Piperazine hydrochloride

Piperazine hydrochloride is produced by conversion of piperazine hydrate with hydrochloric acid. The dry solid product is broken up, then milled and sieved. Piperazine products may be present in the air as vapours or as dust. 

Two industrial chemists suffering from non-immediate rhinitis and asthma on exposure gave similar reactions to a simulated occupational provocation test (Pepys et al. 1972c). These reactions were inhibited by inhalation of sodium cromoglycate. The slow development of reactions in these cases may make it difficult to identify the causal exposure and the provocation tests are therefore of great value. Cutaneous and respiratory sensitivity to piperazine products was reported from many factories by McCullagh (1968). 

Antibiotic Dusts Ampicillin, Benzylpenicillin, 6-AminopeniciIlanic Acid and Related Substances 

Sensitisation of workers engaged in the manufacture of antibiotics by the preparations which may be present in the air is not uncommon. 

Individual patients will be discussed to illustrate the specificity of their sensitivities, for which they provide valuable models for other such studies (Davies et al. 1974). The test method consisted of simulated occupational exposure to atmospheric dusts of the particular agents. 

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Chemical Name 1-[(4-Chlorophenvl)phenylmethyl] 4-[(3-methylphenyl)methyl] piperazine hydrochloride... 

To a solution of 17.2g (0.10 mol) of 3-bromopropionyl chloride in 100 ml of anhydrous benzene was added dropwise with stirring a solution of 8.6 g (0.10 mol) of anhydrous piperazine in 20 ml of dry chloroform over a period of 30 minutes. The temperature rose spontaneously to 45°C during the addition. After the temperature ceased to rise, stirring was continued for another hour. The reaction mixture was then filtered to remove the piperazine hydrochloride by-product. The filtrate was evaporated to dryness and the residue recrystallized from ethanol to obtain the desired N,N -bis-(3-bromopropionyl) piperazine as a white crystalline sol id melting at 103°C to 104°C. The identity of the product was further established by elemental analysis. 

H3C" °CH3 rk-CH, Ln c6h5 2,2-Dimethyl-3-phenyl-l- acetyl-piperazin- Hydrochlorid 90 (F 237-238°) 2... 

CN l-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-[(2,3-dihydro-l,4-benzodioxin-2-yl)carbonyl]piperazine hydrochloride... 

N,N -Dinifro-piperazine, O2N.NC4H8N.NO2 mw 176.14, N 31.81% ndls (from glac acet ac or eth acet), mp 215°, dec on prolonged heating at its mp readily sol in hot xylol mod sol in acet si sol in w, benz chlf can be prepd by treating piperazine hydrochloride with aq AgN02 soln, or by reaction of N,N -dibenzoyl-sulfonyl-piperazine with anhyd HNO3 (Ref 1). It is an expl compd not fully studied (Ref 2)... 

A mixture of 6.6 parts of y-chloro-4-fluorobutyrophenone and 12.5 parts of 1-(2-methoxyphenyl)piperazine, heated for 10 hours at a temperature of 110°C. The reaction mixture is treated with 800 parts of ether and filtered. The ether layer is washed with water, dried over anhydrous potassium carbonate and filtered, whereupon hydrogen chloride gas is introduced into the solution. The precipitate is collected on a filter and dissolved in a mixture of 240 parts of 2-propanol and 80 parts of acetone to yield l-[y-(4-fluorobenzoyl)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride. This monohydrochloride is collected on a filter and dissolved in 240 parts of 2-propanol. Anhydrous, gaseous hydrogen chloride is passed through the solution. On cooling, the l-[y-(4-fluorobenzoyl)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride precipitates. 

The reaction mixture was cooled to 90°C and diluted with ethyl acetate. The solid was filtered off, washed with ethyl acetate and dried. So the l-[5-(l-benzopyran-2-one)]piperazine hydrochloride was obtained, melting point 250°C (dec. recrystallized from ethanol). 

Chemical Name l-[Bis(4-fluorophenyl)methyl]-4(3-phenyl-2-propenyl) piperazine hydrochloride... 

