Hexahydro derivatives

The addition of the anion of a-bromo-a-nitrotoluerie (564) to cyclohexene gave the hexahydro derivative (565) of 3-phenyl-l,2-benzisoxazole (75TL2131). An unusual hexahydro derivative (566) was produced by the bis addition of benzonitrile N-oxide to benzoquinone (67AHC(8)277). 

The and -methylmorphimethines (formula, p. 251) are catalytically hydrogenated to hexahydro-derivatives by saturation of the two ethylenic linkages and opening of the oxide ring. The one from the e-form has m.p. 155° and that given by the -form, m.p. 174-5° (Speyer and Koulen ). 

In the final stage, when the dimethochloride of either Aim thyldesbisneo-strychnidine or that of dimethyldesstrychnidine-D is heated with sodium methoxide in alcohol N (6) is eliminated as trimethylamine and there is formed a mixture of the two desazostrychnidines, a and b, of which the first is amorphous but yields a crystalline methiodide, m.p. 154-5°, and the second is crystalline, m.p. 109-110°, giving a methiodide, m.p. 105-6°. Each yields a hexahydro-derivative, which may be a mixture of stereo-isomerides, and the differenee between the forms a- and h- is probably the result of dissimilar distribution of the three ethylenie linkages thus indi-... 

Another example of this is the loss of acetic acid when delphinine is heated in hydrogen at 200-215°. Just as aconitine is so converted into pyraconitine so delphinine yields pyrodelphinine, C3 H4 0,N, m.p. 208-212°, and similarly a-oxodelphinine, C33H430j qN, under like treatment loses acetic acid and yields pyro-a-oxodelphinine, C3 H3gOgN, which crystallises from methyl alcohol in needles, m.p. 248-250°, after sintering at 238°. This, on hydrogenation, forms a hexahydro-derivative, m.p. 183-5°, presumably by saturation of the benzoyl radical, which therefore leaves unexplained the mechanism by which acetic acid is lost in this pyrolytic reaction (c/. pyropseudaconitine, p. 683). 

The hexahydro derivatives are weakly basic substances, some of them forming hydrochlorides. Dioxohexahydrotriazine yields a 1,5-diacetyl derivative (35), in which the positions of the acetyl groups were determined by acetylation of the A-alkyl derivatives and methylation with diazomethane according to Scheme 4. ... 

The hexahydro derivatives are much less acid than the tetrahydro ones (pKa > 10). Their UV spectra naturally lack the characteristic maxima. The III spectra, however, possess similar absorption to the tetrahydro derivatives in the carbonyl region. It can thus be concluded that they also possess the dilactam structure. 

In a recent variation of this synthesis of the tetrahydro-j8-carboline system, hexahydro derivatives (65) of the salt 55 were cyclized to fully aromatic j8-carbohne derivatives (66a and 66b) on palladium dehydrogenation, presumably by way of an enamine intermediate. ... 

Catalytic hydrogenation of 7,10,10n,ll-tetrahydropyrido[l,2-A][l,2]ben-zothiazine-10,11-dione 5,5-dioxides 40 over 10% Pd/C afforded 7,8,9, 10,10n,l 1-hexahydro derivatives 41 (67JMC223, 68USP3408347). 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

Hydrogenation of pyrene Hydrogenation experiments were carried out with an oxide and a presulphided catalyst and the analysis of the products is shown in Table V, from which it can be seen that the distribution of the products for both catallysts was similar. The principal hydrogenation products were dihydropyrene and hexahydropyrene and lesser amounts of the tetra and decahydro-derivatives were also detected. Two isomeric forms were found for both the hexahydro and decahydro-derivatives. For the hexahydro-derivatives, 1,2,3,6,7,8 hexahydropyrene was the more abundant (ratio 4 3). 

For dibenzofuran, no diphenyl was detected in the product, but phenylcyclohexane and bicyclohexane were detected. Therefore, hydrogenation of at least one of die rings was necessary before ring opening took place. A similar conclusion was found for the analysis of the product from hydrogenation of carbazole. There was evidence for the formation of the hexahydro-derivatives of the two compounds which could make both these compounds effective hydrogen donors. 

It is of interest to mention reduction of benzene and its homologs to the corresponding hexahydro derivatives by heating with anhydrous hydrazine. 

Pyridine and its homologs can be reduced completely to hexahydro derivatives, or partially to dihydro- and tetrahydropyridines. Catalytic hydrogenation is faster than with the corresponding benzene derivatives and gives only completely hydrogenated products. Partial reduction can be achieved by different methods (pp. 55, 56). 

