A method for recovering crude perilla from perilla mother liquor

Abstract

The application discloses a method for recovering perillyl alcohol crude product from perillyl alcohol mother liquor, comprising the following steps: (1) perillyl alcohol in the perillyl alcohol mother liquor is deoximated under the catalysis of acid to generate perillyl aldehyde crude product; (2) perillyl aldehyde is subjected to distillation and impurity removal to obtain perillyl aldehyde with high content; (3) the purified perillyl aldehyde is added into a hydroxylamine solution to perform oximation reaction, and perillyl alcohol crude product can be obtained after the reaction. The method can remove impurities through the distillation method after the perillyl alcohol mother liquor is converted into perillyl aldehyde crude product, and then the oximation is performed again to obtain perillyl alcohol crude product. About 50% of perillyl alcohol in the perillyl alcohol mother liquor can be recovered, and the total yield of perillyl alcohol industrial production is increased.

Description

Technical Field

[0001] This invention belongs to the technical field of perilla lepidium synthesis, specifically relating to a method for recovering crude perilla lepidium from perilla lepidium mother liquor. Background Technology

[0002] Perilla oleracea, scientifically known as (E)-4-(1-methylvinyl)cyclohexenyl-1-carboxaldehyde oxime, also called perilla sugar or perilla extract, is a white needle-like crystal with the distinctive sweet aroma of perilla grass. It is a high-sweetness sweetener. Perilla oleracea is an aldehyde oxime compound. Due to its low water solubility and perceptible minty-licorice off-flavor, it is widely used in the tobacco industry to suppress off-flavors, enhance aroma, and create a mellow and pleasant aftertaste.

[0003] The initial synthesis of perilla stigma involved the oximation of perilla aldehyde extracted from the natural Lamiaceae plant, perilla. However, the low aldehyde content in perilla stigma limited its industrial production. Later, researchers developed chemical synthesis methods for perilla stigma, including: 1. A total synthesis using 5-methyl-3-hexen-2-one or substituted phenol as raw materials. This method requires rare raw materials, involves multiple reaction steps, and results in a low overall yield. 2. A semi-synthetic method using α-pinene from turpentine oil as a raw material. This method has a shorter reaction time and a better yield, but α-pinene oxygen... The reaction to myrtol uses highly toxic selenium dioxide as an oxidant, and the reaction of myrtol to perillol requires high temperature (430℃) and vacuum (0.67~0.90kPa), so it is not suitable for industrial production; 3. Using β-pinene as the starting material, the alcohol is synthesized by epoxidation and ring opening, then oxidized to obtain an aldehyde, and finally oximeized to obtain perillyl. The raw materials in this method are inexpensive and readily available, the synthetic route is short, all synthetic reactions can be carried out in batches and the operation is simple, which is convenient for industrial production. Therefore, this method is often used for the industrial production of perillyl.

[0004] In existing industrial production processes for perilla lepidium, specifically the third method mentioned above, the process of preparing perilla lepidium from β-pinene involves the final oxime oxidation of perilla aldehyde to obtain perilla lepidium. A portion of perilla lepidium remains in the mother liquor due to its high impurity content, making precipitation difficult and resulting in a low yield in current perilla lepidium production methods. Recovering this portion of perilla lepidium in industrial production would significantly improve the yield. Therefore, how to recover crude perilla lepidium from the mother liquor to increase the perilla lepidium yield is a pressing issue that needs to be addressed. Summary of the Invention

[0005] The purpose of this invention is to provide a method for recovering crude perilla from perilla mother liquor. By deoximating the perilla in the mother liquor to aldehyde, followed by distillation purification, and finally oximating it back to perilla, most of the perilla in the mother liquor can be recovered. This method improves the yield of perilla and is safe and simple to operate, making it suitable for large-scale industrial production.

[0006] The above-mentioned objectives of the present invention can be achieved through the following technical solutions:

[0007] A method for recovering crude perilla from perilla mother liquor includes the following steps:

[0008] (1) Deoxime of perilla: Perilla mother liquor and aldehyde aqueous solution are added to a nonpolar solvent, and a small amount of inorganic acid is added for catalysis. The reaction is carried out by heating to obtain the reaction product.

