Method of producing derivatives of tetrahydro-1,3,5-thiadiazin-4-on or salts thereof

专利摘要:
The tetrahydro-1,3,5-thiadiazin-4-one compounds of the general formula <IMAGE> in which R<1>, R<2> and R<3>, which may be identical or different, each denote an alkyl group having from 1 to 8 carbon atoms, an allyl group, a cycloalkyl group having from 3 to 6 carbon atoms, an alkoxyalkyl group with a total of from 3 to 6 carbon atoms, a benzyl group, phenyl group or substituted phenyl group containing one or more substituents from the group comprising alkyl groups having from 1 to 4 carbon atoms, nitro groups, halogen atoms, alkoxy groups having from 1 to 4 carbon atoms and trifluoromethyl groups, and R<2> and R<3> may also represent hydrogen atoms, are useful compounds for the control of insects and mites.
公开号:SU876057A3
申请号:SU782701050
申请日:1978-12-22
公开日:1981-10-23
发明作者:Икеда Кенити；Канно Хидео；Ясуи Митихиро；Харада Тапуо
申请人:Нихон Нохияку Ко.Лтд (Фирма)；
IPC主号:

专利说明:

3 where k and R have the indicated meanings, followed by isolation of the desired product in free form or as a salt. The process is carried out in the presence of a base. Carbamoyl chloride and thiourea can react without the addition of a base. In this case, compound T is obtained in the form of hydrochloride. The reaction is carried out under the action of heat. If the compound is to be obtained in the free state, it is obtained by dissolving the hydrochloride in water while adjusting the pH of the solution to a neutral or slightly alkaline value. The method cannot be used for chlorination of aniline derivatives having substituents on their benzene cores sensitive to chlorination. In this case, it is necessary to carry out an addition reaction in which the product of dehydration — condensation (for example, azomethine or hexahydro-S-triazine) of the aniline derivative and formaldehyde is subjected to reaction with phosgene or trichloromethyl chloroformate. The resulting carbamoyl chloride must be isolated, and the reaction mixture can be used in the subsequent reaction with thiourea. If the substituents in the thiourea molecule differ from each other, then there is a certain tendency towards the positions occupied by substituents in the target compound of formula I. If R and R of the thioure are alkyl groups, the substituent is an alkyl group having a longer carbon chain, or a more bulky alkyl group having a more branched carbon chain attached to a nitrogen atom, will assume its bulkiness determines the chain length of the substituent. Accordingly, if 1, 3-Dialkyl-thio-urea having straight chain alkyl groups is used, then an alkyl group with a large number of carbon atoms | The ode usually occupies a position in compound I. If thiomo-chevine is used with substituents of approximately equal bulkiness, a mixture of compounds of the formula A, is formed. S-Ar1 M-Aei 7 R-S N-Ae B A N-At1 (where Alk and Alk mean alkyl groups having approximately the same degree of branching. In this respect, the phenylalkyl group exhibits the same tendency towards an alkyl group. If the reaction ring formation is carried out using 1-alkyl3-arylthiourea, the aryl group is introduced to the position of R-compound 1. However, even when using such thiourea, if the alkyl group is methyl, sometimes a mixture of the compound with the methyl group is obtained with compound I, sing in the position R whose methyl group is is in position R. Such a mixture in some cases can be divided into two compounds using the difference in their solubilities. The ring formation reaction is associated with the steric structure of bulkiness of the R and R groups. The reaction is carried out in a solvent that does not significantly affect reaction progress. Suitable solvents for use are water, aromatic hydrocarbons such as benzene, toluene and xylene, ketones such as acetone, cyclohexanone and methyl ethyl ketone, ethers such as tetrahydrofuran, dioxane and ethyl ether, halogenated hydrocarbons, such as chloroform, carbon tetrachloride and chlorobenzene, alcohols, such as ethanol and propanol, esters of aliphatic acids, such as ethyl acetate, aliphatic amides, such as dimethylformamide and dimethylacetamide, dimethyl sulfoxide and other solvents, which do not affect the reaction. These solvents can also be used in combinations, such as mixtures of water with organic solvents, in a mixture of organic solvents. Bases used in the reaction include inorganic bases such as potassium hydroxide, sodium hydroxide, aqueous ammonia, potassium carbonate, sodium carbonate and acid sodium carbonate, and organic bases such as triethylamine, pyridine, and 1,8-diazaGicyclo (5l .O) -7ydeken. These bases are used in most cases as an aqueous solution, although they can be used as a powder.
The reaction temperature can be selected in a wide range from -10 to, but the preferred temperature range is from room temperature to about a method using a base (method A) and more than a method without using a base (method c).
Since the reaction between thiourea and N-chloromethyl-N-phenylcarbamoyl chloride is equimolar, the reactants are used in an equimolar ratio or with a slight excess of any reactant. The amount of base used per mole of any reactant is 2 moles, or slightly more for method A and 1 mole or slightly more.
After completion of the reaction, the reaction mixture is treated with an appropriate solvent to extract compound I and the extract solution is washed, dried and freed from solvent to obtain compound I in the form of crystals or oil, which, if necessary, is further purified.
c If compound T needs to be isolated as a salt, then either way B is carried out or compound I is treated with the desired acid. Acids used to make salt are
(5 common inorganic or organic acids and include HC1, HBg,, HzP04, HNO, HC 10,
, formic acid and benzenesulfonic acid.
JO Typical examples of compounds of the formula are given in table. one.
R.
876057
8 Continued table. one
876057
10 Continued table. one
eleven
876057
12
Continued table. one
13
876057
A Continued table. one
15
876057
sixteen .
Continued table. one
17
18
876057 Continuation of the table. one
 N
/ 4 I
S N - R
nineteen
876057
20 Continued table. one
ni 1.
13. 135. 136. 137. 138. 139. YO. 141.. . kk fVi
 1.5090
n-CjjH 1,
,
, 1.5579 T.PL. 65.67C
t-C-H 4 9
 1.5697
-Sb
Cyclohexyl CH CHCH CH CHCH CH CH 2 CH CHCH CH L CHGH, nC, H9 nCJH ,, i V9, 1.5941, 2, n 1.5753 1.5722 1.5719 T.PL. 46-47 ° C T.PL. 92-94C 1-C, H 104-106 0 1,5604 p.SN 4- 9 1,5580 T.PL. 82-8zs l-CjH T.PL. 80-82C 75-77c t-CjH 4 9 n 1.5561 1.5544, n 1.5464.
23
876057
2i
Continued table. one
25 CH. V CH s-c /, 1-CjH, CH Phenyl
CH
CH20CHN CH2
,
C H och-CH ,,
X Z.
Cyclopentyl
18A.
876057
26
Continued table. 1 / n-e H i-c, H S-C.H 4 9
M.p. (decomposition) nj ° 1,
1,5559
1.5572
M.p. 74-75,5С
109-115 s
 U
t t 111-122 С 1ij6-1ii7 C NMR spectrum NMR spectrum Also obtained in the form of a mixture with compound No. 166
185.
27
876057
28 Continuation of table.
29
876057
30 Continued table. I
31
"76057
32
Continued table. one
33
. H
876057 Continuation of the table. one
35
36
876057
Continued table. one
37
38
876057 Continuation of the table. one
39
0
876057 Continuation of the table. one
41
876057
k2 Continued table. one
“H
876057
k Continued table. I
i
876D57
Continued table. J
uh
876057
. 50 Continued table. one
51
Aoo.
4-cl
2-cl
itOI. 4-Cl 2-Cl 02.
2-Cl 3-0
.
3-ci
5-C1
kQk.
3-Cl 5-Cl
05. 3-CI 5-Cl
"About.
3-CI 5-Cl
ii07.
3-Cl 5-Cl 08.
3-Cl5-Cl
09
3-C1
5-C1
410.
5-CI
3-Cl PE. 5-cl
3-cl
12. 3-Cl
5-Cl 4.3.
4-C1
3-cl
. 4-Cl 3-Cl
15. 4-C1
3-Cl 6. 4-Cl
3-cl
417.
4-Cl 3-CI
876057
52 Continued table. one
15
,
- SdN tG £ zbz
  B5602
.
 M.p.
U5-1i 7c
CH
2V
with H
100-102 С
2 580-82С
l-CjH,
n-C, H1 -G M
1-C, H,
81-83 С S 7
-stc H
PZ-115 S
CH: /
1-С, Н 90-92С
78-8l ° C
t-CgH
17
23
, 5699 X
nj, 1.5822
s-c H 1.5862
,
T.PL. 86-88c
C., H
PR 1.5848
n-CgH-j
n-CgH.
T.PL. 104-107C
,
114.5-117,
t-sdn
n-j3 1,5772
53
876057
St Continued table. 1 i Compounds I show strong physiological activity against insects, especially larvae. The larvae treated with the indicated compound, or who ate the food treated with the compound, die from improper molting. Insects sensitive to the compound are, for example, Hemiptera, loleoptera, Dip tera, Lepidoptera, Orthoptera. In addition, many compounds have activity against ticks, some of which retain insecticidal activity against the red citrus mite (Panonychus citri Megregor) and to the spider double mite (Tetranychus urticae Koch) even at a concentration of 1000 parts per million, and the mortality rate is 80 % or higher. Accordingly, the compounds according to the invention are useful as physiologically active substances for controlling harmful insects when applied to plants, corn, and the like. to protect them from damage caused by these insects and mites. For example, the proposed compound can be used as an active substance to protect rice, corn and other grains, vegetables, flowers and ornamental plants, trees, cotton, fruit trees, forests, urchin grains, grass, lawns and wood products from harmful insects. The compound can also be used to control insects that are harmful to the environment, for example, to control mosquitoes and flies. The compound is particularly useful for combating insect pests in rice fields such as brown cicada (Nilaparvata lugens Stad a), small brown cicada (Laodelphax striatellus Fallen), white-backed filly (Sogatella fureifera Norvath), green rice filly (Nephotettix c). cicadas In addition, compared with known insecticides, such as phosphorus compounds and carbamate compounds, the proposed compounds are much less toxic to mammals and, therefore, much safer. For example, 2-1-butylimino-3 isopropyl 5-phenyltetrahydro-1,3,5 thiadiazine -o (compound No.). and 2-t-butyl 756 imino-3-isopropyl-5-p-tolyl-tetrahydro-1, 3,5-thiadiazine-one (compound No. 318) have (for male mice) equal to 10,000 mg / kg, or else above. Many other compounds have an LDyo (for male mice) of 5000 mg / kg or higher. Compared with the known phosphorus insecticides and carbamate insecticides, the proposed compounds possess insecticidal activity at lower concentrations, although the magnitude of the activity depends on the particular insect species. For example, when determining mortality for 7 days after spraying with a compound of brown cicada's larvae, 1-naphthyl-G-methylcarbamate (commercial insecticide NAC) gives a mortality of only 30% at a concentration of 200 parts per million, while Compound No. 318 gives a mortality rate of 100% at a concentration of 100 ppm. To eliminate or eliminate harmful insects and mites, the compound is directly applied to objects that need to be protected, or to insects that need to be destroyed (undiluted spraying). For example, a compound in the form of a liquid, with a purity of 95% or even higher, can be sprayed from an airplane, resulting in a mist of very small particles of liquid. The compound can also be used to treat ponds and ponds populated by larvae, or to treat surrounding water or irrigation water with food for the larvae, to make the surrounding water or food toxic to the larvae. However, the proposed compound is in most cases used in a form suitable for use in combination with application or dilution with an inert carrier, and, if necessary, when mixed with additional agents, to destroy or eliminate harmful insects under the influence of the physiological activity of the compound. The proposed compound is mixed in an appropriate proportion with a suitable inert carrier and, if necessary, with additional agents, so that the compound can be dissolved, dispersed, suspended, displaced, impregnated.
