CN115160235B - 2, 3-dihydro-quinazoline-4 (1H) -ketone compound and ultrasonic synthesis method thereof - Google Patents

2, 3-dihydro-quinazoline-4 (1H) -ketone compound and ultrasonic synthesis method thereof Download PDF

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CN115160235B
CN115160235B CN202210954431.6A CN202210954431A CN115160235B CN 115160235 B CN115160235 B CN 115160235B CN 202210954431 A CN202210954431 A CN 202210954431A CN 115160235 B CN115160235 B CN 115160235B
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dihydro
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quinazoline
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CN115160235A (en
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阳丽
谢蒋平
文桂胶
王霞
罗竣
王丽
何云清
黄勇
孙琳
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Yibin University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems

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Abstract

The invention discloses a 2, 3-dihydro-quinazoline-4 (1H) -ketone compound and an ultrasonic synthesis method thereof, which comprises the following steps: the o-aminobenzamide or the derivative thereof and aldehyde or ketone compounds are dissolved in a solvent, and after simple substance iodine is added, ultrasonic is carried out at room temperature, and standing crystallization is carried out, thus obtaining the product. The synthesis method has the advantages of simple operation, short reaction time, cheap raw materials, quick and convenient operation, simple post-treatment, no need of column purification for product separation, purification of the product only by simple filtration and separation and recrystallization of ethanol water solution, purity of more than 95 percent and low production cost. Meanwhile, the synthesis method only produces water as a byproduct, does not use a metal catalyst, has no metal pollution and residue, adopts alcohol as a solvent, can be recycled, and meets the requirements of green chemical development.

Description

2, 3-dihydro-quinazoline-4 (1H) -ketone compound and ultrasonic synthesis method thereof
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a 2, 3-dihydro-quinazoline-4 (1H) -ketone compound and an ultrasonic synthesis method thereof.
Background
2, 3-dihydro-quinazoline-4 (1H) -ketone substances are important heterocyclic compounds, widely exist in alkaloid and pharmaceutically active molecules, have wide biological and pharmacological activities and medical characteristics, and have the effects of resisting inflammation, cancer, hypertension, bacteria, malaria, HIV, tuberculosis, fungi, anticonvulsant, nicotinic acid receptor 1 agonists, diuretics and the like, and have the in vivo anti-obesity effect. Many derivatives of this class of substances are useful as marketed drugs, such as quinconazole, metolazone (antihypertensive diuretics), fluoroquinolones (sedatives and muscle relaxants), luracil (antineoplastic agents), evodiamine (thermogenic and stimulants), abaconazole (antifungals) and praziquantel (non-steroidal anti-inflammatory agents). The wide variety of biological applications of 2, 3-dihydroquinazolin-4 (1H) -ones has stimulated great interest in methods for their synthesis.
The most efficient and most commonly used method for the synthesis of 2, 3-dihydroquinazolin-4 (1H) -one is currently achieved by the ring condensation of 2-aminobenzamide with an aldehyde. According to the mechanism of circulation, the reaction produces only water as a by-product. The catalytic systems used for the reactions so far mainly comprise the following: the nano composite material of supported solid strong acid, ammonium salt, cyanuric chloride, metal and oxide thereof, and metal-organic frameworks (MOFs). However, the method has the advantages of harsh reaction conditions, long reaction time, high production cost and difficulty in solving the problem of trace metal pollution in the synthesized medicine due to the use of a strong acid catalyst, an acidic ionic liquid, an expensive transition metal catalyst, a toxic catalyst and a method.
The prior art also reports that the ethanol-promoted dichloro titanocene is utilized to catalyze and prepare the 2, 3-dihydro-quinazoline-4 (1H) -ketone derivative, but the transition metal dichloro titanocene is adopted as a catalyst, so that the problem of trace metal pollution in the synthetic medicine is difficult to solve, unsafe factors occur, and the cost of the used catalyst is very high. The rest reports that if the ionic liquid is used as a catalyst to prepare the 2, 3-dihydro-quinazoline-4 (1H) -ketone derivative, the reaction solvent is the ionic liquid, the price is high, the heating is needed for more than 2 hours, the reaction time is long, and the production cost is high; if water or inert gas in an organic solvent is adopted to protect and heat for a plurality of hours, the 2, 3-dihydro-quinazoline-4 (1H) -ketone derivative is obtained, the heating for a plurality of hours (more than 2 hours or 16 hours) is carried out, the reaction time is long, and the production cost is high.
