238 (60% MNa+).
3.11. 1,3,4,10-Тetrahydroacridin-9(2H)-one (17).
The compound 15 (2.17 g, 0.01 mol) was added to DMF (1 mL).
The suspension formed was treated with the ice-cold Vilsmeier
reagent obtained from DMF (2 mL) and POCl3 (0.92 mL, 0.01
mol) under ice-cooling. A white solid precipitated abundantly
within 10-15 min. After 0.5 h the reaction mixture was poured on
ice and treated with aqueous ammonia, the obtained solid was
filtered off and dried to give acridine 17 (1.99 g, (~100%), as a
colorless crystals, mp 358–360 °C (Ref.:22 mp 355–358 °C).
Spectral data for 17 (FTIR, NMR) were identical to the reported
data.15
3.7.3. (4-Amino-6,8-diisopropyl-2H-chromen-2-ylidene)malon-
aldehyde (12b). 84%, light gray powder, mp 295 °C (aq. DMF);
[Found: C, 72.08; H, 6.97; N, 4.62. C18H21NO3 requires C, 72.22;
H, 7.07; N, 4.68%]; νmax(KBr) 3323 (NH2), 2959 (aliphatic C–H),
1692 (CHO) cm-1; δH (400 MHz, DMSO-d6) 9.77 (2Н, br. s,
2СНО), 9.00 (1Н, br. s) and 8.74 (1Н, br. s, NH2), 7.92 (1Н, s, H
Ar), 7.81 (1Н, s, H Ar), 7.59 (1Н, s, Н-3), 3.65–3.69 (1Н, m,
CH(CH3)2), 2.98–3.02 (1Н, m, CH(CH3)2), 1.24–1.30 (12Н, m,
2CH(CH3)2); δC (100 MHz, DMSO-d6) 186.1 (2CHO), 165.8,
157.4, 148.5, 145.2, 137.5, 129.9, 117.7, 113.9, 106.9, 91.7, 33.4,
26.4, 23.8, 22.4; m/z (EI) 299 (8 M+), 271 (100), 254 (87), 238
(5), 121 (5), 91 (5), 43 (17%).
3.12.
N-[(4-Chloro-3,5,6,7-tetrahydrospiro[1,3-benzoxazine-
2,1'-cyclohexan]-8-yl)methylene]-N-methylmethanaminium
perchlorate (19).
The Vilsmeier reagent was prepared from POСl3 (2.76 mL, 0.03
mol) and DMF (6.9 mL, 0.03 mol) with ice cooling. The
compound 18 (2.0 g, 0.009 mol) was added to the Vilsmeier
reagent. The reaction mixture was left to stand at the room
temperature for 0.5 h and then was treated with an ice-cold 15%
aq. solution of NaClO4 (10 mL). The precipitate was filtered off
to give perchlorate 19 (2.38 g, 67%), as yellow cubic crystals, mp
180–182 °C (i-PrOH), νmax(KBr) 3263 (N–H), 2934–2862
(aliphatic C–H), 1637 cm-1; δH (400 MHz, DMSO-d6/ССl4) 9.05
3.8. 2-Methyl-4-oxo-2H-1,3-benzoxazine-3(4H)-carbaldehyde
(14). The Vilsmeier reagent was prepared from POСl3 (0.92 mL,
0.01 mol) and DMF (2.3 mL, 0.03 mol) with ice cooling. The
compound 13 (0.82 g, 0.005 mol) was added to the Vilsmeier
reagent. The reaction mixture was heated on a water bath at 75–

