Some Additional Useful Reactions

First the amino group was converted to a hydroxy group via a diazonium ion (Section 17.10). The benzene ring was reduced with hydrogen and a catalyst to produce cyclohexanol. Oxidation with potassium dichromate (Section 10.14) gave cyclohexanone. The bonds between the carbonyl carbon and both a-carbons were then cleaved by a series of reactions not covered in this book. The carbon of the carbonyl group was converted to carbon dioxide in this process. One-half of the original radioactivity was found in the carbon dioxide, and the other one-half was found in the other product, 1,5-pentanediamine. Additional experiments showed that the 14C in the diamine product was located at C-l or C-5. 

This section presents several additional reactions that are very useful in the synthesis of aromatic compounds because they provide methods to convert substituents that can be attached by electrophilic substitution reactions to other substituents that cannot be attached directly. The mechanisms of these reactions need not concern us here. 

The first of these reactions converts a nitro group to an amino group. This reduction can be accomplished using hydrogen and a catalyst or by using acid and a metal (Fe, Sn, or SnCl2). Examples are provided in the following equations  

This reaction is important because it provides a method to place an amino substituent onto the benzene ring, a substitution that cannot be accomplished directly by electrophilic attack. And, as illustrated in the following example, this opens all of the substitution reactions that can be accomplished through diazonium ion reactions. 

Several procedures can be used to convert the carbonyl group of an aldehyde or ketone to a methylene group. One reaction, known as the Clemmensen reduction, employs amalgamated zinc (zinc plus mercury) and hydrochloric acid as the reducing agent. An example is provided by the following equation  

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The activities of intracellular enzymes give an indication of the activity of certain metabolic pathways. They are classically assayed by performing their specific reactions in vitro, using the conversion of natural or artificial substrates and often some additional detection reaction. The sample preparation procedure involves cell harvesting and preparation of cell extracts. A well-studied example is the metabolic shift in Clostridium acetobutylicum from acid to solvent production, the so-called solvent shift. Andersch et al. [48] studied the activities of 10 different enzymes involved in this shift, in batch cultivations where the shift is self-induced by the products formed, and under continuous culture conditions with an externally induced shift. 

Amongst numerous pretreatment regimes, almost all include histamine 1 (HI) antagonist to antagonize the effects of histamine, and some additionally use a corticosteroid to target the inflammatory response. Other regimens also include ephedrine for bronchodilation as well as cimetidine because of its antagonism at the H2 receptor. If the patients history reveals a serious reaction to... 

Combination of super B rousted acid with simple Bronsted acid or Lewis acid would be a new system for acid catalysis in organic synthesis. The example of super BLA would be an interesting tool for selective organic transformations. We have already shown excellent examples in Scheme 1.3 using the Tf2NH-chiral Lewis acid combined system. Scheme 1.36 exemplifies some additional recent reactions based on pentafluorophenyl bis (triflyl)methane and chiral Lewis acid catalyst [38]. 

Table 5-3. Some additives used in cross-coupling and carbopalladation reactions, see also ref. ...

Many of the most interesting and useful reactions of aldehydes and ketones involve trans formation of the initial product of nucleophilic addition to some other substance under the reaction conditions An example is the reaction of aldehydes with alcohols under con ditions of acid catalysis The expected product of nucleophilic addition of the alcohol to the carbonyl group is called a hemiacetal The product actually isolated however cor responds to reaction of one mole of the aldehyde with two moles of alcohol to give gem mal diethers known as acetals... 

The standard ASTM PCE test is relative and used extensively only for alumina—siUca refractories and raw materials (see Table 5). However, the upper service limit is generally several hundred degrees below the nominal PCE temperature because some load is generally appHed to the refractory duriag service. In addition, chemical reactions may occur that alter the composition of the hot face and therefore the softening poiat. The relationship between PCE numbers and temperature is described ia ASTM C24. 

