DE1518713C - - Google Patents

Description

Esters of terpene alcohols with aliphatic acids, monosubstituted aromatic acids and simple carbamic acids are already from Beilstein's Handbook of Organic Chemistry, Vol. 6, System No. 502 to 510 and Vol. 9 known. '

In Idian Soap Journal 10, No. 10/12 (1945), pp. 57 to 60, Soap, Perfumery and Cosmetics, 26 (1953), pp. 67 to 69, 82, 174 to 177, and U.S. Patent 2,840,583 are also esters of terpene alcohols with aliphatic and aromatic acids and their use as fragrances in indicated by the perfumery. U.S. Patent 2321978 mentions aliphatic esters of terpene alcohols for the manufacture of flotation agents for minerals.

The invention relates to a process for the preparation of compounds of the general formula

T —O —CO —R

in which T is a terpene residue of the composition C _n H ₂ "_ _x or C _n H ₂ " -χΟ with η = 5 to 20 and χ = 0 to 6, which is different from an acyclic terpene, from a monocyclic terpene of the p- Menthan series or of the bisabolon type or from a bicyclic terpene of the camphane or fenchan series by splitting off a hydrogen atom or the hydroxyl group and R is either a saturated 3- or 5-membered alicyclic ring or a phenyl radical or the group substituted by a fluorine.

—N

35

R _{1 represents} hydrogen and R _{2 represents} a low molecular weight alkyl radical, the cyclohexyl, phenyl or the optionally substituted pyridyl radical, R ₁ and R _{2 represent} low molecular weight alkyl or alkenyl radicals, or together with the nitrogen atom the pyrrolidyl, one optionally through Piperidyl radical substituted by alkyl groups and the morpholino radical, as well as their salts.

The compounds according to the invention are produced in a manner known per se by that he

a) a terpene alcohol of the general formula
T -OH · ·,

so

c) a terpene halide of the general formula

T - shark

with an alkali or silver salt of the general formula

A-O-CO-R

where A is an alkali metal or silver, optionally in a solvent at temperatures converts from 20 to 200 ° C or

d) a terpene alcohol of the general formula

T-OH

with an acid of the general formula
. HOOCR

at temperatures between 50 to 250 ° C in the presence of catalysts with elimination of water possibly in an indifferent. Reacts solvent

and the compounds obtained are optionally converted into their salts.

The basic substances for route a) are pyridine, tertiary amines, for example triethylamine and dimethylaniline or soda, potash in question. It is also possible with way a) first from the terpene alcohol using alkali amides, alkali metals or ■ alkali hydrides to produce the corresponding alcoholates and then to react this with the acid halide.

Suitable inert solvents for routes a), b) and c) are, for. B. pyridine, aromatic hydrocarbons, Dioxane, tetrahydrofuran, dimethyl sulfoxide, N-methyl-pyrolidone, acetone.

As catalysts in process route d), for. B. aluminum oxide, zinc chloride, boron trifluoride or mineral acids into consideration.

The products of the process, if they are racemates, can be converted optically by known methods active components are split.

The products of the process have a strong anti-inflammatory effect, especially compared to azulene Effect.

For example
Benzoic acid bisabolyl ester

CH ₃

with an acid halide of the general formula (CH ₃ ^ C = CH — CH ₂ — CH ₂ —C — O

Hal - CO-R

wherein Hai means a halogen atom, in the presence of basic substances in a solvent at temperatures from 0 to 150 ° C or
b) a terpene alcohol of the general formula

T-OH
with an isocyanate of the general formula

O = C = NR ₁

reacts with or without a solvent at temperatures of 50 to 150 ° C or

55

10 g of (-) - a-bisabolol are refluxed with 6.3 g of benzoyl chloride in 20 ml of pyridine for 3 hours. After cooling, it is taken up with benzene, washed with water and then with dilute sodium hydroxide solution. After drying with potassium carbonate, the benzene solution is evaporated. The residue is distilled in vacuo. The main fraction (5 g) boils at 0.5 mm from 170 to 173 ⁰ C.

Example 2 (4-fluoro-benzoic acid) bisabolyl ester

CH ₃ O

= GH - CH ₂ - CH ₂ - C-C-Ο

The ester is prepared analogously to Example 1 from 22.2 g of (-) - a-bisabolol and 13.2 g of cyclopentanecarboxylic acid chloride. Bp ₀₀₁ : 136 ° C. Yield 17g.

