An Inverse Electron Demand Azo-Diels-Alder Reaction of o -Quinone Methides and Imino Ethers: Synthesis of Benzocondensed 1,3-Oxazines

Article abstract of DOI:10.1021/acs.joc.8b00692

We have studied the reactions of o-quinone methide precursors with imino ethers. The reaction provides a versatile route to substituted 1,3-benzoxazines. The proposed reaction mechanism involves the generation of the o-quinone methide intermediates, imino

Full text of DOI:10.1021/acs.joc.8b00692

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An Inverse Electron Demand Azo-Diels-Alder Reaction of o-Quinone
Methides and Imino Ethers: Synthesis of Benzocondensed 1,3-Oxazines
Dmitry Vladimirovich Osipov, Vitaly Aleksandrovich Osyanin, Guzel' D.
Khaysanova, Elvira R. Masterova, Pavel E. Krasnikov, and Yuri N. Klimochkin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00692 • Publication Date (Web): 29 Mar 2018
Downloaded from http://pubs.acs.org on March 29, 2018
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An Inverse Electron Demand Azo-Diels-Alder Reaction of o-Quinone
Methides and Imino Ethers: Synthesis of Benzocondensed 1,3-Oxazines
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Dmitry V. Osipov, Vitaly A. Osyanin,* Guzel’ D. Khaysanova,
Elvira R. Masterova, Pavel E. Krasnikov, Yuri N. Klimochkin
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Department of Organic Chemistry, Chemical Technological Faculty, Samara State Technical University, 244
Molodogvardeyskaya St., Samara 443100, Russian Federation.
Fax +7(846)3322122; Eꢀmail: vosyanin@mail.ru
NH
R2
O
R2
O
R3
MeO
broad substrate scope
yields up to 91%
catalyst free
nitrile equivalent
N
R1
R1
imino-Diels-Alder
R3
simple operation
in situ generated o-QM
50 examples
ABSTRACT: We have studied the reactions of oꢀquinone methide precursors with imino ethers.
The reaction provides a versatile route to substituted 1,3ꢀbenzoxazines. The proposed reaction
mechanism involves the generation of the oꢀquinone methide intermediates, iminoꢀDielsꢀAlder
reaction, and the elimination. This cascade process is a rare example of the participation of imino
ethers as dienophiles.
INTRODUCTION
The use of heteroꢀsubstituted dienes and/or dienophiles in [4+2]ꢀcycloaddition reactions
provides rapid and economic methods for the construction of sixꢀmembered heterocycles.
Preparation of nitrogen heterocycles through the iminoꢀDielsꢀAlder reactions has recently
received much attention.1 As a rule, the imino dienophile is a variant of the azaꢀDielsꢀAlder
reaction requires the use of imines with electron withdrawing substituents, such as Nꢀacyl, Nꢀ
sulfonyl, and Cꢀacylimines. At the same time, there are a limited number of examples involving
electronꢀrich (Cꢀheteroatomꢀsubstituted) imines.
Arenoꢀcondensed 1,3ꢀoxazine derivatives are of significant importance because of their
promising biological activity.2 In particular, they possess antibacterial, antifungal,3a anticancer3b
and antiꢀH5N13c activities, display DNAꢀdependent protein kinase inhibition.3d At the same time,
the natural 1,3ꢀbenzoxazines are extremely rare. Among them there are two isomeric
streptopyrroles isolated from Streptomyces rimosus and exhibiting bacterial protein histidine
kinase inhibitory and antimicrobial activities,4a benadrostin,4b platensimycin B2.4c Besides, 1,3ꢀ
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benzoxazines have been used as precursors in the preparation of chiral bidentate
(phoshinoaryl)benzoxazine ligands for asymmetric catalysis5a,b
polybenzoxazines synthesis5c (Figure 1).
and as monomers for
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Figure 1. Selection of Relevant 1,3-Benzoxazine Derivatives.
Only a few methods for the synthesis of 1,3ꢀbenzoxazines have been reported. Main
method is an acidꢀcatalyzed interaction between oꢀhydroxybenzyl alcohols6a,b or amines5b and
nitriles (Ritter reaction) as well as cyclization of Nꢀ(2ꢀhydroxybenzyl)amides,3c,5b,6c thermolysis
of 3ꢀmethylꢀ4Hꢀ1,2ꢀbrnzoxazine,6d from hydroxynitrones,6e,f oxydation of Nꢀarylideneꢀ1ꢀ(αꢀ
aminobenzyl)ꢀ2ꢀnaphtols with iodobenzene diacetate,3a oneꢀpot condensation of 1,1,3,3ꢀ
tetramethylguanidine, aromatic aldehydes and 2ꢀnaphthols3a (Figure 2) and a very recent
electrochemical CꢀH oxygenation of Nꢀbenzylamides in flow.6g This heterocyclic system can be
also considered as product of [4+2]ꢀcycloaddition between oꢀquinone methides (oꢀQMs) and
nitriles. However, nonꢀactivated nitriles are known to be poor dienophiles and unstable oꢀQMs
act as heterodienes usually only with electronꢀrich olefins. We have proposed that the use in this
reaction of stable oꢀQM precursors and imino ethers as synthetic equivalents of nitriles avoids
these difficulties.
Figure 2. Known Methods for Synthesis of 4Hꢀ1,3ꢀBenzoxazines and 1HꢀNaphto[1,2ꢀe][1,3]oxazines.
oꢀQMs as a heterodiene component in DielsꢀAlder reaction have received great attention
in the construction of a wide variety of chromane skeletons.7 It should be remarked that although
oꢀQMs have been reported to undergo [4+2]ꢀcycloadditions with different carbon dienophiles
there are only a few examples of [4+2]ꢀcycloaddition of in situ generated oꢀQMs to imino
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compounds.8 On the other hand, although imino ethers are widely used for the synthesis of
various nitrogenꢀcontaining heterocyclic compounds,9 they are very seldom utilized as
heterodienophiles. There have been reports of several reactions of imino ethers with 1,2,4,5ꢀ
tetrazines10 and 1,2,3ꢀtriazines11 which may be interpreted as DielsꢀAlder reactions. However,
their use for the synthesis of 4Hꢀ1,3ꢀbenzoxazines has not been described in literature. As a part
of our ongoing interest in developing new synthetic strategies for the construction of condensed
1,3ꢀbenzoxazines,12 we focused our attention on the reaction of oꢀQMs derived from 2ꢀnaphthol
Mannich bases with imino ethers.
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RESULTS AND DISCUSSION
To the best of our knowledge, there is only one report for synthesis of 1Hꢀnaphtho[1,2ꢀ
e][1,3]oxazine from imino ether. Fülöp et al. reported13 the reaction of unsubstituted 1ꢀ
aminomethylꢀ2ꢀnaphthol with ethyl benzimidate in boiling EtOH gave the described earlier 3ꢀ
phenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine 3aa in 37% yield. However, in the case of 1ꢀ(αꢀ
aminobenzyl)ꢀ2ꢀnaphthol and 2ꢀ(αꢀaminobenzyl)ꢀ1ꢀnaphthol only decomposition of the starting
aminomethylnaphthols was observed. We have shown that on heating 1ꢀ
[(dimethylamino)methyl]naphthalenꢀ2ꢀol 1a and methyl benzimidate 2a in boiling DMF, 1Нꢀ
naphtho[1,2ꢀe][1,3]oxazine 3aa was isolated in 90% yield. When the reaction was carried out in
ethanol or acetonitrile, no desired product formation was observed. The high temperature is
necessary to ensure the thermal decomposition of the Mannich base. The scope and generality of
this reaction were then explored. A variety of electronically divergent imino ethers and Mannich
bases of the naphthalene series were examined, and the results are summarized in Table 1. The
reaction proceeded without any problems for a wide range of coꢀreactants bearing electronꢀ
withdrawing and electronꢀdonating substituents on the aryl rings. Products can be easily purified
from impurities by single recrystallization, chromatographic purification is not usually required.
Besides, imino ethers of the heterocyclic series (furan, thiophene, pyridine derivatives) were
involved in this process. However, it should be noted that the reaction with ethyl nicotinimidate
2f is completed in 13–14 hours (compounds 3af,gf), although usually no more than 8 hours are
required. The example of (1ꢀadamantyl)acetimidate 2g shows that not only arylimidates can be
introduced into the reaction (compound 3ag). The mechanism of the reaction is believed to
involve initial elimination of dimethylamine from the Mannich base to afford a highly reactive
1,2ꢀnaphthoquinoneꢀ1ꢀmethide A, which reacts with imino ether to give unstable 2,3ꢀdihydroꢀ
1Hꢀnaphtho[1,2ꢀe][1,3]oxazine cycloadduct B. The subsequent loss of methanol leads to 1Hꢀ
naphtho[1,2ꢀe][1,3]oxazine 3. The formation of this cyclic system may be interpreted as a result
of a LUMOdiene/HOMOdienophileꢀcontrolled [4+2]ꢀcycloaddition reaction. Imino ether plays the
role of heterodienophile and oꢀQM – the role of 1ꢀoxadiene component.
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Table 1. Scope of the reaction
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R1a
R2
Product 3b
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1b)
H (1b)
Ph (1c)
Ph (1c)
Ph (1c)
Ph (1c)
4ꢀClC6H4 (1d)
4ꢀClC6H4 (1d)
3ꢀClC6H4 (1e)
4ꢀFC6H4 (1f)
4ꢀMeOC6H4 (1g)
4ꢀMeOC6H4 (1g)
4ꢀMeOC6H4 (1g)
2ꢀMeOC6H4 (1h)
2ꢀMeOC6H4 (1h)
2ꢀMeOC6H4 (1h)
3,4ꢀ(MeO)2C6H4 (1i)
3,4ꢀ(OCH2O)2C6H4 (1j)
3,4,5ꢀ(MeO)3C6H3 (1k)
2ꢀthienyl (1l)
2ꢀthienyl (1l)
4ꢀpyridyl (1m)
Ph (2a)
3aa, 5h, 90%
3ab, 3h, 85%
3ac, 5h, 65%
3ad, 5h, 74%
3ae, 5h, 77%
3af, 13h, 78%
3ag, 5h, 68%
3ba, 2h, 85%
3bd, 2h, 68%
3ca, 4h, 76%
3cb, 4h, 80%
3cd, 6h, 78%
3ce, 4h, 88%
3da, 4h, 74%
3db, 5h, 76%
3ea, 4h, 66%
3fa, 4h, 91%
3ga, 5h, 71%
3gb, 5h, 88%
3gf, 14h, 83%
3ha, 4h, 78%
3hd, 8h, 65%
3hh, 6h, 80%
3ib, 7h, 85%
3jb, 7h, 67%
3ka, 5h, 85%
3la, 2h, 83%
3le, 4h, 60%
3ma, 5h, 69%
4ꢀBrC6H4 (2b)
4ꢀCF3C6H4 (2c)
2ꢀfuryl (2d)
2ꢀthienyl (2e)
3ꢀpyridyl (2f)
CH2ꢀ1ꢀAd (2g)
Ph (2a)
2ꢀfuryl (2d)
Ph (2a)
4ꢀBrC6H4 (2b)
2ꢀfuryl (2d)
2ꢀthienyl (2e)
Ph (2a)
4ꢀBrC6H4 (2b)
Ph (2a)
Ph (2a)
Ph (2a)
4ꢀBrC6H4 (2b)
3ꢀpyridyl (2f)
Ph (2a)
2ꢀfuryl (2d)
4ꢀMeC6H4 (2h)
4ꢀBrC6H4 (2b)
4ꢀBrC6H4 (2b)
Ph (2a)
Ph (2a)
2ꢀthienyl (2e)
Ph (2a)
a X = H (1a,d-m), X = adamantanꢀ1ꢀyl (1b). b Isolated yields.
It should be noted that good yields of 1Нꢀnaphtho[1,2ꢀe][1,3]oxazines 3 are attained by
the use of 1 equiv. of imino ethers. At the same time, for attaining reasonable yields in the
reactions of oꢀQMs with many others dienophiles, a large excess of the latter is usually
required14 to prevent diꢀ and trimerization of oꢀQMs.
