Iron(III) chloride/diorganyl diselenides promoted regio-and stereoselective cyclization of ortho-alkynylanilides: Synthesis of (Z)-4-(chalcogen) methylenebenzoxazines

Article abstract of DOI:10.1002/adsc.201300925

Intramolecular 6-exo-dig cyclization of ortho-alkynylanilides has been employed in a regioand stereoselective synthesis of (Z)-4-(chalcogen)- methylenebenzoxazines. Several reaction parameters were screened for the efficient cyclization of orthoalkynylani

Full text of DOI:10.1002/adsc.201300925

FULL PAPERS
DOI: 10.1002/adsc.201300925
Iron(III) Chloride/Diorganyl Diselenides Promoted Regio- and
G
Stereoselective Cyclization of ortho-Alkynylanilides: Synthesis of
(Z)-4-(chalcogen)methylenebenzoxazines
Andrꢀ L. Stein,a Filipe N. Bilheri,a Davi F. Back,b and Gilson Zenia,*
a
Laboratꢁrio de Sꢂntese, Reatividade, Avaliażo Farmacolꢁgica e Toxicolꢁgica de OrganocalcogÞnios, CCNE, UFSM,
Santa Maria, Rio Grande do Sul, (homepage: www.ufsm.br) Brazil, 97105-900
Fax : (+55)-55-3220-8978; phone: (+55)-55-3220-9611; e-mail: gzeni@ufsm.br
Laboratꢁrio de Materiais Inorgꢃnicos, CCNE, UFSM, Santa Maria, Rio Grande do Sul, Brazil, 97105-900
b
Received: October 17, 2013; Revised: November 29, 2013; Published online: February 6, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300925.
Abstract: Intramolecular 6-exo-dig cyclization of then subjected to a nitrogen–oxygen exchange reac-
ortho-alkynylanilides has been employed in a regio- tion with ammonium acetate to furnish quinazoline
and stereoselective synthesis of (Z)-4-(chalcogen)- derivatives. The one-pot version of this cyclization,
methylenebenzoxazines. Several reaction parameters starting directly from 2-alkynylanilines, avoiding the
were screened for the efficient cyclization of ortho- previous preparation of ortho-alkynylanilides was
alkynylanilides. Among them, the reaction of ortho- also briefly studied.
alkynylanilides (0.25 mmol) with ironACTHUNRTGNEUNG(III) chloride
(3.0 equiv.) and diorganyl diselenides (0.75 equiv.) in
dichloromethane as solvent gave the products in ac- Keywords: benzoxazines; diorganoyl diselenides; in-
ceptable to good yields. The resulting products were tramolecular 6-exo-dig cyclization; iron; quinazolines
Introduction
such as indoles and benzoxazines.[16] Despite the great
progress made in indole synthesis,[17] only few general
The development of efficient methods to allow the and efficient methods are available for the synthesis
transformation of unsaturated substrates, having an of oxazine derivatives.[18] An improved procedure for
internal nucleophile, in an appropriate distance, into the cyclization of ortho-alkynylanilides was successful-
heterocycles has been widely exploited. In this regard, ly applied by the Saito group.[19] This method involved
transition metal-catalyzed cyclization[1] and electro- a regio- and stereoselective 6-exo-dig cyclization of
philic cyclization[2] have proven to be the most effi- N-acyl-ortho-alkynylanilines producing 4-alkylidene-
cient approaches to the synthesis of heterocycles. 3,1-benzoxazines 3 (Scheme 1) by using PdACHTUNRGTNEUNG(OAc)2 as
Among the use of transition metals, not only palladi- catalyst and acetic acid as additive. In contrast, there
um[3] but also gold,[4] copper,[5] rhodium,[6] platinum,[7] are no examples for the formation of the correspond-
indium,[8] ruthenium[9] and iron salts[10] have been ap- ing Z-alkylidenebenzoxazines, where the two groups,
plied for the synthesis of heterocycles. From these R1 and oxygen, are on opposite sides of the double
metals, the application of iron salts has increased in bond (Scheme 1). The economic and environmental
the last few years due to the low cost, low toxicity, advantages of iron salts in association with the easy
compatibility with solvents, air and with a wide range preparation of diorganyl diselenides,[20] led us to study
of functional groups.[10] Recently, a mixture of FeCl3/ whether iron
ACTHUNRTGNE(GNU III) chloride and diorganyl dichalcoge-
PhSeSePh was found to be an alternative system to nides could be employed as cyclizing agent of ortho-
promote the cyclization of unsaturated substrates.[11] alkynylanilides 1 to prepare Z-alkylidenebenzoxazine
More recently, we have also demonstrated FeCl3/ organoselenium derivatives 2 (Scheme 1).
