CN101558758A - L-alpha-amino acid ester contained Z-configuration anabasine pesticide and preparation method thereof - Google Patents
L-alpha-amino acid ester contained Z-configuration anabasine pesticide and preparation method thereof Download PDFInfo
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- CN101558758A CN101558758A CNA2009100573248A CN200910057324A CN101558758A CN 101558758 A CN101558758 A CN 101558758A CN A2009100573248 A CNA2009100573248 A CN A2009100573248A CN 200910057324 A CN200910057324 A CN 200910057324A CN 101558758 A CN101558758 A CN 101558758A
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Abstract
The invention discloses an L-alpha-amino acid ester contained Z-configuration anabasine pesticide and a preparation method thereof. The structure is shown by a general formula (I). The prior anabasine pesticide only has a function of disinsection and has no function of promoting the growth of crops. The preparation method comprises the following steps: preparing a hydrochlorate of an L-alpha-amino acid methyl ester or ethyl ester; adding the prepared hydrochlorate of the L-alpha-amino acid methyl ester or the ethyl ester, nitenpyram, 37 percent formaldehyde and triethylamine into a round-bottom three-necked flask; and placing the round-bottom three-necked flask containing the solution in a microwave reactor, controlling the reaction temperature not more than 75 DEG C, and carrying out microwave reaction for 30 minutes to prepare the L-alpha-amino acid ester contained Z-configuration anabasine pesticide shown by the general formula (I). The L-alpha-amino acid ester contained Z-configuration anabasine pesticide has the advantages of high efficient insecticidal activity, good insecticidal effect, low toxicity, safety of human beings and livestock, crop growth promotion, simple using method, simple preparation method, and short reaction time.
Description
Technical field
The invention belongs to agricultural chemical insecticide, specifically a kind of Z formula configuration anabasine insecticide and preparation that contains the L-α-An Jisuanzhi.
Background technology
Anabasine insecticide be after organic phosphates, carbamates, pyrethroid insecticides the 4th generation insecticide.The anabasine material is as nAChR (nAChRs) activator, nervous system (nAChRs) to insect optionally works, it has not only shown high-affinity to (nAChRs), but also has shown unionized and medium physicochemical characteristics such as water-soluble.Because it has the unique insecticidal mechanism and the performance of high-efficiency low-toxicity, become the higher effective and lower toxic pesticide new varieties that modern agriculture needs rapidly.Because anabasine compound has the existence of C=N or the two keys of C=C, so anabasine compound has Z formula and two kinds of configurations of E formula.Japan Wu Tian company use chloro-pyridine compounds and acetylcholinesterase conditioning agent have synthesized and have contained chloro pyridine nitroethylene base class compound Nitenpyram, are good insecticides in the E formula configuration anabasine, and sucking property insect is had special efficacy; Du pont company has made the Nitenpyram compound that the Z of higher insecticidal activity formula configuration is arranged by introducing heterocycle.But these not the anabasine pesticide of isomorphism type only have insecticidal action, do not have the function that promotes crop growth.Amino acid is the neccessary composition that constitutes life; Aminoacid ingredient in the agricultural chemicals also has the important function that promotes crop growth except having insecticidal effect.But up to now, countries in the world there is no the production and the use of the anabasine insecticide agricultural chemicals that contains the L-α-An Jisuanzhi.Patent documentation both domestic and external and public publication are not seen the report of the anabasine insecticide that contains the L-α-An Jisuanzhi yet.
The present invention is that raw material has synthesized the serial Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi with the L-a-amino acid in the world first, and has measured the efficient insecticide activity of this insecticide, has realized the new breakthrough of domestic and international anabasine insecticide agricultural chemicals.
Summary of the invention
The present invention seeks to for a kind of Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi that had not only had the efficient insecticide activity but also can promote crop growth is provided;
Another object of the present invention provides the Z formula configuration anabasine method for producing insecticide of the above-mentioned L-of containing α-An Jisuanzhi.
Purpose of the present invention is achieved through the following technical solutions.
