CN107162948B - A kind of synthetic method of amino acid quaternary ammonium carboxylate - Google Patents
A kind of synthetic method of amino acid quaternary ammonium carboxylate Download PDFInfo
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- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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- C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
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Abstract
A kind of synthetic method of amino acid quaternary ammonium carboxylate belongs to compound synthesis technical field.1 mole of alkali metal hydroxide is dissolved in and obtains solution A in the volatile organic solvent that temperature is 20 DEG C~30 DEG C；1 mole of double-strand quaternary ammonium ammonium halide or single-stranded quaternary ammonium ammonium halide are dissolved in and obtain solution B in volatile organic solvent；A is mixed with B, insoluble matter is removed, obtains solution C；Acetylated amino acids are dissolved in volatile organic solvent, and allow the acetylated amino acid anion in acquired solution containing 1 mole, obtain solution D；C is mixed with D, insoluble matter and volatile organic solvent is removed, obtains product.This invention simplifies synthesis steps, and toxicity can be used relatively low and be easier to recycling, tractable organic reagent, improve the purity of amino acid quaternary ammonium carboxylate.
Description
Technical field
The invention belongs to compound synthesis technical fields, and in particular to a kind of synthetic method of amino acid quaternary ammonium carboxylate,
Synthesis resulting product can be used for preventing and treating microorganism infection or environment disinfected.
Background technique
The Chinese invention patent file of Patent No. ZL 201210166719.3 discloses a kind of amino acid quaternary ammonium carboxylic acid
Salt, including the single-stranded quaternary ammonium carboxylate of amino acid and amino acid double-strand quaternary ammonium carboxylate, by negatively charged amino acid yin from
Sub and single-stranded or double-stranded quaternary ammonium cation without halogen is constituted, which can kill mostly in low concentration
Number pathogenic bacteria or virus, it is non-toxic.The disclosed product synthesis step is: the first step, is having volatile organic solvent
It is middle to neutralize the metal hydroxides such as the sodium hydroxide of acetylated amino acids equivalent or potassium hydroxide；Or in water with ice bath
Or the mixture of dry ice acetone keeps low temperature, neutralizes the acetylated amino acids and the metals such as sodium hydroxide or potassium hydroxide of equivalent
Hydroxide；Second step removes volatile organic solvent or water, obtains the amino acid metal salt of solid；Third step, by metal sun
Ion, the salt of amino acid anion are soluble in water, mix with the quaternary ammonium ammonium halide of equivalent；4th step, in above-mentioned aqueous solution
Middle addition organic solvent is mixed to be shaken, and is ultimately formed two layers of liquid of organic phase and water phase, is acetylated amino acids quaternary ammonium in organic phase
Carboxylate；Byproduct metal cation and inorganic anion stay in water phase；5th step, by organic phase and aqueous phase separation, removal
The solvent of organic phase；6th step, water phase is mixed with pure organic solvent again extracts the acetylated amino hydrochlorate of remaining in water,
It repeats to extract three times；7th step removes organic solvent, obtains product.This synthetic method has the following disadvantages: 1. synthesis step phases
To more complicated；2. organic reagent methylene chloride used in recycles and handles more troublesome and have certain toxicity；Go out synthesized by 3.
The material purity come is not high.
Summary of the invention
It is an object of the invention to overcome existing synthesizing amino acid quaternary ammonium carboxylate method, provide a kind of new
Synthetic method.
Synthetic method of the present invention is according to the following steps:
1,1 part mole of alkali metal hydroxide is dissolved in the volatile organic solvent that temperature is 20 DEG C~30 DEG C, is obtained
Solution A；
2,1 part mole of double-strand quaternary ammonium ammonium halide or single-stranded quaternary ammonium ammonium halide are dissolved in volatile organic solvent,
Obtain solution B；
3, obtained solution A and solution B above are sufficiently mixed, wherein the cation of alkali metal and halogen family anion are raw
At the salt insoluble in volatile organic solvent, sufficiently filtering or centrifugation removal insoluble matter, the ammonium hydroxide of quaternary ammonium containing double-strand is obtained
Or the solution C of single-stranded quaternary ammonium ammonium hydroxide；
4, acetylated amino acids are dissolved in volatile organic solvent, and allow the acetyl in acquired solution containing 1 part mole
Change amino acid anion, obtains solution D；
5, it obtained solution C will be mixed above with solution D, and remove insoluble matter, obtain solution E；
6, the volatile organic solvent in solution E is removed, product amino acid quaternary ammonium carboxylate is obtained.
