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Synthesis and tautomeric studies of 1-benzylisobenzofuran and related compounds
SKIS
AND TA-RIG
STUDIES
OF l-BENZYLJ~OEENZOETJFLW
?!ND-C-
Elsarrc@a Chacko,D.J. Sardella,and J. Bornstein* Departmentof Chemistry,E!ostcn College,ChestnutEill, Massachusetts02167
Recently,Smith and wikn&
reportedthat l-knzyl-1-hydroxyphthalan (1) undergoesintra-
molecular loss of water to afford. 1-benzalphthalan (&). benzofuran(g) oouldnotbeisolated, Diels-Alderadduct2 with d&thy1
Althoughthe taumr,
l-benzyliso-
its presencein solutianwas inferredby formationof
aoetylenedicarbcxylate. These investigators, using uv and
nmrSpectrosmpy,were unable to observedirectlythe existenceof an equilibriumbatween~ 2a and its derivatives 2b and iscxrer 6c Fkperiencegained frcxnthe preparationof isoindole _. by retro-Diels-Alder reactioneffectedby flash vacua therrrolysis suggestedto us that the ehsive
l-benzylisobenzofuran (s) might be mle
of this techniqueto the 1,4-epo~aphthalene z3.
to synthesisand isolationby application We now report that flash therolysis of
5c not only affords6c, but is also a practicalmethod for the preparationof lmethylisobenzofuran(6a) and 1,3_dirrethylis&enzofuran (g). In addition,we describethe resultsof spectralstudiesof these heterocycles(6a-c)which corroboratethe claim of Smith and W&-I&~ of the existenceof a tautcxneric equilibriumbetween2c and 6c.
a. Rl=H; R2=H b. R1=H;R2=CH 3 c. R1=C6H5;R2=H 4~ (TableI). In similarfashion, Reactionof 2-benzylfuran4 with benzene 5a gave adductes-t of 2-Emylfuran and 2,5-dkethYlfuranwith benzynegave the knm 1,4-dihydro-l,4epoxynaphthdlenes g
(56%)and 4b (50%),respecti~ely.~Hydrogenationof adducts4a-c in g5%
2508
Nn. *
ethanol with 10% palladiun-ckraxl (40 psi, 20°) for 45 min producedthe correqmnding
1,2,3,4-tetrahyWl,4-epoxymphthalenes5a-c (TableI). Flash thenmlysis of 5a-c at 600° (0.5m) by the usual m&hod2 gave ethyleneand essentiallyquantitativeyields of the correqondingisobenzofurans6a-c aswhite crystalswhichwere collectedin atrapmledby liquidnitrogen. lheseprcductsware extremalyreactiveat mm
teqxsratureand resinified
rapidly. Caqmmds 6a_c were characterized by their spectralproperties(TableII) and by formationof Diels-Alderadducts. Thus, with ~thylacetylenedicarboxyla~l-benzylisola ~0th l-rt&hylisobenzofuran (6a) and 1,3-dinrathyliscbenzofan (6&) . with&&Rbenylmaleimideinether gavemixturesoftheirrespectiveexo-and enaO_adducts~ benzofuran(c) gave? whi&
were
resolvedwith partial successby fractionalcrystallizaticm from ohlorofomhe.
k&ereasanden&-ad&&s&were obtairnadanalyticallypure,~lyendo-adduct 7bwas isolatedinthepure state (TableI).
6
a, R1=CH3, R2=H;b, R1=RZ=CH3; c, Rl=GHZC6Hy
RZ=H
qectnnn of 1-benzyliscdxnz.ofuran (6~) in ClX13 at roan the accmpanying figure. The signalsin SpectrumA are attributable
Thetim-evolutionofthenmr tenperatuxeis shmn
in
solely to 6c (TableII). spectrum C, in amtrast, is identicalto that of 1-benzalphthalan (2cP OF&
The - intelmediateSpa&rmB
shms disappearingsignalsof6&andemerging
signals
J?.quilibriminthiscasewas establishedin about4 hr,whereaswithC6D6 as solvent
Additionof a trace of triflxx-oacetic acid to & in either solvent the equilibration was pra@ly effectedequilibrationalmost instantaneously.Interestingly, upto2Ohrwasrequired.
arrest&by additionofone dropof triethylamine. Similarqxctral studiesconductedinCDC13 on 1-methylisobenzofu (g) and 1,3-dkathyliscbenzofuran(6&) failedto revealtheexistence of atautcanericeguilibri~betWeenthem ~theiroorrespondingl~~ylenephthalanis~rs for thepremmxof furans&and
the latter
&and%.