Contain the Z formula configuration anabasine insecticide of L-α-An Jisuanzhi, general formula (I) is:
Wherein: R is hydrogen, methyl (CH
3), isopropyl (CH (CH
3)
2), benzyl (CH
2C
6H
5), isobutyl group (CH
2CH (CH
3)
2), methylthio ethyl (CH
2CH
2SCH
3), rubigan (p-Cl-C
6H
5) in a kind of.
R ' is methyl (CH
3), ethyl (C
2H
5), n-pro-pyl (n-C
3H
7), normal-butyl (n-C
4H
9) in a kind of.
The Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi of general formula (I) expression, the preparation method is as follows:
The hydrochloride of preparation L-a-amino acid methyl esters or ethyl ester, general formula (II):
A. the L-a-amino acid is dissolved in 1mol/L thionyl chloride-methanol solution, the control temperature prepares L-a-amino acid methyl ester hydrochloride below-5 ℃;
B. the L-a-amino acid is dissolved in ethanolic solution, control temperature below 0 ℃, dripping thionyl chloride, preparation L-a-amino acid carbethoxy hydrochloride;
(2) preparation contains the Z formula configuration anabasine insecticide of L-α-An Jisuanzhi, and general formula (I) as above.
A. the L-a-amino acid methyl esters of above-mentioned (1) preparation or hydrochloride (II), Nitenpyram, 37% formaldehyde, the triethylamine of ethyl ester are put in the three-necked round bottom flask;
B. the three-necked round bottom flask that above-mentioned solution will be housed is put into microwave reactor, and the control temperature is below 75 ℃, and microwave reaction 30 minutes makes the Z formula configuration anabasine insecticide that general formula (I) contains the L-α-An Jisuanzhi.
The Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi with general formula (I) is a raw material, makes emulsion, aqueous suspension and water emulsion pesticide.
The reaction equation of above-mentioned preparation process is:
Main points of the present invention are:
With the L-a-amino acid is raw material, both had the efficient insecticide activity with the best high-efficiency low-toxicity anabasine insecticide Nitenpyram of insecticidal effect in the world today is synthetic, had the Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi that promotes the crop growth function again.
The inventive method makes the hydrochloride (II) of L-α-An Jisuanzhi earlier, makes the Z formula configuration anabasine insecticide (I) that contains the L-α-An Jisuanzhi again.
When synthetic (II), the hydrochloride of different L-α-An Jisuanzhi can adopt diverse ways:
In the preparation of L-a-amino acid ethyl ester, the L-a-amino acid is dissolved in ethanol temperature control dripping thionyl chloride again.When preparation L-a-amino acid methyl ester hydrochloride, adopt 1mol/L thionyl chloride-methanol solution, this synthesising method reacting condition gentleness, the reaction time is short, and easy to operate, product does not need further purification, and yield and purity are all higher.
Adopt novel microwave process for synthesizing to improve productive rate and also greatly shortened the reaction time.For example adopt heating reflux method to need 6 hours usually, the present invention adopts microwave process for synthesizing only to need 30 minutes.
The Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi with general formula (I) expression has good insecticidal activity, and the effective active composition of useful as pesticides is made the various formulations of pesticide.Example emulsion, aqueous suspension and aqueous emulsion etc.
Advantage of the present invention is:
1, has efficient insecticide activity, good disinsection effect.
2, toxicity is low, the person poultry safety.
3, promote crop growth.
4, using method is easy.
5, the preparation method is simple.
6, the reaction time is short.
The present invention is that raw material has synthesized the serial Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi with the L-a-amino acid in the world first, has tangible novelty and creativeness; The present invention has measured the efficient insecticide activity of this insecticide, has significant practicality in modern agriculture production.
Embodiment
Further set forth technical characterstic of the present invention below in conjunction with specific embodiment.
A kind of Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi with efficient insecticide activity, represent with general formula (I):
Wherein: R is hydrogen, methyl (CH
3), isopropyl (CH (CH
3)
2), benzyl (CH
2C
6H
5), isobutyl group (CH
2CH (CH
3)
2), methylthio ethyl (CH
2CH
2SCH
3), rubigan (p-Cl-C
6H
5) in a kind of; R ' is methyl (CH
3) and ethyl (C
2H
5), n-pro-pyl (n-C
3H
7), normal-butyl (n-C
4H
9) in a kind of.
