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This invention is concerned with novel compounds of the formula ##STR1## wherein: R1, R2, R3 and R4 represent hydrogen, methyl, ethyl or isopropyl provided that R1, R2, R3 and R4 are not alike unless they represent methyl, and,
A61K47/62 — Medicinal. Such as the methods described in Houben-Weyl. The compound can be synthesized de novo using conventional solid phase synthesis methods.
R5 and R6 represent hydrogen or methyl.
The compounds of formula I possess organoleptic properties which make them particularly useful as odorants and flavorants.
The invention is also concerned with a process for the manufacture of the compounds of formula I and with fragrance and flavor compositions containing the same.
The compound of formula I can be prepared by:
(a) oxidatively rearranging a compound of the formula ##STR2## wherein R1 to R5 have the above significance
and R6 represents hydrogen, under ring contraction, or
(b) isomerizing a compound of the formula ##STR3## wherein R1 to R5 have the above significance, or
(c) rearranging a compound of the formula ##STR4## wherein R1 and R5 have the above significance
and R7 represents a lower alkyl or aryl group, under ring contraction.
The following Reaction Scheme in which R1 to R7 have the above significance illustrates these three process variants and also the preparation of the starting materials for formulas II, IV and VI. ##STR5##
The substituted 6-methyltetralin of formula VII can be reduced to the bicyclic 1,4-diene of formula II by known reduction methods such as those of Birch [see, for example, A. J. Birch, G. Subba Rao, Advances in Organic Chemistry 8, 1 (1972)] Benkeser [see, for example, R. Benkeser, J. Org. Chem. 24, 854 (1959) and 29, 955, 1313 (1964)]. The reduction may be carried out with an alkali metal or alkaline earth metal such as, for example, lithium, sodium or calcium and an alcohol in liquid ammonia or an alkylamine. A solvent such as diethyl ether, tetrahydrofuran or dimethoxyethane may be used if desired. The temperature of the reaction may range from -40° C. to the boiling point of the amine. It is preferred to conduct the reaction at a temperature 5°-6° C. below the boiling point of the amine.
In addition to the diene of formula II this reduction method also results in the formation of the byproduct tetrahydo compounds of formula II' ##STR6## wherein R1 to R5 have the same significance as above. While the compounds of formula II' are separable from the compounds of formula II by means such as gas chromatography it is not necessary to do so since the presence of these compounds does not adversely affect succeeding reactions, and it is therefore more economical to use such mixtures as the starting materials in the process.
When R6 of formula II represents hydrogen the compounds of formula I may be prepared by process variant (a) described previously. This process comprises an oxidative rearrangement of an olefin, involves a ring contraction and uses thallium (III) nitrate as the reagent [see A. Mc Killop, Pure Appl. Chem. 43, 463(1975)]. This reaction takes place under mild conditions at room temperature in an alcoholic solvent, preferably, methanol. After filtering off the thallium (I) salt, neutralizing the nitric acid by pouring the filtrate onto sodium bicarbonate, and removing the solvent the product can be purified by ordinary distillation methods such as fractional high vacuum distillation. Some dimethyl ketal of the formula ##STR7## wherein R1 and R5 have the above significance, is also formed as a by-product. These compounds of formula III need not be separated from the compounds of formula I since their presence does not have a detrimental effect on the organoleptic properties of the compounds of formula I. If desired, however, the compounds can be separated, (e.g., by Chromatography).
When R6 of formula II represents methyl the preferred synthesis of the compounds of formula I follows process variant (b) described above and outlined in Reaction Scheme I. This synthesis requires compounds of formula IV. The 1,4-dienes of formula II are preferably converted into the bicyclic epoxides of formula IV by known epoxidation methods. Especially preferred methods are those using peracids such as, for example, peracetic acid, and metachloroperbenzoic acid. The isomerization of the bicyclic epoxides of formula IV to the novel compounds of formula I in which R6 represents methyl (process variant b) is preferably carried out in the presence of an acidic catalyst, especially a Lewis acid catalyst such as boron trifloride etherate. The exothermic reaction is preferably carried out with external cooling which allows the temperature in the reaction mixture to be held at a maximum of 50° C. The reaction time is about 30 minutes.
Compounds of formula II in which R6 represents hydrogen may be oxidized to the cis-1,2-diols of formula V by known oxidizing agents such as trimethylamine N-oxide, N-methylmorpholine oxide, hydrogen superoxide, tertiary butyl hydroperoxide/tetramethylammonium acetate, chlorates or potassium permanganate. Osmium tetroxide may be used as the catalyst or when used in stoichiometric amounts, as the oxidizing agent. Solvents such as tert-butanol or acetone are preferred. When osmium tetroxide is used as the oxidizing agent, then pyridine is the preferred solvent. Th oxidation may be carried out in a two-phase system using phase transfer catalysts such as, for example, benzyltrimethylammonium chloride [see, for example, R. Criegee, M. Kropf, Methoden der organischen Chemie (Houben-Weyl), Vol. VI, Part 1a, p. 592, Georg Thieme Verlag Stuttgart 1979]. The cis-1,2-diol of formula V is subsequently converted into the monosulfonate of formula VI in which R7 represents lower alkyl or aryl. This conversion is carried out according to known methods, for example, using the corresponding sulfochloride of the formula R7 --SO2 --Cl in pyridine. The ring contraction required in the conversion of the compounds of formula VI into the compounds of formula I (process variant c) is conveniently carried out by the addition of a strong inorganic base such as, sodium hydroxide or potassium hydroxide in aqueous-alcoholic solutions. The reaction can be run at mild reaction temperatures, preferably at room temperature and is usually complete in less than 24 hours.
Depending on the nature and number of the substitutions R1 to R6, the compounds of formula I can be obtained as mixtures of diastereomers or mixtures of structural isomers. The mixtures can be separated into the individual components by separation techniques such as gas chromatography. It is more economical, however, not to effect a separation and to use the mixtures as such.
As mentioned earlier, a separation of the by-products of formula II' from the compounds of formula II and of the by-products of formula III from the compounds of formula I is not necessary. The presence of the by-products has no detrimental influence on the sensorial qualities of the novel compounds of formula I.
The compounds of formula I have particular organoleptic properties, on the basis of which they are excellently suited as odorant and flavoring substances. They are distinguished, in particular, by a combination of fruity, damascone-like musk notes which hitherto were missing in the pallette of the perfumer. In addition, some of these compounds have an odour in the direction of ambrette-seeds or exhibit berry-like notes of the ionone direction.
On the basis of their natural odour notes the compounds of formula I are suitable, in particular, for modifying known compositions, for example
(a) flowery compositions in which, for example, the warm notes are to be intensified, (e.g., for mens cologne),
(b) fruity compositions such as those of the raspberry type (essence types, compositions of the feminine direction),
(c) tobacco and woody compositions (essence types of the masculine direction) and
(d) compositions with green notes, wherein a desired rounding-off and harmonizing effect are produced.
Preferred compounds are 2,2,5,5-tetramethylbicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone and 2,2,3,5,5-pentamethylbicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone.
The first-named preferred compound may be synthesized by a route outlined in Reaction Scheme II. ##STR8##
Methyl lithium is added to 3,6,6-trimethylcyclohex-2-en-1-one in the presence of a cuprous salt. The resulting saturated tetramethyl-substituted cyclohexanone is subsequently methylated in the 2-position with methyl iodide and the ketone obtained is converted by known methods (1,2-addition) into the tertiary alcohol 1,2,3,3,6,6-hexamethylcyclohexanol. This alcohol is dehydrated in the presence of a mineral acid or a strong organic sulfonic acid, and the resulting hexamethylcyclohexanene is brominated with monobromination occuring on each of the vinylic methyl groups. The resultant dibromide is used as the alkylating agent for the cyclic alkylation of diethyl malonate. The reaction product which results is saponified and decarboxylated according to known methods yieldling 2,2,5,5-tetramethylbicyclo [4.3.0]-non-1(6)-ene-8-carboxylic acid. In the last step, methyl lithium is used to convert the carboxylic acid to the corresponding novel methyl ketone.
As odorant substances, the compounds of formula I on the basis of their original notes described above are suitable, in particular, in combination with a series of natural and synthetic odorant substances such as, for example:
Natural products
such an angelica root oil, galbanum oil, vetiver oil, patchouli oil, sandalwood oil, mandarin oil, ylang ylang oil, cedar oil, pine oil, lavender oil, bergamot oil, lemon oil, orange oil, coriander oil, oak moss, castoreum, ciste labdanum, calamus oil, geranium oil, jasmine absolute, rose oil, cassis absolute, narcissus absolute, vervain absolute etc.