The pyridine ring is easily reduced in the form of its quaternary salts to give hexahydro derivatives by catalytic hydrogenation [446], and to tetrahydro and hexahydro derivatives by reduction with alane aluminum hydride) [447], sodium aluminum hydride [448], sodium bis 2-methoxyethoxy)aluminum hydride [448], sodium borohydride [447], potassium borohydride [449], sodium in ethanol [444, 450], and formic acid [318]. Reductions with hydrides give predominantly 1,2,5,6-tetrahydro derivatives while electroreduction and reduction with formic acid give more hexahydro derivatives [451,452]. 

Diazines (pyrazines) afforded hexahydro derivatives by catalytic hydrogenation over palladium on charcoal at room temperature and 3-4 atm [484, 485] (yield of 2-butylpiperazine was 62% [484], yield of 2,5-diphenylpiperazine 80% [455]). Electrolytic reduction gave unstable 1,2-, 1,4- and 1,6-dihydro-pyrazines [485]. 

Treatment of the iV-methylated product (115) of 3-hydroxypyridine with an ion exchange resin generates the betaine (116 Scheme 97) (71JCS(C)874). Reduction of 1-substituted 3-oxidopyridinium betaines with sodium borohydride gives hexahydro derivatives in good yields <8lH(l6)l883). 

The most extensively investigated 1,2-diazocines are 3,4,5,6,7,8-hexahydro derivatives, of interest in connection with studies on the properties of cyclic azo compounds. These compounds are obtained from the hydrazines (159) usually not isolated, by oxidation with yellow mercury(II) oxide. 3,8-Diaryloctahydrodiazocines are prepared by reduction of the azines dialkyl and unsubstituted derivatives are obtained by hydrolysis of the N,N-bis(ethoxycarbonyl) compounds (69JA3226,70JA4922). Cyclization of 2,7-diaminooctane with IFs gave the 3,3,8,8-tetramethyl compound (78CB596). 

Tetrahydro-l,2-diazocinones (166) are formed in good yield by cyclization of e-keto acids with hydrazine in dilute solution. Standard transformations lead to the hexahydro derivatives (167) and (168) and the octahydrodiazocine (169) (73BSF2029). 

Since it was deemed desirable to remove possible interaction between the benzoate and the furan chromophores for the unambiguous CD analysis, salvinorin A (1) was reduced under cataytic hydrogenation conditions, providing the hexahydro derivative 4 (a 2 1 epimeric mixture at C-13) after... 

Examples of photoreduction processes, brought about by hydrogen abstraction from solvents are the reduction of azobenzene to hydrazo-benzene,81 of 2,3-diphenyl-5,8-quinoxalinedione (CXXXIII) to its hexahydro derivative,148 of pteroxyl-L-glutamic acid to dihydro-2-amino-4-hydroxypteridine-6-aldehyde,80 and of the blue gem-chloro-nitroso compounds CXXXIV-CXXXVI to the corresponding ketox-imes.189... 

In aprotic medium (acetonitrile), quinoxalino[2,3-b]quinoxaline (231) undergoes two reversible reductions to an anion-radical and further to a dianion.367 In 1 1 H20-DMF 231 gives a two-electron wave followed by a four-electron wave. The first reduction leads to 5,12-dihydroquinoxa-lino[2,3-h]quinoxaline (232), whereas the second reduction in a four-electron reaction leads to the 5,5a,6,11,1 la,12-hexahydro derivative (233). On heating with acetic anhydride a triacetyl derivative (234) is obtained367 [Eq. (128)]. 

Reduction of 11-benzyl-l-methyl-1,2,3,4-tetrahydro-6/7-pyrimido[l, 2-b]-isoquinolin-6-one in methanol with sodium borohydride gave m-ll,lla-H-l,2,3,4,ll,lla-hexahydro derivative 41 (88HCA77). 

Reduction of 7-methyl-6,7,8,9-tetrahydro-l l//-pyrido[2,l-b]quinazoline with LAH or sodium borohydride gave a 5,5a,6,7,8,9-hexahydro derivative (95AJC2023). 

Tetrahydro-l 1 //-pyrido[2,l-6]quinazoline hydrate (6 HzO) deteriorated during storage into its 11-oxo derivative (7), or in water at room temperature in the presence of air (85AJC1007). A mixture of the 7-methyl derivative of 6,7,8,9-tetrahydro-ll//-pyrido[2,l-b]quinazoline (6) and its 5,5a,6,7,8,9-hexahydro derivative partially oxidized on standing in air for 6 months to their 11-oxo derivatives (95AJC2023). 

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