Disclosure of Invention
The invention aims to provide a 2, 3-dihydro-quinazoline-4 (1H) -ketone compound and an ultrasonic synthesis method thereof, which can solve the problems.
In order to achieve the purpose, the invention provides an ultrasonic synthesis method of 2, 3-dihydro-quinazoline-4 (1H) -ketone compounds, which comprises the steps of co-dissolving anthranilamide or derivatives thereof and aldehyde or ketone compounds in a solvent, adding elemental iodine, performing ultrasonic treatment at room temperature, standing and crystallizing to obtain the compound;
wherein the power of the ultrasound: 360W, frequency: 40KHz; the ultrasonic time is 15-30 min.
Further, the solvent is methanol, acetonitrile, isopropanol, water, ethyl acetate, petroleum ether, absolute ethanol or ethanol solution.
Further, the volume fraction of the ethanol solution is 50-95%.
Further, the mass ratio of the anthranilamide or the derivative thereof, the aldehyde or ketone compound and the elemental iodine is 1:1:5-40.
Further, the method comprises the following steps after crystallization: and recrystallizing the crude product obtained after crystallization by adopting an ethanol water solution, thus obtaining the 2, 3-dihydro-quinazoline-4 (1H) -ketone, wherein the volume fraction of the ethanol water solution is 70-90%.
The invention also provides the 2, 3-dihydro-quinazoline-4 (1H) -ketone compound synthesized by adopting the ultrasonic synthesis method of the 2, 3-dihydro-quinazoline-4 (1H) -ketone compound.
Further, the structural formula of the 2, 3-dihydro-quinazoline-4 (1H) -ketone compound is shown as a formula (I):
wherein r=h or alkyl, R 1 =h or alkyl, R 2 =phenyl or substituted phenyl; alternatively, r=h or CH 3 ，R 1 And R is 2 Forming cycloalkyl groups.
Further, the 2, 3-dihydroquinazolin-4 (1H) -one compounds are:
in summary, the invention has the following advantages:
1. the invention provides an ultrasonic synthesis method of 2, 3-dihydro-quinazoline-4 (1H) -ketone compounds, which is characterized in that simple substance iodine is used as a catalyst, alcohols are used as solvents, and ultrasonic is adopted to promote the reaction cyclization of o-aminobenzamide and various substituted aldehydes and ketones to form the 2, 3-dihydro-quinazoline-4 (1H) -ketone compounds.
2. The synthesis method has the advantages of simple operation, short reaction time, cheap raw materials, quick and convenient operation, simple post-treatment, no need of column purification in product separation, purification of the product only by simple filtration separation and recrystallization of ethanol water solution, purity of more than 95 percent and low production cost. The synthesis method only produces water as a byproduct, does not use a metal catalyst, has no metal pollution and residue, adopts alcohol as a solvent, can be recycled, and meets the development requirements of green chemical industry.
Drawings
FIG. 1 is a radical trapping experimental reaction mechanism;
FIG. 2 is a graph showing the effect of different solvents on yield;
FIGS. 3 and 4 are representations of the products prepared in example 1;
FIGS. 5 and 6 are representations of the products prepared in example 2;
FIGS. 7 and 8 are representations of the products prepared in example 3;
FIGS. 9 and 10 are representations of the products prepared in example 4;
FIGS. 11 and 12 are representations of the products prepared in example 5;
FIGS. 13 and 14 are representations of the products prepared in example 6;
FIGS. 15 and 16 are representations of the products prepared in example 7;
fig. 17 and 18 are representations of the product prepared in example 18.
Detailed Description
The principles and features of the present invention are described below in connection with the following examples, which are set forth to illustrate, but are not to be construed as limiting the scope of the invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The ultrasonic power in the invention is 360W, and the ultrasonic frequency is 40KHz.
