Professional Documents
Culture Documents
Limonene
A. F. Thomas
Firmenich SA, Research Laboratories, 12 I I Geneva 8, Switzerland
Y. Bessiere
126I Borex, Switzerland
is over 95 % pure, there is sometimes doubt in the literature as
to whether the limonene that was used in any experiment was
further purified or not. The major impurity in the material from
orange oil is myrcene (3); this can be removed by clathration
with tetrakis(4-methy1pyridine)di thiocyanatonickel. l 1 About
1 YOof aldehydes (mainly octanal) is also present, and there are
traces of other monoterpenes. The aldehydes can be removed
by distillation over 0.5 YOsodium hydroxide.
The presence of these impurities has led to widely different
values being determined for the flavour threshold concentration
in water. This has been given as 0.21 p.p.m., and the effect of
non-volatiles on this value has been measured,12 but the
limonene was only 96.5 YOpure, and was probably only distilled
orange oil, so the figures are meaningless. Values of 0.01
p.p.m.13 and 229 p.p.b. (also for 96% pure limonene)" have
been published, but in these papers we are not even informed
which enantiomer was tested, and it is known that the
organoleptic properties of the ( + ) - and the (-)-isomer are
different.I5 Again, the promotion of mouse skin tumours by
orange oil was long assumed to be caused by ( + )-limonene, but
pure ( + )-limonene does not exert this effect.16The toxicology of
limonene is well known;" its metabolism is mostly by allylic
oxidation or formation of an epoxide.lx One of the major
metabolites, uroterpenol glycoside (4), was isolated from urine,
especially of subjects with adrenal hyperplasia or in pregnancy;
this does not occur as an optically pure enantiomer, presumably
because of the variety of enantiomers in dietary limonene.19
(Uroterpenol will be discussed later.) Other metabolites are
known,')" and the conversion of (+)-limonene ( I ) into (+)perillic acid ( 5 ) by Pseudonioncrs incognita has been described .zl
Limonene is reportedly insecticidal ; B B . ' ) B it is toxic to cat fleas
(Ctmocephalidesj e l i ~ ) , ~for
' example, and may play a part in
conferring resistance to trees against attack by insects.'" There
is a simple school experiment to demonstrate the insecticidal
properties of ( + )-limonene."'
1 Introduction
2 Hydrogen Shifts and Disproportionation ; the Action
of Acids and Bases
3 Addition of Water, Alcohols, and other HX-type
Molecules
4 Addition of Halogens, Sulphur, etc.
5 Hydrogenation of Limonene
6 Hydroboration and Related Reactions
7 Oxidation (except Epoxide Formation)
8 The Limonene Epoxides
9 Addition of a C, Unit to Limonene
10 Addition of C, or More to Limonene
1 1 Pyrolysis and Miscellaneous Reactions
12 Biological Reactions of Limonene
13 References
1 Introduction
The production of (+)-limonene ( I ) in Brazil is about 12500
tonnes per year from orange stripper oil, 15000 tonnes per year
from cold-pressed orange oil [over 90% of which is (+)limonene], and about 11000 tonnes per year from other
sections of the citrus industry (orange-essence recovery water,
ete.),' making the annual world production of ( + )-limonene
about 50000 tonnes. Smaller amounts of more or less racemic
limonene (dipentene) are produced as a by-product from the
hydration of turpentine; distillation of turpentine is a source of
(-)-limonene, which can also be distilled from oil of Eucalyptus
s f q y r i a n a , although the purity is not as high as that of the (+)enantiomer. (+)-Limonene is one of the cheapest chiral starting
materials suitable for organic synthesis, and this review is
intended to survey its chemistry.
Until 1877, when Tilden distinguished between terpenes of
the 'turpentine group' and the 'orange group' by the
characterization of crystalline nitroso-derivatives,' there was
considerable confusion regarding the hydrocarbons obtained
from essential oils. Wallach pointed out that hesperidene,
citrene, carvene, di-isoprene, terpilene, kautschine, cynene,
cajeputene, and isoterebentine were all identical to (+)limonene.3 The discovery of ( -)-limonene (from Pinus silvrstrisJ)came a little later, making clear the constitution of the
racemate, dipentene, which had been obtained from the
distillation of rubber." The correct formula was given by
Wagner in 1894,6and the first rational synthesis was by Perkin
in 1905.' Racemic limonene is one of the products of the
pyrolysis of (-)-(S)-a-pinene (2),8 and the conversion of
turpentine into limonene over catalysts such as sodium sulphide
on alumina at 350 "C has been patented.'
We shall use the name 'limonene' for both the racemate and
optically active forms.
The major uses for limonene are in the flavour and fragrance
industries, as a solvent, and in the manufacture of polymers
and adhesives. Its uses as a solvent will not be discussed further
but there are patents, and such use has been increasing on
account of the low toxicity, pleasant odour. and biodegradability of (+)-limonene
Because ( + )-limonene that has been distilled from orange oil
(3)
COOH
(4)
29 1
(5)
292
Q
+
Scheme 1
293
F. THOMAS A N D Y. BESSIERE
!?
X
OR
294
d
c1
(31)
(33)
(34)
Br
(32)
formed in a d d i t i ~ n , ' ~
although 1,8-cineole (26) is a major
component of the products resulting from treatment of aterpineol (21 ; R = H) with an acid.84 Surprises here are,
however, common ; for example, terpin of unspecified stereochemistry is dehydrated by aluminium phosphate and aluminium oxide to give limonene (l), p-cymene (13), and
unidentified p r ~ d u c t s .The
~ ~ authors of this paper were
surprised by the p-cymene, but we are surprised by the
limonene, since we would have expected terpinolene (8) !