PhSeSePh as an efficient system for the preparation
of vinyl selenides,[12] organoselenoisoxazoles,[13] orga-
noselenoisochromenones[14] and organoselenochrome-
nones.[15] The cyclization of ortho-alkynylanilides is an
appropriate way to produce nitrogen heterocycles,
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Andrꢀ L. Stein et al.
Scheme 1. General scheme.
Results and Discussion
forded only the starting materials. These results sug-
gest that due to the strong affinity for nitrogen and
The required ortho-alkynylanilides 1 were obtained oxygen atoms, as well as for the carbon-carbon triple
by Sonogashira cross-coupling of the corresponding 2- bond, a portion of the iron(III) chloride was required
AHCTUNGTRENNUNG
iodoanilines with terminal alkynes, followed by nitro- to complex with these donor ligands, while other por-
gen acylation with acyl chlorides.[19] We started our re- tion reacted with diphenyl diselenide to form the in-
search on the cyclization reaction by studying the termediate which promoted the cyclization and the in-
most appropriate experimental conditions to deliver corporation of PhSe in the heterocycle. Additionally,
the desired products in high yields with a low rate of the isolated yields obtained by using 0.75 equiv. of di-
by-products. To this end, the reaction of ortho-alkyn- phenyl diselenide (PhSeSePh) imply that two PhSe
ACHTUNGTRENNUNG
ylanilide[19] 1a with diphenyl diselenide and FeCl3 was groups from the organoselenium reagents were trans-
optimized in terms of relative rates of reagents, sol- ferred to the substrate. Among the solvents tested, di-
vent, temperature and reaction time. We started our chloromethane proved to be the best choice, whereas
investigation by adding the o-alkynilanilide 1a
(0.25 mmol), at room temperature, under an argon at-
mosphere, to a solution of FeCl3 (1.0 equiv.) and di-
Table 1. Optimization of the cyclization conditions.[a]
phenyl diselenide (1.0 equiv.; which was prepared
10 min before use) in CH2Cl2 (5 mL). Using these
conditions, the benzoxazine 2a was obtained in 41%
yield (Table 1, entry 1). Further loading of different
amounts of ironACHTUNGTRENNUNG(III) chloride and diphenyl diselenide
proved that 3.0 equiv. and 0.75 equiv., respectively,
are required to obtain a better yield and purity of
product 2a. Even though the use of ironACTHNUGRTENUNG(III) chloride
Entry FeCl3
(equiv.)
PhSeSePh
(equiv.)
Solvent Time Yield
[h]
[%][b]
(1.5 or 2.0 equiv.) with diphenyl diselenide (0.5 equiv.)
afforded the benzoxazine 2a in good yields, in such
a case, due to the presence of an indole derivative, as
by-product, the purification processes becomes more
1
2
3
4
5
6
7
8
1.0
1.0
0.5
0.5
0.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.75
0.5
0.75
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
CHCl3 0.5
MeNO2
MeOH 12
1
1
1
1
1
1
1
41
59
59
79
61
88
87
63
1.0
1.2
1.5
1.5
2.0
2.0
2.0
2.0
2.0
2.0
3.0
1.5
3.0
complex. The large amount of ironACTHNUTRGNEUNG(III) chloride re-
quired in this cyclization proved to be necessary not
only to activate the triple bond[21] but also to promote
the selenium incorporation. In fact, when ironACTHNUGTRNEUNG(III)
9
4
74
–
–
chloride (1.0 equiv.) was used in the absence of di-
phenyl diselenide, the indole without the organosele-
nium moiety in the structure was obtained and the re-
mainder of the starting material was recovered. Be-
sides, when the ortho-alkynylanilide 1a was previously
treated with diphenyl diselenide, followed by addition
10
11
12
13
14
THF
12
1
1
CH2Cl2
CH2Cl2
CH2Cl2
74[c]
46[c,d]
48[c,e]
2
[a]
The reactions were performed using the N-[2-(phenyle-
thynyl)phenyl]benzamide (0.25 mmol) and diphenyl dise-
lenide in solvent (5 mL).