8
Tetrahedron
CCEPTED MANUSCRIPT
(1Н, br. s, NH), 7.95 (1Н, s, СН=N+(CH3)2), 3.43 (6Н, s,
Å3, space group C2/c, Z = 16, dcalc= 1.464 g/cm3, ꢀ(MoKa) =
A
СН=N+(CH3)2), 2.64–2.68 (2Н, m, СН2), 2.40–2.44 (2Н, m,
СН2), 1.47–1.99 (12Н, m, 6СН2); δC (100 MHz, DMSO-d6/ССl4)
165.7, 157.2, 143.9, 100.6, 99.2, 21.4, 21.8, 23.5, 89.5 (С-2),
32.0, 24.4; m/z (FAB) 297 (34 M(37Cl)+), 295 (100 M(35Cl)+), 259
(70), 217 (11), 175 (10%).
0.392 мм-1, F(000) = 3328, 17805 reflections were collected up
to 2θmax= 52.792° (7319 unique, Rint = 0.053). Structure was
solved by direct method and refined on F2 with Shelx-2013
software.23 Hydrogen atoms refined in riding model
approximation with Uiso = nUeq of the carrier atom (n = 1.5 for
methyl groups and n = 1.2 for the remaining H-atoms).
Refinement converged at wR2 = 0.161 for all 7319 data, R1 =
0.065 for 5138 reflections with F>4σ(F). Crystal data were
deposited at Cambridge Crystal Database, deposition number
CCDC 1051304.
The microanalysis were not performed in order to prevent an
explosion.
3.13.
[(E)-(4-Chloro-6,7-dihydrospiro[1,3-benzoxazine-2,1'-
cyclohexan]-8(5H)-ylidene)methyl]dimethylamine (20).
To a solution of salt 19 (1.00 g) in MeOH (5 mL), 15% aq.
NaOH (1.5 mL) was added, the mixture was slightly heated for 5
min. After cooling to the room temperature, water (2–3 mL) was
added, the precipitated solid was filtered off, washed with water
to give compound 20 (0.65 g, 87%), as yellow powder, mp 91–93
°C (aq. МеОН); [Found: C, 65.09; H, 7.80; N, 9.45.
C16H23ClN2O requires C, 65.18; H, 7.86; N, 9.50%]; δH (400
MHz, DMSO-d6/ССl4) 6.68 (1Н, s, =СН-N(СН3)2), 2.50–2.54
(2Н, m, СН2), 2.98 (6Н, s, N(СН3)2), 2.23–2.27 (2Н, m, СН2),
1.38–1.84 (12Н, m, 6СН2); δC (100 MHz, DMSO-d6/ССl4) 157.1,
153.7, 140.4 (СН-N(СН3)2), 98.0, 96.8, 92.3 (С-2), 42.9 (2СН3),
34.1 (CH2), 24.9 (CH2), 24.5 (CH2), 23.7 (CH2), 22.5 (CH2), 21.5
(CH2); δC DEPT-135 (100 MHz, DMSO-d6/CCl4) 140.0 (СН-
N(СН3)2), 42.5 (2СН3), 33.7* (CH2), 24.4* (CH2), 24.0* (CH2),
23.2* (CH2), 22.0* (CH2), 21.0* (CH2); *signals in antiphase;
m/z (EI) 296 (29 M(37Cl)+), 294 (79 M(35Cl)+), 258 (100), 251
(50), 243 (31), 229 (15), 215 (21), 200 (16), 191 (11), 176 (30),
161 (21), 149 (16), 134 (32), 81 (40), 43 (46%).
Authors are grateful to our colleagues – prof. Shishkin O. V.
(deceased) and Dr. Zubatyuk R. I. for X-ray studies.
References and notes
1. Minkin, V . I .; Dorofeenko G. N. Russ. Chem. Rev. 1960, 29, 599.
2. Seybold, G. J. Prakt. Chem. 1996, 338, 392.
3. Jones, G.; Stanforth, S. P. Org. React. 1997, 49, 1.
4. Jones, G.; Stanforth, S. P. Org. React. 2000, 56, 355.
5. Su, W.; Weng, Y.; Jiang, L. Yang, Y.; Zhao, L.; Chen, Z.; Li, Z.;
Li. J. The New Journal for Organic Synthesis 2010, 42, 503.
6. Rajput, A. P.; Girase. P. D. IJPCBS 2013, 3, 25.
7. Ushijima, S.; Moriyama, K.; Togo H. Tetrahedron 2012, 68, 4588.
8. Gowda, G. B.; Charanraj, T. P.; Pradeepa Kumara, C. S.; Ramesh,
N.; Thomas, S.P.; Sadashiva, M. P.; Junjappa, H. Tetrahedron
Lett. 2014, 55, 4475.
9. Yu. H.; Zhang, Y.; Li, T.; Liao, P.; Diao, Q.; Xin, G.; Meng, Q.;
Hou, D. RSC Advances 2015, 5, 11293.
10. Varenichenko, S. A.; Farat O. K.; Markov, V. I. Chem.
Heterocycl. Compd. 2015, 11, 1602.
11. Markov, V. I.; Farat, O. K.; Varenichenko, S. A.; Velikaya, E. V.
Mendeleev Commun. 2012, 22, 101.
12. Zefirov, Yu. V.; Zorkii P. M. Russ. Chem. Rev. 1989, 58, 421.
13. Burgi, H.-B.; Dunitz, J. D. Structure correlation. Vol. 2. VCH.
Weinheim. 1994. p.741-784.
14. Hu, M.-K.; Lu, C.-F. Tetrahedron Lett. 2000, 41, 1815.
15. Son, J. K.; Kim, S. I.; Jahng, Y. Heterocycles 2001, 55, 1981.
16. Kondo, K.; Seki, M.; Kuroda, T.; Yamanaka, T.; Iwasaki, T. J.
Org. Chem. 1997, 62, 2877.
17. Gammill, R. B. J. Org. Chem. 1981, 46, 3340.
18. Carlier, P. R.; Han, Y. F.; Chow, E. S.-H.; Li, C. P.-L.; Wang, H.;
Lieu, T. X.; Wong, H. S.; Pang, Y.-P. Bioorg. Med. Chem. 1999,
7, 351.
19. Markov, V. I.; Farat, O. K.; Varenichenko, S. A.; Zaliznaya, K.
V.; Zubatyuk, R. I.; Shishkin, O. V. Chem. Heterocycl. Comp.
2013, 8, 1158.
20. Irvine, J. L.; Piantadosi, C. Synthesis 1972, 10, 568.
21. Van Allan, J. A.; Chang, S. C.; Reynolds, G. A. J. Heterocyclic
chemistry 1974, 11, 195.
X-ray diffraction study of 6a (C17H18N2O2, Mr = 282.33) was
performed at 298 K on a «Xcalibur 3» diffractometer. Crystal
data: monoclinic, a = 14.610(2) Å, b = 8.8414(8) Å, c =
12.5150(19) Å, β = 115.25(2)°, V = 1462.2(4) Å3, space group
P21/c, Z = 4, dcalc= 1.283 g/cm3, ꢀ(MoKa) = 0.085 мм-1, F(000) =
600, 10870 reflections were collected up to 2θmax= 58.3° (3477
unique, Rint = 0.046). Structure was solved by direct method and
refined on F2 with Shelx-2013 software.23 Hydrogen atoms
refined in riding model approximation with Uiso = nUeq of the
carrier atom (n = 1.5 for the water molecule and n = 1.2 for the
remaining H-atoms). Hydrogen atoms of the C17 methyl group
are disordered over two positions with equal occupancies.
Refinement converged at wR2 = 0.159 for all 3477 data, R1 =
0.058 for 1720 reflections with F>4σ(F). Crystal data were
deposited at Cambridge Crystal Database, deposition number
CCDC 1051305.
22. Zigeuner, G.; Gübitz, G. Monatsh. Chem. 1970, 101, 1547.
23. Sheldrick, G. Acta Cryst., Sect. A. 2008, 64, 112.
X-ray diffraction study of 12a (2(C12H9NO3)ꢁH2O, Mr = 448.42)
was performed at 298 K on a «Xcalibur 3» diffractometer.
Crystal data: monoclinic, a = 14.8086(8) Å, b = 6.8292(4) Å, c =
21.3683(10) Å, β = 105.613(5)°, V = 2081.2(2) Å3, space group
P21/n, Z = 4, dcalc= 1.431 g/cm3, ꢀ(MoKa) = 0.107 мм-1, F(000) =
936, 13830 reflections were collected up to 2θmax= 57.2° (4255
unique, Rint = 0.057). Structure was solved by direct method and
refined on F2 with Shelx-2013 software.23 Hydrogen atoms
refined in riding model approximation with Uiso = nUeq of the
carrier atom (n = 1.5 for the water molecule and n = 1.2 for the
remaining H-atoms). Refinement converged at wR2 = 0.131 for
all 4255 data, R1 = 0.056 for 2239 reflections with F>4σ(F).
Crystal data were deposited at Cambridge Crystal Database,
deposition number CCDC 1051306.
X-ray diffraction study of 19 (C16H24N2OCl+·ClO4-, Mr = 395.27)
was performed at 120 K on an «Bruker APEX-II CCD»
diffractometer. Crystal data: monoclinic, a = 24.667(3) Å, b =
14.1313(18) Å, c = 20.611(3) Å, β = 93.473(3)°, V = 7171.3(15)

SUPPORTING INFORMATION
ACCEPTED MANUSCRIPT
The Vilsmeier-Haack formylation of 2,3-dihydro-4H-1,3-
benzoxazin-4-ones and isomeric 1,2-dihydro-4H-3,1-benzoxazin-4-
ones: an effective approach to functionalized 2H-/4H-Chromenes
and Tetrahydroacridines
Oleg К. Farata,b , Victor I. Markova, Svetlana А. Varenichenkoa, Victor V. Dotsenkoc and
Alexander V. Mazepad
aUkrainian State University of Chemical Technology, 49005 Dnepropetrovsk, Ukraine
bDepartment of Chemistry, M. V. Lomonosov Moscow State University, 119991Moscow, Russian Federation
cKuban State University, 350040 Krasnodar, Russian Federation
dA. V. Bogatsky Physico-Chemical Institute, 65080 Odessa, Ukraine
Corresponding author. Tel.: +380562-47-46-70; fax: +380562-47-33-16; e-mail: faratok@mail.ru
1

Corresponding Author
ACCEPTED MANUSCRIPT
E-mail: faratok@mail.ru
General experimental details and procedures
1
13
The H NMR and C NMR spectra were performed on a Bruker Avance II 400
1
instrument (400,13 MHz and 100,62 MHz for H and 13C respectively) in DMSO-
d6, DMSO-d6/CCl4 or DMSO-d6/CF3CO2D with Me4Si as internal standard. The
FTIR spectra were recorded in KBr pellets using a Spectrum one (PerkinElmer)
FT-IR Spectrometer. The mass spectra of compounds 4c–f, 10b, 6a,c–f, 12b, 14
and 20 were recorded on a MX1321 instrument with direct injection of the sample
at an ionization chamber temperature of 200 °C and with 70 eV ionizing electrons.
The FAB spectra of compounds were recorded on a VG7070 spectrometer.
Desorption of the ions from the solution of the samples in meta-nitrobenzyl alcohol
was realized with a beam of argon atoms with energy 8 keV. Chromatographic
analysis of compound 16 was realized on an Agilent 1100 liquid chromatograph
with DAD and ELSD Sedex 75 detectors in conjunction with an LC-MS VL
spectrometer with electrospray ionization. Elemental analysis was performed on a
LECO CHNS-900 instrument. The reactions and the purity of the obtained
compounds were monitored by TLC on Merck Silicagel 60 F-254 plates with 10:1
CHCl3–i-PrOH as eluent.
Compounds 4a–f were synthesized by the method described in literature.16
Compounds 7,17 1518 and 1819 were obtained by the known procedures.
Synthesis of Spirans 4a-f (General method).
H2
O
R
R
(
C
)
n
O
O
OH
NH2
PhMe, p-TSA
reflux 8 h
n
-H2O,
+
(
)
NH
C
R
R
H2
O
4a. R=H; n=2
4b. R=H; n=1
4c. R=i-Pr; n=2 (80%)
4d. R=i-Pr; n=1 (73%)
4e. R=I; n=2 (66%)
4f. R=I; n=1 (68%)
A mixture of the corresponding salicylamide (0.10 mol), ketone (0.12 mol)
and p-TsOH × H2O (0.05 mol) in toluene (70 mL) was refluxed for 8 h with
continuous removal of water with a Dean–Stark trap. In the case of spirans 4a,b,
the mixture was cooled to 10 °C and stirred for 1 h at the same temperature. The
resulting crystals were collected, washed with toluene (10 mL) and i-PrOH (10
mL) and dried at 50 °C. In all other cases, a solvent was evaporated to dryness
2

