A convenient synthesis of 8,8’-spirobi(chromano-1,2-oxaphosphinine) derivatives

Article abstract of DOI:10.1016/j.mencom.2017.03.007

8,8’-Spirobi(chromano-1,2-oxaphosphinines) were obtained by the reaction between phosphorylated derivatives of spirodichromane and arylacetylenes with a high chemoselectivity.

Full text of DOI:10.1016/j.mencom.2017.03.007

Mendeleev
Communications
Mendeleev Commun., 2017, 27, 131–133
A convenient synthesis of 8,8'-spiro-
bi(chromano-1,2-oxaphosphinine) derivatives
Igor O. Nasibullin, Andrey V. Nemtarev* and Vladimir F. Mironova,b
a
a,b
a
b
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy
of Sciences, 420088 Kazan, Russian Federation. E-mail: a.nemtarev@mail.ru
Kazan (Volga Region) Federal University, 420008 Kazan, Russian Federation
DOI: 10.1016/j.mencom.2017.03.007
Me Me
Ar
Me Me
HO
HO
8
,8'-Spirobi(chromano-1,2-oxaphosphinines) were obtained by
O
X
O
OH
OH
O
O
X
P
P
the reaction between phosphorylated derivatives of spiro-
dichromane and arylacetylenes with a high chemoselectivity.
O
O
O
O
Me Me
X = Cl, Br, OH
Me Me
Ar
Spirocyclic polyhydroxyarenes of chromane series are a special
group of polyphenolic compounds that possess a broad spectrum
of practically important properties. Spirocyclic compounds have
nonlinear structures and comprise rigidly bound annular moieties,
owing to which they can be used to obtain polymeric and supra­
molecular compounds with various structures.1 Low­molecular
spirochromane derivatives containing chromophoric groups form
in high yields. According to 31P NMR data, the content of com­
pounds 3a,b in the reaction mixture was 90–95%. It should also
3
1
1
be noted that compound 3a manifests itself in the P­{ H}NMR
spectrum as two closely­spaced singlets (d 198.6 and 199.5) in
p
7.9:1 ratio. This suggests that stereoisomers exist, possibly with
different orientations of the halogen atoms.
–5
Halophosphites 3a,b were converted to chloro­ and bromo­
phosphoranes 4a,b by the reactions with phosphorus pentachloride
3
D holographic gratings and can be employed to create holo­
6
§
graphic data storage systems.
and molecular bromine, respectively (see Scheme 1). Analysis of
Incorporation of four hydroxy groups, which form two catechol
systems, intothespirochromanestructureopensthewaytophospha­
coumarin (areno­1,2­oxaphosphinine) derivatives. The structural
‡
2,2'-Dichloro-8,8,8',8'-tetramethyl-6,6'-spirobi(chromano[6,7-d]-
7
1,3,2-dioxaphosphole) 3a. A solution of compound 2 (2.64 g, 4 mmol) in
chloroform (15 ml) was added to a solution of phosphorus trichloride (2.0 ml,
2
ture for 1.5 h. The solvent and volatile compounds were removed in vacuo
(12 Torr). Crystalline precipitate of compound 3a was formed. Yield 1.8 g
similarity of this class of compounds to natural coumarins and the
presence of a phosphorus atom predetermine the biological activity
of phosphacoumarins and phosphaisocoumarins. For example, Li
3 mmol) in chloroform (10 ml). The mixture was stirred at room tempera­
8
et al. performed a rather comprehensive study of the inhibiting
1
(90%). H NMR (400 MHz, CDCl ) d: 1.41 (s, 6H, Me), 1.61 (s, 6H, Me),
3
effect of phosphorus­containing compounds with isocoumarin
structure on the activity of cholesterol esterase.
