DE2321472A1 - PROCESS FOR MANUFACTURING DIELSALDER ADDUCTS - Google Patents

Description

, j UiA 2 7, April 1973

Or. Ing. A. van der Wenn

Dr. hwi LöQsrer

6510/88

L. Givaudan & Qe Societe Anonyme, Vernier-Geneve (Switzerland)

Process for the preparation of Diels-Alder adducts

The synthesis of α-substituted acrolein derivatives by condensation of low molecular weight aldehydes with formaldehyde is known [MI Faberov, GS Mironov and MA Korshymov, ZH. Prikl. Khim 2>, 2483-91 (1962), CA. 69, 394 (1962), see also German Patent 867,852; German Patent 875,194; US Patent 3,463, 818]. The Diels-Alder reaction of acrolein, methacrolein and other α-substituted acroleins is also known.

It has now become a superior method of preparing Diels-Alder adducts from in situ and reacting introduced dienophiles such as acrolein or α-substituted acroleins and conjugated dienes and dienols.

This superior method of making Diels-Alder, Adducts, which are used in perfumery, exist

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ORIGIN **

- Z-

232U12

in that one has formaldehyde, a second aldehyde of the formula

wherein R _{1 is} H-, CH ₃ -, CH ₅ CH ₂ -, CH ₃ CH ₂ CH ₂ - or (CHJCCHCHH () -.

t,

and a conjugated diene or a conjugated dienol of the formula

CH ₀ = C-C = CH
^R 4 3 ^R 2

wherein R ₂ and E. H- or CH ₃ - and R ₃ H-, CH ₃ -, (CH ₃ ) ₂ C = CHCH ₂ CH ₂ - or (CH ₃ J ₂ (OH) CCH ₂ CH ₂ CH ₂ - represent,

brings to implementation.

A particular characteristic of the present invention is that the dienophiles (the probable condensation products formaldehyde with the second aldehyde) react immediately with the conjugated diene or conjugated dienol, where the Diels-Alder adduct is formed * The dienophiles can also be viewed as acrolein or α-substituted acrolein. The key advantages of the present Method consist in that, firstly, many low molecular weight unsubstituted acroleins are irritating to the skin, eyes and respiratory tract, i.e. working with these substances is extremely unpleasant, .that Second, the pronounced reactivity of acrolein and α-substituted acroleins leads to these products Easily decompose on storage, and thirdly, the combination of the formation of the dienophile with the Diels-Alder reaction does not leads to procedural advantages that are to be underestimated.

3 0 9846/1193

The adducts obtainable by the process according to the invention represent fragrances with a green and / or floral appearance Odor represent and have proven to be extremely valuable for perfumery purposes proven, namely in the production of compositions of the rose, violet and lily of the valley types.

As stated above, the invention consists in a new one Process resulting from the reaction of acetaldehyde or a monosubstituted acetaldehyde with formaldehyde and a conjugated Dien or dienol consists. The reaction is carried out in the presence of an amine or an amine salt as a catalyst .

As aldehydes of the formula R CH ₂ CHO, for example acetaldehyde, propionaldehyde, n-valeraldehyde,. n-butyraldehyde and citronellal are used.

As diene or dienol, for example, myrcene, Myroenol and 2-methyl-1,3-pentadiene Y-3xi; 0i: i & wig find.

An amine, ammonia, an amine salt can be used as a catalyst or an ammonium can be used. Examples of such catalysts are diethylamine, ammonium chloride and ammonium hydroxide.

Of course, other materials can also be present in the reaction vessel. For example, water can be present, especially where formalin (a 3-part aqueous solution of formaldehyde) is used. There is also the presence of oxidation inhibitors such as ζ. B. Ionol (2,6-di-tert-butylcresol) is desirable. If desired, solvents can also be used. Examples of suitable solvents are benzene, toluene, xylene, nitrobenzene, acetone, ether, chlorobenzene, cyclohexane, dioxane, ethanol, butanol, propanol and water.

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The ratio of the reactants can vary within a wide range. Equimolar amounts of formaldehyde, the second aldehyde and the conjugated diene or dienol usually give excellent results, if desired however, the diene or the dienol can also be used in excess, which leads to the rapid consumption of the dienophile formed contributes. Such an excess proves to be particularly advantageous when the dienophile is extremely reactive and accordingly there is a risk that it will be decomposed before reacting with the diene or dienol. The amount of excess however, is reasonably dependent on the costs of the reactants.