under reduced pressure, the solid residue was washed with 5% aq. NaOH solution
ACCEPTED MANUSCRIPT
and filtered off.
6,8-Diisopropylspiro[1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one (4c).
O
NH
O
80%, white powder, mp 165–167 °C (aq. MeOH); [Found: C, 75.86; H, 9.15; N,
4.69. C19H27NO2 requires C, 75.71; H, 9.03; N, 4.65%]; νmax(KBr) 3184 (N–H),
3066 (aromatic C–H), 2965–2862 (aliphatic C–H), 1674 (C=O) cm-1; δH (400
MHz, DMSO-d6/CCl4) 8.43 (1Н, s, NH), 7.41 (1Н, s, Н-5 Ar), 7.17 (1Н, s, Н-7
Ar), 3.22–3.31 (1Н, m, CH(CH3)2), 2.79–2.88 (1Н, m, CH(CH3)2), 1.95–2.07 (2Н,
m, spiro-ring), 1.50–1.70 (7Н, m, spiro-ring), 1.25–1.32 (1Н, m, spiro-ring), 1.21
(12H, d, J 6.1 Hz, 2CH(CH3)2); δC (100 MHz, DMSO-d6/CCl4) 161.4 (С=О),
140.6, 149.9, 128.6 (СH-7), 135.5, 121.4 (СH-5), 117.1, 86.9 (С-2), 35.4 (2СН2),
32.9 (CH(CH3)2), 25.8 (CH(CH3)2), 23.9 (2СН2), 23.8 (CH(CH3)2), 22.6
(CH(CH3)2), 21.6 (СН2); δC DEPT-135 (100 MHz, DMSO-d6/CCl4) 128.3 (СH-7),
121.1 (СH-5), 35.1* (2СН2), 32.5 (CH(CH3)2), 25.5 (CH(CH3)2), 23.9* (2СН2),
23.5 (CH(CH3)2), 22.3 (CH(CH3)2), 21.3* (СН2), *signals in antiphase; m/z (EI)
301 (9 M+), 205 (20), 189 (5), 176 (7), 161 (5), 97 (100), 41 (7%).
1Н NMR signals,
δ, ppm
Correlations
1H-1H COSY
HSQC
22.6, 23.8
21.6
1.21 (d, 2CH(CH3)2)
1.25–1.32 (m, spiro-ring)
1.50–1.70 (m, spiro-ring)
1.95–2.07 (m, spiro-ring)
2.79–2.88 (m, CH(CH3)2)
3.22–3.31 (m, CH(CH3)2)
7.17 (s, Н-7)
2.79–2.88, 3.22–3.31
1.50–1.70
1.95–2.07, 1.25–1.32
21.6, 23.9
35.4
1.50–1.70
1.21
1.21
–
32.9
25.8
128.6
7.41 (s, Н-5)
–
121.4
3

6,8-Diisopropylspiro[1,3-benzoxazine-2,1'-cyclopentan]-4(3H)-one (4d).
ACCEPTED MANUSCRIPT
O
NH
O
73%, white powder, mp 137–140 °C (aq. MeOH); [Found: C, 75.37; H, 8.83; N,
4.91. C18H25NO2 requires C, 75.22; H, 8.77; N, 4.87%]; νmax(KBr) 3183 (N–H),
3066 (aromatic C–H), 2958–2871 (aliphatic C–H), 1669 (C=O) cm-1; δH (400
MHz, DMSO-d6/CCl4) 8.54 (1Н, s, NH), 7.41 (1Н, s, Н-5 Ar), 7.13 (1Н, s, Н-7
Ar), 3.11–3.23 (1Н, m, CH(CH3)2), 2.77–2.91 (1Н, m, CH(CH3)2), 2.03–2.13 (2Н,
m, spiro-ring), 1.72–1.88 (6Н, m, spiro-ring), 1.22 (6H, d, J 6.1 Hz, CH(CH3)2),
1.19 (6H, d, J 6.1 Hz, CH(CH3)2); δC (100 MHz, DMSO-d6/CCl4) 161.9 (С=О),
150.9, 140.6, 135.6, 128.4 (СH-7), 121.5 (СH-5), 117.4, 96.7 (С-2), 37.9 (2СН2),
32.9 (CH(CH3)2), 26.4 (CH(CH3)2), 23.8 (CH(CH3)2), 22.3 (CH(CH3)2), 22.2
(2СН2); δC DEPT-135 (100 MHz, DMSO-d6/CCl4) 128.0 (СH-7), 121.1 (СH-5),
36.9* (2СН2), 32.4 (CH(CH3)2), 26.0 (CH(CH3)2), 23.3 (CH(CH3)2), 21.9
(CH(CH3)2), 21.8* (2СН2), *signals in antiphase; m/z (EI) 287 (8 M+), 205 (29),
189 (6), 176 (10), 161 (9), 83 (100), 41 (10%).
1Н NMR signals,
δ, ppm
HSQC
1.19 (d, CH(CH3)2)
1.22 (d, CH(CH3)2)
1.72–1.88 (m, spiro-ring)
2.03–2.13 (m, spiro-ring)
2.77–2.91 (m, CH(CH3)2)
3.11–3.23 (m, CH(CH3)2)
7.13 (s, H-7)
22.3
23.8
22.2, 37.9
37.9
32.9
26.4
128.4
121.5
7.41 (s, H-5)
4

