Positional isomerization

Positional Isomerization. A different type of isomerization, substituent migration, takes place when di- and polyalkylbenzenes (naphthalenes, etc.) are treated with acidic catalysts. Similar to the isomerization of alkanes, thermodynamic equilibria of neutral arylalkanes and the corresponding carbocations are different. This difference permits the synthesis of isomers in amounts exceeding thermodynamic equilibrium when appropriate reaction conditions (excess acid, fast hydride transfer) are applied. Most of these studies were carried out in connection with the alkylation of aromatic hydrocarbons, and further details are found in Section 5.1.4. 

The AlCl3-catalyzed isomerization of dialkylbenzenes was studied in detail by Allen and coworkers76-79 and Olah and coworkers.80-82 The equilibrium isomer 

Compound (Reaction Conditions) % ortho % meta % para Ref. 

This process probably takes place through a Jt-complex-type intermediate without the complete detachment of the migrating tert-butyl group from the aromatic ring.80 82 

Interconversion of isomeric xylenes is an important industrial process achieved by HF-BF3 or zeolite catalysts (see Section 4.5.2). Studies of xylenes and tri-and tetramethylbenzenes showed that the amount of catalyst used has a pronounced effect on the composition of isomeric mixtures.83 When treated with small amounts of HF-BF3, isomeric xylenes yield equilibrium mixtures (Table 4.2). Using a large excess of the superacid, however, o- and p-xylenes can be isomerized to m-xylene, which eventually becomes the only isomer. Methylbenzenes are well known to form stable a complexes (arenium ions) in superacids, such as HF-BF3. Since the most stable arenium ion formed in superacids is the 2,4-dimethylbenzenium ion (proto-nated m-xylene, 5), all other isomers rapidly rearrange into this ion. The equilibrium concentration of protonated m-xylene in the acidic phase, consequently, approaches 100%. 

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In this section we shall consider three types of isomerism which are encountered in polymers. These are positional isomerism, stereo isomerism, and geometrical isomerism. We shall focus attention on synthetic polymers and shall, for the most part, be concerned with these types of isomerism occurring singly, rather than in combination. The synthetic and analytical aspects of stereo isomerism will be considered in Chap. 7. Our present concern is merely to introduce the possibilities of these isomers and some of the vocabulary associated with them. 

Positional isomerism is conveniently illustrated by considering the polymerization of a vinyl monomer. In such a reaction, the adding monomer may become attached to the growing chain in either of two orientations ... 

Structures [VI] and [VII], respectively, are said to arise from head-to-tail or head-to-head orientations. In this terminology, the substituted carbon is defined to be the head of the molecule, and the methylene is the tail. Tail-to-tail linking is also possible. The term orienticity is also used to describe positional isomerism. 

Conjugation as well as geometric and positional isomerization occur when an alkadienoic acid such as linoleic acid is treated with a strong base at an elevated temperature. CycHc fatty acids result from isomerization of linolenic acid ia strong base at about 250°C (58). Conjugated fatty acids undergo the Diels-Alder reaction with many dienophiles including ethylene, propylene, acryUc acid, and maleic anhydride. 

Most heterocyclic anions may be considered to be derived by loss of a proton from a parent compound, which is therefore the conjugate acid. Such anions have at least one unshared pair of electrons at the anionic site. They are named by appending the suffix -ide , with elision of a terminal e (lUPAC recommendation RC-83.1.1), as in (190)-(193). The site may be specified by a locant placed immediately before the suffix, and so chosen as to be as low as possible consistent with the numbering of the skeleton of the parent compound. The locant may be omitted in order to designate an equilibrating mixture of positionally isomeric anions, which is what one usually obtains in practice. The anion of piperidine is often informally referred to as piperidide . 

The bromination of 3-aroyloxycyclohexanes gives rise to a mixture of stereoisomeric and positionally isomeric addition products. The product composition for Ar = phenyl is shown. Account for the formation of each of the products and describe the factors which will affect the product ratio. 

Cohn points out that position isomerism is of the greatest importance as regards the odours of isomerides, this is strikingly instanced in the case of the tri-nitro tertiary butyl xylenes since the only one possessing the powerful musk odour is that in which the nitro groups are situated each in the meta position to the two others again the ortho-amido-benzaldehyde has a strong odour but the meta and para isomerides are odourless. 