The amount of catalyst used can also be equimolecular (based on conjugated diene); the catalyst can, however, also be in much smaller amounts, for example ί.0% or even less, of this diene or dienol. The catalyst is preferably used in quantities of approximately 0.5 to approximately 0.05 mol of the diene or dienol used. The ionol is usually only used in small amounts, for example 0.1 to 0.5% by weight based on the total amount of the reactants.

The reaction conditions are usually not critical. The reaction temperature can, for example, be in a range from approximately 90 to approximately 160 ^° C., but higher or lower temperatures are also possible. The preferred temperature range is between about 100 and about 140 ^° C.

The reaction can be carried out under atmospheric pressure or at elevated pressure. Under increased pressure should for example a pressure of about 60 p.s.i. (psi χ 0.068 = atm.). It has been shown in practice

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that prints from about 10 to about 100 p.s.i. are preferred. The pressure is of course also dependent on the temperature and the partial pressures of the reactants, in particular from Partial pressure of the material with the lowest boiling point.

The pH of the reaction medium can typically be between about 3 and about 9.

The reaction time depends on the temperature, pressure and the specific reactants. Sensible response times are less than one to about 30 hours.

As said above, the products of the invention Reaction is valuable odoriferous substances. They can be used in odoriferous substance compositions, for example in amounts of approximately 0.1 wt.> £ to about 45 wt. $.

The catalyst used in the following examples was prepared as follows: In a 125 ml three-necked flask, which is equipped with a stirrer, condenser, thermometer and dropping funnel 30 ml of water are added dropwise to 13.1 g (0.18 mol) of diethylamine (cooling, since the reaction is exothermic) at room temperature. The aqueous amine is neutralized by the dropwise addition of approximately 24 ml of 3Q sulfuric acid at room temperature (Cooling!). The pH is adjusted to 7 using a pH meter.

example 1

In a 1 liter flask equipped with a stirrer and thermometer, 103.0 g of propionaldehyde and 149.0 g of a 37% aqueous solution of formaldehyde, 1.8 g of Ionol and Added 218.0 g of distilled myrcene. The catalyst described above is added in such a way that the temperature

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Does not exceed ^{3O 0 C;} relatively little heat is developed. The reaction mixture is placed in a 1 liter Magna Drive autoclave. The batch is heated, while stirring, to a temperature of 130 ^° C. and is kept at this temperature for a further three hours while stirring. The maximum pressure is 60 ρ s i. The autoclave is finally cooled to room temperature and emptied. The progress of the reaction can be followed by gas chromatography at 170 ^° C. (20 M). The reaction mixture is placed in a separatory funnel, the upper organic layer is separated off and washed three times with 100 ml of water each time. After drying over sodium sulfate, the raw material is distilled in a 37 cm column filled with glass bodies. The product, which has a boiling point of 86-91 ° / 0.9-1.0 mm Hg, n ^ ° = 1.4820-1.4846, is an isomer mixture of l-methyl-4- (4-methyl -3-penten-1-yl) 3-cyclohexen-1-carboxaldehyde and 1-methyl-3- (4-methyl-3-penten-1-yl) 3-cyclohexen-1-carboxaldehyde. The yield is 229 g . The structure was confirmed by the IR, NM R, and GC data. Smell of the mixture: spicy, like lilies.

Example 2

Am mixture of 155 g (I ₁ 8 mol) of n-valeraldehyde, 149 g "(1.8 mol) of formalin, an amount of catalyst corresponding to the above, 1.8 g of ionol (BHT) and 66.3 g 2 -methyl-pentadiene 1,3-is placed in a 1-liter Magna Drive autoclave and heated for 3 hours at 16Q ⁰ C., the organic layer is separated from the reaction mixture and washed neutral with water. After drying over magnesium sulphate, the volatile components by means of water jet pump and the product is finally distilled in a 37 cm column filled with glass bodies, giving 70.1 g of a material with a boiling point of 67-69 ° / 0.6-0.7 mm Hg, n ^ = 1.4644 -60.

