Polyfunctional molecules

Polyfunctional molecules (glycols, dibasic acids, hydroxy acids, diamides, etc.). 

This group consists of polymeric peroxides of indeterminate structure rather than polyfunctional molecules of known structure. The compds listed below are considered to be typical of this group ... 

In 1941, Flory80 introduced the concept of hyperbranched macromolecules by polymerization of a trifunctional AB2 monomer (Fig. 5.16). From a chemical point of view, perfectly defined structures were obtained when the monomer reactions were performed step by step At each step, a polyfunctional molecule... 

AB2 reacts selectively with only one antagonist function of a second polyfunctional molecule, the other ones being protected81 (Fig. 5.16). The perfect hyperbranched molecules obtained according to that step-by-step process are called dendrimers. The degree of branching characterizes the structure of a hyperbranched polymer and has been defined by Hawker et al.82 as... 

In considering step polymerisation with polyfunctional molecules a number of assumptions are made. They are (i) that all functional groups are equally reactive, (ii) that reactivity is independent of molar mass or solution viscosity, and (iii) that all reactions occur between functional groups on different molecules, i.e. there are no intramolecular reactions. It is found experimentally that these assumptions are not completely valid and tend to lead to an underestimate of the extent of reaction required to bring about gelation. 

It was only around 1850 that the first amines were discovered by Wurtz [2], who considered them as alkylated (or arylated) derivatives of NH3. Nowadays, it is well known that the amine function is widespread among biologically important compounds, but mostly it is present in polyfunctional molecules such as amino acids, alkaloids, etc. Simple amines are very rare in nature, with the exception of tri-ethylamine and the trimethylammonium ion which come from the putrefaction of proteins. 

Scheme 2.20 gives some examples of the application of the Julia olefination in synthesis. Entry 1 demonstrates the reductive elimination conditions. This reaction gave a good E.Z ratio under the conditions shown. Entry 2 is an example of the use of the modified reaction that gave a good E.Z ratio in the synthesis of vinyl chlorides. Entry 3 uses the tetrazole version of the reaction in the synthesis of a long-chain ester. Entries 4 to 7 illustrate the use of modified conditions for the synthesis of polyfunctional molecules. 

The synthetic applications 440) and mechanistic aspects 4411 of intermolecular photocycloaddition reactions of arenes to olefins have been reviewed recently. Intramolecular cycloadditions442a,b) have been studied in the context of the photochemical behaviour of bichromophoric molecules, as to investigate interchromophoric interactions in polyfunctional molecules. Three types of addition products can be formed in the photocycloaddition of benzene to an alkene (4.37)441. ... 

Since nitroso acetals (223) can be efficiently assembled from very simple molecules and primarily from AN, Scheme 3.154 shows a general strategy for assembling polyfunctional molecules from readily available precursors in a few steps. As will be evident from the preceding data, it is possible to design the stereocenters and chiral molecules. 

A condensation polymer may be defined as a polymer wherein the polymer unit contains fewer atoms less than the monomers from which the polymer is produced. In polymer formation, the condensation occurs between two polyfunctional molecules to produce a large molecule. 

Confining their study to monofunctional molecules, Roberts et al. [38] compared seven different models for predicting human stratum corneum permeability coefficients. The performance of the models was assessed by the adjusted coefficient of determination r2dj and the Akaike Information Criterion (AIC) [39], Both r2dj and AIC allow for comparing models with different numbers of variables (degrees of freedom). Exclusion of polyfunctional molecules led to a comparatively small set of only 24 molecules. The previously reported... 

In polyfunctional molecules, the elec-trophore with the least negative reduction potential is selectively cleaved [164]. A bromine atom at a carbon atom a to a carbonyl group is fairly easily reducible therefore, cpe at the potential in which this C— Br bond is reduced proceeds highly chemoselectively (Fig. 35) [164]. 

The synthesis of a polyfunctional molecule can always be reduced to the problem of constructing differently paired functional group relationships, which (keeping in mind generalisation 1) usually requires the creation of a carbon chain with a number of carbon atoms equal to or smaller than 6 (n < 6). 

In principle, the synthesis of a consonant molecule or a bifunctional relationship within a more complex polyfunctional molecule, does not offer too many difficulties. In fact, all the classical synthetic methods of carbon-carbon bond formation that utilise reactions which are essentially reversible, lead to consonant relationships. For instance, the book by H.O. House "Modem Synthetic Reactions" [22], after dealing, for almost 500 pages, with functional group manipulations, devotes the last 350 pages to carbon-carbon bond formation, all of which lead to consonant relationships. These methods can, actually, be reduced to the following four classical condensations (and their variants) Claisen condensation, aldol condensation, Mannich condensation and Michael addition (Table 2.5). 

The protection of certain fnnctional group and deprotection of the protected derivatives constitute important processes in the synthetic organic chemistry of polyfunctional molecules, including the total synthesis of natural products (Jarowicki and Kocienski 1995). Examples demonstrating some serious improvements to the conventional methods for group deprotection are as follows. 

Branched polyfunctional molecules of star-like and comb-like types are often encountered and, therefore, it is necessary to examine the effect of branching on the chromatographic behaviour of a macromolecule near the critical point. 

Enzymatic reactions provide new tools in the synthesis of polyfunctional molecules... 

Template reactions are now widely claimed but seldom proved. Detailed mechanistic work has not been carried out on many of the more complicated processes, largely because of the level of complexity and the number of steps involved. However, the concept has proved to be useful, especially as a stimulus for the synthesis of very complex, polyfunctional molecules. This aspect of synthetic utility will be covered in Chapter 61.1. 

A considerable number of electrophiles were used, and the dithiane route found great utility for the syntheses of simple monofunctional compounds as well as for polyfunctional molecules, for which the dithiane moiety affords an invaluable temporary protection of a future carbonyl group. Some experimental procedures published in Organic Syntheses — cyclobutanone [277] and 3-hydroxy-l-cyclohexene-l-carboxaldehyde [278] — are illustrative. A similar route to aldehydes [279] makes use of sym-trithiane as a formyl anion equivalent. 

Because it is inexpensive and very simple, the hydrogen atom transfer method is useful for the preparation of many kinds of simple molecules. Its use in complex synthetic tasks is limited because the yields are often modest, a large excess of the H-donor is required, and chemoselectivity is certain to be poor in polyfunctional molecules with several relatively weak C—H bonds. It can be best employed to advantage when the addition of a relatively small molecule to a complex acceptor is required. 

Although the coupling of aiyl halides with alkenes (commonly referred to as the Heck reaction) was first reported more than 25 years ago [ 1 ], only in the past decade has its enormous synthetic potential been realized [2], Within that time, the reaction has been extended to many substrates, including vinyl iodides and bromides and enol triflates. Moreover, the intramolecular variant has become one of the more important reactions for the formation of carbon-carbon bonds and has emerged as a premier method for the construction of quaternary carbon centers. The ability of intramolecular Heck reactions to reliably fashion carbon-carbon bonds in polyfunctional molecules has led to wide application of this reaction at the strategy level for the synthesis of complex natural products [2g],... 

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