Synthesis and pesticidal activity of aminoesters of (+)-α-pinene

Article abstract of DOI:10.1007/s10600-008-9088-x

Optically active (-)-(1R,2R,3R) aminoesters of isopinocampheol (2,6,6-trimethylbicyclo[3.1.1]heptan-3-ol) were synthesized from (+)-α-pinene. The antifidant, juvenoidal, growth-regulating, and herbicidal activities of the newly synthesized compounds were

Full text of DOI:10.1007/s10600-008-9088-x

Chemistry of Natural Compounds, Vol. 44, No. 4, 2008
SYNTHESIS AND PESTICIDAL ACTIVITY OF
AMINOESTERS OF (+)-
α-PINENE
G. V. Kalechits1 and N. G. Kozlov2*
UDC 547.233.07
Optically active (−)-(1R,2R,3R)aminoesters of isopinocampheol (2,6,6-trimethylbicyclo[3.1.1]heptan-3-ol)
were synthesized from (+)-α-pinene. The antifidant, juvenoidal, growth-regulating, and herbicidal activities
of the newly synthesized compounds were studied.
Key words: α-pinene, aminoesters of isopinocampheol, pesticidal activity.
Pinane compounds (2,6,6-trimethylbicyclo[3.1.1]heptane), in particular oxygenated and amino derivatives, are
attractive chemicals not only for their unique structure and availability but also for the potential of practical application. The
principal raw material for preparing pinane compounds is the dominant component of pine turpentine (Pinus silvestris L.),
α-pinene, based on which a wide range of compounds with various types of biological activity has been synthesized [1-3].
In continuation of work [4-6] on the synthesis of functionally substituted pinane derivatives and the study of their
spectrum of biological activity, we synthesized the previously unreported optically active aminoesters of isopinocampheol.
Isopinocampheol (−)-(1R,2R,3R-pinan-3-ol) (1) was prepared by oxidative hydroboration of (+)-α-pinene by the
literature method [7]. Then, reaction of secondary terpene alcohol 1 with chloroacetylchloride in CH Cl in the presence of
2
2
pyridine at the boiling point produced the (−)-(1R,2R,3R) monochloroacetate of isopinocampheol (2) in quantitative yield.
Alkylation with primary (cyclohexylamine) and secondary (dimethylamine, diethylamine, dibutylamine, morpholine, and
piperidine) amines by 2 was performed in diethylether solution. Because the Cl atom in 2 is activated by the carbonyl in the
α-position, the (−)-(1R,2R,3R) aminoesters 3-8 were produced in preparative yields. It is well known that the product yield in
alkylation reactions increases with increasing basicity of the amine. The basicity of the amino group increases in the order
dimethyl-, diethyl-, and dibutylamine. However, the yield of 5 was slightly less due to steric hindrance of dibutylamine. The
better availability of the N atom in piperidine gave a higher yield for 8. We prepared the corresponding (−)-(1R,2R,3R)
hydrochlorides 9-14 and (−)-(1R,2R,3R) methyliodides 15-19 from the synthesized aminoesters. Table 1 lists the yields and
physical chemical constants of the synthesized compounds.
O
O
HNR R
1 2
Et O
2
ClCOCH Cl
Cl
NR R
1 2
2
OH
O
O
CH Cl , Py
2
2
1
2
3 - 8
R1R2 = CH3 (3); R1R2 = C2H5 (4); R1R2 = C4H9 (5); R1 = H, R2 = C6H11 (6)
NR1R2 = morpholine (7); NR1R2 = piperidine (8)
The structures of 2-8 were confirmed by elemental analysis and PMR, IR, and mass spectroscopy.
The PMR spectrum of 2 was characterized by a resonance for the OCOCH Cl protons as a doublet with integrated
2
intensity2H at 4.34 ppm. The spectra of3-8 had resonances for the COCH NR R protons as a doublet with integrated intensity
2
1 2
2H at 3.32 ppm. Resonances of the pinane protons and substituents on the N atom were characteristic for such compounds [8].
1) Institute of the Chemistry of New Materials, National Academy of Sciences of Belarus, 220141, Minsk, ul.
F. Skoriny, 36, e-mail: galvik@ichnm.basnet.by; 2) Institute of Physical Organic Chemistry, National Academy of Sciences of
Belarus, 220072, Minsk, ul. Surganova, 13, e-mail: loc@ifoch.bas-net.by. Translated from Khimiya Prirodnykh Soedinenii,
No. 4, pp. 359-362, July-August, 2008. Original article submitted July 17, 2007.
0009-3130/08/4404-0446 ©2008 Springer Science+Business Media, Inc.
446