3098 46/1 193

Mass spectrum-.MG (180 (10S), 165 (5 #), 162 (296), 152 (756), 151 (I6 / 0), 139 (I / O, 138 (9/0), 137 (600) , 133 (3/0, 129 (2 / o), 127 (2Ji), 124 (2/0, 123 (1Of ₀ ), 122 (2/0, 121 (7/0, 119 (8/0, 117 (Ι9δ), 111 (2/0, 110 (ll #), 109 (43/0, 108 (13/0, 107 (18 #) 105 (8/0, 99 (156), 98 (l / O, 97 (5/0, 96 (6/0, 95 (39/0, 94 (6/0, 93 (18 #), 92 (3/0, 91 (20/0, 85 (2/0, 82 ( 100/0, NMR

(CDClJT, 0.3 (s, l, -CH0), 4.6O (b, l, \ _{e ===} /) 7.90-8.90 (b, 12, aliphatic.), 8.90-9.20 (m, 6, -CHT) The product has a tart, rubber-like, floral scent. It is an isomer mixture of 3,5-dimethyl-in-propyl-3-cyclohexene-1-carboxaldehyde and 2,4-dimethyl-in-propyl-3- cyclohexene-carboxaldehyde.

Example 3

In a 1-liter Magna Drive autoclave, a mixture of 79.2 g (1.8 mol) of acetaldehyde, 149 g (1.8 mole) of a 3 5 $ - aqueous formaldehyde solution and the above mentioned amount of catalyst, 1.8 g of ionol (BHT) and 272 ₉ 2 g myrcenol for 3 St.üiden to 130 ⁰ C heated. The reaction mixture is taken up in ethyl acetate, the solution is washed neutral with water and dried over magnesium sulfate. The product is distilled on a distillation column, with 77.1 g of one

20 material with a boiling point of 147 ° / 2 mm Hg and n _D = 1.4900- · 1.4924 arise. The material is identical to the reaction product of acrolein with myrcenol. It is an isomer mixture of 4- (4-hydroxy-4-methylpent-1-yl) -3-cyclohexene-1-carboxaldehyde and 3- (4-hydroxy-4-methylpent-1-yl) -3-cyclohexene -1-carboxaldehyde. The smell of the mixture is floral, like lily of the valley.

Example 4

A mixture of 130 g (1.8 moles) of n-butyraldehyde, an amount of 309846/1193

232H72

Catalyst equivalent to the above, 14-9 g (1.8 moles) formalin (37% formaldehyde), 1.8 g of Ionol and 218 g of myrcene (1.8 mol) are in a 1 liter stainless steel autoclave for 3 hours heated to 130 °. The organic layer is separated off from the reaction mixture and washed neutral with water. The raw product (305.4 g) is in a 37 cm column, which is filled with glass bodies, distilled, with 79.2 g of a material from

Boiling point 106-109 ° / !, 2-1.4 mm, n ^ 1.4857. Mass spectrum »Μ G. 220 (5%), 192 (3%), 191 (15%), 177 (6%), 163 (5 $), 149 (4%), 136 (3 $), 135 (7 %), 123 (9%), 122 {8%), 121 (11%), 119 (6%), 109 (7%), 107 (13%), 105 (8%), 95 (Ufo), 94 (5%), 93 (27%), 92 (5%), 91 (16%), 85 (4%), 83 (3%), 82 (4%), 81 (15%), 79 ( 17%), 77 (13%), 70 (7%), 69 (100%), NMR (CDCl ₃ ) T, 0.6 (s, l, -CHO), 4.60 (b, l, ^ = K), 4.95 (b, l, _H JQ), 7.6-8.6 T (m, 18, aliphat., Somewhat allyl.), 9 ^ .1 CH,

(t, 3, -CHp). The reaction product is a mixture of isomers of 1-ethyl-4- (4-methyl-3-penten-l ~ yl) -4-cyclohexene-1-carboxaldehyde and 1-ethyl-3- (4-methyl-3-penten-1-yl) -3-cyclohexene-1-carboxaldehyde. The smell of the material is bitter, green, flowery.

