Organic compounds

Abstract

This disclosure relates to taste modifiers of formula (I) ##STR00001## wherein, n is 1, 2 or 3; R.sup.1 is selected from C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 hydroxyalkyl, C.sub.1-C.sub.5 dihydroxyalkyl and CHYCOOH wherein Y is selected from C.sub.1-C.sub.3; R.sup.3 is hydrogen, hydroxy or C.sub.1-C.sub.3 alkoxy; R.sup.4 is hydrogen, or C.sub.1-C.sub.3 alkyl; R.sup.5 is selected from hydrogen, or C.sub.1-C.sub.3 alkyl; or R.sup.4 and R.sup.5 form together a bivalent radical CH.sub.2;
that are able to impart, enhance or modify salt or umami taste.

Claims

1. A comestible composition comprising a compound selected from the group consisting N-piperonyl methylamine, N-piperonyl ethylamine, N-piperonyl n-propylamine, N-piperonyl isopropylamine, N-piperonyl 3-pentylamine, N-piperonyl 2-hydroxyethylamine, N-piperonyl 1,3-dihydroxy-2-propylamine, N-piperonyl alanine, N-vanillyl ethylamine hydrochloride, and N-(2-hydroxyethyl) vanillylamine hydrochloride, a comestibly acceptable salt thereof, or mixtures thereof.

2. The comestible composition according to claim 1 wherein the compound is present in an amount of 1 to 2500 ppm.

3. The comestible composition according to claim 1 comprising monosodium glutamate (MSG) or salt (NaCl).

4. The comestible composition according to claim 3 wherein the monosodium glutamate (MSG) is present in amounts of about 100 to about 500 ppm.

5. The comestible composition according to claim 3 wherein the salt (NaCl) is present in amounts of about 0.4% to about 2 weight %.

6. The comestible composition according to claim 1 selected from food products and beverages.

7. A comestible composition comprising a compound selected from the group consisting N-piperonyl methylamine, N-piperonyl ethylamine, N-piperonyl n-propylamine, N-piperonyl isopropylamine, N-piperonyl 3-pentylamine, N-piperonyl 2-hydroxyethylamine, N-piperonyl 1,3-dihydroxy-2-propylamine, N-piperonyl alanine, N-vanillyl ethylamine hydrochloride, and N-(2-hydroxyethyl) vanillylamine hydrochloride a comestibly acceptable salt thereof, or mixtures thereof, to impart, enhance, or modify an umami- and/or salt-taste in the comestible composition.

8. A method of imparting, enhancing or modifying an umami- and/or salt-taste in a comestible product comprising the steps of: a) providing at least one comestible product, and b) combining the comestible product with a compound selected from the group consisting N-piperonyl methylamine, N-piperonyl ethylamine, N-piperonyl n-propylamine, N-piperonyl isopropylamine, N-piperonyl 3-pentylamine, N-piperonyl 2-hydroxyethylamine, N-piperonyl 1,3-dihydroxy-2-propylamine, N-piperonyl alanine, N-vanillyl ethylamine hydrochloride, and N-(2-hydroxyethyl) vanillylamine hydrochloride or a comestibly acceptable salt thereof, so as to form a modified comestible product comprising at least about 1 ppm of the compound of formula (I).

9. The comestible composition according to claim 2, comprising monosodium glutamate (MSG) or salt (NaCl).

Description

EXAMPLE 1.1: N-PIPERONYL METHYLAMINE

(1) A 250 ml autoclave was charged with 100 ml of methylamine 2M in methanol (81 g, 200 mmol) and benzo[d][1,3]dioxole-5-carbaldehyde (10 g, 66.6 mmol) to give a colourless solution. The autoclave was closed and stirred at 35 C. for 3 hrs. Then 0.8 g of palladium 10% on carbon was added and then the autoclave was pressurized with 5 bar of hydrogen and stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated to furnish brownish oil. Kugelrohr distillation afforded 9.9 g of the title compound as a colourless oil (bp 190-200 C./12-10 mbar). Yield: 90%.

(2) .sup.1H-NMR in CDCl3: 2.42 (3H, s NHCH3) 3.60-3.70 (2H, s, ArCH2-N), 5.85-5.95 (2H, s, OCH2-O), 6.65-6.85 (3H, 2m, 3 aromatic H).

