DE1925841A1 - Quarternary salts - Google Patents

Description

DR. INO. A. VAN DER WERTH _DR . _{FRANZ LEATHER}

91 HAMlUHC 90. MONCHEM .O WU.T..M. .T «. · ■. T.W Τ, ·. «. 1 «α« -0.ΑΜΜ..Τ «. . - T.U-.,

Munich, the 20th Hal 1969 P / Br

Applicant BP CHEMICALS (U.K.) LIMITES, Britannic House »Moor Lane, London, E.C. 2, England

Quaternary salts

The present invention particularly relates to new quaternary salts and their use as bitter flavors as a denaturant for ethyl alcohol or ethyl alcohol containing mixtures.

Compounds which have an extremely bitter taste for humans and animals, including insects and birds, can be used to make materials unapproachable Measures have been made unhealthy. For fiscal reasons, there are regulations in many countries which require that one or more agents be added to an ethyl alcohol which is sold for industrial consumption or for use by the public. Certain of these remedies have the task of improperly smoking the alcohol treated in this way, among other things to prevent it from being drunk. A wiohtige class eolohe r denaturing agent consists of compounds which have an intense bitter taste, such as Qu &A'in ₉ or brucine. This class includes compounds according to the present invention.

009820/1934

The present invention relates to quaternary compounds ▼ on alpha-alkylamino acidic acids of the formula

R ₁ OOCCH ₂ N

C-)

wherein R _{1 is} an alkyl group, a cycloaliphatic group, an aralkyl group, a phenyl group or a substituted phenyl group of the formula

R ^IV R »

III

R ¹¹ R ¹

represents, where R is an Aoyollian hydrocarbon radical

TT TTT TV V

or halogen and R, R, R and R halogen or Waeser-

I V atoff or R and R acyclische Kohlenwasseratoffreat «and

each of R ¹¹ , R ¹¹¹ and R ^IV halogen or hydrogen or

R ¹ and R ^V and any of R ¹¹ , R ¹¹¹ and R ^IV acyclic

II ** see hydrocarbon residues, each of the rest of R, R and R denote halogen or hydrogen, in which furthermore R ₂ and R ^ are alkyl radicals, R ^ is a benzyl, chlorobenzyl or bromobenzene group, A ^ * "'is an anion and η is an integer which is equal to the valence of the anion , represent.,

When R _{1 is} an alkyl group, it preferably contains 1-4 carbon atoms. When ee is a cycloaliphatic group, it can contain 4-8, preferably 6 carbon atoms. When it is aralkyl it preferably contains 7-11 carbon atoms

R ₂ and Rj preferably contain 1 - 4 carbon atoms The type and size of the acyclic hydrocarbon

009820/1934

τ ν
Substituents R and R are only limited by the requirement that they _{should not interfere with the ability of the R 1} group ₉ to form the group R ^ OOO- shown in the general formula I. It is known that one great constituent

I ¥
in the positions of H and R oils can _{prevent the formation of the ester group R 1} OOC- aua compounds from the ijpus R ₁ OH, if R _{1 represents} a eub-titrated phenyl group. If they are acyclic hydrocarbon radicals, then R

to R preferably contain 1-4 carbon atoms. When they represent halogen atoms, it is preferred that λ Bie are chlorine or bromine atoms "

Those R ₁ groups which are substituted phenyl groups with substituents as described above in positions -, 6 or 2, 4, 6 are all particularly useful for the purposes of the present invention.

Fe is assumed that the bitter Geseiasack of the claimed compounds is located in the cation Imt. The anion represented by & _n in the general formula I * can be selected from a wide range of acid @ a without it having any significant influence on the spirit of the Salises, A ^ ^; can Axeo dao to £ 'm a aliphatisohen MonooarboßsäureV "verssugsweiee containing 1 -' β carbon atoms that Moneanion barren aEAE dianion Einei Dioarboneäure, such as maleic acid _e" succinic acid, <AÄlpißeäure, glutaric β o-, m 'or p Fhthalsäiire or an anion containing a trivalent acid such as aβ B ₈ trinellitic acid * trimesic acid or pyromellitic acid represent. Ee can also mean monovalent or divalent ions of inorganic acids, such as chloride, bromide, bisulphate or sulphate ions. Anions of higher valency can be used if they prove suitable.

The use of anions, those of organic carboxylic acids stBmmen, is the use of inorganic

003820/193 *

Acid-derived training is usually preferred because the the former usually give quaternary salts which are less corrosive »salts of benzoic acid, oxalic acid, Tartaric acid and phthalic acid are examples of compounds which are particularly satisfactory in this regard.