[0009] (2) The reaction product obtained in step (1) was allowed to stand and separate into layers to obtain organic phase A. The aqueous layer was extracted twice with a non-polar solvent to obtain organic phase B. Organic phase A and organic phase B were combined and concentrated to obtain crude perillaldehyde.

[0010] (3) The crude perillaldehyde was subjected to vacuum distillation to obtain the refined perillaldehyde;

[0011] (4) Add hydroxylamine hydrochloride to water, dissolve it, add an inorganic base to adjust the pH value, and then add the perilla aldehyde obtained in step (3). After oxime reaction, cool and crystallize to obtain crude perilla levator.

[0012] The perilla mother liquor of the present invention is obtained by sequentially epoxidizing, oxidizing and oximating β-pinene as raw material, wherein the perilla content in the perilla mother liquor is 10-15% by mass.

[0013] The mother liquor of perilla lepidium contains many impurities, making separation difficult. This invention addresses this by subjecting perilla lepidium to a deoxime reaction to obtain crude perilla aldehyde. The crude perilla aldehyde is then purified by vacuum distillation to obtain refined perilla aldehyde. This refined perilla aldehyde is then oxime-treated to obtain crude perilla lepidium, thus achieving the goal of recovering crude perilla lepidium from the mother liquor. This invention converts perilla lepidium into perilla aldehyde, purifies it by distillation to remove impurities, and finally oxime-treats it to obtain crude perilla lepidium, thereby recovering crude perilla lepidium from the mother liquor; effectively recovering 50% of the perilla lepidium product from the mother liquor.

[0014] In the method of the present invention:

[0015] Preferably, the nonpolar solvents in steps (1) and (2) are any one or more combinations of petroleum ether, cyclohexane, and n-hexane.

[0016] More preferably, the nonpolar solvent in steps (1) and (2) is cyclohexane.

[0017] Preferably, the mass ratio of the perilla seed mother liquor to the non-polar solvent in step (1) is 1:(2-8).

[0018] More preferably, the mass ratio of the perilla seed mother liquor to the non-polar solvent in step (1) is 1:5.

[0019] Preferably, the inorganic acid in step (1) is any one or a combination of two of sulfuric acid and nitric acid.

[0020] More preferably, the inorganic acid is sulfuric acid.

[0021] Preferably, in step (1), the molar fraction of the inorganic acid is 1-30%.

[0022] More preferably, the molar fraction of the inorganic acid is 2.5%.

[0023] Preferably, the aldehyde aqueous solution in step (1) is any one or a combination of formaldehyde aqueous solution, acetaldehyde aqueous solution and glyoxal aqueous solution.

[0024] More preferably, the aldehyde aqueous solution is a formaldehyde aqueous solution.

[0025] Preferably, the molar ratio of the aldehyde aqueous solution and the perilla mother liquor in step (1) is (1-5):1.

[0026] More preferably, the molar ratio of the aldehyde aqueous solution to the perilla mother liquor is 2:1.

[0027] Preferably, the reaction temperature of the deoxime reaction in step (1) is 70–90°C.

[0028] More preferably, the reaction temperature of the deoxime reaction is 80°C.

[0029] Preferably, the reaction time of the deoxime reaction in step (1) is 2 to 8 hours.

[0030] More preferably, the reaction time for the deoxime reaction is 4 hours.

[0031] Preferably, the distillation temperature of the vacuum distillation in step (3) is 80-120°C.

[0032] More preferably, the distillation temperature of the vacuum distillation is 110°C.

[0033] Preferably, the vacuum degree of the reduced pressure distillation in step (3) is 40 to 400 Pa.

[0034] More preferably, the vacuum degree is 40 Pa.

[0035] Preferably, the inorganic base in step (4) is any one or a combination of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium bicarbonate.

[0036] More preferably, the inorganic base is sodium carbonate.

[0037] Preferably, the pH value in step (4) is 5.9 to 6.5;

[0038] More preferably, the pH value is 6.0.

