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Aryl esters
w4o4020192 ss.oo+.oo 0 1992 Pergamon Press L.Id
Temhedron Vol. 48. No. 21, pp. 44314438.1992 Prided in Great Britain
Reduction
of DDHQ and TCC Esters by NaBlId-Its Specificity in the Presence of Alkyl/Aryl Esters
Tirumalai R.Kasturi* and Palle V.P.Pragnacharyulu Department Organic Chemistry,Indian Institute of Science Bangalore-560012,1ndia.
(Received in UK 31 March 1992)
ABSTRACT: DDHQ/TCC esters 3a-f,7a-g were prepared either by oxidation of spiroketones 1 with DDQ/o-chloranil or by condensation of acid chloride with DDHQ/TCC. NaBH4 rzduction of unsaturated DDHQ 3a-b and TCC 7a-c any esters gave the corresponding allylic alcohols in good yield without observable l,l-addition products.Reduction of saturated esters 3e,7d, gave and alcohols. Alkyl esters 5 and 6, methyl benzoate the corresponding In phenyl benzoate remained unaffected under these reduction conditions. the reduction of compound 7e containing both alkyl and TCC esters, TCC ester is selectively reduced. Reduction of TCC mono esters 7f-g gave the lactones. The observed facile reduction has been rationalised. agent
is generally accepted that NaBH4, a powerful reducing
It
for aldehydes and ketones, will not reduce carboxylic esters and ortho 1 esters . However, reduction can sometimes be effected by activation of the reagent ecu by its conversion -in situ into lithium magnesium borohydride or to a more reactive aluminium borohydride _ etc2 ,but these methods have their own
limitations.
NaBH4
are
longer
A number of instances wherein reduction of esters by 3 invariably use higher temperatures,
reported in literature
reaction
times
and
large
excess
of
borohydride.
Further,
selectivity in ester reductions have not been achieved. We
have recently reported' the oxidation of spiroketone 1
2,3-dichloro-5,6-dicyano-E_benzoquinone and
2,3-dichloro-5,6-dicyanohydroquinone
esters the
(DDQ) to give either (DDHQ) esters 3
or
only
3 depending on the substituent at /l-position in the furan ring.In 4 investigation on the structure of DDHQ ester 3a, we have
noticed
that
on the NaBH4 been
been made mild
2
DDHQ
course of
NaBHat reduction
reported',
of esters to the best
on the synthetic
conditions
undertook
used
a detailed
3a
mmol)in dry THF at room temparature reduces
mmol) to the allylic alcohol 4a in 80% yield. Even though kinetic have
with
tropones
electron
withdrawing
of our knowledge,
utility
to bring
study
having
of this
about
of this
the
reduction
4431
reduction. reduction with
alcohol
no systematic In view of
ester
a variety
(1
studies study
of the group,
unit has very we
of substrates.
4432
T.R.KASTURI and P.V.P.PRAGNACHARYULU
a.
R=R’=H
b.
R= (-&,,;
c.
R=H
j R’.
a.
R=H
b.
R = o<,,
R’=H
,-, Q-
3
OCH3
CN
z k
CN OR'
DDHQ bY DDHQ
oxidation mono
reaction
of
R:
b.
R =
oc,, i
t.
R=H;
R’z
3a-c
of spiroketones la-c
ester
corresponding
diesters
a.
3d
R’=H
R’ = H
,-, Q-
0CH3
required in this study were with DDQ in refluxing
was
dry
prepared benzene. the of
prepared by trans-esterification 3b with dry MeOH. Diesters 3e-f were prepared by of the corresponding acid chlorides with DDHQ. Structures diester
these esters are evident from their spectral data (Table 1).
Spectroscopic and analytical data of DDEQ and TCC esters
4.0(s,3H),7.45-7.80 (m,3H),8.0-8.15(m,lH) 8.6(bs,lH,OH)
3.90(s,3H),3.93(8,3H) 7.55-7.80(m,3H),8.08.15(m,lH)
3334, 1788, 1698
1758 1734
171
145
67
75
90
7e
7f
7g
low melting
98
1785, 1740
1770
1.2-2.O(m,4H),2.22.75(m,12H),3.7(s,3H)
0.70-0.95(m,3H),l.l1.9(m,30H),2.55(t,2H)
6.58(d,J=16.OHz,lH) 7.3-7.6(m,SH),7.94 (d,J=l6.0Hz,lH)
82
1734 1641
7d
165
3.l(s,4H),3.8 (s,3H,OCH ),6.83 (d,J=8.OH&2H) 8.18(d with further coupling,J=8.0Hz,2H)
6.7(d,J=16.OHz,lH) 7.4-7.8(m,5H),8.0 (d,J=16.0Hz,lH)
72
2250, 3.782
2250, 1750, 1630
7c
80
230
76
70
3f
3e
:
’
Found: C,45.3iH,2.35%.
calcd for
:15I318~~~:~.95 F&n;l: C,43.93iH,1.92%.
calcd for
c,51.9;H,5.8%.
l?hd
&;3$y:4g , -
calcd for
;'f:7!W47 . E&d: C,64.86iH,9.22%.
calcd for
C,57.2;H,2.96%.
