2-koimeterion-3,4-dihydro-2h-1,3-benzoxazin-4-ones exhibiting fluorescence properties and method of production thereof
The invention relates to the field of organic chemistry, namely to new individual compounds of class benzoxazines that exhibit fluorescent properties and can be used as starting products for the synthesis of new heterocyclic systems, as well as substances for sample labeling and additives for reflective paints. Describes 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones of formula I,
where R= H (a), CH3(b) exhibiting fluorescence properties. Also describes 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones as substances for marking, copying and recognition using ultraviolet radiation, 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones as additives for reflective paints and method for producing the above compounds. The technical result obtained new compounds with useful properties. 4 N. and 2 C.p. f-crystals.
The invention relates to the field of organic chemistry, namely to new individual compounds of the class of benzoxazines and method of production thereof, which exhibit fluorescent properties and can be used in the in for sample labeling and additives for reflective paints.
There are various solutions to protect monetary documents, shares, cheques, credit cards, identity cards, passports, using special inks, particularly inks with varying effect, allowing, for example, to move from blue to green depending on the tilt of the document, or paints, which begin to glow only at a certain irradiation, for example, under the action of ultraviolet radiation (see U.S. patent No. 4175776, IPC 42 D 15/00, priority 27.11.78 year). However, the range of these colors at present, small.
Know the use of special paints containing reflecting the substance and, if necessary, aluminum powder (see U.S. patent No. 4066280, IPC 42 D 15/00, priority 03.01.78 year). The disadvantage of applying this paint is the complexity of the drawing on the paper, which leads to restriction of areas of its use relative to the total area of the document.
From literature is known structural analogues of the claimed compounds 2-formylmethylene-4-oxo-3,4-dihydro-2H-1,3-benzoxazines (CHC, 1977, No. 3, S. 322-327).
Structural analogues exhibiting fluorescent properties not identified.
The synthesis is carried out in two stages by slebodnik way it is impossible to obtain 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones, exhibiting fluorescent properties.
The objective of the invention is to develop a simple, one-step retrieval method is not described in the literature 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones, exhibiting fluorescent properties, as well as the expansion of the means, are used as labels to protect documents from unauthorized copying and additives in reflective paint.
The task is carried out by boiling o-gidroksibenziliden arealuxury acids I (a, b) with dicyclohexylcarbodiimide in an inert aprotic solvent according to the scheme:
I, R=H (a), CH3(b); II, R=H (a), CH3(b).
The process is conducted at a temperature of 100-102°C, and in an inert aprotic solvent used 1,4-dioxane.
Compound II (a, b) in the solid state have stable fluorescence (emission in the field of yellow light when =580-595 nm) upon irradiation with UV light of 254 nm. Alcohol and chloroform solutions of compounds II (a, b) have no fluorescence. Fluorescence is retained during storage of the samples under normal conditions for a long time.
From the patent and technical literature were not identified ways to obtain 2-koimeterion-3 original products, solvents in which the reaction takes place, and the temperature, on what basis is it possible to make a conclusion on the compliance of the claimed technical solution the patentability criteria of “novelty” and “inventive step”. The invention is illustrated by the following examples.
Example 1. 2-Penacillin-3,4-dihydro-2H-1,3-benzoxazin-4-one.
A solution of 0.50 g (1,765 mmol) of o-hydroxybenzamide benzoyloxy acid (compound Ia) and 0.36 g (1,765 mmol) dicyclohexylcarbodiimide in 10 ml of absolute dioxane is boiled for 1 hour, cooled, the precipitate of dicyclohexylamine filtered off, the mother liquor is distilled off, the residue is crystallized from benzene. Obtain 0.40 g (85%). Compound Ia. WITH16H11NO3so pl. 198-199°C.
Found, %: C 72,44, N 4,20, N 5,28.
Calculated, %: C 72,45, N 4,18, N 5,28.
Example 2. 2-(4-Methylbenzylamino)-3,4-dihydro-2H-1,3-benzoxazin-4-one.
A solution of 0.52 g (1,765 mmol) of compound IB and 0.36 g (1,765 mmol) dicyclohexylcarbodiimide in 10 ml of absolute dioxane is boiled for 1 hour, cooled, the precipitate of dicyclohexylamine filtered off, the mother liquor is distilled off, the residue is crystallized from benzene. Obtain 0.40 g (82%). Compound IIb. WITH17H13NO3so pl. 185-1B) - pale-yellow crystalline substance, soluble in acetone, chloroform, 1,2-dichloroethane, dimethylsulfoxide, slightly soluble in alkanes, alcohols, insoluble in water. Stable when stored under normal conditions.