Yields were determined by GC analysis.
Isolated yield after column chromatography.
Reaction carried out at 408C.
of ironACHTUNGTRENNUNG(III) chloride (1.0 equiv.) only a trace amount
of the product was obtained and unreacted starting
materials were recovered. We also observed that the
inverse addition of a mixture of diphenyl diselenide
[b]
[c]
[d]
[e]
(1.0 equiv.), iron
ACHTUNGTRENNUNG(III) chloride (1.0 equiv) and CH2Cl2
to a solution of ortho-alkynylanilide 1a in CH2Cl2 af-
Reaction carried out at 08C.
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IronACTHNUTRGNE(UNG III) Chloride/Diorganyl Diselenides
Table 2. ortho-Alkynylanilide cyclization by the combination
FeCl3/ArYYAr.[a]
Scheme 2. Preparation of organoselenobenzoxazine 2a.
the other solvents, such as methanol, tetrahydrofuran
and chloroform were inferior (Table 1, entries 7–11).
With regard to temperature, the use of room tempera-
ture was more beneficial than a lower temperature or
reflux (Table 1, entries 13 and 14). Finally, at various
interval times during the optimization reactions, sam-
ples of the reaction mixture were analyzed by TLC,
which showed that 1 h was the reaction time necessa-
ry for the complete consumption of the starting mate-
rial. Under the optimized condition: ortho-alkynylani-
lide 1a (0.25 mmol), FeCl3 (3.0 equiv.), diphenyl dise-
lenide (0.75 equiv.) in CH2Cl2 (5 mL) as solvent at
room temperature for 1 h, organoselenobenzoxazine
2a was formed in 74% isolated yield (Scheme 2) with
the complete absence of hydrogenated benzoxazine 3
and indole 4 (Scheme 1).
The optimized conditions were then applied to
other ortho-alkynylanilidea 1 and the results are pre-
sented in Table 2. We started by examining the influ-
ence of diorganyl diselenides in the cyclization reac-
tion (Table 2, entries 1–5). The nature of the function-
al groups on the aromatic ring of the diorganyl disele-
nides seems to have influence on the course of the re-
action. In fact, better yields were obtained with
diorganyl diselenides having neutral or electron-do-
nating groups in comparison to those having electron-
withdrawing groups (Table 2, entries 1–4). The reac-
tivity of an alkyl diselenide was also investigated. In
this case, when dibutyl diselenide was employed as or-
ganoselenium source, the yield of the corresponding
product 2e decreased to 44% (Table 2, entry 5). This
low yield can be attributed to losses via syn elimina-
tion of selenoxide formed during purification by
column chromatography. Next, we studied the influ-
ence of the R2 substituent directly bonded to the car-
bonyl group of ortho-alkynylanilides 1 (Table 2, en-
tries 6–9). Thus, the addition of some groups in the ar-
omatic ring R2, such as Me, t-Bu, Br and NO2, had no
influence on the course of the cyclization whereby the
benzoxazines 2f–i were obtained in similar yields.
Substrates bearing both electron-withdrawing and
electron-donating substituents at the 4-position react-
ed to give the desired biaryl products in moderate
yields (Table 2, entries 10–17). The cyclization was
not limited only to diorganyl diselenides. Treatment
of the ortho-alkynylanilide 1 with diphenyl ditelluride,
using the optimized conditions, resulted in the forma-
tion of benzoxazine organotelluro derivative 2r in
54% yield (Table 2, entry 18). In this case, the product
[a]
The reaction was performed in the presence of
1 (0.25 mmol), diorganyl dichalcogenides (0.75 equiv.),
FeCl3 (3.0 equiv.), CH2Cl2 (5 mL) as solvent, under an
argon atmosphere, at room temperature for 1 h.
Yields for isolated products.
Yields determined by gas chromatography.
[b]
[c]
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Andrꢀ L. Stein et al.
2r was obtained as a mixture containing hydrogenen-
ated oxazine and diphenyl ditelluride. Therefore, the
purification to high purity from the mixture was im-
possible. This result represents an additional attrac-
tive feature of our methodology since the higher reac-
tivity of the organotellurium moiety offers the possi-
bility for developing more complex heterocyclic com-
pounds.[22] Concerning the use of disulfides instead of
diselenides or ditellurides, we found some limitations
in this methodology. For example, reaction of diphen-
yl disulfide under the optimized conditions resulted in
the formation of a trace amount of product together
with unreacted starting material.