adsorb or adhere and shape into a suitable preparation, such as, for example, solution, suspension, emulsifiable concentrate, oil sprayer, wettable powder, dust, granules, tablets, grains, paste or aerosol preparation.
The inert carrier can be a solid, liquid or gas. Materials for solid carrier materials include vegetable powders, such as soybean flour, grain flour, wood flour, crust flour, sawdust, tobacco stalk flour, walnut shell flour, wheat bran, ground pulp and plant extraction, fibrous materials such as paper, corrugated cardboard and fabric waste; synthetic polymers, such as powdered synthetic resins and polymer granules (for example, urea-formaldehyde polymer), inorganic or mineral substances in the form of powder or granules with the desired particle size, for example, clay (for example, kaolin, bentonite and acid clay), talc (for example, talc or pyrophyllite), siliceous materials (for example, diatomaceous earths, silica sand, mica, synthetic silicates, finely divided synthetic silicic acid, etc.), powdered sulfur, activated carbon, pumice, calcined diatomoan earth, ground brick, fly ash, and juice, calcium carbonate and calcium phosphate, chemical fertilizers such as ammonium sulfate, ammonium nitrate, urea and ammonium chloride, compost, sodium sulfate, sugars and other soluble substances. These solid carriers are used individually or as mixtures of two or more components. The materials for the carrier liquid are chosen not only from solvents for the active compound, but from substances which do not dissolve it, in which the active compound can be dispersed in the presence of a suitable auxiliary agent. Such liquid materials are used alone or as a mixture of two or more components. Examples are water, alcohols (e.g., methanol, ethanol, butanol, and ethylene glycol), methones (e.g., acetone, methyl dicyl ketone.
76057 .58 Di-11-butyl ketone and cyclohexanone), ethers (for example ethyl ether, dioxane, cellulose, di-propanyl ether and tetrahydrofu 5), apiphatic hydrocarbons (for example gasoline and mineral oils), aromatic hydrocarbons (for example benzene, xylene, solvent) -. naphtha and alkylnaphthalenes), halo-substituted hydrocarbons (for example dichloroethane, chlorobenzenes and hydrocarbon tetrachloride), esters (for example ethyl acetate, dibutyl phthalate and dioctyl phthalate), amides of acids (for example dimethylacetamide, diethyl formamide), nitriles (for example acetonitrile) and dimethyl sulfoxide. Gaseous carriers include freons and other aerosol propellants that
20 are gases under normal conditions.
Auxiliary agents include the following materials, which are used depending on the purpose of use. Often, a combination of two or more additional agents is used, and in some cases no additional agents are used. Surface-active agents are used to emulsify, disperse, dissolve, and / or wet the active compound. Examples are polyoxyethylene alkylaryl ethers, polyoxyethylene alkyl ethers
35 esters, polyoxyethylene esters of higher fatty acids, polyoxyethylene esters of resin acid, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan
40 monooleate, alkyl aryl sulfonates, naphthalene sulfonic acid condensation products, ligninsulfonate and sulfate esters of higher alcohols. The following substances are used as
 dispersion stabilizers, spreading agents and binders for the active compound (rot: casein, gelatin, starch, alginic acid, methylcellulose, carboxymethylcellulose,
50 gum arabic, polyvinyl alcohol, turpentine of dry distillation of wood, rice bran oil, bentonite and ligninsulfonates.
In order to improve the flow properties of solid preparations, waxes, stearates and alkyl phosphates, naphthalenesulfonates and polyphosphates can be used as peptizing agents for dispersion. Defoaming agents such as silicone oil can also be included. The proportion of active compound in the insecticidal composition can be changed as required. A suitable proportion of active compound is usually from 0.5 to 20 ppm in powder or granular formulations and from 0.1 to 90 pbw. in emulsifiable concentrates and wettable powders. To destroy various harmful insects or to protect plants from damage by various insects, insecticidal preparations are used by themselves or. After appropriate dilution or suspension in water or in another medium, and an effective amount of the preparation is applied to plants or to the environment surrounding it. on the site populated by harmful insects. For example, to kill harmful insects in a rice field, an insecticidal preparation is applied to the leaves and stalks of rice plants, either on the soil floor, or into the water that covers the rice field. The amount of consumption when applying an insecticidal preparation varies depending on various factors such as the type of insect selected, the conditions and trends of insects, the weather, the surrounding conditions, the form of the insecticidal preparation, the type of application, the site of application, and the time of year. In the case of an emulsifiable concentrate and a wettable powder, which are usually used in liquid form, the usual method of preparing a spray preparation is dilution to a final concentration of 0.001% by weight or higher in content of the active ingredient. Powder and granules are usually used at a flow rate of from 1 to 10 kg per 10 ares (approximately 100 m). The insecticidal preparation can be used in combination or in conjunction with other pesticides, fertilizers, plant nutrients and plant growth regulators. Examples of insecticides that can be used in a mixture with the proposed insecticide are: O, 0-dimethyl-O- (4-nitro-3 methylfere) and thiophosphate (fenitrothion); 60 0,0-dimethyl 0- (3-methyl-methylthiophenyl) thiophosphate (Bayeid); 0,0-dimethyl 3 (carbethoxyphenylmethyl) dithiopho spat (Elsan); 0,0-diethyl O- (2-isopropyl-methylpyrimidyl-6) thiophosphate (Diazipop); 0,0-dimethyl 2,2,2-trichloro-1-o diethylphosphonate (Dipterex); 0-ethyl-O-p-cyanophenyl phenylphosphonate (Surecide); 0-ethyl-O-p-nitrophenyl phenylthiophosphonate (EPN); 0,0-dipropyl 0-4-methylthiophenyl phosphate (propapos); O, O-dimethyl-3-phthalimidomethyl dithiophosphate (inidan); 0,0-dimethyl 0-dichlorovinyl phosphate (DDVP); O, 0-dimethyl-5- (N-methylcarbamoylmethyl) dithiofosfa.t (dimethoat); O, O-dimethyl-S- (1,2-dicarbethoxyethyl) dithiophosphate (malathon); I-naphthyl N-methylcarbamate (NAC); t-tolit N-methylcarbamate (MTMS); 2-isopropoxyphenyl N-methylcarbamate (PHC), Ethyl-N- (dimethyl-dithiophosphorylacetyl) -N-methylcarbamate (Meckerbam); 3,4-xylyl-M-methylcarbamate (MRMS); 2-z-butylphenyl-M-methylcarbamate (BPMC); 2-isopropylphenyl-M-methylcarbamate (MGRS); 2-chlorophenyl-M-methylcarbamate ((tPMC); 3, 5 xylyl-M-methylcarbamate (CMSJ; 2- (1,3-dioxoran-2-yl) phenyl Nmethylcarbamate (Dioxacarb); 3-1-butylphenyl 11-methylcarbamate (Ferbam); 4-diallylamino-3, 5-DimethylphenylN-methyl-n-m-n-tc (APC), 3-methyl-N- (methylcarbamoyl-oxo-c-thioacetoimidate (CMethomil); N- (2-methyl-n-chlorophenyl) -N, M-dimet) chlorphenamidine); 1, 3-bis {carbamoylthio) -2- (M, M-dimethylamino) propane hydrochloride (Cagtap). Diisopropyl-1,3-dithiolan-2-ylidene malonate (isoprotoblan); N-H (-chlorophenyl) amino carbonyl 2, 6-di-Orobenzamide (diflubenzuron); O, O-dimethyl-S-2- (isopropylthio) ethyl phosphorodithioate (isothioate); O, 0-diethyl-5- 2- (ethylthio) ethyl phosphorodithioate (Disulfoton); 2, 3 Dihydro-2,2-dimethylbenzofu ran-7 yl-M-methylcarbamate (carbafuran). Example 1. 2-Ketilimino-4-phenyl-5 isopropyl tetrahydro-1, 3.5 thiadiazin-4-one (compound No. 66). 3, g (0.02 mol) of M-isopropyl-M-chloromethyl carbamoyl chloride and 3.3 g (0.02 mol of 1-methyl-3 phenylthiourea) are dissolved in 50 ml of benzene. The resulting solution is heated under reflux with stirring in After cooling, the precipitated crystals are collected by filtration, washed with benzene and dissolved in 200 ml of water. The resulting aqueous solution is mixed with 20 ml of a saturated aqueous solution of sodium carbonate and extracted with 100 ml of benzene. The benzene layer is washed with water, dried and concentrated under reduced pressure getting a crystal which are recrystallized from isopropyl alcohol. Melting point 17 - 176 ° C, yield 2.1 g (4 °.) NMR {CO1) cTl, 19 (d, 6H), 3.00 (S, 3N), 4, 42 (S, 2H), 4.30-4.80 (t, 1H), 7.0-7.6 (t, 5H). Example 2. 2-p-tolylimino3-methyl-5 t-butyl-tetrahydro-1,3,5thiadiazin-4-one (compound No. 72). In 50 ml of toluene, 3.7 g (0.02 mol) of Mg-butyl-M-chloromethylcarbamoyl chloride and 3.6 g (0.02 mol) of 1-methyl-3 P tolyl thiomevine are dissolved. The resulting solution is heated under reflux for 2 hours. The precipitated crystals are collected by filtration and washed with acetone (melting point C, with decomposition). The crystals are dissolved in 100 ml of water, 10 ml of 20% sodium hydroxide solution are added and the mixture is extracted with 50 ml of benzene. The crystals obtained by removing benzene under vacuum are recrystallized from isopropanol. Yield 4.3 g (73), melting point PZ-PZ C. NMR (CDC (f 1.48 (S, 9H), 2.30 (S, 3N), 3.35 (S, 3N), 4, 48 (S, 2H, 6.65-7-25 (t, 4H). Similarly, 2- (2-methyl4 chloro) -phenylimino-3-methyl-5-isopropyltetrahydro-1, 3,5-thiadiazine-thiadiazine- 4-one (compound f 67) was obtained from ,, 4 g of D-isopropyl-1-chloromethylcarbamoyl chloride and 4.2 g of methyl-3 (2-methyl-4-chloro) phenylthiourea. 762 Melting point 91-92 C, yield 3.2 g. NMR (SOSTS): Cfl, 20 (s, 6H), 2.10 (S, 3N), 3.45 (S, 3N), 4.30 (S, 2H), 4.45- 4.95 (t. W), 6.55-7.20 (t, 3N). PRI me R 3. 2-t-butylimino3-phenyl-5 t-butyltetrahydro-1, 3.5 thiadiazin-4- he (compound No. 77). 3.7 g (0.02 mol) M-1 was dissolved in 50 ml of acetone -butyl-N-chloromethylcarbamoyl chloride and 3.9 g (0.02 mol) of lt-butyl-3-phenylthiourea With stirring, 2.8 g of potassium carbonate powder was added to the resulting solution and the mixture was heated under reflux for 2 h. The reaction mixture was poured into water and extracted with 50 ml of benzene. The benzene layer was washed with water, dried and concentrated under reduced pressure. The resulting crystals were recrystallized from isopropyl alcohol. Yield 4.1 g (66), melting point 133134 0 NMR (SOSTS): 1.10 (s, 9H), 1.46 (s, 9H), 4.60 (s; 2H), 7.0-7 , 4 (t, 5H). Example 4. 