This reaction was extended to the Mannich bases of the heterocyclic series (quinoline, βꢀ
carboline and indole derivatives). It provides a facile route to the hitherto unknown heterocyclic
systems 4Hꢀ[1,3]oxazino[5,6ꢀh]quinolines 3nb,oa,ob, 1,7,8,9,10,11ꢀhexahydro[1,3]oxazino[5,6ꢀ
e]pyrido[3,4ꢀb]indole 3pa and 1,7ꢀdihydro[1,3]oxazino[5,6ꢀe]indole 3qa (Scheme 1).
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Scheme 1. Extension of the Developed Methodology to Heterocyclic Precursors of oꢀQuinone Methides.
Thus, as Mannich bases can easily be synthesized from naphthols and aldehydes by the
Mannich reaction and imino ethers are readily accessible from nitriles, the reaction described
herein represents a convenient synthesis of 1Нꢀnaphtho[1,2ꢀe][1,3]oxazines.
Attempts to obtain 1Hꢀnaphtho[1,2ꢀe][1,3]oxazines by a threeꢀcomponent reaction from
2ꢀnaphthol, aromatic aldehyde and imino ether gave less satisfactory results. The products
3ah,ca,ra were obtained in lower yields and required purification by column chromatography.
The best results were obtained by carrying out the reaction without a solvent at 130 °C in the
presence of acetic acid (5 mol. %) as a catalyst. Heating of the equimolar mixture of these
reagents in DMF under reflux or at 130 °C does not result in the formation of 1Hꢀnaphtho[1,2ꢀ
e][1,3]oxazines 3ah,ca,ra. The mechanism of the threeꢀcomponent reaction comprise the initial
hydroxyalkylation of 2ꢀnaphthols with aromatic aldehydes to yield unstable alcohols C, which
dehydrate with generation of oꢀQMs. The further transformations lead to 1Hꢀnaphtho[1,2ꢀ
e][1,3]oxazines 3ah,ca,ra (Scheme 2). The lowest yield was found for naphthoxazine 3ra, which
has a strong electronꢀwithdrawing nitro group in the aryl substituent. This finding is likely a
result of the difficulty in generating the corresponding oꢀQM.
Scheme 2. Threeꢀcomponent Condensation of 2ꢀNaphthol, Aromatic Aldehydes and Imino Ethers
Having established a strategy for the synthesis of 1Нꢀnaphtho[1,2ꢀe][1,3]oxazines, its
applicability to the preparation of 4Hꢀ1,3ꢀbenzoxazines 5 was studied. It turned out that phenol
Mannich bases can also be used in the reactions with imino ethers, providing 4Hꢀ1,3ꢀ
benzoxazines 5 in moderate to good yieds. Instead of Mannich bases, 2ꢀhydroxybenzyl alcohols
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can be used as oꢀbenzoquinone methide precursors (Scheme 3). The best results were also
obtained in DMF under reflux. Attempts to extend this reaction to the 4ꢀchloroꢀ2ꢀ
(hydroxymethyl)phenol, however, gave less satisfactory results to furnish the expected product
5ha, maybe because of the relatively greater thermal stability of this hydroxybenzyl alcohol
compared to the oꢀQM precursors containing electronꢀdonating group in benzyl position and
consequent difficulty in generating the oꢀQMs. The sterically hindered 4Hꢀ1,3ꢀbenzoxazines
5ja,ka were obtained in excellent yields, indicating that steric hindrance had no obvious
influence on the efficiency of the method.
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Scheme 3. Synthesis of 2ꢀArylꢀ4Hꢀbenzo[e][1,3]oxazines from Phenol Mannich Bases and 2ꢀ
Hydroxybenzyl Alcohols.
In the case of unsubstituted salicyl alcohol and methyl benzimidate, the content of the
desired 2ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine in the mixture did not exceed 20%. The products of
decomposition and hydrolysis of imino ether, as well as products of conjugated addition of
nucleophiles (methanol, dimethylamine and benzamide) to oꢀQM were identified. The
composition of the reaction mixture is determined by GCꢀMC analysis. Dimethylamine is
formed as a result of partial decomposition of DMF (Scheme 4).
Scheme 4. Reaction of Methyl Benzimidate and Salicyl alcohol
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The interaction of quaternary ammonium salts with imino ethers proceeds also less
unambiguously. Thus, in the reaction between quaternary ammonium salt 6 and methyl 4ꢀ
bromobenzimidate 2b, Nꢀ(2ꢀhydroxybenzyl)benzamide 7 was isolated along with 4Hꢀ1,3ꢀ
benzoxazine 5ab (Scheme 5). The formation of benzamide 7 could be explained by the
hydrolytic cleavage of the benzoxazine 5ab during the treatment of the reaction mixture.
However, the 1,3ꢀbenzoxazine 5ab obtained from the Mannich base under similar conditions
proves to be resistant to hydrolysis. Apparently, at first the protonated form of imino ether under
the action of the iodide ion is converted to an amide (Pinner rearrangement), and then 4ꢀ
bromobenzamide reacts with oꢀQM. The presence of imino ether facilitates the generation of oꢀ
QM from a quaternary ammonium salt 6 by partial deprotonation of phenolic hydroxyl group. It
should be noted that the acidity of quaternary ammonium salts of approximately 2.6ꢀ2.7 orders
of magnitude higher than the corresponding Mannich base.15
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Scheme 5. Formation of Nꢀ(2ꢀHydroxybenzyl)benzamide 7.
At the same time, the reaction between 1ꢀ[(dimethylamino)(phenyl)methyl]naphthalenꢀ2ꢀ
ol and methyl 4ꢀbenzimidate in DMF under reflux in the presence of NaI (1.5 equv.) leads only
to naphtho[1,2ꢀe][1,3]oxazine 3ca in 72% yield. Thus, the presence of nucleophilic iodide ion
and protonated form of imino ether is necessary for the formation of a secondary amide.
It should also be noted that in the preparation of arenoꢀ1,3ꢀoxazines imino ethers must be
used as free bases and not as salts. Indeed, the reaction of methyl 4ꢀmethylbenzimidate
hydrochloride and Mannich base 1c in boiling DMF leads to the formation of 2ꢀnaphthol and
benzaldehyde due to retroꢀMannich reaction as well as 4ꢀmethylbenzamide as a result of Pinner
rearrangement (Scheme 6).
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Scheme 6. Reaction of 2ꢀNaphthol Mannich Base with Methyl 4ꢀMethylbenzimidate Hydrochloride.
The structures of all products were determined on the basis of their analytical and spectral
data. IR spectra of naphtho[1,2ꢀe][1,3]oxazines 3 and 4Hꢀ1,3ꢀbenzoxazines 5 contain the band of
high intensity at 1653–1694 cm−1 attributed to C=N bond. The 1H NMR spectra of products 3, 5
show characteristic 1ꢀH and 2ꢀH singlets at δ 6.34–6.97 and 4.74–5.15 ppm for methyne and
methylene protons, respectively. A distinguishing resonance at 51.7–57.2 ppm for CHꢀ1, 42.8–
43.5 ppm for CH2ꢀ1 and 145.9–147.1 ppm for Cꢀ4a are observed in the 13C NMR spectra of
naphtho[1,2ꢀe][1,3]oxazines 3. A signal in the region of 150.5–153.2 ppm was assigned to Cꢀ3 in
3ꢀarylꢀsubstituted naphtho[1,2ꢀe][1,3]oxazines 3 and Cꢀ2 in 4Hꢀ1,3ꢀbenzoxazines 7. The cyclic
nature of the products is also confirmed by the absence of phenolic OH stretching frequencies in
1
the IR spectra and phenolic proton signal in the H NMR spectra. In the mass spectra of
compounds 5ba, 5eb, one of the main direction of fragmentation is retroꢀDielsꢀAlder reaction,
leading to corresponding oꢀQM and nitrile.
CONCLUSION
A new method for the synthesis of benzocondensed 1,3ꢀoxazines from oꢀQM precursors
(Mannich bases and 2ꢀhydroxybenzyl alcohols) and imino ethers had been developed. The
reaction proceeds via electron demand iminoꢀDielsꢀAlder reaction followed by elimination. The
synthesis by the suggested procedure does not require an excess of any reagents, includes the use
of available reagents, good functional group tolerance, simple experimental steps and product
isolation, chromatographic purification is not usually required. The use of heterocyclic oꢀQM
precursors permits the preparation of 1,3ꢀbenzoxazines fused to heterocyclic rings.
EXPERIMENTAL SECTION
Materials and Characterization. FTIR spectra were taken in KBr pellets. 1H, 13C, 19F and
DEPT NMR spectra were recorded using a 400 MHz NMR spectrometer in CDCl3 or DMSOꢀd6
solutions, relative to residual solvent signal. Chemical shifts and coupling constants were
recorded in units of parts per million and hertz, respectively. Mass spectra were obtained on a
Finnigan Trace DSQ instrument, energy of ionizing electrons was 70 eV. The melting points
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were determined by capillary method and uncorrected. Elemental analysis was carried out on an
automatic CHNS analyzer. The reaction progress was controlled by TLC on aluminum foilꢀ
backed silica gel plates, visualization under UV light and in iodine vapor, eluent CH2Cl2.
1ꢀ[(Dimethylamino)(2ꢀmethoxyphenyl)methyl]naphthalenꢀ2ꢀol (1h). Dimethylamine (31.5
mL of a 33% aqueous solution, 0.21 mol) and 2ꢀmethoxybenzaldehyde (28.3 g, 0.21 mol) were
added to a solution of naphthalenꢀ2ꢀol (30 g, 0.21 mol) in ethanol (40 mL) at 25 ºC. The reaction
mixture was stored at room temperature for 5 days. The precipitate formed was filtered off,
washed with iceꢀcold methanol. Yield: 47 g (73%). Colorless solid, mp 133–135 °С. IR (KBr)
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max: 3100–2400, 2958, 1624, 1600, 1512, 1458, 1415, 1373, 1350, 1246, 1188, 1153, 1138,
1026, 948, 822, 756 cm−1. 1H NMR (400 MHz, CDCl3) δ: 2.21 (s, 3H), 2.56 (s, 3H), 4.03 (s, 3H),
5.78 (s, 1H), 6.81 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.2 Hz, 1H), 7.16–7.25 (m, 3H), 7.34 (t, J =
7.5 Hz, 1H), 7.54 (dd, J = 7.6, 1.6 Hz, 1H), 7.66–7.71 (m, 2H), 7.82 (d, J = 8.7 Hz, 1H), 14.21
(br. s, 1H). 13C NMR (100 MHz, CDCl3) δ: 41.1 (СH3), 45.5 (CH3), 55.7 (CH3), 63.0 (CH),
110.6 (CH), 116.9 (C), 120.1 (CH), 121.6 (2CH), 122.4 (CH), 126.4 (CH), 128.4 (C), 128.6 (C),
128.7 (CH), 129.2 (CH), 129.3 (CH), 129.9 (CH), 132.9 (C), 156.5 (C), 156.8 (C). Anal. Calcd
(%) for C20H21NO2, %: С, 78.11; Н, 6.86; N, 4.58. Found (%): С, 78.15; Н, 6.89; N, 4.56.
General Experimental Procedure for the Synthesis of Areno-condensed 1,3-Oxazines.
A mixture of imino ether (as the base) (2 mmol) and the corresponding precursor oꢀquinone
methide (2ꢀhydroxybenzyl alcohol, phenol or 2ꢀnaphthol Mannich base) (2 mmol) in DMF (8
mL) was heated at reflux until the release of dimethylamine ceased (control on wet indicator
paper). After the indicated time period, the solution was kept at –20 °C overnight. The
precipitate formed was filtered off, washed with iceꢀcold methanol and purified by
recrystallization (method A). If no precipitate was formed, the reaction mixture was poured into
brine (50 mL) to yield a solid product, which was filtered off, washed with water, dried and
purified by recrystallization (method B) or column chromatography (eluent – CHCl3) followed
by recrystallization (method C).
3ꢀPhenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3aa). Method B. Yield: 90%, 465 mg. Colorless
solid, mp 161–162 °C (EtOH) (lit.13 mp 161–162 °C). IR (KBr) υmax: 1680, 1628, 1605, 1518,
1440, 1364, 1331, 1279, 1225, 1177, 1098, 1055, 1016, 806, 775, 748, 692, 671 cm−1. 1H NMR
(400 MHz, CDCl3) δ: 5.15 (s, 2H), 7.22 (d, J = 8.7 Hz, 1H), 7.45–7.59 (m, 5H), 7.70 (d, J = 8.7
Hz, 1H), 7.76 (d, J = 8.7 Hz, 1H), 7.83 (d, J = 8.2 Hz, 1H), 8.12–8.15 (m, 2H). 13C NMR (100
MHz, CDCl3) δ: 43.4 (CH2), 110.8 (C), 116.6 (CH), 122.2 (CH), 124.9 (CH), 127.1 (CH), 127.4
(2CH), 128.4 (2CH), 128.6 (CH), 128.7 (CH), 130.0 (C), 131.1 (CH, C), 132.4 (C), 146.5 (C),
152.3 (C). Anal. Calcd (%) for C18H13NO: С, 83.37; Н, 5.05; N, 5.40. Found (%): С, 83.25; Н,
4.94; N, 5.51.
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3ꢀ(4ꢀBromophenyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ab). Method A. Yield: 85%, 575
mg. Colorless solid, mp 178–179 °С (EtOH–DMF). IR (KBr) υmax: 1678, 1630, 1589, 1518,
1485, 1395, 1364, 1331, 1277, 1225, 1175, 1109, 1094, 1070, 1009, 831, 806, 768, 745, 721,
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706, 664. H NMR (400 MHz, CDCl3) δ: 5.10 (s, 2H), 7.17 (d, J = 8.7 Hz, 1H), 7.45 (t, J = 7.8
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Hz, 1H), 7.53–7.58 (m, 3H), 7.65 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.81 (d, J = 8.2
Hz, 1H), 7.96 (d, J = 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 43.4 (CH2), 110.6 (C), 116.4
(CH), 122.2 (CH), 125.0 (CH), 125.8 (C), 127.1 (CH), 128.7 (CH), 128.8 (CH), 129.0 (2CH),
130.0 (C), 131.2 (C), 131.3 (C), 131.5 (2CH), 146.3 (C), 151.5 (C). Anal. Calcd (%) for
C18H12BrNO: С, 63.92; Н, 3.58; N, 4.14. Found (%): С, 64.00; Н, 3.62; N, 4.08.
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3ꢀ[4ꢀ(Trifluoromethyl)phenyl]ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ac). Method B. Yield:
65%, 425 mg. Colorless solid, mp 175–176 °С (DMF). IR (KBr) υmax: 1678, 1624, 1605, 1589,
1516, 1408, 1327, 1227, 1173, 1130, 1096, 1065, 1015, 856, 810, 748, 671 cm−1. 1H NMR (400
MHz, CDCl3) δ: 5.14 (s, 2H), 7.19 (d, J = 8.9 Hz, 1H), 7.47 (ddd, J = 8.0, 6.9, 1.2 Hz, 1H), 7.56
(ddd, J = 8.2, J = 6.9, J = 1.4 Hz, 1H), 7.66–7.70 (m, 3H), 7.75 (d, J = 8.7 Hz, 1H), 7.82 (d, J =
8.0 Hz, 1H), 8.20 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 43.5 (CH2), 110.5 (C),
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116.4 (CH), 122.2 (CH), 124.0 (q, JС–F = 271.0 Hz, C), 125.1 (CH), 125.3 (q, JС–F = 3.8 Hz,
2CH), 127.2 (CH), 127.7 (2CH), 128.7 (CH), 128.9 (CH), 129.9 (C), 131.2 (C), 132.7 (q, 2J С–F
=
32.4 Hz, C), 135.6 (C), 146.3 (C), 151.1 (C). 19F NMR (376 MHz, CDCl3) δ: –62.7 (s, 3F). Anal.
Calcd (%) for C19H12F3NO: С, 69.72; Н, 3.70; N, 4.28. Found (%): С, 69.87; Н, 3.75; N, 3.61.
3ꢀ(Furanꢀ2ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ad). Method B. Yield: 74%, 370 mg.
Colorless solid, mp 158–160 °С (EtOH). IR (KBr) υmax: 1694, 1628, 1574, 1516, 1489, 1466,
1435, 1400, 1362, 1331, 1288, 1223, 1169, 1099, 1015, 945, 814, 741, 702 cm−1. 1H NMR (400
MHz, CDCl3) δ: 5.15 (s, 2Н), 6.52 (dd, J = 3.4, J = 1.8 Hz, 1H), 7.07 (d, J = 4.1 Hz, 1H), 7.18
(d, J = 8.9 Hz, 1H), 7.46 (ddd, J = 8.2, J = 6.9, J = 1.4 Hz, 1Н), 7.54–7.58 (m, 2Н), 7.70 (d, J =
8.2 Hz, 1Н), 7.75 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 8.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ:
42.9 (CH2), 110.9 (C), 111.5 (CH), 113.1 (CH), 116.4 (CH), 122.2 (CH), 125.0 (CH), 127.1
(CH), 128.6 (CH), 128.8 (CH), 130.0 (C), 131.1 (C), 145.1 (CH), 145.9 (C), 146.1 (2C). Anal.
Calcd (%) for C16H11NO2: C, 77.10; H, 4.45; N, 5.62. Found (%): C, 77.07; H, 4.36; N, 5.49.
3ꢀ(Thiophenꢀ2ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ae). Method B. Yield: 77%, 408 mg.
Colorless solid, mp 180–182 °С (EtOH). IR (KBr) υmax: 1678, 1632, 1516, 1470, 1427, 1400,
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1362, 1331, 1273, 1219, 1177, 1088, 1007, 845, 806, 768, 752, 710, 687 cm−1. H NMR (400
MHz, DMSOꢀd6) δ: 5.04 (s, 2Н), 7.16 (dd, J = 4.6, J = 3.9 Hz, 1H), 7.27 (d, J = 8.9 Hz, 1H),
7.48 (ddd, J = 8.0, 6.9, 1.1 Hz, 1Н), 7.58 (ddd, J = 8.2, 6.9, 1.1 Hz, 1Н), 7.71–7.73 (m, 2Н), 7.77
(d, J = 8.2 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1Н), 7.91 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz,
DMSOꢀd6) δ: 42.8 (CH2), 111.4 (C), 116.7 (CH), 122.9 (CH), 125.5 (CH), 127.7 (CH), 128.3
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(CH), 129.0 (CH), 129.3 (CH), 129.5 (CH), 130.1 (C), 131.0 (CН), 131.3 (С), 136.2 (С), 146.4
(C), 148.5 (C). Anal. Calcd (%) for C16H11NOS: C, 72.43; H, 4.18; N, 5.28; S, 12.08. Found (%):
C, 72.40; H, 4.10; N, 5.37; S, 11.98.
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3ꢀ(Pyridinꢀ3ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3af). Method C. Yield: 78%, 405 mg.
Colorless solid, mp 183–185 °С (EtOH). IR (KBr) υmax: 1680, 1628, 1607, 1585, 1518, 1470,
1422, 1400, 1364, 1333, 1281, 1223, 1200, 1179, 1103, 1011, 818, 745, 704, 687 cm−1. 1H NMR
(400 MHz, CDCl3) δ: 5.13 (s, 2Н), 7.19 (d, J = 8.7 Hz, 1H), 7.37 (dd, J = 8.2, J = 5.0 Hz, 1H),
7.43–7.48 (m, 1Н), 7.53–7.57 (m, 1Н), 7.67 (d, J = 8.2 Hz, 1H), 7.75 (d, J = 9.1 Hz, 1H), 7.81
(d, J = 7.7 Hz, 1H), 8.33–8.36 (m, 1Н), 8.71 (br. s, 1Н), 9.31 (br. s, 1Н). 13C NMR (100 MHz,
CDCl3) δ: 43.4 (СН2), 110.6 (С), 116.4 (СН), 122.2 (СН), 123.2 (СН), 125.1 (СН), 127.2 (СН),
128.2 (С), 128.7 (СН), 128.9 (СН), 129.9 (С), 131.2 (С), 134.8 (СН), 146.1 (С), 148.9 (СН),
150.6 (С), 151.8 (СН). Anal. Calcd (%) for C17H12N2O: C, 78.44; H, 4.65; N, 10.76. Found (%):
C, 78.51; H, 4.66; N, 10.65.
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3ꢀ[(Adamantanꢀ1ꢀyl)methyl]ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ag). Method B. Yield:
68%, 450 mg. Colorless solid, mp 100–102 °С (MeOH). IR (KBr) υmax: 2912, 2846, 1627, 1273,
1238, 1149, 1026, 802, 740, 516 cm−1. 1H NMR (400 MHz, CDCl3) δ: 1.62–1.75 (m, 12H), 1.97
(br.s, 3H), 2.16 (s, 2H), 4.96 (s, 2H), 7.05 (d, J = 8.7 Hz, 1H), 7.41–7.46 (m, 1H), 7.51–7.56 (m,
1H), 7.65 (d, J = 8.2 Hz, 1H), 7.71 (d, J = 8.7 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ: 28.8 (3CH), 33.4 (C), 36.9 (3CH2), 42.8 (3CH2), 42.9 (CH2), 49.4 (CH2), 110.8
(C), 116.5 (CH), 122.1 (CH), 124.7 (CH), 127.0 (CH), 128.5 (CH), 128.6 (CH), 130.0 (C), 131.0
(C), 146.4 (C), 155.4 (C). Anal. Calcd (%) for C23H25NO: С, 83.34; Н, 7.60; N, 4.23. Found (%):
С, 83.40; Н, 7.58; N, 4.18.
8ꢀ(Adamantanꢀ1ꢀyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ba). Method A. Yield:
85%, 670 mg. Colorless solid, mp 221–222 °С (DMF). IR (KBr) υmax: 2905, 2845, 1676, 1609,
1508, 1476, 1450, 1400, 1368, 133, 1281, 1229, 1177, 1098, 1059, 1018, 885, 806, 775, 691,
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669 cm−1. H NMR (400 MHz, CDCl3) δ: 1.78–1.86 (m, 6H), 2.02 (br. s, 6H), 2.15 (br. s, 3H),
5.15 (s, 2H), 7.19 (d, J = 8.7 Hz, 1H), 7.44–7.50 (m, 3H), 7.67–7.74 (m, 4H), 8.12 (d, J = 6.4 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ: 29.0 (3CH), 36.3 (C), 36.9 (3CH2), 43.2 (3CH2), 43.4
(CH2), 110.5 (C), 116.3 (CH), 121.9 (CH), 123.8 (CH), 125.3 (CH), 127.4 (2CH), 128.2 (C),
128.3 (2CH), 128.7 (CH), 131.1 (CH), 131.3 (C), 132.4 (C), 146.1 (C), 147.9 (C), 152.5 (C).
Anal. Calcd (%) for C28H27NO: C, 85.46; Н, 6.92; N, 3.56. Found (%): С, 85.53; Н, 7.00; N,
3.49.
8ꢀ(Adamantanꢀ1ꢀyl)ꢀ3ꢀ(furanꢀ2ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3bd). Method A.
Yield: 68%, 522 mg. Colorless solid, mp 218–220 °С (DMF). IR (KBr) υmax: 2905, 2849, 1686,
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MHz, CDCl3) δ: 1.76–1.83 (m, 6Н), 1.99–2.00 (m, 6H), 2.13 (br. s, 3H), 5.11 (s, 2Н), 6.51–6.52
(m, 1Н), 7.07 (d, J = 3.2 Hz, 1H), 7.13 (d, J = 8.9 Hz, 1H), 7.56–7.71 (m, 5Н). 13C NMR (100
MHz, CDCl3) δ: 29.0 (3СН), 36.3 (С), 36.9 (3СН2), 42.9 (СН2), 43.2 (3СН2), 110.6 (C), 111.6
(CH), 113.2 (CH), 116.1 (CH), 122.0 (CH), 123.7 (CH), 125.4 (CH), 128.1 (C), 128.8 (CH),
131.3 (C), 145.1 (CH), 145.6 (C), 146.03 (C), 146.07 (C), 148.1 (C). Anal. Calcd (%) for
C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found (%):C, 81.51; H, 6.51; N, 3.70.
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1,3ꢀDiphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ca). Method B. Yield: 76%, 510 mg.
