JP2008505868A - Use of alkoxyalkanoic acid amides and in particular novel alkoxyalkanoic acid amides as flavoring agents - Google Patents

Abstract

  The present invention comprises (i) fragrance (1) and / or (ii) formation of ant performance and / or (iii) formation of sensitive emotion and / or (iv) stimulation of salivary secretion of the tongue and / or ( v) relates to the use of certain alkoxyalkanoic acid amides in the form for enhancing ethanol flavor and / or imitating ethanol flavor.

Description

Detailed Description of the Invention

増加した唾液流の効果は、特に口腔洗浄において辛味印象に加えて望ましく、上記物質によっては生じない。天然に存在するアルカミドであるスピラントール（式(3)）及びペリトリン（式(4)）は、一部はこの目的に好適であり、唾液刺激及び刺痛効果に加えて、全ての適用に望ましくない口腔空洞における長期持続性かつしびれさせる効果を表す(cf. H.C.F. Su and R.. Horvat, J. Agric. Food Chem. 1981, vol. 29, pages 115-118)。更にその不飽和な構造のために、合成が困難でありまた酸素及び光の効果に非常に敏感である。 The present invention comprises (i) flavoring and / or (ii) tingling sensation and / or (iii) pungent sensation and / or (iv) stimulation of saliva flow in the mouth and / or (v) ethanol taste. And / or (vi) certain alkoxy in preparations that are preferably consumed for nutrition, used for oral hygiene, or consumed for fun or pharmaceutical preparations as imitation of ethanol taste The use of alkanoic acid amides. The invention further relates to novel alkoxyalkanoic acid amides and preparations comprising the alkoxyalkanoic acid amides to be used in the present invention.
Capsaicin [N- (4-hydroxy-3-methoxybenzyl) -8-methyl- (6E) -nonenamide, formula (1)] and other capsaicinoids have been introduced to various peppers, notably Chile, long before 1871. It has been known as a flavoring agent that produces the pungent taste and heat it originates from. A substance that produces heat or has the effect of producing heat is understood to mean a substance that creates a thermal sensation impression. At appropriately low doses of capsaicinoids (threshold is a dilution of about 1:10 ⁵ ), only pleasant, unclear pungent and hot stimuli are perceived in the mouth, but last longer. However, capsaicin poses problems for chronic gastritis, kidney and liver damage resulting from frequent use and overdose due to its very acute toxicity (LD ₅₀ (mouse oral) 47 mg). Difficult to apply (Rompp Lexikon Naturstoffchemie, Thieme 1997, p. 109). Therefore, there is a need for less problematic pungent substances, regardless of their good sensory characteristics. On the other hand, piperine (1-piperoylpiperidine, formula (2)) exists in white pepper and gives a pungent impression (Rompp Lexikon Naturstoffchemie, Thieme 1997, p. 500). However, it has only about 1% pungent taste compared to capsaicin. In addition, piperine has something reminiscent of the intense inherent flavor of pepper and is therefore limited in use in many preparations. Ethanol (ordinary alcohol) gives an impression of pungent and hot taste at even higher concentrations (from about 1%). On the other hand, ethanol is not allowed in all food products, for example for ethical and religious reasons, and its consumption should be reduced or largely avoided for health reasons.

The effect of increased saliva flow is desirable in addition to the pungent impression, especially in oral cleaning, and is not caused by the above substances. The naturally occurring alkamides spirantol (formula (3)) and peritrine (formula (4)) are partly suitable for this purpose and are undesirable for all applications in addition to salivary irritation and stinging effects It represents a long-lasting and numbing effect in the oral cavity (cf. HCF Su and R. Horvat, J. Agric. Food Chem. 1981, vol. 29, pages 115-118). Furthermore, because of its unsaturated structure, it is difficult to synthesize and is very sensitive to oxygen and light effects.

(5a)
（式中、nは、１又は２の数を示し、またR¹は、(以下で定義されるような)アルキル基を示し、またR²は、（以下で定義されるような）任意に１種以上のヒドロキシ基で置換された低級アルキル基を示す。）
のアルコキシアルカン酸アミド、又は
下式、

(5b)
（式中、nは、１又は２の数を示し、またR¹は、（以下で定義されるような）アルキル基を示し、またmは、１又は２の数を示し、またR'及びR''は、互いに独立して水素原子又はメチル又はエチル基を示すか又は同時にメチレン基を示す。）
のアルコキシアルカン酸アミド、又は
下式、

(5c)
（式中、nは、１又は２の数を示し、またR¹は、（以下で定義されるような）アルキル基を示し、またR²、R³は、それぞれ独立に又は異なる任意に１種以上のヒドロキシ基で置換された同一又は異なる低級アルキル基を示すか又はR²、R³は、同時に（以下で定義されるような）アルキレン基を形成する。）
のアルコキシアルカン酸アミド、又は
式(5a)、(5b)及び/又は(5c)の２種以上の化合物の混合物の、(i)香味剤及び/又は(ii)刺痛覚の生成及び/又は(iii)辛味覚（又は熱さ）の生成及び/又は(iv)口中の唾液流の刺激及び/又は(v)エタノール味の強化及び/又は(vi)エタノール味の模倣としての使用、特に栄養のために消費され、口腔衛生のために使用され又は楽しみ又は経口医薬組成物のために消費される調製物における使用としての提供によって本発明に従って達成される。 The main object of the present invention is to provide a substance suitable for producing stinging stimuli and / or producing pungent / heat stimuli and / or stimulating salivary flow in the mouth (an effect of drooling). . These substances can further mimic the pungent and warm taste impression of ethanol. Furthermore, these materials should preferably have relatively natural aroma and taste characteristics, have no significant numbing effect, be easy to synthesize and be stable. These substances to be provided should be stable for use in preparations that are consumed nutritionally, used for oral hygiene or consumed for fun or oral pharmaceutical preparations.
The above purpose is

(5a)
Wherein n represents a number of 1 or 2, R ¹ represents an alkyl group (as defined below), and R ² is optionally (as defined below). Indicates a lower alkyl group substituted with one or more hydroxy groups.)
An alkoxyalkanoic acid amide of the formula

(5b)
Wherein n represents a number of 1 or 2, R ¹ represents an alkyl group (as defined below), m represents a number of 1 or 2, and R ′ and R ″ independently of one another represents a hydrogen atom or a methyl or ethyl group, or simultaneously represents a methylene group.)
An alkoxyalkanoic acid amide of the formula

(5c)
(Wherein n represents a number of 1 or 2, R ¹ represents an alkyl group (as defined below), and R ² and R ³ are each independently or differently arbitrarily 1 The same or different lower alkyl groups substituted with one or more hydroxy groups or R ² and R ³ simultaneously form an alkylene group (as defined below).
(I) flavor and / or (ii) generation of tingling sensation and / or a mixture of two or more compounds of the formula (5a), (5b) and / or (5c) (iii) generation of pungent taste (or heat) and / or (iv) stimulation of saliva flow in the mouth and / or (v) enhancement of ethanol taste and / or (vi) use as imitation of ethanol taste, especially for nutrition Achieved in accordance with the invention by provision for use in preparations consumed for oral hygiene or used for fun or oral pharmaceutical compositions.