2
2
2
7
.01 (br.d, 2H, two A­parts of two AB­spectra, J 14.0 Hz), 2.15 (br.d,
AB
2
9
H, two B­parts of two AB­spectra, J 14.1 Hz), 6.59 (br.s, 2H, HC ),
.22 (br.s, 2H, HC ). P­{ H} NMR (162 MHz, CDCl ) d : 176.4 (s).
AB
In this study, we suggest an easy and efficient access to
4
31
1
3
P
8
,8'­spirobi(chromano[6,7­e]­1,2­oxaphosphinines) based on the
reaction of phosphorylated derivatives of 6,6',7,7'­tetrahydroxy­
,4,4',4'­tetramethyl­2,2'­spirobichromane 1 with acetylenes. The
2
,2'-Dibromo-8,8,8',8'-tetramethyl-6,6'-spirobi(chromano[6,7-d]-
1,3,2-dioxaphosphole) 3b. A solution of compound 2 (3.83 g, 5.8 mmol)
in chloroform (15 ml) was added to a solution of phosphorus tribromide
(2.2 ml, 23 mmol) in chloroform (5 ml). The reaction mixture was stirred
at room temperature for 1.5 h. Crystalline precipitate of compound 3b was
formed, mp 208°C, yield 3g (89%). H NMR (400 MHz, CDCl ) d: 1.44
(br.s, 6H, Me), 1.63 (br.s, 6H, Me), 2.05 (br.d, 2H, two A­parts of two
4
starting spirochromane 1 was obtained by condensation of 1,2,4­tri­
acetoxybenzene with acetone in the presence of acetic and hydro­
1
9
chloric acids. The structure of the resulting tetraol was confirmed
3
1
by spectral methods ( H NMR spectroscopy, mass spectrometry).
2
AB­spectra, J 14.1 Hz), 2.16 (br.d, 2H, two B­parts of two AB­spectra,
AB
It is known that polyhydroxyarenes are poorly soluble in most
organic solvents. For this reason, tetraol 1 was converted to silyl
ether 2 by the reaction with excess chlorotrimethylsilane in the
2
8
5
31
JAB 14.1 Hz), 6.61 (br.s, 2H, H ), 7.25 (br.s, 2H, H ). P NMR (162 MHz,
CCl ) d : 198.6 (s), 199.5 (s).
4
P
§
2
,2,2,2',2',2'-Hexachloro-8,8,8',8'-tetramethyl-6,6'-spirobi(chromano-
†
presence of triethylamine (Scheme 1). Compound 2 is a dark oily
[
6,7-d]-1,3,2-dioxaphosphole) 4a.A solution of compound 3a (1 g, 2 mmol)
liquid well soluble in dichloromethane. Further, silyl ether 2 was
in dichloromethane (10 ml) was added to a suspension of phosphorus
pentachloride (0.83 g, 4 mmol) in dichloromethane (10 ml). The
reaction mixture was stirred at room temperature for 2 h at room
temperature until complete dissolution of phosphorus pentachloride. The
‡
treated with a phosphorus trihalide taken in excess. The phos­
phorylation occurs under mild conditions to give phosphites 3a,b
†
1
6
,6',7,7'-Tetrakis(trimethylsiloxy)-4,4,4',4'-tetramethyl-2,2'-spiro-
solvent and volatile compounds were removed in vacuo (12 Torr). H NMR
bichromane 2. A solution of chlorotrimethylsilane (2.9 ml, 23 mmol) in
benzene (15 ml) was added dropwise to a solution of spiro chromane 1
(400 MHz, CDCl3) d: 1.35 (s, 6H, Me), 1.57 (s, 6H, Me), 1.99 (d, 2H,
2
two A­parts of two AB­spectra, JAB 14.0 Hz), 2.12 (d, 2H, two B­parts
2
9
(
2.18 g, 5.8 mmol) and NEt (3.2 ml, 23 mmol) in 100 ml of absolute
of two AB­spectra, JAB 14.0 Hz), 6.40 (br.s, 2H, H ), 7.08 (br.s, 2H,
3
4
31
1
benzene. The mixture was stirred at room temperature for 0.5 h. Further,
the mixture was heated up to 90°C and stirred for 1.5 h. On the next day, the
mixture was filtered and the solvent was removed in vacuo. The residue
H ). P­{ H} NMR (162 MHz, CDCl3) dP: –25.7 (s).