Example 1
The invention provides an ultrasonic synthesis method of 2- (4-nitrophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
anthranilamide (1.362 g,10 mmol) and 1mL (10 mmol) of benzaldehyde were weighed, dissolved in 70mL of 95% ethanol, and 0.02mol/L of I was added 2 Ultrasonic at room temperature for 15min to obtain a yellow turbid system (10 mL,0.2 mmol), standing, and precipitating yellow crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallizing with 80% ethanol solution to obtain 2.06g light flaky crystal 2- (4-nitrophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one with the following structural formula:
the melting point of 2- (4-nitrophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one is 217-218 ℃ and the yield is: 92%, the purity of the product can reach more than 95%, the product can be directly used for nuclear magnetic detection, and nuclear magnetic data are as follows:
1 H NMR(400MHz，DMSO-d 6 ): delta 8.26 (t, j=1.9 hz, 1H), 7.62 (dd, j=7.8, 1.7hz, 1H), 7.57-7.46 (m, 2H), 7.46-7.30 (m, 3H), 7.25 (ddd, j=8.1, 7.2,1.6hz, 1H), 7.10 (d, j=1.7 hz, 1H), 6.76 (dd, j=8.3, 1.0hz, 1H), 6.73-6.62 (m, 1H), 5.76 (t, j=1.9 hz, 1H) ppm (as shown in fig. 3).
13 C NMR(101MHz，DMSO-d 6 ): delta 163.53, 147.81, 141.61, 133.25, 128.39, 128.27, 127.30, 126.81, 117.06, 114.93, 114.36, 66.53ppm (as shown in fig. 4).
Example 2
The embodiment provides an ultrasonic synthesis method of 2- (4-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
anthranilamide (1.362 g,10 mmol) and p-chlorobenzaldehyde (1.401 g,10 mmol) were weighed, dissolved in 70mL of 95% ethanol, and 0.02mol/L of I was added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 20min to give a pale yellow cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallizing with 80% ethanol solution to obtain 1.86g white flaky crystal 2- (4-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one with the following structural formula:
the melting point of 2- (4-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one is 207-208 ℃ and the yield is: 72%. The purity of the product can reach more than 95%, the product can be directly used for nuclear magnetic detection, and nuclear magnetic data are as follows:
1 H NMR(400MHz，DMSO-d 6 ): δ8.35 (d, j=2.4 hz, 1H), 7.63 (dd, j=7.9, 1.6hz, 1H), 7.58-7.41 (m, 4H), 7.26 (ddd, j=8.5, 7.2,1.7hz, 1H), 7.16 (s, 1H), 6.77 (dd, j=8.2, 1.1hz, 1H), 6.70 (td, j=7.4, 1.1hz, 1H), 5.79 (d, j=2.3 hz, 1H) (as shown in fig. 5).
13 C NMR(101MHz，DMSO-d 6 ): δ 163.99, 148.13, 141.13, 133.88, 133.47, 130.11, 129.24, 129.17, 128.79, 127.86, 117.77, 115.42, 114.95, 66.27 (shown in fig. 6).
Example 3
The embodiment provides an ultrasonic synthesis method of 2- (4-methylphenyl) -2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
anthranilamide (1.362 g,10 mmol) and p-methylbenzaldehyde (1.2 mL,10 mmol) were weighed out and dissolved in 70mL of 95% ethanol0.02mol/L of I is added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 20min to give a white cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallisation from 80% ethanol solution gives 2.01g of a white powder solid, 2- (4-methoxyphenyl) -2, 3-dihydroquinazolin-4 (1H) -one, of the formula:
the melting point of 2- (4-methoxyphenyl) -2, 3-dihydro-quinazolin-4 (1H) -one is 232-233 ℃ and the yield is: 84%. The purity of the product can reach more than 95%, the product can be directly used for nuclear magnetic detection, and nuclear magnetic data are as follows:
1 H NMR(400MHz，DMSO-d 6 ): delta 8.21 (d, j=2.3 hz, 1H), 7.62 (dd, j=7.8, 1.6hz, 1H), 7.41-7.36 (m, 2H), 7.29-7.14 (m, 3H), 7.04 (s, 1H), 6.75 (dd, j=8.1, 1.0hz, 1H), 6.72-6.62 (m, 1H), 5.72 (d, j=2.2 hz, 1H), 2.30 (s, 3H) (as shown in fig. 7).
13 C NMR(101MHz，DMSO-d 6 ) Delta: 164.11 148.38, 139.16, 138.18, 133.71, 129.27, 127.81, 127.25, 117.53, 115.48, 114.88, 66.87, 21.19 (shown in fig. 8).