The compounds of formulas (5a), (5b) and (5c) take the form of pure enantiomers and / or diastereomers or mixtures thereof in all possible proportions and may have asymmetric carbon atoms.
The following applies in particular to compounds of the formulas (5a), (5b) and (5c).
An alkyl group in the sense of the present invention is a linear, branched or cyclic alkyl group having 1 to 8 carbon atoms, the following groups: methyl, ethyl, n-propyl (compounds 10-13, 15 and 17), n-butyl (see compounds 6-9, 14 and 16 below), n-pentyl and n-hexyl are preferred.
The following applies especially to compounds of formula (5a) and formula (5c).
A lower alkyl group in the sense of the present invention is a linear, branched or cyclic alkyl group having 1 to 5 carbon atoms, optionally substituted with one or more hydroxyl groups, preferably exactly one hydroxyl group, Groups: methyl, ethyl, 2-hydroxyethyl, propyl, 3-hydroxypropyl, 2-propyl, cyclopropyl, butyl, 2-butyl, 3-methylpropyl (ie isobutyl), 2-hydroxy-2-methylpropyl , Cyclobutyl, 1- or 2-methylcyclopropyl, 2-methylpropyl, pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, cyclopentyl and 1-, 2- or 3-methylcyclobutyl, but Particularly preferred are 2-hydroxyethyl (see compounds 16 and 17), isobutyl (see compounds 6 and 10) or 2-methylbutyl (see compounds 7 and 11). That's right.

(5a)
及び

(5b)
（式中、それぞれの場合にn、R¹、R²、m、R'、R''は、(5a)及び(5b)に対して上記に示した意味を有する。）のアルコキシアルカン酸アミドに関する。これらの化合物は、新規である。上記目的及び特に辛味、あるいは熱さ及び/又は刺痛及び/又は唾液流の刺激の提供に対する好適性は、既知の従来技術を考慮して驚くべきことである。 The following applies particularly to equation (5c).
An alkylene group in the sense of the present invention is an alkylene group having 2 to 6 carbon atoms, partly optionally substituted with one or more lower alkyl groups, the following groups: ethylene, propylene, butylene ( Preference is given to formulas 9 and 13 below and pentylene (see formulas 8 and 12 below).
The present invention further comprises the following formula:

(5a)
as well as

(5b)
(Wherein n, R ¹ , R ² , m, R ′, R ″ in each case have the meanings given above for (5a) and (5b)) About. These compounds are novel. The suitability for the above purposes and in particular the provision of a pungent taste, or heat and / or stinging and / or stimulation of salivary flow is surprising in view of the known prior art.

によって説明される。
式5cのいくつかのアルコキシアルカン酸アミドは、既に先述されている。例えば、N,N-ジエチル-3-デシロキシプロピオン酸アミド(CA 187885-89-8)が、抗ウイルス薬及び/又は抗真菌活性物質として米国特許第5,744,631号明細書に記載されている。N,N-ジエチル-2-デシロキシプロピオン酸アミド(CA 88591-89-3)は、動物の腸内寄生虫の治療剤として他のN,N-ジアルキル誘導体とともに米国特許第3,228,832号明細書に記載された。 The alkoxyalkanoic acids of the formulas (5a) and (5b) can be prepared from known alkoxyalkanoic acids or their alkyl esters by methods of amide synthesis known per se (for example practical organic chemistry textbooks).
For example, an alkoxyalkanoic acid can be converted to the corresponding acid chloride and the corresponding alkylamine can be used alone or with the aid of an auxiliary base, with or without a solvent. It can be easily converted to an acid amide and purified by conventional methods (eg, distillation, crystallization, chromatography). This method is shown below.

Explained by
Some alkoxyalkanoic acid amides of formula 5c have already been described above. For example, N, N-diethyl-3-decyloxypropionic acid amide (CA 187885-89-8) is described in US Pat. No. 5,744,631 as an antiviral and / or antifungal active. N, N-diethyl-2-decyloxypropionic acid amide (CA 88591-89-3) is described in U.S. Pat.No. 3,228,832 along with other N, N-dialkyl derivatives as therapeutic agents for animal intestinal parasites. It was described.

However, the use of alkoxyalkanoic acid amides (5a), (5b) or (5c) for the above application is surprising since it has not been known before.
It is particularly surprising for those skilled in the art that the alkoxyalkanoic acid amides to be used in the present invention make impressions described as tingling and / or pungent tastes and / or promote saliva in sensory tests. It was also unpredictable. When used at fairly high concentrations, the sensory impression is relatively strong and relatively long lasting, so the compounds (5a), (5b) and (5c) (and mixtures thereof) are Is significantly preferred.
It is particularly advantageous that the alkoxyalkanoic acid amides of formula (5a) make a taste impression described as stinging and are very saliva-promoting without giving a noticeable pungent and / or hot and / or numbness sensation. It is a thing.
The alkoxyalkanoic acid amide of formula (5b) creates a pleasant pungent and warm feeling impression without showing the tingling and burning impressions of capsaicin derivatives such as dihydrocapsaicin, It is also particularly advantageous that the acid amide is particularly suitable for enhancing the ethanol sensory impression and / or imitating the ethanol sensory impression.
Compounds of formula (5b) where m = 1, R ′ = H and R ″ = H, methyl or ethyl are particularly preferred, especially for their special pungent taste.

Furthermore, the alkoxyalkanoic acid amides to be used in the present invention are considerably more effective than highly unsaturated alkamides such as spirantol (3) or peritrine (4) in terms of the effects of oxidation, light or electromagnetic radiation or other decomposition reactions. Because they are stable and do not have a double bond.
The following alkoxyalkanoic acid amides used in the present invention:
2-Heptyloxyacetic acid N-isobutyramide (Compound 6)
2-Heptyloxyacetic acid N-2- (methylbutyl) amide (Compound 7)
2-Heptyloxyacetic acid N-piperidinide (Compound 8)
2-Heptyloxyacetic acid N-pyrrolidinide (Compound 9)
3-Hexyloxypropionic acid N-isobutyramide (Compound 10)
3-Hexyloxypropionic acid N-2- (methylbutyl) amide (Compound 11)
3-Hexyloxypropionic acid N-piperidinide (Compound 12)
3-Hexyloxypropionic acid N-pyrrolidinide (Compound 13)
2-Heptyloxyacetic acid N- (4-hydroxy-3-methoxybenzyl) amide (Compound 14)
3-Hexyloxypropionic acid N- (4-hydroxy-3-methoxybenzyl) amide (Compound 15)
2-Heptyloxyacetic acid N- (2-hydroxyethyl) amide (Compound 16)
3-Hexyloxypropionic acid N- (2-hydroxyethyl) amide (Compound 17)
And a mixture comprising 2, 3 or more compounds 6-17,
Is particularly preferred.

Due to their special drooling effect, compounds 6 and 7 and other compounds of the formula 5a are particularly preferred.

本発明は、更に本発明で使用される１種以上のアルコキシアルカン酸アミドを含む調製物、半完成品及び香料、香味剤及び味覚組成物を提供する。これに関して、以下の記載及び添付の特許請求の範囲を比較する。

The present invention further provides preparations, semi-finished products and fragrances, flavoring agents and taste compositions comprising one or more alkoxyalkanoic acid amides used in the present invention. In this regard, the following description and the appended claims are compared.