Innumerable different conditions have been described for the
preparation of a-terpineol (21 ; R = H) from terpene hydrocarbons, mostly from turpentine. The most efficient way from
limonene seems to be by using chloroacetic acids and a cationexchange resin ; this gives optically active a-terpineol in 85 O/O
conversion and 99 O/O selectivity ;*' alternatively, formic acid in
the presence of zeolites gives 87-100% conversion and high
selectivity.8i From limonene and acetic acid, with ferric sulphate
as a catalyst, a 6:4 mixture of a- and /3-terpinyl acetates is
efficiently made.8HOxymercuration of limonene followed by
reduction with sodium borohydride gives a-terpineol (21 ;
R = H) [70%], the rest being the diol (24; X = OH) and 1,8cineole (26).89 In fact it has long been known that if this
If
procedure is applied to a-terpineol it leads to 1,8-~ineole.~~)
the mercuration of limonene is carried out in the presence of
sodium lauryl sulphate, the formation of micelles causes the
ionized part of the molecule to be exposed to attack by water
on the periphery, and monohydration raises the yield of
terpineol to 97
The addition of methanol to limonene in the presence of an
acid could not be repeated by Treibs,92who reported that there
was mainly dimerization with a small amount of double
addition. The reaction was taken up again in 1949, when
Royals showed the reaction to be reversible by the fall in the
optical activity of the product (21 ; R = Me) with increasing
reaction time. Royals prepared other terpenyl ethers.93 (See
also refs. 54 and 71). By-products from this reaction would be
expected; although they have not been described, those from
the very similar reaction of pinene and methanol have,94
notably the ethers (27), (28), and (29). Bicyclic systems arising
from the reaction of pinene would, of course, be absent from
the products from limonene. Diol monoethers are known,
being made, for example, from limonene and ethylene glycol in
the presence of an ion-exchange resin.g"(See also ref. 96). The
light-induced addition of methanol to limonene takes a different
course from the acid-catalysed reaction, yielding 52 '/o of the
ethers (27) and (28) with about 13 YOof mentha-1(7),8-diene
(30).9i
The microbiological addition of water to limonene is
mentioned later.
The addition of hydrogen chloride to limonene to give its
monohydrochloride (31)98works well only in the absence of
SR
(39)
(40) R=Ph
NCHO
295
from a-terpinene (9)]. Dimethylphenols with one free orthoposition"' and sesamol (3,4-methylenedioxyphenol)'18 give
similar compounds. The reaction of limonene with phenol has
also been studied in the USSR,"' but the publication was not
available to us.
Addition of nitric acid to limonene has been
The ester that was obtained was reduced (by zinc dust) to aterpineol. 120 The racemization of ( +)-limonene in sulphur
dioxide occurs via the addition complex (37).122Menth- I-ene
also racemizes in liquid
The addition of hydrogen sulphide to limonene was shown to
give menth-1-ene-8-thiol (38) in 1979,124this compound also
being obtainable by the EtAlCIBr- or AlBr,-catalysed addition
of H,S to pinenes.12j This compound is characteristic of
grapefruit flavour, in which it occurs naturally, and has the
lowest recorded flavour threshold of any naturally occurring
substance.126 It is converted into 2,8-epithio-cis-p-menthane
(39) by radical cyclization.126The acid-catalysed addition of
thiophenol to limonene yields 40 YOof 8-phenylthiomenth- I ene (40), but it is difficult to purify the latter above 82%, and
Fourneron et al. preferred to protect the double bond at C-1 of
(+)-limonene by treating it with N-bromosuccinimide in
methanol [which yielded (41)] before acid-catalysed addition of
thiophenol and removal of the protecting groups (using zinc
and acetic acid) to obtain ( -)-(40),12' which they required for
a synthesis of car-2-ene (42).
Di(p-toly1)methyl chloride adds to one double bond of
limonene in the presence of zinc chloride (to the double bonds
at C-8 and C-1 in the ratio of 2.5: 1).12R
In three hours, at 55 "C, hydrogen cyanide in 55 YOsulphuric
acid also adds to both double bonds of limonene. From the
product (43), 1,8-di-isocyanomenthane was prepared by using
phosgene, rearrangement of the isocyano-compounds to 1 3 dicyanomenthane taking place with o-dichlorobenzene at
250 "C. The stereochemistry of the products was not discussed.'29 The addition of isocyanic acid in the presence of
BF, OEt, gave only a-terpinyl isocyanate.130
(47) X=Br
(48) x=1
&Cl
SPh
&SPh
c1
(54)
5 Hydrogenation of Limonene
The first catalytic hydrogenations of limonene, which were
carried out by Sabatier and Senderens at the turn of the
296
QOH
H
p.
H
OH
OH
H
(67) R a e
century, yielded menth-l-ene (57) over copper"" and the
menthanes (58) over nickel."' These results were rapidly
followed by others, e.g. the use of platinum black, which caused
addition of hydrogen in two stages,"$ and the use of pressure.""
