DE2310123A1 - METHOD FOR PREPARING TRIAZOLYLNAPHTHALIMIDES - Google Patents

Description

Bayer Aktiengesellschaft

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509 Leverkusen. Bayerwerk Jo / Bre

2 Feb. 8, 1973

Process for the preparation of triazolyl-naphthalimides

The invention relates to a process for the preparation of triazolyl naphthalimides of the formula

wherein

Ry. = aliphatic radical, cycloaliphatic or arali-

phatic rest
Rp = aliphatic radical

Under aliphatic radicals R. and Rp are in particular straight-chain and branched alkyl and alkenyl radicals with 1-12 C atoms understood. The cycloaliphatic radicals are preferably cycloalkyl radicals with 5-7 carbon atoms, the araliphatic phenylalkyl radicals with 7-12 carbon atoms.

Preferred compounds of the formula I are those in which R ₁ and Rp represent aliphatic radicals having 1-4 carbon atoms.

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R ₁ and R ₂ can, for example, by C ₁ -C ₆ -AlkOXy ,. Hydroxy, cyano, halogen, carboxy can be further substituted. The cycloaliphatic and araliphatic radicals R ₁ can also contain C ₁ -C 6 -alkyl radicals.

Examples of R ₁ and Rp are: methyl, ethyl, n- and i-propyl, n-, iso- and tert-butyl, amyl, hexyl, octyl, decyl, dodecyl, propenyl, ß-hydroxyethyl, tf- Hydroxypropyl, ß, (f-dihydroxypropyl, ß-chloroethyl, cyanoethyl, cyanopropyl, 2-ethylhexyl; additional _{examples for R 1:}
Cyclohexyl, methylcyclohexyl, benzyl, phenethyl.

Monosubstituted 4-triazolyl-naphthalimides have been used so far (British Patent 1 154 995) made in the following way:

a) Condensation of N-substituted 4-hydrazino-naphthalimides in alcohols with flf-oximinoketones to of-oximinohydrazones of formula II

ν / Γ ~ Λ

NH-N = CR ₂

N = CH ^Ιτ

OH
in which R ₁ and Rp have the meaning given above

b) Isolation and careful drying and

c) Treatment of the oximinohydrazones II in water, hydroxyl and solvents free of amino groups, such as acetic acid, dimethylformamide, pyridine, with acylating agents in Presence of basic catalysts (acetic anhydride with sodium acetate, pyridine and tertiary nitrogen bases ^

According to this procedure , the yields of pure 4-triazolylnaphthalimides as a result of side reactions are not quantitative; in general, depending on the nature of the substituent R _{2, they are} in the range from 55 to 65 % of theory.

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The by-products resulting from the side reactions have an adverse effect the lightening effect of the compounds is considerable and must therefore be removed in costly cleaning operations will.

It has now been found that triazolyl- (2) -naphthalimides of the formula I can be obtained in very good yields and technically more advantageous Way can be obtained by hydrazinonaphthalimides of the formula III

NH-NH ₂

III

in which R _{1 has} the meaning given above, with O-acyloximinoketones of the formula IV

IV

Ii H

O NO-CO-R ₃

in which R _{2 has} the meaning given above and R represents a lower alkyl, aryl or alkoxy radical,

condensed in polar solvents and then basic substances, preferably in catalytic amounts, added.

Examples of hydrazinonaphthalimides of the formula III include: 4-hydrazinonaphthalimide, N-methyl, N-ethyl, N-propyl and N-isopropyl-4-hydrazinonaphthalimide, N-n-butyl, N-isobutyl and N-amyl-4-hydrazinonaphthalimide, N-octyl, N-decyl and N-dodecyl-4-hydrazinonaphthalimide, N-2-ethylhexyl, N-ß-hydroxyethyl, N-ß-hydroxypropyl and N-ß-hydroxyisopropyl-4-hydrazinonaphthalimide, N-cyanomethyl-, N-cyanoethyl- and N-ß-chloroethyl-4-hydrazinonaphthalimide, N-cyclohexyl-, N-4-methylcyclohexyl-, N-benzyl- and N-ß-phenethyl-4-hydrazinonaphthalimide.