TABLE 1. Physical Chemical Constants of 2-19
20
Compound
Yield, %
bp, mm Hg; mp, °C
[α]D20, deg
nD
Emp. formula
M+
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
88.3
87.6
84.3
73.7
84.9
86.9
87.2
86.8
87.5
81.2
87.5
88.4
90.3
76.0
77.8
73.9
77.8
80.0
119-120 (4)
103-105 (3)
119-120 (3)
155-157 (3)
157-159 (2)
150 (3)
144-145 (3)
213-214
232-234
274-275
211-212
181-182
216-218
200-201
156-157.5
137-138.5
170-172.5
189-191
−19.0
−17.1
−17.4
−24.2
−24.3
−10.6
−12.4
−15.0
-
1.4820
1.4735
1.4720
1.4672
1.4780
1.4880
1.4870
C12H19ClO2
C14H25NO2
C16H29NO2
C20H27NO2
C18H31NO2
C16H27NO3
C17H29NO2
C14H26NO2Cl
C16H30NO2Cl
C20H38NO2Cl
C18H32NO2Cl
C16H28NO3Cl
C17H30NO2Cl
C15H28NO2J
C17H32NO2J
C21H40NO2J
C17H30NO3J
C18H32NO2J
230.7
239.3
267.4
313.4
293.4
281.3
279.4
275.8
303.8
359.9
329.9
317.8
315.8
381.2
409.3
465.4
423.3
421.3
-
-
-
-
-
-
-
-
-
-
-
-
-
+0.9
−15.0
−8.3
−10.7
−12.5
−9.4
−10.8
______
[M]+ values of all compounds agree with those calculated.
TABLE 2. Antifidant Activity of 2-19 for Yellow Mealworm Beetles
Protection
degree, %
Protection
degree, %
Compound
Isopinocampheol derivative
Monochloroacetate
Dimethylaminoacetate
Diethylaminoacetate
Compound
Isopinocampheol derivative
2
3
4
5
6
7
8
9
10
20
40
80
25
15
35
30
45
40
11
12
13
14
15
16
17
18
19
Dibutylaminoacetate hydrochloride
Cyclohexylaminoacetate hydrochloride
N-morpholineacetate hydrochloride
N-piperidineacetate hydrochloride
Dimethylaminoacetate methyliodide
Diethylaminoacetate methyliodide
Dibutylaminoacetate methyliodide
N-morpholineacetate methyliodide
N-piperidineacetate methyliodide
40
20
40
85
35
83
30
30
20
Dibutylaminoacetate
Cyclohexylaminoacetate
N-morpholineacetate
N-piperidineacetate
Dimethylaminoacetate hydrochloride
Diethylaminoacetate hydrochloride
The IR spectrum of 2 contained an absorption band for the carbonyl near 1745 cm−1 and for C–O–C near 1260 cm−1.
The C–Cl vibrations appeared at 830 cm−1. The IR spectra of 3-19 showed absorption bands in the range 1750-1735 cm−1 due
to C=O stretching vibrations. The C–O–C stretching vibrations appeared in the range 1260-1230 cm−1; of R3N, at 1260-
1275 cm−1. Compounds 6 and 12 contained a band at 3350 cm−1 that was characterized as N–H stretching vibrations.
Mass spectra of 3-8 exhibited peaks for molecular ions, the intensityof which reached 10% of the maximum, and peaks
for decomposition products from electron impact via loss of amino groups: 3, / 44; 4, 72; 5, 128; 6, 97; 7, 86; 8, 84. All
m z
compounds gave ionic fragments with / 137, pinyl; 44, O–C–O; and 58, OCOCH .
m z
2
The antifidant activityofthe isopinocampheol aminoesters and their salts werestudiedrelative tothe yellowmealworm
by the literature method [5]. All tested compounds had more or less antifidant activity. Table 2 lists
beetle
Tenebrio molitor
the results.
Aminoester 4, which contains an -diethylamino group, and its methyliodide 16 in addition to the hydrochloride 14
N
exhibited distinct antifidant activity, the degree of bean-leaf protection for which was above 80%. The solution concentrations
PK for which the leaf protection was 50% were determined for the active compounds. It was 0.24%, 0.18, and 0.15 for 4, 14,
50
447