2,2,2,2',2',2'-Hexabromo-8,8,8',8'-tetramethyl-6,6'-spirobi(chromano-
[6,7-d]-1,3,2-dioxaphosphole) 4b. Bromine (0.6 ml, 12 mmol) was added
to a cooled (–20°C) solution of compound 3b (3.54 g, 6 mmol) in dichloro­
methane (15 ml). The orange precipitate was obtained. 31P­{ H} NMR
(162 MHz, CH2Cl2) dP: –189.0 (br.s).
1
was a dark oil. H NMR (500 MHz, CDCl ) d: 0.21 (s, 18H, SiMe ), 0.25 (s,
3
3
1
1
8H, SiMe ), 1.32 (s, 6H, Me), 1.53 (s, 6H, Me), 1.94 (d, 2H, CH ,
3
2
2
2
8
5
J 13.9 Hz), 2.07 (d, 2H, CH , J 13.9 Hz), 6.15 (s, 2H, H ), 6.76 (s, 2H, H ).
2
©
2017 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
–
131 –

Mendeleev Commun., 2017, 27, 131–133
Me Me
Me Me
HO
HO
Me SiO
3
1
O
8
7
OH
OH
i
O
OSiMe3
ii
2
O 3
Me SiO
O
3
6
4
OSiMe3
5
Me Me
Me Me
1
2
Me Me
Me Me
O
O
O
5
O
4
3
O
HalP
Hal3P
O
O
2
6
iii
iv
O
O
PHal
O
PHal3
1
7
8
O
O
9
Me Me
Me Me
3
3
a Hal = Cl
b Hal = Br
4a Hal = Cl
4b Hal = Br
R
R
O
Me Me
Me Me
O
9
O
10
5
O
O
9a
5a
10a
O
O
O
R
Hal
v
HO
P
8
P
P
P
O
O
Hal
OH
O
6
3
O
7
4a
4
16
15
1
1
Me Me
Me Me
R = H
R = Me
1
2
7
8
5
5
6
a R = H, Hal = Cl
b R = H, Hal = Br
b R = Me, Hal = Br
13
14
R
Scheme 1 Reagents and conditions: i, Me SiCl (4 equiv.), NEt (4 equiv.); ii, PCl or PBr ; iii, PCl or Br ; iv, PhCºCH or 4­MeC H CºCH; v, H O.
3
3
3
3
5
2
6
4
2
the 31P NMR spectra of the reaction mixtures allowed us to deter­
mine the quantitative and qualitative composition of the products.
In fact, the content of phosphorane 4b, which manifested itself as a
observed, which indicates that the reaction occurs rather quickly.
In the P spectrum of the reaction mixture, compound 5b exhibited
31
three doublets (d 9.7, 9.8, and 10.4) in 1:1:2 ratio with similar
p
31
2
broadened signal near d –189.0 in the P NMR spectrum, was
coupling constants ( J
25.8–26.9 Hz). This set of signals
p
PCH
3
1
about 90%. Chlorophosphorane 4a manifested itself in the
P
indicates the formation of a mixture of phosphinine 5b stereo­
spectrum as a singlet around d –25.4; its content in the reaction
isomers due to the chirality of the two phosphorus atoms and the
pseudochirality of the C atom.
p
8
mixture was 95%. Due to the hydrolytic and thermal (in the case
of tribromophosphoranes) instability, compounds 4a,b were not
isolated pure and used in the further reactions with acetylenes as
crude materials.