Aldehydes
such as C10 -, C11 -, C14 -, C16 -, C18 -aldehyde, hydroxycitronellal, cyclamen aldehyde, benzaldehyde, p.-tert.-butyl-α-methylcinnamaldehyde, citral, citronellal, 2,6-dimethyl-5-hepten-1-al, isovaleraldehyde, trans-2-hexenal, sorbic aldehyde, trans-2-octenal, n-octanal, n-nonanal, trans-2-cis-6-nonadienal, 2,4-decadienal, methylnonyl-acetaldehyde etc.
Ketones
such as alpha-ionone, beta-ionone, methylionone, allylionone, acetanisole, 4-(para-hydroxyphenyl)-2-butanone, camphor, menthone, carvone, pulegone etc.
Acetals and ketals
such as phenylacetaldehyde dimethyl acetal, phenylacetaldehyde glycerine acetal, 2-methyl-1,3-dioxolan-2-ethyl acetate, caproaldehyde dimethyl acetal etc.
Ethers
such as eugenol methyl ether, methyl 1-methyl-cyclododecyl ether, anethol, estragol etc.
Phenol compounds
such as vanillin, eugenol, isoeugenol, creosol etc.
Alcohols
such as butanol, n-hexanol, cis-3-hexenol, trans-2,cis-6-nonadienol, cis-6-nonenol, linalool, geraniol, nerol, citronellol, nerolidol, farnesol, benzyl alcohol, phenylethyl alcohol, cinnamic alcohol etc.
Esters
such as ethyl formate, ethyl acetate, isoamyl acetate, t-butylcyclohexyl acetate, Myraldylacetat™ (Givaudan), benzyl acetate, styrallyl acetate, ethyl-α-methylphenyl-glycidate, maltyl isobutyrate, dimethylbenzylcarbinyl butyrate, linalyl acetate, isobutyl acetate, n-amyl butyrate, n-amyl valerate, ethyl palmitate, cinnamyl formate, terpenyl acetate, geranyl acetate, hexyl salicylate, linalyl anthranilate, amyl salicylate, methyl dihydrojasmonate.
Lactones
such as γ-undecalactone, γ-decalactone, γ-nonalactone, δ-decalactone, δ-octalactone, coumarin etc.
Acids
such as lactic acid, butyric acid, α-methylbutyric acid, trans-2-hexenoic acid, trans-2-octenoic acid etc.
Sulphur-containing compounds
such as p-menthane-8-thiol-3-one, dimethyl sulphide and other sulphides and disulphides etc.
Nitrogen-containing compounds
such as methyl anthranilate, indole, isobutylquinoline, various pyrazines, 5-methyl-heptan-3-one oxime etc.
Various additional components often used in perfumery
such as musk ketone, Musk 174™ (12-oxahexadecanolide), Sandela (3-isocamphyl-(5)-cyclohexanol).
The compounds of formula I can be used in wide limits which, for example, can extend in compositions from 0.1% (detergents) to 50% (alcoholic solutions). It will be appreciated that these values are not limiting values, since the experienced perfumer can also produce effects with even lower concentrations or can synthesize novel complexes with even higher concentrations. The preferred concentrations range between 0.5% and 20%. The compositions manufactured with the compounds of formula I can be used for all kinds of perfumed consumer goods (eau de cologne, eau de toilette, essences, lotions, creams, shampoos, soaps, salves, powders, deodorants, detergents, tobacco etc).
The compounds of formula I can accordingly be used in the manufacture of compositions and, as will be evident from the above compilation, a wide range of known odorant substances can be used. In the manufacture of such compositions the known odorant substances specified above can be used according to methods which are known to the perfumer such as, for example, according to W. A. Poucher, Perfumes, Cosmetics and Soaps 2, 7th Edition, Chapman and Hall, London, 1974.
The compounds of formula I are also excellently suited for use in fruit flavours of various kinds, but especially also for the flavouring of tobacco.
As flavouring substances the compounds of formula I can be used, for example, for the production or improvement, intensification, enhancement or modification of fruit flavours of various kinds (e.g. blackberry or apricot flavours). As fields of use for these flavours there come into consideration, for example, foodstuffs (yoghurt, confectionery etc), semi-luxury consumables (tea, tobacco etc) and drinks (lemonade etc).
The pronounced flavour properties of the compounds of formula I enable them to be used in low concentrations. A suitable concentration embraces, for example, the range of 0.01-100 ppm, preferably 0.1-20 ppm, in the finished product, i.e. the flavoured foodstuffs, semi-luxury consumable or drink.
In the flavouring of, for example, tobacco, the concentration can, however, also be higher and can embrace a wider range, for example the range of 1 to 1000 ppm, preferably 50-500 ppm.
The compounds can be mixed with the ingredients used for flavouring substance compositions or added to such flavourants in the usual manner. Under the flavourants used in accordance with the invention there are to be understood flavouring substance compositions which can be diluted or dispersed in edible materials in a manner known per se. They contain, for example, about 0.1-10 wt.%, especially 0.5-3 wt.%. They can be converted according to methods known per se into the usual forms of use such as solutions, pastes or powders. The products can be spray-dried, vacuum-dried or lyophilized.
The known flavouring substances conveniently used in the manufacture of such flavourants are either mentioned in the above compilation or can be concluded readily from the literature such as, for example, from J. Merory, Food Flavourings, Composition, Manufacture and Use, Second Edition, The Avi Publishing Company Inc., Westport, Conn. 1968, or G. Fenaroli, Fenaroli's Handbook of Flavour Ingredients, Second Edition, Volume 2, CRC Press, Inc. Cleveland, Ohio, 1975.
For the manufacture of such usual forms of use there come into consideration, for example, the following carrier materials, thickening agents, flavour improvers, spices and auxiliary ingredients etc:
Gum arabic, tragacanth, salts or brewers' yeast, alginates, carrageen or similar absorbents; indoles, maltol, dienals, spice oleoresins, smoke flavours; cloves, diacetyl, sodium citrate; monosodium glutamate, disodium inosine-5'-monophosphate (IMP), disodium guanosine-5-phosphate (GMP); or special flavouring substances, water, ethanol, propylene glycol, glycerine.
The following Examples illustrate the present invention:
160 ml of methylamine are placed in a three-necked sulphonation flask equipped with a stirrer and a low temperature condenser (filled with CO2 /isopropanol) and 40 g (0.2M) of 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydro-naphthalene and 18 g (0.4M) of ethanol are added. The mixture is cooled to -15° C. and 2.7 g of lithium in small pieces are added. After 10 minutes, there are added a further 9 g (0.2M) of ethanol and subsequently a further 1.4 g (0.2M) of lithium in small pieces. The entire lithium dissolves within 15 minutes. The methylamine is then distilled off and the residue is diluted with hexane. The organic phase is washed neutral with water, dried over sodium sulphate and evaporated. 40 g of crude product are obtained. This product contains (according to GC):
55%: 2,2,5,5,8-Pentamethyl-bicyclo[4.4.0]deca-1(6),8-diene. 1 H-NMR (CDCl3 400 MHz): 0.99 (s, 3H); 1.01 (s, 3H); 1.5 (s, 4H); 1.68 (m, 3H); 2.54 (m, 2H); 2.65 (m, 2H); 5.42 (m, 1H); MS: M+ 204, 189, 175, 161, 133, 119, 105, 93, 81.
7%: 2,2,5,5,8-Pentamethyl-bicyclo[4.4.0]deca-1(10), 7,-diene, 1 H-NMR (CDCl3 400 MHz); 0.63 (s, 3H); 0.99 (s, 3H); 1.03 (s, 3H); 1.07 (s, 3H); 1.69 (s, 3H); 5.43 (m, 1H); 5.50 (m, 1H); MS: 204, 189, 145, 135, 133, 119, 105, 91, 77, 69, 55, 41, 27.
30%: 2,2,5,5,8-Pentamethyl-bicyclo[4,4,0]deca-1(6)-ene.
6%: Starting material.
253.3 g of hydrocarbon mixture containing about 60% of 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]deca-1(6),8-diene are dissolved in 1050 ml of tert.butanol and treated with a solution of 91.65 g of trimethylamine N-oxide dihydrate in 375 ml of water. Thereto there is added a solution of 40 mg of osmium tetroxide in 75 ml of tert.butanol and the mixture is held for 48 hours at 95° C. with good stirring at reflux temperature. The solution is extracted with 2 l of dichloromethane, 1 l of water and 412.5 ml of 2N hydrochloric acid and ice. The organic phase is washed neutral twice with 1 l of water each time and the aqueous phases are extracted with dichloromethane. After drying over magnesium sulphate and concentration on a rotary evaporator, there are obtained 269 g of crude crystals. These are recrystallized from 150 ml of hexane and 80 ml of dichloromethane. There are obtained 167.0 g of crystalline 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]dec-1(6)-ene-8,9-diol of melting point 98°-99.5° C.
