CN101792430A - (Z) type tetrahydro-pyrimidine carboxylic ester derivative and preparation method thereof - Google Patents
(Z) type tetrahydro-pyrimidine carboxylic ester derivative and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to a pesticide and relates to a (Z) type tetrahydro-pyrimidine carboxylic ester derivative and a preparation method thereof. The structure of the target compound of the invention is expressed by a general formula (I). The preparation method comprises the following steps of: firstly preparing hydrochloride of amino-acid ester; and then putting the prepared hydrochloride of the amino-acid ester, nitenpyram, 37% formaldehyde and triethylamine in a three-mouth flask for microwave reaction for 25 minutes to prepare the target compound with the general formula (I) at the temperature of about 65 DEG G. The (Z) type tetrahydro-pyrimidine carboxylic ester derivative has the advantages of high insecticidal activity, good effect, low toxicity to people and livestock and safe use, can be made into various dosage forms with convenient use, and promotes the growth of crops.
Description
Technical field
The invention belongs to crops pesticide, specifically a kind of (Z) type tetrahydro-pyrimidine carboxylic ester derivative and preparation method thereof with insecticidal activity.
Background technology
The pesticide that uses in the agriculture production is an insect of killing the growth that harms the crops, guarantees the important capital goods in the agricultural sector of crop yield.The chemical insecticide agricultural chemicals is fast with its good disinsection effect, desinsection speed, and the development of agriculture production is played an important role.The life-time service of chemical insecticide has also brought some negative effects simultaneously; For example residual the surpassed set quota of sterilant in plant materials, agricultural-food, food, soil brings harm for people's health, brings influence for the growth of farm crop.In order to alleviate edatope pollution, promotion crop growth, guarantee people's food safety, protect human health, the agronomist of countries in the world, chemist, agricultural chemicals expert attach great importance to the research and the invention of novel pesticide for a long time.
Anabasine insecticide be after organic phosphates, amino formate, pyrethroid insecticides the 4th generation sterilant.The anabasine material is as nAChR (nAChRs) agonist, neural system (nAChRs) to insect optionally works, it has not only shown high-affinity to (nAChRs), but also has shown unionized and medium physics-chem characteristic such as water-soluble.Because this insecticides has unique mechanism of action.It optionally works to the neural system nAChR (nAChRs) of insect, not only has high-affinity, but also has shown good physics-chem characteristic.Anabasine insecticide and common insecticides do not have cross resistance, and absorption in efficient, wide spectrum and the good root is not only arranged, tag and stomach poison function, and also low to mammalian toxicity, environmentally safe; Meet the requirement of people to modern agricultural chemicals.But up to this point, still kind is few for anabasine insecticide; And complex manufacturing, yield poorly, the cost height; Can't substitute the medium-term and long-term a large amount of existing pesticide that uses of our times agriculture production at all.So invent the anabasine insecticide new variety of large quantities of different chemical compositions, different substances structure as early as possible; and therefrom filter out insecticidal effect is best, low to the person poultry toxicity, production technique is simple, output is high, cost is low anabasine insecticide kind and replace the medium-term and long-term a large amount of existing pesticides that use of our times agriculture production; be pressing for of agricultural cience and farming techniques progress, agriculture production development; it is the protection environment; pressing for of protection food safety and human health is being of great significance of a task of technical field of pesticide.
Ti304 is to use chloro-pyridine compounds and acetylcholinesterase conditioning agent synthetic first-generation anabasine insecticide.It is a good sterilant in (E) type anabasine, and sucking property insect is had special efficacy.Amino acid is the neccessary composition that constitutes life, and the aminoacid component in the agricultural chemicals also has the vital role that promotes crop growth except having insecticidal effect.Up to now, the chemist of countries in the world, agricultural chemicals expert have sufficient understanding and understanding, but it are promoted that the vital role of crop growth is usually out in the cold efficient, the low toxicity insecticidal action of the anabasine insecticide that contains amino acid ester.Cause the anabasine insecticide research that contains amino acid ester, produce and use seldom, patent documentation both domestic and external and public publication are also few to the report of the anabasine insecticide that contains amino acid ester.
