Piperazines dehydrogenation

With iV-(2-pyridinyl)piperazine substrates, both carbonylation and dehydrogenation occur (Equation (48)). 

By the reaction of Cjq with secondary diamines, dehydrogenated 1,2-diamino-cycloadducts and polyadducts have been isolated. Isomerically pure monoadducts were obtained by the reaction of secondary diamines, for example N,N -dimethyl-ethylenediamine, piperazine, homopiperazine [81], N-ethylethylenediamine and further ethylenediamine derivatives [80], with Cgo between 0 and 110 °C (Figure 3.9) [80,81]. In dilute solutions of the reactants, mono- and bisadducts are predominantly formed even if a large excess of the diamine is used. 

As shown by mass spectrometry and NMR spectroscopy, these amine derivatives of Cgfl, after work up, are dehydrogenated adducts [81]. After nucleophilic addition, the H atoms brought in by the diamines were oxidatively eliminated. The final adduct formation of the secondary diamines proceeds exclusively at [6,6] bonds. Besides the monoadduct, most of the regioisomeric bisadducts of piperazine or N,N -dimefhylethylenediamine and Cjq could be separated by column chromatography. The structure of the monoadduct and some of these bis-adducts were proven by X-ray crystal-structure analysis [90]. 

The continuous vapor phase dehydrogenation of piperazines is effectively carried out over a prereduced 80% CuO-20% Cr2Os catalyst at 350°. In this way 2-ethyl-, 2,6-dimethyl-, and 2,3,5,6-tetramethylpiperazines have been converted into the corresponding pyrazines in 79-89% yield.126-128 Pyrazine itself is obtained from piperazine in 18% yield by the use of 5% Pt on alkali-washed firebrick catalyst.129 The catalytic deamination of diethylenetriamine over alumina-based catalysts at temperatures of 300°-400° gives good... 

The dehydrogenation of piperazines to pyrazine was first achieved by Stoehr (32), who heated piperazine (87) or its hydrochloride with zinc dust or, better, zinc dust and lime to give a yield of approximately 10% pyrazine (88). Since that time a number of publications and patents has described the conversion of piperazines to pyrazines by heating at elevated temperatures with various catalysts usually containing copper chromite (464) but also with palladium-charcoal (465) and platinum on alkali-washed firebrick (466), and also with other reagents. Some of these preparations are summarized in Table II.11 (464-475). 

Some unusual zwitterionic pyrazines have been prepared by dehydrogenation of 1,4-disubstituted piperazine-2,6-diones. Honzl et al. (476a) prepared theanhydro-2,6-dihydroxy-l, 4-diphenyl-3,5-bis(phenylthio)pyrazinium dihydroxide [s/c] (92) (which yields adducts by dipolar cycloaddition of maleic anhydride or formaldehyde) by the reaction of 1,4-diphenylpiperazine-2,6-dione with benzenesulfonyl chloride in pyridine. Tanaka et al. (476b), from I,4-diphenylpiperazine-2,6-dione with benzoyl chloride, and tosyl chloride in pyridine at reflux, obtained the anhydro - 3 - benzoyl - 2,6 -dihydroxy -1,4 -diphenyl - 5 - (p - toly lthio)pyrazinium dihydroxide [src] (93), together with some of the S-p-tolyl analogue of (92). 

A solution of sulfur in dimethylformamide can act as an oxidant of certain A -blocked piperazine-2,5-dione derivatives, resulting in net dehydrogenation (1068). For example, (cis trans)-l,4-diacetyl-3,6-dibenzylpiperazine-2,5-dione (101) reacted with sulfur in dimethylformamide and triethylamine to form, after hydrolytic removal of the acetyl groups, 3-benzyl-6-benzylidenepiperazine-2,5-dione (102) (1968). Oxidation of 1,3,4,6-tetramethylpiperazine-2,5-dione (103) with lead tetraacetate in benzene gave 3,6-diacetoxy-3-acetoxymethyl-l,4,6-trimethylpiperazine-... 

Dehydrogenations of piperazines to pyrazines have been described in Section II.6, and the conversion of piperazine over catalysts (e.g., CuO) to give mostly pyrazine (90-94%) has been studied (1718). The oxidation of 1,4-diphenylpiperazine with manganese dioxide in chloroform at 20° to yield A, A -diformyl-A(, -diphenyl-ethylenediamine has been reported (1719). Formylpiperazines have been reported as formylating agents. Thiophene, 1,4-diformylpiperazine, and phosphoryl chloride are reported to give 2-formylthiophene (1720). 

The steps of prenylation and dehydrogenation which follow (94) in the biosynthesis of these neoechinulins is unknown but from knowledge of echinulin biosynthesis (Scheme 6) introduction of the side chain at C-2 may be the next step. Prenylation of the benzene unit seems, by inspection of structures (97) through (101), to depend on C-8—C-9 unsaturation rather than the structure of the dioxo-piperazine ring. The stereochemistry of the desaturation reaction has been explored with L-tryptophan (85) samples stereospecifically labelled with tritium at... 

Reaction of N-(2-pyridinyl)piperazines with CO and ethylene in the presence of a catalytic amount of Rh4(CO)12 in toluene at 160°C results in a complicated carbonylation reaction, which involves dehydrogenation and carbonylation at a C-H bond (Eq. 29) [43]. In this reaction, the carbonylation proceeds at the C-H bond a to the nitrogen atom substituted by pyridine. It is found that the reaction involves two discrete reactions (a) dehydrogenation of the piperazine ring and (b) carbonylation at a C-H bond in the resulting olefin. An amide functionality can also serve as the directing group for carbonylation at the a C-H bond (Eq. 30) [44]. 

Ethylenediamine undergoes catalytic self-condensation (with loss of 2 Nil,) to give piperazine and subsequently (by dehydrogenation)pyrazine (Pt—AFO, 400°C —38% pyrazine)." ... 

Cu-. [M THarshaw] Copper chromite cat yst for dehydrogenation of alcohols, decomposition of methanol, oxygen scavenging, dehydrogenation of piperazines to pyrazines, methyl ester hydrogenolysis and dehydrogenation. 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

P. G. Sammes has dehydrogenated the iminoethers of piperazine-diones with 2,3-dichloro-5,6-dicyanobenzoquinone 243). Cyclo-L-Pro-L-Pro can be oxidized with this reagent directly to pyrocoll 243). The use of sulfur as oxidizing agent has been successful only with N-acetylated piperazinediones 242). 

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