2,3-DIHYDROPYRANNES, PREPARATION, ET UTILISATION COMME INSECTICIDES

2,3-DIHYDROPYRANS, PROCESSES FOR THEIR PREPARATION, AND METHODS FOR COMBATTING INSECTS THEREWITH

Abrégé anglais

ABSTRACT OF THE DISCLOSURE
A method for combating insects is described. 2,3-
dihydropyrans and their preparation are described.

Revendications

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A 2,3-dihydropyran of the formula:
<IMG> (I)
or an optical isomer thereof.
2. A process for the preparation of a 2,3-dihydropyran
of the formula:
<IMG> (I)
or an optical isomer thereof, which comprises cyclizing a
compound of the formula
<IMG> (VIII)
3. A process as claimed in claim 2, in which the
compound of formula (VIII) is prepared by reacting a hetero-
cyclic nitrogen compound chosen from the group consisting of
pyrrolidine, piperidlne, or morpholine with a ketone of the
general formula
(II)
<IMG>
13

in the presence of a condensing agent to yield an enamine
having a general formula (IIIa)
<IMG> (IIIa)
n being 1 or 2, or (IIIb)
(IIIb)
<IMG>
reacting said enamine with a vinylnitrile of the general
formula
<IMG> (IV)
to yield an intermediate (V) having the general formula
<IMG> (V)
hydrogenating said intermediate (V) to yield an intermediate
(VI) having the general formula
(VI)
<IMG>
reacting said intermediate (VI) with an alkyl magnesium bro-
mide of the general formula
(VII)
<IMG>
14

to yield an intermediate and then hydrolyzing said interme-
diate.
4. A process as claimed in claim 2, in which the com-
pound of formula (VIII) ia prepared by reacting cyclopentyl-
amine or cyclohexylamine with a ketone of the general formula
(II)
<IMG>
to yield an azomethine having the general formula (IX)
<IMG> (IX)
where m is 1 or 2; reacting the azomethine with a Grignard
reagent having an alkyl group of from 1 to 5 carbon atoms
to yield an enaminium salt; reacting the enaminium salt with a
vinylnitrile of the general formula
(IV)
<IMG>
to yield a reaction product and then hydrolyzing said reac-
tion product to yield a compound of the general formula
<IMG> (V)
hydrogenating compound (V) to yield a compound of the general
formula

<IMG> (VI)
reacting compound (VI) with an alkyl magnesium bromide of
the general formula
C2H5 ? MgBr (VII)
to yield an intermediate and then hydrolyzing said inter-
mediate.
5. A method of combating insects comprising subjecting
said insects to the 2,3-dihydropyran set forth in claim 1
in an amount sufficient to attract said insects to a speci-
fic location.
6. The method of claim 5, wherein said 2,3-dihydro-
pyran is applied in conjunction with a solid or liquid
carrier.
7. The method of claim 6, wherein said 2,3-dihydro-
pyran is placed in traps.
8. The method of claim 5, wherein the insect being
combatted is the tobacco beetle Lasioderma serricorne F.
16

Description

L~ ~
The ~resent invention is directed to a 2,3-dihydropyran.
The invention is also directed to processes ~or the prepara-
tion of this compQund and to a methbd ~or the use of the
compound in the control of insects such as tobacco beetles.
4,6-dimethyl~7-hydroxynonane-3-one (Serricornin~ is a
known pheromone component of the female tobacco beetle
Lasioderma serricorne F.; see Tetrahedron Letters _ , 2361
(1979).
The present invention is based on the discovery that
2,6-diethyl-3,5-dimethyl-2,3-dihydro-4H-pyran (anhydroserri-
cornin) is a further, hitherto unknown, pheromone component
of the female tobacco beetle Lasioderma serricorne. The
concentration of anhydroserricornin in the sexual lure of
the tobacco beetle is about 10 times smaller than that of
the serricornin; however, with respect to its sexual luring
action and mating inducing action, anhydroserricornin has,
surprisingly, been found to be about 1,000 times more power-
ful than serricornin.
~ '~