6,8-Diiodospiro[1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one (4e).
ACCEPTED MANUSCRIPT
I
O
NH
I
O
66%, white powder, mp 235–237 °C (aq. DMF); [Found: C, 33.40; H, 2.84; N,
3.06. C13H13I2NO2 requires C, 33.29; H, 2.79; N, 2.99%]; νmax(KBr) 3153 (N–H),
3070 (aromatic C–H), 2936–2850 (aliphatic C–H), 1689 (C=O) cm-1; δH (400
MHz, DMSO-d6) 8.90 (1Н, s, NH), 8.19 (1Н, s, Н-5 Ar), 7.92 (1Н, s, Н-7 Ar),
1.79–2.08 (2Н, m, spiro-ring), 1.42–1.75 (7Н, m, spiro-ring), 1.12–1.28 (1Н, m,
spiro-ring); δC (100 MHz, DMSO-d6) 159.0 (С=О), 154.1, 149.4, 135.2, 119.8,
89.1 (С-2), 87.6 (C-I), 85.5 (C-I), 35.4 (2СН2), 24.1 (2СН2), 21.5 (СН2); m/z (EI)
469 (55 M+), 373 (24), 245 (14), 97 (100%).
6,8-Diiodospiro[1,3-benzoxazine-2,1'-cyclopentan]-4(3H)-one 4f).
(
I
O
NH
I
O
68%, white powder, mp 195–198 °C (aq. DMF); [Found: C, 31.79; H, 2.49; N,
3.14. C13H13I2NO2 requires C, 31.67; H, 2.44; N, 3.08%]; νmax(KBr) 3177 (N–H),
3062 (aromatic C–H), 2971–2878 (aliphatic C–H), 1668 (C=O) cm-1; δH (400
MHz, DMSO-d6) 9.02 (1Н, s, NH), 8.20 (1Н, s, Н-5 Ar), 7.93 (1Н, s, Н-7 Ar),
1.95–2.10 (2Н, m, spiro-ring), 1.65–1.88 (6Н, m, spiro-ring); δC (100 MHz,
DMSO-d6) 159.6 (С=О), 154.8, 149.3, 135.3, 119.9, 94.4 (С-2), 87.9 (C-I), 85.8
(C-I), 37.1 (2СН2), 22.1 (2СН2); m/z (EI) 455 (29 M+), 373 (17), 245 (5), 83
(100%).
Synthesis of oxazines 10a,b and 13 (General method).
R
R
R'
O
OH
NH2
HOAc, (Ac)2O
H2SO4
O
CH3
NH
+
H3C
R'
R
R
O
O
10a R=H; R'=Me (80%)
10b R=i-Pr; R'=Me (70%)
13 R=R'=H (98%)
Concentrated H2SO4 (1 mL) was added to glacial acetic acid (3 mL), and the
solution formed was cooled on ice. A solution of corresponding salicylamide (0.01
5

mol), acetone or acetaldehyde (0.01 mol), and Ac2O (1 mL) in glacial acetic acid
ACCEPTED MANUSCRIPT
(3 mL) was prepared separately. To the mixture obtained, the above ice-cold
solution of H2SO4 and AcOH was added gradually with stirring on an ice bath. The
resulted mixture was stirred for 40 min and left to stay overnight at room
temperature, then pH was adjusted to ~7.0 with aq. Na2CO3 solution. The
precipitate formed was filtered off and recrystallized from aqueous MeOH.
Yield of compound 10a was 80 %, mp 137–138 °C (Ref.16: 136–138 °C).
Yield of compound 13 was 98 %, mp 150–152 °C (Ref.20: 143–147 °C).
6,8-Diisopropyl-2,2-dimethyl-2,3-dihydro-4H-1,3-benzoxazin-4-one (10b).
O
NH
O
70%, white powder, mp 145–147 °C (aq. MeOH); [Found: C, 73.42; H, 8.82; N,
5.30. C16H23NO2 requires C, 73.53; H, 8.87; N, 5.36%]; νmax(KBr) 3183 (N–H),
3066 (aromatic C–H), 2962–2871 (aliphatic C–H), 1674 (C=O) cm-1; δH (400
MHz, DMSO-d6) 8.57 (1Н, s, NH), 7.45 (1Н, s, Н-5 Ar), 7.24 (1Н, s, Н-7 Ar),
3.01–3.15 (1Н, m, CH(CH3)2), 2.78–2.89 (1Н, m, CH(CH3)2), 1.49 (6Н, s, 2CH3),
1.13–1.19 (12H, m, 2CH(CH3)2); δC (100 MHz, DMSO-d6) 161.5 (С=О), 150.7,
140.9, 135.7, 129.2, 121.3, 116.7, 86.7 (С-2), 32.8, 27.2, 27.1, 23.9, 22.3; m/z (EI)
261 (74 M+), 246 (12), 205 (96), 189 (43), 176 (100), 161 (75), 91 (10), 58 (26), 41
(11%).
Synthesis of perchlorates 5a–f (General method).
Method A (with heating).
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01 mol) and
DMF (2.3 mL, 0.03 mol) with ice cooling. The compound 4a (1.1 g, 0.005 mol)
was added to the Vilsmeier reagent. The reaction mixture was heated on a water
bath at 75–85 °C for 1 h (an orange solid was separated within 0.5 h). Then the
reaction mixture was cooled to 10 °C and treated with an ice-cold 15% aq. solution
of NaClO4 (10 mL). The precipitate of the salt 5a was filtered off, dried and
purified by refluxing with toluene. In the case of salts 5b–d, the reaction mixture
was cooled to 10 °C and treated with an ice-cold 15% aq. solution of NaClO4 (10
mL); then pH was adjusted to 8.0–9.0 with aq. NaOH. The solid products were
filtered off, washed and dried to give pure salts 5b–d. For salts 5e,f, the reaction
6

time was 4 h. Caution! Organic perchlorates are potentially explosive. The
ACCEPTED MANUSCRIPT
microanalysis were not performed in order to prevent an explosion.
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-2,3-dihydro-1H-
xanthen-4-yl)methylene]-N-methylmethanaminium perchlorate (5a).
N+
-
ClO4
O
N
N
96%, orange powder, mp 300 °C; νmax(KBr) 2939 (aliphatic C–H), 1708, 1600 cm-
1; δH (400 MHz, DMSO-d6/CCl4) 8.56 (1Н, s, N=CH–N(CH3)2), 8.20 (1Н, s,
СН=N+(CH3)2), 7.76 (1H, d, J 7.6 Hz, H Ar), 7.60–7.68 (2Н, m, H Ar), 7.34–7.42
(1Н, m, H Ar), 3.52 (6Н, s, СН=N+(CH3)2), 3.27 (3Н, s, N=CH–N(CH3)CH3), 3.25
(3Н, s, N=CH–N(CH3)CH3), 2.74–2.81 (2Н, m, 3-СН2 or 1-СН2), 2.59–2.74 (2Н,
m, 1-СН2 or 3-СН2), 1.61–1.78 (2Н, m, 2-СН2); δC (100 MHz, DMSO-d6/CCl4)
172.0, 165.2, 158.3, 155.8, 152.1, 132.3, 125.0, 124.7, 121.5, 119.2, 116.5, 101.9,
42.0, 40.0, 24.6, 24.0, 20.6; m/z (FAB) 310 (100 M+), 265 (6), 218 (11), 149 (33),
136 (35), 121 (12), 107 (24), 89 (19), 76 (27), 68 (21), 52 (29%).
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-1,2-
dihydrocyclopenta[b]chromen-3-yl)methylene]-N-methylmethanaminium
perchlorate (5b).
N+
-
ClO4
O
N
N
80%, red needles, mp 262–265 °C (DMF); νmax(KBr) 2964–2862 (aliphatic C–H),
1674, 1623 cm-1; δH (400 MHz, DMSO-d6) 8.45 (1Н, s, N=CH–N(CH3)2), 8.01–
8.11 (1Н, m, H Ar), 7.97 (1Н, s, СН=N+(CH3)2), 7.61–7.71 (1Н, m, H Ar), 7.39–
7.56 (2Н, m, H Ar), 3.35 (6Н, s, СН=N+(CH3)2), 3.23 (3Н, s, N=CH–N(CH3)CH3),
3.21 (3Н, s, N=CH–N(CH3)CH3), 3.07 (4Н, s, 2СН2); δC (100 MHz, DMSO-d6)
172.8, 157.2, 153.1, 150.6, 144.0, 132.0, 125.6, 125.0, 121.4, 116.5, 114.1, 102.6,
7