The example of the Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi of the present invention's preparation is:
(Ia), (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine ethyl acetate;
(Ib), (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-isopropyl)-ethyl acetate;
(Ic), (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-benzyl)-ethyl acetate;
(Id), (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-methyl)-methyl acetate;
(Ie), (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-benzyl)-methyl acetate;
(If) (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-isopropyl)-methyl acetate;
(Ig), (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-isobutyl group)-methyl acetate.
Embodiment 1:
Preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine ethyl acetate (Ia):
The glycine of 20mL absolute ethyl alcohol and 3.76g is placed the three-necked round bottom flask of 100mL, bathe cooling and drip the new thionyl chloride 6mL that steams with cryosel, temperature control added below-5 ℃ in about 30 minutes.Naturally rising to after the room temperature heating is back to solid and all dissolves the cold slightly white foam shape solid that promptly obtains after continuing to reflux 15 minutes.Excessive thionyl chloride is removed in decompression, and suction filtration is washed with ether in the cooling back, with absolute ethyl alcohol-ether be recrystallized white needle-like crystals (IIa).
With 5.30g Nitenpyram, 3.33g glycine ethyl ester hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 65 ℃ in 5 minutes, and decompression steams solvent after being incubated 30 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: benzinum=column chromatography got yellowish colour purity product in 2: 1, and productive rate is 82.8%.
Elementary analysis: measured value C%51.32 H%6.08 N%17.60
Calculated value C%51.35 H%6.10 N%17.58
IR (KBr compressing tablet cm
-1): 2,951 2,872 1744 (C=O), 1546 (NO
2) 1303 (VasC-O-C) 1251 (VaC-O-C), 1H NMR (CDCl3/400MHz): 8.238-8.243 (d, J=2.0Hz, 1H, pyridine hydrogen), (7.636-7.662 m, 1H, pyridine hydrogen), 7.242-7.263 (d, J=8.4Hz, 1H, pyridine hydrogen), 4.429-4.466 (d, J=14.8Hz, 1H), 4.111-4.165 (q, J=7.2Hz, 2H, COOCH2), 4.067-4.106 (d, J=15.6Hz, 1H), 3.648-3.746 (m, 4H), 3.368 (s, 2H, NCH
2CO) 3.140-3.228 (m, 1H), 2.984 (s, 3H, NCH
3), 2.808-2.891 (m, 1H), 1.204-1.240 (t, J=7.2Hz, 3H, COOCH
2CH
3), 1.083-1.119 (t, J=7.2Hz, 3H, NCH
2CH
3).
Embodiment 2:
Preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-isopropyl)-ethyl acetate (Ib):
The L-alpha-aminoisocaproic acid of 20mL absolute ethyl alcohol and 5.85g is placed the three-necked round bottom flask of 100mL, bathe cooling and drip the new thionyl chloride 6mL that steams with cryosel, temperature control added below-5 ℃ in about 30 minutes.Naturally rising to after the room temperature heating is back to solid and all dissolves the cold slightly white foam shape solid that promptly obtains after continuing to reflux 15 minutes.Excessive thionyl chloride is removed in decompression, and suction filtration is washed with ether in the cooling back, with absolute ethyl alcohol-ether be recrystallized white needle-like crystals (IIb).
With 5.30g Nitenpyram, 4.67g L-alpha-aminoisocaproic acid carbethoxy hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 70 ℃ in 5 minutes, and decompression steams solvent after being incubated 25 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains orange-yellow oily thing.With ethyl acetate: benzinum=column chromatography got yellow pure product in 3: 1, and productive rate is 84.5%.