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Possible O-acyloximinoketones IV include: Acetoximinoacetone, propionyloximinoacetone, benzoyloximinoacetone, 1-acetoximino-butanone- (2), 1-acetoximinopentanone- (2), 1-acetoximino-3-methyl-butanone- (2), 1-acetoximino-3 »3-dimethylbutanone- (2), 1-acetoximino-heptanone- (2), 1-acetoximino-tridecanone- (2), Methoxy- and ethoxycarbonyloximino-acetone.

The Acyloximinoketones IV are derived from the underlying Oximinoketones easily obtainable by acylation with appropriate acid anhydrides, acid chlorides or pyrocarbonic acid esters.

The polar solvents that can be used for the reaction are carboxylic acid dialkylamides, carboxylic acid esters, sulfoxides, Ethers and alcohols; e.g .:

Dimethyl sulfoxide, dimethylformamide, glycol diacetate, glycol methyl ether acetate, Glycol dimethyl ether, but preferably alcohols such as methanol, ethanol, n- and iso-propanol, butanol, Glycol and especially glycol monomethyl ether.

The cyclization reaction is carried out in the temperature range from about 30.degree.-140.degree. C., preferably at 60.degree.-125.degree.

The basic catalysts required to initiate the cyclization can be of inorganic or organic nature, for example:

Alkali and alkali metal hydroxides, alkali carbonates, phosphates, fluorides, alcoholates, carboxylic acid alkali salts and tertiary nitrogen bases. They are concentrated or used in the form of aqueous or alcoholic solutions or suspensions. Examples are:

Lithium, sodium, potassium and calcium hydroxide, sodium and potassium carbonate, sodium and potassium acetate, trisodium and tricallium phosphate, sodium and potassium fluoride, sodium and potassium methylate and ethylate as well as higher alkali alcoholates,

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Trimethylamine, triethylamine, triethanolamine, dimethylethanolamine, Dimethylbenzylamine, N-methylpiperidine and -morpholine.

Under catalytic amounts are amounts of 0.01 to 0.5 mol understood per mole of starting substance. The range 0.05-0.2 mol / mol of starting substance is preferred.

The new process is characterized by its simplicity and economy and delivers significantly improved yields. It is expediently carried out by stirring a concentrated, still easily stirrable suspension of a 4-hydrazinonaphthalimide in a solvent at a slightly elevated temperature with little more than the stoichiometric amount of the desired acyloximinoketone. After a few minutes, the condensation is complete and a small amount of base (about 1/10 mol), for example sodium acetate solution, is then added without intermediate isolation of the crystalline acyloximinohydrazone. After a short time, the hydrazone dissolves under self-heating and the triazolyl-naphthalimide crystallizes out on cooling. Small amounts of by-products can be kept in solution by adding bases such as concentrated ammonia solution and removed with the mother liquors, from which the solvents can easily be recovered for reuse by distillation. By recrystallizing the reaction product once, a triazolylnaphthalimide of perfect color is obtained in yields of 83 to 92 % of theory.

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example 1

283 g (1 mol) of 4-hydrazino-Nn-butylnaphthalimide are introduced into 1.2 liters of glycol monomethyl ether at room temperature. The suspension is heated to 80 ^° C. and 140 g (1.07 mol) of crystallized acetoximinoacetone are quickly stirred in. The yellow suspension becomes temporarily thinner and turns into an easily stirrable paste of orange-colored needles. After 2 to 3 minutes all hydrazine is used up. 25 ml of saturated aqueous sodium acetate solution are added at 80-84 ° C. (= 8 g CH ^ COONa). The suspended hydrazone then dissolves in a clear solution with the temperature rising to 105-110 ° C. within a few minutes. The mixture is stirred for a further 15 minutes at 110-115 ° C. and then allowed to cool. The triazole crystallizes out at approx. 65 ° C. At 30-35 ^° C., 160 ml of concentrated ammonia solution are gradually added. Mixture is then stirred for a further 1/2 hour at 20 ⁰ C after filtered off the triazole and washed tigern on the suction filter with 700 ml of 80, containing some ammonia, aqueous glycol monomethyl ether, and finally with a little methanol to 80 tigern. 520 g of light gray, moist triazole are obtained, dry content: 300-315 g.