Orts-funktion, /. position ftmction. -isomerie, /. place isomerism, position isomerism, Ortsteln, m, Min.) bog iron ore hardpan, ortsverinderlich, a. movable, portable, Orts-verinderung,/. change of position, -wech-sel, m. change of position or location, -zahl, /. position number, index number. 

TABLE 21 Hydrophobicity Indices / for Positionally Isomeric Surfactants RZ ... 

Substitution of two or more hydrogens in benzene results in positional isomerism. Positional isomers have the same formula, but different physical and chemical properties. In disubstituted benzene, three positional isomers are possible, as shown above. If the substituents are the same or different, one is always listed in the 1-position. If the substituents are different, they are listed alphabetically. 

The products of reactions generating double bonds can exhibit positional isomerism, as rotation of the moieties, given before the reaction, is now prevented. This is usually referred to as cis/trans or, as a complementary description, Z/E isomerism. There are first hints that cis/trans or ZjE ratios of the products with micro-reactor processing differ from the corresponding data for conventional processing. 

For example, direct fluorinations with elemental fluorine are kept imder control in this way, at very low conversion and by entrapping the molecules in a molecular-sieve reactor. As with some other aromatic substitutions they can proceed by either radical or electrophilic paths, if not even more mechanisms. The products are dif ferent then this may involve position isomerism, arising from different substitution patterns, when the aromatic core already has a primary substituent further, there may be changed selectivity for imdefined addition and polymeric side products (Figure 1.31). It is justified to term this and other similar reactions new , as the reaction follows new elemental paths and creates new products or at least new... 

On the other hand, in order to preserve the cold properties of the fuel (Cloud Point, Pour Point and low-temperature filterability), it is mandatory not to increase the melting point, that in turn depends on both the saturated compound (stearic acid, C18 0) content and the extent of cis/trans and positional isomerization as the difference in melting point between the cis and trans isomer is at least 15°C according to double bond position as shown in Table 1. 

Table VII. There was no significant difference between the potency of o-chloro-fluorobenzene and p-bromofluorobenzene toward codling moth larvae, but o-bromo-fluorobenzene and p-chlorofluorobenzene must be tested to determine whether the detectable difference is due to the difference in halogen substitution or to position isomerism.

Rando and von E. Doering have investigated the synthetic utility of double bond positional isomerization in the photolysis of a,j8-unsaturated esters,<106)... 

We have designed PBUILD, a new CHEMLAB module, for easy construction of random copolymers. A library of monomers has been developed from which the chemists can select a particular sequence to generate a polymeric model. PBUILD takes care of all the atom numbering, three dimensional coordinates, and knows about stereochemistry (tacticity) as well as positional isomerism (head to tail versus head to head attachment). The result is a model of the selected polymer (or more likely a polymer fragment) in an all trans conformation, inserted into the CHEMLAB molecular workspace in literally a few minutes. 

The ability to devise experiments that can make use of the NOE gives us massively powerful tools which can be used to crack all manner of problems. For example, they can be used in the more trivial sense, as an assignment aid and to tackle problems of positional isomerism. But the area where NOE experiments really come into their own by offering information that no other NMR techniques can offer, is in the field of stereochemistry. Is this group up or down Could this centre have epimerized An NOE experiment could be just what you need. 

If you have successfully read this far, it might have occurred to you that some problems could well be solved by either an NOE-based approach, or by an HMBC approach and you might be wondering which technique would be preferable under such circumstances. In truth, there may not be a right or wrong answer to this question and each problem should be considered on its merits. The selection of experiment may even be down to personal preference or to the hardware available to you. Questions of positional isomerism can often be resolved by either approach. We have seen how our naphthalene problem could be resolved by using an NOE technique (Structure 9.3). 

In addition to this skeletal isomerization reaction, Anderson and Avery (24) showed that in a suitable isotopically labeled hydrocarbon, a reaction leading to positional isomerization occurred. Thus, with n-butane-l-13C as the reactant, the isomerization products were 2-(methyl-13C) propane, and 7i-butane-2-13C ... 

The alkenes make up a homologous series of hydrocarbons with the general formula C H2 . Alkenes show two types of structural isomerism, position isomerism and chain isomerism. Geometrical isomerism also exists because of the lack of free rotation about the C=C double bond. 