Elementary analysis: measured value C%55.56 H%7.11 N%15.43
Calculated value C%55.54 H%7.10 N%15.44
IR (KBr compressing tablet cm
-1): 2,954 2,869 1732 (C=O), 1552 (NO
2) 1301 (VasC-O-C) 1251 (VaC-O-C), 1H NMR (CDCl3/400MHz): 8.301-8.324 (d, J=9.2Hz, 1H, pyridine hydrogen), 7.672-7.763 (m, 1H, pyridine hydrogen), 7.316-7.336 (d, J=8.0Hz, 1H, pyridine hydrogen), 4.511-4.549 (d, J=15.2Hz, 1H), 4.144-4.196 (q, J=7.2Hz, 2H, COOCH
2), 4.113-4.151 (d, J=15.2Hz, 1H), 3.659-3.879 (m, 4H), 3.520-3.556 (t, J=7.2Hz, 1H, NCHCO), 3.223-3.326 (m, 1H), 2.927 (s, 3H, NCH
3), 2.860-2.975 (m, 1H), 1.571-1.749 (m, 1H, CH
2CH), 1.604-1.654 (m, 2H, CH
2CH), 1.267-1.303 (t, J=7.2Hz, 3H, COOCH
2CH
3), 1.150-1.203 (q, J=7.2Hz, 3H, NCH
2CH
3), 0.966-0.981 (d, J=6.0Hz, 3H, CHCH
3), 0.934-0.949 (d, J=6.0Hz, 3H, CHCH
3).
Embodiment 3:
Preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-benzyl)-ethyl acetate (Ic);
L-α-phenyl alanine of 20mL absolute ethyl alcohol and 8.25g is placed the three-necked round bottom flask of 100mL, bathe cooling and drip the new thionyl chloride 6mL that steams with cryosel, temperature control added below-5 ℃ in about 30 minutes.Naturally rising to after the room temperature heating is back to solid and all dissolves the cold slightly white foam shape solid that promptly obtains after continuing to reflux 15 minutes.Excessive thionyl chloride is removed in decompression, and suction filtration is washed with ether in the cooling back, with absolute ethyl alcohol-ether be recrystallized white needle-like crystals (IIc).
With 5.30g Nitenpyram, 5.47g L-α-phenylalanine ethyl ester hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 75 ℃ in 4 minutes, and decompression steams solvent after being incubated 30 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains orange-yellow oily thing.With ethyl acetate: benzinum=column chromatography got yellow pure product in 4: 1, and productive rate is 84.5%.
Elementary analysis: measured value C%59.07 H%6.20 N%14.35
Calculated value C%59.05 H%6.21 N%14.33
IR (KBr compressing tablet cm
-1): 2,937 2,865 1727 (C=O), 1552 (NO
2) 1300 (VasC-O-C) 1250 (VaC-O-C);
1H NMR (CDCl3/400MHz): 8.290-8.300 (d, J=4.0Hz, 1H, pyridine hydrogen), (7.655-7.714 m, 1H, pyridine hydrogen), 7.247-7.343 (m, 5H, Ph) 7.202-7.217 (d, J=6.0Hz, 1H, pyridine hydrogen), and 4.497-4.535 (d, J=15.2Hz, 1H), 4.154-4.191 (d, J=14.8Hz, 1H), 4.084-4.138 (m, 2H, COOCH
2), 3.735-3.920 (m, 4H), 3.213-3.290 (m, 1H), 3.026-3.162 (m, 2H, PhCH
2), 2.871-2.933 (m, 1H), 2.777-2.755 (d, J=8.8Hz 3H, NCH
3), 1.250-1.286 (t, J=7.2Hz, 1H, CH
2CH), 1.135-1.174 (m, 6H).
Embodiment 4: preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-methyl)-methyl acetate (Id).
In 250mL three-necked bottle (being with dry alkali lye absorption plant), add 150mL methyl alcohol, cryosel is bathed and is cooled to below-10 ℃, drip the new thionyl chloride that steams of 21.60mL under the magnetic agitation, the control rate of addition makes reaction temperature be no more than 0 ℃, react and be warming up to room temperature naturally after one hour, thionyl chloride-methanol solution of 150mL 1mol/L.