Example 5
Ν, Ν-dimethyl carbamic acid bisabolyl ester

IO

CH ₃

22 g of (-) - a-bisabolol in 80 ml of toluene are mixed with 7.8 g of sodium amide suspension (50%) at the boiling point. The ammonia gas formed is expelled with nitrogen, then 16 g of p-fluoro-benzoyl chloride are added dropwise. Work-up is carried out as described in Example 1. 11 g of ester are obtained. ₀ Kp., _5: 170 ⁰ C.

20th

. Example 3 Cyclopropanecarboxylic acid bisabolyl ester

CH ₃ (CHO ₂ C = CH-CH ₂ -CH ₂ -COC

(CHa) ₂ C = CH-CH ₂ -CH ₂ -COCN

25 g of (-) - a-bisabolol are added to 50 ml of toluene Boiling temperature with 9 g of sodium amide suspension (50%) converted into the alcoholate, which then with 12 g of NjN-dimethylcarbemic acid chloride to, is set. When the solution is 74, it is washed with water and dried with potassium carbonate and evaporated. The residue is distilled in vacuo. The desired connection is different 0.1 mm at 122 ° C. The yield is 21 g.

CH ₃

This ester is synthesized analogously to Example 1 from 22.2 g (-) - a-bisabolol and 10.4 g cyclopropanecarboxylic acid chloride. Kp _ool: g. 120 ⁰ C. Yield sixteenth

Example 4 Cyclopentanecarboxylic acid bisabolyl ester

CH ₃ O (CHs) ₂ C = CH-CH ₂ -CH ₂ -COC

Examples
Ν, Ν-diethyl carbamic acid bisabolyl ester

(CHa) ₂ C = CH-CH ₂ -CH ₂ -COCN

Production takes place analogously to Example 5 from 22.2 g of (-) - a-bisabolol and 13.5 g of Ν, Ν-diethyl carbamic acid chloride. Bp _o , _o i: 132 ° C. Yield 20 g. .

'Example-7' \

Ν, Ν-Dipropyl-carbamic acid bisabolyl ester

CH ₃ O CH ₂ -CH ₂ -CH ₃

(CHs) ₂ C = CH-CH ₂ -CH ₂ -COCN

CH ₂ -CH ₂ -CH ₃

Production takes place analogously to the example from 22.2 g (-) - a-bisabolol and 16.3 g Ν, Ν-dipropyl-carbamic acid chloride. Kp _{0 0l.} 152 ° C. Yield 24 g.

5 6

Example 8
Ν, Ν-Diisopropyl-carbamic acid bisabolyl ester

CH.

CH CH ₃ O

(CH ₃ ) ZC = CH-CH ₂ -CH ₂ -COCN

' ^V , CH ₃

CH

CH ₃

Production takes place analogously to Example 5 from 22.2 g of (-) - a-bisabolol and 16.3 g of Ν, Ν-diisopropyl carbamic acid chloride. Bp _o , _o i: 135 ° C. Yield 19.5 g. ·

Example9
NjNr Dibutyl carbamic acid bisabolyl ester

CH ₃ O CH ₂ -CH ₂ -CH ₂ -CH ₃

■ ■■■ * * ■ (CHs) ₂ C = CHL-CH ₂ -CH ₂ -COCN

CH ₃

Production takes place analogously to Example 5 from 22.2 g of (-) - a-bisabolol and 18 g of Ν, Ν-dibutylcarbamic acid chloride. _Bp . OjO1: 159 ° C. Yield 17 g.

. Example 10

NjN-diisobutyl-carbamic acid bisabolyl ester CH ₃

CH ₂ -CH CH ₃ O / \

. ■ I II / CH ₃

(CH ₃ ) JC = CH-CH ₂ -CH ₂ -COCN

CH ₃

CH ₂ -CH

. CH ₃

Production takes place analogously to Example 5 from 22.2 g of (-) - <z-bisabolol and 18.5 g of Ν, Ν-diisobutyl carbamic acid chloride. Bp: 150 ° C. Yield 22 g.

Example 11 Ν, Ν-Diallyl-carbamic acid bisabolyl ester

CH ₃ O CH ₂ -CH = CH ₂

■ ■ .... ι ii / '.

(CHa) ₂ C = CH-CH ₂ -CH ₂ -COCN

\ "■■ _. ■ CH ₂ CH — rCH ₂

CH ₃

Production takes place analogously to Example 5 from 20 g of (-) - a-bisaboloi and 14.3 g of Ν, Ν-diallyl carbamic acid chloride. Bp. _Otl : 155 ° C. Yield 16g.