A. Harsch, J. M. Sayer, D. M. Jerina, P. Vouros, HPLC-MS/MS Identification of the Positionally Isomeric Benzo[c]phenanthrene Diol Epoxide Adducts in Duplex DNA , Chem. Res. Toxicol. 2000, 13, 1342 - 1348. 

Garin and Gault 82) reported a hydrogen order of - 3.4 for position isomerization of n-pentane over alumina-supported platinum between 240° and 300°C. They concluded therefore that a surface species that lost 3-4 hydrogen atoms would cyclize. It is not clear to what extent this discrepancy (cf. 77 and 82) may be attributed to different experimental conditions, to different catalysts, or actually to different mechanisms that is, C5 cyclization with participation of unsaturated intermediates. 

However, further a possibility of the formation of several different reaction products in similar processes was reported [97-99]. With the help of microwave irradiation and ultrasonication, the problem of selectivity was also touched in these communications. It was found that three-component reaction of equimolar mixture of 5-amino-Al-arylpyrazole-4-carboxamides, aldehydes, and cyclic (3-diketones in DMF under conventional thermal heating or under microwave irradiation at 150°C yielded pyrazoloquinazolines 68. The treatment at room temperature under ultrasonication gave the same reaction products, although addition of catalytic amounts of hydrochloric acid changed direction and positional isomeric quinazolines 69 were only isolated in this case. 

The mechanism of these MCRs involving Meldrum s acid should include Knoevenagel condensation and Michael addition cascade process [100, 113] (Scheme 37). To form positional isomeric reaction product, arylliden derivatives of Meldrum s acid are attacked by exocyclic NH2-group instead of endocyclic nucleophilic center. 

In addition, we should note that data of H, NMR spectroscopy, mass-spectra, and elemental analysis given in [138] did not contradict the structure of compound 98, being regioisomer of 97. The similar situation had already been shown in the synthesis of 3-aminoimidazo[l,2-a]pyrimidines [139]. Mandair et al. carried out the model MCRs of 2-aminopyrimidine with several aldehydes and isonitrile components in the methanol under the ambient temperamre with the various catalysts. As a result, 3-aminoimidazo[l,2-a]pyrimidine and position isomeric 2-aminoimidazo[l,2-a]pyrimidines were isolated from the reaction mixture in different ratio (Scheme 45). The stmctures of the isomers obtained in this case were confirmed by the X-ray diffraction analysis, as well as the structures of the side-products isolated. 

Figure 10.7) content and the extent of cis-trans and positional isomerization as the difference in melting point between the cis and trans isomers is at least 15 °C according to the double bond position, as shown in Table 10.5. 

The acyl group of an intermediate acyl-HP (e.g., 17) in principle may attack at either nitrogen atom of the pyrimidine ring. Therefore, in addition to ring isomerism another type of isomerism exists for synthesis B, caused by the position of substituents (positional isomerism). 

Co-ordination Position Isomerism.—Here the isomerism occurs through the arrangement of the groups around each cobalt atom with respect to the bridged linkage. For example, there are two dibromo-hexammino-amino-peroxo-dicobaltic bromides which are represented thus ... 

Co(NHa)2py2(N02)2]R. Also, he showed that there are four isomeric salts of molecular formula [Co(en)2(N02)2]R. In this series position isomerism, as well as isomerism of the nitro-group, play a part. 

Ammino-derivatives op Cobalt Salts—Cobaltous Salt Ammines—Cobaltic Salt Ammines—Mononuclear Cobalt-ammines containing One Atom of Cobalt in the Molecule—Cobaltic Salts with Trivalent Cation—Cobalt-ammines Containing Divalent Cation—Cobalt-ammines containing Monovalent Cation—Cobalt-ammines consisting of Non-dissociable Complex— Cobalt-ammines containing Monovalent Anion—Cobalt Salts containing Trivalent Anion—Polynuclear Cobalt-ammines containing Two or more Cobalt Atoms in the Molecule—Cobalt-ammines of Unknown Constitution— Ionisation Metamerism—Polymerisation Isomerism—Valency Isomerism —Co-ordination Position Isomerism—Isomerism due to Asymmetric Cobalt Atoms. 

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