:24:19x475 I . l&A :'
calcd for
Found: Cr60.4iH,3.9iN,5.0%.
calcd for
:2&fl~itN~C:2N r.;,.. 5 7 F&&l: Cs63.4;H,2.87iN,5.6%.
calcd for
422(M+,l), 391(5), 163(100), 77(28).
408(M+,l), 377(50), 244(30), 163(100), 77(25).
534(25), 267(100).
506(M+,15), 244(30), 131(100), 103(50), 77(37).
----____----_---_----------~~~-~~~~~--~~~~~~~~~~~--~~~~ ____________________~~~-~~~--~~~~~~~~~~~~-----~~~~~~-~~~~~~~~~~ I Compound %Yield Analytical Mass m-p (&!$ 'c 9o&?DCl3 data m/z,7OeV, (% intensity)-_--_______-__--_------~~~-~~~~~~~~~~~_~~_-____~~_-~~~~~~--_--~~~~~~~~~~-~~--~~_-_~--~~_~~__~~-~~___---____~_-~~-~~~-~-.
Table 1.
4434
T.R.KAsTuRI~~~PV.P.PRAGNACHARWLU
In a typical experiment, the ester (1 mm011 was treated with NaBii4(2 mmol) in dry THF for about 3.hrs and the product was isolated a
in
pure state by extraction with organic solvent
chromatography
followed
by
column
(silica gel). As seen from Table 2, the unsaturated ester 3a was reduced
to the corresponding allylic alcohol without any observable 1,4 - addition 5
about 80% yield [entry 11. When the corresponding methyl ester
in
was
treated with NaBH4 under similar conditions, no reduction occurred and the starting
material
reduction
Of
was
recovered
esters
3b-e
quantitatively gave
the
[entry
corresponding
f4b614c7i4b, cinnamyl alcohol respecfively)in good yields While
the saturated DDHQ dfester 3f was reduced
propanol,
the
saturated
methyl
ester 6
21.
to
failed
to
Similar alcohols
[entries
3-61.
3-lp-methoxyphenyl)undergo reduction
[entries 7-81. Further, phenyl benzoate was not reduced under similar conditions [entry 91. A 1:l mixture of 3c and the corresponding methyl ester
5c on reduction gave the alcohol 4c and the unreacted methyl
ester
5c [entry lo] indicating selectivity.
R s c.
R=l?‘=H
C.
R:H;R’-_
s
sd b.
R i 0,“; Q
R’.H -
OCHj
Table 2. Reduction of DDEQ esters with BaBB4 ____1_______________~~~__~~~~__~~~~~~~~~~~~~~~~~~~~~~~_----_~~~~~~~~~~~~~ Entry
Ester
% Yield
Entry
Ester
% Yield
reduced of alcohol reduced of alcohol. __~~_~_______111~~~1_--~-__~~~~~~~I--~~~~~~~~~~~~~~~~~~~~~-~~~~~~~--~~~~~~~~-l4
3a
80
6
3e
82
2
5a
0
7
3f
80
3
3b
81
8
6
0
4
3c
92
9
phenyl
0
benzoate 5
3d
40
10
1:l mixture
80% 4c
of 3c & 5c and 5c _________________________________f______~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~--
Reductionof DDHQ andTCC estersby N&H,
We anticipated should
also
behave
that
similarly
tetrachlorocatechol
(TCC) esters
7a-b
in
the NaBH4 reduction. These esters could be [vide prepared by either oxidation of spiroketones 1 with o-chloranil _ infra] adopting the method developed by us for the preparation of DDHQ esters or condensation of the corresponding acid chloride with TCC. As expected, refluxing a solution of spiroketones la-b dry
benzene
formation
with
of
o-chloranil
followed by
work
up
resulted
in
tropones 2a-b along with TCC diesters 7a-b,as evident
spectral data(
in the from
experimental).
e
d.
R = R’.
CH+i&C
o.
R = RI’-
M&H 28k!-
0
0 )
;
1.
R’.H
0 ; R’.CH) 0 0
c.
Diesters 7c-e were prepared by heating the corresponding chloride(2
mmol), The ester
mmol). chloride
prepared from acid and thionyl chloride, with 7f was prepared by
treating
the
TCC
corresponding
acid (1 acid
(lmmol)
with TCC (lmmol). Methylation of 7f with CH2N2 gave 7g. These esters were characterised by spectral and analytical data(Table 1). Reduction corresponding
allylic
of TCC unsaturated esters 7a-c
with NaBH4 gave
alcohols [entries 11-131. TCC diester
of
the
stearic
acid 7d gave stearyl alcohol in high yield [entry 141. As already mentioned, alkyl esters are not reduced under conditions
used
[entries 2,7]. This selectivity
in
protecting one of the carboxylic acids in a dicarboxylic acid molecule
as
ester, while the other
alkyl or
be
the
utilised
TCC
could
could be transformed to alcohol through
DDHQ ester. This could be of some
synthetic utility.
Thus,
the TCC
4436
T.R.KASTURI andP.V.P.PRAGNACHARYULU
diester
of sebacic acid monomethyl ester 7e on reduction with
NaBH4 gave
hydroxy decanoic acid methyl ester [entry 151. TCC mono esters 7f-g on reduction gave lactones[entries
16,171.