2-Ethylimino-3 otolyl-5-t-butyltetrahydro-1, 3,5-thiazin-4-one (compound No. 80). 3.7 g (0.02 mol) of N-1-butyl-M-chloromethylcarbamoyl chloride and 3.8 g of 1-ethyl-3 o-tolylthiourea are dissolved in 50 ml of benzene. While stirring, 8 g of a 20% sodium hydroxide solution was added to this solution, and stirring was continued for another 4 hours at a temperature of 30 L. O. The reaction mixture was poured into water and extracted with 50 ml of benzene. The benzene layer was washed with water and dried. The crystals obtained by removing benzene by distillation recrystallized from isopropyl alcohol. Yield 3.8 g (63), melting point 157-153 ° C. Example 5. 2-Phenylimino-Zphenyl-5-1-butyltetrahydro-1, 3,5-thiadiazine.-4-one (compound t 78). 3.7 g (0.02 mol) of N-1-butyl-M-chloromethylcarbamoyl chloride and 4.6 g of 1,3-diphenylthiourea are dissolved in a mixture of 50 ml of benzene and 10 ml of dimethyl sulfoxide. While stirring at room temperature, 6.1 g of 1,8-aazibicyclo (5.4.0) -7-undecene was added to this solution, and stirring was continued for another 5 hours. The reaction mixture was poured into water and extracted with benzene. The benzene layer was washed with water and dried. The crystals obtained by the removal of benzene by distillation recrystallized from isopropyl alcohol. Yield 4, kg (65%), melting point C. Example 6. 2-Isopropylimino3-isopropyl-5 methyltetrahydro-1, 3.5 thiadiazin-4-one (compound No. 1). To 2.8 g (0.02 mol) of N-methyl-Mhlormethylcarbamoyl chloride dissolved in 50 ml of benzene, 3.2 g (0.02 mol) of 1.3 diisopropylthiourea were added. The mixture was heated under reflux with stirring for 2 hours. After cooling, 10 g of a 301% potassium hydroxide solution and 50 ml of benzene were added to the cm s and the mixture was shaken gently. The separated benzene layer was washed with water, dried and the benzene layer was distilled off in vacuo. The crystals thus obtained were recrystallized from ether. Yield 3.0 g (66). melting point is 7b-77 ° C. NMR () (f: l, 15 (d, 6H),, CO (d, 6H), 3.10 (S, 3N), k, kS (S, 2H), 4.50-4.80 (t , 1H), 3.30-3.80 (t, 1H). Example 7-2-Ethylimino-3.5 diethyl tetrahydro-1,3,5 thiadiazin-4on (compound W 7). To a mixture 3.1 g ( 0.02 mol) -M-ethylN-chloromethylcarbamoyl and 2.6 g (0.02 mol) of 1,3-DIethylthiourea, dissolved in 50 ml of benzene, were added with stirring at room temperature, 8 g of sodium hydroxide 20 solution After stirring for 5 hours, the reaction mixture was poured into water and extracted with HELP with 50 ml of benzene. The benzene layer was washed with water, dried and the benzene was distilled off under vacuum. the oily substance was recrystallized from ether in a yield of 2.8 g (66), melting point 68-70 ° C. NMR (SOSTS) (G: 1.20 (t, 9H), 3.203, 70 (t, 4H), 3.75-4.10 (q 2H), 4.40 (S, 2H). Example 2-Isopropylimino 3-methyl-5-isopropyl tetrahydro-1,3,5 thiadizin-4-one (compound No. 18) 3.4 g (0.02 mol) of M-isopropyl-M-chloromethylcarbamoyl loride and 2.6 g (0.02 mol of 1-isopropyl-3 methylthiourea) were dissolved in 50 MP of benzene. After cooling, precipitated crystals (melting point 198-200c, with decomposition) were collected by filtration, washed with a small amount of acetone, dissolved again in 100 ml of water, 10 ml of potassium hydroxide solution was added and extracted with 100 ml of benzene. The benzene layer was washed with water, dried and benzene was removed by distillation. The crystals thus obtained were recrystallized from ether. The output of 3.8 g (83%). NMR (COClS) O 1.10 (d, 6H), 1.16 (d, 6H), 3.20 (S, 3N), 4.33 (S, 2H), 4.40-4.85 (t. 1H ). 3.30-3.70 (t, 1H). Example 9-2-Methylmino-3. Methyl-5-t-butyltetrahydro-1,3,5 thiadiazin-4-one (Compound No. 31) 3.7 g (0.02 mol) M-1 was dissolved in 50 ml of toluene. -butyl-M-chloromethylcarbamoyl chloride and 2.0 g (0.02 mol) of 1,3-dimethylthiourea. The solution was heated to reflux with stirring for one hour. After cooling, the precipitated crystals (melting point above 220c with decomposition) were collected by filtration, washed with a small amount of acetone, redissolved in 100 ml of water, 10 ml of a 20% sodium hydroxide solution were added, and extracted with 50 ml of benzene. The benzene layer was dried and concentrated under reduced pressure, obtaining 3.5 f (yield 83%) of crystals melting at 51 ° C. NMR (SOS1OSG: 1.47 (S, 9H), 3.03 (S, 3N), 3.14 (S, 3N), 4.53 (S, 2H). Example 10. 2-1-Butylimino3-benzyl -5-butyltetrahydro-1, 3,5-thiadiazin-4-one (compound No. 47). 3.7 g (0.02 mol) of butyl-M-chloromethylcarbamoyl chloride, 4.4 g (0.02 mol) was dissolved in 50 ml of xylene. 8) N-t-butyl-3-benzyl thiourea U X 8 solution of 30% potassium hydroxide solution was added to the X solution stirred at room temperature. The mixture was stirred for 4 hours more with heating from 30 to 30. The reaction mixture was poured into water and extracted 100 The benzene layer was washed with water, dried and benzene was removed by distillation. The oily substance thus obtained was recrystallized from ether to yield 4.5 g (68), melting point 75-76 C.
65
Example 11. 2-Methylimino3-methyl-5 benzyl-tetrahydro-1, 3.5 thiadiazine-one (compound No. 5)
A mixture, g (0.02 mol) of N-benzylM-chloromethylcarbamoyl chloride and 2.0 g (o, 02 mol) of 1.3 dimethylthiourea, was dissolved in 50 ml of ethanol and heated under reflux with stirring for 2 hours. 20 ml of a saturated aqueous solution of potassium carbonate, the mixture was extracted with 100 ml of benzene. The benzene layer was washed with water, dried, and benzene was removed by distillation under reduced pressure, yielding C, O g of crude crystals, which were recrystallized from ether. Yield 3.2 g (63), melting point 93-9 C.
Example 12. 2-1-Butylimino3-methyl-5- (1,1,3,3 tetramethyl) -butyltetrahydro-1, 3,3 thiadizin-1-one (compound No. 63).
In a mixture of 50 ml of benzene and 10 ml of dimethyl sulfoxide, 8 g (0.02 mol) of N- (1, 1, 3,3-tetramethyl) butyl-M-chloromethylcarbamoyl chloride and 2.9 g (0.02 mol) of l were dissolved. -methyl-3-t-butyl thiochemina. While stirring, 2.8 g of potassium carbonate powder was added to the solution and stirring continued for an additional k hours at a temperature of 30 to. The reaction mixture was poured into water and extracted with 50 ml of benzene. The benzene layer was washed with water, dried, and the benzene was removed by distillation under reduced pressure. The oily substance thus obtained was recrystallized from ether. Yield 5) 1 g (82%), melting point 91-93 C.
NMR (SOSTS): 0.97 (S, 9H), 1.50 (S, 6H), 1.90 (S, 2H), 3.18 (S, 3N), l, 5k (S, 2H), 1.20 (s, 9H).
Example 13-2-5-ButyliminoZH-5t-butyltetrahydro-, 3, 5-thiadisin-4-one (compound 1-107).
To 1, g (o, 01 mol) of S-butyl thiourea, dissolved in 20 ml of acetone, was added 8 g of potassium hydroxide solution. To the resulting mixture was added dropwise 1.9 g of Nchloromethyl-Nt-butylcarbamoyl chloride with stirring at room temperature. After stirring for 30 minutes, the reaction mixture was poured into water and extracted with 100 ml of benzene.
76057 6
The benzene layer was dried and concentrated to obtain crude crystals, which were recrystallized from a mixture of ether — iso-5-propyl alcohol. At the same time, 1.6 g (yield 63%) of crystals melting at 98-100 ° C were obtained.
Example 14. 2-Amino-ZN-5-1 butyltetrahydro-1, 3.5 thiadiazin-4 10 (ZN) -one (compound N 109).
To a suspension of 0.8 g (o, 01 mol) thioumaeins and 8 g of a solution of potassium hydroxide in 50 ml of benzene were added dropwise with stirring 15 at room temperature 1.9 g (0.01 mol) of N-chloromethyl-Nt-butylcarbamoyl chloid. After mixing-. for one hour at room temperature, the resulting 20 crystals were collected by filtration and recrystallized from chloroform, yielding 0.75 g (yield 1%) of crystals melting at 123-125 ° C.
Example 15. 2-Methylimino-Z25 methyl-5-phenyltetrahydro-1,3,5 thiadiazin-4-one (compound No. 115).
2.1 g (0.01 mol) of M-chloromethyl-M-phenylcarbamoyl chloride and 1.0 g of 0.01 mol 30 of 1,3-dimethylthiourea are dissolved in 50 ml of benzene. The resulting solution was heated under reflux with stirring for 3 hours. After cooling, the benzene layer was removed from the reaction mixture by decanting. Residual layer
35 washed with a small amount of benzene. The residue (hydrochloride, melting point 1b8-170C, with decomposition) was dissolved in water, 10 ml of 10% aqueous solution of hydrate was added.
40% sodium oxide and extracted with 1Ppm benzene. The benzene layer was washed with water, dried and benzene was distilled off by distillation under reduced pressure to obtain crude crystals, which were recrystallized from isopropyl alcohol. Yield 1.3 g (51%) melting point 68-70 C.
NMR () (/: 3.15 (S, ZN), 3, ZP
(S, 3N), 4.80 (S, 2H), 7.33 (S, 5H). 50
Example 16. 2-Isopropylimino-3-methyl-5-phenyltetrahydro1, 3.5 thiadiazin-4-one (compound N 118).
55B 50 ml of benzene dissolved 2.1 g
(0.01 mol) N-chloromethyl-N-phenylcarbamoyl chloride and 1.3 g (0.01 mol) of 1-isopropyl-3 methylthiourea. Under stirring at room temperature, a solution of a 20% aqueous solution of sodium hydroxide was added to the 67 solution and the mixture was stirred for 6 hours. The reaction mixture was poured into water and extracted with 50 ml of benzene. The benzene layer was washed with water, dried and concentrated to give crude crystals, which were then recrystallized from isopropyl alcohol. Yield 1.3 g (50), melting point 72-73 ,. NMR (SOGTs) SG 1, 15 (d, 6H), 3.29 (S, 3N), 3.25-3.85 {t, 1H), 4.73 (S, 2H), 7.28 (S, 5H ). Example 17. 2-Isopropylimino-3-isopropyl-5 Phenyltetrahydro1, 3,5-thiadiazin-4-one (Compound No. kk). 2.1 g (0.01 mol) of M-chloromethyl-M- was dissolved in 50 ml of benzene. phenylcarbamoyl chloride and 1.6 g (0.01 mol) 1.3 diisopropyl thiourea. The solution was heated under reflux with stirring for 2 hours. The resulting crystals were collected by filtration. The crystals (hydrochloride, melting point 188-190 ° C with decomposition) were washed with a small amount of cold acetone, dissolved in water, 2.8 g of powdered sodium carbonate were added and extracted with 100 ml of benzene. The benzene layer was washed with water, dried, and benzene was removed by distillation to obtain crude crystals, which were then recrystallized from isopropyl alcohol. Yield 1.8 g (62%), melting point. NMR spectrum (), 15 (d, 6H) 1, + 9 (d, 6H), 3.25-3.68 (t, 1H), / 4.82-4.99 (l1, 1H), 4 , 75 (S, 2H), 7.30 (S, 5H). HR spectrum (KBG): x 0.1660. Example 18. 