Indirect replacement

As described in Chapter 8, the indirect replacement of an amino group by a halogen via diazotization of a primary aromatic amine is a valuable route to aryl halides. The chemistry of these processes covering the introduction of all the main halogens can be found in that chapter. 

Indirect replacement of the a-hydrogen atom of carboxylic esters by the nitroso group is remarkable. This procedure uses ketene 0-alkyl O -silyl acetals (1), generated from carboxylic esters, which are treated with nitric oxide or isopentyl nitrite in the presence of titanium(IV) chloride. In the absence of an a-hydrogen a-nitroso esters (2) are obtained. a-Nitroso esters with an a-hydrogen undergo isomerization to oximes of a-keto esters (3 equation 1). Similarly, silyl enol ethers of aldehydes or ketones can be used instead of the carbonyl compound itself for nitrosation. Thus, treatment of enol ether (4) with nitro-syl chloride gives the a-nitroso aldehyde (5 equation 2), which is quite stable at 0 C, but dimerizes at room temperature. 

There is a much wider variety of indirect replacement approaches. In most cases these approaches introduce the labels at structurally predefined positions generated by (formally) oxidative processes, which are then followed in a second step by reductive operations. Examples of such approaches preferentially designed for the introduction of tritium include halogenation followed by tritiodehalogenation, the introduction of carbon-carbon multiple bonds followed by catalytic tritiation, the oxidation of carbon-heteroatom bonds followed by reduction using tritide reagents, etc. These approaches, which do not alter the skeleton of the target in the process, are discussed in Chapter 4, Sections 1-3 and Chapter 10, Sections 10.1.1.2. ... 

Opportunity 1 an indirect replacement approach used demethylation of the A -methyl piperazine moiety to obtain nor-imatinib (29), which was subsequently remethylated with [ CJmethyl iodide (30) to provide a target for PET studies. This labeling position is metabolicaUy unstable and was therefore not suitable for use in ADME studies. 

Similarly, Fig. 5.15a shows a thermally coupled indirect sequence. The condenser of the first column is replaced by a thermal coupling. The four column sections are again marked as 1, 2, 3, and 4 in Fig. 5.15a. In Fig. 5.156, the four column sections are arranged to form a side-stripper arrangement. ... 

Prefractionator arrangements (both with and without thermal coupling) can be used to replace either direct or indirect pairings. 

Indirect sequence pairings should be replaced by side-strippers. 

Fat Content of Milk. Raw milk as well as many dairy products are routinely analyzed for their fat content. The Babcock test, or one of its modifications, has been a standard direct measure for many years and is being replaced by indirect means, particularly for production operations. The Babcock test employs a bottle with an extended and caHbrated neck, milk plus sulfuric acid [7664-93-9] to digest the protein, and a centrifuge to concentrate the fat into the caHbrated neck. The percentage of fat in the milk is read direcflv from the neck of the bottle with a divider or caHper, rea ding to... 

The ring-chlorinated derivatives of toluene form a group of stable, industrially important compounds. Many chlorotoluene isomers can be prepared by direct chlorination. Other chlorotoluenes are prepared by indirect routes involving the replacement of amino, hydroxyl, chlorosulfonyl, and nitro groups by chlorine and the use of substituents, such as nitro, amino, and sulfonic acid, to orient substitution followed by their removal from the ring. 

MNN is obtained in 3—5% yield by the nitration of naphthalene and is present at this level in coml MNN. It is best prepd by indirect methods for example, by the removal of an amino group from an appropriately substituted nitro-naphthylamine. The amine is treated with Na nitrite and acid to form the diazonium salt which is replaced with a H atom by redn with EtOH (Ref 7). It may also be prepd by treatment of 6-nitro-l, 2,3,4-tetrahydronaphthalene with Br to form a dibromo compn (probably the 1,4-isomer), followed by removal of two moles of H bromide by distn in the presence of base (Ref 10). 2-Naphthalenediazonium fluoroborate... 

Nitration can be carried out either directly by introduction of the nitro group in place of a hydrogen atom or by adding it to a double bond, or else indirectly, by introducing into a compd a group which can readily be replaced by or converted to the nitro group... 

The most common indirect nitration method, often used in nitrating phenols, consists of sul-forating the compd and then replacing the sulfo group by a nitro group. The usual nitrating agent for these reactions is coned nitric acid... 

In exptl work, indirect methods of introducing nitro groups find wide application as, for example, the replacement of a halogen (iodine or bromine in an alkyl iodide or bromide) by the nitro group, by means of silver nitrite (the Victor Meyer reaction)... 

The operational duties of these smaller boiler systems vary widely, and for HW closed-loop heating systems, where the boiler is periodically offline, or in indirect heating systems where pipework, valves, or final heating units are exposed to chilly winds or icy conditions, some boiler winterization may be necessary. This is usually provided by replacing some of the water with glycols or other heat transfer fluids. 

The replacement of one halogeno substituent by another at the 2- or 3-position may be done directly by several methods similar transformations at the 5- to 8-positions normally require an indirect route. The following examples illustrate typical procedures. 

A positive feedback between vegetation and atmospheric CO2 will occur if biomass declines. This will happen to the extent that climatic warming causes increased water stress, either through decreased precipitation or increased evap-otransporation, particularly on soils of low water-holding capacity. Decreases in soil nutrient availability, either directly caused by drought or indirectly caused by replacement with taxa with more recalcitrant litter, may further decrease the net release of carbon from the biosphere to the atmosphere. Positive feedback will also arise if the current standing biomass of trees is replaced by small trees, shrubs, and herbs that store less carbon. 

The friction cost method (Koopmanschap et al. 1995) assumes that the human capital approach has a tendency to overestimate the indirect household costs. If a worker is seriously sick or dies, his job will be vacant for some time until a new person is hired or trained. However, the loss will not be there for many years. Therefore, the loss of human capital is calculated not until the time of retirement, but until the time of replacement. This approach is correct for unskilled labor in a situation of unemployment. It fits neither to a fully employed economy nor to a subsistence farmer society where there is no substitution of a father who died. 

HIV/AIDS-induced mortality and morbidity of workers can result in significant economic loss to business, including direct cost due to increased insurance premiums paid by employers, costs due to increased benefits paid by employers, indirect costs due to lost time due to illness, lost and reduced productivity, and other costs, like cost to new training and hiring of staff. Famham and Gorsky (1994) used a Markov model to calculate the expected medical, disability, employee replacement, life insurance, and pension costs to a business firm in the US for an HIV-infected... 

To avoid this damage great efforts were made to improve the cultivation systems. Feder and Tolbert [5] developed special stirrers with low shear damage and Lehmann et al. [6] replaced gas bubbling through indirect aeration by diffusion of oxygen through porous polypropylene membranes. 

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