It was soon recognized that many catalysts effccted not only
hydrogenation but disproportionation ( c ) . g . copper'"'!' and
platinum on charcoal'j'). Some catalytic supports favour
hydrogenation more than dehydrogenation (ZrO, and Tho,)
while some favour dehydrogenation (MgO, CaO, and La20:3).'.i'
The occurrence of undesired disproportionation reactions has
led to the discovery of many methods that give high yields of
menth- 1-ene, for example sodium borohydride and platinum
salts (98 YOyield)'"" or nickel chloride and polyvinylpyrrolidone
with hydrogen.'.j4 A catalyst that contained neodymium and a
silane gave menthene after 1.5 hours'jj and a complex that
contained rhodium trichloride and triphenylphosphine and
which was used as a catalyst in water give menthene after 32
hours and menthane after 76
For preparative
purposes, Newhall has confirmed'"' the utility of Vavon's
platinum catalystlA8rather than palladium or copper for
menth-l-ene, and we have found that a small amount of Raney
nickel is adequate to give over 90 YOof (57).ljXThe configuration
of the fully reduced menthanes (58) has been well established,'"!'
and catalytic reduction generally gives preferentially the tramisomer, but catalytic amounts of cob(1)alamin in aqueous acetic
acid give nearly 70% of the cis-isomer.'"' The readiness of
double-bond rearrangement in limonene during reduction has
been exploited by using hydrogenation over a deactivated
palladium catalyst; this yielded a mixture from which menth-3ene (59) could be isolated, the unchanged limonene being
recycled (racemization was not mentioned, but we can suppose
it to have occurred).161 The reason for this rearrangement-hydrogenation was to make menthone [( +)-(60)] from
the epoxide of (59).162
Most of the catalytic reductions that have been mentioned
yield optically active menthene, but reducing conditions
involving isomerization are known. Thus menth- 1-ene slowly
racemizes when heated in toluene with sodium and ochlorotoluene because of the reversible reaction that occurs
between menth- 1-ene (57) and menth-3-ene (59), the equilibrium
mixture containing 63% of the latter [together with 5 % of
menth-4(8)-ene (6 I )].lfi3
Dehydrogenation of limonene to p-cymene is reported to
occur best over a catalyst of PdO and sulphur on active
charcoal at 220-230 "C,giving 97 YOyield of p-cymene (1 3) in
96% purity.164 On a small scale, iodine yields 65% of pcymene.165
The disproportionation of limonene to p-cymene ( I 3) and
menthane (58) has been known since 1924, with palladium151or
platinum on charcoal166 as catalyst. The dehydrogenation
occurs in two stages; initially 52-53 YOof p-cymene is formed,
OO
/
of menth-8-enes (62). Longer reaction
together with 4-2
(68) R=CMe2CHMe2
(71) R=H
"p
(72) X=OH
( 7 3 ) X=I
(74)
View Online
QOl1OQ
2' 9'9
or1
(79)
HO #*a,
OOH HO +,,
OH
RO.*,
0
(83)
(81 1
(80)
(84)
(85)
297
298
OH
(92)
OMe
(93)
He -
(99) R=CHO
0
$CHO
(100)
ODmEt
(1011
fcHo
(102)
(104) R=CH20H
leads to a small amount of hydrocarbons (including mentha1,4,8-triene and p-cymene) and to mentha- 1,4(8)-dien-9-y1
acetate (95) and trans-carveyl acetate ( 8 5 ; R = Ac).'~, Under
different conditions (and after reduction with NaBH,), zterpineol (21 ; R = H) and P-terpineol (22) were obtained, the
terpins (24; X = H) also having been reported'lj (although the
authors did not seem to appreciate the instability of these on
gas chromatography).
Oxidation of limonene by thallium(III) nitrate is one of the
few routes from it to the bicyclo[3.2. Iloctane structure (another
is mentioned in Section 8, under the 8,9-epoxide). In methanol,
81 YO of the limonene was converted into a mixture of
stereoisomers of (96) and (97) (1 : 4), 19 YOof the products being
unidentified. 246
Early work on the oxidation of limonene by chromyl
but later work led
chloride mentioned a number of product~,'~'
only to a small amount of dihydrocarvone (89).'48
When passed over vanadium pentoxide on pumice at 425 O C ,
limonene yields maleic anhydride.249
The action of N-bromosuccinimide on limonene should lead
to allylic bromination ; the first study reported unstable
brominated products, which were converted in 80 YOyield into
p-cymene (13) by KOH in MeOH.'"" It is likely that the major
brominated product is indeed the expected one (98; X = Br),
Taher and Retamar having converted limonene into carvone by
this route; they used aqueous KOH in dioxane for the
hydrolysis.251The action of t-butyl hypochlorite appears to be
cleaner; the production of (-)-trans-carveyl chloride (98; X =
C1) has been optimized'"' and the latter converted into carveyl
esters with zinc carboxylates. 23:j
View Online
(107)
(108)
299
(109) X = S e ( O ) P h
Y=OH
(110) X=OH Y = S e ( O ) P h
6
Br
(111) X&1
Y=OH
$0.
-\
OH
OH
300
p..kme
the same conditions.293 The bisabolol discrepancy remains
unexplained.
The 8,9-epoxides have been used as intermediates in the
conversion of limonene into the bicyclo[3.2. Iloctane system.