Example 4
The embodiment provides an ultrasonic synthesis method of 2- (4-tert-butylphenyl) -2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
o-aminobenzamide (1.362 g,10 mmol) and p-tert-butylbenzaldehyde (1.7 mL,10 mmol) were weighed into 70mL of 95% ethanol, and 0.02mol/L of I was added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 20min to give a white cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallisation from 80% volume fraction in ethanol gives 2.44g of white needle crystals 2- (4-tert-butyl) 2Butylphenyl) -2, 3-dihydroquinazolin-4 (1H) -one having the structural formula:
the melting point of 2- (4-tert-butylphenyl) -2, 3-dihydroquinazolin-4 (1H) -one is 208-210 ℃. The yield is as follows: 87%. The purity of the product can reach more than 95%, and the product can be directly used for nuclear magnetic detection, and the data are as follows:
1 H NMR(400MHz，DMSO-d 6 ): δ8.20 (t, j=1.9 hz, 1H), 7.63 (dd, j=7.8, 1.6hz, 1H), 7.43 (s, 4H), 7.25 (ddd, j=8.5, 7.1,1.6hz, 1H), 7.05 (s, 1H), 6.74 (d, j=8.1 hz, 1H), 6.72-6.63 (m, 1H), 5.73 (t, j=1.8 hz, 1H), 1.35 (s, 9H) (as shown in fig. 9).
13 C NMR(101MHz，DMSO-d 6 ): δ 164.14, 151.50, 148.42, 139.12, 133.73, 127.84, 127.14, 125.57, 117.53, 115.43, 114.85, 66.93, 34.79, 31.59 (as shown in fig. 10).
Example 5
The embodiment provides an ultrasonic synthesis method of 2- (2-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
anthranilamide (1.362 g,1 mmol) and o-chlorobenzaldehyde (1.1 mL,1 mmol) were weighed into 70mL of 95% ethanol, and 0.02mol/L of I was added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 20min to give a white cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallisation from 80% ethanol solution afforded 2.41g of 2- (2-chlorophenyl) -2, 3-dihydroquinazolin-4 (1H) -one as a white powdered solid having the formula:
the melting point of 2- (2-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one is 205-206 ℃ and the yield is: 93%. The purity of the product can reach more than 95%, and the product can be directly used for nuclear magnetic detection, and the data are as follows:
1 H NMR(400MHz，CDCl 3 ，DMSO-d 6 ): δ8.00 (d, j=1.9 hz, 1H), 7.74-7.64 (m, 2H), 7.40 (dq, j=6.7, 3.8hz, 1H), 7.33 (ddd, j=5.8, 4.7,3.3hz, 2H), 7.21 (dddd, j=8.5, 6.6,4.8,1.7hz, 1H), 6.76 (ddd, j=8.1, 4.0,2.4hz, 2H), 6.72-6.64 (m, 1H), 6.18 (dt, j=5.1, 1.7hz, 1H) (as shown in fig. 11).
13 C NMR(101MHz，CDCl 3 ，DMSO-d 6 ): δ 164.39, 148.04, 138.28, 133.65, 132.48, 130.32, 129.78, 129.07, 127.79, 127.50, 117.86, 115.10, 114.95, 64.19 (as shown in fig. 12).
Example 6
The embodiment provides an ultrasonic synthesis method of 2- (3-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
o-aminobenzamide (1.362 g,10 mmol) and m-chlorobenzaldehyde (1.1 mL,10 mmol) were weighed into 70mL of 95% ethanol, and 0.02mol/L of I was added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 20min to give a white cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallisation from 80% ethanol solution gives 1.86g of 2- (3-chlorophenyl) -2, 3-dihydroquinazolin-4 (1H) -one as a white powder having the formula:
the 2- (3-chlorophenyl) -2, 3-dihydro-quinazolin-4 (1H) -one has a melting point of 185-186 ℃. The yield is as follows: 72%. The purity of the product can reach more than 95%, and the product can be directly used for nuclear magnetic detection, and the data are as follows:
1 H NMR(400MHz，DMSO-d 6 )：δ8.44–8.33(m，1H)，763 (dd, j=7.7, 1.6hz, 1H), 7.54 (q, j=1.4 hz, 1H), 7.50-7.37 (m, 3H), 7.27 (ddd, j=8.1, 7.2,1.6hz, 1H), 7.21 (d, j=1.8 hz, 1H), 6.78 (dd, j=8.3, 1.1hz, 1H), 6.70 (td, j=7.4, 1.1hz, 1H), 5.79 (t, j=2.2 hz, 1H) (as shown in fig. 13).