EXAMPLE 1.2: N-PIPERONYL ETHYLAMINE

(3) A 250 ml autoclave was charged with 100 ml of ethylamine 2M in methanol (81 g, 200 mmol) and benzo[d][1,3]dioxole-5-carbaldehyde (10 g, 66.6 mmol) to give a colourless solution. The autoclave was closed and stirred at 35 C. for 3 hrs. Then 0.8 g of palladium 10% on carbon was added and then the autoclave was pressurized with 5 bar of hydrogen and stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated to furnish the title compound as a colourless liquid (11.4 g; yield 95%). The product was pure according to GC and NMR analysis.

(4) .sup.1H-NMR in CDCl3: 1.05-1.15 (3H, m, NHCH2-CH3), 2.60-2.70 (2H, m, NHCH2-CH3), 3.60-3.70 (2H, s, ArCH2-N), 5.85-5.95 (2H, s, OCH2-O), 6.65-6.85 (3H, 2m, 3 aromatic H).

EXAMPLE 1.3: N-PIPERONYL N-PROPYLAMINE

(5) A 250 ml autoclave was charged with propan-1-amine (10 g, 169 mmol) and benzo[d][1,3]dioxole-5-carbaldehyde (5 g, 33.3 maid) in methanol (100 ml to give a slightly yellow solution. The autoclave was closed and stirred at 35 C. for 3 hrs. Then 1 g of palladium 10% on carbon was added and then the autoclave was pressurized with 5 bar of hydrogen and stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated to yield the title compound as a colourless liquid (6.2 g; yield 96%). The product was pure according to NMR analysis.

(6) .sup.1H-NMR in CDCl3: 0.80-0.90 (3H, m, NHCH2-CH2-CH3), 1.40-1.50 (2H, m, NHCH2-CH2-CH3), 2.45-2.55 (2H, m, NHCH2-CH2-CH3), 3.55-3.65 (2H, s, ArCH2-N), 5.80-5.90 (2H, s, OCH2-O), 6.65-6.85 (3H, 2m, 3 aromatic H).

EXAMPLE 1.4: N-PIPERONYL ISOPROPYLAMINE

(7) A mixture of benzo[d][1,3]dioxol-5-ylmethanamine (8 g, 52.9 mmol) and acetone (20 g, 344 mmol) was stirred at reflux until all starting amine had disappeared as monitored by GC analysis. The excess of acetone was removed by evaporation under reduced pressure. The residual oil was taken in 30 ml of methanol and placed in a 200 ml autoclave. Palladium 10% on carbon (1 g) was added and then the autoclave was pressurized with 3 bar of hydrogen. The mixture was stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated in vacuo. The residual brownish oil was purified by silica gel column chromatography using dichloromethane and heptane as eluent affording the title compound (6.5 g; yield 80%) as a slightly yellow oil.

(8) .sup.1H-NMR in CDCl3: 1.05-1.10 (6H, d, 2CHCH3), 2.70-2.9 (1H, m, NCH), 3.60-3.70 (2H, s, ArCH2-N), 5.85-5.95 (2H, s, OCH2-O), 6.65-6.85 (3H, 2m, 3 aromatic H).

EXAMPLE 1.5: N-PIPERONYL 3-PENTYLAMINE

(9) In a 250 ml round-bottomed flask was added benzo[d][1,3]dioxol-5-ylmethanamine (7 g, 46.3 mmol) to pentan-3-one (8 g, 93 mmol) in methanol (50 ml) to give a yellow solution. The mixture was stirred at reflux until all starting amine had disappeared as monitored by GC analysis. The solvent and the excess of 2-pentanone were removed under reduced pressure to give 10 g of the intermediate imine as a yellow-brown oil. In the next step, a 200 ml autoclave was charged with a mixture of the intermediate imine (8 g, 36.5 mmol) and Pd 10% on carbon (1 g) in methanol (30 ml).

(10) The autoclave was pressurized with 3 bar of hydrogen and stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst and methanol was evaporated in vacuo. The residual brownish oil was purified by vacuum distillation using a Kugelrohr apparatus affording 2.5 g of the title compound as a colourless oil (yield 31%, purity >98%).