The reaction of chloro derivative 4a with terminal acetylenes
occurs by a similar pathway to afford oxaphosphinine 5a (see
10
Scheme 1). As shown previously, the reactions of trichlorophos­
pholes with acetylenes often involve the migration of a chlorine
atom to the aromatic ring of oxaphosphorines with replacement
of hydrogen or one of the substituents (bromine, tert­butyl). In
this case, the chromane system is not attacked by a halogen
atom. This fact is probably due to the donor effect of the oxygen
¶
On addition of arylacetylenes to phosphorane 4b, dissolu­
tion of the latter to give a homogeneous light­brown solution was
¶
2
,2'-Dichloro-6,6,6',6'-tetramethyl-4,4'-diphenyl-8,8'-spirobi(chromano-
6,7-e]-1,2-oxaphosphinine)-2,2'-dioxide 5a. Phenylacetylene (0.88 ml,
mmol) was added to a mixture containing compound 4a (1.3 g, 2 mmol).
[
8
After the reaction was complete (30 min), the volatiles were removed
2,2'-Dibromo-6,6,6',6'-tetramethyl-4,4'-diphenyl-8,8'-spirobi(chromano-
[6,7-e]-1,2-oxaphosphinine)-2,2'-dioxide 5b. Phenylacetylene (2.5 ml,
23.2 mmol) was added to a cooled mixture containing compound 4b
(5.4 g, 6 mmol). The reaction mixture was heated up to room tempe­
rature, the formed precipitate fully dissolved. After the reaction was
complete (30 min), the solvent and volatiles were removed in vacuo
(12 Torr) to give diastereosomers of compound 5b as a pale brown glassy
in vacuo (12 Torr) to afford the pale brown glassy substance being the
1
mixture of diastereoisomers. H NMR (400 MHz, CDCl ) d: 1.22, 1.25
3
(
both s, 6H, Me), 1.52, 1.55 (both s, 6H, Me), 2.02 (br.d, 2H, twoA­parts
2
of two AB­spectra, J 14.3 Hz), 2.16 (br.d, 2H, two B­parts of two
AB­spectra, J 14.3 Hz), 6.18, 6.23 (both d, 2H, H , J
6
Ph), 7.48–7.59 (br.m, 6H, Ph). C NMR (100.6 MHz, CDCl ) d :
3
(
1
AB
2
3 2
24.3 Hz),
AB
PCH
1
0
5
.65, 6.68 (both s, 2H, H ), 7.25 (br.s, 2H, H ), 7.38–7.46 (br.m, 4H,
1
3
31
2
substance. P NMR (162 MHz, CH Cl ) d : 9.7 ( J
25.8 Hz), 9.8
3
C
2
2
P
PCH
6
7
2
2
0.67, 30.71 (both s, C ), 32.23, 32.40 (both s, Me), 45.72 (s, C ), 99.07
( J
26.9 Hz), 10.4 ( J
26.9 Hz).
PCH
PCH
8
10 3
s, C ), 108.22, 108.28 (both d, C , J
8.7 and 8.4 Hz), 111.51,
2,2'-Dibromo-6,6,6',6'-tetramethyl-4,4'-bis(4-methylphenyl)-8,8'-spiro-
bi(chromano[6,7-e]-1,2-oxaphosphinine)-2,2'-dioxide 6b. 4­Methyl­
phenylacetylene (1.85 g, 16 mmol) was added to a cooled mixture
containing compound 4b (3.6 g, 4 mmol). The reaction mixture was
heated up to room temperature, the formed precipitate fully dissolved.
After reaction was complete (30 min), the volatiles were removed in vacuo
(12 Torr) to leave the pale brown glassy substance being the mixture
POCC
3
1
11.93 (both d, C , J 156.5 and 156.6 Hz), 115.89, 116.11 (both d,
PC
4
a
3
5
C , J
(
18.2 and 18.1 Hz), 126.42, 126.62 (both s, C ), 127.36, 127.42
both s, C ), 128.53, 128.58 (both s, C ), 128.78, 128.83 (both s, C ),
29.86, 130.01 (both s, C ), 137.63, 137.70 (both d, C , J
1.3 Hz), 150.27, 150.31 (both d, C , J
53.19 (both s, C ), 156.80, 157.03 (both d, C , J
P NMR (162 MHz, CDCl ) d : 20.0 (d, JPCH 24.5 Hz), 20.3 (d,
PCCC
5a
13
12
14
11 3
1
2
1
21.0 and
PCCC
1
0a 2
9.2 and 9.4 Hz), 153.15,
POC
9a
4 2
2.2 and 2.4 Hz).