On the 100mL three-neck flask, reflux condensing tube is installed and (is met CaCl
2And alkali lye absorption plant) dropping funel and thermometer.50mL methyl alcohol is added in the reaction bulb, bathes with cryosel and be cooled to below-10 ℃, stir and slowly drip the new thionyl chloride that steams of 3.6mL down, control rate of addition in the dropping process, with the temperature that keeps reactant liquor below 0 ℃.Dropwise back one hour above-mentioned solution of continuation stirring and be transferred in the 100mL single port flask that fills 4.45g L-α-Bing Ansuan, added hot reflux one hour, removal of solvent under reduced pressure gets white solid.Above-mentioned solid matter is dissolved in thionyl chloride-methanol solution of 50mL 1mol/L, added hot reflux one hour, decompression steams solvent and gets white solid (IId).
With 5.30g Nitenpyram, 3.33g L-α-Bing Ansuan methyl ester hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 65 ℃ in 6 minutes, and decompression steams solvent after being incubated 25 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains orange-yellow oily thing.With ethyl acetate: benzinum=column chromatography got yellow pure product in 2: 1, and productive rate is 86.2%.
Elementary analysis: measured value C%51.32 H%6.08 N%17.60
Calculated value C%51.31 H%6.10 N%17.63
IR (KBr compressing tablet cm
-1): 2,937 2,874 1734 (C=O), 1550 (NO
2) 1303 (VasC-O-C) 1251 (VaC-O-C),
1H NMR (CDCl3/400MHz): 8.306 (s, 1H, pyridine hydrogen), 7.676-7.742 (t, 1H, J=26.4Hz pyridine hydrogen), 7.278-7.332 (t, J=21.6Hz, 1H, pyridine hydrogen), 4.504-4.560 (m, 1H), 4.111-4.190 (t, J=31.6Hz, 1H), and 3.778-3.814 (m, 4H), 3.732 (s, 3H, COOCH
3), 3.575-3.611 (q, J=14.4Hz, 1H, NCHCO), 3.251-3.269 (m, 1H), 2.970 (s, 3H, NCH
3), 2.888-2.923 (m, 1H), 1.397-1.414 (d, 3H, J=6.8Hz, CHCH
3), 1.132-1.150 (q, J=7.2Hz, 3H, NCH
2CH
3).
Embodiment 5:
Preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-benzyl)-methyl acetate (Ie);
In 250mL three-necked bottle (being with dry alkali lye absorption plant), add 150mL methyl alcohol, cryosel is bathed and is cooled to below-10 ℃, drip the new thionyl chloride that steams of 21.60mL under the magnetic agitation, the control rate of addition makes reaction temperature be no more than 0 ℃, react and be warming up to room temperature naturally after one hour, thionyl chloride-methanol solution of 150mL 1mol/L.
On the 100mL three-neck flask, reflux condensing tube is installed and (is met CaCl
2And alkali lye absorption plant) dropping funel and thermometer.50mL methyl alcohol is added in the reaction bulb, bathes with cryosel and be cooled to below-10 ℃, stir and slowly drip the new thionyl chloride that steams of 3.6mL down, control rate of addition in the dropping process, with the temperature that keeps reactant liquor below 0 ℃.Dropwise back one hour above-mentioned solution of continuation stirring and be transferred in the 100mL single port flask that fills 8.95g L-α-phenyl alanine, added hot reflux one hour, removal of solvent under reduced pressure gets white solid.Above-mentioned solid matter is dissolved in thionyl chloride-methanol solution of 50mL 1mol/L, added hot reflux one hour, decompression steams solvent and gets white solid (IIe).
With 5.30g Nitenpyram, 5.15g L-α-phenylalanine methyl ester hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 75 ℃ in 5 minutes, and decompression steams solvent after being incubated 30 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains orange-yellow oily thing.With ethyl acetate: benzinum=column chromatography got yellow pure product in 3: 1, and productive rate is 82.4%.