41.0, 34.8, 25.1, 24.9; m/z (FAB) 296 (100 M+), 137 (14), 107 (7), 91 (10), 80 (7),
ACCEPTED MANUSCRIPT
53 (10%).
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-diisopropyl-2,3-dihydro-
1H-xanthen-4-yl)methylene]-N-methylmethanaminium perchlorate (5c).
N+
-
ClO4
O
N
N
95%, orange-red powder, mp 215–217 °C. νmax(KBr) 2927 (aliphatic C–H), 1702,
1611 cm-1; δH (400 MHz, DMSO-d6) 8.17 (1Н, s, N=CH–N(CH3)2), 8.13 (1Н, s,
СН=N+(CH3)2), 7.47 (2Н, s, H-5,7 Ar), 3.53–3.59 (1Н, m, CH(CH3)2), 3.46 (6Н, s,
СН=N+(CH3)2), 3.22 (3Н, s, N=CH–N(CH3)CH3), 3.19 (3Н, s, N=CH–
N(CH3)CH3), 2.95–3.05 (1Н, m, CH(CH3)2), 2.77–2.82 (2Н, m, 3-СН2 or 1-СН2),
2.63–2.68 (2Н, m, 1-СН2 or 3-СН2), 1.65–1.75 (2Н, m, 2-СН2), 1.30 (6H, d, J 6.8
Hz, CH(CH3)2), 1.23 (6H, d, J 6.8, CH(CH3)2); δC (100 MHz, DMSO-d6) 172.2,
165.8, 156.0, 148.3, 148.1, 145.2, 135.5, 130.5, 127.8, 119.5, 110.7, 101.2, 41.5,
35.4, 33.2, 26.4, 24.6, 24.1, 24.0, 22.3, 21.0; m/z (FAB) 394 (100 M+), 378 (5), 349
(6%).
1Н NMR signals,
δ, ppm
1H-1H COSY
1.23 (d, CH(CH3)2)
2.95–3.05
3.53–3.59
2.63–2.68, 2.77–2.82
1.65–1.75
1.65–1.75
1.23
1.30 (d, CH(CH3)2)
1.65–1.75 (м, 2-СН2)
2.63–2.68 (м, 1-СН2 or 3-СН2)
2.77–2.82 (м, 3-СН2 or 1-СН2)
2.95–3.05 (м, 1Н, CH(CH3)2)
3.53–3.59 (м, 1Н, CH(CH3)2)
1.30
8

N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-diisopropyl-1,2-
ACCEPTED MANUSCRIPT
dihydrocyclopenta[b]chromen-3-yl)methylene]-N-methylmethanaminium
perchlorate (5d).
N+
-
ClO4
O
N
N
87%, red powder, mp 258–260 °C; νmax(KBr) 2960–2925 (aliphatic C–H), 1624
cm-1; δH (400 MHz, DMSO-d6) 8.42 (1Н, s, N=CH–N(CH3)2), 7.78 (1Н, s,
СН=N+(CH3)2), 7.75 (1Н, s, H Ar), 7.45 (s, 1Н, H Ar), 3.65–3.75 (m, 1Н,
CH(CH3)2), 3.33 (6Н, s, СН=N+(CH3)2), 3.21 (3Н, s, N=CH–N(CH3)CH3), 3.16
(3Н, s, N=CH–N(CH3)CH3), 3.04–3.13 (4Н, m, 2СН2), 2.95–3.03 (1Н, m,
CH(CH3)2), 1.29 (6H, d, J 6.8 Hz, CH(CH3)2), 1.22 (6H, d, J 6.8 Hz, CH(CH3)2);
δC (100 MHz, DMSO-d6) 172.5, 157.3, 152.9, 149.1, 148.6, 145.4, 136.0, 127.4,
121.3, 119.4, 116.0, 101.9, 40.8, 34.5, 33.2, 26.0, 25.1, 24.9, 23.8, 22.8; m/z (FAB)
380 (100 M+), 364 (9%).
N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-diiodo-2,3-dihydro-1H-
xanthen-4-yl)methylene]-N-methylmethanaminium perchlorate (5e).
N+
-
I
ClO4
O
N
I
N
Yellow powder, yield ~54% (calculated for proposed structure), mp 245–252 °C.
This intermediate perchlorate was used on the next step without further
purification.
9

N-[(9-{[(1E)-(Dimethylamino)methylene]amino}-5,7-diiodo-1,2-
ACCEPTED MANUSCRIPT
dihydrocyclopenta[b]chromen-3-yl)methylene]-N-methylmethanaminium
perchlorate (5f).
N+
-
I
ClO4
O
N
I
N
Pink powder, yield ~57% (calculated for proposed structure), mp 225–233
°C. This intermediate perchlorate was used on the next step without further
purification.
Synthesis of perchlorates 5a–d. Method B (at room temperature).
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01 mol) and DMF
(2.3 mL, 0.03 mol) with ice cooling. The compound 4a (1.1 g, 0.005 mol) was
added to the Vilsmeier reagent. The reaction mixture was stirred vigorously at
room temperature for 24 h and maintained as in the method A. The salts 5b–d were
obtained in the same way.
Yield of compound 5a was 88 %.
Yield of compound 5b was 75%.
Yield of compound 5c was 85%.
Yield of compound 5d was 80%.
Synthesis of salts 8 and 11 a,b (General procedure).
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01 mol) and DMF
(2.3 mL, 0.03 mol) with ice cooling. The corresponding oxazine 7 or 10 (0.005
mol) was added to the Vilsmeier reagent. The reaction mixture was left to stand at
room temperature for 24 h. Then the reaction mixture was cooled to 10 °C and
treated with an ice-cold 15% aq. solution of NaClO4 (10 mL). The precipitate of
the corresponding salt 8 or 11 was filtered off, dried and purified by refluxing with
toluene. The microanalysis were not performed in order to prevent an explosion
.
10

ACCEPTED MANUSCRIPT
N-Methyl-N-({[(4Z)-2-phenyl-4H-chromen-4-
ylidene]amino}methylene)methanaminium perchlorate (8).
O
N
-
N+
ClO4
67%, yellow powder, mp 210–213 °C (МеОН); νmax(KBr) 1630–1640 (C=N),
1614 (C=C), 1597 cm-1; δH (400 MHz, DMSO-d6) 9.23 (1Н, s, N–CH=N+(CH3)2),
8.51–8.58 (1Н, m, H Ar), 8.29–8.35 (2Н, m, H Ar), 8.07 (1Н, s, Н-3), 8.01–8.13
(2Н, m, H Ar), 7.62–7.82 (4Н, m, H Ar), 3.52 (3Н, s, CH3), 3.49 (3Н, s, CH3); δC
(100 MHz, DMSO-d6) 166.4, 164.7, 161.6, 155.0, 136.4, 133.5, 130.2, 129.3,
127.3, 127.2, 125.7, 121.2, 118.6, 101.1, 42.9 (СН3), 36.7 (СН3); m/z (FAB) 277
(100 M+), 222 (6%).
N,N'-[2-(4-{[(1E)-(Dimethylamino)methylene]amino}-2H-chromen-2-
ylidene)propane-1,3-diylidene]bis(N-methylmethanaminium) diperchlorate
(11a).
-
ClO4
N+
-
N+
ClO4
O
N
N
90%, yellow powder, mp 223–225 °C (МеОН); νmax(KBr) 2929 (aliphatic C–H),
1622, 1526 cm-1; δH (400 MHz, DMSO-d6) 8.94 (1Н, s, N=CH–N(CH3)2), 8.42–
8.48 (3Н, m, H Ar and СН=N+(CH3)2), 7.89–8.05 (2Н, m, H Ar), 7.63–7.69 (1Н,
m, H Ar), 7.12 (1Н, s, Н-3), 3.61 (6Н, s, СН=N+(CH3)2), 3.46 (3Н, s, N=CH–
N(CH3)CH3), 3.42 (3Н, s, N=CH–N(CH3)CH3), 3.24 (6Н, s, СН=N+(CH3)2); δC
(100 MHz, DMSO-d6) 164.7, 162.4, 160.5, 154.3, 135.6, 127.0, 125.7, 120.4,
118.2, 101.4, 92.1, 48.5, 42.9, 42.6, 36.4; m/z (FAB) 427 (14 (M+37ClO4)+), 425
(42 (M+37ClO4)+), 326 (12), 311 (6), 280 (12), 270 (6), 225 (6), 165 (7%).
11

