Carboxylic Experimental Procedures

Rearrangements and other side-reactions are rare. The ester pyrolysis is therefore of some synthetic value, and is used instead of the dehydration of the corresponding alcohol. The experimental procedure is simple, and yields are generally high. Numerous alkenes have been prepared by this route for the first time. For the preparation of higher alkenes (> Cio), the pyrolysis of the corresponding alcohol in the presence of acetic anhydride may be the preferable method." The pyrolysis of lactones 9 leads to unsaturated carboxylic acids 10 ... 

Oxabicyclo[4.1.0]hept-3-enes with a bromo substituent in position 2 can be converted to oxepins 11 by reaction with an appropriate base such as potassium ter+butoxide or triethylamine (see the experimental procedures for the preparation of the parent system in Houben-Weyl, Vol. 6/ld, pi78 and Vol. 6/4, p462).12,156,157 Usually the reaction products are mixtures of oxepin 11 and benzene oxide 12. In the case of ZerZ-butyl 7-oxabicyclo[4,1.0]hept-3-ene-2-carboxylate, the equilibrium lies completely on the benzene oxide side 12a.158... 

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. 

A facile method for the oxidation of alcohols to carbonyl compounds has been reported by Varma et al. using montmorillonite K 10 clay-supported iron(III) nitrate (clayfen) under solvent-free conditions [100], This MW-expedited reaction presumably proceeds via the intermediacy of nitrosonium ions. Interestingly, no carboxylic acids are formed in the oxidation of primary alcohols. The simple solvent-free experimental procedure involves mixing of neat substrates with clayfen and a brief exposure of the reaction mixture to irradiation in a MW oven for 15-60 s. This rapid, ma-nipulatively simple, inexpensive and selective procedure avoids the use of excess solvents and toxic oxidants (Scheme 6.30) [100]. Solid state use of clayfen has afforded higher yields and the amounts used are half of that used by Laszlo et al. [17,19]. 

Experimental Procedure 4.2.7. Carbonyl Ylide Formation and Intramolecular 1,3-Dipolar Cycloaddition Ethyl 2-Hydroxy-8,9-dimethoxy-3-oxo-1,2,3.5,6,11, 12,13,14,14a-decahydroisoquino[ 1,2-/Iquinoline-2-carboxylate [1143]... 

Polystyrene-bound benzhydryl- or trityl halides react much more rapidly with carboxylates than chloromethyl polystyrene, and the base used to form the carboxylate no longer plays a decisive role in these reactions (see Experimental Procedure 13.7). Support-bound phenyldiazomethanes have been used to prepare esters directly from carboxylic acids under mild reaction conditions. Unfortunately, the diazomethanes required are not easy to prepare, and have not yet found widespread application. 

In Section 15, details are provided for the chemical modification of peptide C-terminal carboxylic acids. Many of these C-terminally modified peptides possess important biological activities and the wide range of experimental procedures may be applicable to the synthesis of novel peptide target structures. 

The p-sulfanyl amides 28 are synthesized from N-protected amino acids 24 via amino alcohols 25, which are converted into (5-acetylsulfanyl amides 26 by a Mitsunobu reaction. The (5-amine disulfide 27 is subsequently coupled with a variety of carboxylic acids, followed by reduction with tributylphosphine in aqueous THF in the presence of pyridine to produce the free thiol 28 (Scheme 5).1211 Detailed experimental procedures for these compounds have not been reported. 

Experimental Procedure. A small portion (1-3 mg) of resin is transferred to an Eppendorf tube and washed with MeOH. To this tube is added the malachite green solution (1 ml) followed by two drops of Et3N. The solution is left to stand at room temperature for 3 min and the resin is washed extensively with MeOH. The presence of free carboxylic acids is indicated by green beads. 

In a convenient experimental procedure, nitrogen heterocycles 3 are alkylated by a mixture of a carboxylic acid 4 and [bis(trifluoroacetoxy)iodo]benzene in boiling benzene or under irradiation in dichloromethane at room temperature (Scheme 2) [11, 12]. A similar procedure has been used for the stereoselective synthesis of C-nucleosides and their analogs via photolysis of the gulonic acid derivatives, (diacetoxy)iodobenzene, and the appropriate heteroaromatic bases [13]. 

The experimental procedures and x-ray photoemission results for the preparation of ultrathin (d = 1.1 nm) polyimide films on polycrystalline silver by co-condensation of PMDA and ODA are described elsewhere [5]. In that work our XPS results suggested that the polyimide chains bond to the silver surface via a carboxylate type bonding. This conclusion was derived from an analysis of the results obtained for the interaction of the monomers (PMDA and ODA) and of the resulting ultra-thin polyimide film. Due to the relatively larger thickness of the polyamic acid films as compared to the monomer adsorbate phases and the polyimide film, no conclusions were possible about the reaction of the polyamic acid with the silver substrate. 