Colorless solid, mp 164–165 °С (EtOH) (lit.2 mp 170–171 ºC). IR (KBr) υmax: 1663, 1599, 1516,
1454, 1439, 1398, 1327, 1275, 1223, 1177, 1098, 1057, 1018, 837, 818, 779, 760, 743, 698, 691
cm−1. 1H NMR (400 MHz, CDCl3) δ: 6.48 (s, 1H), 7.18–7.23 (m, 1H), 7.25–7.31 (m, 2H), 7.38–
7.51 (m, 8H), 7.72–7.75 (m, 1H), 7.82–7.87 (m, 2H), 8.13–8.16 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ: 57.1 (CH), 114.2 (C), 116.7 (CH), 123.2 (CH), 124.9 (CH), 127.2 (CH), 127.6 (CH),
127.8 (2CH), 128.0 (2CH), 128.3 (2CH), 128.7 (CH), 128.9 (2CН), 129.5 (СН), 130.3 (С), 131.2
(СН), 131.6 (C), 132.2 (С), 143.6 (С), 147.0 (C), 151.6 (C). Anal. Calcd (%) for C24H17NO: С,
85.94; Н, 5.11; N, 4.18. Found (%): С, 86.02; Н, 5.16; N, 4.07.
3ꢀ(4ꢀBromophenyl)ꢀ1ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3cb). Method B. Yield:
80%, 660 mg. Colorless solid, mp 202–203 °С (EtOH) (lit.3a mp 201–202). IR (KBr) υmax: 1670,
1589, 1485, 1450, 1393, 1315, 1227, 1096, 1072, 1007, 833, 818, 748, 725, 702 cm−1. 1H NMR
(400 MHz, CDCl3) δ: 6.42 (s, 1H), 7.19 (t, J = 7.4 Hz, 1H), 7.24–7.28 (m, 2H), 7.33–7.41 (m,
5H), 7.53 (d, J = 8.7 Hz, 2H), 7.67–7.70 (m, 1H), 7.79–7.84 (m, 2H), 7.97 (d, J = 8.7 Hz, 2H).
13C NMR (100 MHz, CDCl3) δ: 57.2 (CH), 114.0 (C), 116.6 (CH), 123.2 (CH), 125.0 (CH),
125.9 (C), 127.2 (CH), 127.6 (CH), 128.0 (2CH), 128.7 (CH), 128.9 (2CH), 129.3 (2CH), 129.6
(CH), 130.2 (C), 131.1 (C), 131.5 (2CH), 131.6 (C), 143.4 (C), 146.7 (C), 150.8 (C). Anal. Calcd
(%) for C24H16BrNO: С, 69.58; Н, 3.89; N, 3.38. Found (%): С, 69.67; Н, 3.94; N, 3.31.
3ꢀ(Furanꢀ2ꢀyl)ꢀ1ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3cd). Method B. Yield: 78%,
510 mg. Colorless solid, mp 166–168 °С (EtOH). IR (KBr) υmax: 1678, 1601, 1566, 1516, 1481,
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1396, 1354, 1323, 1227, 1169, 1103, 1011, 945, 833, 806, 760, 741, 694 cm−1. H NMR (400
MHz, CDCl3) δ: 6.44 (s, 1Н), 6.50 (dd, J = 3.4, J = 1.8 Hz, 1H), 7.11 (d, J = 3.4 Hz, 1H), 7.17–
7.22 (m, 1Н), 7.25–7.30 (m, 2Н), 7.33 (d, J = 8.9 Hz, 1H), 7.37–7.43 (m, 4Н), 7.53–7.54 (m,
1Н), 7.70 (dd, J = 6.9, J = 2.5 Hz, 1Н), 7.80–7.84 (m, 2Н). 13C NMR (100 MHz, CDCl3) δ: 56.8
(CH), 111.6 (CH), 113.7 (CH), 114.3 (C), 116.5 (CH), 123.2 (CH), 124.9 (CH), 127.2 (CH),
127.7 (CH), 128.1 (2CH), 128.7 (CH), 128.9 (2CH), 129.6 (CH), 130.2 (С), 131.6 (C), 143.2
(C), 145.0 (С), 145.2 (CH), 145.9 (C), 146.5 (C). Anal. Calcd (%) for C22H15NO2: C, 81.21; H,
4.65; N, 4.30. Found (%):C, 81.33; H, 4.55; N, 4.24.
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1ꢀPhenylꢀ3ꢀ(thiophenꢀ2ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ce). Method B. Yield: 88%,
600 mg. Colorless solid, mp 154–156 °С (EtOH). IR (KBr) υmax: 1667, 1601, 1516, 1427, 1358,
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1319, 1219, 1096, 1007, 833, 807, 748, 714, 702 cm−1. H NMR (400 MHz, CDCl3) δ: 6.41 (s,
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6H), 7.71–7.73 (m, 1H), 7.77 (dd, J = 3.7, J = 1.2 Hz, 1H), 7.81–7.85 (m, 2H). 13C NMR (100
MHz, CDCl3) δ: 57.0 (CH), 114.4 (C), 116.6 (CH), 123.1 (CH), 124.9 (CH), 127.2 (CH), 127.54
(CH), 127.57 (СН), 128.0 (2CH), 128.7 (CH), 128.9 (2CH), 129.3 (CН), 129.5 (CH), 129.6
(CН), 130.2 (С), 131.5 (C), 136.2 (С), 143.4 (С), 146.8 (С), 148.5 (С). Anal. Calcd (%) for
C22H15NOS: C, 77.39; H, 4.43; N, 4.10; S, 9.39. Found (%):C, 77.28; H, 4.49; N, 4.22; S, 9.28.
1ꢀ(4ꢀChlorophenyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3da). Method B. Yield:
74%, 615 mg. Colorless solid, mp 170–172 °С (DMF–EtOH). IR (KBr) υmax: 1672, 1516, 1489,
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1398, 1352, 1319, 1225, 1175, 1098, 1055, 1016, 841, 812, 775, 741, 691, 669 cm−1. H NMR
(400 MHz, CDCl3) δ: 6.44 (s, 1H), 7.24 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 7.38 (d, J =
8.9 Hz, 1H), 7.41–7.51 (m, 5H), 7.65 (dd, J = 7.1, J = 2.1 Hz, 1H), 7.82–7.87 (m, 2H), 8.12 (d, J
= 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 56.4 (CH), 113.6 (C), 116.7 (CH), 123.0 (CH),
125.0 (CH), 127.3 (CH), 127.7 (2CH), 128.4 (2CH), 128.8 (CH), 129.1 (2CH), 129.4 (2CH),
129.8 (CH), 130.1 (C), 131.4 (CH), 131.6 (C), 131.9 (C), 133.3 (C), 142.1 (C), 146.9 (C), 151.8
(C). Anal. Calcd (%) for C24H16ClNO: С, 77.94; Н, 4.36; N, 3.79. Found (%): С, 78.04; Н, 4.44;
N, 3.71.
3ꢀ(4ꢀBromophenyl)ꢀ1ꢀ(4ꢀchlorophenyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3db). Method B.
Yield: 76%, 680 mg. Colorless solid, mp 197–198 °С (EtOH). IR (KBr) υmax: 1672, 1589, 1516,
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1487, 1393, 1350, 1317, 1225, 1171, 1098, 1070, 1009, 837, 826, 810, 745, 721, 662 cm−1. H
NMR (400 MHz, CDCl3) δ: 6.41 (s, 1H), 7.24 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 7.35
(d, J = 9.2 Hz, 1H), 7.41–7.44 (m, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.61–7.63 (m, 1H), 7.81–7.87
(m, 2H), 7.98 (d, J = 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 56.5 (CH), 113.4 (C), 116.6
(CH), 123.0 (CH), 125.1 (CH), 126.0 (C), 127.4 (CH), 128.8 (CH), 129.1 (2CH), 129.3 (2CH),
129.3 (2CH), 129.8 (CH), 130.0 (C), 130.9 (C), 131.6 (2CH, C), 133.4 (C), 141.9 (C), 146.8 (C),
150.9 (C). Anal. Calcd (%) for C24H15BrClNO: C, 64.24; Н, 3.37; N, 3.12. Found (%): C, 64.31;
Н, 3.34; N, 3.21.
1ꢀ(3ꢀChlorophenyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ea). Method B. Yield:
66%, 490 mg. Colorless solid, mp 150–151 °С (DMF–EtOH). IR (KBr) υmax: 1663, 1591, 1518,
1468, 1432, 1425, 1400, 1323, 1223, 1167, 1101, 1059, 1016, 928, 810, 777, 743, 731, 716, 691
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cm−1. H NMR (400 MHz, CDCl3) δ: 6.44 (s, 1H), 7.17–7.28 (m, 3H), 7.38–7.52 (m, 7H), 7.66
(d, J = 8.7 Hz, 1H), 7.83–7.88 (m, 2H), 8.14 (d, J = 8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ:
56.7 (CH), 113.3 (C), 116.7 (CH), 123.0 (CH), 125.0 (CH), 126.2 (CH), 127.3 (CH), 127.76
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(2CH), 127.82 (CH), 128.2 (CH), 128.4 (2CH), 128.8 (CH), 129.8 (CH), 130.12 (C), 130.15
(CH), 131.4 (CH), 131.6 (C), 132.0 (C), 134.7 (C), 145.6 (C), 147.0 (C), 151.8 (C). Anal. Calcd
(%) for C24H16ClNO: С, 77.94; Н, 4.36; N, 3.79. Found (%): С, 77.90; Н, 4.27; N, 3.68.
1ꢀ(4ꢀFluorophenyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3fa). Method B. Yield:
91%, 643 mg. Colorless solid, mp 151–152 °С (DMF–EtOH). IR (KBr) υmax: 1668, 1603, 1501,
1468, 1449, 1398, 1352, 1319, 1217, 1190, 1177, 1155, 1101, 1090, 1057, 1016, 814, 781, 746,
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694, 669 cm−1. H NMR (400 MHz, CDCl3) δ: 6.46 (s, 1H), 6.94–6.99 (m, 2H), 7.34–7.51 (m,
8H), 7.66–7.69 (m, 1H), 7.82–7.87 (m, 2H), 8.12–8.15 (m, 2H). 13C NMR (100 MHz, CDCl3) δ:
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127.2 (CH), 127.7 (2CH), 128.4 (2CH), 128.8 (CH), 129.59 (d, JС–F = 7.6 Hz, 2CH), 129.65
(CH), 130.2 (C), 131.3 (CH), 131.6 (C), 132.1 (C), 139.5 (d, 4JС–F = 2.9 Hz, C), 147.0 (C), 151.6
(C), 162.1 (d, 1JС–F = 245.0 Hz, C). Anal. Calcd (%) for C24H16FNO: С, 81.57; Н, 4.56; N, 3.96.
Found (%): С, 81.42; Н, 4.61; N, 3.87.
1ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ga). Method B. Yield:
71%, 520 mg. Colorless solid, mp 205–206 °С (MeOH). IR (KBr) υmax: 1663, 1582, 1508, 1460,
1441, 1325, 1244, 1229, 1177, 1098, 1034, 1018, 829, 820, 779, 752, 692 cm−1. H NMR (400
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MHz, CDCl3) δ: 3.72 (s, 3H), 6.42 (s, 1H), 6.80 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H),
7.36–7.50 (m, 6H), 7.72 (d, J = 7.8 Hz, 1H), 7.81–7.85 (m, 2H), 8.13 (d, J = 8.7 Hz, 2H). 13C
NMR (100 MHz, CDCl3) δ: 55.3 (CH3), 56.4 (CH), 114.2 (2CH), 114.5 (C), 116.7 (CH), 123.2
(CH), 124.9 (CH), 127.1 (CH), 127.7 (2CH), 128.3 (2CH), 128.7 (CH), 129.1 (2CH), 129.4
(CH), 130.2 (C), 131.2 (CH), 131.6 (C), 132.2 (C), 136.1 (C), 146.9 (C), 151.4 (C), 158.9 (C).
Anal. Calcd (%) for C25H19NO2: С, 82.17; Н, 5.24; N, 3.83. Found (%): С, 82.20; Н, 5.17; N,
3.92.
3ꢀ(4ꢀBromophenyl)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3gb). Method
B. Yield: 88%, 780 mg. Colorless solid, mp 189–190 °С (EtOH). IR (KBr) υmax: 1674, 1609,
1591, 1508, 1485, 1466, 1439, 1395, 1354, 1319, 1246, 1227, 1177, 1096, 1011, 839, 814 cm−1.