1 H-NMR: (400 MHz, CDCl3): δ (ppm) 0.96 (s, 3H); 0.97 (s, 3H); 0.98 (s, 3H); 1.00 (s, 3H); 1.19 (s, 3H); 1.48 (s, 4H); 3.58 (m, 1H).
MS (m /e): 238 (M+), 220, 205, 177, 161, 149, 135, 121, 109, 105
150 g of the diol are dissolved completely at room temperature in 406.8 ml of pyridine while stirring. To this solution (cooled to 0° C.) are added dropwise during 30 minutes 82.9 g of methanesulphonyl chloride and the mixture is stirred at 20° C. for 3.5 hours. The suspension is poured into 1 l of dichloromethane and washed with 2.77 l of 2N hydrochloric acid and with sodium chloride solution. The aqueous phases are extracted twice with 500 ml of dichloromethane each time. The combined organic phases are dried over magnesium sulphate and concentrated on a rotary evaporator. After drying in a high vacuum at room temperature, there are obtained 198.5 g of crystalline monomesylate of the diol which, after recrystallization from dichloromethane/hexane, melts at 100°-104° C. with decomposition.
198.5 g of the crude monomesylate are dissolved completely at room temperature in 1190 ml of methanol and treated with 1190 ml of 3N potassium hydroxide solution. The mixture is stirred at 20° C. for 26 hours, taken up in hexane and washed with water. The aqueous phases are extracted twice with hexane. The combined organic phases are dried over magnesium sulphate and concentrated on a rotary evaporator. There are obtained 134.3 g of oil which is distilled over a 15 cm Widmer column. The fraction of boiling point 70°-76° C./0.03 Torr and nD20 1.4868 (106.4 g) represents pure 2,2,5,5-tetramethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone.
200 g of hydrocarbon mixture containing 60% of 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]deca-1(6),8-diene are dissolved in 2 l of methanol and 280 g (0.71M) of thallium (III) nitrate are added while stirring. A sample is removed (GC) after stirring for 48 minutes at room temperature. The reaction has still not finished. A further 50 g (0.12M) of thallium (III) nitrate are added after stirring for 57 minutes. After stirring for 2 hours the thallium (I) nitrate (184 g, 0.69M) is filtered off. The solution is poured cautiously while stirring on to 160 g of sodium bicarbonate. The mixture is stirred at room temperature for 30 minutes. The methanol is distilled off on a rotary evaporator in the presence of a small amount of sodium bicarbonate. The residue is washed with a small amount of ether. The crude product (208 g) is distilled in a high vacuum. After two-fold distillation (Widmer column, packed column 60 cm), there are obtained 56 g of product.
Separation by gas chromatography and analysis:
72%: 2,2,5,5-Tetramethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone. 1 H-NMR (CDCl3 400 MHz): 0.96 (s, 3H); 0.975 (s, 3H); 1.44 (s, 3H); 2.15 (s, 3H); 2.52 (d, J=8 Hz, 4H); 3.09 (m, J=8 Hz, H3, 1H); IR: 1710 cm-1 ; MS: 220 M30, 205, 177, 161, 145, 133, 119, 105, 91, 79, 55, 43. Odour: ambrette-musk, fruity, damascone.
9%: 1-(2,2,5,5-Tetramethyl-bicyclo[4.3.0]non-1(6)-en-7-yl)-1,1-dimethoxyethane . 1 H-NMR (CDCl3 400 MHz): 0.95 (s, 9H); 1 (s, 3H); 1.08 (s, 3H); 3.29 (s, 3H); 3.34 (q, J=8, J=6 Hz, 1H); 3.43 (s, 3H); MS: 266, 234, 219, 203, 187, 175, 163, 147, 133. 119, 102, 91, 59.
600 ml of methylamine are placed in a three-necked sulphonation flask equipped with a stirrer and a low temperature condenser (filled with CO2 /isopropanol). There are now added 100 g of 1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthalene and 42.6 g (0.92M) of ethanol. The mixture is then cooled to -15° C. and 6.5 g (0.93M) of lithium in small pieces are added within 75 minutes. As long as the lithium has not reacted completely the mixture is cooled to -15° C. and then it is held at reflux temperature overnight. After 19.5 hours and after 25.5 hours, there are added at -15° C. within 30 minutes 3.25 g (0.46M) of lithium. The methylamine is distilled off after 29 hours. The residue is diluted with hexane, washed four times with water, once with 5% sulphuric acid and once more (neutral) with water, dried over sodium sulphate and evaporated. 82 g of crude product are obtained. This product contains (according to GC):
47%: 2,2,4,5,5,8-Hexamethyl-bicyclo[4.4.0]deca-1(6),8-diene. 1 H-NMR (CDCl3 360 MHz): 0.83 (s, 3H); 0.88 (d, J=7 Hz, 3H); 0.96 (s, 3H); 1 (s, 3H); 1.02 (s, 3H): 1.68 (s, 3H); 5.41 (m, 1H); MS: 218, 203, 175, 159, 147, 133, 119, 105, 91 83.
29% 2,2,4,5,5,8-Hexamethyl-bicyclo[4.4.0]dec-1(6)-ene.
154 g of the crude diene (51%, 0.357M) are dissolved in 660 ml of tert.butanol in a three-necked sulphonation flask equipped with a stirrer, a reflux condenser, a thermometer and a protecting gas feed pipe with a bubble counter and treated with a solution of 57 g of trimethylamine N-oxide in 232 ml of water. Thereto there are added 150 ml of a 0.05% solution of osmium tetroxide in tert.-butanol. The emulsion is held at reflux temperature for 48 hours with good stirring. The cooled solution is diluted with 300 ml of ether and washed with 300 ml of saturated sodium chloride solution, 325 ml of 2N hydrochloric acid and ice. The organic phase is washed twice with saturated sodium chloride solution. The aqueous phases are extracted twice with ether. After drying the combined organic phases over magnesium sulphate and concentration on a rotary evaporator, there are obtained 130 g of crude product. By recrystallization from hexane there are obtained 85 g (94%) of 2,2,4,5,5,8-hexamethyl-bicyclo[ 4.4.0]-dec-1(6)-ene-8,9-diol in the form of two isomers.
1 H-NMR: (CDCl3 400 MHz): 0.79 (s, 6H); 0.87 (d, J=7 Hz, 3H); 0.872 (d, J=7 Hz, 3H); 0.92 (s, 3H); 0.98 (s, 3H); 0.97 (s, 3H); 0.972 (s, 3H); 1.02 (s, 6H); 1.1 (s, 3H); 1.29 (s, 3H);
MS: 252 M+, 234, 219, 205, 191, 175, 161, 149, 135, 107, 91, 43.
85 g (0.337 mol) of the 2,2,4,5,5,8-hexamethyl-bicyclo[4.4.0]dec-1(6)-ene-8,9-diol are dissolved at room temperature in 218 ml of pyridine. The solution is now cooled to 0° C. and 30.2 ml of methanesulphonyl chloride are slowly added dropwise during 20 minutes. The mixture is stirred at room temperature for a further 24 hours. The mixture is thereupon diluted with ether and washed with 1.480 l of 2N hydrochloric acid and 400 ml of saturated sodium chloride solution. The aqueous phase is extracted with ether and the combined organic phases are washed neutral with dilute sodium bicarbonate solution, dried over sodium sulphate and evaporated.
Spectral data of the mesylate (two isomers):
1 N-NMR: (CDCl3 400 MHz): 0.795 (s, 3H); 0.807 (s, 3H); 0.875 (d, J=7 Hz, 3H) 0.877 (d, J=7 Hz, 3H); 1.917 (s, 3H); 1.93 (s, 3H); 1.97 (s, 3H); 1.98 (s, 3H); 1.02 (s, 3H); 1.03 (s, 3H); 1.17 (s, 3H); 1.35 (s, 3H); 3.07 (s, 6H); 4.68 (m, 2H);
MS: 330, 312, 297, 234, 219, 201, 191, 175, 149, 135, 119, 105, 95, 83.