PCC
3
1
2
31
of diastereoisomers 6b. P NMR (202.5 MHz, CH Cl ) d : 10.3 (d,
3
P
2
2
P
2J
24.5 Hz).
2
JPCH 25.4 Hz), 10.4 (d, J
2
26.8 Hz), 11.1 (d, J
2
26.8 Hz).
PCH
PCH
PCH
–
132 –

Mendeleev Commun., 2017, 27, 131–133
atom of the chromane system that participates in positive charge
O
O
delocalization at the stage of formation of the s­complex (struc­
ture C) after the formation of a p­complex (A) and s­complex
(B) in the reaction of phosphorane 4 with acetylene (Scheme 2).
Oxaphosphinines 5a,b and 6b were hydrolyzed in a dioxane/
acetone medium to give individual phosphinines 7 and 8†† as
colourless crystalline compounds (see Scheme 1).
O
O
O
O
PHal3
CH
PHal3
Me Me
R
C
Me Me
R
A
B
Based on the detailed analysis of the spectral data, one can
conclude that the reaction of halophosphoranes 4a,b with terminal
arylacetylenes proceeds with a high regioselectivity. Namely, the
ipso­substitution of an oxygen atom in the dioxaphospholane ring
occursatthepara­positiontotheoxygenatomofthespirochromane
system, in agreement with the assumed reaction mechanism that
O
O
O
PHal3
Me Me
R
1
1
we discussed previously.
C
In conclusion, we suggested an efficient chemoselective
approach to 8,8'­spirobi(chromano[6,7­e]­1,2­oxaphosphinines)
that are structural analogues of natural chromanocoumarins, based
on the reaction of phosphorylated derivatives of 6,6',7,7'­tetra­
hydroxy­4,4,4',4'­tetramethyl­2,2'­spirobichromane with aryl­
acetylenes.
Scheme 2
††2
chromano[6,7-e]-1,2-oxaphosphinine)-2,2'-dioxide 7. Hydrolysis of the
,2'-Dihydroxy-6,6,6',6'-tetramethyl-4,4'-diphenyl-8,8'-spirobi-
(
reaction mixture containing 5a or 5b in dioxane affords the colorless
crystals of compound 7.Yield 2.5 g (63%), mp 340°C (decomp.). H NMR
1
(
400 MHz, DMSO­d ) d: 1.03 (s, 6H, Me), 1.42 (s, 6H, Me), 2.04 (d, 2H,
6
This work was supported by the Russian Foundation for Basic
Research (grant no. 16­03­00451).
2
two A­parts of two AB­spectra, J 14.5 Hz), 2.17 (d, 2H, two B­parts of
two AB­spectra, J 14.4 Hz), 6.11 (d, 2H, H , J 18.1 Hz), 6.58 (s, 2H,
AB
2
3 2
AB
5
10
H ), 7.11 (s, 2H, H ), 7.38–7.41 (m, 4H, Ph), 7.52–7.54 (m, 6H, Ph).