(11) .sup.1H-NMR in CDCl3: 0.75-0.95 (6H, m, 2CH2-CH3), 1.30-1.55 (4H, m, 2CH2-CH3), 2.30-2.50 (1H, m, NCH), 3.60-3.70 (2H, s, ArCH2-N), 5.85-5.95 (2H, s, O(CH2-O), 6.65-6.85 (3H, 2m, 3 aromatic H).

EXAMPLE 1.6: N-PIPERONYL 2-HYDROXYETHYLAMINE

(12) In a 250 mL round-bottomed flask was added 2-aminoethanol (8 g, 131 mmol) to a solution of benzo[d][1,3]dioxole-5-carbaldehyde (10 g, 66.6 mmol) in toluene (100 ml) to give a colourless solution. The mixture was stirred at reflux for 3 hrs. The formed water was removed by azeotropic distillation using a Dean stark apparatus. Then toluene was removed on rotary evaporator under reduced pressure. The excess of ethanolamine was removed by vacuum distillation. The remaining residual brownish oil was taken in 30 ml of methanol and placed in a 200 ml autoclave. Palladium 10% on carbon (1 g) was added and then the autoclave was pressurized with 5 bar of hydrogen. The mixture was stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst and methanol was evaporated in vacuo. The residual brownish oil was purified by vacuum distillation using a Kugelrohr apparatus, affording 6.5 g of the title compound as a colourless viscous oil (bp 220-240 C./2-3 mbar). The oil solidified upon standing at room temperature (yield 91%, purity: >95%).

(13) .sup.1H-NMR in CDCl3: 2.65-2.75 (2H, m, NCH2-CH2-OH), 3.55-3.65 (2H, m, NCH2-CH2-OH), 3.60-3.70 (2H, s, ArCH2-N), 5.85-5.95 (2H, s, OCH2-O), 6.65-6.85 (3H, 2m, 3 aromatic H).

EXAMPLE 1.7: N-PIPERONYL 1,3-DIHYDROXY-2-PROPYLAMINE

(14) A 250 ml autoclave was charged with 2-aminopropane-1,3-diol (3.03 g, 33.3 mmol), benzo[d][1,3]dioxole-5-carbaldehyde (5 g, 33.3 mmol) and 30 ml of methanol to give a colourless solution. The autoclave was closed and stirred at room temperature for 3 hrs. Then 0.5 g of palladium 10% on carbon was added. Then the autoclave was pressurized with 5 bar of hydrogen and stirred at ambient temperature until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated to afford 7.2 g of pure title compound as white crystals (yield 96%).

(15) .sup.1H-NMR in DMSO-d6: 2.40-2.55 (1H, m, NHCH), 3.25-3.45 (4H, 2m, 2CH2-OH), 3.60-3.70 (2H, s, ArCH2-N), 5.85-5.95 (2H, s, OCH2-O), 6.70-6.95 (3H, s and 2m, 3 aromatic H).

EXAMPLE 1.8: N-PIPERONYL ALANINE

(16) In a 250 ml autoclave was added benzo[d][1,3]dioxole-5-carbaldehyde (4.89 g, 32.6 mmol) to a mixture of alanine ethyl ester hydrochloride (5 g, 32.6 mmol) and triethylamine (4.54 ml, 32.6 mmol) in methanol (30 ml). The autoclave was closed and stirred at 60 C. for 3 hrs. After the mixture was cooled to room temperature, 0.5 g of palladium 10% on carbon was added and then stirred at ambient temperature under 3 bar hydrogen for 3 hours. The reaction mixture was filtered to remove the catalyst. The filtrate was concentrated to dryness to yield 7.5 g of crude N-piperonyl-alanine ethyl ester.

(17) In the next step, a solution of N-piperonyl-alanine ethyl ester (6 g, 23.88 mmol) in methanol (10 ml) was added to 5% aqueous sodium hydroxide (38.2 g, 47.8 mmol) to give a yellow solution. After 3 hours stirring, the solution was neutralized with 5% HCl. Then 100 ml of ether was added to the solution and stirred for 15 minutes at room temperature. The formed white crystals were filtered, washed with water and ether and then dried in vacuum oven at 50 C. affording 4.5 g of the title compound (yield 84%, purity >95%).

