Prototropic isomerization of spiro[2,3]hexanes 1,1,5-trisubstituted with electron-acceptor groups into 1,3-disubstituted bicyclo[1.1.0]butanes

Article abstract of DOI:10.1007/s11178-005-0143-9

1,1-Dicyano- and 1,1-dialkoxycarbonylspiro[2.3]hexane-1-carbonitriles treated with lithium diisopropylamide or potassium tert-butylate in THF undergo a prototropic isomerization into 3-(2,2-dicyanoethyl)- and 3-(2,2- dialkoxycarbonylethyl)bicyclo[1.1.0]butane-1-carbonitriles respectively. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-005-0143-9

Russian Journal of Organic Chemistry, Vol. 41, No. 2, 2005, pp. 189 -193. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2,
2005, pp. 201-204.
Original Russian Text Copyright Ó 2005 by Razin, Ulin.
Prototropic Isomerization of Spiro[2,3]hexanes
1,1,5-Trisubstituted with Electron-acceptor Groups
into 1,3-Disubstituted Bicyclo[1.1.0]butanes
V.V. Razin and N.V. Ulin
St. Petersburg State University, St. Petersburg, 198904 Russia
Received July 7, 2004
Abstract—1,1-Dicyano- and 1,1-dialkoxycarbonylspiro[2.3]hexane-1-carbonitriles treated with lithium
diisopropylamide or potassium tert-butylate in THF undergo a prototropic isomerization into 3-(2,2-dicyanoethyl)-
and 3-(2,2-dialkoxycarbonylethyl)bicyclo[1.1.0]butane-1-carbonitriles respectively.
Cyclopropanes containing two electron-acceptor
substituents at the same atom of the ring (activated
cyclopropanes) are known [1] to enter into addition
reactions with various nucleophilic agents, among them
also with C-nucleophiles. It was established [2] that
activated cyclopropanes with a third substituent possessing
a CH-acid moiety under the action of bases underwent
a prototropic isomerization resulting in building up a new
ring instead of the opened three-membered one. Dani-
shefsky et al. [3] discovered a cyclopropane-cyclo-
propane isomerization presented below effected by
sodium dimsyl in DMSO.
Bis(alkoxycarbonyl) derivatives I and II were obtained
from available methylenecyclobutane (IV) by a carbene
reaction involving the corresponding ester of diazomalonic
acid. Trinitrile III was prepared from the same precursor
along Boldt procedure [5] in two stages: first was carried
out a photochemical addition of bromomalononitrile, and
then adduct V was subjected to dehydrobromination. The
substituted spirohexanes I and II were obtained as two
diastereomers that were not separated.
The precursor of spirohexane III, bromide V, was also
5
5
1 &5
&1
&1
,ꢀꢀꢀ,,,ꢁꢀ9,
&2 &+
& + 2 + &
B
,9
& + 2 + &
&2 &+
+
KY
&+%Uꢀ&1ꢁ
1ꢀ& + ꢁ
%U
ꢀ1&ꢁ +&
&2 &+
&2 &+
&1
& + 2 &
& + 2 &
9
+
obtained as a mixture of diastereomers. The main E-isomer
Va was isolated from the mixture by crystallization. The
treatment of the latter with triethylamine resulted in an
individual diastereomer of spirohexane III that was
assigned Z-configutation IIIb in keeping with the expected
stereospecific elimination, cf. [6]. In its turn the configura-
tion assigned to bromide Va was assumed based on the
close values of the chemical shifts of H1 (3.65 ppm) in
Va spectrum and that of the model E-3-bromo-3-methyl-
cyclobutane-1-carbonitrile (3.46 ppm) taking into account
that in the spectrum of the Z-isomer of the model the
corresponding signal appeared upfield from 3.17 ppm, cf.
This approach (building of a three-carbon ring at
a sacrifice of opening another one) we have used in the
present study where we report on the new preparation
method for 1,3-disubstituted bicyclobutanes by prototropic
isomerization of spiro[2.3]hexanes 1,1,5-trisubstituted with
electron-acceptor groups.*
We studied the behavior of three substituted spiro-
hexanes I–III in the presence of strong bases, lithium
diisopropylamide or potassium tert-butylate in THF.