Typical examples of quaternary compounds, which please * Ren taste are benzyl, chlorobenzyl or Bromobenzyl quaternary salts of the following alpha-dialkylaminoeigeäureeetert

alpha-diethylaminoethyl acetate, alpha-diethylaminoisopropyl acetate, alpha-dimethylamino-2,4,6-trimethylphenyl acetate, alpha-dimethylamino-2,6-dimethylphenyl acetate, alpha-diethylamino-2,6-dimethylphenyl acetate _o

Typical examples of acids which lead to the formation of SaI ^ zen which have only a low corrosive effect on metals in contact with their solutions in aqueous alcohol are well suited

Benzoic acid,

ο-, m- or p-chlorobenzoic acid, o-, m- or p-toluic acid, o-, m- or p-phthalic acid, Oxalic acid, Tartaric acid.

Two particularly effective compounds which have the general formula I mentioned earlier and which are used for denaturing The hydrogen phthalate salts of the benzyl quaternary derivatives of ethyl alcohol are very useful alpha-diethylamino-2,6-dimethylphenyl acetate and alpha-diethylamino-2,4,6-trimethylphenyl acetate.

These two substances are several times more bitter than Quassln or Brucine and are some of the most bitter

009820/1 934

known connections. When dissolved in ethyl alcohol or in ethyl alcohol / water mixtures, it leaves a bitter taste can be easily determined at concentrations as low as a fraction of 1 ppm. Very little Concentrations are required to give such solutions a distinctly obnoxious taste.

Alpha-diethylamino-2,6 ~ dime ~ ethylphenyl acetate in the form of its benzyl hydrogen phthalate quarternar salt can be used even in concentrations as low as 1 part in 50 million, but the preferred Amount varies with the nature of the product which is to be given a bitter taste. Infplge of Un- ™

different in the nature of the product it is impossible to specify an upper limit, because a bitter taste can be chosen because of its pleasant effect or because of its disgusting character. Normally should it may not be necessary to use amounts greater than 0.1 #. However, it is convenient to prepare concentrated solutions to lower the achievement of the desired extra To facilitate concentrations.

For denaturing purposes, the quantities used will in many cases be determined by the regulations in force in the country concerned. Normally Hen- be - be satisfactory ppm gen in the range of 0.01 i> until the first While the lower limit is often set by regulations, the upper limits can be determined by other factors such as B. the cost or the residue after evaporation of the alcohol can be determined. In the case of alcohol, which is used in some toilet articles such as B ₀ Eau de Cologne is used, it is undesirable that complete evaporation of the preparation from the skin leaves an unsightly residue. For this reason it is often considered desirable to limit non-volatile substances to less than 100 ppm in the preparation.

009820/1934

The compounds of the invention can be made using methods known to the expert _f well known, are readily prepared. In the following example a special production method is described.

example 1

Hydrogen phthalate salt of the benzyl quaternary derivative of alpha-diethylamino-2,6-dimethylphenyl acetate.

2,6-Xylenol was 10 hours at 110-120 ° C in one Flask equipped with a reflux condenser with an equimolecular amount of chloroacetyl chloride ζμΓ reaction · The product was at 90 ° C / 200-300 mm Hg the Subjected to distillation until most of the unreacted chloroacetyl chloride was removed. The crude xylyl chloroacetate ester (20 g) was refluxed with diethylamine (15 g) in benzene for 1.5 hours. The reaction mixture It was then allowed to cool and diethylamine hydrochloride was filtered off. The benzene filtrate was with several Fortionen 8 ^ iger hydrochloric acid extracted and the combined extracts were in the presence of ice with 3 lg * r Potash neutralized. The product was extracted with diethyl ether and the solution with 10 tigern salt water until Washed neutral? The ether was allowed to evaporate and the product obtained was dried in a vacuum desiccator. According to analysis, it consisted of alpha-diethylamino-2,6-dimethylphenyl acetate of a purity of 95.5 9 »» The ester was for 20 hours at 100 ° C with a small Treated excess of Benzylchlorjd, the viscous oily Product was extracted three times with ether and then by adding a ten-fold amount of ethyl acetate was I like a solid product «The product was whitish Powder, which was further purified by fractional precipitation, resulting in essentially pure alpha-dläthylanino-2 ^ -dimethylphenyl acetate in the form of its benzyl

009820/1934

Chloride quaternary compound. This salt was tasted by a panel of 17 people subject.

The chloride salt and a slight excess of sodium hydrogen phthalate were refluxed in ethanol (74 OP Q over normal strength 2) for 5 hours. The reaction mixture was filtered hot to remove sodium chloride and excess sodium hydrogen phthalate. After cooling, the hydrogen phthalate salt was filtered off and recrystallized from ethanol (74 OP). This salt was also subjected to Gesohmaokatesten by a group of 17 people.

The teas were made from solutions of alcohol in the three times the amount of water. A solution of 4 prm dee chlorides in fermentation alcohol (74 OP) was considered bitter found to be a sample of similar alcohol which contained a bitter flavor in an amount which would meet the requirements of the United Kingdom Cuetome ft Ezoiee Regulations corresponded. A similar experiment on a solution of 3 ppm of hydrogen phthalate ases showed that the test group was a good one between the tea solution and the sample according to those mentioned "Regulations" could not differentiate, with bel6 «solutions again as a solution of 1 part of alcohol in 3 parts Waeaer templates.

