Analogs, bicyclic

Higher cycloalkenes, benz-annelated analogs bicyclic and 236-271, 283, 284... 

Analogous bicyclic products with different substitution patterns, e.g. 103 [116], were also synthesized (Scheme 6.46, Eq. 3). Compound 103, which is (in the same way as 96) also an intermediate in the synthesis of steroids, was prepared starting from 102 in the presence of one equivalent (S)-phenylalanine as catalyst [116]. The enantioselectivity of 76% ee was determined after derivatization into a known compound. It is worth noting that for preparation of 103 use of L-proline gave less satisfactory results. A graphical overview of synthesized bicyclic products (related to 96) with different substituted patterns is given in Scheme 6.46. 

Slightly better stereoselectivities were observed in the case of the analogous bicyclic piperidinone derivatives (Equation (21 )).54... 

Most of the compounds were synthesized from the reaction products of cyclic dienes with (a) thiophosgene or (b) chlorosulfonylisocyanate. Analogous bicyclic amidoxime derivatives were devoid of activity. 

Upon prolonged irradiation the quatersilirene 6 rearranges to the disilabicyclohexadiene derivative with two terminal silirene groupds 8 (Eq. 2) [5]. This behavior is no longer unusual since, for example, the bis(silirene) 4 is also smoothly converted to the analogous bicyclic species 5. 

Nucleosides and nucleotides can also be analyzed together. Lamb and Ye [149], for example, used a neutral divinylbenzene polymer (Dionex lonPac NSl), which they coated with an -decyl-substituted bicyclic polyether such as l,10-diaza-4,7,13,16,21,24-hexaoxabicyclo[8.8.8]hexacosane (D2.2.2). This coating results in a chromatographic matrix, on which both ionic and hydro-phobic interactions can occur. The so-called cryptands [150] (like their mono-cyclic analogs, bicyclic polyethers) form rather stable complexes with alkali metals. These metals are included in the cavity of the ring system their presence results in weak covalent bonds between the cation and the two N atoms. 

J.E. Baldwin (1975, 1976A) has developed a biomimetic synthesis which is loosely analogous to the biosynthetic pathway which starts with the so-called Amstein tripeptide. Baldwin used bicyclic dipeptides more suitable for stereoselective in vitro syntheses. 

Fig. 3. Crown compounds/cryptands and analogous inclusion hosts. (1 4) Crown macro rings bicyclic cryptands (5) [37095-49-17, (6) [31250-06-3J, (7) [31364-42-8] (8) [23978-09-8]-, (9) spherical cryptand [56698-26-1]-, (10) cylindrical cryptand [42133-16-4]-, (11) apodand [57310-75-5]-, and (12) a spherand...

More recently, Cheeseman and coworkers have investigated cycloaddition reactions of 2,6-dioxypyrazines (80jCS(Pl)1603). 2,6-Dihydroxy-3,5-diphenylpyrazine (77) reacts with electron deficient dienophiles such as iV-phenylmaleimide, diethyl maleate and diethyl fumarate (Scheme 26) to yield adducts of the 3,8-diazabicyclo[3.2.1]octane class such as (78). This reaction is believed to proceed by way of the betaine (79) and has precedent (69AG(E)604) in that photolysis of the bicyclic aziridine (80) generates analogous betaines which have been trapped in cycloaddition reactions. 

Cyanopyrrole undergoes photochemical rearrangement to 3-cyanopyrrole. If the analogous rearrangement of IV-methyl-2-cyanopyrrole (22) is carried out in methanol, in addition to the 3-cyanopyrrole (24) the bicyclic intermediate (23) is trapped as the methanol adduct (25) (78CC131). 

Some weak electrophilic reagents, which are usually inert toward azoles, also react with quaternized azoles. Diazonium salts yield phenylhydrazones (Scheme 48) in a reaction analogous to the Japp-Klingemann transformation of /S-keto esters into phenylhydrazones in the dithiolylium series illustrated the product has bicyclic character. Cyanine dye preparations fall under this heading (see also Section 4.02.1.6.5). Monomethine cyanines are formed by reaction with an iodo quaternary salt, e.g. Scheme 49. Tri- and penta-methinecar-bocyanines (384 n = 1 and 2, respectively) are obtained by the reaction of two molecules of a quaternary salt with one molecule of ethyl orthoformate (384 n = 1) or/S-ethoxyacrolein acetal (384 n =2), respectively. 

During the course of a mass spectrometric study of D-homo-14-hydroxy steroids, it was necessary to prepare the corresponding C-8 deuterium labeled analogs. The preparation of these uncommon steroid derivatives has been achieved by repeating the Torgov total synthesis [(257) (262)] with a deuterium-labeled bicyclic starting material (258). Both of the resulting 14-hydroxy epimers, (261) and (262), exhibited better than 90% isotopic purity. ... 

Chloroquinoline (401) reacts well with potassium fluoride in dimethylsulfone while its monocyclic analog 2-chloropyridine does not. Greater reactivity of derivatives of the bicyclic azine is evident also from the kinetic data (Table X, p. 336). 2-Chloroquinoline is alkoxylated by brief heating with methanolic methoxide or ethano-lic potassium hydroxide and is converted in very high yield into the thioether by trituration with thiocresol (20°, few hrs). It also reacts with active methylene carbanions (45-100% yield). The less reactive 3-halogen can be replaced under vigorous conditions (160°, aqueous ammonia-copper sulfate), as used for 3-bromoquino-line or its iV-oxide. 4-Chloroquinoline (406) is substituted by alcoholic hydrazine hydrate (80°, < 8 hr, 20% yield) and by methanolic methoxide (140°, < 3 hr, > 90% yield). This apparent reversal of the relative reactivity does not appear to be reliable in the face of the kinetic data (Tables X and XI, pp. 336 and 338) and the other qualitative comparisons presented here. 

A careful and NMR study of 1,5-benzoxazine and 1,5-benzo-diazepine shows that these compounds exist in the amino-thione forms 55 and 56, respectively. Compound 55 displays a solvent-dependent amino/imino tautomerism (92MRC673).Tricyclic compounds 57, analogous to the bicyclics discussed above have been described they exist in the tautomeric form shown below (87BSB399,92BSB995,96BSB345). 

The final chapter by Istvan Hermecz (Chinoin, Ltd., Budapest, Hungary) deals with bicyclic systems containing one ring junction nitrogen and one heteroatom and their benzologs, i.e. pyrido-oxazines, pyrido-thiazines, pyrido-pyridazines, pyrido-pyrazines, pyrido-pyrimidines and their analogs. Much of this material has not been reviewed for forty years, during which time immense advances have occurred. 

The cyclized analog of meralluride is prepared by a similar synthesis. Thus, condensation of camphoric acid (42) (obtained by oxidation of camphor) with ammonia gives the bicyclic succinimide (44). Reaction with allyl isocyanate followed by ring opening and then reaction with mercuric acetate affords the mercury derivative (45) as the acetate rather than the hydroxide as above. Reaction with sodium chloride converts that acetate to the halide (46). Displacement on mercury with the disodium salt of thioglycollic acid affords the diuretic mercaptomerine (47). ... 

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