1H NMR (400 MHz, CDCl3) δ: 3.72 (s, 3H), 6.39 (s, 1H), 6.80 (d, J = 8.7 Hz, 2H), 7.28 (d, J =
8.7 Hz, 2H), 7.35 (d, J = 9.0 Hz, 1H), 7.37–7.44 (m, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.70 (d, J =
7.4 Hz, 1H), 7.80–7.84 (m, 2H), 7.99 (d, J = 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 55.3
(CH3), 56.5 (CH), 114.3 (2CH, C), 116.6 (CH), 123.2 (CH), 124.9 (CH), 125.8 (C), 127.2 (CH),
128.7 (CH), 129.0 (2CH), 129.3 (2CH), 129.5 (CH), 130.2 (C), 131.2 (C), 131.5 (2CH), 131.6
(C), 135.9 (C), 146.7 (C), 150.5 (C), 159.0 (C). Anal. Calcd (%) for C25H18BrNO2: С, 67.58; Н,
4.08; N, 3.15. Found (%): С, 67.63; Н, 4.10; N, 3.06.
1ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀ(pyridinꢀ3ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3gf). Method B.
Yield: 83%, 610 mg. Colorless solid, mp 161–162 °С (EtOH). IR (KBr) υmax: 1674, 1605, 1585,
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1504, 1462, 1416, 1323, 1226, 1173, 1103, 1026, 1011, 818, 756, 706 cm−1. 1H NMR (400 MHz,
CDCl3) δ: 3.71 (s, 3H), 6.41 (s, 1H), 6.80 (d, J = 8.7 Hz, 2H), 7.28–7.45 (m, 6H), 7.67–7.70 (m,
1H), 7.79–7.84 (m, 2Н), 8.37 (dt, J = 8.0, 1.8 Hz, 1Н), 8.68 (d, J = 4.6 Hz, 1Н), 9.33 (s, 1Н). 13C
NMR (100 MHz, CDCl3) δ: 55.3 (СН), 56.4 (СН), 114.2 (С), 114.3 (2СН), 116.5 (СН), 123.17
(СН), 123.23 (СН), 125.0 (СН), 127.2 (СН), 128.2 (С), 128.7 (СН), 129.1 (2СН), 129.6 (СН),
130.2 (С), 131.7 (С), 135.2 (СН), 135.7 (С), 146.6 (С), 149.0 (СН), 149.6 (С), 151.7 (СН),
159.0 (С). Anal. Calcd (%) for C24H18N2O2: C, 78.67; H, 4.95; N, 7.65. Found (%): C, 78.61; H,
4.90; N, 7.52.
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1ꢀ(2ꢀMethoxyphenyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ha). Method B. Yield:
78%, 570 mg. Colorless solid, mp 132–134 °С (EtOH). IR (KBr) υmax: 1667, 1582, 1489, 1465,
1439, 1400, 1327, 1227, 1180, 1096, 1049, 1015, 837, 814, 748, 725 cm−1. 1H NMR (400 MHz,
CDCl3) δ: 4.03 (s, 3H), 6.79 (t, J = 7.6 Hz, 1H), 6.95–6.97 (m, 2H), 7.11 (dd, J = 7.6, J = 1.4 Hz,
1H), 7.16–7.20 (m, 1H), 7.35–7.51 (m, 6H), 7.79–7.83 (m, 3H), 8.15–8.18 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ: 50.5 (CH3), 56.1 (CH), 111.3 (CH), 114.8 (C), 116.5 (CH), 121.3 (CH),
123.3 (CH), 124.8 (CH), 127.1 (CH), 127.8 (2CH), 128.3 (2CH), 128.6 (CH), 128.8 (CH), 129.2
(CH), 129.9 (CH), 130.3 (C), 131.2 (CH), 131.5 (C), 132.2 (2C), 147.0 (C), 152.1 (C), 156.4 (C).
Anal. Calcd (%) for C25H19NO2: С, 82.17; Н, 5.24; N, 3.83. Found (%): С, 82.20; Н, 5.17; N,
3.92.
3ꢀ(Furanꢀ2ꢀyl)ꢀ1ꢀ(2ꢀmethoxyphenyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3hd). Method B.
Yield: 65%, 460 mg. Colorless solid, mp. 163–165 °С (iꢀPrOH). IR (KBr) υmax: 1682, 1624,
1597, 1585, 1477, 1462, 1396, 1327, 1258, 1231, 1169, 1115, 1011, 949, 856, 814, 779, 752
cm−1. 1H NMR (400 MHz, CDCl3) δ: 3.99 (s, 3Н), 6.49 (dd, J = 3.4, J = 1.8 Hz, 1H), 6.77–6.81
(m, 1Н), 6.90 (s, 1H), 6.92 (d, J = 7.8 Hz, 1H), 7.08–7.18 (m, 3Н), 7.31 (d, J = 8.9 Hz, 1H),
7.34–7.42 (m, 2Н), 7.52 (d, J = 0.9 Hz, 1H), 7.76–7.80 (m, 3Н). 13C NMR (100 MHz, CDCl3) δ:
50.1 (СН3), 55.9 (СН), 111.1 (СН), 111.5 (СН), 113.4 (C), 115.0 (C), 116.4 (CH), 121.2 (CH),
123.3 (CH), 124.8 (CH), 127.1 (CH), 128.5 (CH), 128.9 (CH), 129.1 (CH), 129.9 (CH), 130.3
(C), 131.5 (C), 131.9 (C), 145.0 (CH), 145.4 (C), 146.2 (C), 146.6 (C), 156.3 (C). Anal. Calcd
(%) for C23H17NO3: C, 77.73; H, 4.82; N, 3.94. Found (%):C, 77.66; H, 4.80; N, 3.83.
1ꢀ(2ꢀMethoxyphenyl)ꢀ3ꢀ(pꢀtolyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3hh). Method B. Yield:
80%, 607 mg. Colorless solid, mp 154–155 °С (EtOH). IR (KBr) υmax: 1634, 1288, 1226, 1091,
1014, 810, 748, 721 cm−1. 1H NMR (400 MHz, CDCl3) δ: 2.40 (s, 3H), 4.03 (s, 3H), 6.78 (t, J =
7.5 Hz, 1H), 6.94–6.97 (m, 2H), 7.10 (dd, J = 7.6, J = 1.1 Hz, 1H), 7.15–7.19 (m, 1H), 7.23 (d, J
= 8.0 Hz, 2H), 7.35–7.43 (m, 3H), 7.78–7.83 (m, 3H), 8.05 (d, J = 8.0 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ: 21.6 (CH3), 50.3 (CH3), 56.1 (CH), 111.2 (CH), 114.9 (C), 116.6 (CH), 121.3
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(CH), 123.2 (CH), 124.7 (CH), 127.1 (CH), 127.7 (2CH), 128.5 (CH), 128.7 (CH), 128.9 (2CH),
129.0 (CH), 129.7 (C), 129.8 (CH), 130.4 (C), 131.4 (C), 132.5 (C), 141.3 (C), 147.1 (C), 151.9
(C), 156.3 (C). Anal. Calcd (%) for C26H21NO2: С, 82.30; Н, 5.58; N, 3.69. Found (%): С, 82.20;
Н, 5.52; N, 3.62.
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(3ib).
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Method B. Yield: 85%, 805 mg. Colorless solid, mp 156–157 °С (EtOH). IR (KBr) υmax: 1669,
1589, 1512, 1485, 1464, 1450, 1439, 1418, 1396, 1356, 1329, 1275, 1252, 1223, 1175, 1152,
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1138, 1096, 1069, 1059, 1030, 1007, 822, 810, 800, 748, 731, 719 cm−1. H NMR (400 MHz,
CDCl3) δ: 3.79 (s, 3H), 3.82 (s, 3H), 6.38 (s, 1H), 6.72 (d, J = 8.2 Hz, 1H), 6.78 (dd, J = 8.2, J =
2.3 Hz, 1H), 6.99 (d, J = 2.3 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 7.38–7.45 (m, 2H), 7.55 (d, J =
8.7 Hz, 2H), 7.68–7.71 (m, 1H), 7.81–7.86 (m, 2H), 7.98 (d, J = 8.7 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ: 55.9 (CH3), 56.0 (CH3), 56.8 (CH), 111.25 (CH), 111.28 (CH), 114.0 (C), 116.5
(CH), 120.1 (CH), 123.3 (CH), 125.0 (CH), 125.9 (C), 127.2 (CH), 128.7 (CH), 129.3 (2CH),
129.6 (CH), 130.2 (C), 131.2 (C), 131.5 (2CH, C), 136.2 (C), 146.8 (C), 148.5 (C), 149.2 (C),
150.6 (C). Anal. Calcd (%) for C26H20BrNO3: С, 65.83; Н, 4.25; N, 2.95. Found (%): С, 65.94;
Н, 4.12; N, 3.01.
1ꢀ(Benzo[d][1,3]dioxolꢀ5ꢀyl)ꢀ3ꢀ(4ꢀbromophenyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3jb).
Method B. Yield: 67%, 615 mg. Colorless solid, mp 174–176 °С (EtOH). IR (KBr) υmax: 1670,
1591, 1516, 1501, 1487, 1443, 1395, 1319, 1254, 1223, 1173, 1098, 1040, 1009, 935, 833, 810,
735 cm−1. 1H NMR (400 MHz, CDCl3) δ: 5.86 (d, J = 1.4 Hz, 1H), 5.88 (d, J = 1.4 Hz, 1H), 6.34
(s, 1H), 6.71 (d, J = 7.8 Hz, 1H), 6.81 (d, J = 1.8 Hz, 1H), 6.87 (dd, J = 8.2, J = 1.8 Hz, 1H), 7.34
(d, J = 9.2 Hz, 1H), 7.38–7.46 (m, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.70 (dd, J = 7.8, J = 1.4 Hz,
1H), 7.81–7.85 (m, 2H), 7.99 (d, J = 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 56.8, 101.2,
108.5, 114.0, 116.6, 121.3, 123.2, 125.0, 125.9, 127.2, 128.7, 129.3, 129.6, 130.1, 131.1, 131.5,
131.6, 137.7, 146.7, 147.0, 148.1, 150.6. Anal. Calcd (%) for C25H16BrNO3: С, 65.52; Н, 3.52;
N, 3.06. Found (%): С, 65.64; Н, 3.42; N, 3.12.
3ꢀPhenylꢀ1ꢀ(3,4,5ꢀtrimethoxyphenyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ka). Method B.
Yield: 85%, 857 mg. Colorless solid, mp 231–232 °С (DMF). IR (KBr) υmax: 1624, 1277, 1230,
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1099, 1018, 817, 736, 709 cm−1. H NMR (400 MHz, CDCl3) δ: 3.75 (s, 6H), 3.79 (s, 3H), 6.39
(s, 1H), 6.62 (s, 2H), 7.38 (d, J = 9.0 Hz, 1H), 7.41–7.51 (m, 5H), 7.73 (d, J = 8.0 Hz, 1H), 7.82–
7.87 (m, 2H), 8.13–8.17 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 56.2 (2CH3), 57.4 (CH3), 60.8
(CH), 105.1 (2CH), 113.9 (C), 116.6 (CH), 123.2 (CH), 124.9 (CH), 127.2 (CH), 127.7 (2CH),
128.4 (2CH), 128.7 (CH), 129.6 (CH), 130.3 (C), 131.3 (CH), 131.5 (C), 132.1 (C), 137.4 (C),
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139.4 (C), 146.9 (C), 151.6 (C), 153.5 (2C). Anal. Calcd (%) for C27H23NO4: С, 76.22; Н, 5.45;
N, 3.29. Found (%): С, 76.16; Н, 5.40; N, 3.37.