The lactones are formed by reduction of TCC ester followed-by cyclisation. This
was
evident from the fact that methyl benzoate remained
under similar reaction slow in these cases and
conditions
uneffected
[entry 183. Reduction was comparatively
5-108 starting material was recovered
(Table 3).
Table 3. Reduction of TCC esters with NaBHa Entry
Ester
% Yield
Entry
Ester
% Yield
reduced of alcohol reduced of alcohol ____________________~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~_____~~~~~~~~~~~~ 15
65
7a
11
90
7e
12
7b
70
16
7f
65
13
7c
83
17
7g
66
14
7d
85
18
0
methyl benzoate
The
very
attributed phenolic
facile reduction of DDHQ/TCC diesters by NaBHa
to the presence of electron withdrawing groups moiety. Perhaps, in the case
7f-g),the
electron
releasing
of DDHQ/TCC
character of
could
(Cl,CN) in
be the
mono esters (3d,7a-b,
hydroxyl
or
methoxy
group
opposes this effect and hence, the reduction is sluggish. In conclusion, the high yields and selectivity obtained this
method
for the facile reduction of ester functionality
recommend under
mild
conditions, and particularly for the reduction of TCC or DDHQ esters
over
alkyl/aryl esters in a synthetic operation. EXPERIMEN!l'ALSECTION -1 All melting points are uncorrected.IR(k,cm Ispectra were recorded on Perkin-Elmer model 781 spectrophotometer.NMR spectra were recorded on FX-9OQ FT spectrometer with Me4Si as internal standard(6 = 0 MS-DX eV) were recorded on 303 spectrometer.Column (70 ppm).MS chromatography was carried out using silica gel.Ether refers to diethyl ether.All organic exctracts were dried over anhydrous Na2S04. Trans esterification of 3 with dry MeOH A mixture of compound 3 (600 mg) and dry MeOH (500 ml) was heated to after reflux for three days. To the residue in ether (100 ml),obtained removal of methanol, was added diazomethane in ether (30 ml) at 0°C excess After allowing the reaction mixture to stand for five minutes, diazomethane was destroyed by adding little HOAc. The ether solution was washed with water and dried. Ether was removed and the residue obtained
ReductionofDDHQandTCCestersby NaFS&
4437
was chromatographed . Elution with cHc13-hexane (l:l) gave 1:l mixtyre of cis and trans methyl esters 5b (200 mg, 38.5%),IR (nujol) 1730 ;H NMR 1.25 (s)and1.3 (s) (6H), 1.4-2.4 (m,20 Ii), 3.65 (s) and 3.85 (8) (3H), 6.15 (d,J=lO.O Hz,lH),6.25 (d, J=16.0 Hz)(lH),7.3-8.4 (m,lOH). Anal. calcd for c H- 0 C,82.4; H,8.0 Found:C,81.9; H,7.85%. elu ion with CHCl -hexane (2-l) gave 3d (120 mg, 33%), IR '8rege' 'H NMR 1 .3(s 6H? 1 3 2 .4 irn 20H) 1760 (nujol) 4.18 (s,3H), 6.7 (d, J=16.0Hz ,lH) 7:3-8.05 (m,8H)'8.2'(d: :=7.0Hz' ,lH): 8.65 (d,J=16.0Hz,lH). Anal.calcd for C44H4004N2C12 C,72.2; H,5.5; N,3.8. Found:C,71.8; H,5.3; N,3.6%. Oxidation
of spiroketone
la-b with
o-chloranil
A solution of spiroketone la (298 mg) and o-chloranil (270 mg) in dry benzene (50 ml) was refluxed for 24 hrs. It was concentrated and chrgmatographed . Elutiof with CHC13 gave TCC monoester 7a (300 mg) m.p 244 C; IR(nujo1) 1757 ; H NMR 6.07 (d,J=lO.OHz, lH), 7.05-7.60 (m,lOH), 7.77-7.95 (m,lH), 8.05 (d,J=lO.OHz,lH), MS m/e 542 (M+, 14), 297 (22), 296 (96), 268 (80), 239 (loo), 126 (42). Anal.Calcd for C H 0 Cl C,59.7; H, 2.58. Found:C, 59.29; H, 2.27%. Further elution with 27C&;-E$OAc (1O:l) gave tropone 2a. Similar oxidation of spiroketone lb (500 mg) with o-chloranii (270 in dry benzene gave 7b (400 mg); m.p l17°C;IR(nujolr 1760 ; H NMR mg) 1.2(~,6~), l.O-2.2(m,2OH), 6.5(d,3=16.0 Hz,lH), 6.75(s,lH), 6.95(d, J=8.0 7.3-8.0(m,7H),8.5(d,g=l6.0 Hz,lH).Analysis calcTi.for Hz,lH), 7.15(s,lH), C41H3804C14 C,77.36;H,6.O.Found:C,77.12;H,5.92 and 2b. Preparation
of 5c:
Compound 3c (500 mg) and 10% NaOH (100 ml) were refluxed until the yellow colour of the so&id disappeared (48 hr).The white solid was filtered off and dried at 0 C.The dried solid was stirred with 10% HCl (50 for lhr.The solid was exctracted with EtOAc (100 ml), washed with ml) watsr (25 mlx3) and dried. Removal of EtOAc gave the acid 5d (450 mg), m.p 110 C (CHCl ),IR(nujol) 1689 ; 'HNMR 3.6(s,3H,OCH ),5.63(d, J=12.0 Hz,lH) 6.85-7.05 (&7H), 7.1-7.2 $2H), 7.25-7.65 (m,7H?, 7.7-8.0 Tm,3H); MS m/I (relative intensity) 420(M ,lOO), 374(56), 343(44), 313(30),269(24). HRMS H 0 420.1362.Found, 420.1365. calcd'forEZ&!LZPi~ation of this acid 5d (420 mg) with MeOH/H SO methyl ester 5c (400 mg),m.p 80°C (CHCl -pet.ether); IR(thin filz) f72~~'~ NMR 3.4(s,3H),3.45(s,3H),5.45(d,J=12.0 az,lH),6.7-7.8(m,15H). HRMS calcd. 434.1518.Found,434.1555. for C2gH22D4 General chloride
Procedure for the preparation and DDHQ/TCC.