[0039] Preferably, the molar ratio of perillaldehyde to hydroxylamine hydrochloride in the perillaldehyde concentrate in step (4) is 1:(1.5-2);

[0040] More preferably, the molar ratio of perillaldehyde to hydroxylamine hydrochloride in the perillaldehyde premium product is 1:1.5.

[0041] Preferably, the oxime reaction time in step (4) is 1 to 6 hours;

[0042] More preferably, the oxime reaction time is 4 hours.

[0043] Preferably, the oxime reaction temperature in step (4) is 30–70°C;

[0044] More preferably, the oxime reaction temperature is 40°C.

[0045] Compared with the prior art, the present invention has the following beneficial effects:

[0046] (1) This invention involves reacting perilla leaves in the mother liquor with an aldehyde solution to undergo a deoxime reaction, converting the oxime into aldehyde. The aldehyde is then purified by distillation to remove impurities, yielding a high-content perilla aldehyde concentrate. Finally, the concentrate is oximeized back into crude perilla leaves. Approximately 50% of the perilla leaves in the mother liquor can be recovered, thus increasing the overall yield of industrial-scale perilla leaf production.

[0047] (2) The present invention uses a non-polar solvent to carry out the deoxime reaction, which replaces the existing use of nitromethane, a dangerous chemical that is prone to explosion, as the reaction solvent, thus avoiding the risks associated with the use of dangerous chemicals that are prone to explosion in industrial applications. Detailed Implementation

[0048] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited to the following embodiments.

[0049] Unless otherwise specified, all raw materials used in the following examples are commercially available products.

[0050] The specific preparation method of the perilla lepidium mother liquor described in the following examples is as follows: β-pinene is used as a raw material, and peracetic acid is added to carry out an epoxidation reaction to obtain epoxide pinane; epoxide pinane is dissolved in DMF, a catalyst is added, and an isomerization reaction is carried out. After the reaction is completed, the solvent is recovered to obtain perillaldehyde; perillaldehyde is dissolved in dichloroethane, an oxidant is added, and the reaction is carried out. After the reaction is completed, the solvent is recovered to obtain crude perillaldehyde; then, hydroxylamine is added to the crude perillaldehyde for oximeization, and after cooling, crystallization, and filtration, perilla lepidium mother liquor is obtained.

[0051] Example 1

[0052] (1) Add 750 kg of cyclohexane, 136 kg of formaldehyde aqueous solution (content 40%) and 2.3 kg of sulfuric acid to 1000 kg of perilla lepidium mother liquor (mass content: 15%) and stir vigorously. Heat to 80°C and reflux for 4 h. Then let stand to separate into layers to obtain the upper organic phase A. Use 300 kg of cyclohexane to extract the lower aqueous layer twice. Combine the obtained upper organic phases and recover cyclohexane by atmospheric distillation at 85°C to obtain 1080 kg of crude perilla aldehyde (mass content 12%).

[0053] (2) 1080 kg of crude perillaldehyde (content 12%) was concentrated by thin film at 110℃ and 100 Pa to obtain 166 kg of refined perillaldehyde (content 70%).

[0054] (3) Add 80.8 kg of hydroxylamine hydrochloride to the reaction vessel, then add 580 L of water. After the hydroxylamine hydrochloride is completely dissolved, add sodium carbonate to adjust the pH to 6.0. Heat to 40 °C, and add 166 kg of perillaldehyde concentrate (mass content: 70%) dropwise. After reacting for 4 h, allow it to stand and separate into layers, obtaining the upper organic phase. Cool and crystallize to obtain 81.2 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor is 48.7%.

[0055] Example 2

[0056] (1) Add 750 kg of cyclohexane, 204.5 kg of formaldehyde aqueous solution (content 40%) and 2.3 kg of sulfuric acid to 1000 kg of perilla lepidium mother liquor (mass content: 15%) and stir vigorously. Heat to 80°C and reflux for 4 h. Then let stand to separate into layers to obtain the upper organic phase A. Use 300 kg of cyclohexane to extract the lower aqueous layer twice. Combine the obtained upper organic phases and recover cyclohexane by atmospheric distillation at 85°C to obtain 1100 kg of crude perilla aldehyde (mass content 12%).