and 16, respectively. It should be noted for comparison that PK of brestan, triphenyltin acetate (standard), for yellow
50
mealworm beetle was 0.1%. Thus, although the activity of the studied compounds was lower or equal to that of the standard
brestan, the terpenoids and their derivatives are less toxic for warm-blooded animals than the tin-containing preparation and
less polluting of the environment because they are easily biodegraded.
The growth-regulating activity of 2-19 was studied using the literature method [9] in cell culture of sugar beet and
chlorella alga. The test results showed that 2, 5, 8, 9, 15, and 16 had distinct growth-regulating activity relative to chlorella.
Compound 16 acted as a retardant under hothouse conditions; 7, as a plant growth inhibitor. This indicates that searching this
series of compounds for herbicides and photosynthesis inhibitors is promising.
The herbicidal activity of 2-19 was studied using the literature method [10] under hothouse conditions on biotests of
oats, soy, and mustard. Compounds 2, 9, 14, 16, 17, and 19 suppressed development of the test plants by 20-80%. The
herbicidal activity of the prepared compounds was evident only if they were applied to vegetative plants. This is probably
explained by the difficulty of penetrating through the sprouts rather than through the vegetative organs of the plants.
Compounds 2-19 were tested as juvenoids by topical administration of test liquids on six-hour pupae of yellow
mealworm beetle. No noticeable activity was noted.
The toxicity of 2-19 for root-knot nematode larvae in a laboratoryin vitro experiment with concentrations of 0.5-2.0%
for the tested compounds did not exceed 40%.
The results for the pesticidal activityof the isopinocampheol aminoesters showed that 3 had moderate activitywhereas
4 exhibited high pesticidal activity, especially for its methyliodide 16. The activity of the compounds decreased with a further
increase of the molecular weight of the amino group. The only exception was piperidine derivative 8 and its hydrochloride 14.
The results can be used further for directed synthesis of biorational pesticides of the terpenoid series.
EXPERIMENTAL
IRspectra in a thin layer between KBr were recorded on a UR-20 spectrophotometer in the range 400-3800 cm−1. PMR
spectra in CDCl with internal standard TMS were recorded on a WM-360 spectrometer. Mass spectra were recorded in a
3
Varian MAT-311 instrument with cathode emission 1000 mA, ionizing electron energy 70 eV, vaporizer temperature 150-
200°C, and ion-source temperature 200°C. Specific rotations in ethanol at room (20-25°C) temperature were measured on a
Jasko J-20 polarimeter. Melting points were determined on a Kofler microheating stage. GC analysis was performed on a
Vyrukhrom instrument with a FID, 2000 × 3 mm column, Chromaton N-AW-DMCS solid support, Reoplex-400 stationary
phase, 100°C, and carrier gas (N ) at 50 mL/min.
2
20
Isopinocampheol (1) was prepared by oxidative hydroboration by the literature method [7]; α-pinene (n
1.4655,
D
20
[α]
+30.9°), isolated from pine turpentine byfractionational distillation (60 theor. plates). The resulting secondary alcohol
D
20
20
(1) had mp 56-57°C, [α]
−21.8° (c 1%, benzene); lit. [7] mp 55-57°C, [α]
−32.8° (c 10, benzene).
D
D
Isopinocampheol Monochloroacetate (2). A solution of1 (15.4 g, 0.1 mol) in CH Cl (50 mL) and pyridine (7.9 mL)
2
2
was stirred vigorously, treated dropwise with a solution of monochloroacetic acid chloride (11.3 g, 0.1 mol) in CH Cl (25 mL),
2
2
heated to 40°C, and refluxed for 2-5 h with constant stirring. When the reaction was finished the mixture was diluted with water
(100 mL). The organic layer was separated, washed twice with water, and passed over a column of Al O with elution by
2
3
CH Cl . Solvent was distilled off. Vacuum distillation produced isopinocampheol chloroacetate (20.3 g, 88.3%). IR spectrum
2
2
(ν, cm −1): 2960, 2875 (C–H), 1745 (C=O), 1475, 1420, 1370, 1320, 1260 (C–O–C), 1190, 1155, 1006, 980, 830 (C–Cl). Mass
+
spectrum (m/z): 230 (10%) [M] , 137, 121, 107, 93 (100), 78, 67, 58, 56, 49, 44, 35. PMR spectrum (δ, ppm): 1.06 (d, CH
3
on C-2), 1.11 [s, (CH ) C on C-6], 1.2 (m, H-7e), 1.34 (m, H-4a), 1.38 (m, H-4e), 1.46 (m, H-2a), 1.64 (m, H-1), 1.65 (m, H-5,
3 2
H-7a), 4.34 (d, COCH Cl), 4.69 (m, H-3a).
2
Isopinocampheol Aminoacetates 3-8 (general method). Equimolar amounts of isopinocampheol monochloroacetate
(2) and the appropriate amine (dimethyl-, diethyl-, dibutyl-, cyclohexylamine, morpholine, and piperidine) were refluxed in
diethylether for 2-5 h. The reaction mixture was treated with KOH solution (5%). The product was extracted with ether. The
ether extracts were washed with water and dried over calcined CaCl . Ether was distilled off. The residue was vacuum distilled.
2
Isopinocampheol Aminoacetate Hydrochlorides 9-14 (general method). Dry HCl was passed through an ether
solution of 3-8. The resulting precipitate was separated by filtration, washed on the filter with solvent, dried in air, and
recrystallized from CH Cl if needed.
2
2
448

Isopinocampheol Aminoacetate Methyliodides 15-19 (general method). A solution of 3-8 in benzene and a 1.5-fold
excess of methyliodide was heated on a boiling water bath for 5-6 h and left overnight. The resulting precipitate of the
aminoester (3-8) methyliodide was filtered on a Schott filter, washed with a small amount of benzene, pressed, and dried in air
or in a drying cabinet at 40-50°C.
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