100 g of the crude mesylate are dissolved at room temperature in 575 ml of methanol and this solution is left to react at room temperature for 21 hours with 575 ml of 3N potassium hydroxide solution. The mixture is thereupon diluted with ether and washed with a saturated sodium chloride solution. The aqueous phase is extracted with ether. The combined organic phases are neutralized and dried over magnesium sulphate. 73 g of crude product are obtained. By filtration with hexane over 700 g of silica gel there are firstly obtained 11 g of hexamethyltetralin. Elution with 20% ether/hexane gives 51 g of 2,2,3,5,5-pentamethyl-bicyclo[4,3,0]non-1(6)-en-8-yl methyl ketone (two isomers).
1 H-NMR: (CDCl3, 400 MHz): 1.78 (s, 3H); 1.79 (s, 3H); 1.86 (d, J=7 Hz, 3H); 1.87 (d, J=7Hz, 3H); 1.95, 1.96, 1.965, 1.98 (4 s, 18H); 2.15 (s, 3H); 2.157 (s, 3H); 2.52 (m, 8H); 3.105 (m, 2H);
MS: 234 M+, 219, 191, 175, 161, 149, 135, 119, 107, 91, 83, 69, 55, 43.
IR: (liquid) 1710 cm-1.
Odour: After ambrette-seeds, musk.
13 g of hydrocarbon mixture containing 28% of 2,2,4,5,5,8-hexamethyl-bicyclo[4.4.0]deca-1(6),8-diene are dissolved in 80 ml of methanol and 6.5 g (0.01669M) of thallium (III) nitrate are added. After stirring for 30 minutes at room temperature, the thallium (I) nitrate is filtered off and the solution is evaporated in the presence of excess sodium bicarbonate. The crude product is chromatographed over 300 g of silica gel. By elution with 3% ether in hexane there are obtained 900 mg of 2,2,3,5,5-pentamethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone and 670 mg of 1-(2,2,4,5,5-pentamethyl-bicyclo[4.3.0]non-1(6)-en-7-yl)-1,1-dimethoxyetha ne.
Spectral data of the ketal:
1 N-NMR: (CDCl3, 400 MHz): 0.79 (s, 3H); 0.86 (d, J=7 Hz, 3H); 0.955 (s, 3H); 0.962 (s, 3H); 0.995 (s, 3H); 1.155 (s, 3H); 3.21 (s, 3H); 3.25 (t, J=5 Hz, 1H); 3.38 (s, 3H);
MS: 280 M+, 248, 233, 217, 201, 189, 175, 163, 149, 133, 119, 102, 91, 73, 59.
1 H-NMR: (CDCl3, 400 MHz): 1 (s, 12H); 1.5 (s, 4H); 1.64 (s, 6H); 2.57 (s, 4H);
MS: 218 M+, 203, 147, 133, 119, 91, 77, 69, 56, 41.
The compound is purified by gas chromatography.
26 g of 2,2,5,5,8,9-hexamethyl-bicyclo[4.4.0]deca-1(6),8-diene and 3 g of sodium acetate in 200 ml of dichloromethane are placed in a sulphonation flask equipped with a stirrer, the mixture is cooled to -20° C. and 19 g of 40% peracetic acid are added dropwise within 5 minutes while stirring. The mixture is stirred at -10° C. for 45 minutes. The mixture is poured into water, washed with saturated sodium pyrosulphite solution and water and evaporated. The crude product (26 g) contains (according to GC) 70% of 8,9-epoxy-2,2,5,5,8,9-hexamethyl-bicyclo-[4.4.0]non-1(6)-ene.
1 H-NMR: (CHCl3, 400 MHz): 0.94 (s, 6H); 0.98 (s, 6H); 1.34 (s, 6H); 1.44 (m, 4H); 2.21 (d, J=16 Hz, 2H); 2.46 (d, J=16 Hz, 2H);
MS: 234, 219, 201, 191, 177, 161, 135, 119, 107 91, 77, 55, 43.
7.5 g of boron trifluoride etherate are added while stirring to a solution of 26 g of the above crude 8,9-epoxy-2,2,5,5,8,9-hexamethyl-bicyclo[4.4.0]non-1(6)-ene. The temperature rises to 50° C. The mixture is cooled with ice. After stirring for 30 minutes, the mixture is poured into water, washed with saturated sodium bicarbonate solution, dried and evaporated. The crude product (27 g) is chromatographed over 200 g of silica gel. By elution with hexane there are obtained 16 g of 1,1,4,4,6,7-hexamethyl-1,2,3,4-tetrahydro-naphthalene and by elution with 10% ether in hexane there are obtained 6.5 g of 2,2,5,5,8-pentamethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone.
1 H-NMR: (CDCl3, 400 MHz); 0.94 (s, 6H); 0.96 (s, 6H); 1.2 (s, 3H); 1.45 (s, 4H); 2.08 (d, J=13 Hz, 2H); 2.7 (d, J=13 Hz, 2H); 2.13 (s, 3H);
MS: 234 M+, 219, 191, 175, 161, 145, 135, 121, 105, 91, 83, 77, 69, 59, 55.
A solution of 240 g of 3,6-dichloro-3,6-dimethylheptane in 340 g of toluene is added dropwise within 1 hour to a suspension of 20.8 g of aluminium chloride in 333 g of toluene. The mixture is left to react for 50 minutes, 15 g of aluminium chloride are added thereto and the mixture is left to react for a further 10 minutes. The mixture is poured on to ice and extracted with hexane. The organic phase is washed with water, dried over sodium sulphate and evaporated. 274 g of crude product are obtained.
Spectral data of the mixture of 1,1,4,6-tetramethyl-4-ethyl-1,2,3,4-tetrahydro-naphthalene and 1,4,4,6-tetramethyl-1-ethyl-1,2,3,4-tetrahydro-naphthalene:
1 H-NMR: (CDCl3, 400 MHz): 0.76 (t, J=7 Hz, 3H); 0.77 (t, J=7 Hz, 3H); 1.207 (s, 3H); 1.22 (s, 3H); 1.23 (s, 3H); 1.24 (s, 3H); 1.27 (s, 3H); 1.28 (s, 3H); 2.29 (s, 3H); 2.30 (s, 3H); 6.94 (d broad, J=8 Hz, 1H); 7.02 (s broad 1H); 7.105 (s, broad, 1H); 7.11 (d, J=8 Hz, 1H); 7.2 (d, J=8 Hz, 1H);
MS: 216, 201, 187, 173, 145, 131, 115, 105.
700 ml of methylamine are placed in a three necked sulphonation flask equipped with a stirrer and low temperature condenser (filled with CO2 /isopropanol) and 237 g of a mixture of 1,1,4,6-tetramethyl-4-ethyl-1,2,3,4-tetrahydronaphthalene and 1,4,4,6-tetramethyl-1-ethyl-1,2,3,4-tetrahydro-naphthalene are added. The mixture is cooled to -15° C. and reacted with two portions of ethanol (93 g and 47 g) and lithium (15.2 g and 7.6 g). The mixture is held at reflux temperature for 12 hours and 47 g of ethanol and 7.6 g of lithium are again added thereto. Thereupon, the methylamine is distilled off. The residue is diluted with hexane and washed with water, dried and evaporated 233 g of crude product are obtained. This product contains according to GC (area percent):
40% of a mixture of 2,5,5,8-tetramethyl-2-ethyl-bicyclo[4.4.0]deca-1(6),8-diene and 2,2,5,8-tetramethyl-5-ethyl-bicyclo[4.4.0]deca-1(6), 8-diene:
1 H-NMR: (CDCl3, 400 MHz): 0.737 (3H, t, J=7 Hz); 0.747 (3H, t, J=7 Hz); 0.955 (s, 3H); 0.975 (s, 3H); 0.982 (s, 3H); 0.990 (s, 3H); 1.002 (s, 3H); 1.007 (s, 3H); 1.68 (s, broad, 3H); 1.68 (s. 3H, broad); 5.42 (m, 1H); 5.42 (m, 1H);
MS: 218M+, 203, 189, 175, 173, 159, 147, 133, 199, 105, 91, 77, 69; and
45% of a mixture of cis- and trans-2,5,5,8-tetramethyl-2-ethyl-bicyclo[4.4.0]dec-1(6)-ene and 2,2,5,8-tetramethyl-5-ethyl-bicyclo[4.4.0]-dec-1(6)-ene:
1 H-NMR: (CDCl3, 400 MHz): 0.892 (s); 0.905 (s); 0.925 (s); 0.945 (s); 0.950 (s); 0.950 (s); 0.965 (s);
MS: 220M+, 205, 191, 177, 149, 135, 121, 109, 105, 95.