* For preliminary communication see [4].
1070-4280/05/4102-0189Ó2005 Pleiades Publishing, Inc.

RAZIN, ULIN
190
[7]. The structure of compounds I–III was proved using
1H and 13C NMR spectroscopy. The spectral identification
of the spirohexane skeleton of these compounds was
performed by comparison with the data on model nitrile
VI prepared by cyclopropanation of compound IV with
diazomethane. The assignment of configuration in
diastereomers I–III was based on the difference in the
chemical shifts of the carbons in the four-membered ring
analogous to that in the diastereomers 1-
oxaspiro[2.3]hexane-5-carbonitrile (VII) whose
configurational assignment was proved [6]: in the E-
isomers (a) the signals of C3 and C5 are shifted downfield,
and the signal of C4,6 upfield with respect to the
corresponding resonances in the Z-isomers (b). Below
are given the chemical shifts of carbon atoms (d, ppm) in
the four-membered rings for diastereomers of spiro-
hexane compounds Ia, Ib–IIIa, IIIb, VIIa, VIIb.
However since the reaction was carried out in an
aprotic medium at the use of a strong base, the direction
of isomerization should be governed here by an equilibrium
between the carbanion intermediates A and B.
5
5
B
,ꢀꢀꢀ,,,
&1
$
+ 2
5
5
&1
5 +&
&1
B
%
9,,,ꢀꢀꢀ;
R = CO2CH3 (VIII), CO2C2H5 (IX), CN (X).
The relative stability of the latter depends mostly on
the degree of the charge delocalization that is greater in
the B ion. Finally, the target isomerization products VIII–
X arise only on diluting the reaction mixture with water.
The above reasoning on the mechanism of the observed
isomerization is indirectly confirmed by the formation of
cyclobutane XI resulting from treating bicyclobutane X
with sodium methylate.
C3
C4,6
C5
Ia/Ib
33.2/32.5
32.9/32.3
32.3/33.1
32.4/33.2
31.2/31.5
35.6/35.9
17,2/16.6
17.4/16.8
17.0/16.6
15.0/13.5
IIa/IIb
IIIa/IIIb 35.0/34.4
VIIa/VIIb 57.6/56.2
ꢀ1&ꢁ +&
+ &2&+
&+ 21D
&+ 2+
&+ 21D
&+ 2+
Note that the above configurational assignment fully
agrees with already mentioned conclusion on the Z-con-
figuration of compound IIIb.
;
,,,
&1
;,
The isomerization of spirohexanes I–III at room
temperature was a fast process, and the corresponding
substituted bicyclobutanes VIII–X were obtained in
a high yield. The structure of the latter compounds was
conclusively confirmed by their 1H and 13C NMR spectra.
As particular features of the spectral parameters proving
the presence in their structure of a 1-cyanobicyclobutane
fragment should be mentioned the broadened singlets of
the nonequivalent methylene protons of the ring separated
by ~ 0.7 ppm, and the upfield shift of C1 atom located in
the negative region of the d scale, cf. [6, 7].
The observed prototropic isomerization (I–III) ®
(VIII–X) is especially interesting since it is irreversibly
shifted to the bicyclobutane compounds VIII–X contrary
to the greater strain energy of the bicyclobutane skeleton
(63.9 kcal mol-1 [8]) as compared to that of the
spirohexane (56.7 kcal mol-1 ).*
Unlike the situation in the aprotic medium, the equi-
librium between compounds X and III in methanol holds
a position favoring the latter. Further compound III being
an activated cyclopropane [1] and hence unstable under
these conditions suffers a nucleophilic ring opening
effected by sodium methylate to afford cyclobutane XI.
The ready conversion (III) ® (XI) was proved by
a direct experiment. Compound XI was obtained as
a mixture of two diastereomers. The structure of com-
pound XI was proved by comparing its 1H and 13C NMR
spectra with the data of model 1,1,3-trisubstituted cyclo-
butanes [8].
EXPERIMENTAL
1H and 13C NMR spectra were registered on a
spectrometer Bruker DPX-300 at 300.13 and 75.47 MHz
respectrively from solutions in CDCl3. Elemental analyses
were performed on a CHN-analyzer HP-185 B.
