Reagents and experimental procedure

It was shown that amide formation can be suppressed by the appropriate choice of reaction conditions, such as homogeneous solutions, e.g. in DMF, DMSO, HMPA, high acidity and low temperatures (-30 to -5°C). If the peptide hydrazide contains acid-labile protecting groups, e.g. trityl, 2-(4-biphenyl)propyloxycarbonyl, tert-butyloxycarbonyl, tert-butyl esters and ethers, the temperature has to be kept below -20 °C. Generally, tert-butyl or butyl nitrite is used as the organic nitrite, and for sterically hindered peptides amyl nitrite is employed. The time required for full conversion of the hydrazide into the azide may vary between 5 to 30 min and can be monitored by spray reagents (see experimental procedure below). 

The same research group used this approach for Stille couplings in fluorous media [103-105], and for radical reactions amenable to the synthesis of solution libraries [106,107], The great attention which is currently devoted to the FBS should provide in the near future new tools (tagged reagents, solvents, experimental procedures, and so on) to enlarge the set of reactions amenable to fluorous... 

An automated system for clinical analysis consists of the instmment (hardware), the reagents, and the experimental conditions (time, temperature, etc) required for each deterrnination. The reagents plus the experimental conditions are sometimes referred to as the chemistry of the system. The chemistry employed is generally similar to that used in manual assays because most automated assay methods have been adapted from the manual ones. However, automated analy2ers rarely afford the flexibiUty of experimental procedure that is possible in manual analysis. 

Many reagents are able to chlorinate aromatic pyrazole derivatives chlorine-water, chlorine in carbon tetrachloride, hypochlorous acid, chlorine in acetic acid (one of the best experimental procedures), hydrochloric acid and hydrogen peroxide in acetic acid, sulfuryl chloride (another useful procedure), etc. iV-Unsubstituted pyrazoles are often used as silver salts. When methyl groups are present they are sometimes chlorinated yielding CCI3 groups. Formation of dimers and trimers (308 R = C1) has also been observed. 

Experimental chemistry is a very dangerous occupation and extreme care and adequate safety precautions should be taken at all times. Although we have stated the safety measures that have to be taken under specific entries these are by no means exhaustive and some may have been unknowingly or accidentally omitted. The experimenter without prior knowledge or experience must seek further safety advice on reagents and procedures from experts in the field before undertaking the purification of any material. We take no responsibility whatsoever if any mishaps occur when using any of the procedures described in this book. 

The following experimental procedures do not fall into any convenient categories, but all require reagents and techniques of general interest in organic synthesis. 

Pure di-2-propenylzinc2,8,9 10, bis(2-methyl-2-propenyl)zinc11 or di-2-butenylzinc11 are best prepared by the metal exchange between dimethylzinc and the appropriate triallylborane, which is produced in situ from the Grignard reagent and boron trifluoride-diethyl ether complex. The purification is accomplished by distillation, for experimental procedure, see ref 2, p619. 

Other examples of esterification with trialkyloxonium salts have been reported.7,8 The present procedure offers the advantages that the reactive carboxylate ion is generated in sitv and that a low-boiling, nonaqueous solvent is employed, whereby the experimental procedure is considerably simplified. A related method has been reported which utilizes a hindered amine wdth dimethyl sulfate [Sulfuric acid, dimethyl csterj as the alkylating agent.9 The present procedure is carried out under somewhat milder conditions and avoids the use of highly toxic reagents. 

This volume of Organic Syntheses contains twenty-seven checked procedures of value to the modern practicing chemist. One hopes it will also serve to attract students to the charms of skillfully planned and executed experimental work. The majority of the preparations represent specific examples of important, often recently discovered synthetic methods with general applicability. As in previous volumes the preparation of a number of reagents and widely used starting materials is also included. 

This series of reagents is characterized by the use of metals under the appropriate conditions. In this regard, a mixture of zinc dust and titanium tetrachloride in ether provided a useful synthesis of vinyl sulphides43, with the possibility of further substitution alpha to the sulphur atom, as outlined in equation (16). The reaction is easy to carry out and gave yields of 49 to 87%, although the authors do not provide much detail of their experimental procedure and of the purity (chemical or stereochemical) of their products. 

The reaction of tert-alkyl Grignard reagents with carboxylic acid chlorides in the presence of a copper catalyst provides ieri-alkyl ketones in substantially lower yields than those reported here.4,14 The simplicity and mildness of experimental conditions and isolation procedure, the diversity of substrate structural type, and the functional group selectivity of these mixed organocuprate reagents render them very useful for conversion of carboxylic acid chlorides to the corresponding secondary and tertiary alkyl ketones.15... 

In the future, further studies should be addressed to improve the chemose-lectivity and diastereoselectivity of the reductive coupling process, especially searching for novel reagents and milder experimental conditions. As a matter of fact, a few novel reductive couphng procedures which showed improved efficiency and/or stereoselectivity have not been further apphed to optically active imines. For example, a new electrochemical procedure which makes use of the spatially addressable electrolysis platform with a stainless steel cathode and a sacrificial aluminum anode has been developed for imines derived from aromatic aldehydes, and the use of the N-benzhydryl substituent allowed 1,2-diamines to be obtained with good yields and dl-to-meso ratios... 

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