[0057] (2) 1100 kg of crude perillaldehyde (content 12%) was concentrated by thin film at 110℃ and 100 Pa to obtain 169.7 kg of refined perillaldehyde (content 70%).

[0058] (3) Add 82.8 kg of hydroxylamine hydrochloride to the reaction vessel, then add 594 L of water. After the hydroxylamine hydrochloride is completely dissolved, add sodium carbonate to adjust the pH to 6.0. Heat to 40 °C, and add 169.7 kg of perillaldehyde concentrate (mass content: 70%) dropwise. After reacting for 4 h, allow it to stand and separate into layers, obtaining the upper organic phase. Cool and crystallize to obtain 83.2 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor is 49.9%.

[0059] Example 3

[0060] (1) Add 750 kg of cyclohexane, 136 kg of formaldehyde aqueous solution (content 40%) and 8.9 kg of sulfuric acid to 1000 kg of perilla lepidium mother liquor (mass content: 15%) and stir vigorously. Heat to 80°C and reflux for 4 h. Then let stand to separate into layers to obtain the upper organic phase A. Use 300 kg of cyclohexane to extract the lower aqueous layer twice. Combine the obtained upper organic phases and recover cyclohexane by atmospheric distillation at 85°C to obtain 1010 kg of crude perilla aldehyde (mass content 12.1%).

[0061] (2) 1080 kg of crude perillaldehyde (content 12%) was concentrated by thin film at 110℃ and 100 Pa to obtain 157.1 kg of refined perillaldehyde (content 70%).

[0062] (3) 76.7 kg of hydroxylamine hydrochloride was added to the reaction vessel, followed by 550 L of water. After the hydroxylamine hydrochloride was completely dissolved, sodium carbonate was added to adjust the pH to 6.0. The mixture was heated to 40 °C, and 157.1 kg of perillaldehyde concentrate (mass content: 70%) was added dropwise. After reacting for 4 h, the mixture was allowed to stand and separate into layers, yielding the upper organic phase. Upon cooling, crystals were precipitated, yielding 77 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor was 46.2%.

[0063] Example 4

[0064] (1) Add 750 kg of cyclohexane, 136 kg of formaldehyde aqueous solution (content: 40%) and 2.3 kg of sulfuric acid to 1000 kg of perilla mother liquor (mass content: 15%) and stir vigorously. Heat to 80°C and reflux for 8 hours. Then let stand to separate into layers to obtain the upper organic phase A. Use 300 kg of cyclohexane to extract the lower aqueous layer twice. Combine the obtained upper organic phases and recover cyclohexane by atmospheric distillation at 85°C to obtain 1048 kg of crude perilla aldehyde (mass content: 11.8%).

[0065] (2) 1048 kg of crude perillaldehyde (content 11.8%) was concentrated by thin film at 110℃ and 100 Pa to obtain 159 kg of refined perillaldehyde (content 70%).

[0066] (3) 77.5 kg of hydroxylamine hydrochloride was added to the reaction vessel, followed by 556 L of water. After the hydroxylamine hydrochloride was completely dissolved, sodium carbonate was added to adjust the pH to 6.0. The mixture was heated to 40 °C, and 159 kg of perillaldehyde concentrate (mass content: 70%) was added dropwise. After reacting for 4 h, the mixture was allowed to stand and separate into layers, yielding the upper organic phase. Upon cooling, crystals were precipitated, yielding 77 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor was 46.2%.

[0067] Example 5

[0068] (1) 750 kg of n-hexane, 136 kg of formaldehyde aqueous solution (content 40%) and 2.3 kg of sulfuric acid were added to 1000 kg of perilla mother liquor (mass content: 15%) and stirred vigorously. The mixture was heated to 80 °C and refluxed for 4 h. Then it was allowed to stand and separate into layers to obtain the upper organic phase A. The lower aqueous layer was extracted twice with 300 kg of n-hexane. The obtained upper organic phases were combined and the n-hexane was recovered by distillation at 85 °C under normal pressure to obtain 1106 kg of crude perilla aldehyde (mass content 12%).