Analytical TLC was carried out on Silufol UV-254 plates.
The separation and purification of compounds was
* Inasmuch as the data for spiro[2.3]hexane are lacking we give the
strain energy value of 1-oxaspiro[2.3]hexane [9] that is presumably
similarly strained.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 2 2005

PROTOTROPIC ISOMERIZATION OF SPIRO[2,3]HEXANES
191
performed by column chromatography on silica gel L 40/
100 (Chemapol). 3-Methylenecyclobutane-1-carbonitrile
(IV) [10], bromomalononitrile [5], dimethyl(ethyl)
diazomalonates [11], potassium tert-butylate [12], and
butyllithium [13] were prepared by published procedures.
E-3-Bromo-3-(2,2-dicyanoethyl)cyclobutane-1-
carbonitrile (Va). Into a quartz vessel was charged
0.93 g (10 mmol) of nitrile I and 1.45 g (10 mmol) of
bromomalononitrile in 10 ml of CH2Cl2. To remove oxygen
a weak argon flow was passed through the solution for
15 min, and then the UV irradiation was switched on
(from a medium pressure mercury lamp). The irradiation
was continued till complete consumption of the
bromomalononitrile (TLC monitoring). The reaction
continued for ~6 h. On removing the solvent the residue
was recrystallized from CH2Cl2. Yield 1.40 g (59%), mp
Dimethyl E- and Z- 5-cyanospiro[2.3]hexane-
1,1-dicarboxylate (Ia) and (Ib). Into a flask was
charged 0.93 g (10 mmol) of nitrile I, 1.58 g (10 mmol)
of dimethyl diazomalonate, 50 mg of anhydrous copper
sulfate, and 10 ml of octane. The air from the system
was replaced by a flow of argon. The mixture was stirred
at heating to 120°C till the end of nitrogen liberation
(~30 min). On cooling the reaction mixture was diluted
with 10 ml of ether for homogenizing, and the solution
obtained was subjected to column chromatography on
silica gel using as eluent a mixture of light petroleum ether
and ethyl ether, 1:1. The collected fraction contained a
mixture of diastereomers Ia and Ib in a ratio ~1:1
(according to 1H NMR data) as a viscous oily fluid. Yield
1
128°C. H NMR spectrum, d, ppm: 4.24 d [1H, CH(CN)2,
J 7 Hz], 3.66 quint (1H, H1, J 9 Hz), 2.89–3.21 m (4H,
H2,4), 2.67 d (2H, CH2, J 7 Hz). 13C NMR spectrum, d,
ppm: 18.6 (C1), 20.7 [C(CN)2], 43.8 (C2,4), 44.1 (C3),
58.7 (CH2), 111.4 (2 C, CN), 119.5 (CN). Found, %:
C 45.60; H 3.50; N 17.73. C9H7N3. Calculated, %:
C 45.40; H 3.39; N 17.65.
E- and Z-Spiro[2.3]hexane-1,1,5-tricarbonitriles
(IIIa) and (IIIb). a. A solution of 1.67 g (7 mmol) of
bromide Va and 1.0 g (10 mmol) of triethylamine in 10
ml of CH2Cl2 was heated at reflux for 1 h. On cooling
the separated precipitate was filtered off and washed
with dichloromethane (10 ml). The organic layer was
washed with 3% hydrochloric acid, with water, and dried
on sodium sulfate. On removing the solvent we obtained
0.91 g (83 %) of Z-spiro[2.3]hexane-1,1,5-tricarbo-
1
0.91 g (41%). H NMR spectrum, d, ppm: 1.63 s (2H,
H2, Ib), 1.69 s (2H, H2, Ia), 2.42–2,57 m (4H) and 2.65–
2.82 m (4 H), H4,6, Ia + Ib, 3.25 m (1H, H5, Ia), 3.45 m
(1H, H5, Ib), 3.70 s (6H, OCH3, Ia), 3.72 s (6H, OCH3,
Ib). 13C NMR spectra, d, ppm: (Ia) - 17.2 (C5),
25.9 (C2), 32.3 (2 C, C4,6), 33.2 (C3), 35.6 (C1), 52.2 (2C,
OCH3), 121.8 (CN), 167.7 (2C, C=O); (Ib) - 16.6 (C5),
32.5 (C3), 33.1 (2C, C4,6), 35.4 (C1), 52.2 (2C, OCH3),
121.0 (CN), 167.7 (2C, C=O). Found, %: C 59.28;
H 5.73; N 6.12. C11H13NO4. Calculated, %: C 59.19;
H 5.87; N 6.27.
