JPH0491082A - Oxazine derivative and its production - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Industrial Field of Application] The present invention relates to a novel oxazine derivative and a method for producing the same, and more specifically, a Nando or phenanthrooxazine derivative suitable for photochromic materials and photosensitive materials and its production. Regarding the law.

[Prior Art] Spirooxazine compounds are known as photochromic materials that exhibit reversible photoresponsiveness (photochromism), and in particular, 1,3,3-1-limethyline 1 compound represented by the formula [rV] Linonaphthosbirooxazine has been put into practical use as a photochromic material. When photochromic materials are irradiated with light, their structure changes and their light absorption properties change.
The original compound can be restored by irradiation with light of a different wavelength or by heating.

When such photochromism is applied as a memory, it is required to have light resistance and thermal stability so that it can be isomerized immediately by light irradiation and maintain that state stably.

Therefore, attempts have been made to synthesize various indolinonaphtho and phenanthrooxazine derivatives with the aim of improving light resistance, thermal stability, or absorbing long wavelength light.

Many of these spirooxazine derivatives develop a blue to bluish-purple color in response to ultraviolet cotton. Therefore, attempts are being made to obtain other colors. For example, JP-A-62-1450
Publication No. 89 discloses a piberidinonaph l-spirooxazine compound represented by the formula [V] and its derivatives, and these compounds develop a reddish-purple to bluish-purple color when irradiated with ultraviolet rays.

On the other hand, as a photochromic material that does not have a spiro ring, Tetrahedron Letter (Tetrahedron Le
tte-rs) Vol, 22, No, 40
, 3945-3948 (193) discloses a 2H-1,4-okinodine compound represented by the formula [v1].

In addition, conventional methods for producing such oxazine derivatives include enamine compounds obtained from ketones and amines, and
．． The only method available is to use a compound such as 1-di(substituted aromatic group) propylene as a starting material, which limits the range of vine derivatives that can be synthesized. Therefore, there was a problem that the yield was also low.

In particular, some enamine compounds, such as 2-(1-
(pyrrolidinyl)propane was extremely unstable and difficult to handle.

[Problems to be Solved by the Invention] An object of the present invention is to provide a novel oxazine derivative. A further object of the present invention is to provide a method for producing such a novel oxazine compound, particularly a novel method for producing it. Another object of the present invention is to provide a novel photochromic material that has light resistance and thermal stability and is highly practical, starting from readily available raw materials.

[Means for Solving the Problems] The compound of the present invention has the formula -Xi (in the formula, the dotted line may be a condensed benzene ring: Y
represents a 1-pyrrolidinyl group, a piperidino group, a mo/ruphorino group, or a secondary\amino group having the general formula -N, where R1 and R2 each represent an alkyl group, an allyl group, or a phenyl group, and R3 is hydrogen. Alkyl group having 3 to 6 carbon atoms which may be substituted with an atom, hydroxyl group, alkoxy group, acetoxy group or formyl group: Cycloalkyl group having 3 to 6 carbon atoms: Aralkyl group: hydroxyl group, alkoxy group, acetyl group, carboxy alkyl group,
Represents an aryl group, furyl group, thienyl group, pyridyl group, thiazolyl group, benzofuranyl group, benzothienyl group, or indolyl group, which may be substituted with a halogen atom, cyano group, nitro group, hydroxyalkyl group, or vinyl group; R4 represents a hydrogen atom, an alkyl group or an aralkyl group. However, R3 and R' are a novel oxazine derivative represented by one of them being a hydrogen atom and used as a monomer group.

The present invention also provides a secondary amine represented by (A) the general formula [+1] y -H[II] (wherein Y is as described above), (B) a general formula [Ill] (wherein R3 is the same as described in claim 1, and R5 represents a methyl group, -(Cite2□)X, or a vinyl group, where m is the number of 1 or 2, and X is a hydroxyl group, a lower alkoxy group,
It represents an acetoxy group, a halogen atom, a mercapto group, a lower alkylthio group or a phenylthio group, or -(CH2) when R3 and R5 are taken together. -CH=CH-)
may form a group, where n represents the number 2 or 3)
Regarding the method for producing an oxazine derivative represented by the aforementioned general formula [II, which is characterized by reacting the ketone represented by (C) 1-nitroso-2-naphthol or 9.10-phenanthrenequinone monoxime, and the aforementioned (A) and (B) are reacted, and the resulting product is reacted with the above-mentioned (C).

R1 and R2 may be the same or different from each other,
Alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, hexyl, octyl, decyl, dodecyl, octadecyl; allyl groups and phenyl groups are exemplified. As the secondary amino group Y, diethylamino group, diallylamino group, 1-pyrrolidinyl group, piperidino group and morpholino group are preferable, and 1-pyrrolidinyl group is more preferable because they are easy to synthesize and have photochromic properties.