No evidenoacouldbe found
uuderthe conditionsusedinthis study. Unlike&,
isckmzo-
6& deccqmsed rather quickly in solutionat rcun teqerature; the presenceof
retardedthis deuxtpositim m-m&at. triethylamine
CZnqounds&
and gwere
destroyedjm solutionon additim of a trace of trifluoroacatic acid.
instantly
1.88(s,3),2.95(q,2),5.62 (s,2),6.9-7.5B(m,4),[1730] 1.94(s,3),3.38(d,1),3.794.30(q,1),5.6(d,1),6.14-6.43 (m,2),6.99-7.33(m,7),[17301
95-97(7.0) 44-45(0.2) 75.2-75.9 201-201.6 153-153.5
215-217
95 61 90 18 14
607
colorless liq.
wt. crystals
Wt.crystals
Light yellow plates
wt. crystals
5b
SC
7a (exo) 7a (endo)
(e;ibdo)
6c
6b
6a
Compd
(CDC13),d
(Amax)
7.21
357,347.339,332,323,317#293. 281,271,250,208
4.27(s,2),6.58-6.89(m,2),7.027.53(m,7),7.81(9,1).
(m,2)
2.48(s,6),6.46-6.68(m,2),6.93-
(Xmax)
308,244,216
2.56(s,3),6.59-6.81(m,2),7.067.21(m,2),7.74(s,l)
Nmr
357,347,340,332,324,317.309, 291,282,270,251,244,236,207, (Xmax) 375,366,356,347,339,331,325,
W(Heptane),nm.
Spectral Properties of Isobenzofurans
Table II
6.17(m,2),6.84-7.51(m,7), [1720]
2.07(s,3),3.49(s,2),5.96-
1.14-2.19(m,4),3.46(d,2), 5.23(d,1),6.97-7.39(m,4)
1.77(s,3),1.19-2.0(m,4), 6.97-7.12(broad s,4)
1.76(s,3),1.21-2.29(m,4), 5.2(d,1),6.96-8.24 (m,4)
3.55(d,2),5.55(d,1),6.647.42(m,ll)
Pale yellow liq.
98.8-99.5
5a
(CDC13),b,[ir (c=O),cm-'1
64
Nmr
Pale orange needles
sP,°C(mm)
4c
Mp,OC
yd,%
Compd6
Appearance
Properties of Intermediates and Diels-Alder Adducts
Table I
Figure.
Time-Dependency
of NMR
Spectra Room
-1.e
__J-L
e.0
7.0
J__.-_I___
6.0
5.0
4,O
Immediately Dissolution
B.
After
1 Hr.
C.
After
4 Hr.
after
_
is more stable than its o_quinonoid-
the foregoing observations indicate that the phenyl substituent plays an %QXY-
tant role in the tautcxxxic equilibrium kkween apparently greater stability of phthalan z cc&in&ion
A.
these compoutx%3. It is conceivable that the
relative to the phthalans &
of extended conjugation involving the phenyl group
betweenthis groupandthe Acknwledgetwnt.
and g
results from a
and resonance interaction
oxygenatom.
We thank Prof. Alfred G. Redfield of Brandeis University for making
available to us the Bruker WH-90 nmr spectrater
used in this investigation. Purchase of this
instnxwantwas made pssible by National Science Foundation Grants (Z-37156 and GLi-3852. References andNotes J.G. Bnith and R.T. Wikrf!an, J. Org.Chem., 2, 3648 (1974). J.G. Smith and R.T. Wiknmn, Tetrahedron, 30, 2603 (1974). J. Bornstein, D.E. REZ$',and J.E. Shields, Chem. Canmun., 1149 (1972). J. Bornstein, D.E. Remy, and J.E. Shields, Tetrahedron L&t., 4247 (1974). Wiersum and W.J. Mijs [Chem..Ccxtw_m., 347 (1972)1 used this technique for the preparation of the parent iscbenzofuran. (4) R. Paul, C.R. Acad.Sci., ZOO, 1481 (1935). (5) (a) L.F. Fieser and M.J.Haddadin, Can. J. Ckn., 43, 1599 (1965). (b) E. Walthuis, J. Org. Chtxn.,26, 2215 (1961). (6) Satisfactory elemental analyses were obtained for these munds. (7) This value includes both the exo- and endo-adduots.
