Piperazine dihydrochloride

Benzhydrylamine Derivatives Attachment of piperazine nitrogen directly to a benzhydryl carbon leads to a pair of compounds which show vasodilator activity, and which should be useful in disease states marked by impaired blood circulation. Reaction of piperonyl chloride (18) with a mixture of piperazine and piperazine dihydrochloride leads to the monoalkylation product (19). (It may be supposed that the mixture of free base and salt equilibrates to the monobasic salt, thus making the second amine less nucleophilic.) Alkylation of 19 by means of benzhydryl chloride then... 

Pepys, J., Pickering, C.A., and Loudon, H.W., Asthma due to inhaled chemical agents piperazine dihydrochloride, Clin Allergy, 2, 189, 1972. 

Little information exists on the toxicology of piperazine dihydrochloride in humans or in animals. Acute human exposures to the dust have reportedly resulted in irritation to the eyes, mild to moderate skin burns, and sensitization. Exposure levels and duration were not available. Occupational exposures have been associated with occasional cases of asthma. In one factory, several cases of asthma were precipitated by a time-weighted average (TWA) exposure of 1.2mg/m although there were brief exposure peaks of lOOmg/m or higher. There were no new cases noted in a workplace... 

The 2003 ACGIH threshold limit valuetime-weighted average (TLV-TWA) for piperazine dihydrochloride is 5mg/mh... 

ACGIH Piperazine dihydrochloride. Documentation of the TLVs and BEIs, 6th ed, pp 1276-1277. Cincinnati, OH, American Conference of Governmental Industrial Hygienists, 1991... 

Health Safety Executive Regulatory Impact Assessments Proposed Maximum Exposure Limit for Piperazine and Piperazine Dihydrochloride. Jan. 2001. Accessed 4/17/02. . 

Bis(allylamino)-2-chloro-s-triazine l-p,p -Difluorobenzhydryl piperazine dihydrochloride Sodium hydroxide... 

Stage 4 Preparation of l-[2-Phenyl-2-Methoxy]-Ethyl-4-[3-Phenyl-3-Hydroxypropyl]-Piperazine Dihydrochloride -In a double-neck flask equipped with a thermometer and a mechanical stirrer, there is placed in suspension in 800 ml of methanol, 233 grams of l-[2-phenyl-2-methoxy]-ethyl-4-[2-benzoyl-ethyl]-piperazine dihydrochloride (0.55 mol). It is cooled to approximately 5°C, and 46 grams of NaOH pellets dissolved in 80 ml of H20 are added. When the temperature is about 5°C, one addition of 29.2 grams of sodium borohydride in 40 ml H20 is made. The ice-bath is then removed and stirring continued at ambient temperature for 6 hours. 

After evaporation of the solvent, a very thick, colorless oil is obtained. This base is dissolved by 200 ml of absolute ethanol and the quantity of HCI to obtain the dihydrochloride is added. It is left for a few hours over ice, dried, washed with approximately 100 ml of anhydrous ether in order to obtain 190 to 195 grams of l-[2-phenyl-2-methoxy]-ethyl-4-[3-phenyl-3-hydroxy]-propyl-piperazine dihydrochloride after drying at 60°C in vacuo. The yield is 80%. It is recrystallized from absolute ethanol. The product is in the form of white crystalline powder, soluble in water, slightly soluble in alcohol, insoluble in ethyl acetate. 

The oily residue is dissolved in 480 parts of anhydrous diisopropyl ether. This solution is boiled with activated charcoal, filtered and to the clear filtrate is added an excess of 2-propanol, previously saturated with gaseous hydrogen chloride. The precipitated salt is filtered off and recrystallized from a mixture of 2-propanol and ethanol, yielding l-cinnamyl-4-(di-p-fluorobenzhydryl) piperazine dihydrochloride, MP 251.5°C. 

Hydrogen Hydrobromic acid Sodium hydride l-(4-Methoxyphenyl)piperazine dihydrochloride... 

A mixture of 13.4 parts of l-(4-methoxyphenyl)piperazine dihydrochloride, 7.9 parts of l-chloro-4-nitrobenzene, 10 parts of potassium carbonate and 90 parts of N,N-dimethylformamide is stirred and refluxed overnight. The reaction mixture is diluted with water and the product is extracted twice with trichloromethane. The residue is triturated in 4-methyl-2-pentanone. The product is filtered off and crystallized from 1,4-dioxane, yielding 10.5 parts (67%) of l-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine melting point 195.1°C. 

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