2-t-Butylimino3-isopropyl-5 Phenyltetrahydro-1, 3.5 thiadiazin-4-one (Compound No. 145) 2.1 g (0.01 mol) l was dissolved in a mixture of 50 ml of acetone and 10 ml of dimethylformamide l-chloromethyl-N-phenylcarbamoyl chloride and 1.7 g (0.01 mol) of 1-isopropyl-3 1-butyl thiourea. Under stirring at room temperature, 4 ml of a 30% aqueous solution of potassium hydroxide was added to the solution, and the mixture was stirred for an additional 5 hours. The reaction mixture was poured into water. Q was extracted with 100 ml of benzene. The benzene layer was washed with water, dried and concentrated, radiating a 7-viscous oily substance, which was recrystallized from isopropyl alcohol. Yield 2.0 g (65), m.p. 104-10bc. NMR (SPS.TS) with / H, 33 (S, 9H), 1.45 (d, 6H), 4.70 (S, 2H), 4.32-5.00 (t, 1H), 7, 30 (S, 5H). Example 19. 2-Isopropylimino-3-isobutip-5-phenyltetrahydro-1, 3, 5-thiadiazin-4-one (compound No. 149) 2.1 g (0.01 mol) dissolved in a mixture of 50 ml of tetrahydrofuran and 10 ml of bimethyl sulfoxide. ) M-chloromethyl-Mphenylcarbamoyl chloride and 1.7 g (0.01 mol) of 1-isopropyl-3-isobutylthiourea. With stirring at room temperature, 2.1 g of triethylamine was added to the solution and the mixture was stirred for an additional 6 hours. The reaction mixture was poured into water and extracted with 100 ml of benzene. The benzene layer was washed with water, dried and concentrated to give a viscous oily substance, which was recrystallized from isopropyl alcohol. Yield 2.4 g (78), melting point 80-820. NMR (SOSTS) (G 0.90 (d, 6H), 1.15 (d, 6H), 1.70-2.30 (t, 1H), 3.353, 75 (t, 1H), 4.05, (d, 2H), 4.75 (S, 2H), 7.30 (S, 5H), Example 20. 2-1-Butyliumio3-cyclohexyl -5-phenyltetrahydro1, 3 5-thiadiazin-4-one (compound No. 155). In 50 ml of ether, 2.1 g (0.01 mol) of N-chloromethyl-Nphenylcarbamyl chloride and 2.1 g (0.01 mol) 1-cyclohexyl-3-t-butylthiourea with the addition of 1.6 g of pyridine. The resulting solution was stirred for 4 hours at room temperature. The reaction mixture was poured into water and extracted with 100 ml of benzene. The benzene layer was washed with water, dried and concentrated This gave an oily substance that was recrystallized from isopropyl alcohol: I Yield 1.6 g (45%), melting point 86-89 ° C. NMR (CDCl3) cf 1.35 (S, 9H), 1.02, 5 ( M, 11H), 4.75 (S, 2H), 7.33 (S, 5H), Example 21. 2-Benzylimino3-methyl-5Phenyltetrahydro-1, 3.5thiadiazin-4-one (compound, No. 121). In 20 ml of the 6th (w / w) aqueous solution of potassium hydroxide susc69
Pendali 1.8 g (0.01 mol) of 1-methyl-3-benzylthiourea. 2.1 g of N-chloromethyl-M-phenylcarbamoyl chloride was added to the suspension while stirring at room temperature, and the mixture was vigorously stirred for one hour at room temperature. The reaction mixture was poured into water and extracted with 100 ml of benzene. The benzene layer was washed with water, dried, and concentrated to give an oily substance, which was then recrystallized from isopropyl alcohol. Yield 2.0 g (63%), melting point 90-92 ° C.
NMR (COClS) GZ, 35 (S, ZN), i, 50 (S, 2H), 1 “, b5 (S, 2H), 7.00-7.5 (t, YN).
Example 22. 2-n-OctyliminoZ-methyl-5-phenyltetrahydro-1, 3.5 thiadiazine - (- it (compound tf 122).
2.1 (0.01 mol) M-chloromethyl-M-phenylcarbamoyl chloride and 2.0 tons (0.01 mol) of 1-methyl-3-n-octylthiourea were dissolved in ethanol. The solution was heated under reflux with stirring for 3 hours. After cooling, the reaction mixture was poured into water, 3 ml of 2N aqueous sodium hydroxide solution was added and extracted with 100 ml of benzene. The benzene layer was washed with water, dried and concentrated to give a viscous oily substance, which was dissolved in 6N hydrochloric acid and the insoluble substances were removed by extraction with benzene. The aqueous layer was slightly alkalified by adding a 20% w / w aqueous solution of sodium hydroxide and extracted with 50 ml of benzene. The benzene layer was washed with water, dried and concentrated to give a viscous oily substance. The yield of 1.2 g (36%), p 1,5551.
Example 23-2-5-Butylimino3, 5-Diphenyltetrahydro-1,3,5-thiadiazin-α-one (Compound No. 1b3).
2.1 g (0.01 mol) of M-chloromethyl-M-phenylcarbamoyl chloride and 1.9 g (0.01 mol) of 1-butyl-3-phenylthiourea are dissolved in a mixture of 50 ml of ethyl acetate and 10 ml of dimethyl sulfoxide. 1.1 g of powdered sodium carbonate was added to the solution and the mixture was stirred for 3 hours at. Reaction mixture in water and extracted with 50 ml of ethyl acetate. The ethyl acetate layer was washed with water, dried and concentrated.
centered to give crude crystals, which are then recrystallized from isopropyl alcohol. Yield 1.9 g (57%) - melting point 35, 5 ° C.
NMR (CDClI) (f 0.5-1.5 (m, 8H), 3.0-3.5 (m, IH), 4.85 (S, 2H), 7.25 (S, YUN).
Example 2C. 2- (2-Methyl) 10 Phenylimino-3-methyl-5-phenyltetrahydro-1, 3, 3-thiadiazine-one (compound No. 12+).
2.1 g (0.01 mol) of N-chloromethyl-M-phenylcar 15 bamoyl chloride and 1.8 g (0.01 mol) of 1-methyl-3-o-tolylthiourea are dissolved in 50 ml of benzene. 3.1 g of 1,8 diazabicyclo (5.4,4) -undecene were added to the solution while stirring at room temperature.
The mixture was stirred for kh. The reaction mixture was poured into water and extracted with 100 ml of benzene. The benzene solution was washed with water, dried, and then concentrated to obtain neo-purified crystals, which were then recrystallized from isopropyl alcohol. Yield 2.0 g (63%), melting point.
NMR () (-2, B (S, ZN), 3.50
30 (S ЗН), Ц.бВ (S, 2Н), 7.0-7.5 (t, 9Н).
Example 25. 2-Methylimino3- (2-methyl-chloro) phenyl-5-phenyltetrahydro-1, 5.5 thiadiazin-4-one (Compound K ° 1 66).
35
In a mixture of 10 ml of benzene and 10 ml of tetrahydrofuran, 1.4 g (1/150 mop) of M-chloromethyl-M-phenylcarbamoyl chloride and 1.4 g (1/150 mol) of 1-methyl-3 (2-methyl-4 chlorine phenylthio 40 urea. While stirring, 5.5 g of a 10% w / w aqueous solution of sodium hydroxide was added to the solution, and the mixture was vigorously stirred for 4 hours while maintaining
45 this is the reaction temperature at. After completion of the reaction, the benzene layer was washed with water and concentrated to give an oily mixture of 2-methylimino-3- (2-methyl-4-chloro) -phenyl 50 5-phenyltetrahydro-1,3,5 thiadiazin-one and 2- (2-methyl -4-chlorfsniliminoZ-metip-5-fvniltetragidro-1, 3,5-thia-Diazin-4-one.
Connection number 166 can be identified
 from the mixture as follows.
This oily mixture was dissolved with hydrochloric acid (D) hydrochloric acid () and the insoluble material was removed by washing with ethyl acetate. The aqueous layer was slightly alkalified to precipitate crystals, which were then recrystallized from a mixture of isopropyl alcohol-n-hexane, to give 1 ,. g (yield 52 /;) of compound no. 166. Melting point 121-123 ° P. NMR (G.Oc1e) (G.-2.18 (S, 3N), 3.07 (S, 3N; M-CH3),, 92 (S, 2H). Example 26. 2-Methylimino3-methyl-5 - (p-chlorophenyl) -tetrahydro1, 3 | 5-thiadiazin-4-one (compound W 188). 2.4 g (0.01 mol) of N-chloromethyl-N- (p-chlorophenyl) were dissolved in 50 ml of benzene carbamoyl chloride and 1.0 g (0.01 mol) of 1,3-dimethylthiolchine. The solution was heated under reflux and for 1 hour. The resulting crystals were collected by filtration and washed with acetone. The resulting white crystals (hydrochloride, melting point) were dissolved in water , added 5 ml, 20% sodium hydroxide solution, thoroughly shaken and extracted Enzol. The crystals obtained by the removal of benzene by distillation were recrystallized from isopropyl alcohol to obtain 1.6 g (yield 60%) of crystals melting at 98-10 ° C, Example 27. 2-Isopropyl-3-methyl-5- (p-chlorophenyl) -tetrahydro-ro-1,3,5-thiadiazin-4-one (compound No. 189). 6 50 ml of benzene dissolved 2.4 g (0.01 mol) of M-chloromethyl-M- (p- chlorophenyl) -carbamoyl chloride and 1.3 g (0.01 mol) of 1-isopropyl-3-methylthiourea. 8 ml of 10% sodium hydroxide solution was added dropwise to the solution with stirring, and the mixture was further stirred for 4 hours at AO C, 8 water was poured into the reaction mixture and extracted with benzene. The benzene layer was washed with water, dried, and the benzene was removed by distillation, to obtain crystals, which were then recrystallized from isopropyl alcohol. Thus, 2.4 g (yield) of crystals, melting at 10b-108c, was obtained. NMR (SOSTS), 18 {d, 6H), 3.32 (S, 3N), 3.55 (t, 1H), 4.80 (S, 2H) 7.25 (S, 4H). 2.3 g (0.01 mol) of I-isopropyl-3-t-oK Tilty ;; urea and 2.7 g (0.01 mol) of N 772 chloromethyl-M-trifluoromethylphenylcarbamoyl chloride were treated in a similar way, to obtain 2-t -octylimino3-isopropyl-5- (t-trifluoromethylphenyl) tetrahydro-1,3,5-thiadiazin-4-one (compound IJV.266) as an oily substance: p 1.5089 NMR (CDCL) cG4.70 (5 21-1, -N-CH, -S-). Example 28. 2-t-Butylimino3-isopropyl-5- (p-chlorophenyl) -tetrahydro 1,3,5 thiadiazin-4-one (Compound No. 196). 2.4 g (o, 01 mol) of M-chloromethyl-M- (p-chlorophenyl) carbamoyl chloride and 1.7 g (o, 01 mol) of 1-isopropyl-3-f-butylthiomo were dissolved in 50 ml of benzene. . After adding 8 ml of a 15% potassium hydroxide solution, the mixture was left to react by heating from 40 to 50 ° C with stirring for 4 hours. The reaction mixture was poured into water and extracted with benzene. The benzene layer was washed with water, dried and benzene was distilled off by distillation to give crude crystals, which were recrystallized from ethanol. Thus, 2.0 g (yield 62) of crystals, melting at 123-125 ° C, were obtained. Example 29o 2-1-Butylimino3-benzyl-5- (p-chlorophenyl) -tetrahydro1, 3,5-thiadiazin-4-one (Compound No. 204). 2.4 g (0.01 mol) of M-chloromethyl-M- (p-chlorophenyl) carbamoyl chloride and 2.2 g (0.01 mol) and lt-butyl-3-benzylthiourea were added in 50 ml of toluene. After adding 8 ml of 10d sodium hydroxide solution, the mixture was left to react with heating from 40 to 50 ° C, with stirring for 4 hours. The reaction mixture was washed with water and the toluene layer was dried and the toluene was removed by distillation to obtain crude crystals, which were then peresryhallizoali from isopropyl alcohol . Thus, 2.8 g (yield 73) of crystals melting at 87-89 ° C were obtained. Example 30, - 2-t-Bytilyl-3-ethyl-5- (t-chlorofe; yl). tetrahydro1, 3,5-thiodiazin-4-one (compound No. 216). 2.4 g (0.01 mol) of N-chloromethyl N-tm-chlorophenyl) carbamoyl chloride and 1.6 g (0.01 mol) -ethy-3-t-butyl were dissolved in 50 ml of tetrahydrofuran.
73
thiourea After adding 8 ml of potassium hydroxide solution, the mixture was allowed to react by heating from 0 to k with stirring for k hours. The reaction mixture was poured into water and extracted with benzene. The benzene layer was dried and concentrated to give a viscous, oily substance.
nif 1.5683
NMR (CDCI) cG: 3.90 (q 2H,
-N-Cj H), 70 (S, 2H, -J-)
Example 31. 2-1-Butylimino3-5-butyl-5 (m-h.lorphenyl) -tetrahydro-1, 3,5-thiadiazin-α-one (compound No. 225).