Described amino acid quaternary ammonium carboxylate, including the single-stranded quaternary ammonium carboxylate of amino acid and amino acid double-strand quaternary ammonium carboxylic
Hydrochlorate.
If that need to synthesize is double decyl dimethyl oxygen conjunction proline ammonium DAPC in amino acid double-strand quaternary ammonium carboxylate
(Proline, 5-oxo-, ion (1-), N-decyl-N, N-dimethyl-1-decanaminium (1:1)), specific synthesis step
Suddenly it can be such that
Preparation solution A: using dehydrated alcohol as solvent, 1 part mole of alkali metal hydroxide is added thereto, and is heated to
It 20 DEG C~30 DEG C, is stirred well to alkali metal hydroxide and is completely dissolved to get solution A；
Prepare solution B: using dehydrated alcohol as solvent, at room temperature by 1 part mole of double-track suspended self-propelled conveyor
It is added thereto, is stirred well to double-track suspended self-propelled conveyor and is completely dissolved to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 1~10 minute, is generated insoluble in dehydrated alcohol
Metal chloride precipitating, sufficiently filtering or centrifugation removal metal chloride precipitating, obtain double decyl dimethyl Ammonias,
Up to solution C；
Preparation solution D: 1 part mole of pyroglutamic acid is dissolved in dehydrated alcohol, solution is made to get solution D；
Preparation solution E: solution C and solution D are sufficiently mixed, and sufficiently filtering or centrifugation is to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAPC.
If what need to be synthesized is double decyl dimethyl N- acetylalanine ammoniums in amino acid double-strand quaternary ammonium carboxylate
DAAC (1-Decanaminium, N-decyl-N, N-dimethyl-, salt with N-acetylalanine (1:1)), tool
Body synthesis step can be such that
Preparation solution A: using dehydrated alcohol as solvent, 1 part mole of alkali metal hydroxide is added thereto, and is heated to
It 20 DEG C~30 DEG C, is stirred well to alkali metal hydroxide and is dissolved completely in dehydrated alcohol to get solution A；
Prepare solution B: using dehydrated alcohol as solvent, at room temperature by 1 part mole of double-track suspended self-propelled conveyor
It is added thereto, is stirred well to double-track suspended self-propelled conveyor and is dissolved completely in dehydrated alcohol to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 1~10 minute, is generated insoluble in dehydrated alcohol
Metal chloride precipitating, sufficiently filtering or centrifugation removal metal chloride precipitating, obtain double decyl dimethyl Ammonias,
Up to solution C；
Preparation solution D: 1 part mole of acetylation alanine is dissolved in dehydrated alcohol, solution is made to get solution D；
Preparation solution E: solution C and solution D are sufficiently mixed, and sufficiently filtering or centrifugation is to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAAC.
The present invention relates to a kind of synthetic method of amino acid quaternary ammonium carboxylate, this method is suitable for amino acid quaternary ammonium carboxylic
Hydrochlorate is made of negatively charged amino acid anion and amino cation.
The amino acid quaternary ammonium carboxylate suitable for the synthetic method has following general formula:
Wherein A-COO- represents protected amino acid；
A therein represents different amino acid residues；
Wherein R1 and R2 represents straight chain, cycloalkanyl or H；R1 and R2 may be the same or different.
The synthetic method is suitable for amino acid quaternary ammonium carboxylate, and R1 and R2 is 8-18 carbon atom in structural formula
Alkyl, the double chain compound that wherein R1 and R2 may be the same or different.
The synthetic method is suitable for amino acid quaternary ammonium carboxylate, it is characterised in that R1 or R2 is 8-18 in structural formula
The alkyl of a carbon atom, wherein R1 or R2 can be that H, methyl, ethyl, propyl, alkoxy, aromatic radical, naphthenic base etc. are other to be taken
The single chain compound of Dai Ji.
