Aldehydes nucleophilic substitution

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

Nitriles contain the —C=N functional group We have already discussed the two mam procedures by which they are prepared namely the nucleophilic substitution of alkyl halides by cyanide and the conversion of aldehydes and ketones to cyanohydrins Table 20 6 reviews aspects of these reactions Neither of the reactions m Table 20 6 is suitable for aryl nitriles (ArC=N) these compounds are readily prepared by a reaction to be dis cussed m Chapter 22... 

Section 20 18 Nitnles are prepared by nucleophilic substitution (8 2) of alkyl halides with cyanide ion by converting aldehydes or ketones to cyanohydrins (Table 20 6) or by dehydration of amides... 

In general, the reaction between a phenol and an aldehyde is classified as an electrophilic aromatic substitution, though some researchers have classed it as a nucleophilic substitution (Sn2) on aldehyde [84]. These mechanisms are probably indistinguishable on the basis of kinetics, though the charge-dispersed sp carbon structure of phenate does not fit our normal concept of a good nucleophile. In phenol-formaldehyde resins, the observed hydroxymethylation kinetics are second-order, first-order in phenol and first-order in formaldehyde. 

Compound 40 has not yet been synthesized. However, there is a large body of synthetic data for nucleophilic substitution reactions with derivatives of 41 [synthesized from aliphatic and aromatic aldehydes, pyridine, and trimethylsilyl triflate (92S577)]. All of these experimental results reveal that the exclusive preference of pathway b is the most important feature of 41 (and also presumably of 40). 

Nucleophilic substitution of the halogen atom of halogenomethylisoxazoles proceeds readily this reaction does not differ essentially from that of benzyl halides. One should note the successful hydrolysis of 4-chloromethyl- and 4-(chlorobenzyl)-isoxazoles by freshly precipitated lead oxide, a reagent seldom used in organic chemistry. Other halides, ethers, and esters of the isoxazole series have been obtained from 3- and 4-halogenomethylisoxazoles, and 3-chloro-methylisoxazole has been reported in the Arbuzov rearrangement. Panizzi has used dichloromethylisoxazole derivatives to synthesize isoxazole-3- and isoxazole-5-aldehydes/ ... 

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

Reactivity factors in additions to carbon-hetero multiple bonds are similar to those for the tetrahedral mechanism of nucleophilic substitution. If A and/or B are electron-donating groups, rates are decreased. Electron-attracting substituents increase rates. This means that aldehydes are more reactive than ketones. Aryl groups are somewhat deactivating compared to alkyl, because of resonance that stabilizes the substrate molecule but is lost on going to the intermediate ... 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

A way to introduce the primary amino group directly onto the selenophene ring is via the azido compound, obtained by nucleophilic substitution of the bromo derivative with sodium azide. Useful transformations of the azido group are shown in Scheme 12.117 The amino aldehyde (109) is a suitable starting material for the preparation of selenolo[3,2-b]pyridine (110) by the Friedlander reaction.138 Not only can the azido be reduced to an amino... 

The most characteristic and useful reaction is the dimerization with incorporation of certain nucleophiles. It is well-known that simple olefins coordinated by Pd2+ compounds undergo nucleophilic substitutions [Eq. (9)] or addition reactions [Eq. (10)] (16, 17). Water, alcohols, and carboxylic acids are typical nucleophiles which attack olefins to form aldehydes, ketones, vinyl ethers, and vinyl esters. 

Tandem nucleophilic substitution-[2+3] cycloaddition reaction of 4-bromo- and 4-toluenesulfonyloxy aldehydes 77 with sodium azide in DMF at 50 °C affords excellent yields (>80%) of substituted pyrrolo[.2.3.4]oxatriazoles 78 (Scheme 8) <2002HAC307>. 

Cyanohydrin diethyl phosphates 87, easily accessible from propargyl aldehydes or ketones of type 86, reacted with lithium dialkylcuprates or similar reagents via an Sn2 process to give cyanoallenes in moderate to good yields [135]. The transformations 80 —> 81 and 84 —> 85 are only formally also SN2 reactions. Thus, plausible catalytic cycles, which include different short-lived palladium intermediates, have been postulated to explain these nucleophilic substitution reactions [127, 134],... 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

OH activation for nucleophilic substitution Aldehyde or ketone + NH3+ X to give chiral amine... 

Thus the cyclopropanone hydrate 21 is an inhibitor of yeast aldehyde dehydrogenase (ALDH) through the nucleophilic substitution of a hydroxyl group by an enzymic thiol 47 leading to the cyclopropanone hemithioacetal 24 a, Eq. (16) [211. 

DiazotriazoIe 28 (R = Ph) reacted with /-butyl alcohol and 2-propanol to give compounds 148 and 149 (Scheme 40) in comparable yields by carbenic C—H insertion and nucleophilic substitution, respectively [81DIS(B)(42)1892]. In the case of 2-propanol, an oxidation-reduction process, to give the parent triazole and acetone, was also observed to a smaller extent. Also, it was previously reported that 3-diazotriazole 28 (R = COOH) oxidizes primary and secondary alcohols to the corresponding aldehydes and ketones (1898LA33). 

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