Concerning the mechanism pathway, the main ques-
tion is whether the cyclization may occur via an elec-
trophilic cyclization involving the PhSeCl (obtained in
situ by reaction of diphenyl diselenides and FeCl3) or
via an iron selenolate complex.[23] To obtain further
insight in order to rationalize the factors which could
govern the mechanism aspect of this cyclization reac-
tion, we performed some control experiments as fol-
lows: (a) when diphenyl diselenide was added to a so-
lution of ortho-alkynylanilide 1a and FeCl3 in CH2Cl2
the reaction gave only traces of product [Scheme 3,
Eq. (1)]. From this result we conclude that the mech-
anism by which FeCl3 promotes the cyclization to
2
À
form a cyclized Csp Fe intermediate d (Scheme 4)
that could react with diphenyl diselenide to give the
product is improbable; (b) when diphenyl diselenide
was reacted with FeCl3 in CH2Cl2, in the absence of
substrate 1a, no PhSeCl was detectable [Scheme 3,
Eq. (2)]. These results provide the first evidence to
discard the electrophilic cyclization pathway promot-
ed by PhSeCl. However, when PhSeCl, previously
prepared by reaction of diphenyl diselenide with thio-
nyl chloride,[24] was added to a solution of 1a in
CH2Cl2, a 37% yield of the desired product 2a and
Scheme 3. Mechanism investigations.
Scheme 4. Proposed mechanism for the synthesis of organoselenobenzoxazines.
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IronACTHNUTRGNE(UNG III) Chloride/Diorganyl Diselenides
a 43% yield of the indole derivative were obtained
[Scheme 3, Eq. (3)]. When the solution of ortho-
alkynACHTUNGTRENNUNGylanilide 1a, FeCl3 in CH2Cl2 was reacted for 1 h
at room temperature and then PhSeCl was added,
a mixture of product 2a with both hydrogenated oxa-
zine 3 and indole 4 was obtained [Scheme 3, Eq. (4)].
The reaction of ortho-alkynilanilide 1a, with ironACTHUNTGRNEUNG(III)
chloride (1.0 equiv.) in the absence of diphenyl disele-
nide gave a trace of the indole 4a’. In this case, the
ironACHTUNGTRENNUNG(III) chloride acts as a Lewis acid to activate the
triple bond to the nitrogen nucleophilic attack giving
the indole [Scheme 3, Eq. (5)]. Finally, the radical
pathway was not discarded; however, when the reac-
tion of 1a with diphenyl diselenide was carried out in
the presence of TEMPO, a radical inhibitor, 2a was
obtained in 70% yield. This result indicates that the
pathway does not follow the typical radical addition,
where the radical source is PhSeC. All results together
showed that the oxazine 2a formation is dependent
on the iron selenolate complex previously formed.
With this information in hand, we assume that: (i) the
iron selenolate species[21] coordinates to the carbon-
carbon bond to generate an intermediate a,[25] which
activates the carbon-carbon bond towards oxygen
attack, (ii) the anti attack of the oxygen atom on the
activated intermediate produces the oxazine-iron spe-
cies b, which suffers a reductive elimination to give
the desired cyclized product 2 (Scheme 4, pathway 1).
In addition, the Z stereochemistry obtained for ben-
zoxazines 2 is the second piece of evidence to discard
the electrophilic pathway 2 (Scheme 4). In this case,
the coordination of the electrophilic source, PhSeCl,
to the carbon-carbon triple bond could give the inter-
mediate c, (ii) the nucleophilic anti attack of the
oxygen atom on the activated triple bond could pro-
Figure 1. ORTEP view of the compound 2i.
Scheme 5. Preparation of oxazines 2.
duce the E-alkylidenebenzoxazines 2’ which have the cedure furnished oxazines 2a, 2i and 2m in moderate
two groups, PhSe and oxygen, in opposite sides of the yields (Scheme 5).
double bond (Scheme 4, pathway 2). In addition, ana-
As a result of the importance of quinazolines in the
lyzing the results, non-dominant pathway 3, field of pharmacologically active molecules, the devel-
a
Scheme 4, where FeCl3 promotes the cyclization of opment of synthetic approaches using mild reaction
ortho-alkynylanilide to form the intermediate d, conditions remains an attractive area for research.
which reacts with electrophilic PhSeCl to give the ox- One method of synthesizing quinazolines consists of
azine 2 cannot be excluded. As depicted in the study the reaction of oxazines with a nitrogen nucleophilic
for optimization of the conditions, amounts of indole source.[16,27] In this context, we evaluated the use of
derivative 4 were obtained as a result of a 5-endo cy- oxazine 2 as substrate in the reaction with NH4OAc.
