Indian Journal of Ch emi stry
Vol. .:lOB. June 200 1. pp. 510-514
Note
Prepa rati on and molecular rearran ge ment of
2a, 3a-epoxy lupan-1-one catalysed by boro n
trifluoride and by ultra vio let irrad iati on+
S N Bose* & S K Chanda
2
Departmen t of Chemistry, North Benga l Un i versity.
Darjeeling 73--1 430
Receil'ed 25 Nm·e111ber / 999; accepted (re1·ised)
8 A ugust 2000
Using lupeol 7 as lead co mpound 2a. 3a -epoxy lu pan-1-one
11 has been synthes ise d by a sequence of reacti ons. Boron
trinu oride catalysed molecular rearran gement of II in benze ne
yie lds
2-formy i- A-no r- lupan-1 -onc
IS
(enol ized) .
Same
rearrangement is also achieved in dioxane under ph otolyti c
co ndition.
4
3
1
House and Watson have observed that cyc li c epoxy
ketones of the type ( l:n> I ) in the presence of boron
tri lluoride-etherate undergo mo lecular rearrangement
(C hart 1) with reductio n in ring size of ketones and
produce th e keto aldehydes 2. L ater. Kartha and
Chakravarti} studied the ac tion of boron triflu oride on
some sesquiterpene epoxy ketones and epox ides and
fnund th at in each case an aldehyde was formed by
contracti on of a six-membered ring to a fivemembered one. Ganguly et. a/. 3 c:.ll·;ied out BF3catalysed rearrangeme nt of I a. 2a-epoxy lupan-3-one
3 and obtained th e product I - methyl-2a- hydroxylup-l ( I O)en-3-one 4. Here, most probably due to th e
presence of a neopentyl system adjacent to th e epox y
ketone system, methyl migration occulTed instead of
4
ring con trac ti on. In con trast. Chattetjee et. a /. also
stud ied the same rearrangement on th e same substrate
3 and report ed the formati on of th e nor-ke tone 5,
presumab ly formed by the el imination of formyl
initial
product.
2-formyl
group
from
the
cyclopentanone 6. I n this note we wish to repo rt first
the partial sy nthes is o f the: isomeri c epoxy ke tone 11
possessing a neopen tyl sys tem adj acen t to th e epoxy
ketone moiety and then the mol ecul ar rearran gement
of 11 induced by BF3-etherate as well as induced by
ultraviolet irradiat ion to give 2-fonnyi-Anor- lu pan-1one 15.
11
t Presented in part in proceedings of 85' ~cssio n of Indian Science
Congress. Part Ill. page 29. 1-l ydc rabad. 1998.
6
5
Cha rt 1
The starting material for th e preparati on of 11 is
th e triterpene lupco l 7, obtained abundantl y from the
benze ne extract of Zanthoxylu111 budnrngct"' followed
by chromatographic purificati on. Compound 7 on
catal ytic reducti on (Scheme I) furni shed lu pan ol 8,
which on dehydration with phosporu s oxych loride in
pyridine afforded lup-2-ene 9. Oxid ation of 9 with
sodium dichromate in benzene-acetic acid mixture
( I : I ) y ielded the co njugated ketone, l up-2-en- 1-one
10, Armx 220nm, Vm:rx 1667cm·'. Though it was
ex pec ted to give th e key compound 2a, 3a-epoxy
lupan- 1-one 11 on treatment with alka line hydrogen
peroxide, our repeated att empts fai led to obtain the
desi red epoxy ketone 11 . At thi s ju ncture, a literature
survey revea led th at the system 2-en-1-one of rin g-A
in triterpenes is stabl e toward s alkal ine hydrogen
6
perox ide as noted by Barton and coworkers .
Consequentl y, we adopted an alternative meth od for
th e preparati on of th e epoxy keto ne 11. Lup-2-ene 9
on se lenium dioxide oxidation in di oxa ne with a few
drops of water added in it, ga ve the all y li c alcohol,
lup-2-ene-1 a -ol 12 foll owing the reaction condi tions
OTES
5II
a
HO
HO
8
7
, , ;Lv~
01,,,,~~ ..
d
)(
16
15
Scheme I
Reagents and conditions. (a) 1-1 2/ Pd-C. ETOAc, rt . 4hr (b) PC I3• Py , 4 hr, water-bath (c) Na 2Cr 20 7 , C 6 H 6-Ac0H ( I: I), 3hr, re Oux (d)
1-1 20 2• NaO H, rt (e) Se0 2, dioxane. traces of wa ter, 6 hr, re Oux (f) 1/t-CPBA, C HC I3, S°C, 72 hr (g) C r0 3, Py, soc, 48 h (h) BF3 - etherate.