(18) .sup.1H-NMR in DMSO-d6: 1.40-1.50 (3H, d, NHCHCH3), 3.80-3.90 (1H, m, NHCHCH3COOH), 3.9-4.1 (2H, s, ArCH2-NH), 5.85-5.95 (2H, s, OCH2-O), 6.70-6.95 (3H, s and 2m, 3 aromatic H).

EXAMPLE 1.9: N-VANILLYL ETHYLAMINE HYDROCHLORIDE

(19) A 250 ml autoclave was charged with 100 ml of ethylamine 2M in methanol (81 g, 200 mmol) and 4-hydroxy-3-methoxybenzaldehyde (7 g, 46.0 mmol) to give a colourless solution. The autoclave was closed and stirred at 35 C. for 2 hrs. Then 0.9 g of palladium 10% on carbon was added and stirred at ambient temperature under 5 bar of hydrogen until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated to furnish a brownish thick oil, which was dissolved in 20 ml of methanol and then acidified with 1.5M HCl in methanol. To the solution was added 200 ml of diethyl ether and stirred until complete precipitation was achieved. The white precipitate was filtered, washed with ether and then dried in vacuum oven at 35 C. affording 7.9 g of the title compound (yield 75%, purity >95%).

(20) .sup.1H-NMR in DMSO-d6: 1.15-1.25 (3H, m, NHCH2-CH3), 2.70-2.95 (2H, m, NHCH2-CH3), 3.7-3.85 (3H, s, ArOCH3), 3.90-4.10 (2H, m, ArCH2-N), 6.65-6.25 (2H, 2m, 2 aromatic H), 7.25-7.35 (1H, s, aromatic H).

EXAMPLE 1.10: N-(2-HYDROXYETHYL) VANILLYLAMINE HYDROCHLORIDE

(21) A 250 ml autoclave was charged with a mixture of 4-hydroxy-3-methoxybenzaldehyde (5 g, 32.9 mmol) and 2-aminoethanol (2.208 g, 36.1 mmol) in methanol (30 ml) and stirred at room temperature for 2 hrs. Then 0.5 g of palladium 10% on carbon was added and stirred at ambient temperature under 3 bar of hydrogen until no more hydrogen was consumed. The reaction mixture was filtered to remove the catalyst. The filtrate was evaporated to furnish a brownish thick oil, which was dissolved in 20 ml of methanol and then acidified with 1.5M HCl in methanol. To the solution was added diethyl ether until complete precipitation was achieved. The white precipitate was filtered, washed with ether and then dried in vacuum oven at 35 C. affording 4.9 g of the title compound (yield 61%, purity >95%).

(22) .sup.1H-NMR in DMSO-d6: 2.75-2.95 (2H, m, NCH2-CH2-OH), 3.60-3.75 (2H, m, NCH2-CH2-OH), 3.75-3.80 (3H, s, ArOCH3), 3.95-4.10 (2H, m, ArCH2-N), 6.65-7.25 (2H, 2m, 2 aromatic H), 7.25-7.35 (1H, s, aromatic H).

EXAMPLE 2: TASTING OF NaCl SOLUTIONS

(23) An aqueous NaCl solution (0.5% by weight) was prepared (reference) to which 5 ppm of a compound of formula (I) was added.

(24) The samples were tasted by a group of flavourists. The intensity of the umami and salt taste of the NaCl solutions comprising a compound of formula (I) (0.5% NaCl; 5 ppm of a compound of formula (I)) was compared with that of the reference (0.5% NaCl) and rated according to the following intensity scale:

(25) Taste effect much lower than reference: 3

(26) Taste effect lower than reference: 2

(27) Taste effect slightly lower than reference: 1

(28) Taste effect same as reference: 0

(29) Taste effect slightly higher than reference: 1

(30) Taste effect higher than reference: 2

(31) Taste effect much higher than reference: 3

(32) The results (average of ratings given by the individual flavourists) are shown in Table 1 below.