~6C~2~
Accordin~l~, the invention i~ directed to a 2~3-dih~dro-
p~ran of the ~enera,l ~oxmula,
C~3 CH3
/\0~
2 5 C2H5
The compound o~ general ~ormula ~I~ has several asymmetric
centers and the various optical isomers of the compound are
wlthin the scope of the present invention.
Although the 2,6-diethyl-3,5-dimethyl-2,3-dihydroxy-4H-
pyran occurs naturally as a pheromone component of the female
tobacco beetle Lasicderma serricorne, it is of no practical
value due to its low concentration therein, and the diffi-
culties of separating it into a pure form which then may
be used to combat insects as will be disclosed below.
The compound of the present invention may be prepared by
the reaction of a heterocyclic nitrogen compound with a ketone
in the presence of a condensing agent to yield an enamine.
The enamine is then reacted with a vinylnitrile; the result-
ing intermediate is hydro~enated and then reacted withethyl magnesium bromide and hydrolized to yield a hydroxy
ketone. The hydroxy ketone is then cyclized to yield the
2,3-dihydropyran.
Alternatively the compound of the present invention may
be prepared starting with a cycloalkyl amine of 5 to
~.'
J,~ . _

~L~6~Z4~
6 carhons which is reacted with a ketone to yield an azo-
methi~ne, The azomethine i~s reacted with an alkyl Grignard
rea~ent having l to 5 carbons to give an enaminium salt
which is then converted by reaction with a vinylnitrile and
subsequent h~drolysis and hydrogenation to a hydroxy alkyl
nitrile. This intermediate is then reacted with ethyl
magnesium bromide and hydrolized to yield a hydroxy ketone
which is then cyclized to yield the 2,3-dihydropyran.
The 2,3-dihydropyran is used as a synthetic lure in a
method to detect insects comprising applying the compound
of the present invention to a suitable carrier to act as a
baited trap. ~lternatively the insects may be aombated
directly by administering an overdose of the compound or by
combining the compounds with an insecticide or other insect
control agent.
The compound of the present invention has the general
formula
CH3 3
O ~
C2H5 C2H5
~'

~Z4~D
The compound o~ the invention can be obtained by a pro-
ces~ in which pyrrolidi~ne, piperidine o~ morpholine is
reacted with a ketone o~ the ~eneral formula
J ~ tII)
C2H5 CH -CH3
in the presence o~ a condensing a~ent, for example titanium
tetrachloride or a carbodiimide, to give an enamine of the
general ~ormula
~ ~
N (IIIa)
/~ .
C2H5 CH3
with n being 1 or 2, or
~ ~
) (IIIb)
N
3Q 2 5 CH3
~ 4 -

~6~4~
The compounds (~IIa and b) are reacted with a vinylnitrile
of the ~eneral ~ormula
CH3
(IV)
CN
to give a comp4und o~ the general ~ormula
CH3 ~ `H (V)
C2H5 ~ N
the compound (.V) is h~drogenated to give a compound of the
general formula
3 ~ CH3
I (VI)
H ~
C2H5
the compound of formula (VI~ is reacted with ethyl magnesium
bromide of the general formula
C H -MgBr (VII)
and the resulting intermediate is hydrolysed to give a com-
pound of the general formula
C 3 ~ CH3
1 ¦ (VIII)
/ ~ H ~
C2H5 C2H5

z~
The compound .(VIII) thus ob.tained is cyclized~to giye the
2,3-dih~dr~p~xan (~,
Alternat~vely the 2~3-dihydrapyran may be prepared
starting with c~clopent~lamine or cyclohexylamine which is
reacted with a ketone of the general formula II to give an
azomethine of the general formula
(CIH2)m \ / 2 5
~ N = C ~ (IX)
~ CH2-CH3
in which m is 1 or 2.
The azomethine IX is then reacted with a Grignard re-
agent of the general formula
R MgX (X)
.
where R is an alkyl group having from 1 to 5 carbon atoms
and X is a halogen atom. The resulting reaction product
is an enaminium salt of the general forrnula..
~ ~ / C2H~ (XI)
Compound (XI) is then reacted with a vinylnitrile of
the general formula (IV) and is then subsequently hydroliæed
to yield a compound of the general formula (V). Compound
(V) is hydrogenated to yield (VI), reacted with ethyl
magnesium bromide (VII) and hydrolysed to yield (VIIIl which
is then cyclized to yield the 2,3-dihydropyran ~I).
~(