The present invention decides worm amine with alkene and amino acid is raw material, has synthesized a series of (Z) type tetrahydro-pyrimidine carboxylic ester derivatives with insecticidal activity.Product of the present invention (Z) type tetrahydro-pyrimidine carboxylic ester derivative can be made the various pesticide formulation, example emulsion, aqueous suspension and aqueous emulsion etc.The existing low toxicity of the various pesticide formulation, efficient insecticide activity that product of the present invention is made have the function that promotes plant growth again, are a kind of desirable pesticide new varieties that substitutes the existing agricultural chemicals that uses in the current agriculture production.
Summary of the invention
The objective of the invention is for a kind of (Z) type tetrahydro-pyrimidine carboxylic ester derivative with insecticidal activity that had not only had the efficient insecticide activity but also can promote crop growth is provided.
Another object of the present invention provides above-mentioned preparation method with (Z) type tetrahydro-pyrimidine carboxylic ester derivative of insecticidal activity.
The objective of the invention is to be achieved through the following technical solutions.
(Z) type tetrahydro-pyrimidine carboxylic ester derivative, structure is represented with general formula (I):
Wherein:
n＝0
n＝0
n＝1，2
(Z) preparation method of type tetrahydro-pyrimidine carboxylic ester derivative is as follows:
(1) hydrochloride of preparation amino acid ester, general formula (II):
Thionyl chloride is added drop-wise in the alcohol, maintains the temperature at below-5 ℃, after dripping off, rise to room temperature, add amino acid, reflux, unnecessary alcohol is removed in decompression, obtains the amino acid ester hydrochloride;
(2) preparation (Z) type tetrahydro-pyrimidine carboxylic ester derivative:
A. hydrochloride (II), Ti304,37% formaldehyde, the triethylamine of the amino acid ester that above-mentioned (1) is prepared 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, controlled temperature is about 65 ℃, microwave reaction 25 minutes, making general formula is raw material for (Z) type tetrahydro-pyrimidine carboxylic ester derivative c. of (I) with the compound of general formula (I), makes emulsion, aqueous suspension and water emulsion pesticide;
D. the reaction formula of above-mentioned preparation process is:
Step (1):
Step (2):
The mol ratio of Ti304 and amino acid ester hydrochloride is 1: 1.2～1: 1.5 in the step (2).
In the described step (2), the solvent of preparation emulsion, aqueous suspension and water emulsion pesticide is for adding the ethanol or the methanol solution of acid binding agent.
The heating means of described step (2) are microwave heating.
Main points of the present invention are:
With amino acid is raw material, the high-efficiency low-toxicity anabasine insecticide Ti304 reaction best with insecticidal effect in the world today, synthetic (Z) type tetrahydro-pyrimidine carboxylic ester derivative with insecticidal activity.
Preparation method of the present invention is: make the hydrochloride (II) of amino acid ester earlier, make (Z) type tetrahydro-pyrimidine carboxylic ester derivative again.
Adopt microwave process for synthesizing to improve productive rate and also greatly shortened the reaction times.Heating reflux method is adopted in prior art second step reaction, needs 6 hours; The present invention adopts microwave process for synthesizing only to need 25 minutes.
(Z) type tetrahydro-pyrimidine carboxylic ester with general formula (I) expression kills derivative, has good insecticidal activity, and the effective active composition of useful as pesticides is made the various pesticide formulation, example emulsion, aqueous suspension and aqueous emulsion etc.
The present invention decides worm amine with alkene first in the world and amino acid is that raw material has synthesized (Z) type tetrahydro-pyrimidine carboxylic ester derivative that series has insecticidal activity.(Z) the type tetrahydro-pyrimidine carboxylic ester derivative has the effect of good insecticidal activity and promotion crop growth, has tangible novelty, creativeness and practicality.
Advantage of the present invention is:
1, insecticidal activity height, effective.
2, low to the person poultry toxicity, safe in utilization.
3, can be made into multiple formulation, easy to use.
4, promote crop growth.
5, transformation period weak point, soil, plant materials noresidue, environmental safety.
6, the edible portion non agricultural chemical residuum of plant, people's edible safety.
Embodiment:
Further set forth technical characterstic of the present invention below in conjunction with specific embodiment.