R3 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t
Alkyl groups such as ert-butyl, pentyl, hexyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl Cycloalkyl groups such as dichlorobutyl, cyclopentyl, cyclohexyl: 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl, 6 -Substituted alkyl groups such as hydroxyhexyl, 3-methoxypropyl, 3-ethoxypropyl, 3-acetoxypropyl, 2-formylethyl, 3-formylpropyl; aralkyl groups such as benzyl, β-phenylethyl, phenyl, tolyl, 2 -Hydroxyphenyl, 4-hydroxyphenyl, α-hydroxy-4-tolyl, 2-methoxyphenyl, 4-methoxyphenyl,
4-ethoxyphenyl, 4-acetylphenyl, 4-methoxycarbonylphenyl, 4-fluorophenyl, 2
-chlorophenyl, 4-chlorophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3
- Substituted or unsubstituted aryl groups such as nitrophenyl, 4-nitrophenyl, 4-(hydroxymethyl)phenyl, 4-vinylphenyl; 2-furyl, 4-nitro-2
-furyl, 2-thienyl, 3-thienyl, 4-nido-
2-f enyl, 5-nitro-2-thienyl, 2-pyridyl, 4-pyridyl, 2-thiazolyl, 5-thiazolyl,
Examples include substituted or unsubstituted heterocyclic groups such as 3-benzofuranyl, 3-benzothienyl, and 3-indolyl, and when R' described below is an organic group, it is a hydrogen atom. Examples of organic groups include alkyl groups such as methyl and isopropyl; substituted aryl groups such as 4-nitrophenyl and 4-acetylphenyl; 4-pyridyl and 4-nitro-2 Substituted or unsubstituted heterocyclic groups such as -thienyl and 5-nitro-2-thienyl are preferred.

R' is a hydrogen atom when R3 is an organic group: R
When 3 is a hydrogen atom, it is an alkyl group or an aralkyl group produced by rearrangement of R3. Alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 5ec-butyl, tert-butyl, pentyl, hexyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, etc.; aralkyl groups include Examples include benzyl and β-phenylethyl.

The compound of the present invention is characterized in that it does not have a spiro ring structure in its molecule and has a nitrogen atom and a carbon atom at the 2-position of the benzoxazine or naphthoxazine 5, thereby exhibiting photochromic properties. .

The compounds of the present invention can be synthesized by the following two methods.

The first method uses ketone [II], secondary amine [Il+
] and ]1-nitroso-2-naphthol VI]] or 9,10-phenanthrenequinone monoxime [■] are reacted in an organic solvent to obtain an oxazine derivative in one step. The present inventors readily carry out this reaction in an organic solvent, in the presence of molecular sieves, and preferably in the presence of a carboxylic acid as a catalyst, to obtain a naphthoxazine derivative [1a] or a phenanthrooxazine derivative [T b ] was found to be obtained.

(In the formula, Y, R3, R4, and R5 are as described above.) Examples of secondary amines include cyclic amines such as pyrrolidine, piperidine, and morpholine, as well as diethylamine and di-n-
Propylamine, diisobrobylamine, di-n-butylamine, methylhexylamine, methyloctylamine, methyldecylamine, methyldodecylamine, methyloctadecylamine, methylallylamine, ethylallylamine, N-methylaniline, N-ethylaniline, etc. Examples include, preferably pyrrolidine, piperidine,
Morpholine and diethylamine.

R6 is a methyl group: hydroxymethyl, acetoxymethyl, tetraromethyl, bromomethyl, iodomethyl, mercaptomethyl, methylthiomethyl, ethylthiomethyl, n-propylthiomethyl, phenylthiomethyl, hydroxyethyl, methoxyethyl, acetoxy Examples include an electron-negative group-substituted methyl group such as ethyl, an ethyl group, and a vinyl group. Among these, when R6 is a methyl group, this methyl group easily participates in the formation of an oxazine ring through a dehydration reaction.

Furthermore, according to the findings of the present inventors, when the above-mentioned -(C,R2,)X group or vinyl group is used as R5,
When m=1, the X-C bond is cleaved, and when m=2, the cleavage reaction occurs between carbon atoms at α and β positions counting from X, and the double bond of the vinyl group to form an oxazine ring. This is extremely effective for introducing R3, such as a methyl group, as a side chain of an oxazine derivative, which is difficult to introduce with good yield when R6 is a methyl group.Furthermore, when R1 and R6 are combined, In the case of a ketone that forms a cycloalkenyl ring together with a carbon atom, a formyl alkyl group can be introduced as R3 of the oxazine derivative produced by cleavage of the double bond.

Ketones having such R3 and R5 include methyl ethyl ketone, methyl-n-'propyl ketone, methyl isopropyl ketone, methyl-〇-butyl ketone, methyl isobutyl ketone, binacolon, l-phenylpropan-2-one, acetophenone, 2 -Hydroxyacetophenone, 4-hydroxyacetophenone, 2-methoxyacetophenone, 4-methoxyacetophenone, 2
-chloroacetophenone, 4-chloroacetophenone,
2-cyanoacetophenone, 3-cyanoacetophenone, 3-nitroacetophenone, 4-nitroacetophenone, p-diacetylbenzene, 2-acetofuron, 4-
Nitro-2-acetofuron, 2-acetothienone, 4-
Nitro-2-acetothienone, 5-nitro-2-acetothienone, 4-acetylpyridine, 2-acetylthiazole, 3-acetylbenzofuran, 3-acetylbenzothienone, hydroxyacetone, chloroacetone, 4-
Hydroxy-2-butanone, 4-methoxy-2-butanone, 4-acetoxy-2-butanone, methyl vinyl ketone, etc. are exemplified, and as a ketone having a ring formed by R3 and R6 together, cyclobenthe Examples include non, cyclohexenone, and the like. Among these, in order to introduce various R3 in good yield, methyl isopropyl ketone, 4-nitroacetophenone, p-diacetylbenzene, 4-nitro-2-acetothienone, 5-nitro-
2-acetothienone and 4-acetylpyridine are preferred, and for introducing a methyl group as R3 or R4, hydroxyacetone, 4-hydroxy-2-butanone, 4-methoxy-2-butanone and methyl vinyl ketone are preferred.