In 50 ml of xylene, 2, g (0.01 mol) N-chloromethyl-M- (t chlorophenyl) carbamoyl chloride and 1.8 g (0.01 mol) of 1-S-butyl-3 t-butylthiouvine were dissolved. After adding 8 ml of 1 Single solution of sodium hydroxide, the mixture was left to react from kQ to stirring for k hours for heating. The reaction mixture was washed with water, dried, and dry gaseous hydrogen chloride was fed to this xylene solution at room temperature until Crystals have not ceased to precipitate. The crystals were collected by filtration and washed with acetone. Crystals (hydrochloride, melting point Tbb with decomposition,) were suspended in water, 10 ml of 15% potassium hydroxide solution was added, shaken well and extracted with benzene, the benzene layer was dried and benzene was distilled off to obtain 1.9 (yield 60 %) white crystals melting at C.
Example 32 2-Isopropylimino-3-isopropyl-5- (o-chlorophenyl) tetrahydro-1, 3,5-thiadiazin-4-one (Comp. No.
In 50 ml of benzene, 2, g (0.01 mol) of N-chloromethyl-N- {o-chlorophenyl) -carbamoyl chloride and 1.6 g (0.01 mol) of 1,3 diisopropylthiourea were dissolved. After adding 8 ml of a 10% sodium hydroxide solution, the mixture was reacted with heating from 50 to, with stirring, for an hour. The reaction mixture was washed with water, dried, and benzene was distilled from it to give crude crystals, which then recrystallized from isopoopilic
760577
alcohol, receiving 1, 8 g (yield)
crystals, melt cisc at 95-9bS. NMR (COOe) cG1.15 (d, 6H), 1.45 (d, 6H), +, 68 (S, 2H) 3.50 (t, - 1H), 5, 73 (t, 1H), 7 , 15 t, CN).
This method was carried out using 1.7 g (0.01 mol) of 1-isopropyl-3-t-butylthiourea to obtain white crystals (melting point 8810) 2-1-butylimino-3-isopropyl-5 (o-chlorophenyl) - tetrahydro-1,3,5 thiadiazine-tt-oH (compound No.).
The output of 2.3 g (). The crystals were dissolved in benzene and hydrogen chloride gas was introduced into the solution. The precipitated crystals were collected by filtration and washed with acetone, to obtain crystalline hydrochloride, melting at (decomposed), 20 In a similar way, 1.7 g (0.01 mol) of 1-isoprolyl-5-butyl thiourea were dried and 2 2 g (o, 01 mol) L-chloromethyl-M- (p-fluoride (H and carbamoyl chloride, to obtain crystals melting at. The crystals gave a single spot on the thin-layer chromatogram using a mixture of hexane as the developing solvent) acetone (8: 2).
thirty
However, the NMR spectrum showed that the crystals were a mixture of about 1: 1 of compounds No. 361 and HG 362.
2-Isopropylimino-3 5-butyl-5 (p35 fluorophenyl) -te-trahydro-1,3) 5-thiadiazin-α-one:
NMR (CDCL) (G -N-CH-CJI
1, (d, 3N).
40
2-5-Butylimino-3-isopropyl-5- (rfluorophenyl) -tetrahydro-1,3,5-thiadiazine-one:
NMR (CDCI-) cG H-CH-C H
I
45
sn
1.15 (d, 3N).
Example 33. 2-Methylimino3-methyl-5- (p-fluorophenyl) -tetrahydro 50, 3.5 thiadiazin-4-one hydrochloride (compound No. 277)
1.0 g (0.01 mol), 1.3 Dimethylthiourea, and 2.2 g (0.01 mol) of M-chloromethyl-M55 (p-fluorophenyl) -carbamoyl chloride were dissolved in 50 ml of benzene. The solution was heated under reflux with stirring for one hour. Oily substance, po75
the resulting benzene distillation was dissolved in acetone, and the precipitated crystals were collected by filtration and washed with acetone to obtain 2.1 g (yield 85) of white hydrochloride crystals, melting at (with decomposition). A part (1 g) of the crystals was dissolved in 20 ml of water, 5 ml of a 10% solution of sodium hydroxide were added, shaken thoroughly and extracted with benzene. The benzene layer was dried and concentrated to obtain free base crystals, melting at 105-106 C.
Similarly, 1.7 g (0.07 mol) of 1-isopropyl-3t-butylthiourea were reacted with 2.2 g (0.01 mol) of N-chloromethyl-M (fluorophenyl) -carbamoyl chloride to give 2-1-butylimino -3-and opropyl-5- (rfluorophenyl) -tetrahydro-1,3,5-thiadiazin-α-one (compound K 282) as hydrochloride, melting at 195 ° C. Yield 2.8 g (80%). The crystals were suspended in 20 ml of water and treated in a manner similar to that described above, to obtain white crystals of the free base, melting at 109-110 ° C (with decomposition) (isopropanol). Yield 2.0 g (63)
Example 3. 2-Isopropylimino-3-allyl-5- (m-chlorophenyl) -tetrahydro-1, 3,5-thiadiazine-one (compound No. 217) o
2.4 g (0.01 mol) of M-chloromethyl-M- (M-chlorophenyl) carbamoyl chloride and 1.58 g (0.01 mol) of 1-allyl-3-isopropyl thiourea are dissolved in 50 ml of benzene. After adding 8 ml of a 10d sodium hydroxide solution to the resulting solution, the mixture was subjected to reaction with heating from kQ to, with stirring, during C 1. The reaction mixture was washed with water, dried, and concentrated to give a viscous oily substance (Ref. 1.5857) in exit 80.
This oily substance was dissolved in benzene and hydrogen chloride gas was introduced into the solution, yielding hydrochloride, melting at 179 s (with decomposition).
Example 35 2-t-Butylimino3-isopropyl-5- (m-chlorfeNIlJ-tetrahydro-1, 3,5-thiadiazine - + - it (compound No. 211).
2.4 g (0.01 mol)) -chloromethyl-N- (t-chlorophenyl) -carbamoyl chloride and 1.7 g were dissolved in 50 ml of benzene
7605776
(0.01 mol) 1-isopropyl-3-t-butylthiourea. After adding 8 ml of a 10d sodium hydroxide solution, the cwecb was reacted with heating from QT 40 to 50 ° C, stirring for an hour. The benzene layer was washed with water, dried, and concentrated to obtain a viscous oily substance, which was recrystallized from isopropyl alcohol to obtain 1.5 g (yield 45) of white crystals with a melting point of 113-115 ° C. The crystals were dissolved in benzene and hydrogen chloride gas was passed into the solution to obtain the hydrochloride melting at (with decomposition).
Example 36 2-cyclohexyl iminog3-isopropyl-5- (o-chlorophenyl) tetrahydro-1, 3,5-thiadiazin-4-one (compound No. 252).
In 50 ml of benzene, 2.4 g (0.01 mol) of M-chloromethyl-N- (o-chlorophenyl) -carbamoyl chloride and 2.0 g (0.01 mol) of 1-isopropyl-3-cyclohex25 siltiourea were dissolved. After adding 8 ml of a 1L sodium hydroxide solution, the mixture was reacted with heating from 40 to 4 with stirring. After the reaction was completed, the benzene layer was washed with water, dried and concentrated to obtain a viscous oily substance, which was recrystallized from Isopropyl alcohol mixture, n-hex22 san (1: 1), obtaining white crystals, melting at 123 125 ° C, with the output
from szg
.., U.
Example 37. 2-Ethylamino-Stphenyl-5- (o-chlorophenyl) tetrahydro1, 3.5 Thiadiazin-4-one (Compound No. 256).
2.4 g (0.01 mol) of N-chloromethyl-N- (o-chlorophenyl) carbamoyl chloride and 1.8 g (0.01 mol) of 1-ethyl-3-phenylthiourea are dissolved in 50 ml of benzene. After adding 8 ml of a 10% sodium hydroxide solution, the mixture was subjected to reaction with heating from 40 to 5 PS with stirring for 4 hours. After completion of the reaction, the benzene layer was washed with water, dried and concentrated, to obtain a viscous oily substance, which was recrystallized from a mixture of isopropyl alcohol-n-hexane (1: 1), to obtain 0.8 g (14 white crystals, melting at 77–79 ° C).
Example 38. 2-Isopropylimino-3-isopropyl-5 (in-trifluoromethylfe 77
Nile) -tetrahydro-1,3,3-thiadiazine-he (compound No. 1b5).
2.7 g (0.01 mol) of N-chloromethyl-H- (t-trifluoromethylphenyl) carbamoyl chloride and 1.6 g (0.01 mol) of 3 diisopropylthiourea are dissolved in 50 ml of benzene. After adding 8 ml of a 10% sodium hydroxide solution, the mixture was reacted with heating from ku to 50 ° C with stirring for k hours. After completion of the reaction, the benzene layer was washed with water, dried and concentrated to obtain a viscous oily substance, which was recrystallized from a mixture of isopropyl alcohol n-hexane (1: 1), to obtain 1.3 g (yield 36) of white crystals, melting at 6 ° C.
Example 39. 2-t-Bytilymino3-isopropyl-5 (p-toli) tetrahydro1, 3.5 thiadiazine -) - it (compound No. 318).
1.0 g (0.028 mol) of 1.3.5 Tris (p-tolyl) hexahydro - $ - triazine was suspended in 10 ml of tetrahydrofuran. The resulting suspension was added dropwise with stirring to 5 ml of ice-cold benzene, which contained 0.9 g (0 mol) of trichloromethyl chloroformate. After completion of the dropwise addition, the mixture was stirred for one hour at. room temperature. To the mixture was added 20 ml of benzene containing I, g (o, 0083 mol) of 1-nzopropyl-3tbutylamine, After adding 7 ml of 10% sodium hydroxide solution, the mixture was stirred for 6 hours at-40 to 30 ° C. The reaction mixture was washed with water, dried and distilled off the benzene. The crude product thus obtained was recrystallized from isopropyl alcohol to obtain 1.2 g (yield) of white crystals, melting at A8-120 ° C.
NMR (SPNTS) (G, 75 (S, 2H), i, 70 (pp, 1H), 2.35 (S, 3N), 1.7 (d, 6H), 1.35 (S, 9H).
Example 0, 2-benzylimino3-benzyl-5 (p-tolyl) -tetrahydro-, 3, 5-thiadiazin-α-one (Compound D 321).
1.0 g (0.0028 mol) of 1,3,5 tris (p-tolyl) -hexahydro-S-triazine was suspended in 10 ml of tetrahydrofuran. Suspa (i.d. was added dropwise with stirring at room temperature to 5 ml of benzene containing
7605778
J0.9 g (0 mol) of trichloromethyl chloroform. After that, the mixture was stirred for one hour at room temperature. Added to the mixture
5 2.1 g (0.0083 mol) of 1,3-bis (benzyl) thiourea, dissolved in 20 ml of benzene, then 7 ml of 10% sodium hydroxide solution was added. The mixture was stirred for 7 h.
10 at room temperature. The reaction mixture was washed with water, dried and benzene was distilled from it, obtaining crude crystals, which were then recrystallized from isopropyl alcohol, to obtain 1.7 g (yield 5U) of white crystals, melting 1 of tsix at 152-153c.
NMR () d 7.2 (m, IH), 5.32 (S, 2H), / -CH2-), 78 (S, 2H), t, 50
20 (S, 2H, fl-CH2-) 2.32 (S, 3N).
Example 41. 2-Isopropylimino-3 isopropyl-5- (o-tolyl) -tetrahydro-1, 3.5 thiadiazin-α-he (compound No. 301).
25 Solution 2, g (o, 0067 mol) 1,3, 5-tris (o-tolyl) -hexahydro-5-triazine in 10 ml of tetrahydrofuran was added dropwise with stirring at room temperature to 10 ml of benzo-30n, containing 2.0 g (0, P1 mol)
trilomethyl chloroform. After that, the mixture was stirred for 30 minutes at. A solution of 3.2 g (o, 02 mol) of 1,3-diisopropyl thiourea in 30 ml of benzene was added to the mixture, then 16 ml of a 105% solution of sodium hydroxide was added. The mixture was stirred for an hour, washed with water, dried and benzene was distilled from it. The remaining oil and base was mixed with n-hexane and insoluble substances were removed by filtration.
N-hexane was removed from the filtrate by distillation, while 3 g (yield 45) of a colorless oily substance remained.
p 1.5587.,
NMR () about 4.77 (t. 1H, N-CH-), 4.52 (S, 2H), Z.chV (t, 1H, N-CH-),
5 ° 22.3 (S, 3N), 14.9 (d, 6I), 1.17 (d, 6H).
Spent this method using 1.5 g (0.0042 mol) of 1,3,5-tris (o-tolyl) -hexahydro-5-triazine,