` ~6(~0
The invention is further dixected to the use of 2,3-
dihydropyran of the general formula (Il or the early detec-
tion, localisation and com~ating of insect pests, particularly
Lasioderma -serricorne F. The compound of the present inven-
tion may be used in methbds to detect in~estations, to de-
lineate infestations and to estimate insect populations. In
addition, the present invention provides a means for inter-
fering with and confusing mating communication of insects.
Alternatively, insects ma~ be trapped using the compound as
an attractant or directly destroyed using the compound in
conjunction with insecticides.
For these purposes, the compound of the invention, which
is a synthetically prepared lure, can be applied in tobacco
store rooms or other infested areas in an amount sufficient
to attract the insects to a specific location. For example
the compound may be used in baited traps with customary solid
or liquid carrier~, insecticides and/or insect control agents.
Examples o~ suitable carrier materials are paper, corrugated
board, plastics, rubber and the like. In this manner, even
a trivial attack by tobacco beetles can be detected, so that
suitable measures for combating them can be taken in time.
The insects can also be directly combated, for example by
administering an overdose of the sexual lure and thereby
interfering with the mating communication or by administering
a combination of this substance with insecticides or insect
control agents.
.~, .. .

Z ~0
-B-
EXAMPLE
Preparat~n of Anhydroserricornin
The preparations of 2,6-diethyl-3,5-dimethyl-2,3-
dihydroxy-4H-pyran (anhydroserricornin) is described
below.
A. N-~1-Ethyl-1-propenyl)-pyrrolidine
A solution of 104.35 9 of titanium tetrachloride
(0.55 mol) in 100 ml of pentane was added dropwise to a
mixture of 86.15 g of pentan-3-one (1 mol), 213.36 g of
pyrrolidine (3 mols) and 1.8 1. oE pentane, under dry
nitrogen. During this process, the temperature of the
reaction mixture was kept between 0C and 10C by cooling
with ice. The mixture was then stirred for a few more
hours at room temperature and was left to stand overnight.
The pentane was decanted off from the precipitate, and the
latter was carefully hydrolyzed with ice. The aqueous
phase was rendered alkaline with dilute KOH and was
extracted with ether.
The combined organic phas~s wer~ dried over sodium
sulphatet the solvent was removed and the residue was
distilled.
Yield: 74.8 g s 53.7 ~; bp. - 71 - 73C/15 mm
- Literature reference: analogously to WO A~ White,~
H. Weingargen, J. Org. Chem. 32, 213 (1967). ,
B. 5-Oxo-2,4-dimethylheptanitrile
A solution of 63 y ~0.425 1~ of A as prepared above
and 30.3 g (0.425 mol) of methacrylonitrile is heated
under reflux to a boil for 20 hours in 500 ml of absolute

2'~
.~
ethanol. 120 ml of water are then added to the mixture,
and the latter i5 again boiled for 90 minutes. The bulk
of the solvent is then removed; 300 ml of water are added
to the mixture; and the mixture is extracted several time
S with ether. The ether phase is washed several times with
dilute HCl, dried over sodium sulphate, ooncentrated and
distilled in vacuo.
Yield: 32.3 g = 46.6 % bp. - 107 - 113C/15 mm
Literature reference: analogously to G. Storck et al~,
J.A.C.S. 85, 207 (1967).
C. 5-Hydroxy-2,4-dimethylheptanitrile
32.3 g (0.211 mol) of B are carefully added dropwise
to a solution of 5.15 g (0.136 mol) of sodium borohydride
in 500 ml of absolute ethanol and the mixture is then
stirred for two days~ The hydrolysis is effected with
approximately 100 ml of dilute HCl. The solvent is then
stripped off, and the residue is taken up with ether,
washed with water and dried over sodium sulphate. After
the solvent has been removed, the residue is distilled in
vacuo.
Yield: 2S.5 9 ~ 77 %; bp. = 130aC/15 mm
Literature reference: analogously to Organikum
D. 4,6-Dimethyl-7-hydroxy-3-nonanone
~5~5 9 (0.164 mol) of C in 50 ml of absolute ether
are carefully added dropwise to a solution of 0.41 mol of
ethyl-magnesium bromide (obtained from 44.8 g of ethyl
bromide and 10 9 of magnesium chips~ in 660 ml of absolute
ether, and the solution is heated under reflux to the boil
for 3 hours. The mixture is thereafter hydrolyzed over-
night with saturated ammonium chloride solution, the ether