Organic solvents include benzene, toluene, xylene, n
-Hydrocarbons such as hexane and cyclohexane; ethers such as ethyl ether, tetrahydrofuran and dioxane; esters such as ethyl acetate; and nitriles such as acetonitrile. The amount of organic solvent is preferably 13 to 300 parts by weight, more preferably 20 to 100 parts by weight per 1 part by weight of ketone.

Any molecular sieve can be used, and a normal molecular sieve with a pore diameter of 0.3 to 0.5 nm is preferable.The amount of molecular sieve used is preferably 2 to 20 parts by weight per 1 part by weight of ketone. , more preferably 4 to 8 parts by weight.

Examples of carboxylic acids include acetic acid, propionic acid, pivalic acid, and benzoic acid, with acetic acid being preferred. The amount of carboxylic acid used is preferably 1 based on the amine.
It is 0 to 100 mol%.

Although the reaction proceeds at room temperature, it may be carried out with heating, for example, under reflux of the reaction solvent.

Moreover, by carrying out the reaction by this one-stage method in an ultrasonic bath, the reaction time can be shortened and the yield can be improved. Ultrasonic waves have a frequency of 28 to 100kHz
, strength of 100 to 30 ON/cm2 is preferable.

Furthermore, as a second method, the naphthoxazine derivative [Ia] and the phenanthrooxazine derivative [1bl] of the present invention can be obtained by combining a secondary amine represented by the -kazu formula [+1] with a secondary amine represented by the January 9 formula [111]. A reaction product obtained by reaction with a ketone, for example, an enamine compound [IX],
Similarly, 1-nitroso-2-naphthol [■] or 9.1
It can be obtained by reacting with 0-phenanthrenequinomonoxam [■].

rXE [■] [1al (In the formula, Y, R3, and R4 are as described above) As the enamine compound, 2-(1-pyrrolidinyl)butene-1,
2-(1-pyrrolidinyl)=3-methylbutene-1,2
-(1-pyrrolidinyl)-3,3-dimethylbutene-1
,2-(1-pyrrolidinyl)pentene-1,2-(1-
pyrrolidinyl)-3-methylpentene-1 and α-(1
2-(1-pyrrolidinyl)-3-methylbutene-2-(1-pyrrolidinyl)-3-methylbutene- 1 is preferred.

The reaction uses a catalytic amount of carboxylic acid in an organic solvent.

As the organic solvent and carboxylic acid, those similar to those exemplified in the first method are used. In this case, there is no need to use a molecular sieve, and the reaction proceeds at room temperature, but it may be heated, for example, under reflux of the reaction solvent.
Oxazine derivatives represented by Ibl include hydrocarbons such as benzene, toluene, xylene, n-hexane, and cyclohexane, ketone necks such as acetone and methyl ethyl ketone, halogenated hydrocarbons such as chloroform and methylene chloride, and ethyl chloride. Ethers such as ether, tetrahydrofuran and dioxane; esters such as ethyl acetate; alcohols such as methanol, ethanol and isopropyl alcohol; All are soluble in aprotic polar solvents.

[Effects of the Invention] The novel oxazine derivative of the present invention can be easily synthesized using readily available raw materials and dissolves well in various solvents. The oxazine derivative of the present invention in which R3 is an organic group and the liquid (g) containing the same are colorless or pale yellow in the dark, but when excavated by ultraviolet rays, the ring opens and each [I'
a] and [I' bl, and develops a red to blue-purple color.

[1'a:] [I'bl
(In the formula, Y and R3 are as described above.) This coloring quickly returns to its original colorless to pale yellow color when returned to a dark place. In addition, each of [Ia] and [1b] has Y=1-pyrrolidinyl.

For the compound where R''=isopropyl, emat was measured in an ethanol solution.The value was calculated based on the respective open ring states [I'a] and [I'bl]5i,
. A comparison is shown in Table 1.

Table 1 The oxazine derivative of the present invention exhibits rapid color development upon irradiation with ultraviolet rays and quick recovery upon discontinuation of irradiation. It also has excellent secondary light properties and thermal stability. Since it is soluble in various 4M'r4 media, it can be easily added to various polymers such as polyethylene, polystyrene, polyvinyl acetate, polyvinylpyrrolidone, and cellulose acetate.

Furthermore, by the production method of the present invention, novel oxazine derivatives can be obtained. In particular, by the novel one-step method mentioned as the first method, the oxazine derivatives can be easily obtained in a wide range of yields from industrially easily available ketones and secondary amines.

The oxazine derivative of the present invention is extremely useful as a photochromic material for optical recording elements, toys, etc., and various photosensitive and light control materials.

[Example] Hereinafter, the present invention will be explained with reference to Examples. In the examples, parts represent parts by weight, but the present invention is not limited to these examples.

Example 1 2-isopropyl-2-(1-pyrrolidinyl)-28-
Synthesis of naphtho[2,1-b][1,4]oxazine, method 1 8.2 parts of pyrrolidine and 20 parts of molecular sieve with a pore size of 0.4% m were added to 173 parts of toluene and stirred to obtain a mixture. Ta. While stirring this at room temperature, 70 parts of glacial acetic acid,
50 parts of methyl isopropyl ketone and 1-nitrone-2
- 40 parts of naphthol were successively added in this order, and stirring was continued for one day and night. Next, 264 parts of n-hexane, 200 parts of water
1 part and 10 parts of sodium bicarbonate were added sequentially, and after stirring for 15 minutes, the solid was separated. After washing the organic layer with water, 40 parts of alumina was added and stirred for 15 minutes.

