Ring-oxygen substitution

The success of entecavir has boosted the research on carbocyclic nucleosides three main substitutions exist oxygen for carbon, oxygen for sulfur and oxygen for nitrogen, the latest being the least popular in term of number of publications. 

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The structure of guanine illustrates an important feature of substituted pyrimidines and purines Oxygen substitution on the ring favors the keto form rather than the enol Ammo substitution does not... 

Amines are insufficiently nucleophilic to react with most azoles which do not contain a ring oxygen, and the stronger nucleophile NH2 is required. When treated with amide ions, thiazoles can be aminated in the 2-position by NaNHa at 150 °C. Only TV-substituted condensed imidazoles such as 1-alkylbenzimidazole react in such Chichibabin reactions. Imidazoles are aminated by alkaline NH2OH. 

Pyrrole, furan, and thiophene, on the other hand, have electron-rich aromatic rings and are extremely reactive toward electrophilic aromatic substitution— rnore like phenol and aniline than benzene. Like benzene they have six tt electrons, but these tt electrons are delocalized over five atoms, not six, and ar e not held as strongly as those of benzene. Even when the ring atom is as electronegative as oxygen, substitution takes place readily. 

In a synthesis of gibberellic acid, a diene and quinone, both with oxygen-substituted side chains, gave the initial intermediate. Later in the synthesis, an intramolecular D-A reaction was used to construct the A-ring. 

A series of symmetrical and unsymmetrical, hydrophobic and hydrophilic squaraine probes such as 41 (Table 1) with substituted squaraine ring oxygen was developed and compared to conventional oxo-squaraines 10a,b and 13b [18, 50, 98, 107]. The substituent on the squaraine ring have a strong influence on the spectral properties. Substitution of the squaraine oxygen by S, C(CN)2> C(CN)COOR, N(CN), N(OH), C(CN)[PO(OEt)2], indanedione, barbituric, and thiobarbituric acid causes red-shifted absorption and emission spectra [50]. 

It gives an absorption plateau between 282 mp and 295 mp and an absorption peak at 315 mp. It has been amply demonstrated that absorption above 300 mp is due to the presence of a chromophoric group conjugated with an oxygen substituted benzene ring (51), (52), (69), (75). To ascertain the nature of the chromophoric group (carbonyl or ethylenic... 

The olefm ring-closing metathesis (RCM) has been developed into an important synthetic method which is frequently employed in many synthetic endeavors. In many applications the popular Grubbs compound 204 or advanced complexes such as 205 and 206 were used as catalysts [117]. Rutjes and co-workers [118] and Okuro and Alper [119] elegantly used oxygen-substituted allenes to prepare precursors for the... 

SNARF and SNAFL indicators are benzo[c]xanthene dyes that can be described as semi-naphthofluoresceins and semi-naphthorhodafluors, respectively, depending on whether the benzo[c]xanthene ring is substituted at the 10-position with oxygen or with nitrogen, respectively (Whitaker et al., 1991). These indicators, whose p K l values are in the physiological range, exhibit distinct emission bands for the pro-tonated and deprotonated forms so that emission ratio measurements are possible. In SNAFL, the acidic form is more fluorescent, whereas in SNARF, the basic form is more fluorescent. 

A simple example of a ring-opening substitution reaction is the acid-catalysed hydrolysis of epoxides. In the example shown, protonation of the epoxide oxygen improves the leaving group, and an Sn2 reaction may then proceed using water as the nucleophile. Three-membered rings must of necessity... 

Barby et al. [82JCS(P2)249] investigated the conformational equilibria of 2-NR2-substituted oxanes. The cis/trans isomeric 2-NR2-4-Me-derivatives proved to adopt preferred conformations (cis isomers 2-eq-A-eq trans isomers 2-ax-A-eq, except for /ram-2-NHMe-4-Me-oxane preferring the 2-ax-A-eq conformer by only 0.4 kcal mol ) the 2-NR2 monosubstituted oxanes (see Table I) prefer the equatorial position and do not show notable anom-eric interaction with the ring oxygen atom [82JCS(P2)249]. The same is true for 2-NHCOMe-oxane, but not for N3 and NCO substituents, respectively, in the 2-position (70ZOR863) (see Table I). 

As expected (and as is known for simpler systems), substitution by electronegative groups on the carbon adjacent to the ring oxygen leads to a strong preference for the axial conformer (the... 

DiaryInitrosamines undergo fission at the nitrogen-nitrogen bond upon heating (3T>38) In the presence of oxygen, the ring nitro substituted amines are obtained (3T) in the absence of... 

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