Thermal rearrangement of the 8,9-epoxides to the menth- 1-en9-als (65) was described in 1961,294and this reaction also occurs
with acid ion-exchange resins, the reaction going further to
yield optically active 2,6-exo-dimethylbicyclo[3 .2.l]oct-2-en7-endo-01 (121) as the major product together with a little of the
6-endo-methyl isomer.295The racemate of (1 2 1 ) had already
been prepared from geranyl acetate.29'
The mixture of the four possible diepoxides has been known
as long as the 1,2-epo~ides.~~'
Little work was carried out until
1955, when it was again described,297and from 1956 onwards
there are many patents describing the polymerization of
' limonene diepoxide ' with Friedel-Crafts catalysts298or photosensitized cationic polymerization. 299 Although this is a major
use of limonene, there exists no description of the individual
isomers of the diepoxides (122) and they have only one
Chemical Abstracts Service Registry Number. The 1,2-epoxide
group is more reactive towards acid than the 8,9-epoxide
group, and the epoxides of (1 1 1) and (1 12) have been obtained
by treating the mixture of the diepoxides ( 1 22) with hydrochloric
acid under mild conditions.300When the diepoxides are used in
synthesis, the mixture is employed without comment (e.g. the
synthesis of hernandulcin by Mori and Kato301).
The epoxides have been used to protect a double bond in
limonene. Thus Ohloff et al. prepared optically active mentha1,8-dien-4-01 (92) by selenium-dioxide-catalysed oxidation of
( + )-limonene cis-1,2-epoxide ( 1 07), followed by removal of the
epoxide group by treatment with zinc and acetic acid and
sodium iodide,302but the yield was not good. An alternative
suggestion is to reflux the epoxide with lithium and 1 mol % of
biphenyl in ethylene glycol dimethyl ether.303
Limonene diepoxide (122) has been examined for cytotoxic
activity .,04
CIC1
30 1
&.
kOH
(145)
Although the Vilsmeier reaction of [CICH=NMe,]+[CI,PO,]with (+)-limonene gives a yield of only 40 % after 6 days, it is
very useful in that the ( E ) / ( Z ) ratio of the aldehydes (131 ;
R = H) that are formed is 98 :2; this fact led Dauphin to a rapid
synthesis of (E)-atlantone (1 32).325An earlier synthesis of (1 3 1 ;
R = H) was a multi-step one from methyl vinyl ketone.'s26The
isomers of (131: R = H) have been patented as flavour
material^."^
Delay and Ohloff used the anion (c) for adding one carbon
atom to (+)- or to (-)-limonene. Carbonation gives the /j'y
unsaturated acid (1 33 ; R = OH).32H
The corresponding ester is
isomerized (by MeONa in MeOH) to the thermodynamic
mixture of the conjugated esters (131 ; R = OMe) [ ( E ) / ( Z )=
82: 181. After separation, these were used in the synthesis of
or-bisabolenes (1 34) of known stereochemistry.32'H
Carbon tetrachloride reacts with limonene either in the
presence of a
or under the influence of ultraviolet
light33nto yield an addition product (135), hydrolysis of which
(by ethanolic KOH) leads to the optically active acid (131 ;
R = OH),330.331which was also used331for synthesizing (R,E)atlantone from (+)-limonene. Distillation of ( 1 35) in ethylene
glycol (at 200-2 10 "C) gives methyl 4-methylcyclohex-3-enyl
ketone. 33
Carbon oxysulphide reacts with limonene in a dimethyl- or
diethyl-aluminium-catalysed ene reaction to give ( I 33 ; R =
SH).332
The Simmons-Smith reaction of limonene was reported in
1958 to yield exclusively the product (136) of addition to the
isopropenyl double bond, the recovered limonene having
undergone 'little or no racemization' despite a fall by 5 0 %
being recorded in the rotation.333The structure was established
by infrared spectrometry.""4 The same compound ( 1 36) was
obtained by the palladium(n)-acetate-catalysed addition of
diazomethane.335Kropp et al. prepared all of the possible
addition products by irradiation of methylene iodide and
limonene in chloroethane; the yields were, after three hours,
7 % of (136), 47% of (137), and 14% of (l38).""" The
bicyclo[4.1. Olheptane (1 37) has also been prepared by the
reaction of the readily accessible dichlorocarbene addition
but in none of these
product ( I 39) with naphthalenelithi~m,:~:~~
papers were the spectral properties of (137) described; a paper
in which the 13Cn.m.r. spectra of the cyclopropanes ( 1 37) are
given does not say how they were prepared and separated.:':''
One of us has confirmed that the major addition product from
the Simmons-Smith reaction is indeed (136), but that the two
isomers of (137) are also formed (the ratio is about 3: l), and
the reason that the earlier papers missed this was probably that
View Online
302
(154)
COOEt
COOEt
&. ph9
(159)
(157)
QI.
R".
OH
Ph
I
OYNYO
R=
yN"xH
303
F. THOMAS A N D Y. BESSIERE
S02Me
S0,Me
SOZCHZAc
Scheme 2
Scheme 3
13 References
I These figures have been made available from Brazilian sources by
A. N . Henroz, Firmenich Ltda., S. Paulo, Brazil.
2 W. A . Tilden and W. A. Shenstone, J . Chrm. Soc., 1877, 31, 554.
3 0. Wallach and W. Brass, Lic4ig.v Ann. Ch~ni.,1884, 225, 291.
4 0. Wallach, Lic+ig.v Ann. Chem., 1888, 246, 221.
304
5 C. J. Williams, Proc. Roy. SOC.,1860, 10, 516; G. Bouchardat,
Bull. SOC.Chim. Paris, 1875, 24, 108.