After allowing the mixture to stand still and separating the solids, the solvent was distilled off under reduced pressure to obtain 0.7 parts of a reddish-brown oil. 395 parts of ethanol was added thereto, and the precipitated crystals were collected by filtration and further washed with ethanol to obtain 04 parts of flame yellow prismatic crystals.

Melting point, elemental analysis value, NMR δ value, IR of the obtained crystal
The characteristic absorption and thin layer chromatography R values were as follows. However, Rf is Merck's Pre-c
oated TLCPlatesSilica Ge1
Using 60F, 4, n-hexane/ethyl acetate 41
It was obtained by developing with a mixed solvent.

Melting point: 129.5-1305 parts C Elemental analysis value (+1:,, +(,N□O) (%) CHN Calculated value 77.5 7.5 9.5 Actual value
78.0 7.8 9.4H-NMR (CDCJ
l, ) δ0,99 f31(,di,1.17
(38, dl, 1.59t4H, br, s), 2.3
2 (IH, heptet), 2, 63-2.81 f
2H, ml, 2.84-3.01 (2H, m), 7,
05 flH, d), 7.34 (IH, ddl, 7.
53 (IH, dd), 7, 55 (IH, s), 7.
65 flH, d), 7.72 flH, dl, 8, 51
(], 1Ld) IR (KBr) cm-': 1622. 1595R
r: 0.57 As a result, the obtained crystal was 2-isopropyl-2-(1
-pyrrolidinyl)-2H-nando[2,1-b] [
1,4]oxazine. The yield is 1
-6 for the theoretical yield from nitroso-2-naphthol
%Met.

Example 2 Synthesis of 2-isopropyl-2-(1 pyrrolidinyl)-2H-naphtho[2,x-bl[1,4]oxazine,
Method 1 Using Ultrasound A reaction similar to Example 1 was carried out. However, pyrrolidine 2
One reaction using 4.6 parts, 60 parts of molecular sieves with a pore size of 0.4 Hm, 433 parts of toluene, 21.1 parts of glacial acetic acid, 15.0 ffl of methyl isopropyl ketone, and 12.0 parts of 1-nitrone-2-naphthol. While maintaining the temperature below 30°C and stirring, the frequency was 28kHz and the intensity was 150°C.
The process was carried out for 4 hours while applying ultrasonic waves of W/C+T''. In the purification process, 79 parts of n-hexane, 40 parts of water, and 3 parts of baking soda were used.
0 parts and 110 parts of alumina were used. As a result, 5.0 parts of a reddish-brown oil was obtained. Recrystallization was performed using ethanol in the same manner as in Example 1, and pale yellow prismatic crystals 2 were obtained.
．． I got 0 copies.

The melting point, NMR δ value, IR characteristic absorption, and thin layer chromatography R value of the obtained crystal were consistent with those of the crystal of Example 1. As a result, the obtained crystals were 2-isopropyl-2-(1-pyrrolidinyl)-2-day-naphtho[2,
It was confirmed that it was 1-bl[1,4]oxazine.

The yield was 10% based on the theoretical amount from 1-nitroso-2-naphthol.

Example 3 Synthesis of 2-(4-nitrophenyl)-2-(1-pyrrolidinyl)-2H-nando[2,1-bl[1,4]oxazine, Method 1 8.6 parts of pyrrolidine, pore size 0. While stirring a mixture of 45 parts of 3Hm molecular sieves and 173 parts of toluene at room temperature, 62 parts of glacial acetic acid and 10 parts of 4-nitroacetophenone were added.
1 part and 12.6 parts of 1-nitrone-2 naphthol were added in this order, and the 6 solids were separated by stirring for 1 day and night, washed with saturated sodium bicarbonate solution to remove the acid, and then washed with water.

50 parts of alumina was added and stirred for 15 minutes. After separating the solids, the solvent was distilled off under reduced pressure to obtain 20 parts of a light brown oil. This was purified by column chromatography using silica gel using a 4:1 mixed solvent of n-hexane and ethyl acetate as the eluent to produce a pale yellow oil.
The analysis results of the obtained oily product are as follows, and from this, the product is 2-(4-nitrophenyl)-2
-(1-pyrrolidinyl)-2H-naf1- [2,1-
It was confirmed that it was bl[1,4]oxazine. The yield was 20% of theory.

MS fm/zl: 373 (M”)I R
(Neatl cm-' + 1625.1605,
UV (EtOHl nm, non-colored type 352 colored type, decoloring speed is fast and cannot be measured) (-NMR (CDC, 90 MHz) δ: 1,
55-1.91 +4H, m), 2.46-3.11
+4H, m), 7, 23-7.83 (7H, nil,
7.51 (II(,s), 8, 13 +2H, A2B
, ), 8.40 (LH,d Example 4 2-(4-pyridyl)-2-(1-pyrrolidinyl)-2
Synthesis of H-naphtho[2,1-bl[1,4]oxazine, Method 1 A mixture of 11.8 parts of pyrrolidine, 50 parts of molecular sieves with a pore size of 0.4 Hm, and 173 parts of toluene was stirred at room temperature and placed on ice. 101 parts of acetic acid, 10 parts of 4-acetylpyridine
1 part and 1 part and 2 parts of 1-nitrone-2-naphthol were added in this order, and the mixture was further stirred for 1 day and night. After separating the solids, the solids were washed with saturated sodium bicarbonate solution to remove the acid, and then washed with water. 20 parts of alumina was added and stirred for 15 minutes.