1.3 g (0, ОБЗ mol) of trichloromethyl chloroform, 3.0 g (0.013 mol) 1.3 bis (cyclohexyl) thiourea and 11 ml of 10% solution of sodium hydroxide nat79
| ri, while receiving 2.2 g (yield 6) of 2-cyclohexylamino-3-cyclohexyl-5 (o-tolyl) -tetrahydrr-1, thiadiazine-it (compound No. 307) as a colorless oily substance (p | ° 1,5568).
Similarly, 1.7 g (0.00 mol) of hexahydro-1,3,5 tris (p-ethylphenyl) -5-triazine, 1.3 g (o, 006 mol) of trichloromethyl chloroform, 1.3 g (0.012 mol) 1.3 dimethylthiourea and 11 ml of 10% sodium hydroxide solution to obtain 0.8 g (yield 2) of 2-methylimino3-methyl-5 (p-ethylphenyl) -tetrahydro1, 3 5 thiadiazin-4-one (compound No. 331) of the formula
in the form of a colorless oily substance (nj ° 1.5922),
Similarly, 1.7 g (0.00 mol) of hexahydro-1,3, 5-tris (p-ethylphenyl) -S triazine, 1.3 g (o, 006 mol) of trichloromethyl chloroform, 2.2 g (2.2 g) were used. 0.012 mol) of 1-isopropyl-3 t-butylthiourea and 11 ml of a 10% solution of sodium hydroxide to obtain 0.7 g (yield 17%} of 21-butyl lithino-3 isopropyl-5 (p-ethylphenyl) -tetrahydro- 1,3,5 tiediazin4-it (compound No. 113).
Similarly, 2.2 g (o, 006 mol) hexagid {l-1, 3.5 tris ethylphenyl-S-triazine, 1.7 g (o, 008 mol) trichloromethyl chloroform, 3.1 g lS-butyl thiourea and 15 ml of 10% sodium hydroxide solution to obtain 2.7 g (yield: k7%) 2-1-butylimino-3-5-butyl 5- (o-methylphenyl) -tetrahydro-1,3,5-tya, aia in-4-one (compound No. 339) as a colorless, viscous, oily substance (p ojtOl),
Example 42. 2-1-Butylimino3-isopropyl-5- (p-methoxyphenyl-tetrahydro-1, 3,5-thiadiazin-4-one (Compound No. 355)
ABOUT
 -N - C, S - N-C4.Hg-t
7605780
2.7 g (0.007 mol) of 1.3.5 Tris (p-methoxyphenyl) -hexahydro-S-triazine were suspended in 20 ml of tetrahydrofuran. The suspension was added dropwise, with stirring at room temperature, to 10 ml of benzene containing 2.0 g (0.01 mol) of trichloromethyl chloroformate, after which the mixture was stirred for another 30 minutes at
10 30 C. To the mixture was added a solution (0.02 mol) of 1-isopropyl-3-t-butyl thiourea in 30 ml of benzene, then 16 ml of a 10% sodium hydroxide solution was added. The mixture was stirred in
15 for k hours at, washed with water, dried and benzene was distilled off. The remaining oily substance was mixed with n / .. hexane. and insoluble materials were removed by filtration. From filtrate
20 removed n-hexane by distillation, resulting in unpurified crystals, which were then recrystallized from isopropyl alcohol, yielding g (yield 51) of white crystals, melting at 99-101.5 C.
NMR (CDCl 3) sG; 4.64 (S, 2H), i, 59 (m, 1H), 3.75 (S, 3N), 1.43 (d 6H), 1.31 (S, 9H) .
Similarly, 30 2.7 g (0.00b7) 1,3,5-tris (p-methoxyphenyl) hexahydro-5-triazine, 2JO g (0.01 mol) trichloromethyl chloroformate, 3.8 G (0, 02 mol) 1 - $ - butyl-3-1butylthiourea and 16 ml of 10% sodium hydroxide solution to obtain 1.8 g (yield 26%) 2-t-6ytilimino-3-5-butyl-5 (p- methoxyphenyl) tetrahydro-1, 3,5-iadiazin-4-one (compound No. 355) as white crystals, melting at.
NMR (SOSTS) d 4.70 (S, 2H), 4.36 (d, IH), 3.75 (S, 3N), 1; 9 (m, 2H), 1.47 (d, 3H), 1.32 (s, 9H), 0.92 (t, 3H).
In a similar manner, 1.4 g (0.0033 mol) of 1,3,5-tris (p-methoxyphenyl) -hexahydro-S-Jpiazine, 1 g (0.005 mol) of trichloromethyl chloroformmate, 2.1 g (0.01 mol ) 1-isopropyl-3-benzylthiourea and 3 ml of 10d sodium hydroxide solution to obtain 1.9 g (yield S2%} 2 of isopropylimino-3-phenyl-Spermethoxyphenyl-tetrahydro-1,3,5-thiadiazin-one (compound No. 35b) as white crystals melting at 114 C.
NMR (CDCl1) cf5.29 (S 2H, -N-CH-), 4.72 (S, 2H), 3.75 (S, 3N), 3.52 (m, IH), 1.09 (d , 6H). Example 2-t-Butylimino3-isopropyl-5 (o isopropyl) -phenyltetrahydro-1, 3, 5 thiadiazin-α-one (compound fP). To solution 1, g (0.003 mol) of 1.3 5-trio (o-isopropyl) -phenyl-hexahydro-5-triazine in 20 ml of tetrahydrofuran was added dropwise under stirring at room temperature 1.0 g of trichloromethyl chloroformate. After stirring in Within 10 minutes, a solution of 1.7 g of 1-iso-2-3-t-butylthioumachevine in 20 ml of benzene was added to the mixture, then 8 ml of potassium hydroxide solution was added. The mixture was stirred for 3 hours at a temperature of from 40 to 5 (gS. The reaction mixture was poured into water and extracted with 50 ml of benzene. The benzene layer was dried and the benzene was removed by distillation, the crude crystals remained, which were then recrystallized from isopropyl alcohol to obtain 1.7 g (yield 52) of white crystals melting at YuYA-SHE C. Example C. 2-Isopropylimino-3-isopropyl-5- (p-bromophenyl) -tetrahydro-1, 3,5-thiadiazin-one (Match No. 293 ) In 50 ml of benzene, 2.8 g (0.01 mol) of M-chloromethyl-M- (p-bromophenyl) -carbamoyl chloride and 1.6 g of 1.3 diisopropylthiochol were dissolved. During the process of stirring, k ml of a 20% solution of sodium hydroxide was added to the solution and the mixture was reacted at OT.tO temperature for an hour. The reaction mixture was washed with water, dried and benzene was distilled off to obtain crude crystals, which were recrystallized from isopropyl alcohol, to obtain 1.6 g (yield 45) of white crystals, melting at 1. 1 122 C. Example C, 2-t-Butylimino 3-5-butyl-5- (-ethoxy-phenyl / -tetrahydro-1, 3, 5-thiadiazine - + - it (compound No. 368). A solution of 1.50 g (0.0033 mol) of hexahydro-1 .3,5-tris (-ethoxyphenyl) S-triazine in 10 ml of tetrahydrofuran was added dropwise with stirring to 10 ml of benzene containing 1.1 g of phosgene. To the mixture was added 1.88 g of 1-S-butyl-3-t-butylthiocochemia, 15% potassium hydroxide solution. The mixture was stirred for k hours at a temperature from kQ 7 to. The reaction mixture was poured into water and extracted with 50 ml of benzene. The benzene layer was washed with water, dried and concentrated. The crude crystals thus obtained were recrystallized from isopropyl alcohol to obtain 1.7 g (yield 6) of white crystals, melting at 666 ° C. Example 6, 2-Ethylimio-Zethyl-5 (3, -dichlorophenyl) -tetrahydro1, 3,5-thiadiazin-4-one (Compound No. it13). 2.73 g (0.01 mol) (3 (-dichlorophenyl) N-chloromethylcarbamoyl chloride, 30 ml of benzene and 1.32 g (0.01 mol) of 1,3-DI-ethylthiourea) were placed in a conical flask, to obtain a homogeneous The solution was added to a solution of 8 ml of a 10% sodium hydroxide solution and the reactants solution was left to react with stirring in a water bath at a temperature of from 0 to 50 ° C for k hours. After the reaction was completed, the benzene layer was washed with water, dried over anhydrous sodium sulfate and concentrated. The remaining oily substance was recrystallized from isopropyl alcohol, yielding 1 g (yield) of white crystals, melting at 86–88 ° C. Example 47. 2-Benzyl-amino-3-benzyl-5- (3,4-dichlorophenyl) -tetrahydro-1, 3,5-thiadiazine -one (compound no. it23). 2.73 f (0.01 mol) N- (3, -dichlorophenyl) -N chloromethylcarbamoyl chloride, 30 ml of benzene and 2.36 g (P, 01 mol) 1.3 were placed in the reactor. Tibenzylthiourea. To the mixture was added tetrahydrofuran to obtain a homogeneous solution. To the solution was added tetrahydrofuran to obtain a homogeneous solution. 8 ml of a 10% aqueous solution of sodium hydroxide was added to the solution, and the mixture of reactants was reacted with stirring in a water bath at a temperature of 0 to 5 ° C for an hour, after completion of the reaction, the benzene layer was washed with water, dried over anhydrous sodium sulfate and benzene the layer was fed with gaseous hydrogen chloride to obtain the hydrochloride of the target compound. The hydrochloride was added to a mixture of 0 ml of 10; a strong aqueous solution of sodium hydroxide and 30 ml of benzene, to obtain 1.5 g (yield 33) of white crystals of the target compound in ide free of bases which melted at 118-120 ° C. Example 8. 3 1 Butylimino 3-isopropyl-5 (3, -dichlorophenyl) -tet rahydro-1,3 5 Diadiazin-α-he (Compound N ° 1 ()). G (0.01 mol) of N- (3-Dichlorophenyl) -Nchloromethylcarbamoyl chloride, 30 ml of benzene and 1.7 g (0.01 mol) of 1-isopropi-3 t-butylthiomyocherine were placed in the reactor. To the mixture was added dropwise 8 ml of an aqueous solution of sodium hydroxide, sodium hydroxide. The mixture of reactants was reacted with stirring in a water bath at a temperature of from 0 to 4 hours. The reaction mixture was worked up in a manner similar to that described in Example 6, yielding 0.9 g of white crystals melting at 11.5 117 ,. Example 49. 2-Isopropyl but-3-benzyl-5 (3 5 dichlorophenyl) tetrahydro-1,3,5 thiadiazin-4-one (Compound No. 408). 1.37 g (0.005 mol) of M- (3,5-Dichlorophenyl) -Mchloromethylcarbamoyl chloride, 1–04 g (0.0.05 mol) of 1-benzyl-3 isopropyl thiourea and 20 ml of benzene were placed in the reactor. After adding dropwise k ml of a 10% aqueous solution of sodium hydroxide, the mixture of reactants was reacted in a water bath at a temperature of 40 to 50 ° C for 2 hours. After completion of the reaction, the benzene layer was washed with water, dried and gaseous hydrogen chloride was passed through the benzene layer to obtain the target compound hydrochloride. Hydrochloride was added to a mixture of 10 ml of a 10% aqueous solution of sodium hydroxide hydrate and 20 ml of benzene to dissolve the liberated free base in benzene, benzene. The concentrated layer was concentrated and the oily substance obtained as a residue recrystallized from isopropyl alcohol-n-hexane (1: v / v) from the mixture to give 0.8 g (yield 39) of white crystals, melting at 90-9 / - C. Example 50. 2-Isopropyl-but-3-allyl-5 (3, 5-dichlorophenyl) -tetrahydro-T, 3,5-thiadiazin-4-one (combine 1nis number 412). 784 2.73 g (0.01 mol) of N- (3, 5-dichlorophenyl) -N chloromethylcarbamoyl chloride, 1.58 g of 1-allyl-3 isopropyl thiourea and 30 ML benzene were placed in the reactor. To the mixture was added dropwise 8 ml of a 10% aqueous solution of sodium hydroxide and the mixture of reactants was left to react with stirring in a water bath at a temperature of from 40 to 4 hours. After the reaction was completed, the benzene layer was washed with water, dried And concentrated to give an oily substance as a residue. The oily substance was purified by silica gel column chromatography to obtain 0.8 g (yield 22.3%) of oil (4, L5962). Example 51. 