Can be by non-ring group suitable for the amino acid quaternary ammonium carboxylate of synthetic method of the present invention, ring group is acyclic
The aromatic radical You Benzyl base that base or alkoxy replace, tolyl, xylyl, naphthalene, pyridyl group, benzylidene, quinolyl etc..This
The invention synthetic method is suitable for synthesis: tetramethyl acylamino acid ammonium, trimethylethyl acylamino acid ammonium, dimethyl
Diethyl acylamino acid ammonium, dimethyl triethyl group acylamino acid ammonium, tetraethyl acylamino acid ammonium, hexadecanol dimethyl second
Base acylamino acid ammonium, thmethylpropyl acylamino acid ammonium, dimethyl propyl acylamino acid ammonium, methyl tripropyl acyl group ammonia
Base acid ammonium), tetrapropyl acylamino acid ammonium, Methylethyl butyl acylamino acid ammonium, ethyl propyl amyl acyl amino
Sour ammonium, trimethyl allyl acylamino acid ammonium, dimethyl diallyl acylamino acid ammonium, methyl triallyl acyl amino
Sour ammonium, tetraallyl acylamino acid ammonium, octadecyl trimethyl acylamino acid ammonium, double octadecyldimethyl acyl aminos
Sour ammonium, three (octadecyl) methylacyl amino acid ammoniums, four (octadecyl) acylamino acid ammoniums, six decyl triethyl group acyl group ammonia
Base acid ammonium, six decyl dimethyl ethyl acylamino acid ammoniums, six decyl diethylmethyl acylamino acid ammoniums, the double octyls of double decyls
Acylamino acid ammonium, the double hexyl acylamino acid ammoniums of double decyls, and decyl octadecyl dodecyl acylamino acid ammonium.
Synthetic method of the present invention is suitable for synthesizing the acylated amino hydrochlorate containing aromatic radical, comprising: benzene dodecane
Base dimethyl acylamino acid ammonium, o- tolyl dodecyl dimethyl acylamino acid ammonium, m- tolyl dimethyl
Base acylamino acid ammonium, p- tolyl dodecyl dimethyl acylamino acid ammonium, 2,3- tolyl dodecyl dimethyl acyl
Base amino acid ammonium, 2,4- tolyl dodecyl dimethyl acylamino acid ammonium, 2,5- tolyl dodecyl dimethyl acyl group
Amino acid ammonium, 3.4- tolyl dodecyl dimethyl acylamino acid ammonium, 3,5- tolyl dodecyl dimethyl acyl group ammonia
Base acid ammonium, 2- chlorphenyl dodecyl dimethyl acylamino acid ammonium, 3- chlorphenyl dodecyl dimethyl acylamino acid ammonium,
4- chlorphenyl dodecyl dimethyl acylamino acid ammonium, 2,3- dichlorophenyl dodecyl dimethyl acylamino acid ammoniums, 2,
4- chlorphenyl dodecyl dimethyl acylamino acid ammonium, 2,5- dichlorophenyl dodecyl dimethyl acylamino acid ammoniums, 2,
6- dichlorophenyl dodecyl dimethyl acylamino acid ammonium, 3,4- dichlorophenyl dodecyl dimethyl acylamino acid ammoniums,
3,5- dichlorophenyl dodecyl dimethyl acylamino acid ammoniums, 2- pyridyl dodecyl dimethyl acylamino acid ammonium, 3-
Pyridyl dodecyl dimethyl acylamino acid ammonium, 4- pyridyl dodecyl dimethyl acylamino acid ammonium, 2,4- phenodiazines
Phenyl-dodecane base dimethyl acylamino acid ammonium, 3,5- phenodiazine phenyl-dodecane base dimethyl acylamino acid ammoniums, 2- sulphur benzene
Base dodecyl dimethyl acylamino acid ammonium, 3- sulfur phenenyl dodecyl dimethyl acylamino acid ammonium, 4- sulfur phenenyl 12
Alkyl dimethyl acylamino acid ammonium, 2- carboxy phenyl dodecyl dimethyl acylamino acid ammonium, 3- carboxy phenyl dodecyl two
Methylacyl amino acid ammonium, 4- carboxy phenyl dodecyl dimethyl acylamino acid ammonium, benzene hexyl dimethyl acylamino acid ammonium,
Benzene octyldimethyl acylamino acid ammonium, benzene decyl dimethyl acylamino acid ammonium, benzene dodecyl dimethyl acylamino acid
Ammonium, benzene dodecyldimethylamine base acylamino acid ammonium, benzene hexadecyldimethyl benzyl ammonium acylamino acid ammonium, benzene octadecyldimethyl
Acylamino acid ammonium.