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3ꢀPhenylꢀ1ꢀ(thiophenꢀ2ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3la). Method C. Yield: 83%,
567 mg. Lightꢀpink solid, mp 135–136 °С (DMF–EtOH). IR (KBr) υmax: 1667, 1514, 1448,
1435, 1399, 1358, 1323, 1227, 1179, 1098, 1053, 822, 781, 698, 689 cm−1. 1H NMR (400 MHz,
CDCl3) δ: 6.77 (s, 1Н), 6.83–6.86 (m, 2Н), 7.17 (dd, J = 4.8, J = 1.6 Hz, 1H), 7.37 (d, J = 8.7
Hz, 1H), 7.43–7.54 (m, 5Н), 7.84–7.87 (m, 3Н), 8.18–8.21 (m, 2Н). 13C NMR (100 MHz,
CDCl3) δ: 51.7 (СН), 114.3 (С), 116.7 (СН), 123.0 (СН), 125.1 (СН), 125.1 (СН), 125.3 (СН),
126.7 (СН), 127.4 (СН), 128.0 (2СН), 128.4 (2СН), 128.8 (СН), 129.8 (СН), 130.2 (С), 131.6
(CH), 131.6 (2C), 146.7 (С), 147.4 (С), 153.2 (C). 13C NMR (100 MHz, DMSOꢀd6) δ: 51.0
(СН), 115.0 (C), 117.1 (CH), 123.5 (CH), 125.61 (CH), 125.65 (CH), 126.3 (CH), 127.2 (CH),
127.8 (3CH), 129.2 (3CH), 129.9 (C), 130.3 (CH), 131.7 (2C), 132.3 (CH), 146.4 (C), 148.2 (C),
152.2 (C). Anal. Calcd (%) for C22H15NOS: C, 77.39; H, 4.43; N, 4.10; S, 9.39. Found (%): C,
77.25; H, 4.50; N, 4.01; S, 9.47.
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1,3ꢀDi(thiophenꢀ2ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3le). Method C. Yield: 60%, 417
mg. Lightꢀpink solid, mp 173–174 °С (DMF–MeOH). IR (KBr) υmax: 1654, 1427, 1219, 1091,
813, 705 cm−1. 1H NMR (400 MHz, CDCl3) δ: 6.69 (s, 1Н), 6.84 (d, J = 3.4 Hz, 2H), 7.11 (dd, J
= 5.0, J = 3.7 Hz, 1H), 7.15–7.17 (m, 1H), 7.33 (d, J = 9.2 Hz, 1H), 7.42–7.53 (m, 3H), 7.80 (dd,
J = 3.6, J = 1.2 Hz, 1H), 7.83–7.87 (m, 3H). 13C NMR (100 MHz, CDCl3) δ: 51.7 (CH), 114.5
(C), 116.6 (CH), 122.9 (CH), 125.0 (CH), 125.1 (CH), 125.2 (CH), 126.6 (CH), 127.4 (CH),
127.6 (CH), 128.8 (CH), 129.6 (CH), 129.7 (CH), 129.9 (CH), 130.2 (C), 131.5 (C), 136.0 (C),
146.6 (C), 147.4 (C), 149.8 (C). Anal. Calcd (%) for C20H13NOS2: C, 69.14; H, 3.77; N, 4.03; S,
18.45. Found (%):C, 69.22; H, 3.80; N, 3.95; S, 18.34.
3ꢀPhenylꢀ1ꢀ(pyridinꢀ4ꢀyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ma). Method B. Yield: 69%,
465 mg. Colorless solid, mp 163–165 °С (EtOH). IR (KBr) υmax: 1667, 1591, 1514, 1447, 1412,
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1352, 1321, 1275, 1225, 1175, 1098, 1057, 1018, 993, 840, 820, 775, 746, 692, 665 cm−1. H
NMR (400 MHz, CDCl3) δ: 6.46 (s, 1H), 7.28 (dd, J = 4.6, 1.6 Hz, 2H), 7.39 (d, J = 9.0 Hz, 1H),
7.41–7.53 (m, 5H), 7.60–7.63 (m, 1H), 7.83–7.90 (m, 2H), 8.11–8.14 (m, 2H), 8.51 (dd, J = 4.6,
1.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 56.1 (CH), 112.5 (C), 116.7 (CH), 122.8 (CH),
122.9 (2CH), 125.2 (CH), 127.5 (CH), 127.8 (2CH), 128.4 (2CH), 128.9 (CH), 130.0 (C), 130.1
(CH), 131.5 (CH), 131.7 (C), 147.1 (C), 150.4 (2CH), 151.6 (C), 152.4 (C). Anal. Calcd (%) for
C23H16N2O: C, 82.12; H, 4.79; N, 8.33. Found (%):C, 82.24; H, 4.78; N, 8.31.
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2ꢀ(4ꢀBromophenyl)ꢀ4Hꢀ[1,3]oxazino[5,6ꢀh]quinoline (3nb). Method C. Yield: 37%, 250
mg. Colorless solid, mp 177–178 °С (EtOH–DMF). IR (KBr) υmax: 1674, 1634, 1595, 1505,
1487, 1476, 1396, 1379, 1348, 1317, 1281, 1248, 1175, 1117, 1099, 1067, 1013, 829, 792, 721,
702, 665 cm−1. 1H NMR (400 MHz, CDCl3) δ: 4.92 (s, 2H), 7.18 (d, J = 8.3 Hz, 1H), 7.42 (dd, J
= 8.2, J = 4.1 Hz, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.58 (d, J = 8.2 Hz, 2H), 8.10–8.14 (m, 3H),
8.98 (d, J = 4.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 46.1 (CH2), 117.8 (C), 121.6 (CH),
123.9 (CH), 124.3 (CH), 125.9 (C), 128.5 (C), 129.4 (2CH), 131.2 (C), 131.6 (2CH), 136.1
(CH), 138.1 (C), 144.4 (C), 150.7 (CH), 152.6 (C). Anal. Calcd (%) for C17H11BrN2O: С, 60.20;
Н, 3.27; N, 8.26. Found (%): С, 60.26; Н, 3.31; N, 8.18.
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2,4ꢀDiphenylꢀ4Hꢀ[1,3]oxazino[5,6ꢀh]quinoline (3oa). Method C. Yield: 86%, 580 mg.
Colorless solid, mp 179–180 °С (EtOH). IR (KBr) υmax: 1667, 1630, 1595, 1501, 1466, 1450,
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1371, 1314, 1273, 1238, 1175, 1115, 1055, 1028, 827, 754, 731, 700, 685, 675 cm−1. H NMR
(400 MHz, CDCl3) δ: 6.03 (s, 1H), 7.14 (d, J = 8.5 Hz, 1H), 7.25–7.29 (m, 1H), 7.32–7.36 (m,
2H), 7.40–7.52 (m, 7H), 8.09 (dd, J = 8.2, J = 1.6 Hz, 1H), 8.34–8.37 (m, 2H), 9.04 (dd, J = 4.3,
J = 1.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 59.6 (CH), 121.1 (C), 121.8 (CH), 123.7 (CH),
125.3 (CH), 127.8 (CH), 128.0 (2CH), 128.2 (2CH), 128.4 (2CH), 128.5 (C), 128.9 (2CH), 131.3
(CH), 132.2 (C), 136.0 (CH), 138.4 (C), 143.7 (C), 144.0 (C), 150.7 (CH), 152.4 (C). Anal.
Calcd (%) for C23H16N2O: С, 82.12; Н, 4.79; N, 8.33. Found (%): С, 82.24; Н, 4.77; N, 8.25.
2ꢀ(4ꢀBromophenyl)ꢀ4ꢀphenylꢀ4Hꢀ[1,3]oxazino[5,6ꢀh]quinoline (3ob). Method B. Yield:
76%, 630 mg. Colorless solid, mp >300 °С (EtOH). IR (KBr) υmax: 1667, 1632, 1593, 1373,
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1323, 1246, 1173, 1119, 1103, 1065, 1011, 829, 760, 733, 706, 675 cm−1. H NMR (400 MHz,
CDCl3) δ: 6.01 (s, 1H), 7.13 (d, J = 8.5 Hz, 1H), 7.27–7.38 (m, 5H), 7.48 (dd, J = 8.2, J = 4.1
Hz, 1H), 7.52 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 8.5 Hz, 2H), 8.12 (dd, J = 8.2, J = 1.6 Hz, 1H),
8.20 (d, J = 8.5 Hz, 2H), 9.04 (dd, J = 4.1, J = 1.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 59.6
(CH), 120.9 (C), 121.9 (CH), 123.9 (CH), 125.3 (CH), 126.1 (C), 127.9 (CH), 128.0 (2CH),
128.5 (C), 129.0 (2CH), 129.7 (2CH), 131.1 (C), 131.6 (2CH), 136.0 (CH), 138.3 (C), 143.5 (C),
143.8 (C), 150.8 (CH), 151.6 (C). Anal. Calcd (%) for C23H15BrN2O: С, 66.52; Н, 3.64; N, 6.75.
Found (%): С, 66.59; Н, 3.58; N, 6.80.
3ꢀPhenylꢀ7,9,10,11ꢀtetrahydroꢀ[1,3]oxazino[5,6ꢀe]pyrido[3,4ꢀb]indolꢀ8(1H)ꢀone (3pa).
Method B. Yield: 56%, 355 mg. Colorless solid, mp 277–278 °С (EtOH). IR (KBr) υmax: 3400–
3100, 1676, 1661, 1535, 1503, 1433, 1337, 1306, 1292, 1219, 1169, 1128, 1098, 1065, 1024,
802, 773, 689, 671 cm−1. 1H NMR (400 MHz, DMSOꢀd6) δ: 3.07 (t, J = 6.9 Hz, 2H), 3.47 (td, J
= 6.9, J = 2.3 Hz, 2H), 5.10 (s, 2H), 6.98 (d, J = 8.7 Hz, 1H), 7.24 (d, J = 8.7 Hz, 1H), 7.45–7.54
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(m, 3H), 7.57 (s, 1H), 8.01 (d, J = 8.7 Hz, 2H), 11.68 (s, 1H). 13C NMR (100 MHz, DMSOꢀd6) δ:
22.3 (CH2), 41.7 (CH2), 43.5 (CH2), 110.8 (C), 112.7 (CH), 113.9 (CH), 118.4 (C), 121.5 (C),
127.4 (2CH), 129.0 (2CH), 129.1 (C), 131.6 (CH), 132.6 (C), 135.0 (C), 142.4 (C), 151.9 (C),
162.0 (C). Anal. Calcd (%) for C19H15N3O2: С, 71.91; Н, 4.76; N, 13.24. Found (%): С, 71.85;
Н, 4.82; N, 13.18.
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Ethyl 7,8ꢀdimethylꢀ3ꢀphenylꢀ1,7ꢀdihydroꢀ[1,3]oxazino[5,6ꢀe]indoleꢀ9ꢀcarboxylate (3qa).
Method A. Yield: 71%, 495 mg. Colorless solid, mp 208–209 °С (EtOH–DMF). IR (KBr) υmax
:
1686, 1674, 1489, 1435, 1412, 1379, 1360, 1323, 1283, 1225, 1204, 1169, 1152, 1109, 1084,
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1069, 1028, 924, 800, 775, 691 cm−1. H NMR (400 MHz, CDCl3) δ: 1.44 (t, J = 7.3 Hz, 3H),
2.64 (s, 3H), 3.63 (s, 3H), 4.39 (q, J = 7.3 Hz, 2H), 5.20 (s, 2H), 6.93 (d, J = 8.7 Hz, 1H), 7.12
(d, J = 8.7 Hz, 1H), 7.40–7.48 (m, 3H), 8.08 (d, J = 7.3 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ:
12.3 (CH3), 14.7 (CH3), 29.9 (CH3), 46.0 (CH2), 60.1 (CH2), 105.7 (C), 108.6 (CH), 111.0 (C),
111.4 (CH), 122.2 (C), 127.3 (2CH), 128.2 (2CH), 130.8 (CH), 132.7 (C), 134.2 (C), 144.8 (2C),
152.5 (C), 165.8 (C). Anal. Calcd (%) for C21H20N2O3: С, 72.40; Н, 5.79; N, 8.04. Found (%): С,
72.43; Н, 5.84; N, 7.96.
2ꢀ(4ꢀBromophenyl)ꢀ6,7ꢀdimethylꢀ4Hꢀbenzo[e][1,3]oxazine (5ab). Method
B (from
Mannich base). Yield: 57%, 360 mg. Colorless solid, mp 127–128 °С (EtOH). IR (KBr) υmax
:
1667, 1589, 1501, 1458, 1396, 1339, 1269, 1204, 1173, 1119, 1099, 1072, 1003, 868, 837 cm−1.
1H NMR (400 MHz, CDCl3) δ: 2.20 (s, 3H), 2.23 (s, 3H), 4.69 (s, 2H), 6.79 (s, 2H), 7.54 (d, J =
8.7 Hz, 2H), 7.90 (d, J = 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 19.2 (CH3), 19.7 (CH3),
45.2 (CH2), 116.0 (C), 116.4 (CH), 125.6 (C), 126.8 (CH), 128.9 (2CH), 131.5 (2CH), 131.6 (C),
133.2 (C), 136.7 (C), 147.2 (C), 152.2 (C). Anal. Calcd (%) for C16H14BrNO: С, 60.78; Н, 4.46;
N, 4.43. Found (%): C, 60.75; Н, 4.52; N, 4.38.