In the IR spectra of compounds II (a, b), taken in vaseline oil, there is an absorption band of the lactam carbonyl group benzoxazinones cycle in the field 1700-1705 cm-1and broad absorption band ketone arolina groups involved in the formation of intramolecular hydrogen bonds N-chelate-type region 1630-1640 cm-1.
In the PMR spectra of compounds II (a, b), taken in deuterated chloroform, in addition to the group of signals of aromatic protons in the region 7,21-8,10 memorial plaques are the singlet proton of NH group in the area to 13.29-13,30 M. D., singlet vinyl proton in the field 6,00-6,05 M. D. and singlet proton group SN3when 2,40 M. D. (compound IIB).
The proposed method is simple, one-step and allows you to get not described in the literature 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones with good output.
Optical activity of the proposed compounds can be used individually and in compositions for application is from the encoding.
Mixed with the dyes they can be used for the manufacture of fluorescent paints, glow, which is called the UV and short wavelength visible radiation.
1. 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones of General formula I
where R is H(a), CH3(b)
exhibiting fluorescent properties.
2. 2-Koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones of General formula I as agents for marking, copying and recognition using ultraviolet radiation.
3. 2-Koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones of General formula I as additives for reflective paints.
4. The method of obtaining 2-koimeterion-3,4-dihydro-2H-1,3-benzoxazin-4-ones of General formula
where R is H(a), CH3(b)
characterized in that on-hydroxybenzamide arealuxury acid is subjected to interaction with dicyclohexylcarbodiimide in inert aprotic solvent, followed by separation of the desired products.
5. The method according to p. 4, wherein the process is conducted at a temperature of 100-102°C.
6. The method according to PP.4 and 5, characterized in that as the inert solvent used 1,4-dio is
< / BR>represents an optionally substituted divalent residue of benzene, where the substituents are selected from unsubstituted lower alkyl groups, unsubstituted lower alkoxygroup, unsubstituted lower acyl group, a lower allylthiourea, lower alkylsulfonyl group, halogen atom, etc. or unsubstituted pyridine; Ar represents a phenyl group which may be substituted by one to four groups selected from unsubstituted lower alkyl group, the unsubstituted alkoxygroup, low allylthiourea, lower alkylsulfonyl group, and so on, optional substituted amino group, alkylenedioxy; X is-NH-, oxygen atom or sulfur atom; Y is a sulfur atom, sulfoxide or sulfon; Z represents a single bond or-NR2-; R2- the atom of hydrogen or unsubstituted lower alkyl group; l = 2 or 3; m = 2 or 3; n = 1, 2, or 3, or their salts, or their solvate
< / BR>The compounds obtained can be used to obtain hexatriene-fluorophores
< / BR>where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with
< / BR>is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts
FIELD: organic chemistry, chemical technology, herbicides.
SUBSTANCE: invention describes a method for preparing compounds of the formula (I):
wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):
wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,
or (IVb) ,
wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.
EFFECT: improved preparing method.
9 cl, 12 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to oxazolo- and thiazolo-[4,5-c]-quinoline-4-amines of the general formula (I)
wherein R1 is taken among group consisting of oxygen and sulfur atoms; R2 is taken among hydrogen atom, alkyl, alkyl-OH (hydroxyalkyl), alkyl-X-alkyl, alkyl-O-C(O)-N(R5)2, morpholinyl, pyrrolidinyl, alkyl-X-aryl radical, alkenyl-X-aryl radical; each substitute R3 and R4 represents hydrogen atom or substitutes R3 and R4 taken in common form the condensed aromatic or [1,5]-naphthiridine system; X represents -O- or a single bond; R5 represents hydrogen atom. Also, invention describes intermediate compounds, pharmaceutical composition and a method for stimulating biosynthesis of cytokinins (cytokines) based on these compounds. Invention provides preparing new compounds eliciting valuable biological properties.
EFFECT: valuable properties of compounds.
21 cl, 2 tbl, 64 ex
FIELD: organic chemistry, madicine.
SUBSTANCE: tricyclic benzodiazepines of formula I as well as their pharmaceutical acceptable salts, pharmaceutical composition containing the same and methods for hypertension treatment are disclosed. In formula A is -C(O)-; Y is CH2 or CH as olefinic site; X is CH2 or CH as olefinic site S, O or NR3 (R3 is C1-C8-alkyl) with the proviso that when Y is CH, X also is CH; Z is N or CH; R1 is hydrogen, C1-C8-alkyl, C1-C8-alkoxy or halogen; R2 is NR4COAr (R4 is hydrogen; Ar is phenyl optionally substituted with 1-3 substitutes independently selected from C1-C8-alkyl, halogen, hydroxyl, fluorinated C1-C8-alkylthio and another phenyl optionally substituted with substitute selected from C1-C4-alkyl, halogen, and hydroxyl); R5 is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, fluorine, chlorine, hydroxyl or di-(C1-C4)-alkylamino.