(1)
(a) (b) (2) (a) (b) (3) U.E.
at
3.0 lb)
In addition to confirming that benzenoid structure C al tautomer &;
of -6c in CDCl3 Temperature
AND TA-RIG
STUDIES
OF l-BENZYLJ~OEENZOETJFLW
?!ND-C-
Elsarrc@a Chacko,D.J. Sardella,and J. Bornstein* Departmentof Chemistry,E!ostcn College,ChestnutEill, Massachusetts02167
Recently,Smith and wikn&
reportedthat l-knzyl-1-hydroxyphthalan (1) undergoesintra-
molecular loss of water to afford. 1-benzalphthalan (&). benzofuran(g) oouldnotbeisolated, Diels-Alderadduct2 with d&thy1
Althoughthe taumr,
l-benzyliso-
its presencein solutianwas inferredby formationof
aoetylenedicarbcxylate. These investigators, using uv and
nmrSpectrosmpy,were unable to observedirectlythe existenceof an equilibriumbatween~ 2a and its derivatives 2b and iscxrer 6c Fkperiencegained frcxnthe preparationof isoindole _. by retro-Diels-Alder reactioneffectedby flash vacua therrrolysis suggestedto us that the ehsive
l-benzylisobenzofuran (s) might be mle
of this techniqueto the 1,4-epo~aphthalene z3.
to synthesisand isolationby application We now report that flash therolysis of
5c not only affords6c, but is also a practicalmethod for the preparationof lmethylisobenzofuran(6a) and 1,3_dirrethylis&enzofuran (g). In addition,we describethe resultsof spectralstudiesof these heterocycles(6a-c)which corroboratethe claim of Smith and W&-I&~ of the existenceof a tautcxneric equilibriumbetween2c and 6c.
a. Rl=H; R2=H b. R1=H;R2=CH 3 c. R1=C6H5;R2=H 4~ (TableI). In similarfashion, Reactionof 2-benzylfuran4 with benzene 5a gave adductes-t of 2-Emylfuran and 2,5-dkethYlfuranwith benzynegave the knm 1,4-dihydro-l,4epoxynaphthdlenes g
(56%)and 4b (50%),respecti~ely.~Hydrogenationof adducts4a-c in g5%
2508
Nn. *
ethanol with 10% palladiun-ckraxl (40 psi, 20°) for 45 min producedthe correqmnding
1,2,3,4-tetrahyWl,4-epoxymphthalenes5a-c (TableI). Flash thenmlysis of 5a-c at 600° (0.5m) by the usual m&hod2 gave ethyleneand essentiallyquantitativeyields of the correqondingisobenzofurans6a-c aswhite crystalswhichwere collectedin atrapmledby liquidnitrogen. lheseprcductsware extremalyreactiveat mm
teqxsratureand resinified
rapidly. Caqmmds 6a_c were characterized by their spectralproperties(TableII) and by formationof Diels-Alderadducts. Thus, with ~thylacetylenedicarboxyla~l-benzylisola ~0th l-rt&hylisobenzofuran (6a) and 1,3-dinrathyliscbenzofan (6&) . with&&Rbenylmaleimideinether gavemixturesoftheirrespectiveexo-and enaO_adducts~ benzofuran(c) gave? whi&
were
resolvedwith partial successby fractionalcrystallizaticm from ohlorofomhe.
k&ereasanden&-ad&&s&were obtairnadanalyticallypure,~lyendo-adduct 7bwas isolatedinthepure state (TableI).
6
a, R1=CH3, R2=H;b, R1=RZ=CH3; c, Rl=GHZC6Hy
RZ=H
qectnnn of 1-benzyliscdxnz.ofuran (6~) in ClX13 at roan the accmpanying figure. The signalsin SpectrumA are attributable
Thetim-evolutionofthenmr tenperatuxeis shmn
in
solely to 6c (TableII). spectrum C, in amtrast, is identicalto that of 1-benzalphthalan (2cP OF&
The - intelmediateSpa&rmB
shms disappearingsignalsof6&andemerging
signals
J?.quilibriminthiscasewas establishedin about4 hr,whereaswithC6D6 as solvent
Additionof a trace of triflxx-oacetic acid to & in either solvent the equilibration was pra@ly effectedequilibrationalmost instantaneously.Interestingly, upto2Ohrwasrequired.
arrest&by additionofone dropof triethylamine. Similarqxctral studiesconductedinCDC13 on 1-methylisobenzofu (g) and 1,3-dkathyliscbenzofuran(6&) failedto revealtheexistence of atautcanericeguilibri~betWeenthem ~theiroorrespondingl~~ylenephthalanis~rs for thepremmxof furans&and
the latter
&and%.