Glycol monomethyl ether can easily be recovered from the mother liquors by rectification through a short packed column; it can be used again.

For further purification, the wet Rohtriazol in 1.1 liters of dimethylformamide was dissolved at 80 ⁰ C. 80 ml of hydrochloric acid (d = 1.19) and a solution of 8 g of sodium chlorite in 20 ml of water are added in portions over the course of one hour. After the oxidizing agent has been used up, 80 ml of hydrochloric acid (d = 1.19) and 5 g of zinc dust are stirred in in portions. After the zinc has disappeared, another 2 g of sodium chlorite are added as a concentrated aqueous solution and a short time later 10 g of adsorption carbon are added. The mixture is stirred for a short time at 90 ^° C. and the solution is pressed through a heated pressure filter. That

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The filtrate is allowed to cool slowly; At 75 ° C the triazole begins to crystallize out in bright prisms, which are suctioned off at 25 30 ° C. The filter material is washed first with a little 80% dimethylformamide, then with 80% aqueous methanol and dried. 280-304 g (84-91 % of theory) of pure Nn-butyl-4- [4-methyl-v-triazolyl- (2) I -naphthalimide are obtained.

Used instead of N-n-butyl-4-hydrazinonaphthalimide the N-substituted 4-hydrazino-naphthalimides listed in each case in the table below are obtained in an analogous manner Manner and in similar yields the following N-substituted 4- [4-methyl-v-triazolyl- (2) J -naphthalimides:

example
1 R ₁ used N-substituted
4-hydra inonaphthaimide a
b
C.
d
e CH ₃
C ₂ H ₅
C ₂ H ₄ OH N-methyl
N-ethyl
N-ß-hydroxyethyl
Nn propyl
Nn-butyl f _CH2 . _CH / ^C 4 ^H 9 N- (2-ethyl) hexyl G ⁿ " ^C 12 ^H 25 N-n -dodecyl H <E> N-cyclohexyl i -®- ° ^Η 3 N- (4-methyl-) cyclohexyl k CH ₂ -Q N-benzyl

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The acetoximinoacetone used was prepared as follows:

1180 ml of acetone are mixed with 10 ml of hydrochloric acid (d = 1.195). 4.0 mol of isopropyl nitrite are distilled into this mixture from a developing apparatus at 0-5 ° C. (This nitrite developer was charged with 280 g of sodium nitrite, 520 ml of water and 325 ml of 97 # technical isopropanol, into which one drips 324 ml of hydrochloric acid (d = 1.195) from a dropping funnel.) The mixture is stirred for about 1/4 hour at 0 - 5 ° C and then add 11 g of anhydrous sodium acetate. Acetone and isopropanol are distilled off under reduced pressure gradually to 20 Torr from a maximum of 55-6O ⁰ C warm water bath. The white oximinoacetone remaining in the flask is mixed with 358 ml of acetic anhydride at 30.degree.-35.degree. It is ensured that the temperature does not rise above 45 ° C. The acetylation is complete after about 45 minutes. Initially distilling acetic acid and small amounts of low-boiling by-products in 10-12 Torr of a maximum of 65 to 70 ⁰ C hot water bath and finally sets the distillation at the oil pump continues being subtracting all up to 1 Torr Boiling. Subsequently, the Hauplauf at 1 torr and 50 55 ⁰ C τ is distilled off quickly. After inoculation with a crystal of acetoximinoacetone, the product solidifies in the receiver cooled to 0 ° C. to form a colorless crystal mass, from which a few percent of non-crystallized, liquid components are decanted after some time. This gives 408-420 g of colorless, coarsely crystalline 98-99% acetoximinoacetone (78-80 % of theory, based on the nitrite used).

