Heterocyclic base

Analyses of bases have included the study of ammonium orotate monohydrate (13). Orotic acid (6-carboxyuracil) is closely related to the pyrimidine bases, and proves to exist in the diketo tautomeric form 

Guanine (15), studied as the monohydrate, also exists in the keto tautomeric form. The crystal structure is composed of planar sheets of guanine molecules with interplanar spacing 3.30 A, the molecules being held 

An example of yet another mode of packing is provided by the crystal structure of A/ -(AMsopentenyl)-2-methylthioadenine (17), in which the molecules exist in the AT(9)-H tautomeric form, and are linked across inversion centres by pairs of N-H N [2.88 and 2.99 A] hydrogen bonds to form 

In contrast to the emphasis placed on the crystal rather than the molecular structures of the compounds discussed above, the conformation of 1,3-bis-(8-theophylline)propane (18 n = 3) is of considerable importance. This compound was studied since, of the series of compounds theophylline and 

The analysis reveals that the molecule is folded such that the two theophylline residues lie directly over each other with separations in the range 2.S8—3.53 A. The molecules also stack in columns, the theophylline-theophylline intermoiecular separation being about 3.40 A. These columns are cross-linked by N-H O (2.74 A) and O-H O (2.83 A) hydrogm bonds, the latter involving water molecules of oystallization. 

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Styphnates. Aromatic hydrocarbons (and also some amines and heterocyclic bases) form 1 1-addition products with styphnic acid (2 4 6-trinitroresorcinol),... 

Except in the case of the 4,5-diphenyl derivatives, these compounds are obtained as their hydrohalide salts tvith yields of 70 to 90% the free heterocyclic base is obtained by treatment with weak alkali. 

In Table III-33 results for the methylation of thiazoles in acetic acid are given (lead tetraacetate is used as radical source), but in this case some discrepancies appear, the acidic medium being too weak, and the heterocyclic base not fully protonated. Thiazole has also been methylated by the DMSO-H2O2 method (201), and the results are in agreement with those described previously. 

The most versatile derivative from which the free base can be readily recovered is the picrate. This is very satisfactory for primary and secondary aliphatic amines and aromatic amines and is particularly so for heterocyclic bases. The amine, dissolv in water or alcohol, is treated with excess of a saturated solution of picric acid in water or alcohol, respectively, until separation of the picrate is complete. If separation does not occur, the solution is stirred vigorously and warmed for a few minutes, or diluted with a solvent in which the picrate is insoluble. Thus, a solution of the amine and picric acid in ethanol can be treated with petroleum ether to precipitate the picrate. Alternatively, the amine can be dissolved in alcohol and aqueous picric acid added. The picrate is filtered off, washed with water or ethanol and recrystallised from boiling water, ethanol, methanol, aqueous ethanol, methanol or chloroform. The solubility of picric acid in water and ethanol is 1.4 and 6.23 % respectively at 20°. 

The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate salts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pKg value of the base to ensure almost complete formation of the cation. They are extracted with diethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines (isocyanides) are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

Firefly luciferin is an exanple of an azole that contains a benzene ring fused to the five-rnernbered ring. Such structures are fairiy common. Another example is benzimidazole, present as a structural unit in vitfflnin B12. Some compounds related to benzimidazole include purine and its fflnino-substituted derivative adenine, one of the so-called heterocyclic bases found in DNA and RNA (Chapter 28). 

The preparation of enamines by reduction of aromatic heterocyclic bases and their quaternary salts or of lactams is not the most useful approach (97). The lithium aluminum hydride reduction of N-acyl enamines has been used with both fruitful and unsuccessful results. A series of 3-N-acetyl -d -cholestenes (104) has been prepared by desulfurization of the appropriate thiazolidine (105) (98,99). Lithium aluminum hydride reduction of the... 

Heterocyclic bases which readily form quaternary salts with the more usual reagents will also react with suitably activated aryl and heterocyclyl halogen compounds, the classic case being the salt formed from pyridine and l-chloro-2,4-dinitrobenzene. Reactions of this type have been studied by Chapman et Salt formation between... 

Analogous to other N-oxides of polynitrogen heterocyclic bases, quinoxaline 1-oxide and phenazine 9-oxides undergo quater-... 

The reversible hydration of nitrogen-containing heterocyclic bases and their hydroxy and mercapto derivatives is acid-base catalyzed and, at constant pH, the reactions obey first-order rate equations. 2 26.27-33... 

Highly selective synthesis of polyfunctionalized heterocycles based on ring expansion of squaric acid derivatives 97YGK785, 98SL1167. 

N-Heterocycles based on aromatic unsaturated ketones 98MI13. 

Chemistry of C-nucleosides of fused heterocyclic bases 98AHC(70)163. 

Nitroenamines and related compottnds have been used for synthesis of a variety of heterocyclic compottnds. Rajappahassummaiized the chemistry of nltroenamines fseeSecdon4.2. Anga and coworkers have developed the synthesis of heterocycles based on the reacdon of nltropytidones or nltropyrimldmone v/ith nucleophiles. For example, 2-subsdntted 3-nltro-pyridmes are obtained by the reacdon of l-methyl-3,5-dinitro-2-pyridones wiih ketones in the presence of ammonia fEq. 10.82. ... 

N— compounds used as acid inhibitors include heterocyclic bases, such as pyridine, quinoline and various amines. Carassiti describes the inhibitive action of decylamine and quinoline, as well as phenylthiourea and dibenzyl-sulphoxides for the protection of stainless steels in hydrochloric acid pickling. Hudson e/a/. refer to coal tar base fractions for inhibition in sulphuric and hydrochloric acid solutions. Good results are reported with 0-25 vol. Vo of distilled quinoline bases with addition of 0 05m sodium chloride in 4n sulphuric acid at 93°C. The sodium chloride is acting synergistically, e.g. 0-05m NaCl raises the percentage inhibition given by 0-1% quinoline in 2n H2SO4 from 43 to 79%. Similarly, potassium iodide improves the action of phenylthiourea . 

Samples of DNA isolated from different tissues of the same species have the same proportions of heterocyclic bases, but samples from different species often have greatly different proportions of bases. Human DNA, for example, contains about 30% each of adenine and thymine and about 20% each of guanine and cytosine. The bacterium Clostridium perfringens, however, contains about 37% each of adenine and thymine and only 13% each of guanine and cytosine. Note that in both examples the bases occur in pairs. Adenine and thymine are present in equal amounts, as are cytosine and guanine. Why ... 

Molecules of DNA consist of two complementary polynucleotide strands held together by hydrogen bonds between heterocyclic bases on the different strands and coiled into a double helix. Adenine and thymine form hydrogen bonds to each other, as do cytosine and guanine. 

For further Pummerer reactions with silylated heterocyclic bases see Refs. 414a—414i in Handbook of Nucleoside Synthesis , H. Vorbruggen, C. Ruh-Pohlenz, Wiley-Inter-science. New York, 2001... 

It was later shown that aziridine reacts over mixtures of zinc and chromium oxides on alumina at 400°C to give the same products as those obtained from mixtures of NH3 and acetylene [221]. Aziridine, which would form by addition of NH3 to acetylene followed by IH (Scheme 4-8), was thus postulated to be an intermediate in the formation of acetonitrile (by dehydrogenation), monoethylamine (by hydrogenation) and all other heterocyclic bases (by ammonolysis and subsequent reactions) [221]. 

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