1
nitrile (IIIb), mp 122°C. H NMR spectrum, d, ppm:
1.92 s (2 H, H2), 2.68–2.82 m (2H) and 2.91–3.07 m
(2H), H4,6, 3.35–3.50 m (1H, H5). 13C NMR spectrum,
d, ppm: 9.0 (C1), 16.6 (C5), 28.5 (C2), 31.5 (2 C, C4,6),
34.4 (C3), 112.7 (2 C, CN), 120.0 (CN). Found, %:
C 68.75; H 4.59; N 26.91. C9H7N3. Calculated, %:
C 68.78; H 4.49; N 26.73.
Diethyl E- and Z- 5-cyanospiro[2.3]hexane-1,1-
dicarboxylates (IIa) and (IIb) were prepared by
procedure similar for the above described for compounds
Ia and Ib. On separating the reaction mixture by column
chromatography on silica gel we obtained oily substance
composed of a mixture of diastereomers IIa and IIb in
a ratio ~1:1 (according to 1H NMR data). Yield ~40%.
1H NMR spectrum, d, ppm: 1.36 t (6H, CH3, J 7 Hz,
IIa), 1.47 t (6H, CH3, J 7 Hz, IIb), 1.62 s (2H, H2, IIb),
1.68 s (2H, H2, IIa), 2.43–2.58 m (4 H) and 2.72–2.89
m (4H), H4,6, IIa + IIb, 3.25 m (1H, H5, IIb), 3.51 m
(1H, H5, IIa), 4.33 q (4 H, OCH2, J 7 Hz, IIa), 4.48 q
(4H, OCH2, J 7 Hz, IIb). 13C NMR spectra, d, ppm:
(IIa) - 14.0 (2C, CH3), 17.4 (C5), 25.9 (C2), 32.4 (2C,
C4,6), 32.9 (C3), 35.8 (C1), 61.3 (2C, OCH2), 122.1
(CN), 167.5 (2C, C=O); (IIb) - 14.0 (2C, CH3), 16.8
(C5), 26.0 (C2), 32.3 (C3), 33.2 (2C, C4,6), 35.7 (C1), 61.3
(2C, OCH2), 121.3 (CN), 167.5 (2C, C=O). Found, %:
C 61.92; H 7.01; N 5.31. C13H17NO4. Calculated, %:
C 62.14; H 6.82, N 5.57.
b. Likewise using instead of bromide Va the mixture
of bromides Va, Vb recoved from the mother liquor after
recrystallization of bromide Va (see above) we obtained
a mixture of E- and Z-spiro[2.3]hexane-1,1,5-tri-
carbonitriles (IIIa) and (IIIb). From the 13C NMR
spectrum of this mixture by subtracting the signals of
IIIb component was revealed the 13C NMR spectrum
of isomer IIIa, d, ppm: 9.3 (C1), 17.0 (C5), 27.8 (C2),
31.2 (2 C, C4,6), 35.0 (C3), 113.0 (2 C, CN), 120.3 (CN).
Spiro[2.3]hexane-5-carbonitrile (VI). To 100 ml
of diazomethane ether solution prepared from 10.3 g
(0.1 mol) of nitrosomethyl urea was added at cooling to
0°C first 1.40 g (15 mmol) of nitrile IV and then a
dispersion of 0.225 g (1 mmol) of palladium acetate. The
mixture was stirred at 0°C till the end of gas evolution
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RAZIN, ULIN
192
(~1 h), and then thereto was added again the same amount
of diazomethane and Pd(OAc)2, the cooling was removed,
and the stirring was continued for ~2 h till complete
consumption of initial nitrile IV (monitoring by 1H NMR
spectroscopy). The solution obtained was filtered,the ether
was distilled off, and the residue was distilled in a vacuum.
atmosphere at external cooling (-20OC) was added in
one portion 0.45 g (4 mmol) of freshly sublimed potassium
tert-butylate. In 10 min the cooling was removed, and
the stirring was continued for 1 h more, and then the
reaction was terminated. The reaction mixture was diluted
with 30 ml of ether, and 10 ml of ammonium chloride
saturated solution was added thereto. The organic layer
was washed with water and dried on magnesium sulfate.