A 25% NaOH solution (320 ml, 2.0 mol) is added dropwise to a stirred solution of l-(3-chlorophenyl)-piperazine hydrochloride (196.5 g, 1.0 mol) and l-bromo-3-chloropropane (99.0 ml, 1.0 mol) in acetone (200 ml) while maintaining temperature of 0°-10°C. After the addition is completed, the mixture is allowed to warm to room temperature and is stirred for 18 hours. The upper organic phase is then separated and concentrated under reduced pressure. The residual oil is taken up in 250 ml acetone and filtered. The filtrate is concentrated under reduced pressure and the oily residue is dissolved in 1 L of 15% boiling HCI solution. A viscous oil is separated from the cooled mixture and poured into 1 L of ice-H20 with vigorous stirring. 

To a solution of n-butanol (316 ml), water (24 ml) and N-(2-tetrahydrofuroyl)piperazine (20 g) were added, while stirring, 4-amino-2-chloro-6,7-dimethoxyquinazoline (22.2 g). The reaction mixture was heated to reflux and the reflux was maintained for about 9 h. Then the reaction mixture was cooled to room temperature and stirred at this temperature for about 10-12 h. The crystals were collected by filtration, washed with n-BuOH and dried in vacuo at 40-50°C to yield 40.1 g (94%) of the l-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(tetrahydrofuroyl)piperazine hydrochloride dihydrate... 

Two synthetic routes for 3-[4-[4-(2-methoxyphenyl)piperazin-l-yl]butyl]-thieno[3,4-d]pyrimidine-2,4-dione 316 were described by Russell et al. (90JHC1761). Carbamate 310a, prepared by treating a mixture of amine hydrochloride 309 and ethyl chloroformate with dilute sodium hydroxide, was reacted with 4-[(2-methoxyphenyl)piperazin-l-yl]butanamine 313 in the presence of trimethylaluminum/toluene. The yield of 316 was a modest 20%. However, when bromobutyl urea 314 was heated with l-(2-methoxyphenyl)piperazine hydrochloride 315 in the presence of sodium bicarbonate and sodium iodide in propan-2-ol, compound 316 was obtained in 84% yield. The first route was also used to synthesize thieno[3,4-d]py-rimidine-2,4-dione 312 in 36% yield from 310a and 4-(2-methoxyphenyl)-1-piperazinethanamine 311. 

SYNS DIHYDROCHLORIDE SALT OF DIETHYL-ENEDIAMINE DOWZENE DHC PIPERAZINE HYDROCHLORIDE... 

This is formed by condensing 4-chloro-8-nitrophenyIarsinie acid (1 mol.) with piperazine hydrochloride ( 2-5 mols.) in 1200 c.c. of lOJV sodium hydroxide. The mixture, after heating for thirty minutes, is jjre-cipitated by adding hydrocliloric acid, a 65 per cent, yield being obtained. 

Distillation of a mixture of piperazine or piperazine hydrochloride with lime and zinc dust also gives pyrazine (32). In addition, pyrazine has been prepared from oxidation of aminoacetaldehyde with mercuric chloride and sodium hydroxide (23, 255, 256) from bromoacetaldehyde and ammonia in ether followed by the action of mercuric chloride (237) from 2-aminoacetal by heating with anhydrous oxalic acid at 110-190° or by heating its mercuric chloride or platinic chloride double salt with hydrochloric acid (30,31) and from diacetylamine (28). 

Some work in our laboratories was also devoted to improve the preparation process of carbamoyl chlorides containing tertiary alkylamine functions,such as N-chloro-carbonyl, N -methyl piperazine hydrochloride. This carbamoyl chloride is for example used in the synthesis of the sedative and hypnotic pharmaceutical Zopiclone as shown in scheme 122 (Ref. 175). 

Piperazine Hydrochloride 142-64-3 Potassium Nitrate 7757-79-1 Pyruvic Acid 127-17-3... 

Synonyms/Trade Names Piperazine hydrochloride [Note The monochloride, C4H10N2XHCI is also commercially available.] ... 

Piperazineethanol 1-Piperazineethanol. SeeN-Hydroxyethylpiperazine Piperazine hydrochloride. See Piperazine dihydrochloride... 

Amyl bromide isobutyrate butyrate Piperazine hydrochloride... 

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