[0069] (2) 1106 kg of crude perillaldehyde (content 12%) was concentrated by thin film at 110℃ and 100 Pa to obtain 170 kg of refined perillaldehyde (content 70%).

[0070] (3) Add 82.9 kg of hydroxylamine hydrochloride to the reaction vessel, then add 595 L of water. After the hydroxylamine hydrochloride is completely dissolved, add sodium carbonate to adjust the pH to 6.0. Heat to 40℃ and add 170 kg of perillaldehyde concentrate (mass content: 70%) dropwise. After reacting for 4 h, allow it to stand and separate into layers to obtain the upper organic phase. Cool and crystallize to obtain 83.3 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor is 50%.

[0071] Example 6

[0072] (1) 750 kg of cyclohexane, 199.5 kg of acetaldehyde aqueous solution (content: 40%) and 2.3 kg of sulfuric acid were added to 1000 kg of perilla lepidium mother liquor (mass content: 15%) and stirred vigorously. The mixture was heated to 80 °C and refluxed for 4 h. Then it was allowed to stand and separate into layers to obtain the upper organic phase A. The lower aqueous layer was extracted twice with 300 kg of cyclohexane. The obtained upper organic phases were combined and the cyclohexane was recovered by distillation at atmospheric pressure at 85 °C to obtain 1077 kg of crude perilla aldehyde (mass content: 11.9%).

[0073] (2) 1077 kg of crude perillaldehyde (content 11.9%) was concentrated by thin film at 110℃ and 100 Pa to obtain 164.8 kg of refined perillaldehyde (content 70%).

[0074] (3) Add 80.3 kg of hydroxylamine hydrochloride to the reaction vessel, then add 576 L of water. After the hydroxylamine hydrochloride is completely dissolved, add sodium carbonate to adjust the pH to 6.0. Heat to 40℃ and add 164.8 kg of perillaldehyde concentrate (mass content: 70%) dropwise. After reacting for 4 h, allow it to stand and separate into layers, obtaining the upper organic phase. Cool and crystallize to obtain 80.7 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor is 48.5%.

[0075] Example 7

[0076] (1) Add 750 kg of cyclohexane, 136 kg of formaldehyde aqueous solution (content 40%) and 2.3 kg of sulfuric acid to 1000 kg of perilla mother liquor (mass content: 15%) and stir vigorously. Heat to 90°C and reflux for 4 h. Then let stand to separate into layers to obtain the upper organic phase A. Use 300 kg of cyclohexane to extract the lower aqueous layer twice. Combine the obtained upper organic phases and recover cyclohexane by atmospheric distillation at 85°C to obtain 1049 kg of crude perilla aldehyde (mass content 12%).

[0077] (2) 1049 kg of crude perillaldehyde (content 12%) was concentrated by thin film at 110℃ and 100 Pa to obtain 161.8 kg of refined perillaldehyde (content 70%).

[0078] (3) 79 kg of hydroxylamine hydrochloride was added to the reaction vessel, followed by 566 L of water. After the hydroxylamine hydrochloride was completely dissolved, sodium carbonate was added to adjust the pH to 6.0. The mixture was heated to 40 °C, and 161.8 kg of perillaldehyde concentrate (mass content: 70%) was added dropwise. After reacting for 4 h, the mixture was allowed to stand and separate into layers, yielding the upper organic phase. Upon cooling, crystallization was observed, yielding 79.2 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor was 47.5%.

[0079] Example 8

[0080] (1) Add 750 kg of cyclohexane, 272 kg of formaldehyde aqueous solution (content 40%) and 2.3 kg of sulfuric acid to 1000 kg of perilla mother liquor (mass content: 15%) and stir vigorously. Heat to 80°C and reflux for 4 h. Then let stand to separate into layers to obtain the upper organic phase A. Use 300 kg of cyclohexane to extract the lower aqueous layer twice. Combine the obtained upper organic phases and recover cyclohexane by atmospheric distillation at 85°C to obtain 1070 kg of crude perilla aldehyde (mass content 11%).