After the solid was separated by furnace, the solvent was distilled off under reduced pressure to obtain 28 parts of a reddish-brown oil. This was purified by column chromatography using silica gel using a 4:1 mixed solvent of n-hexane and ethyl acetate as an eluent to obtain 30 parts of a pale yellow oil.

The analysis results of the obtained oil are as follows, and from this, the product is 2-(4-pyridyl)-2-(1-pyrrolidinyl)-2day-naphtho[2,1-bl[1, 4]
It was confirmed to be oxazine. Yield is 1 of the theoretical amount
It was 1%.

MS (+n/z): 329 (M')L
R(Neatl cm-': 1642.15
92U V [EtOHl nm, uncolored: 353
Colored type: Fast decoloring rate and unmeasurable H-NMR (CDC, 90MHz δ: 1,
45-1. , 88 (4H, ml, 2.42-3.07
(4H, m), 7.08-7.77 (8H, m),
8.36-8.66f3H,m) Example 5 2-(4-nitro- and 5-nitrothienyl)-2-(
1-pyrrolidinyl)-2H-nando[2,1,-b]
Synthesis of [1,4] Oxazine, Method 1 A mixture of 8.3 parts of pyrrolidine, 40 parts of molecular sieves with a pore size Q of 4 nm, and 173 parts of toluene was stirred at room temperature, and 7.0 parts of glacial acetic acid and 4-nitrochloride were added. and 10.0 parts of a 2.3:1 mixture of 5-nitrothiophene and 12.1 parts of 1-nitrone-2-naphthol in this order;
The mixture was further stirred for one day and night. After separating the solids, the solids were washed with saturated sodium bicarbonate solution to remove the acid, and then washed with water. Alumina 5
0 parts was added and stirred for 15 minutes. After separating the solids,
The solvent was distilled off under reduced pressure to obtain 12 parts of a reddish-black oil. This was purified by column chromatography using silica gel using a 4:1 mixed solvent of n-hexane and ethyl acetate as an eluent to obtain 2.0 parts of a yellow-green oil.

The analysis results of the obtained oily substance are as follows, and it was confirmed from this that the oily substance was a mixture of isomers having the following structure.

[Xal:2-(4-nitrothienyl)-2-(l-pyrrolidinyl)-2day-naphtho[2,1-b] [1,
4] Oxazine [xb]: 2- (5-nitrothienyl)-2-
(1-pyrrolidinyl)-2H-naphtho[2,1-b]
[1,4]Oxazine MS (m/z): 379 (M'')I
R(Neatl cm-' + 1615, 15
85U V fEtOHl nm, uncolored 368
Colored type: Fast decoloring speed (unmeasurable HNMR (CDC4'z, 90MHzl δ1, 5
3-1, 93 (4H, ml, 2.54-3.23
(4)1. m), it should be noted that [Xal [X
b] is the ratio of the 5-position proton of the thienyl group (δ: 8.1.7.d) due to the former and the 3-position proton of the thienyl group (δ: 6.93.d) due to the latter in H-NMR.
When calculated by the integral ratio of the signal with [Xa
l:[Xb]=3:2.

The total yield was 9% based on the theoretical amount.

Example 6 Pyrrolidine and 1-nitrone-
A one-step reaction with 2-naphthol gave the respective corresponding oxazine derivatives.

When R was determined by thin layer chromatography under the same conditions as in Example 1, the following results were obtained.

2-(2-hydroxyphenyl)-2-(1-pyrrolidinyl)-2H-nando[2,1-b][1,4]oxazine R, = 0.68 2-(2-thienyl)-2-( 1-pyrrolidinyl)-2
H-naphtho[2,1-b] [1,4]oxazine R, = 0.68 2-(2-furyl)-2-(1-pyrrolidinyl)-2H
-nando[2,1-b] [1,4]oxazine R, = 0.58 Example 7 2-isopropyl-2-(l-pyrrolidinyl)-2H-
fs-f:/to0 [9,10-b] [1,4]
Synthesis of Oxazine, Method 1 82 parts of pyrrolidine and 20 parts of molecular sieve with a pore size of 0.4 Hm were added to 173 parts of toluene, and while stirring,
7.0 parts of glacial acetic acid, 5.0 parts of methyl isopropyl ketone and 5.2 parts of phenanthrene monoxime were added in this order, and stirring was continued for one day and night. Next, 264 parts of n-hexane, 200 parts of water, and 10 parts of sodium bicarbonate were added, and after stirring for 15 minutes, the solid was separated by furnace. After washing the organic layer with water, 80 parts of alumina was added and stirred for 15 minutes.

After standing still to separate out the solids, the solvent was distilled off under reduced pressure.
0.5 part of a pale yellow oil was obtained. Yield is 65% of theoretical amount
Met.