ACHTUNGTRENNUNGclization, however, after the determination of the best A brief optimization of the conditions for this reac-
conditions, only 6-exo products were obtained, which tion revealed that the use of an excess of NH4OAc
were determined by NMR and confirmed by X-ray (10 equiv.) afforded the quinazoline 6a in 67% yield.
diffraction analysis (Figure 1).[26]
Furthermore, under these experimental conditions,
We next turned our attention to the preparation of quinazolines 6b and 6c were also obtained in 54%
oxazines 2 starting directly from 2-alkynylanilines 5 and 64% yields, respectively (Scheme 6).[28]
avoiding the previous prepartion of ortho-alkynylani-
lide 1. In view of this, aniline 5 was reacted with acid
chloride (1.0 equiv.) in CH2Cl2 (5 mL) for 4 h. Then, Conclusions
a solution of diphenyl diselenide and FeCl3 in CH2Cl2
was subsequently added. The resulting solution was In conclusion, we have found that the mixture of
stirred for 1 h at room temperature. This one-pot pro- FeCl3 and diorganyl dichalcogenides is a valuable
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Andrꢀ L. Stein et al.
Scheme 6. Preparation of quinazolines 6a–c.
combination as a cyclization promoter of ortho-alkyn-
ACHTUNGTRENNUNGylanilides to prepare benzoxazine derivatives. The re-
General One-Pot Procedure for Iron-Promoted
Cyclization of N-Acyl-ortho-alkynylanilines and
sults obtained demonstrate that: (a) the optimized re-
action conditions were compatible with a large variety
of functional groups, including electron-rich and elec-
tron-poor substrates; (b) the cyclization was stereose-
lective, affording exclusively the Z-alkylidenebenzox-
azines; (c) the cyclization was also regioselective
giving only the 6-exo-dig-cyclized products; (d) Z-al-
kylidenebenzoxazines proved to be potential sub-
strates for quinazoline derivatives. In addition, a one-
pot version for this cyclization, starting directly from
2-alkynylanilines, avoiding the previous preparation
of ortho-alkynilanilides gave the benzoxazine deriva-
tives in moderate yields. Finally, different from the
bad reputation that organoselenium compounds have
gained, with respect to bad smell, instability and high
toxicity, the compounds prepared in this study were
stable and odourless. Besides, they are currently
under pharmacological and toxicological investiga-
tions showing positive preliminary results.
Diorganoyl Dichalcogenides
In a Schlenck tube, under argon atmosphere, a mixture of
the benzoyl chloride (1.01 equiv.), the appropriate 2-alkynyl-
AHCTUNGTREaGNNNU niline (0.25 mmol) in dry CH2Cl2 (5 mL) was stirred for 4–
6 h at room temperature. Then, diphenyl diselenide
(0.75 equiv.) and FeCl3 (3 equiv.) were subsequently addi-
tioned. The resulting solution was stirred for 1 hour at room
temperature. After this the solution was diluted with di-
chloromethane (10 mL), and washed with saturated aqueous
NaCl (3ꢅ10 mL). The organic phase was separated, dried
over MgSO4, and concentrated under vacuum. The residue
was purified by flash chromatography on silica gel using n-
hexane/CH2Cl2 60/40 v/v as the eluent.
(Z)-2-Phenyl-4-[phenyl(phenylselanyl)methylene]-4H-
benzo[d]ACHTUNGETRN[UNNG 1,3]oxazine (2a): Yellow solid; mp 139–1418C;
1
yield: 0.084 g (74%). H NMR (CDCl3, 200 MHz): d=8.38–
8.33 (m, 2H), 7.56–7.45 (m, 3H), 7.39–7.04 (m, 12H), 6.81–
6.73 (m, 1H), 6.54–6.49 (m, 1H); 13C NMR (CDCl3,
50 MHz): d=155.7, 140.4, 140.3, 136.8, 135.5, 131.8, 131.2,
130.6, 130.1, 129.7, 128.6, 128.5, 128.4, 128.2, 127.6, 127.5,
126.6, 126.2, 125.6, 121.3, 111.8; MS (relative intensity):
m/z=453 (23), 296 (100), 267 (25), 165 (28), 77 (12); anal.
calcd. for C27H19NOSe: C 71.68, H 4.23, N, 3.10; found: C
71.75, H 4.30, N 3.16.