A mixtgre heated at 100 C mixture was again solid separated and with water chromatographed was crystallised esters are given General
was hrs.
procedure
of DDHQ
or 'FCC
esters
from
acid
of acid (2 mmols) and thionyl chloride (2.5 Rlmols) was for one hour. After addition of DDHQ Or TCC (1 nznol) the heated for 2 hrs. Water was added after cooling and the was extracted with EtOAc. The EtOAc extract was washed dried . The residue obtained after removal of EtOAc was . Elution with CHCl -hexane (3:l) gave the ester, which from CHCl -hexane. 2 pectral and analytical data of these in Table. 3. for
reduction
of esters.
To a solution of ester (1 mmol) in dry THF (20 ml), NaBH4 (2 mmol) added at O" C-The mixture was stirred at the same temperature for 2 and further at room temperature for 2 hrs. THF was removed & vacua,
4438
T.R.KAsTuIu~~~P. V.P.PRAGNACHARYULU
excess
NaBH was quenched with saturated NH4Cl solution, and the organic compound ex 0 ratted with ether. The ether layer was washed with water and column dried. Removal of ether gave alcohol which was purified by chromatography. Acknowledgement We thank Prof.George R.Pettit, ASU, Tempe, Arizona for a generous gift of monomethyl ester of sebacic acid,Dr.Amitabha Sarkar,NCL,Pune for a few mass spectra reported herein and Dr.A.Srikrishna for helpful discussions. Financial assistance from CSIR, New Delhi is gratefully acknowledged. References and Notes 1.
2.
3.
4. 5. 6.
7.
1956, Mead,E.J; Shoaf,C.J.; J.Am.Chem.Soc., a.Brown,H.C; -78,3616. b.Chaikin,S.W; Brown,W.G.; Ibid 1949, II, 122. c.Tschesche,R; Snatzke,G.;Chem.Berl955,88,1558. 3864. 1956,2, d.Kupchan,S.M; Johnson,W.S.; J.Am.Chem.Soc, 1954,173 Gabor,V.; Nuture(London), Fuchs,O; a.Kollonitsch,J; 125;1955,175.346. 6209. b-Brown I,H.C-ead E.J; Subbarao,B.C;J.Am.Chem.Soc..1955.77. c.Brown,H.C; Subbara0,B.C;J.Am.C hem.Soc.,1956,78,2582. d.Brown,H.C;Krishnamurthy,s; Tetr ahedron,l979,2,572. 1961, 2, 81. a.,Schenker; Angew.Chem., 1963, 2743 . b.,Barnett,J1.E.B; Kent,P.W.; J.Chem.Soc., Yamleda,s.: Koga,K; Matsuo,H; Ohki,s; Matsuo,I; C. ,Seki,H; 1965, 13, 995. Chem.Pharm.Bull(Tokyo), 1967, 15, 1948. ibz, d.Seki,H; Koga,K; Yamada,S.; Rm,G.; Synthesc Communications, e.Bianco,A; Passacantilli,P; 1988, 18(15),1765. Kasturi,T.R;Pragnacharyulu,P.V.P;Madhusudanareddy,G;Jayaram,S.K;Singh, S.B.; Tetrahedron(communicated1. 1970, 35, 1505. Takahashi,S; Cohen,L.A J.Org.Chem., :lH NMR 3334 Soectrosconic data of 4b : semi solid. IR(neat) 1,25(s,3H);1.3(s,lH),l.3-2.4(m,2OH),4.4(d with allilic coupling ,3=6.0 Hz,2H),6.l(doublet of triplet,z=l2.0 and 6.OHz,lH),6.9(m,lOH).Analysis calcd. for C 5H O2 ~,85.4;H,8.1. Fo8nd: C,85.2;H,8.0. Spectroscopis d@a of 4c: m.p 70 C;IR(thin film) 3412 ;lH NMR and 6.0 3.65(s,3H),3.95-4.2(m,2H),5.5(doublet of triplet,;r=l2.0 Hz,lH),6.4(d with allylic coupling,;r=lZ.O Hz,lH),6.9-8.l(m,l4H).MS m/e 406(M ,100),388(25),269(35).HRMS calcd. for C28H2203 ,406.1569. Found, 406.1564.