Example 5 -

A mixture of 218 g of myrcene, the amount of catalyst indicated above, 79.2 g of acetaldehyde, 149 g of formalin and 1.8 g Ionol (BHT) are heated for 3 hours at 130 ⁰ C in a 1 liter autoclave. The organic layer is separated from the reaction mixture, washed neutral with water and distilled, with 25 g of a product with a boiling point of 84-94 ° / 0.5-1.0 mm Hg,

ηΞ 1.4908. The material is identical to the reaction product of the Diels-Alder reaction of myrcene and CH ₂ = CHCHO (ex acetaldehyde plus formaldehyde). The product is an isomer mixture of 3- (4-methyl-3-penten-1-yl) -3-cyclohexene-1-carboxaldehyde and 4- (4-methyl-3-penten-1-yl) -3 -

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cyclohexene-1-carboxaldehyde. The smell of the material is fresh, fruity (melon).

Example 6

A mixture of 104.4 g (l _f 8 mol) propionaldehyde, the above-mentioned amount of catalyst, 149 g (1.8 mol) formalin, 1.8 g Ionol (BHT) and 66.3 g (0.81 mol) 2-methyl-1,3-pentadiene is heated to 160 ° for 3 hours in a 1 liter stainless autoclave. The organic layer is separated off from the reaction mixture and washed neutral with water. The raw material is distilled in a 37 cm column, which is filled with glass bodies, whereby 16 g of a product with a boiling point of 44 ° / 0.6 mm

20th
Hg and n _D 1.4685 arise. Mass spectrum: MW 152 ($ 2), 137 (12 *), 134 (7 *), 125 ($ 2), 124 (17 *), 123 (32 *), 121 (5 *), 119 (6/0 , HO (9 *), 109 (44 *), 108 (10 *), 3 07 (12 *), 105 (6 *), 97 (3 *), 96 (4 *), 95 (20 *), 94 (7 *), 93 (14 *), 91 (20 *), 83 (10 *), 82 (100 *). NMR (CDOL-) T, 0.3 (s, l.-CHO), 4.62 (b ,!, ^^), 7.70-8.80 (m, 8, aliphat., Some alOyl.), 8.90 (s, 3, -> CH,), 8.99 (d, J = 4 cps, 3, -CH-CH The product has a green, fruity odor; it is an isomer mixture of 1,2,4-trimethyl-3-cyclohexene-1-carboxaldehyde and 1,3,5-trimethyl-3-cyclohexene-1-carboxaldehyde .

example 1

A mixture of 277 g (1.8 mol) of citronellal, the amount of catalyst given above, 149 g of formalin, 1.8 g of Ionol (BHT) and 66.3 g (0.81 mol) of 2-methyl-l, 3- ^{Pentadiene is heated to 160 °} C. for 3 hours in a 1 liter stainless autoclave. The organic layer is separated from the reaction mixture, washed neutral with water and distilled in a column, whereby 23 g of a product with a boiling point of 140 ° / 0.7 mm Hg are obtained, mass spectrum MW 248 (3 *), 233 (2 *) , 230 (4 *), 228 (2 *),

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. - ίο -. . ■ ■

220 (2 $), 219 (1 $), 215 (2%), 205 (1 $), 19.2 (2 $), 177 (2 $), 174 (IJi), 173 (I / O, 167 (2 $), $ 166 ($ 2), $ 165 ($ 3), $ 163 ($ 2), 162 (IJi), $ 137 ($ 33), $ 136 ($ 11), $ 135 ($ 43). NMR (CDCl ₃ ) T , 0.3 (β, Ι, -CHO), 4.6-5.3 (b, '2, - ^) , 7 * 8-9.2 (complex pattern, 24 aliphatic protons). The reaction product is an isomer mixture of 3, 5-dimethyl-1- (6 ~ methyl-5-hepten-2-yl) -3-cyclohexene-1-carboxaldehyde and 2,4-dimethyl-1- (6-methyl-5-hepten-1-yl) - 3-cyclohexene-l-carboxaldehyde. Odor: fresh, green, rainy, grapefruit.

