Piperazines reviews

As demonstrated in the previous sections of this review, microwave-assisted reactions allow rapid product generation in high yield under uniform conditions. Therefore, they should be ideally suited for parallel synthesis and/or combinatorial chemistry applications. The first example of parallel reactions performed under micro-wave irradiation conditions involved the nucleophilic substitution of an alkyl iodide with 60 diverse piperidine or piperazine derivatives (Scheme 12.22) [71]. Reactions were performed in a multimode microwave reactor in individual sealed polypropy-... 

The reader is further directed to the excellent reviews of Fischer and Hortan et al. on the chemistry and biology of the privileged structure of the piperazine scaffold [16, 17]. Moreover, Dinsmore et al. and Martins et al. provided a systematic, comprehensive, and contemporary overview on the synthetic methods to DKP with a focus on the classical sequential syntheses [18, 19]. 

Studies with tryptophan and tyrosine derivatives and with tryptophan- or tyrosine-containing dipeptides or piperazine-2,5-diones (diketopiperazines, DKP) revealed structural moieties that affect the fluorescence quantum yield of these aromatic amino acids (for a review, see... 

The objective of the present review is to discuss all aspects of the chemistry of piperazine-2,5-diones and their synthesis, physical chracter-istics, chemical reactivity and applications. Earlier reviews had focused on certain specific topics thus the review by Sammes (75FOR51) is mainly oriented toward natural products containing the piperazine-2,5-dione ring, whereas the one by Anteunis (78BSB627) deals exhaustively with conformational aspects of the ring, as well as those of the side chains. 

The methylene groups at positions 3 and 6 of piperazine-2,5-diones are known to undergo facile condensation with aldehydes to form the corresponding a,/3-unsaturated amides. Two earlier reviews have dealt with this subject. (75FOR51 80FOR251). The review by Sammes covers the literature to 1972 on the synthesis, stereochemistry, and reactivity of... 

Piperazine-2,5-diones and related lactim ethers are covered by S. Rajappa and M. V. Natekar of the National Chemical Laboratory, Pune, India. Their chapter represents the first comprehensive review of these highly important intermediates for the preparation of a wide variety of natural products. 

In each subsection, any examples of syntheses that lead directly to pyrazines usually precede any that afford di-, tetra-, or hexahydropyrazines (piperazines) in that order. Examples of any pre-1978 syntheses in each broad category may be located from the cross-references (e.g., H 49) to appropriate subsections in Barlin s parent volume.1686 Less comprehensive reviews of primary syntheses in the pyrazine series have appeared in recent years.743,1287,1426,1677... 

Examples of photorearrangement in nitrones and heteroaromatic N-oxides have again been described, and the subject has been critically reviewed. The hydroxyoxaziridines (81) have been prepared by irradiation of the corresponding 1-pyrroline 1-oxides (82), ° whereas photorearrangement of the dinitrone (83) gave the oxaziridines (84) and (85) and the lactam (86) oxaziridines (84), (85), and (86) were converted into the piperazine-2,5-dione (87) by further irradiation. ... 

The chemistry of hydropyrazines (including piperazines) has not been treated in the comprehensive manner used for the pyrazines in this volume because it is, strictly speaking, beyond the scope of this work. To provide an entry to the literature, references to reviews of the older literature are summarized in Table XI.1 (35-39, 1524-1534), and a selection of preparations and reactions, drawn from more recent publications are discussed. 

Pratt (36) in 1957 published a comprehensive review which included reduced pyrazines (di- and tetrahydropyrazines, piperazines, and piperazinones), and the literature prior to 1957 is generally not further examined. 

A number of reviews of piperazinones, particularly piperazin-2,5-diones, has been published. These are listed in Table XI.1 and some references to other data are recorded below. 

The preparation and reactions of piperazine-2,S-diones has been much discussed in the reviews mentioned above and in papers by Sammes and co-workers (314, 314a, 1066-1068, 1078,1127,1128, 1616). 

Sterically pure piperazinediones have been prepared from formate salts of dipeptide methyl esters (1622). The conformation of piperazine-2,5-diones has been reviewed (1623). 

Previous reviews of piperazines are listed in Table XL 1, and Kurgan et al. (1645) have also covered various aspects of piperazine chemistry. Some more recent literature is described below. 

The preparation of piperazines from ethylenediamines has been dealt with in earlier reviews some additional references are as follows heating of 1,2-bis(diethyl-amino)ethylene with A(,(V -dimethylethylenediamine at 120° gives 2-diethylamino-... 

This volume summarizes published pyrazine chemistry with emphasis on syntheses, properties, and reactions of pyrazines and pyrazine iV-oxides (Chapters 1-X). Treatment of theoretical aspects is minimal. Although not strictly relevant. Chapter XI is presented as a summary of earlier reviews and more recent literature of reduced pyrazines (including piperazines). The literature recorded in Beilstein to 1929 and Chemical Abstracts through 1978 (Volume 89) has been covered together with selected references to 1980. Whereas every reasonable effort has been made to incorporate most significant material, no attempt has been made to include all relevant data. Tables have been incorporated in the text to extend the range of examples. 

All possible reduced derivatives of pyrazine (I), and several of those of its benzo analogues quinoxaline (2) and phenazine (3), are known <84CHEC-I(3)157>. There are four dihydropyrazines, the 1,2-, 2,3-, 1,4- and 2,5-isomers, two tetrahydropyrazines, the 1,2,3,4- and 1,2,3,6-, and hexa-hydropyrazine or piperazine, the last of which is omitted in this review. The reduced quinoxalines are the 1,2- and 1,4-dihydro compounds and 1,2,3,4-tetrahydroquinoxaline. The only known reduced phenazine is 1,4-dihydrophenazine. 

Over 120 references to this heterocyclic ring system has appeared since Mosby1 reviewed the literature and found 28 references prior to 1957. The octahydro derivatives, in addition to being called 1,4-diaza-bicyclo 4.3.0)nonanes or 1,2-trimethylenepiperazines, are also known as anhydrides or lactams of proline with a second amino acid or as diketo-piperazines. The disproportionately large number of octahydro derivatives of this ring system will be treated separately in Section IV,D. 

---