10 g hydrocarbon mixture containing 37% of 2,5,5,8-tetramethyl-2-ethyl-bicyclo[4.4.0]deca-1(6),8-diene and 2,2,5,8-tetramethyl-5-ethyl-bicyclo[4.4.0]deca-1(6),8-diene are dissolved in 200 ml of methanol and 6.62 g of thallium (III) nitrate are added while stirring. After stirring for 1.5 hours, the mixture is filtered and stirred in the presence of an excess of sodium bicarbonate and evaporated. The purification of the product is carried out by chromatography.
Spectral data of the mixture of the cis and trans isomers of 2,5,5-trimethyl-2-ethyl-bicyclo[4.3.0]non-1,6-en-8-yl methyl ketone:
1 H-NMR: (CDCl3, 400 MHz); 0.76 (t, J=7 Hz, 3H); 0.76 (t, J=7 Hz, 3H); 0.917 (s, 3H); 0.927 (s, 3H): 0.955 (s, 3H); 0.965 (s, 3H); 0.970 (s, 3H); 0.977 (s, 3H); 2.154 (s, 3H); 2.155 (s, 3H); 3.080 (m, 1H); 3.085 (m, 1H);
IR: (liquid): 1710 cm-1 ;
MS: 234M+, 219, 205, 191, 175, 161, 147, 131, 119, 105, 91, 77, 69, 43.
Odour: Fruity, musk, slightly woody.
302 g of concentrated sulphuric acid are placed in a three-necked sulphonation flask equipped with a stirrer, cooled at -10° C. and a solution of 99 g of 5-methyl-hex-1-en-5-ol in 377 g of toluene is slowly added dropwise within 1.25 hours. The mixture is stirred at the same temperature for a further 2.5 hours, then diluted with hexane and poured on to ice. The aqueous phase is extracted twice with hexane. The combined organic phases are washed with a saturated sodium carbonate solution and dried over sodium sulphate. The crude product (126 g) is distilled. In this manner there are obtained 73.8 g of 80% 1,1,4,6-tetramethyl-1,2,3,4-tetrahydro-naphthalene of boiling point 110° C./4×10-2 mm Hg.
1 H-NMR: (CDCl3, 400 MHz): 1.24 (s, 3H); 1.275 (d, J=7 Hz, 3H); 1.28 (s, 3H); 2.29 (s, 3H); 2.85 (M, 1H); 6.96 (d, J=8 Hz, broad, 1H); 6.98 (s, broad, 1H); 7.21 (d, J=8 Hz, 1H);
MS: 128M+, 173, 137, 143, 131, 115, 105, 91, 77 65, 51, 41.
225 ml of ethylamine are placed in a three-necked sulphonation flask equipped with a stirrer and a low temperature condenser (filled with CO2 /isopropanol), then 18.4 g (0.4M) of ethanol and 38 g of 1,1,4,6-tetramethyl-1,2,3,4-tetrahydro-naphthalene (80%) are added. 2.8 g (0.4M) of lithium are added within 10 minutes. The mixture is now stirred at room temperature for 1.5 hours. 10 g of ethanol (0.2M) and 1.5 g of lithium are then added thereto. The mixture is left to react for 2.5 hours. The ethylamine is thereupon distilled off. The residue is diluted with hexane. The organic phase is washed neutral with water, dried over sodium sulphate and evaporated. 35 g of crude product are obtained.
This product contains (according to GC): 43% of 2,2,5,8-tetramethyl-bicyclo[4.4.0]deca-1(6),8-diene.
1 H-NMR: (CDCl3, 400 MHz): 0.98 (s, 3H); 0.99 (s, 3H); 1.02 (d, J=7 Hz, 3H); 1.67 (m, 3H); 5.43 (m, 1H);
MS: 190M+, 175, 147, 130, 119, 105, 81, 77, 65, 55, 41.
24 g of crude 2,2,5,8-tetramethyl-bicyclo[4.4.0]deca-1(6),8-diene (43%) in 120 ml of tert.butanol are treated with a solution of 10.5 g of trimethylamine N-oxide in 43 ml of water in a three-necked sulphonation flask equipped with a stirrer, a reflux condenser, a thermometer and an argon flow with a bubble counter. 50 ml of a 0.05% solution of osmium tetroxide in tert.butanol are added thereto. The resulting emulsion is held at reflux temperature for 96 hours with good stirring. The cooled solution is diluted with ether and washed with a saturated sodium chloride solution, with 2N hydrochloric acid and with ice-water. The aqueous phases are extracted twice with ether. After drying the combined organic phases over magnesium sulphate and concentration on a rotary evaporator, 24 g of crude product was obtained. By recrystallization from hexane there are obtained 6 g of 2,2,5,9-tetramethyl-bicyclo[4.4.0]dec-1(6)-ene-8,9-diol of melting point 121°-123° C.
1 H-NMR: (CDCl3, 400 MHz): 0.975 (d, J=7 Hz, 3H); 0.977 (s, 3H); 0.99 (s, 3H); 1.22 (s, 3H); 3.59 (q, J=6 Hz, J=13 Hz, 1H);
MS: 224M+, 206, 191, 177, 163, 150, 135, 121, 107, 95, 74, 55, 43.
5 g (0.0265 mol) of 2,2,5,9-tetramethyl-bicyclo[4.4.0]dec-1(6)-ene-8,9-diol are dissolved at room temperature in 17 ml of pyridine. The solution is then cooled to 0° C. and 2.36 ml of methanesulphonyl chloride are slowly added dropwise during 20 minutes. The mixture is stirred at room temperature for 24 hours. The mixture is diluted with ether and washed with 1.480 l of 2N hydrochloric acid and 400 ml of saturated sodium chloride solution. The aqueous phase is extracted with ether. The combined organic phases are washed neutral with a dilute sodium bicarbonate solution, dried over sodium sulphate and evaporated. 4.1 g of crude monomesylate are obtained.
1 H-NMR: (CDCl3, 400 MHz): 0.97 (d, J=7 Hz, 3H); 0.985 (s, 3H); 1 (s, 3H); 1.29 (s, 3H); 3.07 (s. 3H); 4.68 (q, J=6 Hz, J=7 Hz, 1H);
MS: 287, 267, 206, 173, 163, 147, 131, 121, 107, 95, 91, 79, 69, 57, 41.
4 g of the crude mesylate are dissolved at room temperature in 25.1 ml of methanol and stirred at room temperature for 12 hours with 25.1 ml of 3N potassium hydroxide solution. The mixture is diluted with ether and washed with a saturated sodium chloride solution. The aqueous phase is extracted with ether. The combined organic phases are neutralized and dried over magnesium sulphate. 4 g of crude product are obtained. 1 g of 1,1,4,6-tetramethyltetralin is firstly obtained by filtration with hexane over silica gel. Elution with 20% ether/hexane gives 1.8 g of 2,2,5-trimethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone.
1 H-NMR: (CDCl3, 400 MHz); 0.965 (s, 3H); 0.9725 (d, J=7 Hz, 3H); 0.98 (s, 6H); 2.16 (s, 3H);
MS: 206M+, 191, 173, 163, 147, 133, 119, 107, 105, 91, 77, 69, 55, 43.
Odour: Damascone-like, ionine-like; after berries, tobacco.
250 ml of ethylamine are placed in a three-necked sulphonation flask equipped with a stirrer and a low temperature condenser (filled with CO2 /isopropanol). 2.36 g of methanol and 8 g of 1,1,6-trimethyl-4-isopropyl-1,2,3,4-tetrahydro-naphthalene are added. 0.5 g (0.074M) of lithium is added within 1 minute. The mixture is left to react under reflux for 12 hours. Thereupon, the same amounts of lithium and methanol are again added and the mixture is stirred at room temperature for 7 hours. The ethylamine is then distilled off and the residue is diluted with hexane. The organic phase is washed neutral with water, dried over sodium sulphate and evaporated. 6.9 g of crude product are obtained. This product contains (according to GC): 88% of 2,2,8-trimethyl-5-isopropyl-bicyclo[4,4,0]nona-1(6),8-diene.
1 H-NMR (CDCl3, 400 MHz): 0.71 (d, J=7 Hz, 3H); 0.945 (d, J=7 Hz, 3H); 0.975 (s, 3H); 0.98 (s, 3H); 1.66 (s, broad 3H); 5.43 (m, 1H);
MS: 218M+, 175, 159, 145, 133, 119, 105, 91.