C 6 1-1 6 . I hr. rt (I) hv > 290 nm, d ioxa ne, O.S hr, rt.
presc ribed by Vystrc il et . a / 7 . Compound 12 was
epox idised7 with metachl oro-perbenzoic acid in
chl oroform to yield th e epoxy alcohol, 2a, 3a-epoxy
lupan-l a-ol 13. We have prepared th e key compound ,
2a, 3a-epoxy lupan-1 -one 11 by the chromium
triox ide- pyridin e ox idati on of 13. In 1 HNMR
spectrum , appearance of reso nances at 8 3.1 (doubl et,
.I = 4Hz) and 8 3.27 (doubl et, J = 4 Hz) enabled us to
ass ign 2a, 3a-epoxy ketone stereochemi stry fo r 11.
Vys trcil and coworkers7 settl ed th e stereochemi stry of
13, the precursor of 11 , as 2a, 3a-epoxy lupan-1 a -ol
by carrying out its co nversio n with LAH to 2a, 3adihydroxy lupane of know n structure. Boro n
tri fl uoride catalysed rearrangement of 11 in dry
benze ne at ambient temperature affo rded th e rin g A
contracted keto aldehyde, 2-formyi- A-nor-lupan-1 one 14 in 60% yield . It prac ti call y ex ists in so luti on as
the enoli zed for m 15. The structure of the rearranged
produ ct was dedu ced by the phys ical techni ques UV ,
IR, NMR and mass spectra (see Experimental). Of the
two possible enoli zed forms 15 and 16, the forme r
one 15 was supported by aldehydi c proton si nglet at
q 9.4 in th e 1H NMR anal ys is.
The mechan istic as pects of th e ri ng co ntraction
reacti on have been th oroughl y in vesti gated 1.2_ Most
possibl y th e ion 17 (Chart 2) generated by the attack
of BF3 on 11 gives ri se to carbocati on 18 which
eventuall y rearranges to the ring co ntracted product
14. The whole process mi ght be sy nchronous.
The photorearrangement of cycli c epoxy ketones is
we ll documented 8·9· Upon photolys is, they afford I ,3diketones or keto-aldehydes. We have carri ed out
irradi ati on of 11 in dioxane at A> 290 nm at ambinet
temperature under argo n-atmosphere for 0.5 hr. We
have been able to isolate the sa me keto-aldehyde 14 in
good yield (52%). Since the initial prod uct 14 is al so
INDIAN 1 CHEM. SEC B,JUNE 2001
512
e
F3 B"-..~
0
_..o~-~o~
0
5<'
HOC~
14
11
Chart 2
photolabile, irradiation for an extended period resuhs
in a complex reaction mixture giving a low yield of
14.
This photoreaction occurs from excited singlet
9
manifold 8· via a diradical generated by homolysis of
9
Ca-0 bond, the retention of configuration a in the
resulting
~-diketones
obtained
from
the
stereoisomeric steroidal epoxy ketones supports the
of
a
predominantly
concerted
proposition
rearrangement maintaining close orbital overlap
9
throughout the entire radical migration • Accordingly,
the mechanistic pathway of th e photorearrangement
of 11 studied by us can be depicted as in Figure 2.
The diradical 19 or 20 generated initially on
photoexcitation rearranges to the keto-aldehyde 14 by
a process in which the bond-migration and carbonylformation steps are concerted.
Though the ketoketene 21 could be an attractive
intermed iate, no product corresponding to this
intermediate has been isolated.
In conclusion , the molecular rearrangement
conducted by us on isomeric epoxy ketone I ll,
induced by either BF3-etherate at ambient temperature
or under photolytic condition, enabled us to obtain the
ring contracted keto-aldehyde 14 in line with the
finding of the original workers 1• Though Chatterjee et
a/. 4 did not obtain the rearranged ring contracted ketoaldehyde 6, but obtained a ring contracted ketone 5,
presumably formed
y deformylation of the
intermediate keto-aldehyde 6. Incidentally, we did not
observe the formation of methyl migrated product of
the type 4 isobted by Ganguly et al 3 .
