1- nitrophenyl piperazines

Amino-2-methoxyphenyl)perhydropyrido[l,2-tf]pyrazine was prepared from a 2-(5-nitro-2-methoxyphenyl)-3-one derivative by catalytic hydrogenation over Pd/C catalyst, followed by the reduction of the 3-oxo group by treatment with BH3-THF complex <1999WO99/042465>. A nitro group was reduced to an amino group in 2-[4-(3-nitrophenyl)piperazin-l-yl]butyl]perhydropyrido[l,2-tf]pyrazine-l,4-dione <2001JME186>, in 8-hydroxy-... 

The iV-( -nitrophcnyl)pipcrazinc-2-carbonitrilc 251 (Y = NBOC) was reductively cyclized to the tricyclic /V-oxides 252 (Y = NBOC) either by catalytic hydrogenation, or by electrochemical reduction. Electrochemical reduction gave lower yield. Compounds 251 were prepared by electrochemical cyanation of the iV-(o-nitrophenyl)piperazine 250. The jV-oxides 252 were further hydrogenated to the 2,3,4,4 ,5,6-hexahydro-l//-pyrazino[l,2- ]quinoxaline 253 (Y = NBOC) (Scheme 46) <2001EJ0987>. 

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. 

The DE approach was shown [102] to be successful in establishing a good approximation of the disordered crystal structure of the perhydrotriphenylene/1-(4-nitrophenyl)piperazine inclusion compound [102], despite the considerable computational effort required for the simulation of diffuse scattering data. This application is also notable for the use of parallel computing concepts to exploit the implicit parallelism of evolutionary algorithms in order to increase computational efficiency. 

A,A,A, A -(Tetramethyl)-p-phenyl-enediamine, monoperchlorate 1.21 l-Methyl-4-(4-nitrophenyl)piperazine 0.590... 

Piperazine gave l-(p-nitrophenyl)piperazine (186) (O2NC6H4CI-P, K2CO3, AcMe, 125°C, sealed, 20 h 54% note sluggish reaction, even with activation of aryl halide by a nitro group). 

Fig. 3 SPEM images cf pcrhydrotripenylene inclusion crystals with a dipolar guest molecule [l-(4-nitrophenyl)piperazine], thinned in three steps. A two-dimensional mapping of the pyroelectric response in the channel direction is shown for a constant modulation frequency of the heating laser source of 415 Hz. Color code red=positive current blue=negative current Low color intensity no current.Moving from the outer to the inner part of the needle-shaped crystal shows that at all depths, there are two main domains of opposite polarization althou somehow interpenetrating. In the middle cf the needle, a cone-shaped structure cf polarity distribution is seen, which is typical for a Markov-type growth in two dimensions. Qualitative agreement with stochastic simulations is obtained. (View this art in color at www.dekker.com.)...

Piperazine NH group of 9-fluoro-10-(l-piperazinyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7e]-l,4-benzothiazine-6-carboxylate was reacted with 4-nitrophenylsulfonyl chloride, 2,6-dichloropyrazine, 2,6-dichloropyridine in DMF in the presence of pyridine, and with 4-nitrophenyl isothiocyanate in aqueous acetone in the presence of KOH (01MIP13). A side chain amino group on a 2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazin-7-one skeleton was acylated (OOMIPIO). 

The efficiency of the catalysis would also depend on the binding of the substrate to the piperazine-2,5-dione by means of weak forces. Imanishi and his group (85BCJ497) have sought to achieve this by means of hydrophobic interactions. They have chosen as substrates p-nitrophenyl esters of long-chain fatty acids the hydrocarbon chain would enter into... 

A solution of 4-nitrophenyl chloroformate (43.0 g, 231 mmol, 5.5 equiv.) in DCM (200 mL) was added dropwise over a period of 0.5 h to a stirred suspension of Wang resin (45.0 g, 42.3 mmol) in DCM (600 mL) and pyridine (52.0 mL, 644 mmol, 15 equiv.). After completion of the addition, the mixture was stirred at room temperature for 3 h, and then filtered, lire resin was washed with DCM (5 x 300 mL) and then added portionwise to a stirred solution of piperazine (38.2 g, 444 mmol. 11 equiv.) in DMT1 (600 mL.). which led to an increase in the tempera-hue of the mixture and a color change to yellow-orange. The resulting mixture was shaken at room temperature for 13 h, then liltered, and the resin was extensively ashed w itli DMF. DCM, methanol, and finally with further DCM. After drying in aii, about 15 g of resin-bound pipera/ine was obtained. 