Example 8 Synthesis of 2-(4-acetylphenyl)-2-(1-pyrrolidinyl)-28-naphtho[2,1-b][1,,4]oxazine, Method 1 8.8 parts of pyrrolidine, pore size 0.4H
While stirring a mixture of 40 parts of molecular sieves and 347 parts of toluene at room temperature, 7.3 parts of glacial acetic acid, 10.0 parts of p-diacetylbenzene and 8.6 parts of 1-nitroso-2-naphthol were sequentially added in this order. The mixture was further stirred for one day and night. After the solid was separated by furnace, it was washed with saturated sodium bicarbonate solution to remove the acid, and then washed with water. 70 parts of alumina was added to give 15
Stir for a minute. After separating the solids, the solvent was distilled off under reduced pressure to obtain 16 parts of a black-rimmed oil. This was analyzed by column chromatography using silica gel. Purification was performed using a mixed solvent of n-hexane and ethyl acetate as an am'L agent to obtain 1.0 part of a pale green oil.

The analysis results of the obtained oil are as follows, and from this, the product is 2-(4-acetylphenyl)-2-(1
-pyrrolidinyl)-2H-naphtho[2゜1-b] [
1,4]oxazine. The yield was 5% of theory.

MS (mlz): 370 (M") IR (Neat) cm-': l 685.1
620, UV fEtOH) nm, uncolored type 3
53 Colored type 2 Discoloration resolution is fast and unmeasurable H-NMR (CDC, 90MHz) δ・1.5
1-2.08 (4H, ml, 2.44-3.24 f4
H, m), 2, 58 f3H, s), 7.18-8.1
4 (6H, ml, 8, 53 flH, d) The compound having two oxazine structures obtained when both acetyl groups in the raw material diketone react is
Not found.

Example 9 2-Methyl-2-(1-pyrrolidinyl)-2d-naphtho[2,1-b][1,4]oxazine and its isomer synthesis, first method involving cleavage reaction 384 parts of pyrrolidine,
While stirring a mixture of 80 parts of molecular sieves with a pore size of 0.5 Hm and 433 parts of toluene at room temperature, pivalic acid 2
76 parts of hydroxyacetone, 20.0 parts of hydroxyacetone, and 37.4 parts of 1-nitrone-2-naphthol were added in this order, and the mixture was further stirred for 3 hours. After separating the solids, add saturated sodium bicarbonate solution,
Then, the mixture was washed with water, 500 parts of alumina was added, and the mixture was stirred for 15 minutes. After separating the solids, the solvent was distilled off under reduced pressure to obtain 19 parts of a reddish-black oil. This was applied to a column using silica gel and a mixture of n-hexane and ethyl acetate as eluent.
Purification by column chromatography using a mixed solvent gave 2 parts of a pale red oil and 5 parts of a pale yellow oil.

The results of the analysis are shown in Table 2, whereby the former is 2-methyl-2-(1-pyrrolidinyl)-2H-naphtho[2,1-b] [1,4
]oxazine, and the latter was found to be 3-methyl-2=(1-pyrrolidinyl)-2H-naphtho[1,2-b][1,4]oxazine represented by the formula [X I b] . The yield is 3 for the former based on the theoretical amount.
%, and the latter was 9%. No 2-hydroxymethylated oxazine derivative derived from the hydroxymethyl group of the raw material hydroxyacetone was found.

Table 2 This is because the hydroxyl group of the hydroxymethyl group and the carbon atom are cleaved by the reaction shown in the following formula, the remaining carbon atom participates in the formation of an oxazine ring, and the methyl group is bonded to the oxazine ring. It is considered that [XIa] was produced by this reaction, and a part of this methyl group was further rearranged to produce [XIb].

[11a] [II[a
[■] (Note) * Conditions are the same as in Example 1 Example IO Instead of hydroxyacetone, a methyl group is substituted as R3 of formula [III], and a methyl group or ethyl group substituted with various electron-negative groups as R8. An experiment similar to Example 8 was conducted using various ketones having a vinyl group or a vinyl group. In either case, [XIa] into which a methyl group is introduced as R3 in formula [1a] and R4 when the methyl group is rearranged.
The production of [Xrb] was observed, and no oxazine derivative having an electron negative group-substituted alkyl group or vinyl group as R3 was produced. Table 3 shows the ketones used and the yields based on the theoretical amounts.

Table 3 Example 11 2-methyl-2-piperidino-2H-naphtho[2,1-
b] Synthesis of [1,4]oxazine and its isomers,
Method 1 involving a cleavage reaction While stirring a mixture of 460 parts of piperidine, 80 parts of molecular sieve with a pore size of 0.4 Hm, and 173 parts of toluene at room temperature, 33.6 parts of glacial acetic acid and 200 parts of hydroxyacetone were added.
and 187 parts of 1-nitroso-2-naphthol were added in this order, and the mixture was further stirred for 1 day and night. After separating the solids,
The mixture was washed with saturated sodium bicarbonate solution and then with water, and 50 parts of alumina was added thereto, followed by stirring for 15 minutes. After separating the solids, the solvent was distilled off under reduced pressure to obtain 28 parts of a reddish-black oil. This was purified by column chromatography using a 41 part mixture of n-hexane and ethyl acetate with silica gel in the column and 2 parts of a pale red oil and 0 parts of a dark yellow oil. .2 parts were obtained.

The results of the analysis are shown in Table 4, which shows that the former is 2-methyl-2-piperidino-2H-naphtho[2,1-b][1,,4]oxazine represented by the formula [XIIa]. , the latter is 3-methyl-2-biberidino 2H-naphtho[1,2-bl
[t,43 It turned out to be oxazine. The yield was 7% for the former and slightly less than 1% for the latter based on the theoretical amount. No 2-hydroxymethylated oxazine derivative derived from the hydroxymethyl group of the raw material hydroxyacetone was found.