(Z) type tetrahydro-pyrimidine carboxylic ester derivative, represent with general formula (I):
Wherein:
n＝0
n＝0
n＝1，2
The example of (Z) type tetrahydro-pyrimidine carboxylic ester derivative of the present invention's preparation is:
(Ia) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-3-methyl propionate;
(Ib) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-ethyl 3--propanoate;
(Ic) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-3-isopropyl propionate;
(Id) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-2-propionic acid n-propyl;
(Ie) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-4 butyric acid isopropyl ester;
(If) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base sec-butyl acetate;
(Ig) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-4 ' methyl-2-isopropyl isovalerate;
(Ih) (Z)-and 4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-3 ' methyl-2-isopropyl butyrate.
Embodiment 1:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-3-methyl propionate (1a).
In 100mL three-necked bottle (being with dry alkali lye absorption unit), add 20mL methyl alcohol, cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, obtain sulfur oxychloride-methanol solution.In sulfur oxychloride-methanol solution, add the 4.453g Beta-alanine, reflux 1 hour, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be that (II a), productive rate is 96.54% to the Beta-alanine methyl ester hydrochloride.
With 2.707g Ti304,1.675g Beta-alanine methyl ester hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 81.23%.
Ultimate analysis: measured value: C%51.35 H%6.10 N%17.58
Calculated value: C%51.32 H%6.08 N%17.60
IR(KBr，cm
-1)v
max?2951，2872，1744(C＝O)，1546(NO
2)，1303(v
asC-O-C)，1251(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.308-8.313(d，J＝2.4Hz，1H，Pyridine)，7.687-7.742(d×d，J
1＝J
2＝2.4Hz，1H，Pyridine)，7.326-7.346(d，J＝8.0Hz，1H，Pyridine)，4.496-4.533(d，J＝14.8Hz，1H)，4.165-4.203(d，J＝15.2Hz，1H)，3.778-3.814(m，4H)，3.718(s，3H，COO?CH
3)，3.630-3.667(m，4H)，3.229-3.300(m，1H)，2.980(s，3H，NCH
3)，2.917-2.953(m，1H)，2.803-2.862(q，2H，NCH
2CH
3)，2.558-2.591(t，2H，J＝13.2Hz)，1.175-1.211(t，J＝14.4Hz，3H，NCH
2CH
3)。
Embodiment 2:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-ethyl 3--propanoate (1b).
Add 20mL ethanol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, obtain sulfur oxychloride-ethanolic soln.In sulfur oxychloride-ethanolic soln, add the 4.453g Beta-alanine, reflux 1 hour, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be Beta-alanine ester second hydrochloride (II b), productive rate is 95.76%.
With 2.707g Ti304,1.843g Beta-alanine carbethoxy hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 82.56%.
Ultimate analysis: measured value: C%51.48 H%6.34 N%17.02
Calculated value: C%51.49 H%6.36 N%17.00
IR(KBr，cm
-1)v
max2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.288-8.294(d，J＝2.4Hz，1H，Pyridine)，7.672-7.699(d×d，J
1＝J
2＝2.4Hz，1H，Pyridine)，7.302-7.323(d，J＝8.4Hz，1H，Pyridine)，4.478-4.516(d，J＝15.2Hz，1H)，4.132-4.188(m，3H)，3.612-3.653(m，4H)，3.205-3.275(m，3H)，2.968(s，3H，NCH
3)，2.903-2.938(m，1H)，2.782-2.845(q，2H，NCH
2CH
3)，2.522-2.556(t，J＝13.6Hz，3H，CH
2COOCH
2CH
3)，1.240-1.275(t，J＝14.0Hz，3H，COOCH
2CH
3)，1.152-1.188(t，J＝14.4Hz，3H，NCH
2CH
3)。
Embodiment 3:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-3-isopropyl propionate (1c).
Add the 20mL Virahol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, sulfur oxychloride-aqueous isopropanol.In sulfur oxychloride-aqueous isopropanol, add the 4.453g Beta-alanine, reflux 2 hours, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be Beta-alanine isopropyl ester hydrochloride (II c), productive rate is 90.28%.
With 2.707g Ti304,2.012g Beta-alanine isopropyl ester hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 80.16%.