6 G. Wagner, Ber. Dtsch. Chem. Ges., 1894, 27, 1636, 2270.
7 W. H. Perkin, jr., J . Chem. SOC.,1904, 85, 416; F. W. Kay and
W. H. Perkin, jr., ibid., 1906, 89, 1640.
8 J. J. Gajewski and C. M. Hawkins, J . Am. Chem. Soc., 1986, 108,
838.
9 L. G. Wideman and L. A. Bente (Goodyear Tire & Rubber Co.),
U.S. P. 4508930, April 2, 1985 [Appl. 632746, July 20, 19841
(Chem Abstr., 1985, 103, 123729).
10 For example: in the manufacture of childrens balloons, T.
Ishihara (Polychem. Kogyo Co. Ltd), Jpn. P. 48-40894, Nov. 27,
1973 [Appl. 45-68 144, Aug. 3, 19701 (Chem. Abstr., 1975, 83,
60951); in household cleaning fluids, Chem. Murk. Rep., 1987,
231, No. 21, p. 30, although the low flash point has given rise to
discussion about complete safety in such use (see ibid., April 11,
1988, p. 38); as solvent for cleaning paint brushes, H. Scheidel
(Scheidel Georg Jr., GmbH), Ger. Offen. 2843764, April 10, 1980
[Appl. Oct. 6, 19781 (Chem. Abstr., 1980, 92, 217085); as solvent
of varnishes for cleaning, restoring art objects, C. C. Goetz, Br. P.
1176043, Jan. 1, 1970 (Chem. Abstr., 1970, 72, 88296). See also
Chem. Murk. Rep., Feb. 1, 1988, p. 23.
1 1 F. P. McCandless, Flavour Znd., 1971, 2, No. 1, p. 33.
12 E. M. Ahmed, R. A. Dennisom, R. H. Dougherty, and P. E.
Shaw, J. Agric. Food Chem., 1978, 26, 192.
13 R. G. Buttery, R. M. Seifert, D. G. Guadagni, and L. C. Ling,
J . Agric. Food Chem., 1971, 19, 524; R. G . Buttery, D. R. Black,
D. G . Guadagni, L. C. Ling, G . Connolly, and R. Teranishi,
ihid., 1974, 22, 773.
14 J. Pino, R. Torricella, and F. Orsi, Nuhrung, 1986, 30, 783.
15 L. Friedman and J. G . Miller, Science, 1971, 172, 1044; J.
Limacher, Firmenich SA, personal communication.
16 J. A. Elegbede, T. H. Maltzman, A. K. Verma, M. A. Tanner,
C. E. Elson, and M. N. Gould, Carcinogenesis (London), 1986, 7,
2047.
17 D. L. J. Opdyke, Food Cosmet. Toxicol., 1978, 16, 809.
18 J. W. Regan and L. F. Bjeldanes, J. Agric. Food Chem., 1976,24,
377, and references cited therein.
19 A. P. Wade, G. S. Wilkinson, F. M. Dean, and A. W. Price,
Biochem. J., 1960, 101, 727; F. M. Dean, A. W. Price, A. P.
Wade, and G . S. Wilkinson, J . Chem. Soc.., C, 1967, 1893.
20 R. Kodama. T. Yano, K. Furukawa, K. Koda, and H. Ide,
Xenohiotica, 1976, 6, 377.
21 J. Rama Devi and P. K. Bhattacharyya, /ndiun J . Biochem.
Biophjvs., 1977, 14, 288, 359.
22 C. Tsujigaito, K. Nagata, and K. Koyama (Shinto Paint Co. Ltd;
Toyo Aerosol Industry Co. Ltd), Jpn. Kokai Tokkyo Koho 5393187, Aug. 15, 1978 [Appl. 52-8031, Jan. 27, 19771 (Chem.
Ahsrr., 1979, 90, 17691).
23 V. Dotolo, U.S. P. 4 379 168, April 5, 1983 [Appl. 130 138, March
14, 19801 (Chem. Ahsfr., 1983, 99, 1838).
24 W. F. Hink and B. J. Fee, J. M e d . Entomol., 1986, 23, 400 (Clicwt.
Ahstr., 1986, 105, 129406).
25 M. A. Johnson and R. Croteau, A.C.S. Meeting, Miami Beach,
April 1986, Abstract 127. AGFC Division.
26 J. H. Beatty, J. Chem. Educ., 1986, 63. 768.
27 R. N. Ammeraal (American Maize Products Co.), Ger. Offen.
3716509, Nov. 26, 1987 [U.S. Appl. 865059, May 20, 19861
(Cliem. Ahstr., 1987, 108, 114587).
28 R. Lauricella. J . Kechayan, and H. Bodot, J . Phys. Chem., 1977,
81, 542.
29 W. Offermann and A. Mannschreck, Org. Mugn. Reson., 1984,22,
355.
30 G. Lukacs and A, Neszmelyi. Tetrahedron Lett., 1981, 22, 5053;
R. Richerz, W. Amman, and T. Wirthlin, J. Mugn. Rcson., 1981,
45, 270; F. Bohlmann, R. Zeisberg, and E. Klein, Org. Mugn.
Reson., 1975, 7, 426.
31 M. F. Leopold, W. W. Epstein, and D. M. Grant, J . Am. Clicm.
Soc,, 1988, 110, 616.