N,N'-[2-(4-{[(1E)-(Dimethylamino)methylene]amino}-6,8-diisopropyl-2H-
ACCEPTED MANUSCRIPT
chromen-2-ylidene)propane-1,3-diylidene]bis(N-methylmethanaminium)
diperchlorate (11b).
-
ClO4
N+
-
N+
ClO4
O
N
N
Yellow powder, yield 85% (calculated for proposed structure), mp 220–227 °C.
This intermediate diperchlorate was used on the next step without further
purification.
Synthesis of benzopyrans 6a–f (General method).
The corresponding salt 5a-f (1.0 g, 0.002 mol) was dissolved in hot DMF (5
mL). To the obtained solution, an aqueous 15 % NaOH solution (1.5 mL) was
added and the mixture was stirred vigorously at 60–75 °C for 5 min. The
precipitated solid of corresponding compound 6a–f was filtered off. If no solid
precipitated, the solution cooled to the room temperature and water was added.
N'-(4-Formyl-2,3-dihydro-1H-xanthen-9-yl)-N,N-dimethylimidoformamide
(6a).
CHO
O
N
N
85%, yellow-green needles, mp 175–177 °C (aq. МеОН); [Found: C, 72.41; H,
6.49; N, 9.98. C17H18N2O2 requires C, 72.32; H, 6.43; N, 9.92%]; νmax(KBr) 2932–
2852 (aliphatic C–H), 1632 (СНО) cm-1; δH (400 MHz, DMSO-d6) 10.13 (1Н, s,
СНО), 7.70 (1Н, s, N=CH–N(CH3)2), 7.49–7.56 (1Н, m, H Ar), 7.33–7.42 (1Н, m,
H Ar), 7.19–7.26 (1Н, m, H Ar), 7.10–7.18 (1Н, m, H Ar), 3.03 (3Н, s, СН3), 3.01
(3Н, s, СН3), 2.50 (2H, 3-СН2 or 1-СН2, overlapped with DMSO signals), 2.25–
2.29 (2Н, m, 1-СН2 or 3-СН2), 1.52–1.56 (2Н, m, 2-СН2); δH (400 MHz, DMSO-
d6/CF3CO2D) 10.00 (1Н, s, СНО), 8.41 (1Н, s, N=CH–N(CH3)2), 7.58 (1Н, d, J
12

7.6 Hz, H-5 Ar), 7.50 (1Н, t, J 7.6 Hz, H-6 Ar), 7.34 (1Н, d, J 8.1 Hz, H-8 Ar),
ACCEPTED MANUSCRIPT
7.25 (1Н, t, J 7.4 Hz, H-7 Ar), 3.27 (3Н, s, СН3), 3.31 (3Н, s, СН3), 2.58–2.70
(2Н, m, 3-СН2 or 1-СН2), 2.28–2.40 (2Н, m, 1-СН2 or 3-СН2), 1.55–1.75 (2Н, m,
2-СН2); δC (100 MHz, DMSO-d6) 184.2 (СНО), 162.5, 154.6, 151.6, 146.9, 130.2,
124.0, 123.3, 120.8, 115.2, 110.9, 109.0, 33.8, 24.7, 27.0, 20.1; m/z (EI) 282 (100
M+), 265 (16), 253 (60), 239 (13), 210 (10), 196 (6), 181 (11), 152 (5), 127 (7), 77
(8), 58 (6), 43 (17%).
N'-(3-Formyl-1,2-dihydrocyclopenta[b]chromen-9-yl)-N,N-
dimethylimidoformamide (6b).
CHO
O
N
N
83%, yellow-green needles, mp 196–198 °C (aq. МеОН); [Found: C, 71.51; H,
5.97; N, 10.40. C16H16N2O2 requires C, 71.62; H, 6.01; N, 10.44%]; νmax(KBr)
2924 (aliphatic C–H), 1630 (СНО) cm-1; δH (400 MHz, DMSO-d6) 9.77 (1Н, s,
СНО), 8.08 (1Н, s, N=CH–N(CH3)2), 7.71–7.77 (1Н, m, H Ar), 7.32–7.40 (1Н, m,
H Ar), 7.15–7.24 (2Н, m, H Ar), 2.51–3.07 (3Н, s, СН3), 3.02 (3Н, s, СН3), 2.76–
2.85 (2Н, m, СН2), 2.55 (2Н, m, СН2); δC (100 MHz, DMSO-d6) 180.4 (CHO),
166.2, 155.5, 152.2, 143.2, 129.7, 124.0, 123.8, 122.2, 118.6, 155.5, 112.0, 33.8,
23.2; m/z (FAB) 269 (100 MH+), 239 (11%).
N'-(4-Formyl-5,7-diisopropyl-2,3-dihydro-1H-xanthen-9-yl)-N,N-
dimethylimidoformamide (6c).
CHO
O
N
N
90%, yellow powder, mp 188–190 °C (aq. МеОН); [Found: C, 75.47; H, 8.32; N,
7.69. C23H30N2O2 requires C, 75.38; H, 8.25; N, 7.64%]; νmax(KBr) 2927–2864
13

(aliphatic C–H), 1651 (СНО) cm-1; δH (400 MHz, DMSO-d6) 10.19 (1Н, s, СНО),
ACCEPTED MANUSCRIPT
7.66 (1Н, s, N=CH–N(CH3)2), 7.24 (1Н, s, H Ar), 7.19 (1Н, s, H Ar), 3.35–3.43
(1Н, m, CH(CH3)2), 3.05 (6Н, m, N=CH–N(CH3)2), 2.86–2.91 (1Н, m, CH(CH3)2),
2.49–2.53 (2Н, m, 3-СН2 or 1-СН2), 2.29–2.34 (2Н, m, 1-СН2 or 3-СН2), 1.56–
1.62 (2Н, m, 2-СН2), 1.29 (6H, d, J 6.8 Hz, CH(CH3)2), 1.21 (6H, d, J 6.8 Hz,
CH(CH3)2); δC (100 MHz, DMSO-d6) 183.4 (CHO), 162.8, 154.6, 148.0, 147.0,
142.9, 134.1, 125.3, 120.3, 118.9, 110.4, 108.7, 33.8, 33.1, 26.8, 24.4, 23.9, 22.3,
21.2, 20.3; m/z (EI) 366 (100 M+), 349 (8), 337 (36), 322 (6), 59 (8), 43 (19%).
N'-(3-Formyl-5,7-diisopropyl-1,2-dihydrocyclopenta[b]chromen-9-yl)-N,N-
dimethylimidoformamide (6d).
CHO
O
N
N
85%, yellow powder, mp 133–136 °C (aq. МеОН); [Found: C, 75.11; H, 8.08; N,
7.99. C22H28N2O2 requires C, 74.97; H, 8.01; N, 7.95%]; νmax(KBr) 2925 (aliphatic
C–H), 1630 (СНО) cm-1; δH (400 MHz, DMSO-d6) 9.79 (1Н, s, СНО), 8.07 (1Н, s,
N=CH–N(CH3)2), 7.48 (1Н, s, H Ar), 7.17 (1Н, s, H Ar), 3.33 (1H, m, CH,
overlapped with a peak of water), 3.07 (3Н, s, N=CH–N(CH3)CH3), 3.03 (3Н, s,
N=CH–N(CH3)CH3), 2.89–2.99 (1Н, m, CH(CH3)2), 2.79–2.89 (2Н, m, СН2),
2.51–2.60 (2Н, m, СН2), 1.22 (12H, d, J 6.8 Hz, 2CH(CH3)2); δC (100 MHz,
DMSO-d6) 180.0 (CHO), 166.5, 158.4, 147.6, 144.2, 143.6, 134.2, 125.1, 121.6,
118.8, 118.0, 111.6, 33.9, 33.1, 27.2, 24.0, 23.3, 23.2, 22.4; m/z (EI) 352 (100 M+),
337 (6), 323 (21), 308 (16), 280 (14), 44 (7%).
N'-(4-Formyl-5,7-diiodo-2,3-dihydro-1H-xanthen-9-yl)-N,N-
dimethylimidoformamide (6e).
CHO
I
O
N
I
N
85%, yellow powder, mp 295–300 °C (aq. DMF); [Found: C, 38.31; H, 3.05; N,
5.29. C17H16I2N2O2 requires C, 38.23; H, 3.02; N, 5.24%]; νmax(KBr) 2925
14