Ultimate analysis: measured value: C%53.57 H%6.65 N%16.46
Calculated value: C%53.58 H%6.63 N%16.44
IR(KBr，cm
-1)v
max?2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.301-8.307(d，J＝2.4Hz，1H，Pyridine)，7.683-7.711(d×d，1H，J
1＝J
2＝2.4Hz，Pyridine)，7.320-7.340(d，J＝8.0Hz，1H，Pyridine)，4.993-5.088(m，1H，COOCH)，4.495-4.533(d，J＝15.2Hz，1H)，4.160-4.198(d，J＝15.2Hz，1H)，3.616-3.680(m，4H)，3.22?3-3.293(m，1H)，2.980(s，3H，NCH
3)，2.919-2.954(m，1H)，2.804-2.859(q，2H，NCH
2CH
3)，2.515-2.547(t，J＝12.8Hz，3H，CH
2COOCH
2CH
3)，1.240-1.255(d，J＝6.0Hz，6H，CH(CH
3)
2)，1.168-1.204(t，J＝14.4Hz，3H，NCH
2CH
3)。
Embodiment 4:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-2-propionic acid n-propyl (1d).
Add the 20mL n-propyl alcohol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, sulfur oxychloride-n-propyl alcohol solution.In sulfur oxychloride-n-propyl alcohol solution, add 4.453g L-α-Bing Ansuan, reflux 2 hours, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be L-α-Bing Ansuan n-propyl hydrochloride (IId), productive rate is 91.14%.
With 2.707g Ti304,2.012g L-α-Bing Ansuan n-propyl hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 79.81%.
Ultimate analysis: measured value: C%53.56 H%6.62 N%16.45
Calculated value: C%53.58 H%6.63 N%16.44
IR(KBr，cm
-1)v
max?2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.331-8.336(d，J＝2.0Hz，1H，Pyridine)，7.706-7.800(d×d，1H，J
1＝J
2＝2.8Hz，Pyridine)，7.335-7.356(d，J＝8.4Hz，1H，Pyridine)，4.529-4.582(q，J＝21.4Hz，1H，NCH)，4.171-4.209(d，J＝15.2Hz，1H)，4.084-4.118(t，J＝5.6Hz，2H，COOCH
2)，3.750-3.877(m，4H)，3.604-3.621(m，1H)，3.237-3.327(m，1H)，2.996(s，3H，NCH
3)，2.884-2.950(m，1H)，1.648-1.738(m，2H，CH
2CH
3)，1.431-1.446(d，J＝6.0Hz，3H，CHCH
3)，1.175-1.211(t，J＝14.4Hz，3H，NCH
2CH
3)，0.950-0.987(t，J＝14.8Hz，3H，CH
2CH
3)。
Embodiment 5:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-4 butyric acid isopropyl ester (1e).
Add the 20mL Virahol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, sulfur oxychloride-aqueous isopropanol.In sulfur oxychloride-aqueous isopropanol, add the 5.153g γ-An Jidingsuan, reflux 2 hours, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be γ-An Jidingsuan isopropyl ester hydrochloride (II e), productive rate is 89.74%.
With 2.707g Ti304,1.675g γ-An Jidingsuan isopropyl ester hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 78.93%.
Ultimate analysis: measured value: C%54.55 H%6.90 N%15.95
Calculated value: C%54.60 H%6.87 N%15.92
IR(KBr，cm
-1)v
max?2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.311-8.317(d，J＝2.4Hz，1H，Pyridine)，7.706-7.726(d×d，1H，J
1＝J
2＝2.4Hz，Pyridine)，7.331-7.350(d，J＝7.6Hz，1H，Pyridine)，4.986-4.045(m，1H，COOCH)，4.501-4.539(d，J＝15.2Hz，1H)，4.165-4.202(d，J＝14.8Hz，1H)，3.614-3.660(m，4H)，3.227-3.296(m，1H)，3.005(s，3H，NCH
3)，2.918-2.970(m，1H)，2.508-2.523(q，2H，NCH
2CH
3)，2.362-2.395(t，J＝13.2Hz，3H，CH
2COO?CH)，1.854-1.885(m，2H，CH
2CH
2COOCH)，1.238-1.254(d，J＝6.4Hz，6H，CH(CH
3)
2)，1.180-1.213(t，J＝13.2Hz，3H，NCH
2CH
3)。
Embodiment 6:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base sec-butyl acetate (1f).