2-t-Butylimino3-5-6util-5 (p-ethoxyphenyl) -tetrahydro-1, 3.5 thiadiazin-4-one (compound No. 368). A solution of 2.7 g (0.00b mol) of 1,3,5 tris- (p-ethoxyphenyl) -hexahydro-3 triazine in 10 ml of tetrahydrofuran was added dropwise with stirring at room temperature to 10 ml of benzene containing 1.8 g (0.009 mol) of trichloromethyl chloroformate, the mixture was stirred for 20 minutes at 40 ° C. To the mixture was added a suspension of 3.1 g (0.017 mol) of 1-Sbutyl-3-t-butylthiourea in 20 ml of benzene, after which 15 g were added 10 aqueous sodium hydroxide solution. The mixture of reactants was stirred for 3 hours at 40 ° C, after which the reaction mixture was washed with water, dried, and benzene was distilled off. The residual oily substance was mixed with n-hexane and the insoluble material was removed from it by filtration. Upon removal of n-hexane from the filter by distillation, crude crystals were obtained, which were then recrystallized from isopropyl alcohol to obtain 3.2 g (yield 53) of white crystals, melting at 66-b7 C. Similarly, using 2.4 g (0.006 mol ) 1, 3,5-tris- (2,3dimethylphenyl) hexahydro-5-triazine, 1.8 g (0.009 mol) of trichloromethyl chloroformate, 3.1 g (cP, 017 mol) of 1-ethyl-3-cyclohexyl thiourea and 15 g of a 10% aqueous solution of sodium hydroxide, obtained 3.5 g (yield 61%) of 2-cyclohexylimino-Zethyl-5- (2,3-dimethylphenyl1-tetrahydro-1, 3.5 thiadiazin-4-one (Compound No.382) in the form of white crystals melting at. Z, g (0.006 mol), 1,3,5-trihio (2.3 Dimethylphenyl) -hexagilpo-S-tripiazine, 1.8 g (0.009 mol) of trichloromethyl chloroformate , 2.9 g (0.017 mol) -1-isopropyl-3 t-6 ythylthiomochevine and 15 g of a 10% aqueous solution of sodium hydroxide to obtain 2.5 g (yield) 2-C-butylimino-3 isopropyl-5- ( 2,3-Dimethylphenyl) -tetrahydro-1, 3.5 thiadiazine-it (compound K) as white crystals, melting at. Similarly, 1.6 g (0, mol) 1.3, (2,3-dimethylphenyl) hexahydro-5-triazine, 1.2 g (0.006 mol) of trichloromethyl chloroformate, 2.7 g (0.012 mol) of 1-benzyl were used. -3t-butylthiourea and 11 g of a 10% aqueous solution of sodium hydroxide to obtain 2.5 g (yield 53) of 2-1-butylimino-3-benzyl-5- (2,3-dimethylphenyl) -tetrahydro-1,3 , 5 thiadiazine-oi (compound ff 386) as a colorless oily substance (1.5769). Example 52. 2-Isopropylimino-3-methyl 5 (p-isopropoxyphenyl) tetrahydro-1, 3,5-thiadiazin-one (compound tf 570). A solution of 2.8 g (0.006 mol) of 1,3,5 tris- (p-isopropoxyphenyl) -hexahydro-S-triazine in 10 ml of tetrahydrofuran was added dropwise at room temperature to 10 ml of benzene containing 1.8 g (0.009 mol) trichloromethane chloroformate and the mixture was stirred for 20 minutes at lOC. A suspension of 2.2 g (0.017 mol) of 1-methyl-3-isopropyl thiourea in 20 ml of benzene was added to the mixture, then 15 g of 10% was added dropwise aqueous solution of sodium hydroxide for about one hour. After that, the mixture was stirred for another 2 h at SOС. The reaction mixture was washed with water and the remaining benzene layer was thoroughly mixed with 20 mg of OG hydrochloric acid to obtain the hydrochloride of the target compound. The aqueous layer containing the hydrochloride was washed again with fresh benzene, made basic with an alkaline solution and extracted with benzene. The benzene layer was washed with water, dried, and benzene was distilled from it. The residue was recrystallized from isopropyl alcohol. 786 yielding 1.2 g (yield 23) of white crystals, melting at 112-113 0. 2.8 g (0.006 mol) of 1,3,5-tris (p-isopropoxyphenyl) hexahydro - $ - triazine , 1.8 g (o, 009 mol) of trichloromethyl chloroform, 2.6 g (0.016 mol), 1.3 diisopropyl thiourea, and 15 g of a 10% sodium hydroxide aqueous solution to give 1, g (yield 2) 2-isopropylimine O— 3-isopropyl-5- (p-isopropoxyphenyl) -tetrahydro-1, 3,5-thiadiazin-α-he (compound No. 372) as white crystals, melting at 60-61 ° C. Similarly, 2.2 g (o, 006 mol) of 1,3,5-trio p-isopropoxyphenyl) hexahydro-5-triazine, 1.8 g (0.009 mol) of trichloromethyl chloroformate, 3.0 g (0.016 mol) of 1- S-butyl-3t-butylthiourea and 15 g of a 10% aqueous solution of sodium hydroxide to obtain 1.5 g (yield 2-t-butyl-3-3-t-butyl-5 (rhizopropoxyphenyl) -tetrahydro-1,3 5thiadiazine -4-one (compound N 37) as a colorless oily substance (1,) In a similar way, 2.0 g (0.00 mol) of 1,3,5-tris (p-isopropoxyphenyl) hexahydrotriazine, 1,2 g (0.006 mol) of trichloromethyl chloroformate, 3.1 g (0.012 mol / 1.3 dibenzyl ioureas and 11 g of an aqueous solution of sodium hydroxide to obtain 1.5 g (yield 28) of 2-benzylimino-3-benzyl-5 (p-isopropoxyphenyl) -tetrahydro-1,3,5-thiadiazin-4- it (compound M ° 375) as white crystals, melting at. Example 53. 2-Isopropylimino-3-methyl-5- (2, -dimethylphenium) -tetrahydro-1, 3.5 thiadiazine-one (compound tf 377). In a manner analogous to that described in Example 51, the reaction was carried out using 2, g 0.006 mol 1.3.5 trio 2, + - dimethylphenyl-hexahydrotriazine, 1.8 g 0.009 mol trichloromethyl chloroformate, 2.1 g 0.016 mol 1-methyl-3-isopropyl thiourea and 15 10% aqueous solution of sodium hydroxide. After completion of the reaction, the n-hexane insoluble substance was removed by filtration, and the i-hexane was removed from the filtrate by distillation. The residue was dissolved in ether and gaseous hydrogen chloride was passed through the ether solution. An oily insoluble in ether was immediately released and settled on the bottom. After removing the solvent, an excess amount of the aqueous alkaline solution was added to the oily substance and extraction was performed with benzene. The benzene layer was washed with water, dried, and concentrated to obtain 0.9 g (yield 19) of a colorless oily substance (Ref. 1.567).
Similarly, 2, Cg (0.006 mol), 1,3,5-trio (2, dimethylphenyl) -hexahydro-5-triazine, 1.8 g (0.009 mol) trichloromethyl chloroformate, 2.5 g (0.0016 mol ) 1,3 diisopropyl thiourea and 15 g of 10 dn aqueous solution of sodium hydroxide to obtain 1.2 g (yield 22) of 2-isopropylimino-3-isopropyl-5 (2, -dimethylphenyl) -tetrahydro-1,3 5thiadiazine-it ( compound ff 378) as a slightly yellow oily substance (n | j ° 1.5589).
Similarly, 2, g (0.006 mol) of 1,3,5-trio (2, -dimethylphenyl) -hexahydro-5-triazine, 1.8 g (0.009 mol) of trichloromethyl chloroform, 2.9 g (0.016 mol) of 1- isopropyl-3-t-butylthiochemina and 15 g of a 10% aqueous solution of sodium hydroxide to obtain –1.0 g (18 yield) 2-1-butylimino-3-isopropyl-5- (2, -dimethylphenyl) - tetrahydro1, 3,5-thiadiazine-it (compound 379) as white crystals, melting at 99100 °.
In a similar manner, 373 g (0.007 mol) of 1,3,5-three-thrio (2-methyl-chloropy) -hexagidro-S-triazine- 2.0 g (0.01 mol) of trichloromethyl chloroformate, 3.2 g (0.018 mol) 1-isopropyl-3 1-butyl thymmobidine and 18 101% aqueous solution of sodium hydroxide to obtain 0.5 g (7% yield) of 2-t-butyl-3-isopropyl-5- (2-methyl-chlorophenyl) tetrahydro-1 3,5-thiadiazin-4-one (compound H 387) as white crystals, melting at 122-123 °.
Similarly, 2.7 g (0.02 mol) of N-methylene-2,6-dimethylaniline, 270 g of trichloromethyl chloroformate, 2.0 g (0.02 mol) of 1.3 dimethyl thiourea and 18 g of 10-aq. Water were used. solution G7 1drata sodium oxide to obtain 0.6 g (yield 120) 2-methylimino-3-methyl-5- (2,6-dimethylphenyl) tetrahydro-1, 3,5-tiadizin-4-one (compound N 389 ) as a colorless oily substance (p 1.59b7).
Similarly, 2.7 g (0.6 mol) of methylene-2,6-dimethylaniline, 2.0 g (o, 01 mol) of trichloromethyl chloroformate, 3.3 g (0.019 mol) of 1-isopropyl-5-t-butirythioumachine and 18 g of a 10% aqueous solution of sodium hydroxide to obtain 0.3 g (7 yield) of 2-1-butylimino-3-isopropyl-5- (2,6-dimethylphenyl) -tetrahydro1, 3,5 Diadiazine-it ( Compound No. 388) as white crystals, melting at 103-104 ° C.
five
Example 5. 2-Isopropylimino-3-methyl-5- (2,6-diethylphenyl) -tetrahydro-1, 3,5-thiadiazine-one (compound N ° 393).
A solution of 1.6 g (0.01 mol N-methy flax-2,6-diethylaniline in 20 ml of benzene was added dropwise with stirring to 10 ml of a toluene solution containing 1.2 g of phosgene. After stirring for 10 minutes to the mixture
5, 1.3 g (0.01 mol; 1-methyl 3-isopropyl thiourea) was added and the mixture was heated under reflux for one hour. To the reaction mixture, 100 ml of water was added and the benzene layer was removed. The aqueous layer was made alkaline with 5 ml of 30% solution potassium hydroxide and extraction was carried out with 100 ml of benzene. The benzene layer was pro-oil with water, dried and concentrated to obtain a viscous oily substance. The oily substance was recrystallized from isopropyl alcohol to obtain 1.7 g yield of 56% white crystals, melting at 1060 .
Example 55. 2-Isopropyl. Ino-3 isopropyl-5- (2,6-diethylphenyl) tetrahydro-1, 3,5-tialiazin-α-one (Compound No. 395 "
five
A solution of 1.6 g (0.01 mol of N-methylene-2, 6-diethylanilino in 10 ml of benzene was added with stirring to 10 ml of benzene containing 1.1 g of trichloromethyl chloroformate. After stirring for 10 minutes, the solution was added to the mixture 1.6 g 0.01 mol of 1,3-diisopropyl thiourea in 20 ml of benzene and the mixture was heated under reflux with stirring for one hour. 100 ml of water was added to the reaction mixture and shaken thoroughly. The aqueous layer was separated and mixed with 5 ml of a 30% aqueous solution of potassium hydroxide, precipitating an oily substance which Extracted with benzene. The benzene layer was washed with water, dried and concentrated to a viscous oily substance, which was recrystallized from isopropanol-n-hexane (8: 2) to obtain 1 g (yield) of white crystals, melting at 8990 ° C. NMR (COCl3) (G: 3.50 (t, 1H N-CH Y: -N-CH2-5),, 8 + (m, 1H; ".SO (S, I. C. Example 56. 2- 1-Butylimino5-ethyl-5-phenyl-tetrahydro-1, 3.5 thiadiazin-α-one (compound ff 130. A solution of ifi g of aniline in 250 ml of ethyl alcohol was mixed with 75 ml of 37% formalin and the mixture was mixed for 30 minutes at room temperature. The precipitated crystals were collected by filtration, washed with ethyl alcohol and recrystallized from hot benzene to obtain 1,3,5-triphenylhexahydro-5-triazine, having a melting point at TZO-PZ C. To a solution of 1.2 g of trichloromethyl chloroformate in CHi 10 ml benzene was added dropwise with stirring a solution of 1.0 g (0.0033 mol) of the indicated 1.3.5 triphenyl-hexahydro-5-triazine in 20 ml of tetrahydrofuran, and then a solution of 1.6 g of 1-ethyl-3-1 -butylthiourea in 20 ml of benzene and 8 ml of an aqueous solution of potassium hydroxide. The mixture was heated to 40 ° C with the reactant and stirred for 5 hours. The reaction mixture was poured into water and the separated benzene layer was washed with water and dried. The crude crystals obtained by removal of benzene by distillation recrystallized from isopropyl alcohol to obtain 1.0 g (yield) of white crystals, melting at. In a similar manner, 1.0 g of 1,3,5triphenylhexahydro-S-tripiazine, 1.1 g of trichloromethyl chloroformate and 1.7 g of 1-isopropyl 3-t-butyl thiourea were reacted to obtain 1 .2 g (AO yield) 2-t -butylimino-Zizopropyl-5-phenyl-tetrahydro-1, 3 5thiadiazin-4-one (compound () as white crystals melting at. The test results for insecticidal activity against the brown cicada larva (Ni laparvate Cugens Stahl) are given in Table 2. Table 2
91
69 71 72 75 80 82.
100
100
100
100
100
80 83 87
100
100
100
100
123,126
100
100 127 129
100
70
90