Elementary analysis: measured value C%58.29 H%5.95 N%14.78
Calculated value C%58.31 H%5.93 N%14.75
IR (KBr compressing tablet cm
-1): 2,949 2,872 1732 (C=O), 1552 (NO
2) 1301 (VasC-O-C) 1252 (VaC-O-C);
1H NMR (CDCl3/400MHz): 8.261-8.266 (d, J=2.0Hz, 1H, pyridine hydrogen), 7.656-7.662 (m, 1H, pyridine hydrogen), 7.271-7.319 (m, 5H, Ph) 7.226-7.243 (d, J=6.8Hz, 1H, pyridine hydrogen), 4.472-4.510 (d, J=15.2Hz, 1H), 4.136-4.174 (d, J=15.2Hz, 1H), and 4.088-4.126 (m, 1H), 3.767-3.871 (m, 4H), 3.725 (s, 3H, COOCH
3), 3.619-3.627 (m, 1H), 3.027-3.053 (m, 2H, PhCH2), 2.877 (S, 3H, NCH3), 1.205-1.245 (t, J=16Hz, 1H, CH2CH), 1.133-1.168 (t, J=14,3H, NCH
2CH
3);
Embodiment 6: preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-isopropyl)-methyl acetate (If).
In 250mL three-necked bottle (being with dry alkali lye absorption plant), add 150mL methyl alcohol, cryosel is bathed and is cooled to below-10 ℃, drip the new thionyl chloride that steams of 21.60mL under the magnetic agitation, the control rate of addition makes reaction temperature be no more than 0 ℃, react and be warming up to room temperature naturally after one hour, thionyl chloride-methanol solution of 150mL 1mol/L.
On the 100mL three-neck flask, reflux condensing tube is installed and (is met CaCl
2And alkali lye absorption plant) dropping funel and thermometer.50mL methyl alcohol is added in the reaction bulb, bathes with cryosel and be cooled to below-10 ℃, stir and slowly drip the new thionyl chloride that steams of 3.6mL down, control rate of addition in the dropping process, with the temperature that keeps reactant liquor below 0 ℃.Dropwise back one hour above-mentioned solution of continuation stirring and be transferred in the 100mL single port flask that fills 5.85g L-alpha-aminoisocaproic acid, added hot reflux one hour, removal of solvent under reduced pressure gets white solid.Above-mentioned solid matter is dissolved in thionyl chloride-methanol solution of 50mL 1mol/L, added hot reflux one hour, decompression steams solvent and gets white solid (IIf).
With 5.30g Nitenpyram, 3.67g L-alpha-aminoisocaproic acid methyl ester hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 65 ℃ in 8 minutes, and decompression steams solvent after being incubated 20 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains glassy yellow grease.With ethyl acetate: benzinum=column chromatography got yellow pure product in 3: 1, and productive rate is 85.7%.
Elementary analysis: measured value C%53.58 H%6.63 N%16.44
Calculated value C%53.60 H%6.62 N%16.45
IR (KBr compressing tablet cm
-1): 2,954 2,869 1732 (C=O), 1552 (NO
2) 1301 (VasC-O-C) 1251 (VaC-O-C),
1H NMR (DMSO/400MHz): 8.304-8.323 (d, J=7.6Hz, 1H, pyridine hydrogen), (7.740-7.810 m, 1H, pyridine hydrogen), 7.464-7.509 (d, J=18.0Hz, 1H, pyridine hydrogen), 4.504-4.515 (d, J=4.4Hz, 1H), 4.191-4.229 (d, J=15.2Hz, 1H), and 3.782-3.929 (m, 4H), 3.624 (s, 3H, COOCH
3), 3.514-3.545 (t, J=12.4Hz, 1H, NCHCO), 3.135-3.184 (m, 1H), 2.980 (s, 3H, NCH3), 2.889-2.915 (m, 1H), 1.476-1.644 (m, 1H, CH2CH), 1.603-1.624 (m, 2H, CH2CH), 1.105-1.123 (q, J=7.2Hz, 3H, NCH2CH
3), 0.929-0.943 (d, J=5.6Hz, 3H, CHCH
3), 0.877-0.891 (d, J=5.6Hz, 3H, CHCH
3).
Embodiment 7: preparation (2H, 6H)-4-[[(6-chloro-3-picolyl) ethylamino-]-2,6-dihydro-3-methyl-5-nitro]-1-pyrimidine-(1 '-isobutyl group)-methyl acetate (Ig).