The alkoxyalkanoic acid amides (or mixtures thereof) used in the present invention can be further used in cosmetic or dermatological preparations to cause thermal irritation of the skin.
In a preferred embodiment of the invention, the alkoxyalkanoic acid amides (or mixtures thereof) of the invention are combined with one or more other substances that have a pungent taste and / or produce a hot sensation or (especially) a pungent plant extract. Used. In this way, particularly approximate sensory characteristics can be achieved corresponding to the preparation. In particular, the combination of alkoxyalkanoic acid amide and spicy plant extract used in the present invention in a ratio of 0.01: 1 to 100: 1, preferably 0.1: 1 to 10: 1, produces pleasant sensory characteristics.
Substances that have a pungent taste or generate heat sensation and are suitable for combination include capsaicin, dihydrocapsaicin, gingerol, paradol, shogaol, piperine, alkanoic acid N-vanillylamide described in WO 2003/106404. In particular, nonanoic acid N-vanillylamide, peritrine or spirantol, 2-nonenoic acid N-4-hydroxy-3-methoxyphenylamide, alkyl ethers of 4-hydroxy-3-methoxybenzyl alcohol, especially 4-hydroxy-3-methoxy Benzyl-n-butyl ether, alkyl ethers of 4-acyloxy-3-methoxybenzyl alcohol, especially 4-acetoxy-3-methoxybenzyl n-butyl ether and 4-acetoxy-3-methoxybenzyl n-hexyl ether, 3-hydroxy-4 Alkyl ether of 3-methoxybenzyl alcohol, 3,4-dimethoxybenzyl Alkyl ethers of alcohols, alkyl ethers of 3-ethoxy-4-hydroxybenzyl alcohol, alkyl ethers of 3,4-methylenedioxybenzyl alcohol, (4-hydroxy-3-methoxyphenyl) acetamide, especially (4-hydroxy-3 -Methoxyphenyl) acetic acid Nn-octylamide, vanillomandelic acid alkylamide, ferulic acid phenethylamide described in EP 1,323,356, alkenoic acid N-alkylamide, nicotinaldehyde, methyl nicotinate, propyl nicotinate, 2-butoxyethyl nicotinate, Examples include benzylnicotiate, 1-acetoxychavicol, polygodial, and isodomenitol.

More preferred is a combination with a pungent and saliva stimulating alkene carboxylic acid N-alkylamide (see eg DE 103 51 422).
Pungency plant extracts suitable for combination are all plant extracts suitable for nutrition that evoke a pungent and / or heat impression. In this regard, examples of preferred plant extracts include pepper extract (piper subspecies, especially pepper nigurum), willow extract (polygonam subspecies, especially willow), onion subspecies extract (especially onion and garlic). Extract), radish extract (radish subspecies), horseradish extract (horseradish), black (black pepper) extract, wild or yellow mustard (white pepper subspecies, especially Noragarashi and white pepper), pesticide chrysanthemum root extract (chrysanthemum) Subspecies, especially Anacylcus pyrethrum L.), cornflower extract (beans subspecies), Sichuan pepper extract (Santocsirum subspecies, especially salamander), spirantes extract (spirantes subspecies, especially Dutch sennich), Chile extract (capsicum subspecies, especially Capsicum spp.), Paradise powder extract (Aflamum subspecies, especially Flamumum melegueta [Rose] K. sham. (Aframomum melegueta [Rose] K. Schum.)), Ginger extract (Ginger subspecies, especially ginger), galangal extract (Kaempferia galanga or Alpinia galangal) and yaborangi Extracts (Shaborandi species, in particular Shaborandi subsp. Jaborandi).

Spicy plant extracts are often obtained from corresponding fresh or dried plants or plant parts, but especially white, green or black peppercorn, willow seeds, onions and garlic, radish roots, horseradish, mustard seeds, cornflower It can be obtained from roots, insecticidal chrysanthemum roots, part of plants derived from Santoxillum species, part of plants derived from spiranthus, Chile pods, paradise or ginger particles or Galangal roots. For this purpose, preferably pre-ground dry plant parts are extracted with a solvent generally suitable for nutrients and products consumed for fun at temperatures ranging from 0 ° C. to the boiling point of the respective solvent. Then, filter and concentrate the filtrate completely or partially by concentration, lyophilization or spray drying. The crude extract thus obtained is then further treated with steam at a pressure of eg 0.01 mbar to atmospheric pressure and / or dissolved in a solvent suitable for foodstuffs and products consumed for fun. Suitable solvents for food and products consumed for enjoyment include, for example, water, ethanol, methanol, propylene glycol, glycerol, acetone, dichloromethane, diethyl ether, hexane, heptane, triacetin, vegetable oil or vegetable fat, ultra Examples include critical carbon dioxide or a mixture of the above solvents.
In particular, in a preferred embodiment of the present invention, the alkoxyalkanoic acid amides (or mixtures thereof) of the present invention are used in combination with other substances that cause stinging and / or salivary irritation or plant extracts containing these substances. .

Examples of substances that cause stinging or saliva stimulation include specific unsaturated alkamides (eg, peritoline, spirantol, shogaol), alkaloids (eg, pilocarpine), and saliva-promoting peptides (eg, substance P, tachykinin, fisalemin), Furthermore, it is possible to use simple fruit acids (eg citric acid, tartaric acid).
In another particularly preferred embodiment of the invention, the alkoxyalkanoic acid amides (or mixtures thereof) of the invention are used in combination with one or more substances that produce a physiological cooling effect.
Examples of substances that produce a physiological cooling effect include menthol and menthol derivatives (for example, L-menthol, racemic menthol), menthyl ether (for example, (l-menthoxy) -1,2-propanediol, (l-menthoxy) -2 -Methyl-1,2-propanediol, menthyl methyl ether), menthyl esters (eg menthyl acetate, menthyl isobutyrate, menthyl lactate, menthyl (2-methoxy) acetate, menthyl (2-methoxyethoxy) acetate, menthyl pyroglutamate) ), Menthyl carbonate (eg menthyl propylene glycol carbonate, menthyl ethylene glycol carbonate, menthyl glycerol carbonate), semiester of menthol and dicarboxylic acid (eg menthyl succinate, menthyl glutarate), menthane carbonate Boxyamide (e.g. menthanecarboxylic acid N-ethylamide), menthone and menthone derivatives (e.g. menthone glycerol ketal), 2,3-dimethyl-2- (2-propyl) butanoic acid derivatives (e.g. 2,3-dimethyl-2- ( 2-propyl) butanoic acid N-methylamide), isopulegol or its ester (l-(-)-isopulegol, l-(-)-isopulegol acetate), menthane derivatives (for example, p-menthane-3,8-diol) ), Cubebol, pyrrolidone derivatives of cycloalkyldione derivatives (eg 3-methyl-2- (1-pyrrolidinyl) -2-cyclopenten-1-one) or itlin can be used.

(5a)

(5b)

(5c)
又は式(5a)、(5b)及び(5c)の２種以上の混合物に関し、それぞれの場合において、n、m、R¹、R²、R³、R'及びR”は、上記の意味を有する。 The present invention is a preparation that is further consumed for nutrition, used for oral hygiene or consumed for fun, in achieving tingling and / or pungent and / or thermal sensations and Effective amounts in producing saliva flow and / or enhancing or mimicking ethanol taste, preferably in achieving stinging or pungent taste, or in producing saliva flow, or enhancing or mimicking ethanol taste Effective amount of formula (5a), (5b) or (5c)

(5a)

(5b)

(5c)
Or in relation to a mixture of two or more of the formulas (5a), (5b) and (5c), in each case n, m, R ¹ , R ² , R ³ , R ′ and R ″ have the above meanings Have.