Example 12
Bisabolyl pyrrolidinocarboxylate

CH ₃ O

I Il

(CHj) ₂ C = CH-CH ₂ -CH ₂ -COC-

Example 14
2,6-dimethyl-piperidinocarboxylic acid bisabolyl ester

γτι r \ CH ₃

f ³ ? K

(CH ₃ ) ZC = CH-CH ₂ -CH ₂ -C-Ο-C-NH ^>

CH ₃

Production takes place analogously to Example 5 from 5 g

. The preparation is analogous to Example 5 5 g of _{the HersteIlung SUC t ana, Example} 5 _{of 20 g of}

.... (- ^ - a-Bxsabolol and 3.2 g Pyrrolidinocarbonsaure- _{(_) a bisabolol and 17j5 g of} 2,6-dimethyl-piperidinochlond, Kp _{0, 5:} 165 ° C Yield 5 g of carboxylic acid chloride K _{P.. O1} : 165 to 170 ° C yield

15th

Example 13
Piperidinocarboxylic acid bisabolyl ester

CH ₃ O

■ / I · ■ Il

(CH ₃ ) ZC = CH-CH ₂ -CH ₂ -COCN

Example 15

Morpholinocarboxylic acid bisabolyl ester CH ₃ O

. : i Il / -ν

25 (CHa) ₂ C = CH-CH ₂ -CH ₂ -COC-NH ^ O

Production takes place analogously to Example 5 from 20 g Production takes place analogously to Example 5 from 15.5 g

(-) - a-bisabolol and 13.3 g of piperidinocarboxylic acid - (-) - a-bisabolol and 12.5 g of morpholinocarboxylic acid chloride. ₀ Kp., _2: 172 ° C. Yield 8g. 35 chloride: bp _{o> O} i: 169 ° C. Yield 5.5g.

B ei s ρ ie I 16

'-Pyrrolidinocarboxylic acid linalyte ester

CH ₃ O

. . r ii.

(CH ₃ ) zC = CH-CH ₂ -CH ₂ -COCN

CH = CH ₂

Production takes place analogously to Example 2 from 20 g of linalool and 17.6 g of pyrrolidinocarboxylic acid chloride. _{Bp OiO1} : 103 ° C. Yield 17g. ',,'".

. .. · -. ■ ':.' ■■ "■■. ■■■■. ■ ', ■ ^ Example 17

'N-Cyclohexyl-carbamic acid oryl ester

CH ₃ - O

(CH ₃ ) zC = CH - CH ₂ —CH ₂ -C = CH-CH ₂ -OC-NH-

15.4 g of ner oil are heated to 100 ° C. with 12.5 g of cyclohexyl isocyanate. Self-heating causes the temperature to rise to 130 ° C. After V ₂ hours, the reaction product is distilled in vacuo. B.p. ₀₀ i: 135 ° C. Yield 20g. . ;

,. Example 18

; ., '. Citronellyl N-phenylcarbamic acid

I Il

= CH-CH ₂ -CH ₂ -CH-CH ₂ -CH ₂ -OC-Nh-

11 g of phenyl isocyanate are added to 15.6 g of citronellol. As a result of self-heating, the temperature rises to about 100 ° C. After 1 hour, the batch is distilled in vacuo. .Kp. _O10 s: 155 ° C. Yield 16 g.

'309 616/168

9 10

Example N-n-butyl-carbamic acid citronellyl ester

CH ₃

(CH ₃ ) ZC = CH-CH ₂ -CH ₂ -CH-CH ₂ -CH ₂ -OC-NH-Ch ₂ -CH ₂ -CH ₂ -CH ₃

14.6 ml of n-butyl isocyanate are added to 20 g of citronellol, whereupon self-heating to 85 ^° C. occurs. After ¹ _1/2 hours the product is distilled in vacuo. Bp ₀₀₁ : 125 ° C. Yield 21 g.

B is ρ ie 1 20
Citronellyl N- [2-phenylamino-pyridyl- (5)] -carbamic acid

CH ₃ O _:

(CH ₃ J ₂ C = CH-CH ₂ -CH ₂ -CH-CH ₂ -CH ₂ -O- € - '"NH

18.5 g of 2-phenylamino-5-amino-pyridine are added in 60 ml of acetone at 3O ⁰ C with 21.8 g Chlorameisensäurecitronellylester. When the addition is complete, the solvent is evaporated off. The residue is taken up with chloroform, washed once with water and once with sodium bicarbonate. The solution is dried with potassium carbonate and evaporated. The residue crystallizes from methyl ethyl ketone gasoline. 103 ° C. Yield 14 g. .

