Alcohols carbodiimides

RCO2H, R OH, DCC/DMAP, Et20, 25°, 1-24 h, 70-95% yield. This method is suitable for a large variety of hindered and unhindered acids and alcohols." Carbodiimide i was developed to make the urea by-product water soluble and thus easily washed out. ... 

By a suitable choice of activating reagents, primary and secondary alcohols can be selectively oxidi2ed to carbonyl compounds in good yields at room temperatures. Typical activating reagents are acetic anhydride, sulfur trioxide—pyridine, dicyclohexyl carbodiimide, and phosphoms pentoxide (40). 

The facile and selective oxidation of both primary and secondary hydroxy groups with certain nucleotides led Pfitzner and Moffatt (48) to explore the scope of the carbodiimide-methyl sulfoxide reagent with steroid and alkaloid alcohols. Relatively minor differences were apparent in the rate of oxidation of epimeric pairs of 3- and 17- hydroxy steroids whereas the equatorial lLx-hydroxyl group in several steroids was readily oxidized under conditions where the axial epimer was unreactive [cf. chromic oxide oxidation (51)]. 

Calcium hydride, for drying of lert-butyl alcohol, 41, 7 CARBODIIMIDE, DrPHENYL-, 43, 31 Carbodiumdes, from isocyanates, 43, 31... 

The activation of DMSO toward the addition step can be accomplished by other electrophiles. All of these reagents are believed to form a sulfoxonium species by electrophilic attack at the sulfoxide oxygen. The addition of the alcohol and the departure of the sulfoxide oxygen as part of a leaving group generates an intermediate comparable to C in the carbodiimide mechanism. 

More recently, the fixation efficiency on cotton of Cl Reactive Red 177 (7-43) and its 4-carboxyphenylazo analogue in the presence of various carbodiimides (including 7-44 and 7.45) was investigated, as well as homogeneous reactions of selected carboxylic acids with alcohols (including acetylcellulose in acetone). The carboxylated dye reacted more effectively with cotton cellulose in the presence of cyanamide rather than dicyandiamide,... 

Further work with the same dye (7.43) and carbodiimides (7.44 and 7.45) concentrated on this problem of limited efficiency. Cotton fabric padded with the dye phosphonate solution was aftertreated with the carbodiimide dissolved in various alcoholic solutions to avoid hydrolytic decomposition. Under these conditions cyanamide was much more effective than dicyandiamide. With conventional reactive dyes the efficiency of the dye-fibre reaction is limited by competing hydrolysis of the active dye. Although phosphonated or carboxylated reactive dyes do not hydrolyse, their level of fixation is limited by competing hydrolysis of the carbodiimide activator [46]. 

During their study of the synthesis of Paludrine-analogues, Curd, Rose et al. (58) observed that ammonolysis in ethanol of the S-methylisothio-urea (XVIII R = p-ClCeH4 Alk = isoPr) gave, instead of the expected Paludrine (XIX), the 0-ethylisourea (XXI). Their interpretation of this result (postulating the intermediate formation of a carbodiimide (XX), and subsequent addition of ethanol) appears open to question, however, because carbodiimides are known to react with alcohols only with difficulty except in the presence of catalysts (767, 373). In the absence of ethanol, aminolysis of XVIII by isopropylamine yields 1-p-chloro-phenyl-4,5-diisopropylbiguanide as expected (58). 

The reaction of alcohols with diarylcarbodiimides [16, 35, 36] is catalyzed by sodium alkoxides but not by triethylamine. Recently Schmidt and Moos-miiller [37, 38] found that cuprous chloride (0.075 mole/100 mmole dialkyl-carbodiimide) catalyzes the reaction of primary, secondary, and tertiary alcohols with aliphatic carbodiimides to give O Af -trialkylpseudoureas. Several examples of the use of these methods are described in Tables I and II. 

In the condensation of diols, halogenated alcohols, amino alcohols, cyclic hydroxy ethers, or other bifunctional hydroxy compounds with carbodiimides, 5-, 6-, and 7-membered 1,3-O-N- or l,3-7V,7V-heterocyclics are obtained [14]. 