Method C (from quaternary ammonium salt 6). Yield: 37%, 235 mg. Along with 5ab,
amide 7 was isolated.
4ꢀBromoꢀNꢀ(2ꢀhydroxyꢀ4,5ꢀdimethylbenzyl)benzamide (7). Yield: 32%, 215 mg.
Colorless solid, mp 207–208 °С (CHCl3). IR (KBr) υmax: 3318, 3100–2600, 1628, 1589, 1560,
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1501, 1483, 1439, 1389, 1317, 1296, 1238, 1072, 1011, 835, 760 cm−1. H NMR (400 MHz,
DMSOꢀd6) δ: 2.03 (s, 3H), 2.07 (s, 3H), 4.31 (d, J = 5.5 Hz, 2H), 6.56 (s, 1H), 6.84 (s, 1H), 7.64
(d, J = 8.2 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 8.91 (t, J = 5.5 Hz, 1H), 9.16 (s, 1H). 13C NMR
(100 MHz, DMSOꢀd6) δ: 19.0 (CH3), 19.7 (CH3), 38.5 (CH2), 117.1 (CH), 122.5 (C), 125.5 (C),
126.4 (C), 130.0 (2CH), 130.2 (CH), 131.9 (2CH), 133.9 (C), 136.0 (C), 153.2 (C), 166.1 (C).
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Anal. Calcd (%) for C16H16BrNO2: С, 57.50; Н, 4.83; N, 4.19. Found (%): С, 57.58; Н, 4.90; N,
4.15.
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6,7ꢀDimethylꢀ2ꢀ[4ꢀ(trifluoromethyl)phenyl]ꢀ4Hꢀbenzo[e][1,3]oxazine (5ac). Method B.
Yield: 56%, 342 mg. Colorless solid, mp 145–146 °С (EtOH). IR (KBr) υmax: 1667, 1620, 1582,
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1501, 1458, 1408, 1327, 1269, 1246, 1169, 1123, 1099, 1069, 1018, 853, 675 cm−1. H NMR
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(400 MHz, CDCl3) δ: 2.21 (s, 3H), 2.24 (s, 3H), 4.74 (s, 2H), 6.80 (s, 1H), 6.82 (s, 1H), 7.67 (d,
J = 7.8 Hz, 2H), 8.15 (d, J = 7.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 19.2 (CH3), 19.7
(CH3), 45.3 (CH2), 115.8 (C), 116.4 (CH), 124.0 (q, 1JС–F =271.0 Hz, C), 125.2 (q, 3JС–F =3.8 Hz,
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2CH), 126.8 (CH), 127.7 (2CH), 132.5 (q, JС–F =31.5 Hz, C), 133.4 (C), 135.9 (C), 136.8 (C),
147.1 (C), 151.7 (C). Anal. Calcd (%) for C17H14F3NO: С, 66.88; Н, 4.62; N, 4.59. Found (%):
C, 66.98; Н, 4.51; N, 4.65.
6ꢀMethoxyꢀ2ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine (5ba). After completion of the reaction,
the solvent was distilled off in vacuo, the residue was recrystallized from aqueous methanol and
then again from methanol. Yield: 44%, 280 mg. Colorless solid, mp 56–57 °С (MeOH). IR
(KBr) υmax: 1678, 1612, 1501, 1462, 1447, 1427, 1354, 1319, 1285, 1254, 1319, 1285, 1254,
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1204, 1088, 1065, 1030, 1003, 930, 841, 826, 795, 779, 694, 671 cm−1. H NMR (400 MHz,
CDCl3) δ: 3.78 (s, 3H), 4.77 (s, 2H), 6.57 (d, J = 3.0 Hz, 1H), 6.76 (dd, J = 8.7, J = 3.0 Hz, 1H),
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6.95 (d, J = 8.7 Hz, 1H), 7.40–7.49 (m, 3H), 8.03–8.06 (m, 2H). C NMR (100 MHz, CDCl3) δ:
45.8 (CH2), 55.7 (CH3), 110.5 (CH), 113.7 (CH), 116.5 (CH), 120.0 (C), 127.4 (2CH), 128.3
(2CH), 131.0 (CH), 132.5 (C), 143.4 (C), 153.1 (C), 156.6 (C). MS (EI, 70 eV): m/z (%)=239
(М+, 20), 136 (М+–PhCN, 100), 108 (M+–PhCN–CO, 43), 103 (6), 78 (21), 65 (42). Anal. Calcd
(%) for C15H13NO2: С, 75.30; Н, 5.48; N, 5.85. Found (%): C, 75.42; Н, 5.39; N, 5.93.
6ꢀ(Adamantanꢀ1ꢀyl)ꢀ2ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine (5ca). Method A. Yield: 76%,
522 mg. Colorless solid, mp 135–136 °С (DMF). IR (KBr) υmax: 2899, 2845, 1674, 1503, 1449,
1341, 1250, 1217, 1175, 1155, 1125, 1090, 1063, 806, 773, 691, 669 cm−1. 1H NMR (400 MHz,
CDCl3) δ: 1.72–1.81 (m, 6H), 1.86–1.90 (m, 6H), 2.10 (br. s, 3H), 4.79 (s, 2H), 6.96 (d, J = 8.5
Hz, 1H), 7.03 (d, J = 2.1 Hz, 1H), 7.22 (dd, J = 8.5, J = 2.1 Hz, 1H), 7.39–7.49 (m, 3Н), 8.03–
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8.06 (m, 2H). C NMR (100 MHz, CDCl3) δ: 29.0 (3CH), 36.0 (C), 36.8 (3CH2), 43.4 (3CH2),
45.8 (CH2), 115.1 (CH), 118.6 (C), 122.5 (CH), 124.6 (CH), 127.4 (2CH), 128.3 (2CH), 131.0
(CH), 132.5 (C), 147.3 (C), 148.3 (C), 153.0 (C). Anal. Calcd (%) for C24H25NO: С, 83.93; Н,
7.34; N, 4.08. Found (%): C, 84.05; Н, 7.31; N, 3.99.
1ꢀ[2ꢀPhenylꢀ4Hꢀbenzo[e][1,3]oxazinꢀ6ꢀyl]ethanꢀ1ꢀone (5da). Method B. Yield: 72%,
360 mg. Colorless solid, mp 135–137 °С (EtOH). IR (KBr) υmax: 1674, 1587, 1495, 1423, 1283,
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1250, 1229, 1169, 1117, 1076, 1057, 1030, 961, 887, 839, 777, 692, 671, 662 cm−1. H NMR
(400 MHz, CDCl3) δ: 2.57 (s, 3H), 4.82 (s, 2H), 7.06 (d, J = 8.2 Hz, 1H), 7.41–7.51 (m, 3H),
7.69 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 7.1 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ:
26.5 (CH3), 45.3 (CH2), 115.8 (CH), 119.5 (C), 126.9 (CH), 127.4 (2CH), 128.4 (2CH), 129.1
(CH), 131.4 (CH), 131.7 (C), 134.0 (C), 152.1 (C), 153.2 (C), 196.7 (C). Anal. Calcd (%) for
C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found (%): C, 76.59; Н, 5.16; N, 5.39.
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1ꢀ[2ꢀ(4ꢀBromophenyl)ꢀ4Hꢀbenzo[e][1,3]oxazinꢀ6ꢀyl]ethanꢀ1ꢀone (5db). Method B.
Yield: 81%, 535 mg. Colorless solid, mp 187–188 °С (EtOH). IR (KBr) υmax: 1674, 1612, 1589,
1501, 1423, 1396, 1362, 1281, 1250, 1231, 1173, 1130, 1115, 1084, 1015, 999, 826, 721, 664
cm−1. 1H NMR (400 MHz, CDCl3) δ: 2.57 (s, 3H), 4.80 (s, 2H), 7.05 (d, J = 8.5 Hz, 1H), 7.56 (d,
J = 8.5 Hz, 2H), 7.69 (s, 1H), 7.84 (dd, J = 8.5, J = 1.4 Hz, 1H), 7.91 (d, J = 8.5 Hz, 2H). 13C
NMR (100 MHz, CDCl3) δ: 26.5 (CH3), 45.2 (CH2), 115.8 (CH), 119.3 (C), 126.1 (C), 126.9
(CH), 129.0 (2CH), 129.1 (CH), 130.6 (C), 131.7 (2CH), 134.2 (C), 151.4 (C), 152.9 (C), 196.6
(C). Anal. Calcd (%) for C16H12BrNO2: C, 58.20; H, 3.66; N, 4.24. Found (%): C, 58.22; Н,
3.49; N, 4.16.
2ꢀ(4ꢀBromophenyl)ꢀ6,8ꢀdiꢀtertꢀbutylꢀ4Hꢀbenzo[e][1,3]oxazine (5eb). Method B. Yield:
80%, 640 mg. Colorless solid, mp 185–187 °С (iꢀPrOH). IR (KBr) υmax: 2967, 2909, 2866, 1678,
1589, 1481, 1393, 1362, 1346, 1277, 1223, 1200, 1169, 1123, 1088, 1069, 999, 837, 721, 664
cm−1. 1H NMR (400 MHz, CDCl3) δ: 1.31 (s, 9H), 1.48 (s, 9H), 4.77 (s, 2H), 6.91 (d, J = 2.3 Hz,
1H), 7.24 (d, J = 2.3 Hz, 1H), 7.58 (d, J = 8.7 Hz, 2H), 7.96 (d, J = 8.7 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ: 30.2 (3CH3), 31.6 (3CH3), 34.7 (C), 34.9 (C), 46.2 (CH2), 118.4 (C), 120.8
(CH), 122.7 (CH), 125.5 (C), 129.0 (2CH), 131.6 (2CH), 131.7 (C), 136.0 (C), 145.8 (C), 147.1
(C), 152.4 (C). MS (EI, 70 eV): m/z (%)=399 (М+, 7), 218 (M+–BrC6H4CN, 35), 203 (M+–
BrC6H4CN–CH3, 100), 161 (M+–BrC6H4CN–C4H9, 36), 57 (C4H9, 8). Anal. Calcd (%) for
C22H26BrNO: С, 66.00; Н, 6.55; N, 3.50. Found (%): C, 65.89; Н, 6.64; N, 3.40.
6,8ꢀDiꢀtertꢀbutylꢀ2ꢀ[4ꢀ(trifluoromethyl)phenyl]ꢀ4Hꢀbenzo[e][1,3]oxazine (5ec). Method
B. Yield: 60%, 467 mg. Colorless solid, mp 90–91 °С (EtOH). IR (KBr) υmax: 2957, 2901, 2847,
1672, 1601, 1479, 1447, 1408, 1364, 1321, 1277, 1229, 1219, 1200, 1163, 1123, 1088, 1064,
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1016, 1005, 851, 671 cm−1. H NMR (400 MHz, CDCl3) δ: 1.32 (s, 9H), 1.50 (s, 9H), 4.81 (s,
2H), 6.92 (d, J = 2.5 Hz, 1H), 7.26 (d, J = 2.5 Hz, 1H), 7.72 (d, J = 8.2 Hz, 2H), 8.22 (d, J = 8.2
Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 30.2 (3CH3), 31.5 (3CH3), 34.7 (C), 34.9 (C), 46.3
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(CH2), 118.3 (C), 120.9 (CH), 122.9 (CH), 124.0 (q, JС–F = 270.8 Hz, C), 125.4 (q, JС–F = 3.8
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(C). Anal. Calcd (%) for C23H26F3NO: C, 70.93; H, 6.73; N, 3.60. Found (%):C, 71.02; H, 6.70;
N, 3.54.
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8ꢀ(Adamantanꢀ1ꢀyl)ꢀ6ꢀ(tertꢀbutyl)ꢀ2ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine (5fa). Method B.
