Reactions with Other Functional Groups

Chapter 8. Nucleophilic Species That Form Carbon-Carbon Bonds 

There is a rather useful reaction with amides. Organolithium reagents react with DMF to give aldehydes.. An example is the reaction of 231 with s c-butyllithium to give the aryl-lithium reagent (see sec. 8.5.F for directed ortho metalation reactions). Subsequent reaction with DMF and hydrolysis gave a 91% yield of aldehyde 232 in Yamaguchi s synthesis of the radulanins.  

Organolithium addition to acid derivatives gives the disconnections  

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Competitive Reactions with Other Functional Groups 675... 

Natural rubber, low molecular carboxylated Natural rubber, low molecular, amine end groups Hycar Hycar BF Goodrich BF Goodrich 1 Reaction with other functional groups in J polymer... 

E. Organolithium Reagents Reaction with Other Functional Groups... 

E. Organolithium Reagents Reaction with Other Functional Groups The disconnection for ketone formation from the acid is ... 

These are the same three steps used in part 1 of the previous mechanism. This reaction produces HCl as a by-product. The HCl can often produce undesired reactions with other functional groups that might be present in the compound, so pyridine is used to remove the HCl as it is produced. 

Conversion of the alcohol into the ester could be achieved either via an acid-catalyzed Fischer esterification (ROH + RCO2H) or the via addition of an alcohol to an acid chloride (ROH + RCOCl). The latter method is preferable, because acidic conditions (employed by the first method) could produce undesired side reactions with other functional groups present. 

If R2 contains an a-hydrogen the method cannot be applied as enaminc formation occurs. Bisamides (or -carbamates) are often used in amidoalkylations of aryl and reactive methylene compounds, but the rather harsh reaction conditions severely limit application in the synthesis of more complicated molecules with other functional groups. 

Although the aminolysis of esters to amides is auseful synthetic operation, usually it presents some disadvantages in terms of drastic reaction conditions, long reaction times or strong alkali metal as catalyst, which are usually not compatible with other functional groups in the molecule [6]. For this reason, enzymatic aminolysis of carboxylic acid derivatives offers a clean and ecological way for the preparation of different kind of amines and amides in a regio-, chemo-, and enantioselective manner. 

Either because of potential interference with other functional groups present in the molecule or because of special structural features, the following reactions require careful selection of reagents and reaction conditions. Identify the special requirements in each reactant and suggest appropriate reagents and reaction conditions for each transformation. 

In order to explore the generality of this new domino reaction the conversion of various primary amines with 2-341 and the cyclohexane analogue was investigated (Scheme 2.81). For example, the reaction proceeds with high yields when benzyl- or (2-phenylethyl)amine are used (entries 1 and 2). In comparison, sterically more hindered amines such as 2-butylamine produced much lower yield (entry 4) Furthermore, the reaction tolerates other functional groups, such as an unprotected hydroxyl group (entry 5), and variation of the enone ring size is possible (entries 6 and 7). More recent results have revealed that the addition of Sn(OTf)2 or In(OTf)2 makes the transformation more reliable. 

Numerous examples of modiflcations to the fundamental cyclodextrin structure have appeared in the literature.The aim of much of this work has been to improve the catalytic properties of the cyclodextrins, and thus to develop so-called artificial enzymes. Cyclodextrins themselves have long been known to be capable of catalyzing such reactions as ester hydrolysis by interaction of the guest with the secondary hydroxyl groups around the rim of the cyclodextrin cavity. The replacement, by synthetic methods, of the hydroxyl groups with other functional groups has been shown, however, to improve remarkably the number of reactions capable of catalysis by the cyclodextrins. For example, Breslow and CO workersreported the attachment of the pyridoxamine-pyridoxal coenzyme group to beta cyclodextrin, and thus found a two hundred-fold acceleration of the conversion of indolepyruvic acid into tryptophan. 

Nitro compounds in presence of carbonyl group are selectively reduced to amines in the presence of Raney nickel catalyst. Hydrazine reduces nitrdes yielding hydrazones. Under controlled reaction conditions other functional groups, including nitroso and oxime, may be reduced. Many partially hydrogenated derivatives, such as azo-, hydrazo-, and azoxy compounds may be obtained by partial reduction with hydrazine. Reaction with chlorobenzene yields benzene. 

Epoxy resins are cured [29] by reaction of the epoxy group with other functional groups to give linear, branched, or cross-linked products as described in Eq. (2) and in Table 3. 

With these remarks on heterogeneous processes we conclude our discussion of hydrolytic reactions and other reactions involving nucleophilic species. We should point out that we have taken a close look at only a few representative structural moieties that may undergo these types of reactions in the environment. Nevertheless, the general knowledge that we have acquired in this chapter should put us in a much better position to evaluate the importance of such reactions for other functional groups that form part of environmental organic chemicals. 

The ring-opening of oxiranes, leading to the formation of isomeric carbonyl compounds by the action of acid catalysts as a result of rearrangement, is of continuing interest (refs. 1-4). However, most of these studies focus mainly on the transformations of terpene oxides or oxiranes with other functional groups in the liquid phase, under homogeneous reaction conditions. 

IBX possesses a great selectivity for the reaction with alcohols and the interaction with other functional groups normally demands more severe experimental conditions. According to Santagostino et al.,83 phenols and anilines react with IBX producing complex and dark colored reaction mixtures. Nevertheless, it is possible to selectively oxidize alcohols in the presence of certain phenols that are not very electron rich.88b... 

Pettitt and Stouffer [59] described the use of isopropyl esters, prepared by reaction with 2-bromopropane and sodium hydride, for the GC of amino acids. The above reagent also reacts with other functional groups, which can be of practical significance for the... 

In the course of the reactions, the other functional groups are also derivatized. Hydroxyamino acids and Tyr react with alkyl chloroformate with the formation of carbonate esters, Cys and CysH provide thiocarbonates, and the imidazole nitrogen of His is also protected. The indole functional group of Try does not change, Pro forms a stable carbalkoxydithiocarbamate and Arg does not provide any volatile product. The derivatives were separated successfully (except the pair Leu-De) on 5% of QF-1 with temperature programming (94-235°C). The reproducibility of the method was stated to be 5%. Using an FID and ECD, 10-10 and 10-13 mol of amino acids, respectively, can be determined. 

As with other functional groups, we will discuss how ethers are formed and how they react. Ethers (other than epoxides) are relatively unreactive, however, and they are not frequently used as synthetic intermediates. Because they are stable with many types of reagents, ethers are commonly used as solvents for organic reactions. In this chapter, we consider the properties of ethers and how these properties make ethers such valuable solvents. 

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