6.9 g of 2,2,8-trimethyl-5-isopropyl-bicyclo[4.4.0]nona-1(6),8-diene are dissolved in 70 g of methanol and 12 g of thallium (III) nitrate are added while stirring. After stirring for 20 minutes at room temperature, the thallium (I) nitrate formed is filtered off and the solution is evaporated in the presence of an excess of sodium bicarbonate. The crude product is chromatographed over 100 g of silica gel. 2 g of 2,2-dimethyl-5-isopropyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone are obtained.
1 H-NMR: (CDCl3, 400 MHz): 0.712 (d, J=7 Hz, 3H); 0.93 (d, J=7H, 3H); 0.965 (s, 6H); 2.165 (s, 3H); 3.115 (m, 1H);
MS: 234M+, 219, 191, 173, 163, 147, 133, 119, 105, 91, 77, 69, 55, 43
IR: (liquid) 1710 cm-1
Odour: Fruity, damascone-like.
7.3 g of 4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2-indanecarboxylic acid are dissolved in 150 ml of tetrahydrofuran and treated slowly while cooling with ice and stirring vigorously with 47.3 ml of methyl lithium (1.6 molar in ether). After stirring for 3 hours at room temperature, the mixture is poured on to ice, extracted with ether, washed with water, dried over sodium sulphate and evaporated. After distillation of the crude product, there are obtained 5.6 g of 2,2,5,5-tetramethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone as a colourless liquid of boiling point 53°-60° C./0.01 mm Hg.
The 4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2-indanecarboxylic acid used as the starting material can be prepared as follows:
5.3 g of magnesium shavings are covered with 100 ml of ether and 30.8 g of methyl iodide are added dropwise in such a manner that the mixture boils slightly. After the addition of 100 ml of ether, the mixture is held at reflux temperature for a further 3 hours, cooled by means of an ice-bath and treated with 20.7 g of copper (I) iodide. After stirring for 15 minutes at 0° C., a solution of 10 g of 3,6,6-trimethyl-2-cyclohexenone in 40 ml of ether is added and the mixture is stirred at 0° C. for a further 3 hours. The green suspension is subsequently poured on to ice, acidified with 2N hydrochloric acid and extracted with ether. The insoluble constituents of the organic phase are filtered off, the filtrate is washed with dilute sodium thiosulphate solution, dried and evaporated. After distillation of the crude product, there are obtained 8.5 g of 2,2,5,5-tetramethylcyclohexanone as a colourless liquid of boiling point 60°-67° C./13 mm Hg.
106.9 ml of n-butyl lithium (2 molar in hexane) are added dropwise while cooling with ice to a solution of 21.6 g of diisopropylamine in 340 ml of ethylene glycol dimethyl ether. After stirring for 30 minutes at 0° C., a solution of 23.2 g of 2,2,5,5-tetramethylcyclohexanone in 100 ml of ethylene glycol dimethyl ether is added while cooling with ice. The mixture is stirred at room temperature for a further 45 minutes, again cooled to 0° C. and 213.9 g of methyl iodide are added thereto rapidly. The mixture is stirred at 50° C. for 45 minutes, cooled, poured on to ice and extracted with ether. After washing the organic phase with 5% hydrochloric acid and diluted sodium hydrogen carbonate solution, it is dried over sodium sulphate and evaporated. Distillation of the crude product on a spinning band column gives 13.7 g of 2,2,5,5,6-pentamethylcyclohexanone as a colourless liquid of boiling point 86°-94° C./16 mm Hg.
26 g of 2,2,5,5,6-pentamethylcyclohexanone are dissolved in 500 ml of ether and treated slowly at -20° C. with 113.5 ml of methyl lithium (1.5 molar in ether). After stirring for 3.5 hours at 0° C., the mixture is poured on to ice, acidified with 1N hydrochloric acid, extracted with ethyl acetate, dried and evaporated. Distillation of the crude product gives 25.9 g of 1-hydroxy-1,2,2,5,5,6-hexamethylcyclohexane as a colourless liquid of boiling point 87°-92° C./10 mm Hg.
25.9 g of 1-hydroxy-1,2,2,5,5,6-hexamethylcyclohexane are dissolved in 600 ml of benzene and, after the addition of a spatula tip of p-toluenesulphonic acid, held at boiling temperature on a water separator for 3 hours. The mixture is cooled, treated with sodium carbonate, stirred briefly, filtered and the benzene is distilled off at normal pressure. Distillation of the residue gives 21 g of 1,2,3,3,6,6-hexamethyl-1-cyclohexene as a colourless liquid of boiling point 65°-67° C./10 mm Hg.
21 g of 1,2,3,3,6,6-hexamethyl-1-cyclohexene are dissolved in 600 ml of carbon tetrachloride. After the addition of 45 g of N-bromosuccinimide and a spatula tip of α,α'-azoisobutyronitrile, the mixture is held at reflux temperature for 3 hours, cooled, the resulting succinimide is filtered off and the filtrate is evaporated. After filtration of the crude product over silica gel [eluting agent: hexane/ether (2:1)], there are obtained 38 g of 1,2-dibromomethyl-3,3,6,6-tetramethyl-1-cyclohexane as a colourless oil which solidifies in a freezer.
38 g of 1,2-dibromomethyl-3,3,6,6-tetramethyl-1-cyclohexene and 18.7 g of diethyl malonate are dissolved in 150 ml of ethanol and heated to 80° C. At this temperature there is added dropwise a solution of 5.4 g of sodium in 250 ml of ethanol. The mixture is subsequently held at reflux temperature for a further 6 hours. After cooling, the mixture is poured on to ice, acidified with 1N hydrochloric acid, extracted with ether, washed with water and evaporated. This crude product is chromatographed on silica gel [eluting agent: hexane/ether (4:1)]. There are obtained 18.4 g of diethyl 4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2,2,-indanebiscarboxylate as a not quite uniform colourless oil. The further purification is carried out in the next step.
18.4 g of diethyl 4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2,2-indanebiscarboxylate are dissolved in 500 ml of ethanol and treated with a solution of 64 g of potassium hydroxide in a mixture of 200 ml of ethanol and 50 ml of water. After heating at reflux temperature for 6 hours, the mixture is cooled, the majority of the alcohol is distilled off on a rotary evaporator, the residue is poured on to ice, acidified with 2N hydrochloric acid, extracted repeatedly with ethyl acetate, dried and evaporated. The thus-obtained crude product is heated to 160° C. for 5.5 hours and subsequently chromatographed on silica gel [eluting agent: hexane/ether (2:1)]. After recrystallization from pentane, there are obtained 6.5 g of 4,5,6,7-tetrahydro-4,4,7,7-tetramethyl-2-indanecarboxylic acid in the form of colourless crystals of melting point 125°-129° C.
In the following formulation Examples,
'compound 1' stands for 2,2,5,5-tetramethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone,
'compound 2' stands for 2,2,3,5,5-pentamethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone,
'compound 3' stands for 2,2,5-trimethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone,
'compound 4' stands for 2,5,5-trimethyl-2-ethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone and
'compound 5' stands for 2,2,5,5,8-pentamethyl-bicyclo[4.3.0]non-1(6)-en-8-yl methyl ketone.
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A. Raspberry flavour Parts by weight |
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Ethyl palmitate 0.05 0.05 Geraniol 0.2 0.2 Methylionone 0.6 0.6 Ethyl vanillin 1.0 1.0 Amyl valerate 1.0 1.0 Benzyl acetate 2.0 2.0 C16 -aldehyde 2.5 2.5 Ethyl formate 4.0 4.0 Amyl acetate 6.0 6.0 Ethyl butyrate 6.0 6.0 Isobutyl acetate 23.0 23.0 Ethyl acetate 33.5 33.5 Propylene glycol 920.15 905.15 Compound 1 (10% in ethanol) -- 15.0 1,000.00 1,000.00 |
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B. Tobacco flavour Parts by weight |
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Linalyl acetate (10% in ethanol) 0.3 0.3 Cinnamaldehyde (10% alcoholic) 0.4 0.4 Geraniol 0.5 0.5 Angelica root oil 0.5 0.5 Amyl butyrate 1.0 1.0 Amyl valerate 1.0 1.0 Vanillin 2.0 2.0 C18 -aldehyde 2.0 2.0 Petitgrain oil (Paraguay) 2.0 2.0 Benzaldehyde 2.5 2.5 Orange oil (concentrated 10-fold) 5.0 5.0 C14 -aldehyde 15.0 15.0 Alcohol 967.8 957.8 Compound 1 -- 10.0 1,000.0 1,000.0 |
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By adding compound 1 to the above composition the fruity note present in the composition is clearly intensified. The slightly fatty note is advantageously enveloped (covered); there appears an additional note which is reminiscent of fully ripe apricots.