Synthetic method of the present invention is suitable for synthesizing amino acid quaternary ammonium carboxylate, connects on tetravalence ammonium ion
Fat or alicyclic ring can by containing 1-30 carbon atom linear paraffin or branched paraffin group replace；1-30 carbon atom can also be contained
Straight or branched alkoxyl roll into a ball replace.Can substituted alicyclic group include: n- hexyl pyridinium halide (n-
Hexylpyridinium halide), n- octyl pyridinium halide (n-octylpyridinium halide), n- decyl halogenation
Pyridine (n-decylpyridinium halide), n- dodecyl pyridinium halide (n-dodecylpyridinium
), halide n- myristyl pyridinium halide (n-tetradecylpyridinium halide), n- cetylpyridinium halide pyrrole
Pyridine (n-hexadecylpyridinium halide), hexyl dimethyl pyridinium halide (n-hexyllutidinium
), halide octyldimethyl pyridinium halide (n-octyllutidinium halide), decyl dimethyl pyridinium halide
(n-decyllutidinium halide), dodecyl dimethyl pyridinium halide (n-dodecyllutidinium
), halide dodecyldimethylamine base pyridinium halide (n-tetradecyllutidinium halide), etradecyldimethylamine
Base pyridinium halide (n-hexadecyllutidinium halide), hexyl methyl pyridinium halide (n-
Hexylpicolinium halide), octyl methyl pyridinium halide (n-octylpicolinium halide), decyl methyl
Pyridinium halide (n-decylpicolinium halide), dodecyl methyl pyridinium halide (n-
Dodecylpicolinium halide), tetradecylmethyl pyridinium halide (n-tetradecylpicolinium
), halide cetyl methyl pyridinium halide (n-hexadecylpicolinium halide), hexyl halogenated quinoline (n-
Hexylquinolinium halide), octyl halogenated quinoline (n-octylquinolinium halide), decyl halogenated quinoline
(n-decylquinolinium halide), dodecyl halogenated quinoline (n-dodecylquinolinium halide), ten
Tetra-alkyl-phosphonium halide quinoline (n-tetradecylquinolinium halide), cetylpyridinium halide quinoline (n-
Hexadecylquinolinium halide), hexyl halogenation isoquinolin (n-hexylisoquinolinium halide) is pungent
Base halogenation isoquinolin (n-octylisoquinolinium halide), decyl halogenation isoquinolin (n-
Decylisoquinolinium halide), dodecyl halogenation isoquinolin (n-dodecylisoquinolinium
), halide myristyl halogenation isoquinolin (n-tetradecylisoquinolinium halide), cetylpyridinium halide is different
Quinoline (n-hexadecylisoquinolinium halide), hexyl halogenation quinazoline (n-hexylquinazolinium
), halide octyl halogenation quinazoline (n-octylquinazolinium halide), decyl halogenation quinazoline (n-
Decylquinazolinium halide), dodecyl halogenation quinazoline (n-dodecylquinazolinium halide),
Myristyl halogenation quinazoline (n-tetradecylquinazolinium halid), cetylpyridinium halide quinazoline (n-
Hexadecylquinazolinium halide), hexyl halogenation quinoxaline (n-hexylquinoxalinium halide) is pungent
Base halogenation quinoxaline (n-octylquinoxalinium halide), decyl halogenation quinoxaline (n-decylquinoxalinium
), halide dodecyl halogenation quinoxaline (n-dodecylquinoxalinium halide), myristyl halogenation quinoxaline
(n-tetradecylquinoxalinium halide), cetylpyridinium halide quinoxaline (n-
Hexadecylquinoxalinium halide), hexyl pyridinium halide (n-hexylpyridopyridinium halide),
Octyl pyridinium halide (n-octylpyridopyridinium halide), decyl pyridinium halide (n-
Decylpyridopyridinium halide), dodecyl pyridinium halide (n-dodecylpyridopyridinium
), halide myristyl pyridinium halide (n-tetradecylpyridopyridininum halide), and cetylpyridinium halide
Pyridine (n-hexadecylpyridopyridinium halide)
Acylamino acid portion suitable for the amino acid quaternary ammonium carboxylate of synthetic method of the present invention, in structure
Dividing includes: acyl group leucine, acyl group valine, acylphenylalanines, acyl-proline, acylalaninies, acyl group isoleucine,
Acyl Tyrosine, acylglycine, acyl group methionine, acyl-lysine, acyl group serine, acyl group asparagine, acyl group day
L-aminobutanedioic acid, sulfonylmethyl cysteine, pyroglutamic acid.