The coupling of carboxyl-containing compounds to amino groups of the polypeptide carrier is usually performed with an excess of carboxyl groups and an equivalent amount of the water-soluble carbodiimide around pH 5 at room temperature. In some cases where the hapten is not water soluble, it is usually dissolved in DMF or dioxane. In such cases it is also possible to prepare the hydroxysuccinimide ester using dicyclo-hexylcarbodiimide and couple this ester directly to the carrier. The experimental procedure will be demonstrated by two examples. 

Carbenoid addition of diazocarbonyl compounds to pyrrole, A -alkylpyrroles, indole, N-alkylindoles, imidazole, and benzimidazole does not result in cyclopropanation, but leads to the formal products of carbene insertion into a heterocyclic C-H bond (see Houben-Weyl, Vol.E19b, ppll58 and 1334). However, Af-acylpyrroles, and Af-acylindoles - " have successfully been converted into 2-azabicyclo[3.1.0]hex-3-ene-exo-6-carboxylates and alkyl-1,la,2,6b-tetrahydrocyclopropa[ ]indole-exo-l-carboxylate, respectively (for an experimental procedure, see Houben-Weyl, Vol.E19b, pll60). 

Experimental procedures for the preparation of 3-chloro-3-phenoxy-3/f-diazirine ° and 3-fluoro-3-methoxy-3//-diazirine are given in Houben-Weyl, Vol. E19b, p 1655 and 1656, respectively for the preparation of dimethyl 3-chloro-3-methoxycyclopropane-tra s-l,2-di-carboxylate, see Houben-Weyl, Vol. E19b, pl657. 

In the investigation of organic compounds in sediments the experimental procedures invariably include a separation scheme to divide and simplify total sediment extracts into suitable fractions of different polarity. Typically, this experimental procedure will yield a number of fractions containing principally hydrocarbon, ketone, carboxylic alcohol or polar components. The reconstituted ion (RIC) from gc-ms analysis of three such discussed herein to illustrate the observed of marker compounds in marine sediments and inferred biological origins. 

A MW-assisted protocol for the synthesis of azides, thiocyanates, and sulfones has been developed (Scheme 12) that has proved to be a useful alternative, as the use of environmentally deterimental volatile chlorinated hydrocarbons is avoided.All the reactions with these readily available halides or tosylates have shown significant increase in reactivity, thus reducing the reaction times with substantial improvement in the yields. Various functional groups such as ester, carboxylic acid, carbonyl, and hydroxyl were unaffected under the mild reaction conditions employed. This method involves simple experimental procedures and product isolation which avoids the use of phase-transfer catalysts, and is expected to contribute to the development of greener strategy for the preparation of various azides, thiocyanates, sulfones, and other useful compounds. 

The introduction of 0-acyl thiohydroxamates (mixed anhydrides of carboxylic acids with thiohydroxamic acids) by the Barton group in 1983 [1] has provided one of the mildest and most convenient and versatile sources of carbon-centered radicals which fulfill the above criteria, and can hence, in Sir Derek s own words, be described as disciplined . Since their preparation from carboxylic acids is extremely straightforward, and since they have demonstrated a rapacious radicophilicity in a wide variety of very useful transformations, it is no surprise that these derivatives are commonly named either as Barton esters or by the acronym PTOC (pyridine thiocarbonyl) esters. The ongoing development of this chemistry has been summarized over the years in several useful reviews [2], and some of the tried and tested experimental procedures have also been collated [3]. 

Among the ethers of prolinol, (5)-2-methoxymethylpyrrolidinc [SMP, (S)-10] has found most applications. It is readily prepared from prolinol by the normal sodium hydride/iodo-methane technique9,13 (sec also Section 2.3. for O-alkylations of other amino alcohols) and is also commercially available. An improved synthesis from proline avoids the isolation of intermediates and gives the product (which is highly soluble in water) by continuous extraction14. SMP has been used as the lithium salt in deprotonation and elimination reactions (Section C.) and as an auxiliary for the formation of chiral amides with carboxylic acids, which in turn can undergo carbanionic reactions (Sections D.l.3.1.4., D.l. 1.1.2.. D.l. 1.1.3.1., in the latter experimental procedures for the formation of amides can be found). Other important derivatives are the enamines of SMP which are frequently used for further alkylation reactions via enolates (Sections D.l.1.2.2.. where experimental procedures for the formation of enamines are... 

---