[0081] (2) 1070 kg of crude perillaldehyde (content 11%) was concentrated by thin film at 110℃ and 100 Pa to obtain 151 kg of refined perillaldehyde (content 70%).

[0082] (3) 73.7 kg of hydroxylamine hydrochloride was added to the reaction vessel, followed by 528 L of water. After the hydroxylamine hydrochloride was completely dissolved, sodium carbonate was added to adjust the pH to 6.0. The mixture was heated to 40 °C, and 151 kg of perillaldehyde concentrate (mass content: 70%) was added dropwise. After reacting for 4 h, the mixture was allowed to stand and separate into layers, yielding the upper organic phase. Upon cooling, crystals were precipitated, yielding 74 kg of crude perillaldehyde (content: 90%). The recovery rate of crude perillaldehyde in the perillaldehyde mother liquor was 44.3%.

[0083] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for recovering a perillyl alcohol crude product from a perillyl alcohol mother liquor, characterized in that, The method comprises the following steps: (1) perilla alcohol deoximation: adding a perilla alcohol mother liquor and an aqueous aldehyde solution into a non-polar solvent, adding an inorganic acid for catalysis, heating for reaction, and obtaining a reaction product; (2) standing and separating the reaction product obtained in step (1) into an organic phase A, extracting the aqueous layer twice with a non-polar solvent to obtain an organic phase B, combining the organic phase A and the organic phase B, and concentrating to obtain a perilla aldehyde crude product; (3) performing vacuum distillation on the perilla aldehyde crude product to obtain a perilla aldehyde fine product; (4) adding hydroxylamine hydrochloride into water, dissolving, adding an inorganic base to adjust the pH value, adding the perilla aldehyde fine product obtained in step (3), and performing oximation reaction, and cooling and crystallizing to obtain a perilla alcohol crude product. In steps (1) and (2), the non-polar solvent is any one or a combination of multiple of petroleum ether, cyclohexane and n-hexane; in step (1), the perilla alcohol mother liquor is a perilla alcohol mother liquor obtained by performing epoxidation, isomerization, oxidation and oximation reaction on β-pinene as a raw material, and then performing cooling and crystallization and filtering; the content of perilla alcohol in the perilla alcohol mother liquor is 10-15% by mass ratio.

2. The method for recovering perillyl alcohol crude product from perillyl alcohol mother liquor according to claim 1, characterized in that, In step (1), the mass ratio of the perilla alcohol mother liquor to the non-polar solvent is 1:(2-8).

3. The method for recovering perilla piperita crude product from perilla piperita mother liquor according to claim 1, characterized in that, The amount-of-substance fraction of the inorganic acid is 1-30%.

4. The method for recovering perillyl alcohol crude product from perillyl alcohol mother liquor according to claim 1, characterized in that, In step (1), the molar ratio of the aqueous aldehyde solution to the perilla alcohol mother liquor is (1-5):

1.

5. The method for recovering perillyl alcohol crude product from perillyl alcohol mother liquor according to claim 1, characterized in that, In step (1), the reaction temperature of the deoximation reaction is 70-90°C, and the reaction time of the deoximation reaction is 2-8h.

6. The method for recovering perilla piperita crude product from perilla piperita mother liquor according to claim 1, characterized in that, In step (3), the temperature of the vacuum distillation is 80-120°C.

7. The method for recovering perilla piperita crude product from perilla piperita mother liquor according to claim 1, characterized in that, In step (3), the vacuum degree of the vacuum distillation is 40-400 pa.

8. The method for recovering perillyl alcohol crude product from perillyl alcohol mother liquor according to claim 1, characterized in that, In step (4), the inorganic base is added to adjust the pH value to 5.9-6.

5.

9. The method for recovering perillyl alcohol crude product from perillyl alcohol mother liquor according to claim 1, characterized in that, In step (4), the molar ratio of perilla aldehyde contained in the perilla aldehyde fine product to hydroxylamine hydrochloride is 1:(1.5-2).