Table 4 Example 12 2-Methyl-2-morpholino-2H-nando[2,1-
Synthesis of [1,4]oxazine, Method 1 involving cleavage reaction A mixture of 47.0 parts of morpholine, 80 parts of molecular sieve with a pore size Q of 4 nm, and 1300 parts of toluene was mixed with 33.6 parts of glacial acetic acid while stirring at room temperature. part, hydroxyacetone 2
0.0 part and 18.7 parts of 1-nitroso-2-naphthol were added in this order, and the mixture was further stirred for 1.5 hours. Solid? After being separated, it was washed with saturated sodium bicarbonate solution and then with water, and dried over anhydrous sodium sulfate. After one solid was separated, the solvent was distilled off under reduced pressure to obtain 18 parts of a reddish-black oil. This was purified by column chromatography using silica gel in the column and a 4 part 1 mixed solvent of n-hexane and ethyl acetate as the eluent to obtain 13 parts of a pale red oil.

The results of the analysis are as follows, whereby the product is 2-methyl-2-morpholino-2H-naphtho[2,1
-bl[1,4]oxazine was confirmed. The yield was 13% based on the theoretical amount. No 2-hydroxymethylated oxazine derivative derived from the hydroxymethyl group of the raw material hydroxyacetone was found.

M S fm/zl ・282 (M”)I R(N
eatj cm-' + 1640.1616, U
V fEtOHl nm, ungarnished, 360,345
Colored type: Fast decolorization rate and unmeasurable HNMR (CDCl5, 9t1MHzl δ1
, 59 (3H, sl, 2.60-2.92 (4t(
, ml, 3.49-3.88 (4H, ml, 7.08
(IH, dl, 7.47 (II, sl, 7.23-7.
92 f411 ml, 8, 55 flHldl Example 13 2-Methyl-2-diethylamino-2H-naphtho[2,
1-bl Synthesis of [1,4]oxazine and its isomers, method 1 involving cleavage reaction A mixture of 3 diethylamines, 5 parts, 180 parts of molecular resin with a pore size of 0.4 Hm, and 867 parts of toluene was stirred at room temperature. while 33.6 parts of glacial acetic acid, 20.0 parts of hydroxyacetone and 18.7 parts of 1-nitrone-2-naphthol.
of the mixture were added in this order, and the mixture was further stirred for 2 hours. Solid? After the mixture was washed with saturated sodium bicarbonate solution and then with water, 30 parts of alumina was added and stirred for 15 minutes. After separating the solids, the solvent was distilled off under reduced pressure to obtain 12 parts of a red oil. This was purified by column chromatography using silica gel in the column and an 8.1 part mixed solvent of n-hexane and ethyl acetate as the eluent, resulting in 1 part of a pale red oil and 0.5 part of a pale yellow oil. part was obtained.

The results of the analysis are shown in Table 5, whereby the former is 2methyl-2-diethylamino-2H-nando[2,1-b] [1,
4] oxazine, the latter having the formula [X Ill b ]
It was found to be 3-methyl-2-diethylamine-2H-nando[1,2-b][1,4]oxazine shown by The yield is 3% for the former based on the theoretical amount.
, the latter was 2%. No 2-hydroxymethylated oxazine derivative derived from the hydroxymethyl group of the raw material hydroxyacetone was found.

[Xmako[Xn[bkoTable 5 (Note) *: Conditions are the same as Example 1 Example 14 2-Methyl-2-(N-methylanilino)=2H-nando[2,1-b] [1, 4] First method involving synthesis of oxazine and cleavage reaction Synthesis of an oxazine derivative was attempted in the same manner as in Example 8, except that N-methylaniline was used as the secondary amine. As in Example 8, the hydroxyl group of hydroxyacetone is removed, resulting in an oxazine derivative having a methyl group, 2-methyl-2-(N-methylanilino)-2day-naphtho[2
, 1-b][1,4]oxazine was obtained.

The R value determined by thin layer chromatography as in Example 1 was 0.64.

Example 15 2-isopropyl-2-(1-pyrrolidinyl)-28-
Synthesis of Nando[2,1-b][1,4]oxazine, Method 2 4 obtained from pyrrolidine and methyl isopropyl ketone
6 parts of 2-(l-pyrrolidinyl)-3-methylbutene-
1 was dissolved in 866 parts of toluene, and 8.4 parts of acetic acid was added. Next, 23 parts of 1-nitroso-2-naphthol [■] was added, and the mixture was stirred at room temperature for 1 hour to react. After the reaction, the mixture was washed with saturated sodium bicarbonate solution to remove acetic acid, and then washed with water. It was dried over anhydrous sodium sulfate and heated under reduced pressure to distill off toluene. The residue was dissolved in 330 parts of n-hexane, 100 parts of alumina was added, and the mixture was stirred for 30 minutes. The solid was separated, and n-hexane was distilled off from the liquid by heating under reduced pressure. 16 parts of ethanol was added to this and left to stand, and after several hours, the precipitated crystals were collected by filtration. In this way, 5 parts of pale yellow prismatic crystals of the desired substance were obtained.

The results of the melting point, NMR4IR and R of the obtained crystals were as follows.

Melting point: ]29.5-1305℃ H-NMR (CDC) δ.

0.99f3H,d), 1.17(3H,d), 1
, 69 (4H, br, s), 2.32 (IH, he
ptet l, 2, 63-2.81 C2H, m),
2.84-3.01 f2H, m).