32 A. Akhila, D. V. Banthorpe, and M .G. Rowan, Plijroc.liemi.vtr~,
1980, 19, 1433.
33 R. Ryhage and E. von Sydow, Actu Climi. Scund.. 1963, 17, 2025;
A . F. Thomas and B. Willhalm, Helv. Cliini. Actu, 1964, 47, 475.
34 D. Harris, S. McKinnon, and R. K. Boyd, Org. Muxv. Spi)c*trom.,
1979, 14. 265; see also F. Friedli, ;bid., 1984, 19, 183. A very full
discussion of the energetics of the retro-Diels-Alder fragmentation
of limonene under various conditions in the mass spectrometer
has been given by M . Vincenti, S. R. Horning, and R. G . Cooks,
Org. Muss Spectrom., 1988, 23, 585.
View Online
F. THOMAS A N D Y. BESSIERE
305
306
144 For example: W. H. Reiland, Jr. (Sun Oil Co.), U S . P. 3274 113,
Sept. 20, 1966 [Appl. Aug. 28, 19631 (Chem. Ahstr., 1966, 65,
184074.
145 R. M. Scarborough, Jr., A. B. Smith, 111, W. E. Barnette, and
K. C . Nicolaou, J . Org. Chem., 1979, 44, 1742.
146 P. Sabatier and J. B. Senderens, C . R . Hebd. Seances Acad. Sci.,
1902, 134, 1130.
147 P. Sabatier and J. B. Senderens, C . R . Hehd. Seunces Acad. Sci.,
1901, 132, 1256.
148 G. Vavon, Bull. Soc. Chim. Fr.. 1914, 15, 282.
149 W. Ipatiev, Ber. Dtsch. Cliem. Ges., 1910, 43, 3547.
150 P. Sabatier and G. Gaudion, C . R . Hebd. Seances Acad. Sci., 1919,
168, 671.
151 N. Zelinsky, Ber. Dtsch. Chem. Ges., 1924, 57, 2058.
152 Y. Tanaka, H . Hattori. and K. Tanabe, Bull. Chem. Soc. Jpn.,
1978, 51. 3641.
153 C. A. Brown and H. C. Brown, J. Org. Chem.. 1966, 31, 3989.
154 H. C. Brown, Agency of Ind. Sci. Tech. 557014537, taken from
J. Syntli. Methods, 1982, 76013~.
155 G. Jeske, H. Lauke. H. Mauermann, H. Schumann. and T. J.
Marks, J . An?. Cliem.Soc., 1985, 107, 8 11 I .
156 C. Larpent. R. Dabard, and H. Patin, Tetrtrhedron Lett., 1987, 28,
2507.
157 W. F. Newhall, J . Org. Chem., 1958. 23, 1274.
158 W. Schenk and A. F. Thomas, unpublished work.
159 H. van Bekkum. D. Medema. P. E. Verkade, and B. M. Wepster.
Red. Truv. Chim. Puj9.s-Bus, 1962, 81, 269.
160 A. Fischli and P. M. Muller, Hell?. Chim. Actu, 1980. 63, 1619.
161 H. Nagashima, T. Ogura, K. Takayama, T. Sato, and T. Matsui
(Takasago Perfumery Co. Ltd), Jpn. Kokai Tokkyo Koho 5412345, Jan. 30, 1979 [Appl. 52-78306, June 30. 19771 (Chem.
Ahstr.. 1979, 91. 20802).
162 H. Nagashima. T. Ogura. K. Takayama. T. Sato. and T. Matsui
(Takasago Perfumery Co. Ltd), Jpn. Kokai Tokkyo Koho 549247, Jan. 24. 1979 [Appl. 52-7277 I . June 2 I , 19771 (Chcni.
Ahstr.,
1979. 90, 204308).
163 H. Pines and H. E. Eschinazi, J . Am. Cliem.Soc., 1956, 78, I 178.
164 R. Martin and W. Gramlich (BASF), Ger. Offen. 3607448. Sept.
10, 1987 (Cliem. Ahstr., 1987, 107, 219472).
165 T.-L. Ho, Chem I d . (London), 1987, 295.
166 R. P. Linstead, K. 0. A. Michaelis, and S. L. S. Thomas, J . Clwni.
Soc.. 1940, I 139.
167 H. E. Eschinazi and E. D. Bergmann, J . Ani. Chcni.Soc., 1950.
72. 5651.
168 K. Kindler and K. Luhrs, Liebigs Ann. C h ~ m .1965,
,
685, 36.
169 K. Kindler and K. Luhrs, Chem. Ber.. 1966, 99, 227. There are a
few incorrect formulae in these two papers, and one in J . March.
'Advanced Organic Chemistry', 3rd edn., Wiley, New York, 1985,
p. 1107, where limonene is shown to be dehydrogenated to a
menthatriene instead of to p-cymene.
170 G . Brieger and T.-H. Fu, J . Chuw. Soc., Chrm. Commun., 1976,
754.
171 F. W. Semmler. Liehigs Ann. Chem., 1904, 34, 3125.
172 R. Dulou and Y. Chretien-Bessiere, C.R . Hrhrl. Secrncc~.~
Aceid.
Sci., 1959, 248, 216; Bull. Soc. Chim. Fr., 1959. 1362.
173 H. C. Brown and G. Zweifel, J . Am. Chem. Soc., 1961, 83,
1241.