These preparations of the present invention optionally contain other basic basic supplemental and additional substances for food or products consumed for fun or preparations used for oral hygiene. Including. This preparation is generally from 0.0000001% to 10% by weight, preferably 0.00001, based on the total weight of the preparation of one or more alkoxyalkanoic acid amides of formula (5a), (5b) and / or (5c). Although it is ˜1% by mass, it is particularly preferably 0.00001% by mass to 0.1% by mass. Other conventional basic, auxiliary and additional substances for food or products consumed for fun or preparations used for oral hygiene are 0.0000001 to 99.9999999 mass based on the total mass of the preparation %, Preferably 10-80% by weight. Furthermore, the preparation may contain water in an amount of up to 99.9999999% by weight, preferably 5-80% by weight, based on the total weight of the preparation.
Preparations that can be consumed for nutrition or fun are, for example, baked goods (e.g. bread, dried biscuits, cakes, other baked goods), confectionery (e.g. chocolate, bar chocolate products, other bar products, Fruit gum, boiled soft sweets, chewing gum), alcoholic or non-alcoholic beverages (e.g. coffee, tea, wine, wine-containing beverages, beer, beer-containing beverages, liqueurs, spirits, brandy, sparkling fruit beverages, isotonic beverages, Soft drinks, nectars, fruit and vegetable juices, fruit or vegetable juice preparations), instant drinks (eg, instant cocoa drinks, instant tea drinks, instant coffee drinks), meat products (eg, ham, raw sausage or dried sausage preparations) , Seasoned with spices or seasoned fresh food or salted Meat products), eggs or egg products (dried eggs, egg whites, yolks), cereal products (e.g. breakfast cereal, mousse river, pre-cooked rice products), dairy products (e.g. milk drinks, dairy ice cream, Yogurt, kefir, raw cheese, soft cheese, hard cheese, dried milk powder, whey, butter, buttermilk), fruit preparation (e.g. stored food, fruit ice, fruit sauce, fruit filling), vegetable preparation (e.g. ketchup, Sauces, dried vegetables, frozen vegetables, pre-cooked vegetables, vegetable storage foods), snack products (eg baked or fried potato crisp or potato dough products, extrudates based on maize or peanuts), fats and oils Base products or emulsions thereof (eg mayonnaise, remoulade, dressing), other ready meals and soups (eg dry soup, instant -Loop, precooked soup), spices, seasoning blends and in particular seasonings, which are for example used in snack field. A preparation in the sense of the present invention can also be used as a semi-finished product in the manufacture of other preparation products for consumption of nutrition or fun. Preparations in the sense of the present invention further include capsules, tablets (uncoated and coated tablets such as intestinal coatings), dragees, granules, pellets, solid mixtures, dispersions in liquid phases, emulsions, It can take the form of powders, solutions, pastes or other preparations suitable for armpit or chewing as food supplements.

Preferred combinations with alkoxyalkanoic acid amides used in the present invention, in particular pungent extracts, mimic the pungent taste of alcoholic beverages or preparations with alcoholic beverages and thereby alcohol content in alcoholic beverages or alcoholic beverage preparations It can be completely replaced while reducing the amount or maintaining the same sensory rating.
The taste reminiscent of an ethanol taste is determined in particular substantially by the amount of alkoxyalkanoic acid amide. Ethanol is present in these preparations of the present invention in a maximum amount of 0.5% by weight if the goal is to reduce the alcohol compared to a comparative product of nearly identical taste. This type of preparation preferably contains less than 0.1% by weight of ethanol.
The preparations according to the invention are preferably in the form of fragrances, flavorings or taste compositions or seasonings.
The alkoxyalkanoic acid amides of formula (5a), (5b) and / or (5c) or the preparations of the invention preferably avoid the thirst that occurs when consuming maize, potato or rice flour crisps and snacks and Can be used in seasonings to enhance the sensory impression.
Preferred seasonings include, for example, alkoxyalkanoic acid amides that may be used in the present invention, synthetic, natural or natural same flavoring agents and carriers such as maltodextrins, eg salts such as common salts, and eg paprika And spices such as pepper, sweeteners such as saccharin, and flavor enhancers such as monosodium glutamate and / or inosine monophosphate.
Preparations used for oral hygiene are in particular dental treatments such as toothpastes, dental gels, toothpastes, mouthwashes, chewing gums and other oral care agents.
Dental care agents containing alkoxyalkanoic acid amides used in the present invention are generally abrasive systems (abrasives or polishes) such as silica, calcium carbonate, calcium phosphate, aluminum oxide and / or hydroxylapatite, surface active substances. For example, sodium lauryl sulfate, sodium lauryl sarcosinate and / or cocamidopropyl betaine, wetting agents such as glycerol and / or sorbitol, thickeners such as carboxymethylcellulose, polyethylene glycol, carrageenan and / or Laponites ( Registered trademark), sweeteners such as saccharin, flavor modifiers such as lactisol, masking agents such as hydroxyflavanones, cooling substances such as menthol or menthol derivatives, stabilizers and active substances such as sodium fluoride, Sodium monofluorophosphate, tin difluoride, quaternary ammonium fluoride, zinc citrate, zinc sulfate, tin pyrophosphate, tin dichloride, mixtures of different pyrophosphates, triclosan, cetylpyridinium chloride, aluminum lactate, potassium citrate, Contains potassium nitrate, potassium chloride, strontium chloride, hydrogen peroxide, flavoring and / or sodium bicarbonate.

Chewing gums containing alkoxyalkanoic amides used in the present invention are generally chewing gum bases, ie chewing substances that resemble plastic when chewed, various sugars, sugar substitutes, sweeteners, sugar alcohols, wetting agents , Thickeners, emulsifiers, flavoring agents and stabilizers.
The present invention is further an oral pharmaceutical preparation of formula (5a) effective to achieve a trigeminal effect (stimulation), preferably in achieving a stinging or pungent sensation or producing saliva flow Or an alkoxyalkanoic acid of (5b) or a mixture of two or more compounds of formula (5a) or (5b).
Oral pharmaceutical preparations in the sense of the invention are, for example, capsules, tablets (uncoated and coated tablets, eg enteric coatings), dragees, granules, pellets, solid mixtures, liquid phase dispersions, emulsions. , Powders, solutions, pastes or other preparations suitable for armpit or chewing, which in addition to the alkanoic acid amide used in the present invention, further active substances suitable for other pharmaceutically active substances or food supplements And used as prescription drugs, pharmacy drugs or other drugs or food supplements.
Other pharmaceutically active substances or active substances suitable for food supplements include, for example, vitamins, minerals, antibiotics, bactericidal, fungicidal, antiviral, antiparasitic, antifungal or other antimicrobials Active agents, agents for treating aging, agents for treating internal diseases, such as therapeutic agents for cardiovascular diseases, benign or malignant tumors (eg, cytostat), cancer inhibitors, dementia diseases It may be a prophylactic or therapeutic agent, an agent for improving cognitive ability, a substance that reduces blood coagulation, a therapeutic agent for eye diseases, an active substance for lowering fever and an active substance for reducing inflammatory diseases.

Preparations in the sense of the present invention are capsules, tablets (uncoated and coated tablets such as enteric coatings), dragees, granules, pellets, solid mixtures, dispersions in the liquid phase, emulsions, powders, solutions, It may be in the form of other preparations suitable for armpit or chewing as a paste or food supplement.
The preparation of the present invention comprising one or more alkoxyalkanoic acid amides of formula (5a), (5b) or (5c) comprises an alkoxylic acid amide as a substance, as a solution or in the form of a solid or liquid carrier mixture. It can be prepared by blending into a base preparation that can be consumed for nutrition, used for oral hygiene, or consumed for fun. The preparation of the invention in the form of a solution is advantageously converted to a solid preparation by spray drying.
In an optionally preferred embodiment, in the preparation of the preparation of the invention, the alkoxyalkanoic acid amide and optionally other components of the preparation of the invention are primarily used as starting materials from emulsions, liposomes, eg phosphatidylcholines. , Microspheres, nanospheres or matrix extrudates suitable for capsules, granules or products consumed for food and fun, for example starch, starch derivatives, cellulose or cellulose derivatives (for example hydroxy Propylcellulose), other polysaccharides (eg alginate), natural fats, natural waxes (eg beeswax, carnauba wax) or proteins such as gelatin.