In 250mL three-necked bottle (being with dry alkali lye absorption plant), add 150mL methyl alcohol, cryosel is bathed and is cooled to below-10 ℃, drip the new thionyl chloride that steams of 21.60mL under the magnetic agitation, the control rate of addition makes reaction temperature be no more than 0 ℃, react and be warming up to room temperature naturally after one hour, thionyl chloride-methanol solution of 150mL 1mol/L.
On the 100mL three-neck flask, reflux condensing tube is installed and (is met CaCl
2And alkali lye absorption plant) dropping funel and thermometer.50mL methyl alcohol is added in the reaction bulb, bathes with cryosel and be cooled to below-10 ℃, stir and slowly drip the new thionyl chloride that steams of 3.6mL down, control rate of addition in the dropping process, with the temperature that keeps reactant liquor below 0 ℃.Dropwise back one hour above-mentioned solution of continuation stirring and be transferred in the 100mL single port flask that fills 7.25g L-α-valine, added hot reflux one hour, removal of solvent under reduced pressure gets white solid.Above-mentioned solid matter is dissolved in thionyl chloride-methanol solution of 50mL 1mol/L, added hot reflux one hour, decompression steams solvent and gets white solid (IIg).
With 5.30g Nitenpyram, 4.34g L-α-valine methyl ester hydrochloride, 3.3mL triethylamine and 3.8mL concentration is that 37% formalin is dissolved in the 30mL ethanol together, the three-neck flask that mixed reaction solution is housed is placed microwave reactor, temperature adjustment is 70 ℃ in 5 minutes, and decompression steams solvent after being incubated 30 minutes, adds that 20mL is water-soluble to be separated and extract at twice with 40mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains glassy yellow grease.With ethyl acetate: benzinum=column chromatography got yellow pure product in 2: 1, and productive rate is 83.2%.
Elementary analysis: measured value C%54.60 H%6.87 N%15.92
Calculated value C%54.63 H%6.88 N%15.90
IR (KBr compressing tablet cm
-1): 2,964 2,875 1731 (C=O), 1553 (NO
2) 1300 (VasC-O-C) 1249 (VaC-O-C),
1H NMR (CDCl3/400MHz): 8.283-8.317 (d * d, J=13.6Hz, 1H, pyridine hydrogen), (7.736-7.788 m, 1H, pyridine hydrogen), 7.310-7.330 (d, J=8.0Hz, 1H, pyridine hydrogen), 4.488-4.496 (d, J=3.2Hz, 1H), 4.130-4.239 (d * d, 1H), and 3.723-3.810 (m, 4H), 3.701 (s, 3H, COOCH
3), 3.632-3.638 (d, J=2.4Hz, 1H, NCHCO), 3.036-3.065 (m, 1H), 2.957 (s, 3H, NCH
3), 2.928-2.949 (m, 1H), 1.217-1.252 (m, 1H, CHCH), 1.039-1.079 (q, J=16Hz, 3H, NCH
2CH
3), 0.961-0.947 (d, J=5.6Hz, 3H, CHCH
3), 0.904-0.920 (d, J=5.6Hz, 3H, CHCH
3).
Embodiment 8:
The insecticidal activity assay of target compound: adopt national southern test center S.O.P. to measure.
(1) test target:
Brown plant-hopper (Nilaparvata legen), mythimna separata (Mythima separata), aphis craccivora (Aphismedicagini); Above worm kind is indoor raising for many generations throughout the year or many for the worm kind from field collection indoor feeding.
(2) instrument and equipment:
Electronic analytical balance, culture dish, liquid-transfering gun, Potter spray tower, writing brush.
(3) chemicals treatment:
Take by weighing the former medicine of certain mass with analytical balance (0.0001g), add the solvent (DMF) that contains 0.1% Tween-80, be mixed with 1～5% preparation.Take by weighing the preparation of certain mass, adding distil water is mixed with the soup of measuring desired concn with the dilution of acetone drop method.
Estimate SOP (insecticide volume) according to pesticide bioactivity, general sieve concentration is selected 500mg/L.