EFFECT: improved pharmaceutical composition for hypertension treatment.
12 cl, 5 tbl, 52 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new compounds of the general formula (1)
wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.
EFFECT: valuable medicinal properties of compounds, improved method for treatment.
26 cl, 1 tbl, 119 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacology.
SUBSTANCE: invention relates to gyrase inhibitors that reduce amount of microorganisms in biological sample by contacting the indicated sample with compound of the formula (I): , to a method for treatment of bacterial infection by using compounds of the formula (I), compounds of the formula (I) and a pharmaceutical composition comprising compounds of the formula (I). Invention provides the enhanced effectiveness of treatment.
EFFECT: valuable medicinal properties of gyrase.
54 cl, 5 tbl, 13 ex
FIELD: organic chemistry, medicine, hematology.
SUBSTANCE: invention elates to new compounds that inhibit activated blood coagulating factor X (Fxa factor) eliciting the strong anti-coagulating effect. Invention proposes compound of the formula (1): Q1-Q2-C(=C)-N-(R1)-Q3-N(R2)-T1-Q4(1) wherein R1, R2, Q1, Q2, Q4 and T1 have corresponding values, and Q2 represents the group of the formula: wherein R9, R10 and Q5 have corresponding values also, or its salt, solvate or N-oxide. Invention provides the development of a novel compound possessing strong Fxa-inhibiting effect and showing the rapid, significant and stable anti-thrombosis effectin oral administration.
EFFECT: valuable medicinal properties of compounds.
13 cl, 1 tbl, 195 ex
FIELD: biochemistry, medicine, in particular new bioactive compounds having peptide hormone vasopressin agonistic activity.
SUBSTANCE: disclosed are compounds of general formula 1 or 2 or tautomers, or pharmaceutically acceptable salts thereof, wherein W represents N or C-R4; R1-R4 are independently H, F, Cl, Br, alkyl, O-alkyl, NH2, NH-alkyl, N(alkyl)2, NO2 or R2 and R3 together may form -CH=CH-CH=CH-; G1 represents bicyclic or tricyclic condensed azepine derivatives selected from general formulae 3-8 wherein A1, A4, A7, and A10 are independently CH3, O, and NR5; A2, A3, A9, A11, A12, A14, and A15 are independently CH and N; or A5 represents covalent bond and A6 represents S; or A5 represents N=CN and A6 represents covalent bond; A8 and A12 are independently NH, N-CH3 and S; A16 and A17 both represent CH2 or one of A16 and A17 represents CH2 and the other represents CH(OH), CF2, O, SOa, and NR5; R5 represents H, alkyl, CO-alkyl, and (CH2)bR6; R6 represents phenyl, pyridyl, OH, CO2H; a = 0-2; b = 1-4; Y represents CH or N; Z represents CH=CH or S; and G2 represents group selected from groups of formulae 9-11 wherein Ar represents phenyl, pyridyl, naphthyl, and mono- or polysubstituted phenyl, pyridyl, wherein substituents are selected from F, Cl, Br, alkyl, NO2; D represents covalent bond or NH; E1 and E2 both are H, OMe, F, or one of E1 and E2 represents OH, O-alkyl, OBn, OPh, OAc, F, Cl, Br, N2, NH2, NHBn or NHAc and the other represents H; or E1 and E2 together form =O, -O(CH2)gO- or -S(CN2)gS-; F1 and F2 both represent H or together form =O or =R; L represents OH, O-alkyl, NH2, NH-alkyl, and NR9R10; R7 represents COR8; R8 represents OH, O-alkyl, NH2, NH-alkyl, N(alkyl)2, pyrolidinyl, and piperidinyl; R9 and R10 both are alkyl or together form -(CH2)h-; V represents O, N-CN or S; c = 0 or 1; d = 0 or 1, e = 0 or 1; f = 0-4; g = 2 or 3; h = 3-5, with the proviso, that both d and e are not 0. Also disclosed are pharmaceutical composition having agonistic activity in relate to V2 receptor, method for treatment one or more diseases (e.g., enuresis, nycturia, diabetes insipidus, hemorrhage disorders, urinary incontinence.
EFFECT: new compounds with value biological characteristics.
41 cl, 19 tbl, 193 ex