Example 21 '^.

Ν, Ν-dianylcarbamic acid geranyl ester

CH ₃ CH ₂ -CH = CH ₂

25 g of geraniol are mixed in 50 ml of toluene at boiling point with 12.7 g of 50% sodium amide suspension and then with 26 g of diallyl carbide. , amyl chloride implemented. In the distillation, 26 g of Ν, Ν-diallyl carbamic acid geranyl ester are obtained. Kp. ₀ . ₀₁

12O ⁰ C.

Example 22 Mementhyl pyrrolidinocarboxylate

H ₃ C-CH-CH ₃

O — C — NH

40

45

CH,

5 °

- -CH =

Example 24

Bornyl pyrrolidinocarboxylate

II />

O — C — NH

■ Production takes place analogously to Example 5 from 20 g of borneol and 17.5 g of pyrrolidinocarboxylic acid chloride. B.p. _{0> 1} : 115 ° C; M.p. 37 ° C. Yield 23g.

Production takes place analogously to Example 5 from 20 g of menthol and 17.3 g of pyrrolidinocarboxylic acid chloride. _{B.p. OiO1} : 115 ⁰ C; M.p. 56 ^° C. Yield 22 g.

Example 23. L-pyrrolidinocarboxylic acid a-terpinyl ester

55 B bis ρ ie 1 25 DN-cyclohexyl-carbamic acid phenyl ester

H, C

60

Production takes place analogously to Example 5 from 20 g of La-terpineol and 17.5 g of pyrrolidinocarboxylic acid chloride. Kp _{0, 05:} 120 ° C;. Mp 43 ° C. Yield 22g.

65 Production takes place analogously to Example 17 from 15.4 g of fenchol and 12.5 g of cyclohexyl isocyanate. Kp _ool: g. 130 ⁰ C. Yield 19th

Example 26
Elinalyl 4-fluorobenzoate

CH ₃ CH ₃ O

\ I Il

C = CH-CH ₂ -CH ₂ -C-O-C

CH ₃

CH
CH ₂

18.5 g of linalool in 100 ml of toluene are mixed with 7.8 g of sodium amide suspension (50%) at the boiling point. After the ammonia has been driven off with nitrogen, 16g4-fluorobenzoyl chloride is added dropwise to the solution. The mixture is _subsequently stirred at 110 ^° C. ^{after 1 J for 2 hours.} The cooled solution is washed twice with water, dried with potassium carbonate and evaporated. The residue is fractionated twice under vacuum. Bp _O7 : 123 ° C. Yield 13g.

—N-

20th

Claims (1)

Claim: Process for the preparation of terpene esters of the general formula ■■■ '.. T - O - CO - R in which T- is a terpene radical of the composition C _n H ₂ "_ _x or C _n H ₂ " _ _X O with η = 5 to 20 and x = 0 to 6, which is different from an acyclic terpene, from a monocyclic terpene of the p-menthane series or of the bisabolon type or from a bicyclic terpene of the camphan or fenchan series by splitting off a hydrogen atom or the hydroxyl group and R is either a saturated 3- or 5-membered alicyclic ring or a phenyl radical or the group substituted by a fluorine 40 R _{1 represents} hydrogen and R _{2 represents} a low molecular weight alkyl radical, the cyclohexyl, phenyl or the optionally substituted pyridyl radical, R ₁ and R _{2 represent} low molecular weight alkyl or alkenyl radicals or together with the nitrogen atom the pyrrolidyl, one optionally substituted by alkyl groups Piperidyl radical and the morpholino radical mean, as well as their salts, thereby marked t ,. that in a manner known per se ■ a) a terpene alcohol of the general formula T-OH with an acid halide of the general formula _V Hal -CO-R where Hai means a halogen atom, in the presence of basic substances in a solvent at temperatures from 0 to 150 ⁰ C or b) a terpene alcohol of the general formula T-OH
with an isocyanate of the general formula with or without a solvent at temperatures of 50 to 150 ⁰ C or reacts c) a terpene halide of the general formula T - shark with an alkali or silver salt of the general formula A-O-CO-R in which A denotes an alkali metal or silver, optionally reacts or in a solvent at temperatures from 20 to 200 ⁰ C d) a terpene alcohol of the general formula T-OH with an acid of the general formula
HOOCR at temperatures between 50 to 250 ° C in the presence of catalysts with elimination of water optionally reacted in an inert solvent and the compounds obtained are optionally converted into their salts. ■