Experimental Section
General Procedure for Iron-Promoted Cyclization of
N-Acyl-ortho-alkynylanilines and Diorganoyl
Dichalcogenides
(Z)-2-Phenyl-4-[phenyl(para-tolylphenylseleno)methy-
lene]-4H-benzo[d]ACTHNUTRGNEUNG[1,3]oxazine (2b): Yellow solid; mp 182–
1848C; yield: 0.091 g (78%). 1H NMR (CDCl3, 200 MHz):
d=8.39–8.33 (m, 2H), 7.53–7.43 (m, 3H), 7.32–7.08 (m,
9H), 6.87–6.71 (m, 3H), 6.51–6.46 (m, 1H), 2.21 (s, 3H);
13C NMR (CDCl3, 50 MHz): d=155.7, 140.3, 140.0, 137.6,
136.8, 135.7, 131.8, 131.2, 130.6, 130.1 129.6, 129.3, 128.5,
128.4, 128.2, 127.5, 126.6, 126.2, 125.5, 124.3, 121.3, 112.4,
21.1; MS (relative intensity): m/z=467 (6), 296 (100), 266
(25), 218 (11), 165 (24), 77 (25); HR-MS: m/z=468.0895,
calcd. for C28H21NOSe (M+H+): 468.0866.
To a Schlenck tube, under argon atmosphere, containing
a mixture of FeCl3 (3 equiv.) in dry CH2Cl2 (4 mL) was
added
the
appropriate
diorganoyl
dichalcogenide
(0.75 equiv.). The resulting solution was stirred for 10 min at
room temperature. After this the appropriate N-acyl-ortho-
alkynylaniline (0.25 mmol) in CH2Cl2 (1 mL) was added and
resulting solution was stirred at room temperature for
1 hour. After this the solution was diluted with dichlorome-
thane (10 mL), and washed with saturated aqueous NaCl
(3ꢅ10 mL). The organic phase was separated, dried over
MgSO4, and concentrated under vacuum. The residue was
purified by flash chromatography on silica gel using n-
hexane/CH2Cl2 60/40 v/v as the eluent.
(Z)-4-[(para-Chlorophenylseleno)
ACHTUNGERTN(NUNG phenyl)methylene]-2-
phenyl-4H-benzo[d][1,3]oxazine (2c): Yellow solid; mp 216–
AHCTUNGTRENNUNG
2188C; yield: 0.076 g (62%). 1H NMR (CDCl3, 200 MHz):
d=8.37–8.32 (m, 2H), 7.53–6.99 (m, 14H), 6.82–6.74 (m,
1H), 6.54–6.49 (m, 1H); 13C NMR (CDCl3, 50 MHz): d=
155.6, 140.7, 140.3, 136.8, 134.0, 132.8, 131.9, 131.1, 130.6,
129.9, 128.7, 128.6, 128.5, 128.2, 127.8, 126.7, 126.3, 125.6,
121.1, 111.3, 106.9; MS (relative intensity): m/z=487 (10),
296 (100), 207 (69), 165 (39), 77 (29); anal. calcd. for
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IronACTHNUTRGNE(UNG III) Chloride/Diorganyl Diselenides
C27H18ClNOSe: C 66.61, H 3.73, N 2.88; found: C 66.80, H References
3.78, N 2.92.
(Z)-4-[(para-Fluorophenylseleno)
ACHTUNGERTN(NUNG phenyl)methylene]-2-
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3582.
phenyl-4H-benzo[d][1,3]oxazine (2d): Yellow solid; mp
AHCTUNGTRENNUNG
147–1498C; yield: 0.081 g (69%). 1H NMR (CDCl3,
200 MHz): d=8.39–8.34 (m, 2H), 7.54–7.47 (m, 3H), 7.35–
7.03 (m, 10H), 6.81–6.66 (m, 3H), 6.53–6.46 (m, 1H);
13C NMR (CDCl3, 50 MHz): d=162.6, 155.4, 140.1, 139.6,
138.2, 136.3, 131.8, 131.2, 130.6, 129.6, 128.6, 128.4, 128.1,
127.9, 127.6, 125.4, 122.4; MS (relative intensity): m/z=471
(12), 296 (100), 267 (32), 207 (48), 165 (37), 105 (13), 73
(30); anal. calcd. for C28H21FNOSe: C 68.94, H 3.86, N 2.98;
found: C 69.05, H 3.90, N 3.03.