In another preferred production method, the alkoxyalkanoic acid amide is first complexed with one or more suitable complexing agents, for example cyclodextrins or cyclodextrin derivatives, preferably β-cyclodextrin. And used in this complex form.
The preparations according to the invention are particularly suitable and the matrix is chosen such that a long lasting flavor effect is obtained so that the release of the alkoxyalkanoic acid amide from the matrix is delayed.
Preferably, the preparation of the present invention has a pungent taste, produces a heat stimulus or produces stinging or saliva stimulation or a physiological cooling effect or at least one plant extract containing these substances, resulting in at least one kind of plant extract. Including substances.
Furthermore, conventional basic, auxiliary and additive substances of food or products consumed for enjoyment can be used as other ingredients of the nutritional or enjoyable preparations of the present invention. For example, water, fresh or prepared mixture, vegetable or animal basic materials or ingredients (eg raw, baked, dried, fermented, smoked and / or boiled meat, eggs, bones, cartilage, fish, Shellfish and shellfish, vegetables, fruits, herbs, nuts, vegetable or fruit juices or pastes or mixtures thereof), digestible or indigestible carbohydrates (eg sucrose, maltose, fructose, glucose, dextrin, amylose, amylopectin, Inulin, xylan, cellulose), sugar alcohols (eg, sorbitol, mannitol, xylitol), natural or hardened oils (eg, tallow, lard, palm kernel oil, coconut fat, unsaturated vegetable fat), fatty oils (eg, sunflower oil) , Peanut oil, corn oil, thistle oil, olive oil, walnut oil, fish oil, soybean oil, sesame Oil), fatty acids or salts thereof (for example, potassium stearate, potassium palmitate), protein-containing amino acids or non-protein-containing amino acids and compounds thereof (for example, taurine, creatine, creatinine), peptides, natural or synthetic proteins (for example, gelatin) ), Enzymes (eg peptidase, glucosidase, lipase), nucleic acids, nucleotides (inositol phosphate), flavor enhancers (eg monosodium glutamate, 2-phenoxypropionic acid, hydroxyflavanone as described in EP 1,258,200), emulsifier ( For example, lecithin, diacylglycerol), stabilizers (carrageenan, alginate, locust bean gum, guar gum), preservatives (eg benzoic acid, sorbic acid), antioxidants (eg tocopherol or derivatives thereof, Ascos Rubic acid or derivatives thereof), chelating agents (eg citric acid), organic or inorganic acidulants (eg apple acid, acetic acid, citric acid, tartaric acid, phosphoric acid), bitter substances (eg quinine, caffeine, limonin) , Sweeteners (eg saccharin, cyclamate, asphaltame, neotame, neohesperidin, dihydrochalcone, tagatose, sucralose), mineral salts (eg sodium chloride, potassium chloride, magnesium chloride, sodium phosphate), enzyme browning inhibitors ( Eg, sulfite, ascorbic acid), essential oils, plant extracts, natural or synthetic colorants or colored pigments (eg carotenoids, flavonoids, anthocyanins, chlorophyll and derivatives thereof), spices, and perfume compounds and synthetic, natural or natural identical Flavors and It may be used as a sense compound.

All further conventional active, basic, auxiliary and additional substances for oral pharmaceutical preparations can be used as other compounds for the oral pharmaceutical preparation of the present invention. Active, basic, auxiliary and additional substances can be converted into oral application forms in a manner known per se. This occurs using inert, non-toxic, auxiliary substances suitable for pharmaceutical use. These are among others carriers (eg microcrystalline cellulose), solvents (eg liquid polyethylene glycol), emulsifiers (eg sodium dodecyl sulfate), dispersants (eg polyvinyl pyrrolidone), synthetic and natural biopolymers (Eg, albumin), stabilizers (eg, antioxidants such as ascorbic acid), colorants (eg, inorganic pigments such as iron oxide) or flavor and taste collectors.
The preparations according to the invention preferably comprise a flavor composition and / or a perfume of the preparation for perfecting and refining the taste. Suitable flavor compositions include, for example, synthetic, natural or natural-same flavor compounds and perfume compounds, but also particularly include other pungent and / or heat generating substances or plant extracts.
A further feature of the present invention relates to the use of the preparations of the present invention aimed at semi-finished products, especially flavored end products made from semi-finished products.

The preparation of the present invention used as a semi-finished product comprises the alkoxyalkanoic acid amide used in the present invention and optionally one or more other taste and flavor compounds, and optionally further various carriers and auxiliary substances. Or generally from 0.0001% to 95% by weight, in particular from 0.001 to 80% by weight, but in particular from 0.01% to 50% by weight, based on the total weight of the preparation of the various solvents.
Particularly preferred end product flavoring agents are alkoxyalkanoic acid amides (or mixtures thereof) that can be used in the present invention, or one or more substances that have a pungency and / or produce heat irritation or (especially) these A semi-finished product comprising in combination with a pungent plant extract containing the substance and / or in combination with other substances that cause pungent and / or salivary irritation or a plant extract containing these substances, Optionally further comprising various carriers and auxiliary substances and / or various solvents.

Preparation of alkoxyalkanoic acid amide (Example 1) Preparation of 2-heptyloxyacetic acid N-isobutyramide (6) Isobutylamine (80.9 g, 1.1 mol) was first added with acetone (180 ml) and sodium hydroxide solution (45 g / 450 ml). Acetone solution (180 ml) of 2-heptyloxyacetyl chloride (193.2 g, 1 mol) was weighed under a nitrogen atmosphere. The mixture was stirred overnight and 200 g of water was added to separate the oil. The organic phase was dissolved in ethyl acetate and precipitated with n-hexane. After crystallization at −20 ° C., the product is isolated using a cooled Nutsche filter (62 g yield 25%, GC 98.8 area%) to obtain a further fraction of GC> 99% from the mother liquor Was possible.

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 6.61 (1H, bs, NH), 3.93 (2H, s, H-2), 3.50 (2H, t, J = 6.6 Hz, H-1 ') , 3.13 (2H, dd, J = 6.5 Hz, J = 6.4 Hz, H-1``), 1.80 (1H, m, J = 6.7 Hz, H-2 ''), 1.61 (2H, m, J approx. 6.5 Hz, H-2 '), 1.40 1.26 (8H, m, H-3' H-6 '), 0.93 (6H, d, J = 6.7 Hz, H-3``), 0.89 (3H, t, J = 7.0 Hz, H-7 ') ppm.

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 169.91 (C, C-1), 71.90 (CH ₂ , C-1 '), 70.23 (CH ₂ , C-2), 46.05 (CH ₂ , C -1 ''), 31.77 (CH ₂ , C-2 ''), 29.53 (CH ₂ , C-2 '), 29.06 (CH ₂ ), 28.54 (CH, C-2``), 26.05 (CH ₂ ), 22.59 (CH ₂ , C-6 '), 20.08 (2 × CH ₃ , C-3''), 14.07 (CH ₃ , C-6') ppm.

MS (EI): m / z = 28 (23%), 29 (28%), 41 (44%), 43 (40%), 44 (27%), 57 (100%), 60 (76%) , 72 (22%), 115 (92%), 229 (<1%, M ^+. ).