Form amino acid quaternary ammonium carboxylate to make amino acid become anion and quaternary ammonium group, through frequently with method be
Make amino acid acetylation:
Some amino acid residues have side shoot chain, these side shoot chain belt charges and also have chemical activity, such as cystine, rely ammonia
Acid, asparatate.In order to synthesize amino acid quaternary ammonium carboxylate of the invention, the chemical activity of side shoot chain need be eliminated.It is right
In cystine, a methyl generation-SCH can be met on its sulfydryl (- SH)3Group.Sulphydryl activity is high, can cause some covalent
Learn reaction.And-SCH3Group is stablized, no chemical activity.
Fig. 1 is that synthetic method synthesis DAPC is related to using the present invention, and main indexes are by having peak value at 2.0~2.5PPM
Summation and the ratio of peak value at 0.8~1.0PPM are about 4:6.
Fig. 2 is using synthetic method synthesis DAPC of the invention, and main indexes are by having peak value at 2.0~2.5PPM
Summation and the ratio of peak value at 0.8~1.0PPM are about 4:6.
Fig. 3 is using synthetic method synthesis DAAC of the invention, and main indexes are by having peak value at 1.9~2.1PPM
Ratio with peak value at 0.8~1.0PPM is about 3:6.
Fig. 4 is synthesized according to specific synthesis step disclosed in granted patent (patent No.: ZL 201210166719.3)
DAPC, main indexes are about 2.1 by there is the ratio of peak value at peak value summation and 0.8~1.0PPM at 2.0~2.5PPM:
6 < 4:6.
Fig. 5 is synthesized according to specific synthesis step disclosed in granted patent (patent No.: ZL 201210166719.3)
DAPC, main indexes are about 2.7 by there is the ratio of peak value at peak value summation and 0.8~1.0PPM at 2.0~2.5PPM:
6 < 4:6.
Fig. 6 is synthesized according to specific synthesis step disclosed in granted patent (patent No.: ZL 201210166719.3)
DAPC, main indexes are about 2.3 by there is the ratio of peak value at peak value summation and 0.8~1.0PPM at 2.0~2.5PPM:
6 < 4:6.
In Fig. 1, Fig. 2, Fig. 4, Fig. 5, Fig. 6, had peak value summation and peak value at 0.8~1.0PPM at 2.0~2.5PPM
Ratio is about that 4:6 refers to No. 3 positions and the double decyls two of 4 hydrogen and cationic portion on No. 4 positions on anion part pyroglutamic acid
The ratio of 6 hydrogen on two methyl of methyl ammonium duplex ends illustrates the ratio of anion and cation if meeting 4:6
Value is to constitute compound according to the ratio of 1:1, illustrates that purity is very high.If not meeting the ratio, illustrate anion and sun from
The ratio of son constitutes compound not in accordance with the ratio of 1:1, illustrates that compound purity is not high.
Thus we are it follows that the synthetic method used synthesizes DAPC, better than according to (the patent No.: ZL of granted patent
201210166719.3) disclosed in synthesis step synthesize DAPC.
In Fig. 3, the ratio of peak value is about that 1:6 refers to anion at had peak value and 0.8~1.0PPM at 1.9~2.1PPM
The double dimethylammonium duplex ends of 3 hydrogen and cationic portion on the N- acetylalanine of part on the methyl of acetyl group end
Two methyl on the ratio of 6 hydrogen illustrate that the ratio of anion and cation is ratio according to 1:1 if meeting 3:6
Value constitutes compound, illustrates that purity is relatively high.If not meeting the ratio, illustrate that the ratio of anion and cation is not
Compound is constituted according to the ratio of 1:1, illustrates that compound purity is not relatively high.
The synthetic method synthesis DAAC that we can be utilized as a result, meets zwitterion 1:1 composition, illustrates pure
It spends relatively high.
It is an advantage of the invention that overcoming the synthetic method of granted patent (patent No.: ZL 201210166719.3)
Disadvantage, realize: 1. simplify synthesis step；2. toxicity can be used relatively low and be easier to recycling, tractable organic reagent；3.
Improve the purity of amino acid quaternary ammonium carboxylate.
Detailed description of the invention
Fig. 1 is the NMR figure of 1 products therefrom of embodiment.
Fig. 2 is the NMR figure of 2 products therefrom of embodiment.
Fig. 3 is the NMR figure of 3 products therefrom of embodiment.
Fig. 4 is the NMR figure of 1 products therefrom of comparative example.
Fig. 5 is the NMR figure of 2 products therefrom of comparative example.
Fig. 6 is the NMR figure of 3 products therefrom of comparative example.