On removing the solvent and recrystallization of the
residue we obtained 0.34 g (72%) of compound X,
1
Yield 1.30 g (81%), bp. 72–74OC (10 mm Hg). H NMR
spectrum, d, ppm: 0.53 br.s (4 H, H1,2), 2.39–2.48 m
(2H) and 2.57–2.66 m (2 H), H4,6, 3.25 quint (1 H, H5).
13C NMR spectrum, d, ppm: 11.0 and 12.0 (C1 and C2),
17.6 (C3), 17.7 (C5), 35.1 (2 C, C4,6), 122.7 (CN). Found,
%: C 78.51; H 8.41. C7H9N. Calculated, %: C 78.46;
H 8.47.
1
mp 83°C (CH2Cl2). H NMR spectrum, d, ppm:
1.62 br.s (2H, endo-H 2,4), 2.30 br.s (2H, exo-H 2,4),
2.73 d (2H, CH2, J 7 Hz), 4.14 t (1H, CH, J 7 Hz). 13
C
NMR spectrum, d, ppm: -2.4 (C1), 20.6 (C3), 23.1 (CH),
30.8 (CH2), 40.0 (2 C, C2,4), 111.5 (2 C, CN), 117.7 (CN).
Found, %: C 68.74; H 4.68; N 26.88. C9H7N3. Calculated,
%: C 68.78; H 4.49; N 26.73.
Izomerization of spirohexanes Ia, Ib and IIa,
IIb. To a solution of 4 mmol of diisopropylamine in 10 ml
of anhydrous ethyl ether at–78°C was added by a syringe
6.8 ml (4 mmol) of 0.58 M butyllithium solution in pentane.
Then the stirring was started, and the mixture was
warmed to –20°C. To the mixture at this temperature
3 mmol of spirohexane Ia, Ib or IIa, IIb was added. In
15 min the reaction mixture was diluted with water
solution of ammonium chloride. The ether layer was
separated, the water layer was extracted with ether
(3...15 ml). The combined organic solution was washed
with water and dried on magnesium sulfate. On removing
the solvent the reaction product was purified by column
chromato-graphy on silica gel.
3-Dicyanomethyl-3-methoxymethylcyclobutane-
1-carbonitrile (XI). a. A solution of 157 mg (1 mmol)
of bicyclobutane X in 10 ml (5 mmol) of 0.5 M methanol
solution of sodium methylate was heated at reflux for
3 h. The solution obtained was concentrated in a vacuum,
diluted with water, and thoroughly extracted with ether.
The extracte was washed with a saturated solution of
NH4Cl and with water, and dried on magnesium sulfate.
On removing the solvent we obtained 163 mg (86%) of
analytically pure compound XI (oily substance) composed
of a mixture of two diastereomers (a and b)* in a ratio
3-(2,2-Dimethoxycarbonylethyl)bicyclo[1.1.0]-
1
1
1.5 : 1 (according to H NMR spectrum). H NMR
spectra, d, ppm: (a), 2.57-2.78 m (4H, H2,4), 3.29-3.42 m
(1 H, H1), 3.43 s (3 H, OCH3), 3.70 s (2 H, OCH2),
4.15 s [1 H, CH(CN)2]; (b), 2.42-2.57 m (4 H, H2,4);
3.10-3.26 m (1H, H1), 3.42 s (3H, OCH3), 3.56 s (2H,
OCH2), 4.16 s [1 H, CH(CN)2]. 13C NMR spectra, d,
ppm: (a), 15.9 (C1), 28.8 (CH), 30.9 (2 C, C2,4),
42.3 (C3), 59.3 (OCH3), 74.8 (OCH2), 111.0 (2C, CN),
121.2 (CN); (b), 15.9 (C1), 29.6 (CH), 31.2 (2C, C2,4),
41.4 (C3), 59.3 (OCH3), 73.0 (OCH2), 110.7 (2C, CN),
120.0 (CN). Found, %: C 63.32; H 5.74; N 22.33.