(Example 2) Preparation of 2-heptyloxyacetic acid N- (2-methylbutyl) amide (7)
2-Methylbutylamine (2.11 g, 24 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water), and 2-heptyloxyacetyl chloride (4.0 g, 20 mmol) in acetone ( 4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (2.13 g, 44% yield, GC 96.1 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 6.61 (1H, bs, NH), 3.93 (2H, s, H-2), 3.50 (2H, t, J = 6.6 Hz, H-1 ') , 3.24 (1H, dt, J = 13.2 Hz, J = 6.1 Hz, H-1 ''), 3.12 (1H, dtd, J = 13.2 Hz, J = 7.0 Hz, J = 6.3 Hz, H-1 '' ), 1.65 1.53 (2H, m), 1.46 1.25 (8H, m), 1.18 (1H, m), 0.92 (3H, t, J = 7.5 Hz, H-4``), 0.91 (3H, d, J = 6.7 Hz, H-5``), 0.89 (3H, t, J = 6.8 Hz, H-7 ') ppm.

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 169.90 (C, C-1), 71.89 (CH ₂ , C-1 '), 70.26 (CH ₂ , C-2), 44.32 (CH ₂ , C -1 ''), 34.94 (CH ₂ , C-2 ''), 31.79 (CH ₂ , C-5 '), 29.55 (CH ₂ , C-2'), 29.09 (CH ₂ , C-4 ') , 27.02 (CH, C-3``), 26.08 (CH <sub>2</sub> , C-3 '), 22.60 (CH <sub>2</sub> , C-6'), 17.15 (CH <sub>3</sub> , C-5 ''), 14.08 (CH <sub>3</sub> , C-6 '), 11.28 (CH <sub>3</sub> , C-4``) ppm.

MS (EI): m / z = 41 (28%), 43 (59%), 44 (26%), 57 (88%), 60 (48%), 71 (35%), 73 (28%) , 76 (23%), 129 (100%), 243 (<1%, M ^+. ).

The theoretical value of HRMS: C ₁₄ H ₂₉ O ₂ N is 243.2198, and the experimental value is 243.2185.

Example 3 Preparation of 2-heptyloxyacetic acid N-piperidinide (8) Piperidine (2.14 g, 24 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water) to give 2- A solution of heptyloxyacetyl chloride (4.0 g, 20 mmol) in acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (2.03 g, 42% yield, GC> 95 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 4.12 (2H, s, H-2), 3.54 (2H, t, J approx. 5.5 Hz, H-2``, H-6 ''), 3.49 (2H, t, J = 6.7 Hz, H-1 '), 3.44 (2H, t, J approx. 5.5 Hz, H-2``, H-6''), 1.69 1.52 (8H, m), 1.38 1.26 (6H, m), 0.88 (3H, t, J = 6.9 Hz, H-7 ') ppm.

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 167.73 (C, C-1), 71.50 (CH ₂ , C-1 '), 70.71 (CH ₂ , C-2), 46.21 (CH ₂ , C -2`` / C-6 ''), 42.90 (CH <sub>2</sub> , C-2`` / C-6 ''), 31.81 (CH ₂ , C-5 '), 29.65 (CH ₂ , C-2' ), 29.11 (CH ₂ , C-4 '), 26.53 (CH ₂ , C-3`` / C-5''), 26.06 (CH <sub>2</sub> , C-3'), 25.63 (CH <sub>2</sub> , C-3 `` / C-5 ''), 24.54 (CH ₂ C-4 ''), 22.62 (CH ₂ , C-6 '), 14.09 (CH ₃ , C-7') ppm.

MS (EI): m / z = 41 (23%), 43 (12%), 55 (11%), 57 (19%), 69 (14%), 70 (10%), 84 (14%) , 112 (72%), 127 (100%), 241 (<1%).

HRMS: C ₁₄ H ₂₇ O ₂ N has a theoretical value of 241.22042 and an experimental value of 241.22021.

Example 4 Preparation of 2-heptyloxyacetic acid N-pyrrolidinide (9) Pyrrolidine (2.03 g, 28 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water). A solution of heptyloxyacetyl chloride (4.5 g, 23 mmol) in acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (2.8 g, 54% yield, GC> 95 area%).

Example 5 Preparation of 3-hexyloxypropionic acid N-isobutyramide (10) Isobutylamine (2.14 g, 30 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water). A solution of 3-hexyloxypropionyl chloride (4.0 g, 20 mmol) in acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (1.83 g, 40% yield, GC> 95 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 6.48 (1H, bs, NH), 3.66 (2H, dd, J = 6.0 Hz, J = 5.5 Hz, H-3), 3.46 (2H, t, J = 6.6 Hz, H-1 '), 3.08 (2H, dd, J = 6.8 Hz, J = 6.0 Hz, H-1``), 2.47 (2H, dd, J = 6.0 Hz, J = 5.5 Hz, H-2), 1.77 (1H, m, J = 6.7 Hz, H-2``), 1.58 (2H, m, H-2 '), 1.38 1.26 (8H, m), 0.92 (6H, d, 6.7 Hz), 0.89 (3H, t, J = 7.0 Hz, H-7 ') ppm.

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 171.77 (C, C-1), 71.38 (CH ₂ , C-1 '), 66.99 (CH ₂ , C-3), 46.69 (CH ₂ , C -1 ''), 37.14 (CH ₂ , C-2), 31.67 (CH ₂ , C-4 '), 29.65 (CH ₂ , C-2'), 28.47 (CH, C-2``), 25.92 (CH ₂ , C-3 '), 22.61 (CH ₂ , C-5'), 20.10 (2 × CH ₃ , C-3 ''), 14.09 (CH ₃ , C-6 ') ppm.

MS (EI): m / z = 30 (100%), 41 (46%), 43 (97%), 55 (56%), 57 (87%), 73 (60%), 85 (85%) , 86 (61%), 144 (93%), 229 (24%).

HRMS: C ₁₃ H ₂₇ O ₂ N has a theoretical value of 229.2042 and an actual measurement value of 229.2029.

Example 6 Preparation of 3-hexyloxypropionic acid N- (2-methylbutyl) amide (11)
2-methylbutylamine (2.18 g, 30 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water), and 3-hexyloxypropionyl chloride (4.0 g, 20 mmol) in acetone ( 4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (1.58 g, 33% yield, GC> 95 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 6.45 (1H, bs, NH), 3.66 (2H, dd, J = 6.0 Hz, J = 5.5 Hz, H-3), 3.46 (2H, t, J = 6.6 Hz, H-1 '), 3.20 (1H, dt, J = 13.3 Hz, J = 6.0 Hz, H-1``), 3.07 (2H, ddd, J = 13.2 Hz, J = 7.2 Hz, J = 5.9 Hz, H-1``), 2.47 (2H, dd, J = 6.0 Hz, J = 5.5 Hz, H-2), 1.62 1.50 (4H, m), 1.46 1.26 (6H, m), 0.90 (3H, t, 7.5 Hz, H-4``), 0.90 (3H, d, J = 7.0 Hz, H-5 ''), 0.89 (3H, t, J = 6.8 Hz, H-7 ') ppm .

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 171.81 (C, C-1), 71.39 (CH ₂ , C-1 '), 66.99 (CH ₂ , C-3), 44.89 (CH ₂ , C -1 ''), 37.14 (CH ₂ , C-2), 34.85 (CH, C-2 ''), 31.68 (CH ₂ , C-4 '), 29.65 (CH ₂ , C-2'), 27.00 (CH ₂ , C-3``), 25.91 (CH <sub>2</sub> , C-3 '), 22.61 (CH <sub>2</sub> , C-5'), 17.17 (CH <sub>3</sub> , C-5 ''), 14.03 (CH <sub>3</sub> , C-6 '), 11.27 (CH <sub>3</sub> , C-4``) ppm.