Specific embodiment
The present invention will be further described with embodiment and comparative example below, but the scope of the present invention is not by lifting implementation
The limitation of example.
Embodiment 1
It synthesizes double decyl dimethyl oxygen and closes proline ammonium DAPC (Proline, 5-oxo-, ion (1-), N-decyl-N, N-
Dimethyl-1-decanaminium (1:1)) specific synthesis step it is as follows:
Preparation solution A: dehydrated alcohol 10mL is taken, the KOH of 0.0024mol is dissolved in wherein, and is heated to 30 DEG C, is sufficiently stirred
It mixes to KOH and is completely dissolved to get solution A；
Preparation solution B: dehydrated alcohol 10mL is taken, at room temperature by the double-track suspended self-propelled conveyor of 0.0024mol
It is added thereto, is stirred well to double-track suspended self-propelled conveyor and is completely dissolved to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 5 minutes, the chlorination insoluble in dehydrated alcohol is generated
Potassium precipitating, sufficiently filtering or centrifugation removal potassium chloride precipitating, obtain double decyl dimethyl Ammonias to get solution C；
Preparation solution D: the pyroglutamic acid of 0.0024mol is dissolved in dehydrated alcohol, solution is made to get solution D；
Preparation solution E: solution C and solution D are sufficiently mixed to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAPC.
Take appropriate product to be NMR (see Fig. 1).
Embodiment 2
It synthesizes double decyl dimethyl oxygen and closes proline ammonium DAPC (Proline, 5-oxo-, ion (1-), N-decyl-N, N-
Dimethyl-1-decanaminium (1:1)) specific synthesis step it is as follows:
Preparation solution A: dehydrated alcohol 20mL is taken, the KOH of 0.005mol is dissolved in wherein, and is heated to 30 DEG C, is sufficiently stirred
It mixes to KOH and is completely dissolved to get solution A；
Preparation solution B: dehydrated alcohol 15mL is taken, at room temperature adds the double-track suspended self-propelled conveyor of 0.005mol
Enter wherein, is stirred well to double-track suspended self-propelled conveyor and is completely dissolved to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 5 minutes, the chlorination insoluble in dehydrated alcohol is generated
Potassium precipitating, sufficiently filtering or centrifugation removal potassium chloride precipitating, obtain double decyl dimethyl Ammonias to get solution C；
Preparation solution D: the pyroglutamic acid of 0.005mol is dissolved in dehydrated alcohol, solution is made to get solution D；
Preparation solution E: solution C and solution D are sufficiently mixed to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAPC.
Take appropriate product to be NMR (see Fig. 2).
Embodiment 3
Synthesizing amino acid double-strand quaternary ammonium carboxylate is double decyl dimethyl N- acetylalanine ammonium DAAC (1-
Decanaminium,N-decyl-N,N-dimethyl-,salt with N-acetylalanine(1:1))
Preparation solution A: using dehydrated alcohol as solvent, the KOH of 0.0025mol is dissolved in wherein, and is heated to 20 DEG C~30
DEG C, it is stirred well to KOH and is completely dissolved to get solution A；
Prepare solution B: using dehydrated alcohol as solvent, at room temperature by double decyl dimethyl chlorinations of 0.0025mol
Ammonium is added thereto, and is stirred well to double-track suspended self-propelled conveyor and is completely dissolved to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 1~10 minute, is generated insoluble in dehydrated alcohol
Potassium chloride precipitating, sufficiently filtering or centrifugation removal potassium chloride precipitating, double decyl dimethyl Ammonias are to get solution C；
Preparation solution D: the N- acetylation alanine of 0.0025mol is dissolved in dehydrated alcohol, solution is made to get solution
D；
Preparation solution E: solution C and solution D are sufficiently mixed to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAAC.
Take appropriate product to be NMR (see Fig. 3).