Temhedron Vol. 48. No. 21, pp. 44314438.1992 Prided in Great Britain
Reduction
of DDHQ and TCC Esters by NaBlId-Its Specificity in the Presence of Alkyl/Aryl Esters
Tirumalai R.Kasturi* and Palle V.P.Pragnacharyulu Department Organic Chemistry,Indian Institute of Science Bangalore-560012,1ndia.
(Received in UK 31 March 1992)
ABSTRACT: DDHQ/TCC esters 3a-f,7a-g were prepared either by oxidation of spiroketones 1 with DDQ/o-chloranil or by condensation of acid chloride with DDHQ/TCC. NaBH4 rzduction of unsaturated DDHQ 3a-b and TCC 7a-c any esters gave the corresponding allylic alcohols in good yield without observable l,l-addition products.Reduction of saturated esters 3e,7d, gave and alcohols. Alkyl esters 5 and 6, methyl benzoate the corresponding In phenyl benzoate remained unaffected under these reduction conditions. the reduction of compound 7e containing both alkyl and TCC esters, TCC ester is selectively reduced. Reduction of TCC mono esters 7f-g gave the lactones. The observed facile reduction has been rationalised. agent
is generally accepted that NaBH4, a powerful reducing
It
for aldehydes and ketones, will not reduce carboxylic esters and ortho 1 esters . However, reduction can sometimes be effected by activation of the reagent ecu by its conversion -in situ into lithium magnesium borohydride or to a more reactive aluminium borohydride _ etc2 ,but these methods have their own
limitations.
NaBH4
are
longer
A number of instances wherein reduction of esters by 3 invariably use higher temperatures,
reported in literature
reaction
times
and
large
excess
of
borohydride.
Further,
selectivity in ester reductions have not been achieved. We
have recently reported' the oxidation of spiroketone 1
2,3-dichloro-5,6-dicyano-E_benzoquinone and
2,3-dichloro-5,6-dicyanohydroquinone
esters the
(DDQ) to give either (DDHQ) esters 3
or
only
3 depending on the substituent at /l-position in the furan ring.In 4 investigation on the structure of DDHQ ester 3a, we have
noticed
that
on the NaBH4 been
been made mild
2
DDHQ
course of
NaBHat reduction
reported',
of esters to the best
on the synthetic
conditions
undertook
used
a detailed
3a
mmol)in dry THF at room temparature reduces
mmol) to the allylic alcohol 4a in 80% yield. Even though kinetic have
with
tropones
electron
withdrawing
of our knowledge,
utility
to bring
study
having
of this
about
of this
the
reduction
4431
reduction. reduction with
alcohol
no systematic In view of
ester
a variety
(1
studies study
of the group,
unit has very we
of substrates.
4432
T.R.KASTURI and P.V.P.PRAGNACHARYULU
a.
R=R’=H
b.
R= (-&,,;
c.
R=H
j R’.
a.
R=H
b.
R = o<,,
R’=H
,-, Q-
3
OCH3
CN
z k
CN OR'
DDHQ bY DDHQ
oxidation mono
reaction
of
R:
b.
R =
oc,, i
t.
R=H;
R’z
3a-c
of spiroketones la-c
ester
corresponding
diesters
a.
3d
R’=H
R’ = H
,-, Q-
0CH3
required in this study were with DDQ in refluxing
was
dry
prepared benzene. the of
prepared by trans-esterification 3b with dry MeOH. Diesters 3e-f were prepared by of the corresponding acid chlorides with DDHQ. Structures diester
these esters are evident from their spectral data (Table 1).
Spectroscopic and analytical data of DDEQ and TCC esters
4.0(s,3H),7.45-7.80 (m,3H),8.0-8.15(m,lH) 8.6(bs,lH,OH)
3.90(s,3H),3.93(8,3H) 7.55-7.80(m,3H),8.08.15(m,lH)
3334, 1788, 1698
1758 1734
171
145
67
75
90
7e
7f
7g
low melting
98
1785, 1740
1770
1.2-2.O(m,4H),2.22.75(m,12H),3.7(s,3H)
0.70-0.95(m,3H),l.l1.9(m,30H),2.55(t,2H)
6.58(d,J=16.OHz,lH) 7.3-7.6(m,SH),7.94 (d,J=l6.0Hz,lH)
82
1734 1641
7d
165
3.l(s,4H),3.8 (s,3H,OCH ),6.83 (d,J=8.OH&2H) 8.18(d with further coupling,J=8.0Hz,2H)
6.7(d,J=16.OHz,lH) 7.4-7.8(m,5H),8.0 (d,J=16.0Hz,lH)
72
2250, 3.782
2250, 1750, 1630
7c
80
230
76
70
3f
3e
:
’
Found: C,45.3iH,2.35%.
calcd for
:15I318~~~:~.95 F&n;l: C,43.93iH,1.92%.
calcd for
c,51.9;H,5.8%.
l?hd
&;3$y:4g , -
calcd for
;'f:7!W47 . E&d: C,64.86iH,9.22%.
calcd for
C,57.2;H,2.96%.