MS (EI): m / z = 30 (82%), 43 (100%), 55 (43%), 71 (40%), 73 (46%), 84 (31%), 85 (64%) , 86 (46%), 158 (59%), 243 (14%, M ^+. ).

The theoretical value of HRMS: C ₁₄ H ₂₉ O ₂ N is 243.2198, and the experimental value is 243.2163.

Example 7 Preparation of 3-hexyloxypropionic acid N-piperidine (12) Piperidine (2.14 g, 24 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water). A solution of -heptyloxyacetyl chloride (4.0 g, 20 mmol) in acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (1.72 g, 36% yield, GC> 95 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 3.75 (2H, t, J = 7.0 Hz, H-3), 3.55 (2H, dd, J = 6.0 Hz, J = 5.5 Hz, H-2 '',H-6''), 3.44 (2H, t, J = 6.7 Hz, H-1'), 3.44 (2H, dd, J = 6.0 Hz, J = 5.5 Hz, H-2``, H- 6``), 1.69 1.52 (8H, m), 1.38 1.26 (6H, m), 0.88 (3H, t, J = 6.9 Hz, H-6 ') ppm.

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 169.27 (C, C-1), 71.35 (CH ₂ , C-1 '), 67.17 (CH ₂ , C-3), 46.81 (CH ₂ , C -2`` / C-6 ''), 42.61 (CH <sub>2</sub> , C-2`` / C-6 ''), 33.74 (CH ₂ , C-2), 31.71 (CH ₂ , C-4 ') , 29.69 (CH ₂ , C-2 '), 26.48 (CH ₂ , C-3`` / C-5''), 25.84 (CH ₂ , C-3'), 25.57 (CH ₂ , C-3 ''/C-5''), 24.58 (CH ₂ C-4''), 22.63 (CH ₂ , C-5'), 14.05 (CH ₃ , C-6 ') ppm.

MS (EI): m / z = 41 (28%), 43 (33%), 55 (23%), 56 (21%), 69 (28%), 84 (61%), 112 (73%) , 141 (52%), 156 (100%), 241 (3%, M ^+. ).

The theoretical value of HRMS: C ₁₄ H ₂₇ O ₂ N is 241.02042, the experimental value is 241.2045.

Example 8 Preparation of 3-hexyloxypropionic acid N-pyrrolidinide (13) Pyrrolidine (2.03 g, 24 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water). A solution of heptyloxyacetyl chloride (4.5 g, 23 mmol) in acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (3.01 g, 58% yield, GC> 91 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 3.77 (2H, t, J = 6.8 Hz, H-3 or H-1 '), 3.48 3.44 (4H, m, H-1'', H- 5``), 3.44 (2H, t, J = 6.7 Hz, H-3 or H-1 '), 2.56 (2H, tt, J = 6.8 Hz, J = 0.6 Hz, H-2), 1.98 1.81 ( 4H, m, H-2``, H-3 ''), 1.55 (2H, m, H-2 '), 1.36 1.24 (6H, m, H-3', H-4 ', H-5' ), 0.88 (3H, t, J = 7.0 Hz, H-6 ') ppm.

MS (EI): m / z = 41 (18%), 43 (48%), 55 (41%), 56 (23%), 70 (60%), 71 (20%), 98 (78%) , 127 (50%), 142 (100%), 227 (3%, M ^+. ).

Example 9 Preparation of 2-heptyloxyacetic acid N- (4-hydroxy-3-methoxybenzyl) amide (14)
4-Hydroxy-3-methoxybenzylamine hydrochloride (1 g, 5.3 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water) and 2-heptyloxyacetyl chloride (1 g, 5.2 mmol). ) In acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (0.5 g, ˜30% yield, GC> 95 area%).

MS (HPLC-APCI +): m / z = 310.15 (20%, [M + H] ⁺ ), 618.81 (100%), 619.74 (22%, [2M + H] ⁺ ).

Example 10 Preparation of 3-hexyloxypropionic acid N- (4-hydroxy-3-methoxybenzyl) amide (15)
4-Hydroxy-3-methoxybenzylamine hydrochloride (1 g, 5.3 mmol) was first added to acetone (4 ml) and sodium hydroxide solution (1 g / 10 ml water) to give 2-hexyloxypropionyl chloride (1 g, 5.2 mmol). ) In acetone (4 ml) was weighed under a nitrogen atmosphere. The mixture was stirred overnight, 20 g of water was added and the mixture was extracted with ethyl acetate. Complete concentration by evaporation gave the product as a yellow oil (0.5 g, ˜30% yield, HPLC> 95 area%).

¹ H-NMR (CDCl ₃ , 400 MHz): δ = 6.88 (1H, d, J = 8.0 Hz, H-5``), 6.82 (1H, d, J = 2.0 Hz, H-2 ''), 6.79 (1H, ddd, J = 8.0 Hz, 1.9 Hz, 0.5 Hz, H-6``), 5.67 (1H, b, NH?), 4.41 (2H, d, J = 6.0 Hz, H-7 '' ), 3.97 (2H, s, H-2), 3.88 (3H, s, O-CH ₃ ), 3.48 (2H, t, J = 6.7 Hz, H-1 '), 1.56 (2H, m, H- 2 '), 1.38 1.20 (8H, m, H3', H-4 ', H-5', H-6 '), 0.87 (3H, t, J = 7.1 Hz, H-7') H, HHh ppm .

¹³ C-NMR (CDCl ₃ , 100 MHz): δ = 169.80 (C, C-1), 146.69 (C, C3``), 145.17 (C, C-4 ''), 130.01 (C, C-1 ''), 120.81 (CH, C-6 ''), 114.41 (C-5 ''), 110.64 (C-2 ''), 71.93 (CH ₂ , C-1 '), 70.18 (CH ₂ , C -2), 55.96 (CH ₃ , O-CH ₃ ), 42.78 (CH ₂ , C-7 ''), 31.74 (CH ₂ , C-5 '), 29.44 (CH ₂ , C-2'), 29.03 (CH ₂ , C-4), 25.99 (CH ₂ , C-3), 22.57 (CH ₂ , C-6 '), 14.06 (CH ₃ , C-7') ppm.

MS (HPLC-APCI +): m / z = 310.02 (50%, [M + H] ⁺ ), 618.62 (100%), 619.68 (23%, [2M + H] ⁺ ).

Application Example 1 Sensory test The substance to be tested (see below) was dissolved in ethanol and then the ethanol solution was diluted with an 11% sugar solution (final concentration: C). In the test, about 5 ml of sugar solution was drowned each time. If the threshold for this substance was known, a value slightly above the threshold was chosen for testing. This solution was tested by a group of 6-8 testers.

a) Properties of 2-heptyloxyacetic acid N-isobutyramide (Example 1, Compound 6):

c = 10ppm: Saliva flow increases slowly, slight biting at the tip of the tongue, milder and less pungent than trans-peritrine.

b) Properties of 3-hexyloxypropionic acid N-isobutyramide (Example 5, Compound 10)

c = 10ppm: Drooling, stinging, slightly cold

c) Properties of 3-hexyloxypropionic acid N- (4-hydroxy-3-methoxybenzyl) amide (Example 10, Compound 15):

c = 10ppm: Spicy, tingling, heat effect, long lasting, slight saliva irritation.