Example 2

28.4 g (0.1 mol) of 4-hydrazino-Nn-butyl-naphthalimide are stirred in 120 ml of dimethylformamide. This suspension is heated to 80 ^° C. and 14.2 g (0.11 mol) of crystallized acetoximinoacetone are added. After a few minutes there is no hydrazino

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connection more detectable (spot test with o-naphthoquinone sulfonic acid or thin-layer chromatogram). A suspension of 0.4 g of sodium fluoride in 3 ml of hot water is then added and the reaction mixture is stirred at 100 ° C. for a further hour. The solution is allowed to cool while stirring, the resulting triazolyl naphthalimide crystallizing out. At approx. 50 ° C, 17 ml of concentrated ammonia solution is added, whereby by-products with a violet color dissolve. The precipitated product is filtered off with suction, washed with a little 80% aqueous and ammonia-containing dimethylformamide and purified by dissolving it from dimethylformamide. 27.8 g (83 % of theory) of Nn-butyl-4- [4-methyl-v-triazolyl] naphthalimide are obtained.

If 15.8 g of propionyloximinoacetone are used instead of acetoximinoacetone and if you proceed as indicated, the same product is obtained in the same yield and purity.

Example 3

26 g (0.1 mol) of N-ethyl-4-hydrazinonaphthalimid be Acetoximinobutanon--1 is heated in 125 ml of glycol monomethyl ether 15.8 g (0.11 mol) of (2) with stirring to 80 ⁰ C. After a short time the hydrazine has disappeared and 3 ml of concentrated sodium acetate solution are then added. The mixture is stirred for a further 1/2 hour at 105-110 ⁰ C and then allowed to cool to give added 20 ml of concentrated ammonia solution at ca. The precipitated crystal needles are filtered off with suction at room temperature, washed with 80% aqueous, ammonia-containing methanol and redissolved from dimethylformamide. After drying, beige-colored needles of N-ethyl-N- [4-ethyl-v-triazolyl- (2 ) ~ \ -naphthalimide are obtained in a yield of 26.8 g (= 84 % of theory).

The hydrazinonaphthalimides listed in each case are obtained in an analogous manner and acetoximinoketones the following triazolylnaphthalimides of the formula I:

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1 Q 8 1

at
game
3 R ₁ R ₂ 4-hydrazino
naphthalimide Acetoximinoketone a
b C ₂ H ₅ -CH (CH,) ₂ N-ethyl
N-ethyl 1-acetoximino
butanone- (2)
1-acetoximino-3-
methyl butanone (2) C. C ₂ H ₅ C (CHj) ₃ N-ethyl 1-acetoximino-3,3-
dimethyl butanone
(2) d ° A -CH (CH,) ₂ N-n-butyl 1-acetoximino-3-
methyl-butanone- (2) e C ₄ H ₉ c (c " ₃ , ₃ N-n-butyl .1-acetoximino-3,3-
dime ethyl butanone
(2)

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Claims (1)

Claims '. Process for the preparation of triazolyl-naphthalimides of the formula 0 N ß2 wherein R- = aliphatic, cycloaliphatic, araliphatic Remainder Rp = aliphatic remainder, characterized in that 4-hydrazinonaphthalimides the formula NH-NH ₂ wherein R _{1 has} the meaning given above, with O-acyloximinoketones of the formula R ₂ -C-CH O NO-CO-R ₃ wherein R, for a lower alkyl, aryl or alkoxy radical and R _{2 has} the meaning given above Le A 14 847 - 11 - 409836/1081 condensed in polar solvents and then basic substances, preferably in catalytic amounts, added. 2. The method of claim 1 , wherein R ₁ = aliphatic radical with 1-12 carbon atoms, cycloaliphatic radical with 5-7 carbon atoms, araliphatic radical with 7 * 12 carbon atoms R2 = aliphatic radical with 1-12 carbon atoms 3. Process according to Claim 1 , in which R ^ and R_ = aliphatic radicals with 1-4 carbon atoms 4. The method according to claim 1, characterized in that the reaction between 30 and 140 ° C, preferably 60 and 125 ° C is carried out. Le A 14 847 - 12 - 409836/1081