In the incorporation of the composition in tobacco the intensified fruity note is of advantage and in addition, the tobacco note present is intensified in an advantageous manner. ______________________________________ |
C. General flowery perfumery base Parts by weight |
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Terpineol 260 Hydroxycitronellal 220 Cinnamic alcohol substitute 120 Phenylethyl alcohol 100 Cinnamyl formate 20 Linalool 15 Terpenyl acetate 10 Musk ketone 10 Geranyl acetate 10 Jasmine (synthetic) 10 Eugenol 5 Indole [10% in dipropylene glycol (DPG)] 5 C10 -aldehyde (10% in DPG) 5 p-Methylacetophenone 5 Undecalactone 5 500 |
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D. Perfumery complex in the direction of eau de cologne Parts by weight |
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Bergamot oil 200 Methyl dihydrojasmonate 200 Sandalwood oil 200 |
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E. Perfumery composition with a rose character Parts by weight |
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Phenylethyl alcohol 300 Geraniol 250 Jasmine 'lavage' (aqueous distillate) 200 Citronellol (extra) 100 Musk ketone 50 α-Ionone 30 C10 -aldehyde (10% in propylene glycol) 5 C11 -aldehyde (10% in propylene glycol) 5 940 |
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F. Perfumery chypre Parts by weight |
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1-Methylcyclododecyl methyl ether 200 Bergamot oil 150 Hydroxycitronellal 100 Pine oil (Pumillon) 80 Citronellol 80 Petitgrain oil 60 Musk 174 ™ Givaudan (12-oxahexadecanolide) 60 Coriander oil 40 Galbanum oil 40 Cedarwood oil 40 Patchouli oil 40 Lemon oil 40 Elemi oil 10 Oak moss (decolorized) 20 960 |
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G. Perfumery base with a fruity character Parts by weight |
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Ethyl-methyl-phenyl glycidate 50 Ethyl acetoacetate 15 Dimethyl-benzyl butyrate 15 Maltyl isobutyrate 10 Benzyl acetate 10 Ethyl acetate 5 Lemon oil 5 Dipropylene glycol 890 970 |
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H. Perfumery base with a generally flowery character Parts by weight |
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Terpineol 260 Hydroxycitronellal 220 Cinnamic alcohol (substitute) 100 Cinnamyl formate 20 Linalool 15 Terpenyl acetate 10 Musk ketone 10 Geranyl acetate 10 Jasmine (synthetic) 10 Eugenol 5 Indole (10% in DPG) 5 C10 -aldehyde (10% in DPG) 5 p-Methylacetophenone 5 Undecalactone 5 DPG 100 900 |
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J. Perfumery base with a fruity character Parts by weight |
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Ethyl-methyl-phenyl-glycidate 50 Ethyl acetoacetate 15 Dimethyl-benzyl butyrate 15 Maltyl isobutyrate 10 Benzyl acetate 10 Ethyl acetate 5 Lemon oil 5 Dipropylene glycol 795 900 |
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K. Perfumery base in the direction of chypre Parts by weight |
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1-Methyl-cyclododecyl methyl ether 200 Bergamot oil 150 Hydroxycitronellal 100 Pine needle oil 80 Citronellol 80 Petitgrain oil 60 Coriander oil 40 Galbanum oil 40 Cedarwood oil 40 Patchouli oil 40 Lemon oil 40 Elemi oil 10 Oak moss (decolorized) 20 Dipropylene glycol 60 960 |
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L. Perfumery base in the direction of rose Parts by weight |
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Phenylethyl alcohol 300 Geraniol 250 Jasmine 'lavage' (aqueous distillate) 200 Citronellol (extra) 100 α-Ionone 40 C10 -aldehyde (10% in dipropylene glycol) 5 C11 -aldehyde (10% in dipropylene glycol) 5 900 |
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M. Perfumery base in the direction of tobacco Parts by weight |
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α-Tert.butylcyclohexyl acetate 400 Jasmine oil (synthetic) 300 Musk ketone 40 Sandela ® [3-isocamphyl-(5)- 40 cyclohexanol] Styrallyl acetate 30 Coumarin 20 Isobutylquinoline (10% in DPG) 10 Lavender oil 10 Vetiver oil 10 Galbanum oil 10 Vassura oil 10 Dipropylene glycol 40 920 |
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Perfumery base in the direction of tulip Parts by weight |
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Phenylethyl alcohol 100 Myraldylacetat ™ [4-(4-methyl-3- 100 pentenyl)-3-cyclohexen-1-yl]methyl acetate Methyl dihydrojasmonate 100 Acetal CD (glycerine acetal of phenyl- 100 acetaldehyde) Hydroxycitronellal 160 Farnesol 40 Hexyl salicylate 30 Terpineol 30 Cyclamen aldehyde 20 Linalool 20 Linalyl anthranilate 10 Amyl salicylate 10 C11 -aldehyde (10% in DPG) 10 Benzyl acetate 8 Hexenyl benzoate 8 Hexenyl acetate (10% in DPG) 8 p-Cresyl isobutyrate (10% in DPG) 6 Indole (10% in DPG) 6 Syringa aldehyde 4 Dimethyl acetal hydratropaldehyde (10% in DPG) 30 DPG 100 900 |
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O. Perfumery base in the direction of leather Parts by weight |
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Styrax (natural) 250 Castoreum (anhydrous) 150 Bergamot oil 100 Musk infusion (3% in ethanol) 100 Vetiver oil 100 Labdanum resinoid 100 Birch tar (dephenolized, 10% in DPG) 50 Musk ketone 25 Sandalwood oil 10 Vanillin 10 Ciste labdanum (Spanish) 5 Dipropylene glycol 60 960 |
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By adding 40 parts of compound 3 a violet effect is obtained in the above leather base.
<p>Chemistry and Technology of Polyols for PolyurethanesMihail Ionescu</p><p>Chemistry and Technology of Polyols for Polyurethanes</p><p>Mihail Ionescu</p><p>Rapra Technology LimitedShawbury, Shrewsbury, Shropshire, SY4 4NR, United Kingdom Telephone: +44 (0)1939 250383 Fax: +44 (0)1939 251118 http://www.rapra.net</p><p>First Published in 2005 by</p><p>Rapra Technology LimitedShawbury, Shrewsbury, Shropshire, SY4 4NR, UK</p><p>2005, Rapra Technology</p><p>All rights reserved. Except as permitted under current legislation no part of this publication may be photocopied, reproduced or distributed in any form or by any means or stored in a database or retrieval system, without the prior permission from the copyright holder. A catalogue record for this book is available from the British Library.</p><p>Every effort has been made to contact copyright holders of any material reproduced within the text and the authors and publishers apologise if any have been overlooked.</p><p>ISBN: 978-1-84735-035-0</p><p>Typeset, printed and bound by Rapra Technology Limited</p><p>This book is dedicated to the memory of Dr Jack Buist, an exceptional personality in the eld of polyurethane chemistry and technology. His vision on the advanced technologies in the polyurethane industry, his brilliant scientic activity leading to unanimous worldwide recognition, the exceptional career at ICI Polyurethanes, his work as founding editor of the international journal, Cellular Polymers and Progress has had great impact on the general worldwide development of polyurethane chemistry and polyurethane technology in the last ve decades of the twentieth century. Dr Jack Buist will be forever, one of polyurethane's great men and has truly earned his place alongside Professor Otto Bayer, Professor Kurt C Frisch, Dr Adnan AR Sayigh, Dr Carlo Fiorentini and Dr Guenter Oertel in the Polyurethane's Hall of Fame.</p><p>Chemistry and Technology of Polyols for Polyurethanes</p><p>Contents</p><p>Contents1 Polyols ............................................................................................................ 1 1.1 Introduction ........................................................................................... 1 References ....................................................................................................... 9 2 Basic Chemistry of Polyurethanes ................................................................. 13 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Reaction of Isocyanates with Alcohols ................................................. 13 Reaction of Isocyanates with Water ...................................................... 14 Reaction of Isocyanates with Urethanes ............................................... 15 Reaction of Isocyanates with Urea Groups ........................................... 15 Reaction of Isocyanates with Carboxylic Acids .................................... 15 Dimerisation of Isocyanates.................................................................. 16 Trimerisation of Isocyanates ................................................................. 17 Reaction of Isocyanates with Epoxide Compounds .............................. 17 Reaction of Isocyanates with Cyclic Anhydrides................................... 17</p><p>2.10 Prepolymer Technique .......................................................................... 23 2.11 Quasiprepolymer Technique ................................................................. 24 2.12 One Shot Technique ............................................................................. 24 2.13 Several Considerations on the Polyaddition Reaction .......................... 25 References ..................................................................................................... 27 3 The General Characteristics of Oligo-Polyols ............................................... 31 3.1 Hydroxyl Number ................................................................................ 32 3.1.1 3.2 Hydroxyl Percentage ................................................................ 34</p><p>Functionality ........................................................................................ 34</p><p>v</p><p>Chemistry and Technology of Polyols for Polyurethanes</p><p>3.3 3.4 3.5 3.6 3.7 3.8 3.9</p><p>Molecular Weight and Molecular Weight Distribution ......................... 39 Equivalent Weight ................................................................................ 40 Water Content ...................................................................................... 41 Primary Hydroxyl Content ................................................................... 41 Reactivity ............................................................................................. 