174 K. Ziegler, F. Krupp, and K. Zosel, Angcw~.Cliem., 1955, 67, 425;
Liebigs Ann. Cheni., 1960, 629, 241 ; cf: B. A. Pawson, H.-C.
Cheung, S. Gurbaxani, and G. Saucy, J . Am. Chem. Sol.., 1970.
92, 336.
175 J. Albaiges, J. Castello, and J. Pascual, J . Org. Chmi., 1966. 31,
3507.
176 G . Ohloff, W. Giersch, K.-H. Schulte-Elte, and E. sz. Kovlits,
Heh. Cliim. Actu, 1969, 52, 1531.
177 K.-H. Schulte-Elte and G. Ohloff, Helv. Chin?. Actcr, 1967, 50,
153.
178 J. F. Blount, B. A. Pawson, and G. Saucy, Chcw. Commun., 1969,
715.
179 1. Uzarewicz and A. Uzarewicz, Pol. J . Chem., 1979, 53, 1989; see
also ref. 189.
180 H. C. Brown, S. U. Kulkarni, C. Gundu Rao, and V. D. Patil,
Tetrahedron, 1986, 42, 55 15.
181 A. V. Kuchin, G. A. Tolstikov, V. P. Yur'ev, V. I. Ponomarenko,
G. N. Kurilenko, R. A. Nurushev, and L. I. Akhmetov, Zh.
Obshch. Khim., 1980, 50, 91 I (Chem. Ahstr., 1980, 93, 71 842).
182 N. Satyanarayana and M. Periasamy, Tetrahedron Lett., 1984.25,
2501 ; P. Le Maux and G. Simonneaux, J . Mol. Cutal., 1984, 26,
195.
183 H. C. Brown and K. J. Murray, Tetrahedron, 1986, 42, 5497.
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
307
308
292 R. M. Carman, K. L. Greenfield, and W. T. Robinson, Aust. J .
Chem., 1986, 39, 21.
293 R. M. Carman, J. J. De Voss, and K. L. Greenfield, Aust. J .
Chem., 1986, 39, 441.
294 J. P. Bain, W. Y. Gary, and E. A. Klein (Glidden C o . ) , U.S. P.
3014047, Dec. 19, 1961 [Appl. Aug. 27, 19531 (Chem. Ahstr., 1962,
57, 1 2 5 5 7 ~ ) .
295 A. F. Thomas, F. Rey, 0. Guntern, and C. Perret, unpublished
work.
296 I . Kitagawa, S. Tsuji, F. Nishikawa, and H. Shibuya, Chem.
Phurm. Bull., 1983, 31, 2639.
297 G . V. Pigulevskii and I . S. Khozina, Zh. Obshch. Khim., 1955, 25,
416 (Chem. Absir., 1956, 50, 2 5 0 0 ~ ) .
298 G. A. Trigaux, Mod. Plust., 1960, 38, 147, gives a list of useful
properties incurred by use of limonene diepoxide in polymerizations.
299 J. V. Crivello and J. L. Lee, Macromolecules, 1981, 14, 1141.
300 L. A. Mukhamedova,
F. G. Nasybullina,
and
M. 1.
Kudryavtseva, Izv. Akud. Nuuk SSSR, Ser. Khim.. 1979, 847
(Chem. Abstr., 1979, 91, 74710).
301 K. Mori and M. Kato, Tetrahedron Lett., 1986, 27. 981.
302 G . Ohloff, W. Giersch, R. Naf, and F. Delay, Hcdv. Chini. Actu,
1986, 69, 698.
303 M. A. Pasha and B. Ravindranath, Inncliun J . Chcni., Sect. B, 1983,
22, 1149 (Chem. Ahstr., 1984, 100, 209545).
304 J. A. Hendry, R. F. Homer, F. L. Rose, and A. L. Walpole, Br. J .
Phurmucol., 1951, 6, 235.
305 E. P. Demole and P. Enggist (Firmenich SA), Eur. Pat. Appl.
54847, June 30, 1982; W. Pickenhagen and E. P. Demole, IXth
Internat. Congress of Essential Oils, Singapore. March 13- 17,
1983. Abstracts Book 3, p. 1.
306 0. Kriewitz, Ber. Dtsch. Chem. Ges., 1899, 32, 57.
307 H. J. Prins, Chem. Weekbl., 1917, 14, 932; 1919, 16, 1510; Kun.
Akud. Wetensch. Amsterdum, Wisk. en Nutk. A,fii., 1920, 27, 1496
(Chem. Zentrufhl., 1918, I, 168: 1919, 111, 1001; 1920, I, 423).
308 R. Lombard and J. Adam. Bull. Soc. Chim. Fr., 1953, C24; ibid.,
1954, 1216.
309 G . Ohloff, Arch. Phurm. Ber. Dtsch. Phurni. Ges., 1954, 287, 258.
310 A. T. Blomquist, J. Verdol, C. L. Adami, J. Wolinsky, and D. D.
Phillips, J . Am. Chem. Soc., 1957, 79, 4976.
31 1 K. Suga, A . Matsuda, and S. Watanabe, Nippon K L I ~ UZusdii,
~U
1958, 79, 724 (Chem. Ahstr., 1960, 54, 4656e).
312 J. Colonge and J. Crabalona, Bull. Soc. Cliini. Fr., 1960, 98.
313 Y. Watanabe, Nippun Kuguku Zusshi, 1959, 80, 1063 (Cheni.
Ahstr., 1961, 55, 3591e); Y. Watanabe, Y . Matsubara, and C.-Y.