13 C NMR(101MHz，DMSO-d 6 ): δ 163.91, 147.95, 144.89, 133.95, 133.47, 130.77, 128.73, 127.85, 127.20, 125.86, 117.82, 115.38, 114.96, 66.05 (shown in fig. 14).
Example 7
The present example provides a method for the ultrasonic synthesis of 1 'H-spiro [ cyclohexane-1, 2' -quinazoline ] -4 '(3' H) -one, comprising the steps of:
anthranilamide (1.362 g,10 mmol) and cyclohexanone (10 mL,10 mmol) were weighed into 70mL of 95% ethanol, and 0.02mol/L of I was added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 15min to give a white cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallizing with 80% ethanol solution to obtain 1.857g white powdery solid with the following structural formula:
the melting point is 226-227 ℃ after detection. The yield is as follows: 86%. The purity of the product can reach more than 95%, and the product can be directly used for nuclear magnetic detection, and the data are as follows:
1 H NMR(400MHz，DMSO-d 6 ): delta 7.91 (d, j=1.9 hz, 1H), 7.57 (dd, j=7.7, 1.6hz, 1H), 7.22 (ddd, j=8.1, 7.1,1.7hz, 1H), 6.81 (dd, j=8.2, 1.0hz, 1H), 6.65-6.59 (m, 2H), 1.75 (dt, j=10.9, 4.5hz, 2H), 1.58 (dqd, j=12.9, 7.7,4.5hz, 6H), 1.49-1.37 (m, 1H), 1.32-1.19 (m, 1H) (as shown in fig. 15).
13 C NMR(101MHz，DMSO-d 6 )：δ163.23，146.78，133.15，127.12 116.51, 114.59, 114.45, 67.83, 37.17, 24.66, 20.90 (as shown in fig. 16).
Example 8
The embodiment provides an ultrasonic synthesis method of 2-methyl-2-phenyl-2, 3-dihydro-quinazolin-4 (1H) -one, which comprises the following steps:
anthranilamide (1.362 g,10 mmol) and acetophenone (1.2 mL,10 mmol) were weighed into 70mL of 95% ethanol, and 0.02mol/L of I was added 2 (10 mL,0.2 mmol) and sonicated at room temperature for 40 min to give a white cloudy solution, which slowly precipitated white crystals. Filtering, washing the surface of the precipitate with a small amount of absolute ethyl alcohol, and removing soluble impurities to obtain a crude product. Recrystallisation from 80% ethanol solution gives 1.93g of a white powdery solid of the formula:
the melting point is 224-226 ℃ after detection. The yield is as follows: 81%. The purity of the product can reach more than 95%, and the product can be directly used for nuclear magnetic detection, and the data are as follows:
1 H NMR(400MHz，DMSO-d 6 ): δ8.78 (d, j=1.7 hz, 1H), 7.64 (d, j=1.7 hz, 1H), 7.49 (ddt, j=6.6, 5.6,1.5hz, 3H), 7.32-7.26 (m, 2H), 7.24-7.15 (m, 2H), 6.77 (dd, j=8.1, 1.1hz, 1H), 6.58 (ddd, j=8.0, 7.2,1.1hz, 1H), 1.65 (s, 3H) (as shown in fig. 17).
13 C NMR(101MHz，DMSO-d 6 ): δ 164.29, 148.14, 147.65, 133.76, 128.43, 127.70, 127.49, 125.62, 117.29, 115.47, 114.75, 70.60, 31.18 (as shown in fig. 18).
Test example 1
1.1
In the invention, elemental iodine is used as a catalyst, and ethanol is used as a solvent, so that the elemental iodine is easy to generate free radicals under the ultrasonic condition, and the ethanol has good solubility and dispersibility to iodine, so that the elemental iodine and the ethanol have special performance to the ultrasonic synthesis method. The embodiment provides a free radical capture experiment to verify the special performance of the iodine simple substance to the experimental process, and the free radical capture experiment and the result are as follows:
TABLE 1 free radical Capture experiment results
According to the four control experimental data, the speed of product precipitation is obviously slowed in the ultrasonic process of adding 1 equivalent of 2 equivalent of the free radical scavenger 2, 6-tetramethylpiperidine oxide (TEMPO) compared with the speed of product precipitation without adding the free radical scavenger, and the turbidity phenomenon (product is insoluble and no product is generated) of 4 equivalent of the free radical scavenger TEMPO in the ultrasonic process is avoided. Indicating that the reaction was successfully prevented from proceeding after the addition of the radical scavenger. Experiments show that the type of reaction between anthranilamide and benzaldehyde is a radical reaction, and the possibility of this reaction mechanism is speculated as shown in fig. 1.