(33) TABLE-US-00001 TABLE 1 Taste intensity Intensity Taste Sample Umami Salt (NaCl) 0.5% NaCl (reference) 0.00 0.00 N-piperonyl 3-pentylamine 0.00 0.50 N-piperonyl ethylamine 0.25 0.75 N-piperonyl isopropylamine 0.00 0.50 N-piperonyl 2-hydroxyethylamine 0.00 0.75 N-piperonyl 1,3-dihydroxy-2-propylamine 0.50 1.00 N-piperonyl alanine 0.00 0.50 N-vanillyl ethylamine hydrochloride 0.67 0.67 N-piperonyl 1-hydroxy-2-butylamine* 0.33 0.67 N-(2-hydroxyethyl) vanillylamine hydrochloride 0.67 0.33 N-piperonyl methylamine 0.00 0.25 N-piperonyl n-propylamine 0.00 1.00 *Purchased from ChemBridge, product number 7961435

EXAMPLE 3: TASTE ENHANCEMENT

(34) Six solutions were prepared: A a solution of 0.5% NaCl B a solution of 0.5% NaCl and 0.03% MSG (monosodium glutamate) C a solution of 0.5% NaCl and 0.015% Ribo (disodium 5-ribonucleotides=E635) D a solution of 0.5% NaCl and 5 ppm of a compound of formula (I) E a solution of 0.5% NaCl and 0.03% MSG and 5 ppm a compound of formula (I) F a solution of 0.5% NaCl and 0.015% Ribo and 5 ppm of a compound of formula (I)

(35) The samples were tasted by a group of 5-10 flavourists aged between 30 and 60. The taste of solution D was compared with that of A to determine the enhancement effect of a compound of formula (I) on NaCl. Similarly, solution E was compared with solution B and solution F with solution C to determine the enhancement effect of a compound of formula (I) on MSG and Ribo respectively. The effect was marked on a linear scale between 0 and 10, the greater the value the greater the effect. For a reference, the taste solutions of B and C were compared with A as well. The results are summarized in Table 2, below.

(36) TABLE-US-00002 TABLE 2 Taste intensity Sample NaCl MSG Ribo solution A (salt reference) 0.0 solution B (MSG reference) 5.0 solution C (Ribo reference) 5.0 N-piperonyl ethylamine 1.3 6.6 5.6 N-piperonyl 1,3-dihydroxy-2- 2.3 5.0 5.0 propylamine N-piperonyl 3-pentylamine 1.0 6.3 5.3 N-piperonyl 1-hydroxy-2-butylamine 1.0 5.3 5.0

(37) As can be seen from the results above, the addition of compounds of formula (I) to a solution having umami- and/or salt taste imparts the intensity of umami- and/or salt taste.

EXAMPLE 4: BOUILLON

(38) A vegetarian bouillon mix was prepared from 204.71 g of sodium chloride, 147.76 g of dextrose monohydrate (ex Tapioca), 0.19 g of celery oleoresin, 0.19 g of oleoresin coriander seed, 418.64 g maltodextrin 5-8 DE, 37.65 g vegetable oil soya bean refined, 28.24 g yeast standard light, 3.76 g of onion powder, 3.76 g of garlic powder, 0.47 g of white pepper and 154.35 g of potato starch.

(39) 32 g of the well-mixed ingredients was added to 1 L of boiling water and stirred until completely dissolved.

(40) A small group of flavourists (2 male, 2 female) compared the taste of the reference bouillon with that of the following bouillons: A a batch of the same bouillon containing 10 ppm of N-piperonyl ethylamine: The flavourists agreed that the test bouillon was more umami, more salty, slightly sweeter and had a slightly more powdery volatile effect than the reference bouillon. B a batch of the same bouillon containing 10 ppm of N-piperonyl 3-pentylamine: The flavourists agreed that the test bouillon was more umami, sweeter and more lingering than the reference bouillon.

EXAMPLE 5: BREAD

(41) A bread flour mixture was prepared by mixing 1250 g of wheat flour, 250 g of white wheat flour and 60 g of yeast. Two salt mixtures were added to separate flour mixtures: A 20 g of NaCl B 20 g of NaCl and 0.02 g N-piperonyl ethylamine

(42) Doughs were prepared by mixing the ingredients and adding 900 g of water. The doughs were allowed to rise at room temperature for 2 hours and baked at 220 C. for 45 minutes.

(43) A panel of professional tasters compared the breads. The bread B was unanimously preferred over reference bread A.