:24:19x475 I . l&A :'
calcd for
Found: Cr60.4iH,3.9iN,5.0%.
calcd for
:2&fl~itN~C:2N r.;,.. 5 7 F&&l: Cs63.4;H,2.87iN,5.6%.
calcd for
422(M+,l), 391(5), 163(100), 77(28).
408(M+,l), 377(50), 244(30), 163(100), 77(25).
534(25), 267(100).
506(M+,15), 244(30), 131(100), 103(50), 77(37).
----____----_---_----------~~~-~~~~~--~~~~~~~~~~~--~~~~ ____________________~~~-~~~--~~~~~~~~~~~~-----~~~~~~-~~~~~~~~~~ I Compound %Yield Analytical Mass m-p (&!$ 'c 9o&?DCl3 data m/z,7OeV, (% intensity)-_--_______-__--_------~~~-~~~~~~~~~~~_~~_-____~~_-~~~~~~--_--~~~~~~~~~~-~~--~~_-_~--~~_~~__~~-~~___---____~_-~~-~~~-~-.
Table 1.
4434
T.R.KAsTuRI~~~PV.P.PRAGNACHARWLU
In a typical experiment, the ester (1 mm011 was treated with NaBii4(2 mmol) in dry THF for about 3.hrs and the product was isolated a
in
pure state by extraction with organic solvent
chromatography
followed
by
column
(silica gel). As seen from Table 2, the unsaturated ester 3a was reduced
to the corresponding allylic alcohol without any observable 1,4 - addition 5
about 80% yield [entry 11. When the corresponding methyl ester
in
was
treated with NaBH4 under similar conditions, no reduction occurred and the starting
material
reduction
Of
was
recovered
esters
3b-e
quantitatively gave
the
[entry
corresponding
f4b614c7i4b, cinnamyl alcohol respecfively)in good yields While
the saturated DDHQ dfester 3f was reduced
propanol,
the
saturated
methyl
ester 6
21.
to
failed
to
Similar alcohols
[entries
3-61.
3-lp-methoxyphenyl)undergo reduction
[entries 7-81. Further, phenyl benzoate was not reduced under similar conditions [entry 91. A 1:l mixture of 3c and the corresponding methyl ester
5c on reduction gave the alcohol 4c and the unreacted methyl
ester
5c [entry lo] indicating selectivity.
R s c.
R=l?‘=H
C.
R:H;R’-_
s
sd b.
R i 0,“; Q
R’.H -
OCHj
Table 2. Reduction of DDEQ esters with BaBB4 ____1_______________~~~__~~~~__~~~~~~~~~~~~~~~~~~~~~~~_----_~~~~~~~~~~~~~ Entry
Ester
% Yield
Entry
Ester
% Yield
reduced of alcohol reduced of alcohol. __~~_~_______111~~~1_--~-__~~~~~~~I--~~~~~~~~~~~~~~~~~~~~~-~~~~~~~--~~~~~~~~-l4
3a
80
6
3e
82
2
5a
0
7
3f
80
3
3b
81
8
6
0
4
3c
92
9
phenyl
0
benzoate 5
3d
40
10
1:l mixture
80% 4c
of 3c & 5c and 5c _________________________________f______~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~--
Reductionof DDHQ andTCC estersby N&H,
We anticipated should
also
behave
that
similarly
tetrachlorocatechol
(TCC) esters
7a-b
in
the NaBH4 reduction. These esters could be [vide prepared by either oxidation of spiroketones 1 with o-chloranil _ infra] adopting the method developed by us for the preparation of DDHQ esters or condensation of the corresponding acid chloride with TCC. As expected, refluxing a solution of spiroketones la-b dry
benzene
formation
with
of
o-chloranil
followed by
work
up
resulted
in
tropones 2a-b along with TCC diesters 7a-b,as evident
spectral data(
in the from
experimental).
e
d.
R = R’.
CH+i&C
o.
R = RI’-
M&H 28k!-
0
0 )
;
1.
R’.H
0 ; R’.CH) 0 0
c.
Diesters 7c-e were prepared by heating the corresponding chloride(2
mmol), The ester
mmol). chloride
prepared from acid and thionyl chloride, with 7f was prepared by
treating
the
TCC
corresponding
acid (1 acid
(lmmol)
with TCC (lmmol). Methylation of 7f with CH2N2 gave 7g. These esters were characterised by spectral and analytical data(Table 1). Reduction corresponding
allylic
of TCC unsaturated esters 7a-c
with NaBH4 gave
alcohols [entries 11-131. TCC diester
of
the
stearic
acid 7d gave stearyl alcohol in high yield [entry 141. As already mentioned, alkyl esters are not reduced under conditions
used
[entries 2,7]. This selectivity
in
protecting one of the carboxylic acids in a dicarboxylic acid molecule
as
ester, while the other
alkyl or
be
the
utilised
TCC
could
could be transformed to alcohol through
DDHQ ester. This could be of some
synthetic utility.
Thus,
the TCC
4436
T.R.KASTURI andP.V.P.PRAGNACHARYULU
diester
of sebacic acid monomethyl ester 7e on reduction with
NaBH4 gave
hydroxy decanoic acid methyl ester [entry 151. TCC mono esters 7f-g on reduction gave lactones[entries
16,171.
