Piperazine, derivatives reactions

The reaction is a two-stage reaction with the initial formation of the alkanolamine soap followed by dehydration to form the alkanolamide. At the same time, significant quantities of amine esters and amide esters are formed by the side reaction. If a dialkanolamine is used as the starting material, smaller amounts of amine diester and amide diester are formed as well as some morpholine and piperazine derivatives. Reaction of dialkanolamines... 

Syntheses of piperazine derivatives by combining microbial and chemical reactions 99YGK466. 

Though dental afflictions constitute a very significant disease entity, these have received relatively little attention from medicinal chemists. (The fluoride toothpastes may form an important exception.) This therapeutic target Is, however, sufficiently Important to be the focus of at least some research. A highly functionalized piperazine derivative that has come out of such work shows prophylactic activity against dental caries. Condensation of the enol ether 1 of thiourea with ji-pentylisocyanate gives the addition product 1J. Reaction of this with diamine 78, derived from piperazine, leads to substitution of the methylthio moiety by the primary amine, in all likelihood by an addition-elimination sequence. There is thus obtained ipexidine (79). ... 

Reaction Conditions Temperaturc=603 W/F=200 g h mol, NHa/EAsSO EDA ethylenediamine, El ethyleneimine, PA piperazine derivatives CHA chabazite, FAU faujasite 00, LTL Linde type L, MOR mordenite, EDTA-MOR Na-mordenite was treated with EDTA and then ion-exchanged to H-form, MFl ZSM5. 

Microwave-assisted reactions allow rapid product generation in high yield under uniform conditions. Therefore, they should be ideally suited for parallel synthesis applications. The first example of parallel reactions carried out under microwave irradiation conditions involved the nucleophilic substitution of an alkyl iodide with 60 diverse piperidine or piperazine derivatives (Scheme 4.22) [76]. Reactions were carried out in a multimode microwave reactor in individual sealed polypropylene vials using acetonitrile as solvent. Screening of the resulting 2-aminothiazole library in a herpes simplex virus-1 (HSV-1) assay led to three confirmed hits, demonstrating the potential of this method for rapid lead optimization. 

This effect of solvent polarity on the product distribution is in agreement with the proposed reaction scheme. A solvent such as acetone favors a reaction involving charge destruction, such as the alkyl halide formation from the aziridinium ion with the counter ion. Thus acetone favors piperazine formation. A solvent of high polarity favors charge stabilization or charge transfer such as the polymerization steps. Therefore, polymer or piperazine derivatives can be prepared by the proper choice of solvent. 

Removal of the amine moiety in piperazine derivatives in acidic medium " is thought to occur from the enolic form of the ammonium salt, at least at very low pH values. However,. step b has not been interpreted entirely from the mechanistic point of view, as far as the participation of ammonium/enolate structures is concerned. Several cyclic transition states have been envisaged, some of which involve the presence of a hydroxy group or the enolic form of the P-aminoketone. In particular, the participation of OH groups belonging to other molecules, such as carboxyacids present in the reaction medium, cannot be excluded. " By contrast, a nucleophilic attack by an acid anion on the carbonyl C atom has been claimed to be the rate-determining step for deamination in the reaction between p-aminoketones and triethyl phosphite in dimethylformamide. ... 

IR data from the model compounds indicate that the amino end groups of the ATBN can react with the double bond in the polyester. In fact, the 1645 cm-1 absorption due to the double bond almost disappeared after 40 min at 100 °C, and the absorption due to the amino groups (N-H) also diminished considerably (Figure 1). A Michael-type addition reaction between the secondary amino hydrogen of piperazine derivatives and the activated double bonds of diethylfumarate in the polyester is known (5, 6). 

The reaction of ethyl thiophen-2-carboxylate with triphenylphosphine-CCI4 gave (159), which upon acidic hydrolysis afforded the dichloromethyl ketone. 2-Thenoyl chloride reacts with some piperazine derivatives. Trimethylsilyldiazomethane has been used as a safe reagent in the Arndt-Eistert reaction for the transformation of 2-thenoyl chloride into benzyl 2-thienylacetate. ... 