7, 05 [114, d), 7.34 (IH, dd)
, 7.53 fl)1. dd), 7, 55 (IH,
sl, 7.65 (IH, d), 7.72 (It(,
dl, 8.51 flH, d) I R(KBr) cm-': 1622. l 5
95R,: 0.57 (Conditions, Example 1.! [tfi)
As a result, the obtained crystals were 2-isopropyl-2-(1
-pyrrolidinyl)-2H-naf)-[2,1-bl
It was confirmed that it was [1,4]oxazine. The yield was 13% of the theoretical yield from -nitroso-2-naphthol.

Example 16 2-isopropyl-2-(1-pyrrolidinyl)-2H-
Synthesis of phenanthro[9,xo-bl[1,4]oxazine, second method 1 obtained from pyrrolidine and methyl isopropyl ketone
6 parts of 2-(1-pyrrolidinyl)-3-methylbutene-
1 was dissolved in 260 parts of toluene, and 8.4 parts of acetic acid was added. Then phenan 1 helenquinone monoxime [IX]
10 parts were added, and the mixture was stirred and reacted at room temperature for 5 hours. After the reaction, acetic acid was removed by washing with saturated sodium bicarbonate solution, and then with water. It was dried over anhydrous sodium sulfate and heated under reduced pressure to distill off toluene. The residue was dissolved in 132 parts of n-hexane, 80 parts of alumina was added, and the mixture was stirred for 30 minutes. The solid was separated and n-hexane was distilled off from the liquid by heating under reduced pressure to obtain 3 parts of a pale yellow oil. 6 NMR δ value, IR characteristic absorption, mass spectrum, and The R2 values of thin layer chromatography were as follows.

H-NMR (CDC, mu) δ 0, 98 (3H, d), 1.21 (3H, d), 1
．． 39-1.8N41+, ml, 2.44 (lH, h
eptet), 2.53-3.21 (41 parts m), 7
．． 31-7.74 (5H, ml.

8, 16-8.74 f4H, ml IRfNeat) cm-': 1608.1555
MS (m/zl: 344 (M')R,: 0.5
4 (Conditions: same as Example 1) As a result, the obtained oil was 2-isopropyl-2-(1-pyrrolidinyl)-2
It was confirmed to be 8-phenanthro[9,10-bl[1,4]oxazine. The yield was 19% of the theoretical yield from phenanthroquinone monoxime.

Example 17 In the same manner as in Examples 15 and 16, the following compounds were obtained using enamines as starting materials. Thin layer chromatography was performed under the same conditions as in Example 1 to determine each R7.

2-ethyl-2-(1-pyrrolidinyl)2H-nando[
2,1-b f, 1.4]oxazine R, = 0.55 2-propyl-2-(]-pyrrolidinyl)2H-nando[2,1-k)] [1,,4]oxazine R, =0.58 2-isobutyl-2-(]-pyrrolidinyl)2H-nando[2,1-bco[1,4]oxazine R, =0.60 2-tert-butyl-2-(1-pyrrolidinyl) −
2H-naphtho[2,x-b] [1,4]oxazine R, = 0.60 2-phenyl-2-(l-pyrrolidinyl) 2H-naphl
-[2,1-b] [1,4]oxazine Rf=0.63 2-phenyl-2-(l-pyrrolidinyl)-2H-phenanthro[9,10-b] [1,4]oxazine R,= 0.58

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, the dotted line may be a condensed benzene ring; Y
represents a 1-pyrrolidinyl group, a piperidino group, a morpholino group, or a secondary amino group having the general formula ▲A mathematical formula, a chemical formula, a table, etc. are available▼; Here, R^1 and R^2 each represent an alkyl group, an allyl group, etc. represents a group or a phenyl group; R^
3 is a hydrogen atom; an alkyl group having 3 to 6 carbon atoms that may be substituted with a hydroxyl group, an alkoxy group, an acetoxy group, or a formyl group; a cycloalkyl group having 3 to 6 carbon atoms; an aralkyl group; a hydroxyl group, an alkoxy group, an acetyl group group, a carboxyalkyl group, a halogen atom, a cyano group, a nitro group, an aryl group optionally substituted with a hydroxyalkyl group or a vinyl group, a furyl group, a thienyl group, a pyridyl group,
Thiazolyl group, benzofuranyl group, benzothienyl group,
or represents an indolyl group; R^4 represents a hydrogen atom, an alkyl group or an aralkyl group. However, one of R^3 and R^4 is a hydrogen atom and the other is an organic group). 2. (A) General formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [II] Secondary amine represented by (in the formula, Y is the same as described in claim 1), (B) General formula [III] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [III] (In the formula, R^3 is the same as described in claim 1, and R^5
represents a methyl group, - (C_mH_2_m) , or R^3 and R^5 together -(CH_2)_n
-CH=CH-) group, where n represents the number 2 or 3) and (C) 1-nitroso-2-naphthol or 9,10-phenanthrenequinone monoxime General formula [I] according to claim 1, characterized in that the general formula [I] is reacted with
A method for producing an oxazine derivative shown in 3. The manufacturing method according to claim 2, wherein R^5 is -(CH_2)_mX or a vinyl group (where m and X are the same as described in claim 2). 4. The general formula according to claim 1, characterized in that (A) and (B) according to claim 2 are reacted, and the obtained product is reacted with (C) according to claim 2. A method for producing an oxazine derivative represented by [I].