Embodiment 4
Other amino acid quaternary ammonium carboxylates are available to be prepared with method, such as:
Double Decylamino carboxylate (N, N-dimethyl-N, the N-di-n-decylammonium N- of proline dimethyl
acetylated proline carboxylate)
Double Decylamino carboxylate (N, N-dimethyl-N, the N-di-n-decylammonium N- of phenylalanine dimethyl
acetylated phenylalanine carboxylate)
Double Decylamino carboxylate (N, N-dimethyl-N, the N-di-n-decylammonium N- of serine dimethyl
acetylated serine carboxylate)
Double Decylamino carboxylate N, N-dimethyl-N, the N-di-n-decylammonium N- of isoleucine dimethyl
acetylated isoleucine carboxylate
Double decyl carboxylate N, N-dimethyl-N, the N-di-n-decylammonium N- of cystine dimethyl
acetylated S-methyl cystine carboxylate
Pyroglutamic acid coconut oil dimethyl benzyl carboxylate N-Dodecyl-N, N-dimethyl-benzyl-ammonium-
5-oxopyrrolidine-2-carboxylate
Comparative example 1
Double decyls are synthesized according to the synthesis step disclosed in granted patent (patent No.: ZL 201210166719.3)
Dimethyl oxygen closes proline ammonium DAPC (Proline, 5-oxo-, ion (1-), N-decyl-N, N-dimethyl-1-
Decanaminium (1:1)):
1) NaOH for first weighing 0.03mol, is dissolved in deionized water, makes solution weight 30g, and cooling.
2) pyroglutamic acid 0.03mol is weighed again to be dissolved in the NaOH aqueous solution of above-mentioned 30g.Reaction product is sodium pyroglutamate
Aqueous solution obtains solution A.
3) it weighs 0.025mol didecyl Dimethy ammonium chloride to be dissolved in 160g deionized water, obtains solution B.
4) it mixes well A liquid and B liquid to obtain solution C.
5) quality of solution C is about 200g.
6) it takes solution C 200g that 400ml methylene chloride is added, and 10 grams of sodium chloride is added, sufficiently stir evenly, be put into extraction flask
In shake up rear stratification again 30 minutes.
7) it takes subnatant to vacuumize rotary evaporation 30 minutes, obtains product DAPC.
8) extraction is repeated three times.Obtain product DAPC.
9) appropriate product is taken to be NMR (see Fig. 4).
Comparative example 2
Double decyls two are synthesized according to synthesis step disclosed in granted patent (patent No.: ZL 201210166719.3)
Methyl oxygen closes proline ammonium DAPC (Proline, 5-oxo-, ion (1-), N-decyl-N, N-dimethyl-1-
Decanaminium (1:1)):
1) NaOH for first weighing 0.025mol, is dissolved in deionized water, makes solution weight 20g, and cooling.
2) pyroglutamic acid 0.025mol is weighed again to be dissolved in the NaOH aqueous solution of above-mentioned 20g.Reaction product is pyroglutamic acid
Sodium water solution obtains solution A.
3) it weighs 0.005mol didecyl Dimethy ammonium chloride to be dissolved in 130g deionized water, obtains solution B.
4) it mixes well A liquid and B liquid to obtain solution C.
5) quality of solution C is about 150g.
6) it takes solution C 150g that 400ml n-butanol is added, sufficiently stirs evenly, be put into extraction flask and shake up rear stratification 30 again
Minute.
7) it takes upper liquid to vacuumize rotary evaporation 30 minutes, obtains product DAPC.
8) extraction is repeated three times.Obtain product DAPC.
9) appropriate product is taken to be NMR (see Fig. 5).
Comparative example 3
Double decyls two are synthesized according to synthesis step disclosed in granted patent (patent No.: ZL 201210166719.3)
Methyl oxygen closes proline ammonium DAPC (Proline, 5-oxo-, ion (1-), N-decyl-N, N-dimethyl-1-
Decanaminium (1:1)):
1) LiOH for first weighing 0.025mol, is dissolved in deionized water, makes solution weight 20g, and cooling.
2) pyroglutamic acid 0.025mol is weighed again to be dissolved in the lithium hydroxide aqueous solution of above-mentioned 20g.Reaction product is Jiao Gu
Propylhomoserin sodium is water-soluble, obtains solution A.
3) it weighs 0.005mol didecyl Dimethy oronain to be dissolved in 130g deionized water, obtains solution B.
4) it mixes well A liquid and B liquid to obtain solution C.
5) quality of solution C is about 150g.
6) it takes solution C 150g that 400ml n-butanol is added, sufficiently stirs evenly, be put into extraction flask and shake up rear stratification 30 again
Minute.
7) it takes upper liquid to vacuumize rotary evaporation 30 minutes, obtains product DAPC.
8) extraction is repeated three times.Obtain product DAPC.
9) appropriate product is taken to be NMR (see Fig. 6).