~L6~
- 1 O-
phase is separated off, the aqueous phase is extracted
several times with ether and the combined organic phases
are dried over magnesium sulphate.
The crude product is not isolated, but is immediately
further processed.
Serricornin can also be isolated from the erude
product after removal of the solvent (in a neutral medium).
The process according to the stages A to D thus also
represents an excellent process for the preparation of
serricornin.
E . 2, 6 -Diethyl-3,5-dimethyl -2, 3-dihydro-4H-pyran
The ether phase contained D is stirred for approxi-
mately 1 hour over 10% strength hydro~hloric acid and
separated off, and the aqueous phase is extracted several
times with ether. The combined ether extracts are dried
over a mixture of sodium sulphate and sodium carbonate, the
solvent is removed and the residue is distilled in vacuo.
Yield: 7.3 g - 26.5 %; b~. = 89 - 93C/20 mm
The anhydroserricornin obtained according to the pro-
cedure above is identical with natural anhydroserricornin
in the sexual lure of the female tocacco beetle Lasioderma
serricorne~ By means of a gas chromatographic examina~ion
of a pheromone extract from female tobacco beetlea which had
not mated, natural anhydroserricornin was first detected and
isolated. A gas chromatograph Fractovap 2101 of Messrs.
Carlo Erba, with a glass capillary (WCOT ~wall coated open
tube] coated with Superox as the separating phase) r length
25 m, diame~er 0.2 mm, was used for this purpose. Helium
(3 ml/min) was used as the carrier gas; the split was 1:20;
the temperature pro~r2m was established as follows:

Temperature program: 60 to 180~C at 3.3C/min.
The anhydroserricornin peak appeared after about 4
minutes; the peak of the serricornin appeared after about
20 minutes.
The structure of anhydroserricornin was determined by
mass spectroscopy and was finally confirmed by an indepen-
dent synthesis according to the example above
Pheromone Activity
Tests for comparing the pheromone activities of
serricornin and anhydroserricornin are reported below.
Lasioderma serricorne, which also attack the tissue
of plant species other than Nicotiana tabacum, were bred
from crushed corn with an additive of 5% of dried beer
yeast, at 26 + 1C and at 55+5~ relative atmospheric
humidity, and with a photoperiod of 14 hours light and 10
hours darkness. Male and female beetles were recognized
either by external distinguishing characteristics of the
pupae, or by microscopic examination of the sex organs of
the imagines.
For the comparison of the pheromone activites of
serricornin and anhydroserricornin, tests were carried out
using laboratory-bred populations of tobacco beetles.
- 50 male and 50 female tobacco beetles, at an age of 5 to
10 days after the emergence from the pupal state, were
conditioned for 24 hours in a 2 l~ glass vessel, covered
with perforated aluminium foil which has a central slit.
Rectangular strips of filter paper (12 x 3 cm), împreg-
nated with increasing quantities of sQrricornin or anhydro-
serricornin, were hung from the covering of the glassvessels. Soon thereafter, the male beetles were observed

2 1~(~
to fly in the direction of the small region (diameter about
8 mm) which contains one or other of the abovementioned
components. After landiny, the beetles ~ravel in a cir-
cular and zigzag-like pattern to the pheromone source,
where they aggregate for varying lengths o~ tlme. The
number and duration of the visits and copulation attempts
prove to be dependent on the component present and the
dosage (observation time 30 min.). A comparison of these
parameters shows that the ac~tivity of anhydroserricornin
1~ is about l,QOO times greater than that of the serricornin.
Within a range of 10 6 _ 10 2 micrograms, the increase in
the attractive action in the case of anhydroserricornin
is considerably greater than for serricornin. For a
dose of 10 1 micrograms and more, an adaptation to both com-
ponents is shown (cf. Fig. 1). In the presence of 10 ~up to la micrograms of anhydroserricornin, male tobacco
bettles gather in great numbers on both sides of the treated
section of paper and attempt to copulate with one another.
Serricornin applied in the same quan~ity merely causes a
2Q few bettles to perform this gathering and copulation.
3Q
- 12 -
~ A