As can be seen from fig. 1 and table 1, the ultrasonic synthesis reaction of the present invention is a radical reaction, and the composition of iodine or its salt is difficult to generate iodine radical initiation reaction.
Meanwhile, the ethanol solutions with different concentrations of iodine in the examples can also complete the synthesis process, the concentration of the ethanol solution with higher concentration than the concentration of the ethanol solution with lower concentration than the concentration of the ethanol solution with higher concentration than the concentration of the ethanol solution with lower concentration.
1.2
Meanwhile, other solvents are adopted to complete the synthesis process of the invention, such as absolute ethyl alcohol instead of 95% ethanol, and common solvents such as methanol, acetonitrile, isopropanol, water, ethyl acetate, petroleum ether and the like can all be used to obtain target products. The reaction phenomenon is slightly different, for example, the crude product obtained by using petroleum ether as a solvent is black, and the color is different from that of the product, but the material becomes white after recrystallization, and the yield is lower than that of absolute ethyl alcohol. While the yields of the remaining solvents are relatively low, the yields are highest when ethanol is used as the solvent.
Taking the preparation of 2-phenyl-2, 3-dihydro-quinazolin-4 (1H) -one as an example, an ethanol solution of o-aminobenzamide, benzaldehyde and iodine is adopted, after 15min is determined to be the optimal ultrasonic time at 20-30 ℃, other conditions are kept unchanged, common polar and nonpolar solvents are explored, and the results are shown in Table 2 and FIG. 2:
TABLE 2 solvent optimization
1.3
Simultaneously, six common laboratory proton and aprotic solvents are used as research objects, and under the condition that the ultrasonic time, the ultrasonic temperature and the iodine concentration are consistent, the influence of the solvents on the quality of the product is researched. The reaction of the anthranilamide and the benzaldehyde is selected, and the solvent condition is optimized, so that the quality of the product is highest when 95% ethanol and ethanol are used as solvents, the quality of the product is the highest, the difference between the quality of the product and the quality of the product is small, and the 95% ethanol is selected from the economic aspect.
In the course of the experiment, the crude product obtained in petroleum ether as solvent was black, different from the product of other solvents, but monitored as the same substance by TLC. The crude product was found to be a target product in a lower yield than absolute ethanol by the fact that the material became white after recrystallization and the melting point was consistent with the Rf value of TLC of the product.
Although specific embodiments of the invention have been described in detail with reference to the accompanying drawings, it should not be construed as limiting the scope of protection of the present patent. Various modifications and variations which may be made by those skilled in the art without the creative effort are within the scope of the patent described in the claims.

Claims (2)

1. The ultrasonic synthesis method of the 2, 3-dihydro-quinazoline-4 (1H) -ketone compound is characterized by comprising the following steps:
co-dissolving o-aminobenzamide or derivatives thereof and aldehyde or ketone compounds in a solvent, adding elemental iodine, performing ultrasonic treatment at room temperature, and standing for crystallization to obtain the compound;
wherein the power of the ultrasonic wave is 360W, the frequency of the ultrasonic wave is 40KHz, and the time of the ultrasonic wave is 15-30 min; the solvent is ethanol solution with the volume fraction of 95%;
the mass ratio of the anthranilamide or the derivative thereof, the aldehyde or ketone compound to the elemental iodine is 1:1:5-40;
the 2, 3-dihydro-quinazoline-4 (1H) -ketone compounds are as follows:
、/>、/>、、/>、/>or->。
2. The method for ultrasonic synthesis of 2, 3-dihydroquinazolin-4 (1H) -one compound according to claim 1, further comprising the following steps after crystallization: and recrystallizing the crude product obtained after crystallization by adopting an ethanol water solution, wherein the volume fraction of the ethanol water solution is 70-90%.
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