The lactones are formed by reduction of TCC ester followed-by cyclisation. This
was
evident from the fact that methyl benzoate remained
under similar reaction slow in these cases and
conditions
uneffected
[entry 183. Reduction was comparatively
5-108 starting material was recovered
(Table 3).
Table 3. Reduction of TCC esters with NaBHa Entry
Ester
% Yield
Entry
Ester
% Yield
reduced of alcohol reduced of alcohol ____________________~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~_____~~~~~~~~~~~~ 15
65
7a
11
90
7e
12
7b
70
16
7f
65
13
7c
83
17
7g
66
14
7d
85
18
0
methyl benzoate
The
very
attributed phenolic
facile reduction of DDHQ/TCC diesters by NaBHa
to the presence of electron withdrawing groups moiety. Perhaps, in the case
7f-g),the
electron
releasing
of DDHQ/TCC
character of
could
(Cl,CN) in
be the
mono esters (3d,7a-b,
hydroxyl
or
methoxy
group
opposes this effect and hence, the reduction is sluggish. In conclusion, the high yields and selectivity obtained this
method
for the facile reduction of ester functionality
recommend under
mild
conditions, and particularly for the reduction of TCC or DDHQ esters
over
alkyl/aryl esters in a synthetic operation. EXPERIMEN!l'ALSECTION -1 All melting points are uncorrected.IR(k,cm Ispectra were recorded on Perkin-Elmer model 781 spectrophotometer.NMR spectra were recorded on FX-9OQ FT spectrometer with Me4Si as internal standard(6 = 0 MS-DX eV) were recorded on 303 spectrometer.Column (70 ppm).MS chromatography was carried out using silica gel.Ether refers to diethyl ether.All organic exctracts were dried over anhydrous Na2S04. Trans esterification of 3 with dry MeOH A mixture of compound 3 (600 mg) and dry MeOH (500 ml) was heated to after reflux for three days. To the residue in ether (100 ml),obtained removal of methanol, was added diazomethane in ether (30 ml) at 0°C excess After allowing the reaction mixture to stand for five minutes, diazomethane was destroyed by adding little HOAc. The ether solution was washed with water and dried. Ether was removed and the residue obtained
ReductionofDDHQandTCCestersby NaFS&
4437
was chromatographed . Elution with cHc13-hexane (l:l) gave 1:l mixtyre of cis and trans methyl esters 5b (200 mg, 38.5%),IR (nujol) 1730 ;H NMR 1.25 (s)and1.3 (s) (6H), 1.4-2.4 (m,20 Ii), 3.65 (s) and 3.85 (8) (3H), 6.15 (d,J=lO.O Hz,lH),6.25 (d, J=16.0 Hz)(lH),7.3-8.4 (m,lOH). Anal. calcd for c H- 0 C,82.4; H,8.0 Found:C,81.9; H,7.85%. elu ion with CHCl -hexane (2-l) gave 3d (120 mg, 33%), IR '8rege' 'H NMR 1 .3(s 6H? 1 3 2 .4 irn 20H) 1760 (nujol) 4.18 (s,3H), 6.7 (d, J=16.0Hz ,lH) 7:3-8.05 (m,8H)'8.2'(d: :=7.0Hz' ,lH): 8.65 (d,J=16.0Hz,lH). Anal.calcd for C44H4004N2C12 C,72.2; H,5.5; N,3.8. Found:C,71.8; H,5.3; N,3.6%. Oxidation
of spiroketone
la-b with
o-chloranil
A solution of spiroketone la (298 mg) and o-chloranil (270 mg) in dry benzene (50 ml) was refluxed for 24 hrs. It was concentrated and chrgmatographed . Elutiof with CHC13 gave TCC monoester 7a (300 mg) m.p 244 C; IR(nujo1) 1757 ; H NMR 6.07 (d,J=lO.OHz, lH), 7.05-7.60 (m,lOH), 7.77-7.95 (m,lH), 8.05 (d,J=lO.OHz,lH), MS m/e 542 (M+, 14), 297 (22), 296 (96), 268 (80), 239 (loo), 126 (42). Anal.Calcd for C H 0 Cl C,59.7; H, 2.58. Found:C, 59.29; H, 2.27%. Further elution with 27C&;-E$OAc (1O:l) gave tropone 2a. Similar oxidation of spiroketone lb (500 mg) with o-chloranii (270 in dry benzene gave 7b (400 mg); m.p l17°C;IR(nujolr 1760 ; H NMR mg) 1.2(~,6~), l.O-2.2(m,2OH), 6.5(d,3=16.0 Hz,lH), 6.75(s,lH), 6.95(d, J=8.0 7.3-8.0(m,7H),8.5(d,g=l6.0 Hz,lH).Analysis calcTi.for Hz,lH), 7.15(s,lH), C41H3804C14 C,77.36;H,6.O.Found:C,77.12;H,5.92 and 2b. Preparation
of 5c:
Compound 3c (500 mg) and 10% NaOH (100 ml) were refluxed until the yellow colour of the so&id disappeared (48 hr).The white solid was filtered off and dried at 0 C.The dried solid was stirred with 10% HCl (50 for lhr.The solid was exctracted with EtOAc (100 ml), washed with ml) watsr (25 mlx3) and dried. Removal of EtOAc gave the acid 5d (450 mg), m.p 110 C (CHCl ),IR(nujol) 1689 ; 'HNMR 3.6(s,3H,OCH ),5.63(d, J=12.0 Hz,lH) 6.85-7.05 (&7H), 7.1-7.2 $2H), 7.25-7.65 (m,7H?, 7.7-8.0 Tm,3H); MS m/I (relative intensity) 420(M ,lOO), 374(56), 343(44), 313(30),269(24). HRMS H 0 420.1362.Found, 420.1365. calcd'forEZ&!LZPi~ation of this acid 5d (420 mg) with MeOH/H SO methyl ester 5c (400 mg),m.p 80°C (CHCl -pet.ether); IR(thin filz) f72~~'~ NMR 3.4(s,3H),3.45(s,3H),5.45(d,J=12.0 az,lH),6.7-7.8(m,15H). HRMS calcd. 434.1518.Found,434.1555. for C2gH22D4 General chloride
Procedure for the preparation and DDHQ/TCC.