70 2t
100
100
247
100
about
100
876057
92
Continued table. 21
100

100
100
willow
100

100 150
100,151
100,152
100 155
50,156
100,157
100
80 159 162
100,293
100 29
100
295
100,297
100 29, 100
300
100 301 100
93
876057
9 Continued table. 2
95
378
100
100 379 380
100 381
80 332
100 383
100 38i
100
385
100 387
100 388
100
100 390 39
100
100 395 398
100
100
399
koo
100 0
100 02
100 406
80
80 07 409
75
876057
96
Continued table. 2
421
60,422
60,425
60,426
70,427
10Q 428
100
Compounds fP 2 f, 88
Results obtained 7 days after treatment of Compound No. 126,428, results obtained 5 days after treatment.
97
Insecticidal activity against white-backed larva chi876057 was determined.
98 Continued table. 2
20 cadas (Sogatella fureifera Horvath), the results are shown in Table. 3
Table 3
99

100 151 TOO 152 100 196 100 197 100 198 100
100
220 221 100
22
80
80 225 Zk
100,245
100 282
100
The activity of the arachnoid, two-spotted "scout" (Tetranychus urticae Koch) was determined.
59 63 65
100
100
about
100
100
876057 Continuation of the table. 3
328
100
100 100
333
100 100
352
then 0
353
100 0 100
355
100
395
90
100 100
100 100 100 100 100
40 The results obtained are presented in Table. four.
Table C
216
100
100
80
70
219
221
100
100
101 Note.
876057
102 Continued table. k Compounds No. 2 to No. 88: results 2 days after treatment. , Compounds No. 188 - 28: results 5 days after treatment.
103
0
876057 Continued ta6l „I
107
Activity of the green rice-cicada larvae (Nephotettix eincticeps Uhber) was detected
876057
108 Continued tabl. 5
The results are shown in Table. 6
109
876057
no
Table 6
113
876057
1U Continued table. 7
115876057
Insecticidal active116 Continued. eight
117
28it
10Q 285
100,291
100 102
100 303
100 31
100 316
80 318
100 319
100 Insecticidal activity against bug larvae (Togohemipterus Scott),
118
139
100
140
126
100
118
876057 Continuation of the table. 9
itil
100
412 100 70 90
+22
80
151
100
100
152
50 The results obtained are shown in Table. 10, Table 10 Insecticidal activity against
cabbage moth larvae (Plutilla Xylostella Linne).

权利要求:
Claims (2)
[1]
Invention Formula
The method of obtaining derivatives of tetrahydro-1, 3.5 thiadiazin-A-one. general formula
About N- N / "
.
23 R and R can be the same where R
hydrogen or alkyl, allyl, cycloalkyl, alkoxyalkyl containing from 3 to 6 carbon atoms, benzyl, phenyl, unsubstituted or substituted by one or two groups selected from the following number: alkyl C.-C ,, nitro, halogen , alkoxy or trifluoromethyl, or their salts, consisting in the fact that carbamyl chloride of the general formula II
n 1)
- ci
NO- С CH2Ci
in tab. eleven.
Table 11
where R is as defined above, is reacted with the thiourea of general formula III
2 3 R NH С NH R
i
where R and R are as defined above,
with the subsequent selection of the target product in free form or in the form of salt.
[2]
2. The method of claim 1, wherein the process is carried out in the presence of a base.
Prior
itet for at 3a to a mn, 06 „77 with R - phenyl; R and
- hydrogen alkyl Ci-Cg, allyl, cycloalkyl Cg - C, alkoxyalkyl C-C., benzyl, phenyl, unsubstituted or substituted by one or two groups selected from the following number: alkyl Ci-C., alkoxy C-Cj, halogen or trifluoromethyl.
06/29/07 with R = g alkyl, allyl, Cjj-C cycloalkyl, alkoxyalkyl; R - cycloalkyl 1L, alkoxyalkyl 876057120 The obtained results are given
121876057122
07/30/77: R - alkyl, allyl, Sources of information, cycloalkyl, alkoxyalkyl, phenyl, taken into account during the examination
02.28.78 when R is phenyl, replacing 1. Weigand - Hilgetag. Methods valuable alkyl, alkoxy Cj-Cj, experiment in organic chemistry. halo, trifluoromethyl. M., them., 1968, p. .

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同族专利:

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FR2393798A1|1979-01-05|

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IT1109653B|1985-12-23|

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FR2393798B1|1982-01-08|

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NL175694C|1984-12-17|

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NL971006I1|1997-08-01|

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DE2824126C2|1984-06-20|

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MX6009E|1984-09-24|

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

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US4452795A|1981-09-03|1984-06-05|Ciba-Geigy Corporation|5-Phenoxyphenyl-tetrahydro-1,3,5-thiadiazin-4-ones|

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US4443445A|1981-09-10|1984-04-17|Ciba-Geigy Corporation|Imidazo- and pyrimido-1,3,5-thiadiazin-4-ones|

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JPH0566362B2|1985-02-25|1993-09-21|Nihon Nohyaku Co Ltd|

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AU615280B2|1988-07-08|1991-09-26|Mitsui Toatsu Chemicals Inc.|Novel thiadiazines, process for production thereof, and insecticidal and acaricidal agents comprising the thiadiazines|

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EP2127522A1|2008-05-29|2009-12-02|Bayer CropScience AG|Active-agent combinations with insecticidal and acaricidal properties|

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EP2382865A1|2010-04-28|2011-11-02|Bayer CropScience AG|Synergistic active agent compounds|

法律状态:

优先权:

---

申请号 | 申请日 | 专利标题

---

JP6813877A|JPS5539547B2|1977-06-09|1977-06-09|

---

JP7759477A|JPS6121954B2|1977-06-29|1977-06-29|

---

JP9157077A|JPS5519213B2|1977-07-30|1977-07-30|

---

JP2255078A|JPS5539550B2|1978-02-28|1978-02-28|

---