45 Specic Gravity .................................................................................... 47 Viscosity ............................................................................................... 47</p><p>3.10 Colour ................................................................................................. 48 3.11 Acid Number........................................................................................ 48 References .................................................................................................... 50 4 Oligo-Polyols for Elastic Polyurethanes ........................................................ 55 4.1. Polyalkylene Oxide Polyether Polyols .................................................. 55 4.1.1 4.1.2 4.1.3 4.1.4 4.1.5 4.2 4.3 Synthesis of Polyether Triols Based on Glycerol Homopolymers of PO .............................................................. 64 Kinetics of PO Addition to Glycerol ......................................... 75 Random Copolyethers PO-EO (Heteropolyether Polyols) ........ 93 Polyether Polyols Block Copolymers PO-EO .......................... 101 Technology for Polyether Polyol Fabrication ......................... 119</p><p>Anionic Polymerisation of Alkylene Oxides Catalysed by Phosphazenium Compounds ......................................................... 148 High Molecular Weight Polyether Polyols Based on Polyamine Starters. Autocatalytic Polyether Polyols ........................... 152</p><p>References ................................................................................................... 155 5 Synthesis of High Molecular Weight Polyether Polyols with Double Metal Cyanide Catalysts (DMC Catalysts) ................................................. 167 References ................................................................................................... 178 6 Polymer Polyols (Filled Polyols) .................................................................. 185</p><p>vi</p><p>Contents</p><p>6.1 6.2</p><p>Graft Polyether Polyols....................................................................... 186 The Chemistry of the Graft Polyether Polyols Synthesis ..................... 187 6.2.1 6.2.2 6.2.3 6.2.4 Generation in situ of NAD by Grafting Reactions .................. 193 Stabilisation of Polymer Dispersions in Polymer Polyols with Macromers (Reactive NAD) .............................. 197 Nonreactive Nonaqueous Dispersants .................................... 204 The Mechanism of Polymer Particle Formation in Polymer Polyols Synthesis by Radical Polymerisation ............. 207</p><p>6.3</p><p>The Technology of Polymer Polyols Manufacture by Radical Processes................................................................................ 209 6.3.1 Synthesis of Polymer Polyols by Using Preformed Aqueous Polymeric Lattices .................................................... 214</p><p>6.4 6.5 6.6</p><p>PHD Polymer Polyols (Polyurea Dispersions) ..................................... 215 Polyisocyanate Polyaddition (PIPA) Polymer Polyols .......................... 219 Other Polymer Polyols........................................................................ 223 6.6.1 6.6.2 6.6.3 Epoxy Dispersions .................................................................. 223 Polyamide Dispersions............................................................ 225 Aminoplast Dispersions .......................................................... 226</p><p>References ................................................................................................... 227 7 Polyether Polyols by Cationic Polymerisation Processes .............................. 235 7.1 7.2 7.3 Polytetrahydrofuran (Polytetramethylene Glycols) ............................ 235 High Molecular Weight Polyalkylene Oxide Polyols by Cationic Polymerisation................................................................. 245 Polyether Diols and Triols, Copolymers THF-alkylene Oxides ........... 249</p><p>References ................................................................................................... 257 8 Polyester Polyols for Elastic Polyurethanes ................................................. 263 8.1 8.2 Chemistry of Polyester Polyol Synthesis.............................................. 264 Consideration of the Kinetics of Polyesterication Reactions ............. 270</p><p>vii</p><p>Chemistry and Technology of Polyols for Polyurethanes</p><p>8.2.1 8.2.2 8.2.3 8.3 8.4 8.5</p><p>Self Catalysed Polyesterication Reactions (Without Catalyst).................................................................. 270 Side Reactions in Polyesterication ........................................ 274 Hydrolysis Resistant Polyester Polyols ................................... 276</p><p>Technology for Polyester Polyols Fabrication ..................................... 277 Poly (-caprolactone) Polyols.............................................................. 279 Polycarbonate Polyols ........................................................................ 285</p><p>References ................................................................................................... 289 9 Polybutadiene Polyols ................................................................................. 295 9.1 9.2 9.3 Polybutadiene Polyols by Radical Polymerisation of Butadiene .......... 295 Synthesis of Polybutadiene Polyols by Radical Polymerisation of Butadiene ............................................................... 299 Synthesis of Polybutadiene Polyols by Anionic Polymerisation of Butadiene ............................................................... 301</p><p>References .................................................................................................. 303 10 Acrylic Polyols ............................................................................................ 305 References ................................................................................................... 309 11 Polysiloxane Polyols ................................................................................... 311 References ................................................................................................... 315 12 Polyols for Rigid Polyurethanes - General Considerations .......................... 317 References ................................................................................................... 319 13 Polyether Polyols for Rigid Polyurethane Foams ......................................... 321 13.1 The Polyaddition of Alkylene Oxides to Hydroxyl Groups ................ 325 13.1.1 The Mechanism of Alkylene Oxide Polyaddition to Hydroxyl Groups Catalysed by the Tertiary Amines .............. 326 13.2 Polyether Polyols Technologies for Rigid Foam Fabrication ............... 336viii</p><p>Contents</p><p>13.2.1 Anionic Polymerisation of PO (or/and EO) Initiated by Polyols which are Liquid at the Reaction Temperature ...... 343 13.3 Kinetic Considerations Concerning the Alkoxylation of Polyols to Rigid Polyether Polyols ...................................................... 347 13.3.1 Anionic Polymerisation of PO (or/and EO) Initiated by High Melting Point Polyols which are Solid at the Reaction Temperature ............................................................ 353 References ................................................................................................... 366 14 Aminic Polyols ............................................................................................ 371 References ................................................................................................... 379 15 Rigid Polyols Based on the Alkoxylation of Aromatic Compounds Condensates with Aldehydes ...................................................................... 381 15.1 Mannich Polyols................................................................................. 381 15.2 Novolak-Based Polyether Polyols ....................................................... 400 15.3 Bisphenol A Based Polyols .................................................................. 403 15.4 Resorcinol Based Diols ....................................................................... 406 15.4 Melamine-Based Polyols for Rigid Polyurethanes ............................... 407 References ................................................................................................... 414 16 Polyester Polyols for Rigid Polyurethane Foams ......................................... 419 16.1 Aromatic Polyester Polyols from Bottom Residues Resulting in DMT Fabrication............................................................ 421 16.2 Aromatic Polyester Polyols from Polyethylene Terephthalate Wastes (Bottles, Films, Fibres) ...................................... 422 16.3 Aromatic Polyester Polyols Based on Phthalic Anhydride (PA) ........... 424 16.4 Other Methods for the Synthesis of Polyester Polyols for Rigid Foams ...................................................................................... 426 References ................................................................................................... 431</p><p>ix</p><p>Chemistry and Technology of Polyols for Polyurethanes</p><p>17 Polyols from Renewable Resources - Oleochemical Polyols ........................ 435 17.1 Vegetable Oil Polyols (Oleochemical Polyols) .................................... 443 17.1.1 Synthesis of Vegetable Oil Polyols by using Reactions Involving Ester Groups........................................... 450 17.1.2 Synthesis of Vegetable Oil Polyols by using Reactions Involving the Double Bonds ................................... 455 17.1.3 Other Reactions Involving Reactions of Double Bonds of Vegetable Oils ............................................. 463 17.1.4 Other Renewable Materials .................................................... 469 References .................................................................................................. 470 18 Flame Retardant Polyols ............................................................................. 477 18.1 Chlorine and Bromine Containing Polyols.......................................... 481 18.2 Phosphorus Polyols ........</p>