Add the 30mL sec-butyl alcohol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 4 hours, sulfur oxychloride-sec-butyl alcohol solution.In sulfur oxychloride-sec-butyl alcohol solution, add the 3.753g glycine, reflux 2 hours, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be glycine Zhong Ding ester hydrochloride (IIf), productive rate is 81.69%.
With 2.707g Ti304,2.012g glycine Zhong Ding ester hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 72.36%.
Ultimate analysis: measured value C%53.56 H%6.60 N%16.47
Calculated value C%53.58 H%6.63 N%16.44
IR(KBr，cm
-1)v
max?2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.327-8.332(d，J＝2.0Hz，1H，Pyridine)，7.730-7.755(d×d，1H，J
1＝J
2＝2.0Hz，Pyridine)，7.332-7.35?3(d.J＝8.4Hz，1H，Pyridine)，4.890-4.968(m，1H，COOCH)，4.524-4.562(d，J＝15.2Hz，1H)，4.153-4.191(d，J＝15.2Hz，1H)，3.730-3.809(m，4H)，3.429(s，2H，NCH
2COOCH)，3.230-3.318(m，1H)，3.077(s，3H，NCH
3)，2.885-2.975(m，1H)，1.573-1.665(m，2H，CH
2CH
3)，1.248-1.264(t，J＝6.4Hz，3H，CHCH
3)，1.168-1.203(t，J＝14.0Hz，3H，NCH
2CH
3)，0.901-0.938(t，J＝13.8Hz，3H，CH
2CH
3)。
Embodiment 7:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-4 ' methyl-2-isopropyl isovalerate (Ig).
Add the 20mL Virahol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, sulfur oxychloride-aqueous isopropanol.In sulfur oxychloride-aqueous isopropanol, add 4.453g L-alpha-aminoisocaproic acid, reflux 2 hours, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be L-alpha-aminoisocaproic acid isopropyl ester hydrochloride (II g), productive rate is 92.57%.
With 2.707g Ti304,2.685g L-alpha-aminoisocaproic acid isopropyl ester hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 77.24%.
Ultimate analysis: measured value: C%56.50 H%7.35 N%14.95
Calculated value: C%56.46 H%7.32 N%14.96
IR(KBr，cm
-1)v
max?2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.308-8.329(d，J＝8.4Hz，1H，Pyridine)，7.678-7.780(d×d，1H，J
1＝J
2＝8.4Hz，Pyridine)，7.327-7.347(d，J＝8.0，Hz，1H，Pyridine)，5.076-5.013(m，1H，COOCH)，4.522-4.560(d，J＝15.2Hz，1H)，4.117-4.155(d，J＝15.2Hz，1H)，3.704-3.878(m，4H)，3.491-3.528(t，J＝15.2Hz，1H，NCHCH
2)，3.247-3.320(m，1H)，2.936(s，3H，NCH
3)，2.862-2.916(m，1H)，1.597-1.718(m，3H)，1.254-1.214(d，J＝8.4Hz，6H，COCH(CH
3)
2)，1.176-1.214(t，J＝15.2Hz，3H，NCH
2CH
3)，0.943-0.989(d×d，J
1＝J
2＝6.0Hz，6H，CH(CH
3)
2)。
Embodiment 8:
Preparation (Z)-4-[(6-chloro-3-picolyl) ethylamino]-3-methyl-5-nitro-1-1,2,3,6-tetrahydro-pyrimidine base-3 ' methyl-2-isopropyl butyrate (Ih).
Add the 30mL Virahol in the 100mL three-necked bottle (being with dry alkali lye absorption unit), cryosel is bathed and is cooled to-10 ℃～-15 ℃, drip the new sulfur oxychloride that steams of 3.60mL under the magnetic agitation, the control rate of addition makes temperature of reaction be no more than-5 ℃, react and be warming up to room temperature naturally after 1 hour, sulfur oxychloride-aqueous isopropanol.In sulfur oxychloride-aqueous isopropanol, add 4.453g L-α-Xie Ansuan, reflux 2 hours, removal of solvent under reduced pressure and excessive sulfur oxychloride, obtain white solid, white solid gets white needle-like crystals with dehydrated alcohol-ether recrystallization, be L-α-Xie Ansuan isopropyl ester hydrochloride (II h), productive rate is 88.43%.