Experimental Section
General. Melting points were determined in a
sulphuric acid bath and are uncorrected. The pet.ether
used throughout the investigation had B.P. 60-80°C.
1
H NMR spectra were recorded on a VNXL-200
spectrophotometer in CDCI 3 soluti on using TMS as
internal reference; IR spectra on a Pye Unicam-Sp300S and UV on a shimad Zu UV-240
spectrophotometers; and mass spectra (ElMS) on a
Jeol JMS-0300 mass spectrophotometer, using direct
sample introducti on into the ion source at 70 eV. TLC
was done on chromatoplate of silica gel G (E.M erck)
and spots were visuali sed by exposing the plates in
iodine vapour.
Isolation of lupeol 7. Stem-bark o f Zanthoxylun1
budrunga 5 was extracted in a soxhlet apparatus for
20 hr. with benzene. The extract was concentrated and
purified by column ch romatography over silica gel.
Elution with pet-ether-ethyl acetate (9: 1) as eluent
gave lupeol 7 as white solid, crystallised from
chloroform-methanol as needless mp 214- l5°C (lit. 10
1
mp 215-l6°C); IR (nujal): 3420 (OH), 1630, 890 cm(=CH2).
Lupanol 8. To a solution of lupeol 7 (21 mmoles)
in ethyl acetate (450 mL) was added Pd-C (5 %, !g)
and hydrogenated for 5 hr. Pd-C was removed by
filtration and the filtrate on concentration afforded
11
fine white needles of lupanol 8, mp 202-03°C (lit mp
201-02°C), IR (nujal : 3390 em·' (OH), C3oHs20 (M+
428 m/z).
Preparation of luP'-2-ene 9. To a solution of
lupanol 8 (16 mmoles) in dry pyridine (200 mL) was
added phosphorus oxychloride (25 mL). The reaction
mixture was refluxed on a water-bath for 4 hr and
then overnight at room temperature. It was poured on
ice-water. The precipitated brown solid obtained on
filtration was chromatographed on silica gel. Elution
NOTES
with pet. ether gave lup-2-ene 9 (65%) as, white solid
mp 190-l92°C (lit. 12 mp 192-93°C); IR (nujal) :1630,
850 em·' (C =C).
Preparation of lup-2-en-1-one 10. To a solution
of lup-2-ene 9 (11 mmoles) in benzene-acetic acid
(1: I, 300 mL) sodium dichromate (15 mmoles) was
added and the mixture refluxed for 3 hr_ The excess
oxidant was destroyed by addition of methanol (20
mL). The reaction mixture was extracted with ether
(500 mL), washed with Na 2C0 3 and then with water
until neutraL The brown mass obtained on
evaporation was chromatographed over silica geL
Elution with pet. ether-ethyl acetate (4:1) as eluent
gave 10 as white solid (55%), mp 194-95°C, UY
(C H30H ): Amax 220 nm, IR (nujal): 1667, 1625cm· 1
(conj ugated ketone).
Alkaline hydrogen peroxide treatment of lup-2en-1-one 10. To a solutio of 10 (2.5 mmoles) in
dioxane (50 mL) was added aquous hydrogen
peroxide (30%, 8 mL) and aqueous NaOH (6N, I 0
mL) and stirred over a period of 2 hr. After usual
work-up unchanged startin g material 10 was
recovered in almost quantitative yield (mp and mmp).
Preparation of Iup-2-en-1a-of 12. To a solution of
9 (5.2 mmoles) in dioxane (200 mL) Se02 (6.7 mmole)
was added. After addition of traces of water (4 drops)
the reaction was retluxed for 8 hr. The warm filtrate
obtained on removal of Se was poured into aquous
KOH solution (2.5%, 1.2L). The precipitated solid was
chromatographed over si lica geL Elution with
pet.ether-ethyl acetate (3: I) gave a white solid which
on crystallisation from chloroform-methanol gave
needles of lup-2-en-1a-ol 12, mp 201-02°C (lit. 7 mp
203-04°C), C 30 H500 (M+426 m/z), IR (nujal) : 3424
(OH), 1625, 862 em·' (C=C), 1HNMR : 80.7 - 1.1
(8C H3S), 3.6 (m, IH, CHOH), 5.5 (d, 1H, 1 =12Hz C3
-H) and 5.7 (q, 1H, C 2 - H). AnaL Calcd for C3oHsoO :
C, 84.44; H, 11.81. Found: C, 84.12; H, 11.61%.