Example 8

A mixture of 130 g (1.8 mol) of n-butyraldehyde of the above amount of catalyst, 149 g of formalin, 1.8 g of Ionol (BHT) and 66.3 g (0.81 mol) of 2-methyl 1-1, 3-pentadiene is heated to 160 ° for 3 hours in a 1 liter stainless steel autoclave. The organic layer is separated off, washed neutral with water, distilled in a column and dried. .TBs result in 20.2 g of a product with a boiling point of 60 ° / 0.8 mm Hg, η £ ^υ 1.4724. Mass spectrum j MG, $ 166 ($ 15), $ 139 ($ 14), $ 138 ($ 20), $ 137 ($ 78), $ 123 ($ 24), $ 109 ($ 46), $ 107 ($ 18), $ 96 ($ 8) .95 ($ 47), 93 ($ 24), 91 ($ 24), 83 ($ 19) ^ 82. ($ 100). HMR (CDCl ₃ ) T 0.25 (s, l, -CHO), 4.6 (b, l, / ~~), 7.5-8.6 (broad, 9, aliphatic. Saturated), 8.95 (d, J = 4 cps, 3 , CH ₃ -CH), 9.02 (t, J = 3 cps, 3, CH ₃ -CH ₂ ). The product has a green, vegetative naphthalene odor. It is an isomer mixture of 2,4-dimethyl-1-ethyl-3-cyclohexene-1-carboxaldehyde and ^ 5-dimethyl-1-ethyl-4-cyclohexene-1-carboxaldehyde.

"*. Example 9

A mixture of 103.0 g propionaldehyde, 149 g formaldehyde (37 $ solution), 1.8 g of Ionol, 218.0 g of myrcene and

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25, Og ammonium chloride is in a 1 liter autoclave 3 Heated to 130 ° for hours. The organic layer is separated from the reaction mixture and washed neutral with water and dried over magnesium sulfate. The reaction product is in a 37 cm column, which is filled with glass bodies, distilled, with a product with a boiling point of 89-91 ° / 0.9 mm Hg

20th

and n _D 1.4842-50 is obtained in an amount of 128.2 g. the

IR, HMR and GC data for this product are identical with the reaction product of the Diels-Alder reaction of myrcene and CH-X-C-CHO (ex condensation of propionaldehyde and formaldehyde). CHp odor and structure are otherwise identical to the product of Example 1.

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Claims (1)

232H72 Claims 1. Process for the preparation of compounds of Formulas and II wherein R _{1 is} H-, CH, -, CH ₅ CH ₂ -, CH ₅ CH ₂ CH ₂ - or (CH ₅ ) ₂ C = CHCH ₂ CH ₂ CH (CH ₅ ) -, and R ₄ H- or CH ₅ - and R ₅ H-, CH ₅ -, (C ^) ₂ C = CHCH ₂ OH ₂ - or (CH ₅ J ₂ (OH) CCH ₂ CH ₂ CH ₂ - represent, characterized in that one formaldehyde, a second Aldehyde of the formula '. . R ₁ CH ₂ CHO where R, has the above meaning, and a conjugated diene or conjugated dienol of the formula CH ₂ = C-C ₂ = C-C = CH 3 0 9 8 4 6/1193 wherein R ^ to R. have the above meaning, brings to implementation. 2. The method according to claim 1, characterized in that the reaction is carried out in the presence of a catalyst. 5. The method according to claim 1 or 2, characterized in that the second aldehyde and propionaldehyde used as conjugated diene myrcene. 4. The method according to claim 1 or 2, characterized in that as the second aldehyde n-valeraldehyde and as conjugated diene 2-methy1-1,3-pentadiene is used. 5. The method according to claim 1 or 2, characterized in that acetaldehyde is used as the second aldehyde and myrcenol used as a conjugated diene. 6. The method according to claim 1 or 2, characterized in that the second aldehyde and n-butyraldehyde used as diene myrcene. 7. The method according to claim 1 or 2, characterized in that the second aldehyde and acetaldehyde Dien myrcene used. 8. The method according to claim 1 or 2, characterized in that the second aldehyde and propionaldehyde Diene 2-methyl-1,3-pentadiene is used. 9. The method according to claim 1 or 2, characterized in that the second aldehyde used is citronellal and the diene used is 2-methyl-1 _r 3-pentadiene. 309846/1193 ■ -14- 232U72 10. The method according to claim 1 or 2, characterized in that n-butyraldehyde is used as the second aldehyde and as Diene 2-methyl-1,3-pentadiene is used. 309846/1193