Claims (4)
1. a kind of synthetic method of amino acid quaternary ammonium carboxylate, the amino acid quaternary ammonium carboxylate has following general formula:
A-COO- represents protected amino acid,
A represents different amino acid residues,
R1 and R2 represents straight chain, cycloalkanyl or H, and R1 and R2 may be the same or different,
It is characterized in that this method is according to the following steps:
(1), 1 part mole of alkali metal hydroxide is dissolved in the volatile organic solvent that temperature is 20 DEG C~30 DEG C, is obtained molten
Liquid A；
(2), 1 part mole of double-strand quaternary ammonium ammonium halide or single-stranded quaternary ammonium ammonium halide are dissolved in volatile organic solvent, is obtained
Solution B；
(3), obtained solution A and solution B above are sufficiently mixed, wherein the cation of alkali metal is generated with halogen family anion
Salt insoluble in volatile organic solvent, sufficiently filtering or centrifugation removal insoluble matter, obtain the ammonium hydroxide of quaternary ammonium containing double-strand or
The solution C of single-stranded quaternary ammonium ammonium hydroxide；
(4), acetylated amino acids are dissolved in volatile organic solvent, and allow the acetylation in acquired solution containing 1 part mole
Amino acid anion, obtains solution D；
(5), it obtained solution C will be mixed above with solution D, and remove insoluble matter, obtain solution E；
(6), the volatile organic solvent in solution E is removed, product amino acid quaternary ammonium carboxylate is obtained；
Described amino acid quaternary ammonium carboxylate includes the single-stranded quaternary ammonium carboxylate of amino acid and amino acid double-strand quaternary ammonium carboxylic acid
Salt.
2. synthetic method as described in claim 1, it is characterised in that: synthesis is in amino acid double-strand quaternary ammonium carboxylate
Double decyl dimethyl oxygen close proline ammonium DAPC (Proline, 5-oxo-, ion (1-), N-decyl-N, N-dimethyl-1-
Decanaminium (1:1)), synthesis step are as follows:
Preparation solution A: using dehydrated alcohol as solvent, 1 part mole of alkali metal hydroxide is added thereto, and is heated to 20 DEG C
It~30 DEG C, is stirred well to alkali metal hydroxide and is completely dissolved to get solution A；
It prepares solution B: using dehydrated alcohol as solvent, 1 part mole of double-track suspended self-propelled conveyor being added at room temperature
Wherein, double-track suspended self-propelled conveyor is stirred well to be completely dissolved to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 1~10 minute, the metal insoluble in dehydrated alcohol is generated
Chloride precipitating, sufficiently filtering or centrifugation removal metal chloride precipitating, obtain double decyl dimethyl Ammonias to get
Solution C；
Preparation solution D: 1 part mole of pyroglutamic acid is dissolved in dehydrated alcohol, solution is made to get solution D；
Preparation solution E: solution C and solution D are sufficiently mixed, and sufficiently filtering or centrifugation is to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAPC.
3. synthetic method as described in claim 1, it is characterised in that synthesis is in amino acid double-strand quaternary ammonium carboxylate
Double decyl dimethyl N- acetylalanine ammonium DAAC (1-Decanaminium, N-decyl-N, N-dimethyl-, salt
With N-acetylalanine (1:1)), synthesis step are as follows:
Preparation solution A: using dehydrated alcohol as solvent, 1 part mole of alkali metal hydroxide is added thereto, and is heated to 20 DEG C
It~30 DEG C, is stirred well to alkali metal hydroxide and is dissolved completely in dehydrated alcohol to get solution A；
It prepares solution B: using dehydrated alcohol as solvent, 1 part mole of double-track suspended self-propelled conveyor being added at room temperature
Wherein, double-track suspended self-propelled conveyor is stirred well to be dissolved completely in dehydrated alcohol to get solution B；
Solution C: mixed solution A and solution B at room temperature is prepared, is stirred 1~10 minute, the metal insoluble in dehydrated alcohol is generated
Chloride precipitating, sufficiently filtering or centrifugation removal metal chloride precipitating, obtain double decyl dimethyl Ammonias to get
Solution C；
Preparation solution D: 1 part mole of acetylation alanine is dissolved in dehydrated alcohol, solution is made to get solution D；
Preparation solution E: solution C and solution D are sufficiently mixed, and sufficiently filtering or centrifugation is to get solution E；
It obtains product: with the dehydrated alcohol of Rotary Evaporators recycling solution E, obtaining product DAAC.
4. the synthetic method of amino acid quaternary ammonium carboxylate as described in claim 1, it is characterised in that in the general formula R1 or/
It is the alkyl of 8~18 carbon atoms with R2.
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