Similar taste tests with alcoholic solutions of the Hy # rögenphthalat8alze8 in three times the amount of water were carried out, with a solution of 23 ppm as a standard Qua3βin in alcohol dissolved in three times the amount of water The hydrogen phthalate salt was found to be approximately seven times more bitter than that equal weight of quassin.

BATH ORIGINAL

00332 0/1934

Example 2

Benzoate salt of the benzyl quaternary derivative of alpha-Dläthylamino ~ 2 ₁ 6-dimethylphenyl acetate.

alpha-diethylamino ~ 2,6-dimethylphenyl acetate in the form of his Benzyl chloride salts, prepared as in Example 1, were Heated to reflux with sodium benzoate in ethanol (74 OP) for 5 hours. After filtration, the product had a bitter taste different from that of chloride or Hydrogen phthalate salts could not be distinguished practically, which confirms that it is relatively unimportant is which anion / is present "

Example 3

Chloride salt of the benzyl quaternary derivative of alpha-diethylamino-isopropyl acetate.

Chlores8iga acid was used without a catalyst with a large Brought excess of isopropanol to the reaction. Most of the water / leopropanol azeotrope was taken from the reflux The mixture is removed by means of a take-off point above a ten-tray column, a fraction with a boiling point 149 - 151 ° C, consisting largely of isopropylchloroacetate, was then collected «The reaction with ethylamine was similar to Example 1, but the number Watery ablutions were kept to a minimum, in view of the greater solubility of the t-Ainins ,, the Quarteriiierung with benzyl chloride was similar to Example 1.

Example 4

Using the procedure described in Example 1, the quaternary Jhloridsalze were based on the the following phenols are formed:

BATH ORIGINAL

0 0 9 3 2 0 / ■> 9 3 *

Cresol,

2 , 4,6-triraethylphenol _P
2,6-chlorophenol "

The compounds were found to be extremely bitter «Example 5

The methyl, ethyl, and benzyl chloroacetateeters were prepared using methods well known in the art Using the procedure of Example 3, the Ohio- Ride salts of the benzyl quaternary derivatives of alpha-diethyl ™ aminomethyl, ethyl or benzyl acetates, prepared in this way were all found to be bitter-tasting compounds

BATH ORIGINAL 009820/1934

Claims (5)

Sponsorship claims 1st Quaternary compounds of alpha-DlalkylaminoeBsigsäureeetern of the formula R ₁ OOCCH ₂ I. 4 y wherein R _{1 is} an alkyl group, a cycloaliphatic group, an aralkyl group, a phenyl group or a substituted phenyl group of the formula III R ^IV R ^V represents * where R is an acyclic hydrocarbon TT TTT TV V rest or halogen and R, R, R and R halogen or IV
Hydrogen or R and R acyclic hydrocarbons radicals and each of R ¹¹ , R ¹¹¹ and R ^{IV are} halogen or hydrogen or R and R and any of ΊΓ, R and R acyclic carbon dioxide radicals , each of the remainder of R ¹¹ , R ¹¹¹ and R ^{IV are} halogen or hydrogen, in which further R ₂ and R * alkyl radicals, «Ine benzyl, chlorobenzyl or bromobenzyl group, a ~ '"in anion and η an integer, which is the valens dta anion is" 009820/1934 2. Compounds according to claim 1, characterized in that R _{1 represents} a phenyl group substituted in positions 2 and 6 or 2, 4 and 6. 3. Compounds according to any one of claims 1 or 2, characterized kermzelehnst that Hp and R, 1 x 4 carbon atoms contain. 4. Compounds according to one of the preceding claims, characterized in that the anion A _n ^ "'of benzoic acid, o- _f m- or p-chlorobenzoic acid, o-, m ~ or p-toluic acid, o-, m- or p - Phthalic acid, oxalic acid or tartaric acid. 5. Bensyl or chlorobenzyl quaternary disc van alphe diethylaminoethyl acetate, alpha-diethylaminoieopropyl acetate, alpha-dimethylamino, 2,4,6-trimethylphenyl acetate, alpha-diinethylamino-2,6-dimethylphenyl acetate and alpha-diethylamino-2,6-dimethylphenyl acetate. 6 «Quaternary ßalae according to claim 5» characterized in that that the anion is bensoate, oxalate, hydrogen phthalate or tartrate is. 7 = ethyl alcohol or mixtures containing ethyl alcohol, characterized in that ice is denatured by means of a compound according to one of the "preceding claims. S ₀ use of a compound or composition, according to tinem of claims 1 bic 7 as a flavoring agent _o 9c agents against animals including birds and insects, characterized in that ee is a compound or composition according to any one of claims 1 to 7. 009820/193 * ORIGINAL BATHROOM