More recently, a series of monoacylated piperazine derivatives 303 were obtained by the reaction of the activated ester 301 (from CDMT and the carboxylic acid) with piperidine. The reactions were carried out in dichloromethane, using 1 equiv of NMM (Equation 52) <2003TL3855>. 

Ary [piperazine derivatives 672 have wide applications as pharmaceuticals. Their conventional syntheses were achieved by heating the hydrochlorides of diethanolamine 669 and aniline derivatives 671 at about 240 °C for 8 h. The reaction was considered a good candidate for MW assistance as the reactants could couple effectively with MWI owing to their polarity. Sublimation and polymerization were controlled by adjusting the time for MWI. The time was reduced drastically to... 

The antihistamine dmg cetirizine, which is a piperazine derivative, is a racemic mixture, and has been used in the treatment of rhinitis and hay fever. It is available over the counter as the well-known ZYRTEC (McNeil-PPC, Inc). However the levo-rotatory R-enantiomer (10.29) was later found to be the more active form and is now on the market as the prescription dmg XYZAL (Sanofi-Aventis U.S. LLC). An approach for the synthesis of the enantiomers of cetirizine is expressed by Scheme 10.11, wherein chiralty in the dmg is introduced at an early stage in the synthesis. Thus, compound 10.28 was synthesized in racemic form then converted into diastereoisomeric salts with an optically active tartaric acid. To procure the (—)-enantiomer of 10.28, the resolution was performed with (-l-)-tartaric acid for the (-l-)-enantiomer, the resolution employed (—)-tartaric acid. After separation of the salts by crystallization, the 10.28 enantiomers were released by treatment with base and each then converted to optically active cetirizine enantiomers or related compounds by use of the general reaction suggested by Scheme 10.11 for the synthesis of the (R)-isomer of cetirizine. 

Later, Shaw and co-workers further employed sugar derived aldehydes 312 as electrophiles in the chalcogeno-MBH reaction (Scheme 2.170). The resulting allyl chlorides 313 can be easily transformed into allylamines 314 via treatment with various amine (Et2NH, pyrrolidine, piperidine and piperazine derivatives) (Scheme 2.170). They also evaluated these allyl chlorides and allylamines for their biological activity and found that (Z)-keto allyl chlorides possess antimycobacterial activity. ... 

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. 

This was her first exposure to cetirizine or any other piperazine derivative, and on recovery she reported no previous history of allergic drug reactions or concomitant use of any other medication or alcohol [3 ]. Although fixed drug eruptions have been previously reported with both cetirizine and levocetirizine [SEDA-31, 30] anaphylaxis caused by systemic antihistamines is very rare, particularly in the absence of known previous exposure. The authors speculated that the potential antigenic nature of the piperazine ring may have been a factor [4 ]. 

Carreira has recently described Pd-catalyzed N-arylation reactions of N-Boc-2,6-diazaspiro[3.3]heptane [240]. For example, the coupling of this nucleophile with 2-bromotoluene proceeded in 97% yield using the Pd2(dba)3/BINAP catalyst system (Eq. 43). This core may serve as a useful structural analog to the piperazine ring, which is a common moiety in many biologically active molecules and pharmaceuticals. A number of studies have examined Pd-catalyzed N-arylation reactions of piperazine derivatives [217, 241, 242] and other rigid cyclic diamine... 

Figure 3.9 The decomposition of the artificiai sweetener aspartame appears to be reiativeiy complex. First, the water of crystallisation is lost at about 130°C. This is followed by the elimination of methanol at 180°C and the formation of a piperazine ring. This reaction takes place in an extremely narrow temperature range of just 20 K for 1-99% conversion. The SDTA curve shows that the piperazine derivative melts at 250°C.

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