Preparation of la-hydroxy-2a, 3a-epoxy lupane
13. To a solution of 12 ( 10.5 mmoles) in chloroform
(55 mL) was added m-CPBA (14.6 mmoles). The
reaction mixture was kept at 5°C for 72 hr, extracted
with ether (250 mL), washed with Na2C03 solution
and then with water until neutraL The white solid
obtained on evaporation of solvent, was crystallised
from chloroform-methanol to furnish pure 13 (72%),
mp 233-34°C (lit. 7 mp 232°C); C3oH5002 (M+ 442
mlz), AnaL Calcd for C 3oHs 002; C, 81.33, H, 11 .35.
Found: C, 81.47; H, 11.09%.
513
Preparation of 2a, 3a-epoxy Iupan-1-one 11. To
a solution of 13 (2.5 mmoles) in pyridine (20 mL) was
added a slurry of Cr03 (3.6 mmoles) in pyridine
( 15 mL) at soc and kept at this temperature for 48 hr.
The reaction mixture was diluted with ethyl acetate
(200 mL). The precipitate was filtered off. The clear
brown filtrate was treated with aqueous HCI (10%),
washed with water until neutraL Evaporation of the
solvent left a brown mass which was chromatographed over silica geL Elution with pet. ether-ethyl
acetate (4: 1) yielded a white solid which on
crystallisation from chloroform-methanol afforded
fine needles of 11 (48%) mp 191 °C ; IR (nujal):
1695 em·' (C = 0) ; 1H NMR: 8 0.72- 1.1 (8CH 3S),
3.11 (d, I H, J =4Hz, Cr H) and 3.27 (d, I H, 1 =4Hz,
C 2-H); Mass : 440 (M+), 397 m/z(M+-isopropyl).
AnaL Calcd. for C30 H 500 2: C, 81.81; H, 10.91. Found :
C, 81.45; H 10.68%.
BF3-etherate rearrangement of 11. Preparation
of 2-formyi-A-nor-Iupan-1-one 14. The epoxy
ketone 11 (1.2 mmoles) in dry benzene (25 mL) was
treated with freshly distilled BF3-etherate (5 mL) at
room temperature for I hr. The reaction mixture was
diluted with water, extracted with ether and washed
with water. On evaporation a thick gum was obtained
which was purified by chromatography over silica
geL Pet. ether-ethyl acetate (7:3) eluted a white sol id
(60%), mp 93-94°C, UY (MeOH); A111,,227 nm,
shifted to 292 nm in 0.1M NaOH, IR (nujal):
3450(0H), 1710 (unsaturated aldehyde), 1595 (C=C)
cm- 1, 1H NMR: 8 0.7-1.2 (8CH 3S), 3.11(d, 1H, 1 =
4Hz C 3-H), 3.27 (d, 1H, J = 4Hz, C 2-H) and 9.4 (s,
1H, -CHO); Mass : 440 (M+), 397 m/z (M+isopropyl). AnaL Calcd for C 30 H4802: C, 81.81; H,
1091. Found: C, 81.55; H, 16.72%.
Photolysis of 11 : Formation of 2-formyi-A-norlupan-1-one 14. A solution of 11 (1 .1 mmole) in dry
dioxane (100 mL) was irradiated for 0.5 hr with
medium pressure mercury lamp placed in a central
water-cooled pyrex immersion well under argon
atmosphere at ambient temperature. Evaporation of the
solvent in a rotary vacuum evaporator followed by
chromatography of the crude product on silica gel
using pet. ether-ethyl acetate (7 : 3) as eluent gave a
white solid (52%) which was found to be identical with
14 by mp and mmp determinations and by comparison
of spectral (UY, IR, 1H NMR and mass) data.
514
INDIAN J CI-IEM. SEC B, JU E 2001
Acknowledgement
The au thors are grateful to Dr S Lahiri, lACS,
Jadavpur, Calcutta for providing laboratory faci liti es
fo r irradiation experimen t with medium press ure
mercury lamp and to the Director, CDR!, Lucknow
for 1 H NM R and mass spectral data.
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