(Z)-4-[ButylselenoACHTUNGTREN(NUNG phenyl)methylene]-2-phenyl-4H-
benzo[d][1,3]oxazine (2e): Yellow solid; mp 61–638C; yield:
ACHTUNGTRENNUNG
0.048 g (44%). 1H NMR (CDCl3, 200 MHz): d=8.49–8.44
(m, 1H), 7.67–7.62 (m, 2H), 7.54–7.22 (m, 11H), 2.36 (t, J=
7.2 Hz, 2H), 1.52 (quint, J=7.2 Hz, 2H), 1.24 (sext, J=
7.2 Hz, 2H), 0.77 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3,
50 MHz): d=156.0, 141.7, 141.3, 138.4, 131.5, 130.3, 129.9,
129.2, 128.2, 128.1, 127.9, 127.5, 127.1, 126.3, 125.6, 122.2,
110.6, 32.2, 27.1, 22.8, 13.5; MS (relative intensity): m/z=
433 (38), 375 (37), 295 (100), 267 (40), 207 (30), 165 (89), 77
(27); HR-MS: m/z=434.1025, calcd. for C25H23NOSe:
434.1023 (M+ H+).
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(Z)-4-[Phenyl(phenylseleno)methylene]-2-para-tolyl-4H-
benzo[d]ACHTUNGTRENNUNG[1,3]oxazine (2f): Yellow solid; mp 105–1078C;
1
yield: 0.089 g (77%). H NMR (CDCl3, 200 MHz): d=8.26–
8.22 (m, 2H), 7.36–6.98 (m, 14H), 7.78–6.71 (m, 1H), 6.53–
6.48 (m, 1H), 2.42 (s, 3H); 13C NMR (CDCl3, 50 MHz): d=
155.8, 142.3, 140.4, 136.8, 135.4, 130.6, 129.6, 129.1, 128.9,
128.5, 128.4, 128.3, 128.1, 127.5, 127.4, 126.3, 126.0, 125.6,
121.1, 111.5, 96.3, 21.6; MS (relative intensity): m/z=467
(6), 310 (43), 281 (34), 207 (100), 165 (28), 73 (62); anal.
calcd. for C28H21NOSe: C 72.10, H 4.54, N 3.00; found: C
72.26, H 4.61, N 3.07.
(Z)-2-(para-tert-Butylphenyl)-4-[phenyl(phenylseleno)-
methylene]-4H-benzo[d]ACTHUNRGTNE[NUG 1,3]oxazine (2g): Yellow solid; mp
133–1358C; yield: 0.091 g (72%). 1H NMR (CDCl3,
200 MHz): d=8.31–8.26 (m, 2H), 7.54–7.49 (m, 2H), 7.36–
7.03 (m, 12H), 6.79–6.70 (m, 1H), 6.53–6.49 (m, 1H), 1.36
(s, 9H); 13C NMR (CDCl3, 50 MHz): d=155.9, 155.4, 140.7,
137.2, 135.4, 131.6, 130.7, 129.7, 129.0, 128.5, 128.4, 128.1,
127.9, 127.5, 126.3, 126.2, 125.7, 125.4, 125.2, 121.3, 111.6,
35.0, 31.2; MS (relative intensity): m/z=509 (21), 352 (100),
296 (42), 207 (68), 165 (92), 57 (61); anal. calcd. for
C31H27NOSe: C 73.22, H 5.35, N 2.75; found: C 73.41, H
5.41, N 2.80.
Acknowledgements
[19] T. Saito, S. Ogawa, N. Takei, N. Kutsumura, T. Otani,
We are grateful to FAPERGS (PRONEX-10/0005-1),
CAPES (SAUX) and CNPq (CNPq/INCT-catalise) for the fi-
nancial support. CNPq is also acknowledged for the fellow-
ships.
Org. Lett. 2011, 13, 1098.
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oxidized to diselenides upon air exposure.
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508
asc.wiley-vch.de
ꢄ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 501 – 508