Yield: 86%, 823 mg. Colorless solid, mp 164–166 °С (iꢀPrOH). IR (KBr) υmax: 2959, 2909,
2847, 1678, 1605, 1474, 1450, 1346, 1319, 1277, 1250, 1188, 1123, 1107, 1088, 1065, 868, 772,
687 cm−1. 1H NMR (400 MHz, CDCl3) δ: 1.32 (s, 9H), 1.83–1.91 (m, 6H), 2.16 (br. s, 3H), 2.20
(br. s, 6H), 4.79 (s, 2H), 6.91 (d, J = 2.3 Hz, 1H), 7.21 (d, J = 2.3 Hz, 1H), 7.44–7.52 (m, 3H),
8.17–8.20 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 29.1 (3CH), 31.6 (3CH3), 34.7 (C), 37.1
(3CH2), 37.2 (C), 41.0 (3CH2), 46.3 (CH2), 118.5 (C), 120.7 (CH), 122.7 (CH), 127.5 (2CH),
128.3 (2CH), 130.9 (CH), 132.9 (C), 136.4 (C), 146.2 (C), 147.0 (C), 153.2 (C). Anal. Calcd (%)
for C28H33NO: С, 84.17; Н, 8.32; N, 3.51. Found (%): C, 84.25; Н, 8.24; N, 3.61.
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8ꢀ(Adamantanꢀ1ꢀyl)ꢀ6ꢀmethylꢀ2ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine (5ga). Method B.
Yield: 78%, 680 mg. Colorless solid, mp 135–136 °С (DMF–MeOH). IR (KBr) υmax: 2905,
2874, 2847, 1678, 1607, 1470, 1449, 1346, 1277, 1236, 1200, 1150, 1105, 1092, 1063, 1013,
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851, 773, 685, 673 cm−1. H NMR (400 MHz, CDCl3) δ: 1.81–1.89 (m, 6H), 2.14 (br. s, 3H),
2.17–2.20 (m, 6H), 2.30 (s, 3H), 4.75 (s, 2H), 6.71 (d, J = 1.4 Hz, 1H), 6.96 (d, J = 1.4 Hz, 1H),
7.43–7.51 (m, 3H), 8.15–8.19 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 21.2 (CH3), 29.1 (3CH),
36.8 (C), 37.1 (3CH2), 40.9 (3CH2), 46.0 (CH2), 119.1 (C), 124.3 (CH), 126.4 (CH), 127.5
(2CH), 128.3 (2CH), 130.9 (CH), 132.8 (C), 133.7 (C), 136.9 (C), 146.3 (C), 153.3 (C). Anal.
Calcd (%) for C25H27NO: С, 83.99; Н, 7.61; N, 3.92. Found (%): C, 84.09; Н, 7.53; N, 3.80.
6ꢀChloroꢀ2ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine (5ha). After completion of the reaction, the
solvent was distilled off in vacuo, the residue was dissolved in methanol, water was added until
the solution became cloudy and allowed to stand for 2 days at room temperature and then for 12
hours at –20 °C. The precipitated product was filtered off and recrystallized from methanol.
Yield: 22%, 107 mg. Colorless solid, mp 80–82 °С (MeOH). IR (KBr) υmax: 1678, 1585, 1489,
1447, 1420, 1342, 1277, 1238, 1184, 1119, 1088, 1061, 868, 810, 775, 691 cm−1. 1H NMR (400
MHz, CDCl3) δ: 4.75 (s, 2H), 6.95 (d, J = 8.7 Hz, 1H), 7.04 (d, J = 2.3 Hz, 1H), 7.18 (dd, J =
13
8.7, J = 2.3 Hz, 1H), 7.41–7.51 (m, 3H), 8.03 (d, J = 8.5 Hz, 2H). C NMR (100 MHz, CDCl3)
δ: 45.2 (CH), 117.0 (CH), 120.9 (C), 126.0 (CH), 127.4 (2CH), 128.2 (CH), 128.4 (2CH), 129.6
(C), 131.3 (CH), 131.9 (C), 148.1 (C), 152.6 (C). Anal. Calcd (%) for C14H10ClNO: С, 69.00; Н,
4.14; N, 5.75. Found (%): C, 68.89; Н, 4.10; N, 5.71.
2ꢀ(4ꢀBromophenyl)ꢀ4ꢀphenylꢀ4Hꢀbenzo[e][1,3]oxazine (5ib). Method B. Yield: 81%, 590
mg. Colorless solid, mp 133–135 °С (EtOH). IR (KBr) υmax: 1667, 1585, 1489, 1454, 1396,
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1323, 1300, 1242, 1219, 1180, 1111, 1088, 1011, 845, 752, 698 cm−1. H NMR (400 MHz,
CDCl3) δ: 5.84 (s, 1H), 6.95 (d, J = 7.6 Hz, 1H), 7.06 (dd, J = 7.4, J = 1.2 Hz, 1H), 7.10 (dd, J =
8.2, J = 0.9 Hz, 1H), 7.23–7.30 (m, 2H), 7.32–7.38 (m, 4H), 7.56 (d, J = 8.5 Hz, 2H), 8.00 (d, J =
8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 58.9 (CH), 115.7 (CH), 122.6 (C), 125.2 (CH),
125.9 (C), 127.5 (CH), 127.6 (CH), 127.8 (2CH), 128.4 (CH), 128.8 (2CH), 129.3 (2CH), 131.2
(C), 131.6 (2CH), 144.0 (C), 148.5 (C), 151.4 (C). Anal. Calcd (%) for C20H14BrNO: С, 65.95;
Н, 3.87; N, 3.85. Found (%): C, 66.08; Н, 3.78; N, 3.93.
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2,4,4ꢀTriphenylꢀ4Hꢀbenzo[e][1,3]oxazin (5ja). Method B. Yield: 80%, 578 mg. Colorless
solid, mp 192–193 °С (DMF–MeOH). IR (KBr) υmax: 1659, 1584, 1491, 1483, 1445, 1315, 1296,
1277, 1227, 1215, 1179, 1113, 1096, 1067, 1024, 1005, 928, 781, 756, 702, 692 cm−1. 1H NMR
(400 MHz, CDCl3) δ: 6.92 (dd, J = 7.8, J = 1.4 Hz, 1H), 7.09–7.13 (m, 1H), 7.19–7.34 (m, 12H),
7.42–7.52 (m, 3H), 8.21–8.24 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 65.4 (C), 115.8 (CH),
124.5 (CH), 125.7 (C), 126.9 (2CH), 127.9 (5CH), 128.3 (2CH), 128.5 (CH), 128.6 (4CH), 129.4
(CH), 131.2 (CH), 132.3 (C), 147.4 (2C), 149.1 (C), 151.9 (C). Anal. Calcd (%) for C26H19NO:
С, 86.40; Н, 5.30; N, 3.88. Found (%): C, 86.31; Н, 5.37; N, 3.77.
2'ꢀPhenylspiro[adamantaneꢀ2,4'ꢀbenzo[e][1,3]oxazine] (5ka). Method A. Yield: 84%,
553 mg. Colorless solid, mp 138–139 °С (DMF). IR (KBr) υmax: 2893, 2847, 1653, 1580, 1493,
1479, 1470, 1449, 1315, 1285, 1267, 1206, 1175, 1101, 1057, 1024, 881, 779, 746, 694 cm−1. 1H
NMR (400 MHz, CDCl3) δ: 1.59 (d, J = 12.8 Hz, 2H), 1.81 (br. s, 4H), 1.96 (br. s, 2H), 2.17–
2.23 (m, 4H), 2.82 (d, J = 12.4 Hz, 2H), 7.15–7.21 (m, 2H), 7.25–7.29 (m, 1H), 7.42–7.50 (m,
3H), 7.80 (dd, J = 7.8, 1.4 Hz, 1H), 8.15–8.18 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 27.4
(CH), 27.6 (CH), 33.9 (2CH2), 34.9 (2CH2), 37.4 (2CH), 38.9 (CH2), 60.4 (C), 116.3 (CH), 123.9
(CH), 126.9 (CH), 127.0 (CH), 127.9 (2CH), 128.4 (2CH), 131.0 (CH, C), 132.3 (C), 151.4 (C),
152.3 (C). Anal. Calcd (%) for C23H23NO: С, 83.85; Н, 7.04; N, 4.25. Found (%): C, 83.80; Н,
6.94; N, 4.13.
Three-component Synthesis of 1H-Naphtho[1,2-e][1,3]oxazines 3ah, 3ca, 3ra. A
mixture of imino ether (7 mmol), 2ꢀnaphthol (7 mmol) and aromatic aldehyde (7 mmol) was
heated at 130 °C for 6 h without a solvent in the presence of a catalytic amount of acetic acid
(0.02 g, 0.35 mmol). The mixture was cooled, suspended in methanol (5 mL), the precipitate was
filtered off and purified by recrystallization.
1ꢀPhenylꢀ3ꢀ(pꢀtolyl)ꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ah). Yield: 47%, 1.15 g. Colorless
solid, mp 156–158 °С (EtOH). (lit.12 mp 194–195 ºC). IR (KBr) υmax: 1667, 1626, 1599, 1516,
1493, 1454, 1398, 1356, 1327, 1223, 1194, 1179, 1098, 1072, 1057, 1018, 837, 816, 779, 762,
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745, 691 cm−1. H NMR (400 MHz, CDCl3) δ: 2.40 (s, 3H), 6.45 (s, 1H), 7.17–7.29 (m, 5H),
7.37–7.44 (m, 5H), 7.72–7.74 (m, 1H), 7.81–7.85 (m, 2H), 8.02 (d, J = 8.2 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ: 21.6 (CH3), 57.1 (CH), 114.3 (C), 116.7 (CH), 123.2 (CH), 124.8 (CH),
127.1 (CH), 127.5 (CH), 127.7 (2CH), 128.0 (2CH), 128.7 (CH), 128.8 (2CH), 129.0 (2CH),
129.4 (CH, C), 130.3 (C), 131.5 (C), 141.5 (C), 143.7 (C), 147.0 (C), 151.7 (C). Anal. Calcd (%)
for C25H19NO: С, 85.93; Н, 5.48; N, 4.01. Found (%): С, 85.88; Н, 5.54; N, 3.93.
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1,3ꢀDiphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ca). Yield: 61%, 1.43 g. Product was
identical in spectral characteristics to a sample prepared previously.
1ꢀ(3ꢀNitrophenyl)ꢀ3ꢀphenylꢀ1Hꢀnaphtho[1,2ꢀe][1,3]oxazine (3ra). Yield: 24%, 0.64 g.
Colorless solid, mp 172–173 °С (DMF). IR (KBr) υmax: 1670, 1628, 1528, 1474, 1443, 1400,
1
1346, 1323, 1277, 1223, 1177, 1103, 1057, 1018, 829, 806, 779, 733, 691 cm−1. H NMR (400
MHz, CDCl3) δ: 6.57 (s, 1H), 7.40–7.52 (m, 7H), 7.58–7.61 (m, 1H), 7.67 (d, J = 7.8 Hz, 1H),
7.84–7.87 (m, 1H), 7.90 (d, J = 8.9 Hz, 1H), 8.07 (dd, J = 8.0, J = 0.9 Hz, 1H), 8.14 (d, J = 7.1
13
Hz, 2H), 8.29 (s, 1Н). C NMR (100 MHz, CDCl3) δ: 56.5 (CH), 112.5 (C), 116.8 (CH), 122.7
(2CH), 123.1 (CH), 125.2 (CH), 127.6 (CH), 127.8 (2CH), 128.5 (2CН), 129.0 (CН), 129.9 (C,
CН), 130.3 (CН), 131.6 (СН), 131.6 (С), 131.7 (С), 134.1 (СН), 145.6 (С), 147.1 (С), 148.7 (С),
152.1 (С). Anal. Calcd (%) for C24H16N2O3: С, 75.78; Н, 4.24; N, 7.36. Found (%): С, 75.71; Н,
4.19; N, 7.30.
ACKNOWLEDGMENT
This work was supported by Russian Science Foundation (grant 17ꢀ73ꢀ10400, study of oꢀQM
precursors) and by the Russian Foundation for Basic Research (grant 17ꢀ03ꢀ01158 a, study of
threeꢀcomponent condensation).
Supporting Information
Copies of 1H, 13C, and 19F NMR spectra for new synthesized compounds.
This material is available free of charge via the Internet at http://pubs.acs.org.
ORCID
Dmitry V. Osipov: 0000ꢀ0001ꢀ9217ꢀ0792
Vitaly A. Osyanin: 0000ꢀ0001ꢀ5482ꢀ3940
Notes
The authors declare no competing financial interest.
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