Notes (a) Loaded with the Yamaguchi method, (b) Fmoc-amino acid loaded with DIC/ DMAP, deprotected and reacted with bromo-acid. (c) Symmetric diamine loaded on the nitrophenyl carbonate derivative of Wang resin and subsequently reacted with bromo-acid. (d) Piperazine carboxamide scaffold reacted with the nitrophenyl carbonate derivative of Wang resin. 

Scheme 3.2.4 shows the synthetic route employed for the synthesis of linker-head intermediate 14 from half-sided Boc-protected amine 13 [28], via urea formation, mediated by 4-nitrophenyl chloroformate with 1-Cbz-piperazine, followed by hydrogenation of the Cbz group with palladium on carbon. 

Based on an aminoalkylurethane linker attached to the Wang resin 155, Zaragoza et al. developed a solid-phase synthesis of 1,2,3-triazoles. Thus, as shown in Scheme 4.1.30, Wang resin 84 was primarily treated with 4-nitrophenyl chloroformate 153 in the presence of pyridine to give 154 and then reacted with piperazine in DMF to produce 155. Subsequent reaction with a freshly prepared solution of 3-oxobutyric acid phenyl ester afforded resin-bound 3-oxobutyryl piperazine 156. In the presence of triethylorthoformate, the condensation of 156 with primary aliphatic amines readily produced the corresponding 3-amino-2-butenoic acid amides attached to the solid support (157). 

The kinetics of the aminolysis of 5 -4-nitrophenyl X-thiobenzoates (39) by a series of alicyclic secondary amines in H2O/DMSO (4 1) at 298 K were determined and yielded excellent linear Yukawa—Tsuno plots for piperidine, piperazine, and morpholine with p = 0.90-1.23 and r=0.57-0.67. It was thus concluded that the mechanism of the aminolysis of (39) is stepwise, with breakdown of the tetrahedral intermediate being rate determining." ... 

A very interesting method of polycondensation of active esters containing nucleic acid bases with diamines was described by Hattori and co-workers (87). Di-p-nitrophenyl methylsuccinate with thymine or theophylline was condensed with piperazine. The reaction was carried out in a pyridine/methylene chloride mixture or dimethyl formamide (DMF) in the presence of a copolymer of styrene and styrene derivatives with adenine groups as a template. The strong interaction between the complementary groups (adenine in the template and thymine in the monomer) leads to the template effect. The maximum acceleration effect was observed for copol5uners with adenine content about 54% in the case of polycondensation with piperazine. 

The kinetics of the aminolysis of 4-nitrophenyl acetate by piperidine were studied in nine ILs and compared to data in nine organic solvents. The rates in the ILs were about equivalent to those in MeCN and THF, and for [Bmim]BF4, the rate was only sevenfold less than that in DMSO (dimethyl sulfoxide). A Br0nsted-type plot for the aminolysis of [Bmim]BF4 by four secondary amines (piperidine, morpholine, formylpiperazine, and l-(2-hydroxyethyl)piperazine), which could only be generated after determination of their pKa values (which was accomplished by cyclic voltammetry at a P-Pt electrode), was linear (P = 0.77) and revealed that the mechanism was stepwise, different from the concerted mechanism found in conventional solvents. ... 

From the available methods, the most promising one for the synthesis of polyamides under mild conditions is the aminolysis of reactive esters XXV [54] which is known to proceed without racemization. One can remember that the active ester method employing p-nitrophenyl, -2,4-dinitrophenyl, or pentachlorophenylester derivatives are used for the stepwise synthesis of long-chain peptides. This was extensively studied in the aminolysis of piperazine with the rigid sterically hindered ( )-bicyclo-2,2,2-octane-trans-2,3-dicar-boxylic ester obtained under mild conditions following Scheme XXV. 

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