1
3
1
6
References
C­{ H} NMR (100.6 MHz, DMSO­d ) d : 30.36 (s, C ), 32.46 (s, Me),
6
C
3
7
8
10
3
4
5.01 (s, C ), 99.35 (s, C ), 107.70 (d, C , J
6.8 Hz), 113.60 (d, C ,
16.4 Hz), 127.09 (s, C ), 127.35 (s,
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POCC
1
4a
3
5
J
170.1 Hz), 117.04 (d, C , J
PC
a
PCCC
12
5
13
14
11
C ), 128.77 (s, C ), 129.15 (s, C ), 129.50 (s, C ), 139.05 (d, C ,
3
10a
2
9a
J
18.7 Hz), 150.81 (d, C , J
6.8 Hz), 152.06 (C ), 152.35 (d,
PCCC
POC
4
2
31
2
C , J 1.9Hz). P NMR (162 MHz, DMSO­d ) d : 5.8 (d, J 18.0 Hz).
MS (MALDI­TOF), m/z: 668.9 (calc. for C H O P , m/z: 668.6).
PCC
6
P
PCH
37
34
8 2
2
780.
2
,2'-Dihydroxy-6,6,6',6'-tetramethyl-4,4'-bis(4-methylphenyl)-8,8'-spiro-
5
A. R. Tuktarov, L. M. Khalilov, K. K. Babievskii, A. R. Akhmetov, V. I.
bi(chromano[6,7-e]-1,2-oxaphosphinine)-2,2'-dioxide 8. Hydrolysis of the
reaction mixture containing 6b in dioxane affords the colorless crystals
of compound 8. Yield 1.6 g (58%), mp 343°C (decomp.). 1H NMR
(
2
B­parts of two AB­spectra, J 14.4 Hz), 2.39 (C Me, 6H), 6.04 (d,
2
H , AA'­part of AA' BB'­spectrum, J 7.6 Hz), 7.33 (m, 4H, H , BB'­part
ofAA' BB'­spectrum, J 7.6 Hz). C­{ H} NMR (150.9 MHz, DMSO­d )
d : 21.32 (C Me), 30.39 (s, C ), 31.14 (s, C ), 32.49 (s, C ), 45.06 (C ),
9
1
Sokolov and U. M. Dzhemilev, Mendeleev Commun., 2015, 25, 273.
6 H. Audorff, R. Walker, L. Kador and H.­W. Schmidt, Chem. Eur. J.,
011, 17, 12722.
2
400 MHz, DMSO­d ) d: 1.15 (s, 6H, Me), 1.42 (s, 6H, Me), 2.03 (d,
6
7
8
9
V. Mironov, T. Zyablikova, I. Konovalova, R. Musin and M. Khanipova,
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2
H, two A­parts of two AB­spectra, J 14.4 Hz), 2.16 (d, 2H, two
AB
2
14
AB
3
2
10
5
H, H , J 18.1 Hz), 6.54 (s, 2H, H ), 7.14 (s, 2H, H ), 7.28 (m, 4H,
PH
45, 1955.
1
3
3
13
HH
W. Baker and D. M. Besly, J. Chem. Soc., 1939, 195.
3
13
1
6
10 V. F. Mironov,A. T. Gubaidullin, R. R. Petrov, I.A. Litvinov,A.A. Shtyrlina,
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1
4
6
15
16
7
C
8
10
3
3 1
9.36 (C ), 107.70 (d, C , J
6.9 Hz), 113.20 (d, C , J 170.4 Hz),
POCC
PC
5a
4
a
3
5
17.10 (d, C , J
16.2 Hz), 127.08 (s, C ), 127.43 (s, C ), 128.73 (s,
PCCC
12
13
11
3
14
C ), 129.74 (s, C ), 136.18 (d, C , J
18.8 Hz), 139.11 (s, C ),
PCCC
9a
50.86 (d, C1 , J
0a
2
6.8 Hz), 152.03 (s, C ), 152.34 (d, C , J 1.9 Hz).
P NMR (162 MHz, DMSO­d ) d : 6.1 (d, J
4 2
1
POC
PCC
3
1
2
17.8 Hz). MS (MALDI­
6
P
PCH
TOF), m/z: 696.9 (calc. for C H O P , m/z: 696.6).
Received: 23rd June 2016; Com. 16/4968
38
36
8 2
–
133 –