No evidenoacouldbe found
uuderthe conditionsusedinthis study. Unlike&,
isckmzo-
6& deccqmsed rather quickly in solutionat rcun teqerature; the presenceof
retardedthis deuxtpositim m-m&at. triethylamine
CZnqounds&
and gwere
destroyedjm solutionon additim of a trace of trifluoroacatic acid.
instantly
1.88(s,3),2.95(q,2),5.62 (s,2),6.9-7.5B(m,4),[1730] 1.94(s,3),3.38(d,1),3.794.30(q,1),5.6(d,1),6.14-6.43 (m,2),6.99-7.33(m,7),[17301
95-97(7.0) 44-45(0.2) 75.2-75.9 201-201.6 153-153.5
215-217
95 61 90 18 14
607
colorless liq.
wt. crystals
Wt.crystals
Light yellow plates
wt. crystals
5b
SC
7a (exo) 7a (endo)
(e;ibdo)
6c
6b
6a
Compd
(CDC13),d
(Amax)
7.21
357,347.339,332,323,317#293. 281,271,250,208
4.27(s,2),6.58-6.89(m,2),7.027.53(m,7),7.81(9,1).
(m,2)
2.48(s,6),6.46-6.68(m,2),6.93-
(Xmax)
308,244,216
2.56(s,3),6.59-6.81(m,2),7.067.21(m,2),7.74(s,l)
Nmr
357,347,340,332,324,317.309, 291,282,270,251,244,236,207, (Xmax) 375,366,356,347,339,331,325,
W(Heptane),nm.
Spectral Properties of Isobenzofurans
Table II
6.17(m,2),6.84-7.51(m,7), [1720]
2.07(s,3),3.49(s,2),5.96-
1.14-2.19(m,4),3.46(d,2), 5.23(d,1),6.97-7.39(m,4)
1.77(s,3),1.19-2.0(m,4), 6.97-7.12(broad s,4)
1.76(s,3),1.21-2.29(m,4), 5.2(d,1),6.96-8.24 (m,4)
3.55(d,2),5.55(d,1),6.647.42(m,ll)
Pale yellow liq.
98.8-99.5
5a
(CDC13),b,[ir (c=O),cm-'1
64
Nmr
Pale orange needles
sP,°C(mm)
4c
Mp,OC
yd,%
Compd6
Appearance
Properties of Intermediates and Diels-Alder Adducts
Table I
Figure.
Time-Dependency
of NMR
Spectra Room
-1.e
__J-L
e.0
7.0
J__.-_I___
6.0
5.0
4,O
Immediately Dissolution
B.
After
1 Hr.
C.
After
4 Hr.
after
_
is more stable than its o_quinonoid-
the foregoing observations indicate that the phenyl substituent plays an %QXY-
tant role in the tautcxxxic equilibrium kkween apparently greater stability of phthalan z cc&in&ion
A.
these compoutx%3. It is conceivable that the
relative to the phthalans &
of extended conjugation involving the phenyl group
betweenthis groupandthe Acknwledgetwnt.
and g
results from a
and resonance interaction
oxygenatom.
We thank Prof. Alfred G. Redfield of Brandeis University for making
available to us the Bruker WH-90 nmr spectrater
used in this investigation. Purchase of this
instnxwantwas made pssible by National Science Foundation Grants (Z-37156 and GLi-3852. References andNotes J.G. Bnith and R.T. Wikrf!an, J. Org.Chem., 2, 3648 (1974). J.G. Smith and R.T. Wiknmn, Tetrahedron, 30, 2603 (1974). J. Bornstein, D.E. REZ$',and J.E. Shields, Chem. Canmun., 1149 (1972). J. Bornstein, D.E. Remy, and J.E. Shields, Tetrahedron L&t., 4247 (1974). Wiersum and W.J. Mijs [Chem..Ccxtw_m., 347 (1972)1 used this technique for the preparation of the parent iscbenzofuran. (4) R. Paul, C.R. Acad.Sci., ZOO, 1481 (1935). (5) (a) L.F. Fieser and M.J.Haddadin, Can. J. Ckn., 43, 1599 (1965). (b) E. Walthuis, J. Org. Chtxn.,26, 2215 (1961). (6) Satisfactory elemental analyses were obtained for these munds. (7) This value includes both the exo- and endo-adduots.
(1)
(a) (b) (2) (a) (b) (3) U.E.
at
3.0 lb)
In addition to confirming that benzenoid structure C al tautomer &;
of -6c in CDCl3 Temperature