(aliphatic C–H), 1674 (СНО) cm-1; δH (400 MHz, DMSO-d6) 10.29 (1Н, s, СНО),
ACCEPTED MANUSCRIPT
8.05 (1Н, s, N=CH–N(CH3)2), 7.73 (1Н, s, H Ar), 7.72 (1Н, s, H Ar), 3.04 (3Н, s,
CH3), 3.01 (3Н, s, CH3), 2.50–2.55 (2Н, m, 3-СН2 or 1-СН2), 2.24–2.30 (2Н, m, 1-
СН2 or 3-СН2), 1.51–1.57 (2Н, m, 2-СН2); δC (100 MHz, DMSO-d6) 185.1 (CHO),
166.0, 161.8, 155.1, 145.5, 144.8, 132.2, 123.6, 111.8, 110.2, 88.1 (C-I), 85.4 (C-
I), 34.9, 33.9, 24.5, 20.8, 19.9; m/z (EI) 534 (100 M+), 505 (19), 152 (7), 42 (34%).
N'-(3-Formyl-5,7-diiodo-1,2-dihydrocyclopenta[b]chromen-9-yl)-N,N-
dimethylimidoformamide (6f).
I
CHO
O
I
N
N
80%, pink powder, mp 300 °C (aq. DMF); [Found: C, 37.09; H, 2.75; N, 5.44.
C16H14I2N2O2 requires C, 36.95; H, 2.71; N, 5.39%]; νmax(KBr) 2924 (aliphatic C–
H), 1615 (СНО) cm-1; δH (400 MHz, DMSO-d6/CF3CO2D) 9.74 (1Н, s, СНО),
8.42 (1Н, s, N=CH–N(CH3)2), 8.09 (1Н, s, H Ar), 7.81 (1Н, s, H Ar), 3.28 (3Н, s,
CH3), 3.21 (3Н, s, CH3), 2.84–2.88 (2Н, m, СН2), 2.52–2.60 (2Н, m, СН2); m/z
(EI) 520 (100 M+), 505 (7), 491 (13), 476 (7), 139 (9), 44 (40%).
Synthesis of benzopyrans 9 and 12a, b (General method).
The corresponding salt 8 or 11 (1.0 g) was dissolved in MeOH (5 mL) and
treated with 15 % aq. NaOH solution (1.5 mL), the mixture was slightly heated for
a few minutes. After cooling to the room temperature, water (3–4 mL) was added,
the precipitated solid was filtered off, washed with water to give benzopyrans 9,
12.
2-Рhenyl-4H-chromen-4-imine (9).
O
NH
78%, white powder, mp 68–70 °C (Ref.:21 66–67 °C) (МеОН); δH (400 MHz,
DMSO-d6) 9.00 (1Н, с, NH), 8.12–8.19 (1Н, m, H Ar), 7.83–8.01 (2Н, m, H Ar),
7.45–7.66 (5Н, m, H Ph), 7.33–7.37 (1Н, m, H Ar), 6.87 (1Н, s, Н-3); δC (100
15

MHz, DMSO-d6) 178.1, 155.9, 152.2, 133.1, 130.9, 129.4, 127.8, 126.2, 125.1,
+
ACCEPTED MANUSCRIPT
121.1, 118.2, 117.3, 94.0; m/z (FAB) 222 (100% MH ); m/z (FAB+NaI) 244 (36%
MNa+).
(4-Аmino-2H-chromen-2-ylidene)malonaldehyde (12a).
CHO
O
CHO
NH2
80%, pink powder, mp 300 °C (aq. DMF), mp of hydrate 220–222 °C (aq. MeOH);
[Found: C, 66.89; H, 4.18; N, 6.46. C12H9NO3 requires C, 66.97; H, 4.22; N,
6.51%]; νmax(KBr) 3369, 3348 (NH2), 1615 (CHO) cm-1; δH (400 MHz, DMSO-d6)
9.86 (2Н, br. s, 2СНО), 9.14 (1Н, br. s) and 8.85 (1H, br. s, NH2), 8.20 (1Н, d, J
8.1 Hz, H Ar), 7.79–7.86 (2Н, m, H Ar), 7.69 (1Н, d, J 8.1 Hz, H Ar), 7.53 (1Н, t,
J 7.6 Hz, H Ar); δC (100 MHz, DMSO-d6) 185.8 (2CHO), 167.3, 156.5, 152.8,
134.4, 125.2, 123.2, 118.2, 114.5, 106.8, 91.4; m/z (FAB) 216 (83 MH+) (83), 186
(26), 170 (11%); m/z (FAB+NaI) 238 (60% MNa+).
(4-Amino-6,8-diisopropyl-2H-chromen-2-ylidene)malonaldehyde (12b).
CHO
O
CHO
NH2
84%, light gray powder, mp 295 °C (aq. DMF); [Found: C, 72.08; H, 6.97; N,
4.62. C18H21NO3 requires C, 72.22; H, 7.07; N, 4.68%]; νmax(KBr) 3323 (NH2),
2959 (aliphatic C–H), 1692 (CHO) cm-1; δH (400 MHz, DMSO-d6) 9.77 (2Н, br. s,
2СНО), 9.00 (1Н, br. s) and 8.74 (1Н, br. s, NH2), 7.92 (1Н, s, H Ar), 7.81 (1Н, s,
H Ar), 7.59 (1Н, s, Н-3), 3.65–3.69 (1Н, m, CH(CH3)2), 2.98–3.02 (1Н, m,
CH(CH3)2), 1.24–1.30 (12Н, m, 2CH(CH3)2); δC (100 MHz, DMSO-d6) 186.1
(2CHO), 165.8, 157.4, 148.5, 145.2, 137.5, 129.9, 117.7, 113.9, 106.9, 91.7, 33.4,
26.4, 23.8, 22.4; m/z (EI) 299 (8 M+), 271 (100), 254 (87), 238 (5), 121 (5), 91 (5),
43 (17%).
16