Although the emphasis in this chapter has been on tbe synthesis and mechanism of formation of simple enamines, brief mention will be made of the addition of amines to activated acetylenes to indicate the interest and activity in this area of substituted enamines. Since such additions tend to be stereospecific, inclusion in this section seems apropos. The addition of amines to acetylenes has been much studied 130), but the assigning of the stereochemistry about the newly formed double bond could not be done unequivocally until the techniques of NMR spectroscopy were well developed. In the research efforts described below, NMR spectroscopy was used to determine isomer content and to follow the progress of some of the reactions. 

The intermediacy of ketenes in some enamine acylation reactions using acid chlorides was described above (386,387). Direct addition of ketene to enamines was studied simultaneously by several groups (414-420). The initially formed aminocyclobutanone products could be isolated in some instances, depending on the substitution of the initial enamine. Opening to give either the acylated enamine or the alternative vinylogous amide was found to occur spontaneously or on heating, particularly in adducts derived from enamines with an olefinic proton. 

When hexamethylphosphoramide, (NMe2)3PO, is used as solvent only the second reaction occurs. The synthetic utility of KSiHa can be gauged from Table 9.7 which summarizes some of its reactions. In addition, PCI3 gives polymeric (PH) t, CO2 gives CO plus HCO2K (formate), and N2O gives N2 + H2 (plus) some Sifli in each... 

The mechanism of cyclization of diaminopyrimidines by nitrous acid appears not to have been studied in detail. For the preparative procedure an aqueous solution of alkaline nitrite is treated with the diaminopyrimidine either in the form of a salt or with simultaneous addition of hydrochloric or acetic acid. The first phase of the reaction is usually carried out at 0°C, in some cases the reaction being terminated by heating to 50-60°C. With diaminopyrimidines which are sparingly soluble in water, the reaction was carried out in an organic solvent using amylnitrite. Excess nitrous acid can possibly attack the amino groups present. This was employed in some cases for the preparation of the hydroxy derivatives. ... 

Let us take as an example some of the reaction series listed in Table IX, e.g. the oxidation of the 2-methylmercaptobenzothiazoles. The calculations are summarized in Table X, which is self-explanatory. In these calculations the deviations from regression were used as measure of error, but, when duplicate determinations are available, additional degrees of freedom for replication are obtainable, and should be used as measure of error. 

Drowsiness is the most common reaction seen with the use of skeletal muscle relaxants. Additional adverse reactions are given in die Summary Drug Table Drugp Used to Treat Musculoskeletal Disorders. Some of the adverse reactions tiiat may be seen with the administration of diazepam include drowsiness, sedation, sleepiness, letiiargy, constipation or diarrhea, bradycardia or tachycardia, and rash. 

Tacrine is particularly damaging to the liver and can result in hepatotoxicity. Because tacrine is more likely to cause adverse reactions and drug interactions, it must be administered more frequently (4 times a day) and is rarely used in current therapy. Donepezil has fewer and milder side effects than tacrine It is considered the agent of first choice However, some patients may achieve a better response with one drug than another. Additional adverse reactions are listed in the Summary Drug Table Cholinesterase Inhibitors. 

Today microemulsions are used in catalysis, preparation of submicron particles, solar energy conversion, extraction of minerals and protein, detergency and lubrication [58]. Most studies in the field of basic research have dealt with the physical chemistry of the systems themselves and only recently have microemulsions been used as a reaction medium in organic synthesis. The reactions investigated to date include nucleophilic substitution and additions [59], oxidations [59-61], alkylation [62], synthesis of trialkylamines [63], coupling of aryl halides [64], nitration of phenols [65], photoamidation of fluoroolefins [66] and some Diels-Alder reactions. 

To clarify the characteristics of AMDase, the effects of some additives were examined using phenylmalonic acid as the representative substrate. The addihon of ATP and coenzyme A did not enhance the rate of the reaction, different from the case of malonyl-CoA decarboxylase and others in those, ATP and substrate acid form a mixed anhydride, which in turn reacts with coenzyme A to form a thiol ester of the substrate. In the present case, as both ATP and CoA-SH had no effect, the mechanism of the reaction will be totally different from the ordinary one described above. It is well estabhshed that avidin is a potent inhibitor of the formation of the biotin-enzyme complex. In the case of AMDase, addition of avidin has no influence on the enzyme activity, indicating that AMDase is not a biotin enzyme. 

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