C10H11N3O. Calculated, %: C 63.48; H 5.86; N 22.21.
butane-1-carbonitrile (VIII). Yield 75 %, uncrystal-
1
lizable oily substance. H NMR spectrum, d, ppm:
1.32 br.s (2H, endo-H2,4), 2.06 br.s (2 H, exo-H2,4),
2.60 d (2H, CH2, J 7 Hz), 3.68 t (1H, CH, J 7 Hz),
3.78 s (6H, OCH3). 13C, d, ppm: -2.9 (C1), 23.4 (C3),
27.3 (CH2), 39.3 (2 C, C2,4), 50.5 (CH), 52.7 (OCH3),
118.9 (CN), 168.5 (C=O). Found, %: C 59.39; H 5.77;
N 6.31. C11H13NO4 Calculated, %: C 59.19; H 5.87;
N 6.27.
3-(2,2-Diethoxycarbonylethyl)bicyclo[1.1.0]-
butane-1-carbonitrile (IX). Yield 71%, oily substance.
1H NMR spectrum, d, ppm: 1.30 t (6 H, CH3, J 8 Hz),
1.33 br.s (2H, endo-H2,4), 2.10 br.s (2H, exo-H2,4),
2.61 d (2H, CH2, J 7 Hz), 3.64 t (1H, CH, J 7 Hz),
4.26 q (4 H, OCH2, J 8 Hz). 13C NMR spectrum, d, ppm:
-2.9 (C1), 13.9 (2 C, CH3), 23.5 (C3), 27.2 (CH2), 39.5
(2C, C2,4), 50.9 (CH), 61.7 (2C, OCH2), 119.0 (CN),
168.1 (2C, C=O). Found, %: C 62.02; H 7.01; N 5.39.
C13H17NO4. Calculated, %: C 62.14; H 6.82; N 5.57.
b. Likewise from 79 mg (0.5 mmol) of spirohexane
IIIb was obtained 71 mg (75%) of compound XIa, XIb
in diastereomers ratio ~ 2 : 1.
REFERENCES
1. Danishefsky, S., Acc. Chem. Res., 1979, p. 66.
2. Danishefsky, S., Dynak, J., Hatch, W.E., and Yamamoto, M.,
J. Am. Chem. Soc., 1974, vol. 96, p. 1256.
3-(2,2-Dicyanoethyl)bicyclo[1.1.0]butane-1-
carbonitrile (X). To a solution of 0.47 g (3 mmol) of
trinitrile IIIb in 5 ml of THF while stirring in an argon
* The configurations of diastereomers XIa, b were not assigned.
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PROTOTROPIC ISOMERIZATION OF SPIRO[2,3]HEXANES
193
3. Danishefsky, S., Dynak, J., and Yamamoto, M., Chem.
Commun., 1973, p. 81.
4. Razin, V.V., Grokhotova, O.E., and Ulin, N.V., Zh. Org. Khim.,
1999, vol. 35, p. 64
5. Boldt, P., Schulz, L., and Etzemuller, J., Chem.Ber., 1967,
vol. 100, p. 1281.
8. Wiberg, K.B., Angew. Chem., 1986, vol. 98, p. 312.
9. Kas’yan, L.I., Seferova, M.F., and Porubleva, L.V., Zh. Org.
Khim., 1992, vol. 28, p. 449.
10. Cripps, H.N., Williams, J.K., and Sharkey, W.H., J. Am.
Chem. Soc., 1959, vol. 81, p. 2723.
11. Regitz, M., Synthesis, 1972, p. 351.
6. Razin, V.V. and Ulin, N.V., Zh. Org. Khim., 2003, vol. 39,
p. 44.
12. Fieser, L. F. and Fieser, M., Reagents for Organic Synthesis,
NewYork: Wiley-Intersci., 1972.
7. Razin, V.V., Ulin, N.V., Raev, V.A., Zadonskaya, N.Yu., and
Zuev, D.S., Zh. Org. Khim., 2003, vol. 39, p. 51.
13. Amonoo-Neizer, E.H., Shaw, R.A., Slovin, D.O., and
Smith, B.C., Inorg. Synth., 1966, vol. 8, p. 20.
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