A mixtgre heated at 100 C mixture was again solid separated and with water chromatographed was crystallised esters are given General
was hrs.
procedure
of DDHQ
or 'FCC
esters
from
acid
of acid (2 mmols) and thionyl chloride (2.5 Rlmols) was for one hour. After addition of DDHQ Or TCC (1 nznol) the heated for 2 hrs. Water was added after cooling and the was extracted with EtOAc. The EtOAc extract was washed dried . The residue obtained after removal of EtOAc was . Elution with CHCl -hexane (3:l) gave the ester, which from CHCl -hexane. 2 pectral and analytical data of these in Table. 3. for
reduction
of esters.
To a solution of ester (1 mmol) in dry THF (20 ml), NaBH4 (2 mmol) added at O" C-The mixture was stirred at the same temperature for 2 and further at room temperature for 2 hrs. THF was removed & vacua,
4438
T.R.KAsTuIu~~~P. V.P.PRAGNACHARYULU
excess
NaBH was quenched with saturated NH4Cl solution, and the organic compound ex 0 ratted with ether. The ether layer was washed with water and column dried. Removal of ether gave alcohol which was purified by chromatography. Acknowledgement We thank Prof.George R.Pettit, ASU, Tempe, Arizona for a generous gift of monomethyl ester of sebacic acid,Dr.Amitabha Sarkar,NCL,Pune for a few mass spectra reported herein and Dr.A.Srikrishna for helpful discussions. Financial assistance from CSIR, New Delhi is gratefully acknowledged. References and Notes 1.
2.
3.
4. 5. 6.
7.
1956, Mead,E.J; Shoaf,C.J.; J.Am.Chem.Soc., a.Brown,H.C; -78,3616. b.Chaikin,S.W; Brown,W.G.; Ibid 1949, II, 122. c.Tschesche,R; Snatzke,G.;Chem.Berl955,88,1558. 3864. 1956,2, d.Kupchan,S.M; Johnson,W.S.; J.Am.Chem.Soc, 1954,173 Gabor,V.; Nuture(London), Fuchs,O; a.Kollonitsch,J; 125;1955,175.346. 6209. b-Brown I,H.C-ead E.J; Subbarao,B.C;J.Am.Chem.Soc..1955.77. c.Brown,H.C; Subbara0,B.C;J.Am.C hem.Soc.,1956,78,2582. d.Brown,H.C;Krishnamurthy,s; Tetr ahedron,l979,2,572. 1961, 2, 81. a.,Schenker; Angew.Chem., 1963, 2743 . b.,Barnett,J1.E.B; Kent,P.W.; J.Chem.Soc., Yamleda,s.: Koga,K; Matsuo,H; Ohki,s; Matsuo,I; C. ,Seki,H; 1965, 13, 995. Chem.Pharm.Bull(Tokyo), 1967, 15, 1948. ibz, d.Seki,H; Koga,K; Yamada,S.; Rm,G.; Synthesc Communications, e.Bianco,A; Passacantilli,P; 1988, 18(15),1765. Kasturi,T.R;Pragnacharyulu,P.V.P;Madhusudanareddy,G;Jayaram,S.K;Singh, S.B.; Tetrahedron(communicated1. 1970, 35, 1505. Takahashi,S; Cohen,L.A J.Org.Chem., :lH NMR 3334 Soectrosconic data of 4b : semi solid. IR(neat) 1,25(s,3H);1.3(s,lH),l.3-2.4(m,2OH),4.4(d with allilic coupling ,3=6.0 Hz,2H),6.l(doublet of triplet,z=l2.0 and 6.OHz,lH),6.9(m,lOH).Analysis calcd. for C 5H O2 ~,85.4;H,8.1. Fo8nd: C,85.2;H,8.0. Spectroscopis d@a of 4c: m.p 70 C;IR(thin film) 3412 ;lH NMR and 6.0 3.65(s,3H),3.95-4.2(m,2H),5.5(doublet of triplet,;r=l2.0 Hz,lH),6.4(d with allylic coupling,;r=lZ.O Hz,lH),6.9-8.l(m,l4H).MS m/e 406(M ,100),388(25),269(35).HRMS calcd. for C28H2203 ,406.1569. Found, 406.1564.