(Comparative test)

d) Characteristics of dihydrocapsaicin

c = 100ppb: Slightly delayed onset of effect in pharyngeal cavity, aggressive, tingling pungent taste (chile, faint heat generation), lasting longer

e) Properties of 2E, 4E-decadienoic acid N-isobutyramide (trans-peritrine)

c = 10ppm: Severe stinging and numbness aftertaste

部分Ａ及びＢの成分は、各部分個別に予め混合されており、減圧下25-30℃で30分一緒に十分攪拌した。部分Ｃは、予め混合され、かつＡ及びＢに添加される。Dを添加し、その混合物を減圧下25-30℃で30分攪拌する。減圧を解除した後、練り歯磨きを仕上げかつ包装してよい。

感覚記載：舌の上のいかなる刺痛なしであるが、咽頭腔の後ろのわずかな刺痛を有する明らかに知覚できる、唾液-刺激効果；持続性のない心地よさ。 (Application 2) Use as a flavoring agent in toothpaste

The ingredients of parts A and B were premixed separately for each part and were thoroughly stirred together at 25-30 ° C. under reduced pressure for 30 minutes. Part C is premixed and added to A and B. D is added and the mixture is stirred under reduced pressure at 25-30 ° C. for 30 minutes. After releasing the vacuum, the toothpaste may be finished and packaged.

Sensory description: without any stinging on the tongue, but clearly perceptible with slight stinging behind the pharyngeal cavity, saliva-stimulating effect; unsustainable comfort.

部分Ａ〜Ｄを混合して徹底的に練った。粗混合物を処理してすぐに使えるチューイングガム、例えば薄いひも状形態を形成し得る。


(Application test 3) Use as a flavoring agent in chewing gum without sugar

Parts A to D were mixed and kneaded thoroughly. The crude mixture can be processed to form a ready-to-use chewing gum, such as a thin string form.

部分Ａ及びＢの成分をそれぞれ各部分に対して混合する。部分Ｂを、混合物が均質になるまでゆっくりと部分Ａにかき混ぜながら入れる。 (Application Example 4) Use of mouthwash as a flavoring agent

The ingredients of parts A and B are mixed for each part. Slowly stir Part B into Part A until the mixture is homogeneous.

パラチニットを水中、１６５℃に溶解し、混合物を１１５℃に冷却する。香味剤及びエタノール溶液を添加して混合した後、混合物を型に注ぎそのまま固定する。 (Application Example 5) Use as a sugar-free boiling sweetener

Palatinite is dissolved in water at 165 ° C and the mixture is cooled to 115 ° C. After the flavoring agent and the ethanol solution are added and mixed, the mixture is poured into a mold and fixed as it is.

スクロースを115℃の水に溶解する。グルコースシロップを添加し混合物を140℃にする。香味剤とエタノール溶液を添加し、混合の後、混合物を130-135℃の温度で型に注ぎ、そのまま固定した。 (Application Example 6) Use as a flavoring agent in a boiled sweetener

Dissolve sucrose in 115 ° C. water. Glucose syrup is added and the mixture is brought to 140 ° C. A flavoring agent and an ethanol solution were added, and after mixing, the mixture was poured into a mold at a temperature of 130-135 ° C and fixed as it was.

(Application Example 7) Use of fried cranky snacks as seasoning 100g of unseasoned tortilla chips and 7g of dry cheese flavorant for snacks and 0.07g of 3-hexyloxypropionic acid N-isobutyramide Sprinkle the mixture of Example 5).

(Application Example 8) Use for cream filling for biscuits
100 g of standard cream filling is thoroughly mixed with 0.4 g of strawberry flavor and 0.1 g of 3-hexyloxypropionic acid N-isobutyramide (Example 5).

これを調製するために、全ての成分量を混合し香味剤を最後に計量する。 (Application example 9) Use as an alcohol flavor enhancer in apple brandy

To prepare this, all ingredient amounts are mixed and the flavor is finally weighed.

これを調製するためにすべての成分を混合して香味剤を最後に計量する。 Application Example 10 Use in an alcohol-free preparation as an alcohol mimic

To prepare this, all ingredients are mixed and the flavor is finally weighed.

Claims (11)

The following formula,

(5a)
(Wherein n represents a number of 1 or 2, R ¹ represents an alkyl group, and R ² represents a lower alkyl group optionally substituted with one or more hydroxy groups.)
An alkoxyalkanoic acid amide of the formula

(5b)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, m represents a number of 1 or 2, and R ′ and R ″ are independently of each other. A hydrogen atom or a methyl or ethyl group or a methylene group at the same time.)
An alkoxyalkanoic acid amide of the formula

(5c)
(Wherein n represents a number of 1 or 2, R ¹ represents an alkyl group, and R ² and R ³ are each independently or differently substituted with one or more hydroxy groups. The same or different lower alkyl groups are shown, or R ² and R ³ simultaneously form an alkylene group.)
Or a mixture of two or more compounds of the formula (5a), (5b) and / or (5c),
(i) flavor and / or (ii) tingling sensation and / or (iii) pungent sensation and / or (iv) stimulation of saliva flow in the mouth and / or (v) enhancement of ethanol taste and / or Or (vi) use as an imitation of ethanol taste.   2. Use according to claim 1 in a preparation consumed for nutrition or fun or used for oral hygiene.   Use according to claim 1 in an oral pharmaceutical preparation. Preparations consumed for nutrition, used for oral hygiene or consumed for fun, in achieving stinging and / or pungent and / or heat and / or in producing saliva flow and An effective amount in enhancing or mimicking ethanol flavor,

(5a)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, and R ² represents lower alkyl optionally substituted with one or more hydroxy groups.)
An alkoxyalkanoic acid amide of the formula

(5b)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, m represents a number of 1 or 2, and R ′ and R ″ are independently of each other. A hydrogen atom or a methyl or ethyl group or a methylene group at the same time.)
An alkoxyalkanoic acid amide of the formula

(5c)
(Wherein n represents the number of 1 or 2, R ¹ represents an alkyl group, and R ² and R ³ are each independently the same or optionally substituted with one or more hydroxy groups. Different lower alkyl groups or R ² and R ³ simultaneously form an alkylene group.)
Or a mixture of two or more compounds of formula (5a), (5b) and / or (5c). An oral pharmaceutical preparation, which has an effective amount of formula for achieving stinging and / or pungent and / or thermal sensation and / or in generating saliva flow and / or enhancing or mimicking ethanol flavor:

(5a)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, and R ² represents lower alkyl optionally substituted with one or more hydroxy groups.)
An alkoxyalkanoic acid amide of the formula

(5b)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, m represents a number of 1 or 2, and R ′ and R ″ are independently of each other. A hydrogen atom or a methyl or ethyl group or a methylene group at the same time.)
Or a mixture of two or more compounds of the formulas (5a) and / or (5b).   6. A preparation according to claim 4 or 5, comprising one or more additional substances that have a pungent taste and / or generate a thermal sensation.   7. A preparation according to any one of claims 4 to 6 comprising one or more additional substances that produce tingling sensation or saliva stimulation.   The preparation according to any one of claims 4 to 7, comprising at least one substance that produces a physiological cooling effect.   9. A preparation according to any one of claims 4 to 8 in the form of a semi-finished product.   The preparation according to any one of claims 4 to 9, which is in the form of a fragrance, a flavoring agent or a taste composition or a seasoning formulation. The following formula,

(5a)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, and R ² represents a lower alkyl group optionally substituted with one or more hydroxy groups.)
An alkoxyalkanoic acid amide of the formula

(5b)
(In the formula, n represents a number of 1 or 2, R ¹ represents an alkyl group, m represents a number of 1 or 2, and R ′ and R ″ are independently of each other. A hydrogen atom or a methyl or ethyl group or a methylene group at the same time.)
An alkoxyalkanoic acid amide.