HETEROATOMS AND HETEROCYCLIC COMPOUNDS

Any heteroatom (usually O, N, or S) in a carbon chain is a good point for a disconnection and I shall write CO, CN, or CS above the arrow when I use these disconnections. TM 234 can be made this way. How would you actually do it  

Analysis We must choose the bond away from the aromatic ring as displacements on PhBr are almost impossible. 

The double bond is so far away from the hydroxyl group that we shall have to alter the oxidation level before we can continue  

Amines are slightly more of a problem because the same disconnection is no good  

Because it will be impossible to prevent polyalkylation since the product is more nucleophilic than the starting material  

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Klemm, L.H. 1995. A numerical measure of the degree of oxidation (DOX) of an organicmol-ecule, with special attention to heteroatoms and heterocyclic compounds. J. of Heterocycl. Chem. 32, 1509-1512. 

G. HETEROATOMS AND HETEROCYCLIC COMPOUNDS 1. HETEROATOMS. ETHERS. AND AMINES... 

Protons bound to heteroatoms in heterocyclic compounds are likely to be very mobile in solution and, where two or more heteroatoms are present in a structure, different isomers (tautomers) may be in equilibrium. As a case in point, consider the nucleotide bases (indicates the point of attachment to the sugar-phosphate backbone). 

For the purpose of classification in the Beilstein System, all organic compounds are divided into three basic types, viz. acyclic compounds (Volumes 1-4), isocyclic (i.e. carbocyclic) compounds (Volumes 5-16), and heterocyclic compounds (Volumes 17-27). Heterocyclic compounds are further subdivided according to the nature and number of the ring heteroatoms. All heterocycles... 

Electrophilic substitution is an important type of reactions for five-membered heterocycles with one heteroatom and enables compounds with various substituents to be obtained. The present work is devoted to certain features of substrate and positional selectivities in electrophilic substitution reactions of derivatives of pyrrole, furan, thiophene and selenophene, and also the corresponding benzannulated systems, which had not been explained until recently. In a recent review (05RKZ(6)59), these problems were mainly discussed for thiophenes, while in a previous review (94H(37)2029) only monocyclic pyrrole, furan and thiophene derivatives were considered. 

Sulfur containing heterocycles are also common Compounds m which sulfur is the heteroatom m three four five and six membered rings as well as larger rings are all well known Two interesting heterocyclic compounds that contain sulfur-sulfur bonds are hpoic acid and lenthiomne... 

Substances that contain one or more atoms other than carbon as part of a nng are called heterocyclic compounds Rings m which the heteroatom IS oxygen nitrogen or sulfur rank as both the most common and the most important... 

As might be anticipated from the behaviour of the parent heterocycles, C-2 of indole, benzo[i]furan and benzo[i]thiophene (Table 13) is shifted to lower field than C-3. However, the shifts for C-2 (O, 144.8 Se, 128.8 S, 126.1 NH, 124.7 Te, 120.8) and C-7a (O, 155.0 Se, 141.3 S, 139.6 NH, 135.7 Te, 133.0) in the benzo[i] heterocycles vary irregularly (80OMR(l3)3l9), and the sequence is different to that observed for C-2 in the parent heterocycles, namely 0>Se>Te>S>NH. Also noteworthy is the upheld position of C-7, especially in indole and benzofuran, relative to the other benzenoid carbons at positions 4, 5 and 6. A similar situation pertains in the dibenzo heterocycles (Table 14), where not only are C-1 and C-8 shifted upheld in carbazole and dibenzofuran relative to the corresponding carbons in dibenzothiophene and fluorene, but similar, though smaller, shifts can be discerned for C-3 and C-6 in the former compounds. These carbon atoms are of course ortho and para to the heteroatom and the shifts reflect its mesomeric properties. Little variation in the carbon-hydrogen coupling constants is observed for these dibenzo compounds with V(qh) = 158-165 and V(c,h) = 6-8 Hz. 

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

The NMR spectra of heterocyclic compounds with seven or more ring members are as diverse as the shape, size and degree of unsaturation of the compounds. NMR is perhaps the most important physical method to ascertain the structure, especially the conformational statics and dynamics, of large heterocycles. Proton-proton coupling constants provide a wealth of data on the shape of the molecules, while chemical shift data, heteroatom-proton coupling constants and heteronuclear spectra give information of the electronic structure. Details are found in Chapters 5.16-5.22. Some data on seven-membered rings are included in Table 10. 

Heterocyclic compounds are normally classified according to the size of the heterocyclic ring and the nature and number of the heteroatoms, and the present work is organized on this basis. 

Part 1 (Volume 1) deals with (a) the nomenclature and the literature of heterocyclic compounds (Chapters 1.02 and 1.03), (b) various special topics (Chapters 1.04-1.15), and (c) rings containing less common heteroatoms (Chapters 1.16-1.22). 

Whereas the fulvalenes 1-6 are relatively unstable hydrocarbons and therefore largely of theoretical interest, their heteroatom analogs demand considerable attention in synthetic chemistry and material sciences. Tlie general principle of heterocyclic chemistry to relate heterocyclic compounds to carbocyclic ones was the driving force for the synthesis and their application to heteroful-valenes. Numerous heterocyclic derivatives iso-rr-electronic with, for example, heptafulvalene 3 were accessible in which pairs of carbon atoms linked by double bonds were replaced by heteroatoms capable of contributing two tt-electrons. By this principle, the well-known tetrathiafulvalene and its derivatives have been synthesized successfully (Scheme 2). 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

Another method of ascertaining the nature of the reacting species is to compare the reactivity of a heterocyclic compound with its derivative methylated at the heteroatom. Thus Katritzky and Ridgewell507 measured first-order rate coefficients (lO7 ) for reaction of 2,6-dimethoxypyridine, 2,4,6-trimethylpyridine and 1,2,4,6-tetramethylpyridinium sulphate with tritiated sulphuric acid over a range of temperatures (Table 145). 

The reactivity of heterocyclic dienes is determined by the nature and number of heteroatoms and, in the case of heteroaromatic compounds, also by the aromatic character. Furans undergo Diels-Alder reactions with strong dienophiles and generally afford cxo-cycloadducts which are thermodynamically more stable than the kinetically favoured c z/o-adducts. 

Topics in Heterocyclic Chemistry presents critical accounts of heterocyclic compounds (cyclic compounds containing at least one heteroatom other than carbon in the ring) ranging from three members to supramolecules. More than half of the more than 10000 compounds hsted in Chemical Abstracts are hete-rocychc compounds. The branch of chemistry deahng with these heterocyclic compounds is called heterocyclic chemistry, which is the largest branch of chemistry and as such the chemical hterature appearing every year as research papers and review articles is vast and can not be covered in a single volume. 

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