Piperazin-2-ones reactions

This gas-phase reaction is run at less than 300°C and under 250 bar in the presence of hydrogen and nickel catalysts with various promoters such as Co, Fe, and Re. Excess ammonia determines the selectivity, and secondary reactions can give higher amines such as piperazine. One of the key advantages of this process is the absence of the chloride by-products46. 

We know the mass of sample (0.312 6 g), so we need to find the mass of piperazine. The experiment gives us the mass of the product piperazine diacetate (0.712 1 g) made from piperazine. How much piperazine is contained in 0.712 1 g of piperazine diacetate Each mole of piperazine diacetate contains one mole of piperazine in Reaction 7-1. If we compute the moles of piperazine diacetate product, we can find the moles of piperazine in the sample. From the moles of piperazine, we can calculate the grams of piperazine and its weight percent. 

Treatment of a mixture of ortho anisidine and bis(2-hydroxy-ethyl) amine with hydrogen chloride affords the aryl-substituted piperazine, 171. (The first step in this reaction probably consists in conversion of at least one hydroxyl group to the chloride this then serves to alkylate the aromatic amine.) Alkyla-... 

B) A mixture of 2.4 parts of 1 acetyl-4-(4-hydroxyphenyl)piperazine, 0.4 part of sodium hydride dispersion 78% 75 parts of dimethylsulfoxide and 22.5 parts of benzene is stirred for one hour at 40°C. Then there are added 4.2 parts of cis-2-(2,4-dichlorophenyl)-2-(1 H-imidazol-1 -ylmethyl)-1,3-dioxolan-4-ylmethyl methane sulfonate and stirring is continued overnight at 100°C. The reaction mixture Is cooled and diluted with water. The product is extracted with 1,1 -oxybisethane. The extract is dried, filtered and evaporated. The residue Is crystallized from 4-methyl-2-pentanone. The product is filtered off and dried, yielding 3.2 parts (59%) of cis-1-acetyl-4-[2-(2,4-dichlorophenyl)-2-(1 H-imidazol-1-ylmethyl)-13-di-oxolan-4-ylmethoxy] phenyl] piperazine MP 146°C. 

Hydroxyethyl)piperazin-l-yl]propyl -8T/-l,2,5-oxadiazolo[3.4-y/]dibcnz[/),/]azepine 1-oxide (19) is the major product (80%) from the reaction of Opipramol (18, see Introduction) with an excess of nitrous acid at 37 rC.218 10- 3-[4-(2-Hydroxyethyl)piperazin-l-yl]propyl -2-nitro-9-acridone (0.1 %). one of numerous minor products formed in this reaction, is a powerful mutagen. 

The presence of a rather more complex substituent on the remote piperazine nitrogen atom is consistent with tranquilizing activity. The preparation of one such agent, 16, begins with reaction of thioxanthone 11 (obtained by a sequence analogous to that used to... 

The central piperazine core of 396 has been synthesized from reaction of 2-bromobenzofuran-3-one 394 and l-methyl-l//-imidazole-2-carboxamide 395 in acetonitrile at elevated temperatures (Equation 106) <1999H(50)259>. 

In addition to the ionic liquid-mediated procedure in solution (see Scheme 6.112), Leadbeater and coworkers also presented a solid-phase protocol for a one-pot Mannich reaction employing the above mentioned chlorotrityl linker [67]. In this approach, p-chlorobenzaldehyde and phenylacetylene were condensed with readily prepared immobilized piperazines (Scheme 7.56). 

Scheme 7.56 One-pot Mannich reaction utilizing polymer-supported piperazine.

Nitrone cycloaddition reactions with alkynes have been widely used for the synthesis of imidazolidine nitroxides (736) and (737), containing chelating enam-ino ketone groups (821). Different heterocyclic systems were obtained, such as 3-(2-oxygenated alkyl)piperazin-2-ones (738) (822), also compounds containing the isoxazolo[3,2-i]indole ring system (739) (823) and a new class of ene-hydroxylamino ketones- (l )-2-( 1-hydroxy-4,4,5,5-tetraalkylimidazolidin-2-ylidene)ethanones (740) (824) (Fig. 2.46). 

The simplest isolable species that fits this description is piperazine (27) with an enthalpy of formation44 of 29.4 kJ mol-1. Can we reliably estimate this value in terms of the conceptually simpler acyclic amines, acyclic polyamines, alicyclic amines or other heterocycles One may estimate it simply as the sum of the enthalpy of formation of cyclohexane (2, n = 6) and twice the exchange energy, S5. The predicted value is 21 kJmol-1, suggestive of at least 7 kJmol-1 of strain. Do not forget that 27 should enjoy stabilization as befits its being a vie-diamine. This destabilization is twice that of piperidine (3, n = 6) as relatedly defined by its measured enthalpy of formation and that estimated by summing the enthalpy of formation of cyclohexane and 1 -85. Equivalently, disproportionation reaction 30 is found to be thermoneutral. 

Very efficient cross coupling reactions of tin derivatives with [4- F]fluorobro-mo and [4- F]fluoroiodobenzenes have been carried out [162, 163] (Scheme 42). Reaction of the appropriate piperazine with [4- F]fluorobro-mobenzene under Hartwig-Buchwald conditions [187] yields [ F]RP 62203 in high specific activity and biologically usable amounts. This method appears superior to the one described previously starting from [ F]fluoronitrobenzene (Scheme 18). 

Trazodone Trazodone, 2-[3-[4-(m-chlorophenyl)-l-piperazineyl]propyl]-s-triazolo[4,3-a] piridine-3(2H)-one (7.3.8), is synthesized from 2-chloropiridine, the reaction of which with semicarbazide gives s-triazolo-3-one[4,3-a]pyridine (7.3.7). Alkylation of this product using l-(3-chloropropyl)-4-(3-chlorophenyl)piperazine gives trazodone (7.3.8) [61,62]. 

Solventless reaction of 6-bromo-8-cyclopentyl-2-methylsulfinyl-8//-pyrido[2,3-r7 pyrimidin-7-one 195 with tert-butyl 4-(6-aminopyridin-3-yl)piperazine-l-carboxylate 196 at 120 °C for 1 h followed by deprotection in the presence of gaseous HCl afforded the amine derivative 197 (Equation 14) <2003W02003062236>. 

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