Huang, Kogyo Kuguku Zusshi, 1959, 62, 1630 (Chmi. Ahstr., 1962,
57, 13963~).
314 A. T. Blomquist and R. J. Himics, J . Org. Chem.. 1968, 33, 1156.
315 K. Suga and S . Watanabe, Bull. Chem. Soc. Jpn., 1959, 32, 1100.
316 C. Bordenca and W. A. Lazier (Food Machinery and Chemical
Corp.), U.S. P. 2584539, Feb. 5, 1952 (the formula in Choii.
Ahsir., 1952, 46, 8 6 7 6 ~must be incorrect).
317 W. H. Clement and M. Orchin, Ind. Eng. Chem., Prod. R m . Dev.,
1965, 4, 283.
318 D. Evans, J. A. Osborn, and G. Wilkinson, J . Chcm. Soc., A ,
1968, 3133.
319 C. K. Brown and G . Wilkinson, Teiruhedrun Lett., 1969, 1725.
320 K. Kogami, 0.Takahashi, T. Yanai, and J. Kumanotani,
Yukuguku, 1973, 22, 316 (Chem. Ahstr., 1973, 79, 92400).
321 M. Takeda, H. Iwane, and M. Kyo (Mitsubishi Petrochemical
Co. Ltd), Jpn. Kokai Tokkyo Koho 55-47638, April 4, 1980
[Appl. 53-120046, Sept. 29, 19781(Chem. Ahstr., 1980,93,94894);
J. Hagen and K. Bruns (Henkel K. G . aA.), Ger. Oflen. 2849742,
May 22, 1980 [Appl. Nov. 16, 19791 (Chem. Ahstr., 1980, 93,
186613); H. Bahrmann, B. Cornils, C. D. Frohning, and J. Weber
(Ruhrchemie A. G.), Eur. Pat. Appl. 8459, March 5, 1980; Ger.
Appl. 2837480, Aug. 28, 1978 (Chem. Ahstr., 1980, 93, 94891).
322 P. W. N. M. van Leeuwen and C. F. Roobeek, J . Orgunomc~t.
Chem., 1983, 258, 343.
323 M. Takeda, K. Miyoshi, and T. Hashimoto (Mitsubishi Petrochemical Co. Ltd), Jpn. Kokai Tokkyo Koho 55-38337, March
17, 1980 [Appl. 53- 1 1 1 9 19, Sept. 12, 19781 (Chem. Ahstr., I980,93,
167734).
324 J . Weber, W. Bernhagen, and H. Springer (Ruhrchemie A. G.),
Ger. Offen. 2921 619, Dec. 4, 1980 [Appl. May 28, 19791 (Chem.
Ahsir., I98 1, 94, 208 434).
325 G . Dauphin, Synthesis, 1979, 799.
326 J. H. Babler, D. 0. Olsen, and W. H. Arnold, J . Org. Chrm.,
1974, 39, 1656.
327 B. D. Mookherjee, R. A. Wilson. M. H. Vock, and M. H. Zam-
F. THOMAS A N D Y. BESSIERE
369 K. Alder and A. Schmitz, Liebigs Ann. Chem., 1949,565, 118; see
also K . Alder, in Progr. Chem. Org. Nut. Prod., 1953, 10, 54.
370 H. E. Eschinazi and H. Pines, J . Org. Chem., 1955, 20, 1666.
371 T. Doiuchi, H. Yamaguchi, and Y. Minoura, Eur. Polymer J . ,
1981, 17, 961.
372 W. A. Tilden, J . Chem. Soc., 1884, 45, 410.
373 G. Egloff, M. Herrman, B. L. Levinson, and M. F. Dull, Chem.
Rev., 1934, 14, 287. The yield of isoprene is reported to be up to
68 YO; cJ H. Staudinger, H. W. Klever, and J. Prodrom, Ber.
Dtsch. Chem. Ges., B, 1942, 75, 2064.
374 H. Pines and J. Ryer, J . Am. Chem. Soc., 1955, 77, 4370.
375 S. G . Traynor, K. J. Crowley, and W. Cocker, J . Chem. Res.,
1981, (S)175; ( M ) 2101.
376 K. J. Crowley and S. G. Traynor, Tetrahedron, 1978, 34, 2783.
377 H. von Euler and L. Ahlstrom, Ark. Kemi, 1932, 11A, No. 2
(Chem. Zentralbl., 1932, 11, 3486).
378 V. E. Levine and E. Richman, Biochem. J . , 1933, 27, 2051, also
developed a colour reaction with SbCl, and acetic anhydride; R.
Delaby, S. Sabetay, and M. Janot, C . R . Hebd. Seances Acad. Sci.,
1934, 198, 276.
379 J. E. Arnet and R. Pettit, J . Am. Chem. Soc., 1961, 83, 2954.
380 J.-B. Chen, G.-X. Lei, Z . - S . Jin, L.-H. Hu, and G.-C. Wei, J .
Chem. Soc., Chem. Commun., 1988, 73 1 .
381 J. E. Baldwin, R. M. Adlington, Y. Ichikawa, and C . J. Kneale, J .
Chem. Soc., Chem. Commun., 1988, 702.
382 M . F. Leopold, W. W. Epstein, and D. M. Grant, J . Am. Chem.
Soc., 1988, 110, 616.
309