With 2.707g Ti304,2.348g L-α-Xie Ansuan isopropyl ester hydrochloride, 1.8mL triethylamine and 2.0mL concentration is that 37% formaldehyde solution is dissolved in the 30mL ethanol together, the three-necked flask that mixed reaction solution is housed is placed microwave reactor, 5 minutes internal heating to 65 ℃, and keep 65 ℃ of reactions after 20 minutes decompression steam solvent, add 10mL water dissolution and divide three extractions with the 60mL ethyl acetate.Combining extraction liquid spends the night with anhydrous magnesium sulfate drying, steams solvent, obtains yellow oil.With ethyl acetate: sherwood oil=column chromatography got faint yellow oily thing in 3: 1, and productive rate is 78.13%.
Ultimate analysis: measured value: C%55.53 H%7.12 N%15.45
Calculated value: C%55.56 H%7.11 N%15.43
IR(KBr，cm
-1)v
max?2949，2870，1741(C＝O)，1548(NO
2)，1305(v
asC-O-C)，1254(v
aC-O-C)。
1H?NMR(CDCl
3，ppm，400MHz)δ：8.307-8.334(d，J＝9.6Hz，1H，Pyridine)，7.648-7.792(d×d，1H，J1＝J2＝8.0Hz，Pyridine)，7.328-7.349(d，J＝8.4Hz，1H，Pyridine)，4.321-4.255(d，J＝15.2Hz，1H)，4.069-4.103(d，J＝15.2Hz，1H)，3.242-3.320(m，4H)，3.044-3.069(m，1H)，2.965(s，3H，NCH
3)，2.869-2.965(m，1H)，1.645-1.734(m，3H)，1.162-1.201(t，J＝15.6Hz，3H，NCH
2CH
3)，1.080-1.101(t，J＝8.4Hz，3H，CH
2CH
2CH
3)，0.936-0.990(d×d，J
1＝J
2＝6.8Hz，6H，CH(CH
3)
2)。
The above is the preferred embodiments of the present invention only, is not limited to the present invention, and for a person skilled in the art, the present invention can have change and change.All any modifications of being done within the spirit and principles in the present invention, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (5)
1. (Z) type tetrahydro-pyrimidine carboxylic ester derivative with insecticidal activity, structure are with general formula (I) expression:
Wherein:
n＝0
n＝0
n＝1，2
。
2. (Z) type tetrahydro-pyrimidine carboxylic ester derivative with insecticidal activity according to claim 1,
Its preparation method is as follows:
(1) hydrochloride of preparation amino acid ester, general formula (II):
Thionyl chloride is added drop-wise in the alcohol, maintains the temperature at below-5 ℃, after dripping off, rise to room temperature, add amino acid, reflux, unnecessary alcohol is removed in decompression, obtains the amino acid ester hydrochloride;
(2) preparation (Z) type tetrahydro-pyrimidine carboxylic ester derivative:
A. hydrochloride (II), Ti304,37% formaldehyde, the triethylamine of the amino acid ester that above-mentioned (1) is prepared 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 controlled temperature is about 65 ℃, and microwave reaction 25 minutes makes (Z) type tetrahydro-pyrimidine carboxylic ester derivative that general formula (I) has insecticidal activity.
C. the compound with general formula (I) is a raw material, makes emulsion, aqueous suspension and water emulsion pesticide;
D. the reaction formula of above-mentioned preparation process is:
Step (1):
Step (2):
3. the preparation method with (Z) type tetrahydro-pyrimidine carboxylic ester derivative of insecticidal activity according to claim 2 is characterized in that: the mol ratio of Ti304 and amino acid ester hydrochloride is 1: 1.2～1: 1.5 in the step (2).
4. the preparation method with (Z) type tetrahydro-pyrimidine carboxylic ester derivative of insecticidal activity according to claim 2, it is characterized in that: in the described step (2), the solvent of preparation emulsion, aqueous suspension and water emulsion pesticide is for adding the ethanol or the methanol solution of acid binding agent.
5. the preparation method with (Z) type tetrahydro-pyrimidine carboxylic ester derivative of insecticidal activity according to claim 2, it is characterized in that: the heating means of described step (2) are microwave heating.
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