Reactions at the Functional Groups

Knoevenagel condensation of cyanoacetamide to ethyl [3- C]acetoacetate and cyclization afforded 3-cyano-4-methyl-2,6-dihydroxy[4- C]pyridine (330)- Chloro-dehydroxylation upon treatment with POCI3, Pd-catalyzed hydro-dehalogenation and saponification of the cyano function converted 330 into 4-methyl[3- C]nicotinic acid (321).  

Reaction conditions 1. HjNNHMe, benzene reflux, 1 h 2. xylene reflux, 2 h 3.aq. NaOH 5 %, reflux, 3 h 

With nitrous acid, ethyl [3- C]acetoacetate forms the corresponding isonitroso derivative, which is readily hydrolyzed to give ethyl 2,3-dioxo[3- C]butyrate 13341. This compound served as a key intermediate in one of the classical preparation procedures of p- Cllactic acid, which was accessible in two steps through treatment with aqueous sodium hydroxide and thermolytic decarboxylation .  

Reaction conditions 1. NaNOj, H2SO4, H2O 0 °C, 2 h 2. HNO2, AS2O5 ether  

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By using these observed rate constants for hydrolysis and condensation, a detailed formalism has been developed that treats the various reactions at the functional-group level (7-9). The observed rate constants were reported (8) for the acid-catalyzed hydrolysis and condensation of monomeric species prepared from Si(OCH3)4 (tetramethoxysilane [TMOS]). In this chapter, we report the observed rate constants for condensation of the dimeric species (CH30)3Si-0-Si(0CH3)3. 

In most of the reactions that we have described here, the substrate has been modified by reaction at the functional group, and the hydrocarbon framework has remained unchanged. In Example 2.1, ethanol reacted with hydrogen bromide at the site where the hydroxyl group is attached to produce bromoethane... 

Where a polymer has functional groups in the main chain, typical of polymerization by step-reaction chemistry or chain poljunerization of heterocyclic monomers, the fimctional groups in the chain are often the weakest and may nndergo reactions which do not produce radicals. Thermal degradation by random scission, without significant yield of volatiles is typical of polymers such as polyesters, polyamides, and polyurethanes, all of which undergo thermolysis by reaction at the functional groups (5). 

Substitution at the Alcohol Group. Acylation of the OH group by acylating agents such as acid chlorides or anhydrides is one of the important high yielding substitution reactions at the OH group of lactic acid and its functional derivatives. AUphatic, aromatic, and other substituted derivatives can be produced. 

These reactions at particular functional groups of the sample molecule are closely related in an inverse sense with those reagents which bring their own functional group into the molecule. The numerous aldehyde — acid reactions are an example. Numerous monographs of such reactions are already included in Volume la. Their reac-... 

Do not be put off by the structures instead, you should be looking at the functional groups and the changes involved. The reactions are relatively simple. 

Step polymerizations proceed by the stepwise reaction between the functional groups of reactants as in reactions such as those described by Eqs. 1-1 through 1-3 and Eqs. 1-6 through 1-8. The size of the polymer molecules increases at a relatively slow pace in such polymerizations. One proceeds from monomer to dimer, trimer, tetramer, pentamer, and so on... 

Metathesis reactions may be intramolecular and ring-closing diene metathesis (RCM, implicated in Scheme 1.13, see Chapter 12) allows disconnections in retro-synthetic analysis otherwise of little use. The normal disconnection of the macrocyclic amide in Scheme 1.13 would be at the amide but, because of the ready reduction of alkenes to alkanes, the alternative disconnection now becomes a viable option. And since any of the C—C linkages could be formed by RCM, such a disconnection allows far greater synthetic flexibility than the conventional disconnection at the functional group. 

The identities of the two VL complexes are not known with certainty, but the available evidence suggests the -557 ppm-type products arise from monodentate reaction at the carboxylate group, whereas the -544 ppm products derive from monodentate reaction at the nitrogen functionality. Additional products from amino acids with reactive sidechains, as found in serine or aspartic acid, have not been reported.51V chemical shifts for products formed with histidine are similar to those observed for other amino acids, except that an additional signal (-571 ppm) has been observed [66],... 

The attack of ammonia at the ester is rather improbable, given the presence of the two ketone functions. Reaction at the PhCO group will be disfavored by loss of conjugation. Hence we see attack at the acetyl group, with subsequent elimination of the strongest conjugate base. 

Section 2.7 showed that it is often convenient to view a molecule as being composed of two parts the functional group, where reactions occur, and the alkyl group, sometimes called the backbone of the compound. The alkyl group is just the alkane part of the molecule and, like alkanes, does not tend to enter into reactions. In most cases it does not matter what the exact structure of the alkyl group is, because the reactions occur at the functional group. 

We hope that our survey of the important methods for reduction has shown you that, by choosing the right reagent, you can often react the functional group you want. The chemoselectivity you obtain is kinetic chemoselectivity—reaction at one functional group is simply faster than at another. Now look at the acylation of an amino alcohol (which is, in fact, a synthesis of the painkiller isobu-caine) using benzoyl chloride under acid conditions. The hydroxyl group is acylated to form an ester. Yet under basic conditions, the selectivity is quite different, and an amide is formed. 

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