2-Methyl-4-oxo-2H-1,3-benzoxazine-3(4H)-carbaldehyde (14).
ACCEPTED MANUSCRIPT
O
N
CHO
O
The Vilsmeier reagent was prepared from POСl3 (0.92 mL, 0.01 mol) and DMF
(2.3 mL, 0.03 mol) with ice cooling. The compound 13 (0.82 g, 0.005 mol) was
added to the Vilsmeier reagent. The reaction mixture was heated on a water bath at
75–80 °C for 1 h. Then the reaction mixture was cooled to the room temperature,
treated with water (10 mL) and left to stand at r.t. The precipitate was filtered off
to give the imide 14 (0.86 g, 90%) as white powder, mp 60–62 °C (aq. МеОН);
[Found: C, 62.98; H, 4.82; N, 7.39. C10H9NO3 requires C C, 62.82; H, 4.74; N,
7.33%]; νmax(KBr) 1714 (imide) cm-1; δH (400 MHz, DMSO-d6) 9.27 (1Н, s,
СНО), 7.93 (1Н, d, J 7.8 Hz, H-8 Ar), 7.69 (1Н, t, J 7.7 Hz, H-7 or H-6 Ar), 7.23
(1Н, t, J 7.6 Hz, H-6 or H-7 Ar), 7.12 (1Н, d, J 8.3 Hz, H-5 Ar), 6.37–6.44 (1Н, q,
J 6.2 Hz, Н-2), 1.42 (3Н, d, J 6.2 Hz, СН3); δC (100 MHz, DMSO-d6) 160.0
(CHO), 159.8 (CO), 155.4, 137.1, 128.1, 123.0, 117.9, 115.5, 78.8 (С-2), 18.8
(СН3); m/z (EI) 191 (6 M+),163 (24), 148 (11), 120 (100), 92 (47), 65 (12), 39 (10),
31 (27%).
The hydrolysis of imide 14.
To a solution of compound 14 (1.91 g, 0.01 mol) in MeOH (10 mL), water
(4 mL) was added and the mixture was left to stand at the room temperature for 12
h. The colorless needles of oxazine 13 were filtered off, the yield was 1.55 g (95
%), mp 150–152 °C (Ref.20: 143–147 °C).
9-Chloro-1,2,3,4-tetrahydroacridine (16).
N
Cl
Method A.
The compound 15 (2.17 g, 0.01 mol) was added to DMF (1 mL). The
suspension formed was treated with the ice-cold Vilsmeier reagent obtained from
DMF (6 mL) and POCl3 (2.75 mL, 0.03 mol) under ice-cooling. A yellow solid
precipitated abundantly within 10–15 min. After 0.5 h the reaction mixture was
poured on ice and treated with aqueous ammonia, the obtained solid was filtered
off and dried to give acridine 16. The yield is 2.17 g (~100%), mp 68–70 °C
17

(Ref.:14 mp 68–70 °C). Spectral data for 16 (FTIR, NMR) were identical to the
reported data.14
ACCEPTED MANUSCRIPT
Method B.
The compound 17 (1.99 g, 0.01 mol) was added to DMF (1 mL). The
suspension formed was treated with the ice-cold Vilsmeier reagent obtained from
DMF (4 mL) and POCl3 (1.83 mL, 0.02 mol) under ice-cooling. A yellow solid
precipitated abundantly within 10–15 min. After 0.5 h the reaction mixture was
poured on ice and treated with aqueous ammonia, the obtained solid was filtered
off and dried to give acridine 16. The yield was 2.17 g (~100%), yellow crystals,
mp 68–70 °C.
1,3,4,10-Тetrahydroacridin-9(2H)-one (17).
H
N
O
The compound 15 (2.17 g, 0.01 mol) was added to DMF (1 mL). The
suspension formed was treated with the ice-cold Vilsmeier reagent obtained from
DMF (2 mL) and POCl3 (0.92 mL, 0.01 mol) under ice-cooling. A white solid
precipitated abundantly within 10-15 min. After 0.5 h the reaction mixture was
poured on ice and treated with aqueous ammonia, the obtained solid was filtered
off and dried to give acridine 17. The yield was 1.99 g (~100%), colorless crystals,
mp 358–360 °C (Ref.:22 mp 355–358 °C). Spectral data for 17 (FTIR, NMR) were
identical to the reported data.15
N-[(4-Chloro-3,5,6,7-tetrahydrospiro[1,3-benzoxazine-2,1'-cyclohexan]-8-
yl)methylene]-N-methylmethanaminium perchlorate (19).
-
N+
ClO4
O
NH
Cl
The Vilsmeier reagent was prepared from POСl3 (2.76 mL, 0.03 mol) and DMF
(6.9 mL, 0.03 mol) with ice cooling. The compound 18 (2.0 g, 0.009 mol) was
added to the Vilsmeier reagent. The reaction mixture was left to stand at the room
temperature for 0.5 h and then was treated with an ice-cold 15% aq. solution of
18

NaClO4 (10 mL). The precipitate was filtered off to give perchlorate 19 (2.38 g,
ACCEPTED MANUSCRIPT
67%), as yellow cubic crystals, mp 180–182 °C (i-PrOH), νmax(KBr) 3263 (N–H),
2934–2862 (aliphatic C–H), 1637 cm-1; δH (400 MHz, DMSO-d6/ССl4) 9.05 (1Н,
br. s, NH), 7.95 (1Н, s, СН=N+(CH3)2), 3.43 (6Н, s, СН=N+(CH3)2), 2.64–2.68
(2Н, m, СН2), 2.40–2.44 (2Н, m, СН2), 1.47–1.99 (12Н, m, 6СН2); δC (100 MHz,
DMSO-d6/ССl4) 165.7, 157.2, 143.9, 100.6, 99.2, 21.4, 21.8, 23.5, 89.5 (С-2),
32.0, 24.4; m/z (FAB) 297 (34 M(37Cl)+), 295 (100 M(35Cl)+), 259 (70), 217 (11),
175 (10%). The microanalysis were not performed in order to prevent an
explosion.
[(E)-(4-Chloro-6,7-dihydrospiro[1,3-benzoxazine-2,1'-cyclohexan]-8(5H)-
ylidene)methyl]dimethylamine (20).
N
O
N
Cl
To a solution of salt 19 (1.00 g) in MeOH (5 mL), 15% aq. NaOH (1.5 mL) was
added, the mixture was slightly heated for 5 min. After cooling to the room
temperature, water (2–3 mL) was added, the precipitated solid was filtered off,
washed with water to give compound 20 (0.65 g, 87%), as yellow powder, mp 91–
93 °C (aq. МеОН); [Found: C, 65.09; H, 7.80; N, 9.45. C16H23ClN2O requires C,
65.18; H, 7.86; N, 9.50%]; δH (400 MHz, DMSO-d6/ССl4) 6.68 (1Н, s, =СН-
N(СН3)2), 2.50–2.54 (2Н, m, СН2), 2.98 (6Н, s, N(СН3)2), 2.23–2.27 (2Н, m,
СН2), 1.38–1.84 (12Н, m, 6СН2); δC (100 MHz, DMSO-d6/ССl4) 157.1, 153.7,
140.4 (СН-N(СН3)2), 98.0, 96.8, 92.3 (С-2), 42.9 (2СН3), 34.1 (CH2), 24.9 (CH2),
24.5 (CH2), 23.7 (CH2), 22.5 (CH2), 21.5 (CH2); δC DEPT-135 (100 MHz, DMSO-
d6/CCl4) 140.0 (СН-N(СН3)2), 42.5 (2СН3), 33.7* (CH2), 24.4* (CH2), 24.0*
(CH2), 23.2* (CH2), 22.0* (CH2), 21.0* (CH2); *signals in antiphase; m/z (EI) 296
(29 M(37Cl)+), 294 (79 M(35Cl)+), 258 (100), 251 (50), 243 (31), 229 (15), 215
(21), 200 (16), 191 (11), 176 (30), 161 (21), 149 (16), 134 (32), 81 (40), 43 (46%).
19

ACCEPTED MANUSCRIPT
1H NMR spectrum (DMSO-d6/CCl4, 400 MHz) of 6,8-diisopropylspiro[1,3-benzoxazine-2,1'-cyclohexan]-4(3H)-one (4c).
O
NH
O
0.98
7.45 7.40
1.00
7.20
7.50
7.35
7.30
7.25
7.15
7.10
Chemical Shift (ppm)
DMSO-d6
0.98
8.5
1.00
1.01 1.01
3.0
2.08 7.17 13.24
2.0 1.5 1.0
20
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
2.5
Chemical Shift (ppm)