Carbinolamines, 87 Carbodiimides, 205-222 reaction with alcohols, 170 Carbon monoxide, as reducing agent, 336 a-Carbonyl azo compounds, 324, 326 Caro s add (permonosulfuric add), 408 oxidation with, 409 preparation of, 409 Chloramine T, 377 Chloroacetylenes 120-122 4-Chloro-l, 2-butadiene, 33 Chlorocyclohexenyl acetylene, 121 1 -Chloro-2-JV,N-diphenylaminoacetylene, 128-129... 

Preparation of Pseudoureas by the Reaction of Carbodiimides with an Alcohol Catalyzed by... 

An advantage of polymer-based reagents is that both the excess and the spent reagent are easily separated from the product. Bruno Linclau of the University of Southampton has reported J. Org. Client. 2004, 69,5897) the preparation of a polymer-bound carbodiimide. Exposure of the polymer to alcohol gives a family of O-alkylisoureas that smoothly convert carboxylic acids to the corresponding esters. Methyl, benzyl, ally and p-nitrobenzyl transfer smoothly. The polymeric (-butyl reagent could not be prepared. 

Zirconium and hafnium dialkylamides are highly reactive compounds. They undergo (i) protolytic substitution reactions with reagents such as alcohols, cyclopentadiene and bisftrimethylsilyOamine 63 64 (ii) insertion reactions with C02, CS2, COS, nitriles, phenyl isocyanate, methyl isothiocyanate, carbodiimides and dimethyl acetylenedicarboxylate 69-72 and (iii) addition reactions with metal carbonyls.73 These reactions are summarized with reference to Zr(NMe2)4 in Scheme 1. 

Chloro-l-methylpyridinium iodide (683) functions as an important mediator in a variety of different reactions. Esters are formed in high yield from acids and alcohols when reacted with one equivalent of (683) in the presence of two equivalents of triethylamine (Scheme 158) (75CL1045). cv-Hydroxy acids are lactonized under similar conditions (76CL49). The pyridinium salt (683) will also convert thioureas into carbodiimides (77CL575) and pyridine-2-thiones to pyridyl sulfides (75CL1159). 

In contrast to phosphonic acids, H-phosphinic acids can be coupled with alcohols using carbodiimides to give H-phosphinates 83 (Scheme 31, Table 12).[63-1231 These H-phosphinates 83 afford the corresponding phosphonic acids 84 directly by oxidation with NaI04[123l or by treatment with bis(trimethylsilyl)amide followed by carbon tetrachloride, triethylamine, and waterJ63 Alternatively, as described above (Section 10.10.2.1.3), H-phosphinates may also be converted into the phosphonochloridates by oxidation with carbon tetrachloride and then coupled to nucleophiles other than water, f63-75-76 ... 

However, aqueous, alcoholic, and carboxylic acid solvents and similarly reactive substituents must be avoided since they would competitively consume the carbodiimide. The advantage of this method is the ability to use water-soluble reagents to facilitate the reaction workup. a,p-Didehydropeptides containing AAla[29 34 and AAbut3536 residues have been synthesized in our laboratory by this method (Table 5). In another method reported by Ogura et alJ10SI direct p-elimination of Ser derivatives was carried out by treatment with an equimolar amount of DSC and tertiary amine under mild conditions. 

Both aliphatic alcohols and phenols have been immobilized as esters of support-bound carboxylic acids. The esterification can be achieved by treatment of resin-bound acids with alcohols and a carbodiimide, under Mitsunobu conditions, or by acylation of alcohols with support-bound acyl halides (see Section 13.4). 

The mechanism of carbodiimide-mediated amide formation is outlined in Figure 13.4. The first intermediate formed during the reaction of a carbodiimide with a carboxylic acid (or an ammonium carboxylate [56]) is an O-acylisourea [1]. Under acidic conditions [57,58], this intermediate reacts with acids to yield anhydrides, and with alcohols, phenols, HOBt, or other compounds containing hydroxyl groups, to yield the corresponding esters. The carbodiimide is thereby transformed into a urea. 

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