(4) test method:
A. paddy rice brown planthopper screening---the quantitative spray-on process of culture dish seedling worm:
The paddy rice seedling is fixed in the culture dish with crystobalite sand; Use CO
2Anaesthetize 3 mid-term in age nymph, place under the POTTER spray tower spraying.The spraying back covers with the transparent plastic cup, is put in the observation ward behind the mark.Check result behind the 72h.
B. mythimna separata screening---soak the seedling feeding method:
Maize leaves is fully soaked into the back dry in the shade naturally in soup, put into culture dish, connect 3 mid-term in age larva, add a cover mark and be placed in the observation ward.Check result behind the 72h.
C. aphis craccivora screening---infusion process
If the broad bean blade is cut off two ends, and the back side is placed on the fritter cotton up, places in the plastic culture dish, adds low amounts of water, connects aphis craccivora and becomes aphid to produce aphid.Remove into aphid behind the 24h, continue behind the cultivation 2d blade behind the abundant 5s of infiltration, to be placed on the cotton natural airing again in soup.Check result behind the 24h.
Table 1 has been enumerated Z formula configuration anabasine insecticide Ia～Ig of containing the L-α-An Jisuanzhi and has been 500,100 and handles the lethality of brown plant-hopper, mythimna separata, aphis craccivora during 20ppm in concentration.Test data in the table shows: the Z formula configuration anabasine insecticide Ia～Ih that contains the L-α-An Jisuanzhi all has insecticidal activity, and wherein to kill the brown plant-hopper activity the highest for Ia, can reach 100% when concentration 100ppm.It is the highest that Ie, Ig kill the mythimna separata activity, can reach 80-100% when concentration 100ppm.Even especially Ie also has 50% the activity of killing to mythimna separata when the low concentration of 20ppm, significantly insecticidal effect is arranged.The Z formula configuration anabasine insecticide Ia, Id, Ie, And if the Ig that contain the L-α-An Jisuanzhi all have the higher activity of killing to aphis craccivora when concentration 500ppm.
Table 1: contain the killing rate (%) of the Z formula configuration anabasine insecticide Ia～Ig of L-α-An Jisuanzhi to brown plant-hopper, mythimna separata, aphis craccivora
The embodiment of the invention described above is not limited to the present invention.For a person skilled in the art, the preparation method of product of the present invention can change.Within the spirit and principles in the present invention all, that is done is equal to replacement, improves etc., all should be included within protection scope of the present invention.
Claims (2)
1. Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi, general formula (I) is:
Wherein: R is hydrogen, methyl (CH
3), isopropyl (CH (CH
3)
2), benzyl (CH
2C
6H
5), isobutyl group (CH
2CH (CH
3)
2), methylthio ethyl (CH
2CH
2SCH
3), rubigan (p-Cl-C
6H
5) in a kind of; R ' is methyl (CH
3) and ethyl (C
2H
5), n-pro-pyl (n-C
3H
7), normal-butyl (n-C
4H
9) in a kind of.
2. Z formula configuration anabasine insecticide that contains the L-α-An Jisuanzhi, the preparation method is as follows:
(1) hydrochloride of preparation L-a-amino acid methyl esters or ethyl ester, general formula (II):
A. the L-a-amino acid is dissolved in 1mol/L thionyl chloride-methanol solution,, the control temperature prepares L-a-amino acid methyl ester hydrochloride below 0 ℃;
B. the L-a-amino acid is dissolved in ethanolic solution, below the control temperature-5 ℃, dripping thionyl chloride, preparation L-a-amino acid carbethoxy hydrochloride;
(2) preparation contains the Z formula configuration anabasine insecticide of L-α-An Jisuanzhi, and general formula (I) as above.
A. the L-a-amino acid methyl esters of above-mentioned (1) preparation or hydrochloride (II), Nitenpyram, 37% formaldehyde, the triethylamine of ethyl ester are put in the three-necked round bottom flask;
B. the three-necked round bottom flask that above-mentioned solution will be housed is put into microwave reactor, and the control temperature is below 75 ℃, and microwave reaction 30 minutes makes the Z formula configuration anabasine insecticide that general formula (I) contains the L-α-An Jisuanzhi.
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