Isocyanates from carboxylic acids

Isocyanates from carboxylic acid chlorides via carboxylic acid azides... 

Isocyanates from carboxylic acid azides CON3 — - N C 0... 

Without additional reagents Isocyanates from carboxylic acid azides s. 21, 780... 

The classic Curtius route to isocyanates from carboxylic acids via the acyl azides involves three separate synthetic steps, two of which are potentially explosive. 

A variety of non-volatile tertiary amine bases, which would either completely favor the ammonium phosphate salt and/or form an ammonium phosphate salt that could be removed prior to distillation by precipitation and filtration, were evaluated. Only l,8-his(dimethylamino) naphthalene, known for its bidentate nature [255], which most probably favors the formation of the ammonium phosphate salt, furnished benzyl isocyanate in good yield and with high purity [256). About 75% of the ammonium phosphate salt was removed by precipitation and filtration prior to distillation. Consequently, a simple method for the synthesis of high purity isocyanates from carboxylic acids was developed using DPPA and 1,8-his(dimethylamino) naphthalene. Yields evaluated for the monoisocyanates ranged from 60% to 81.5% (Table 4.17) [256]. 

Typical procedure Preparation of isocyanates from carboxylic acids, DPPA, and 8-bis(dimethylamino)naphthalene [256] The carboxylic acid (40 mmol) was dissolved... 

Isocyanates from carboxylic acid amides GONHg N C O... 

Syntheses of isocyanates from carboxylic acids/ and by the thermolysis of N-substituted 4-hydroxy-2-oxazolidones have recently appeared. In the latter method, the oxazolidones are prepared from amines and the overall reaction thus represents a conversion of amines to isocyanates without the use of phosgene. 

Sodium methoxide Isocyanates from carboxylic acid esters via aminimides... 

Support-bound isocyanates can be conveniently prepared from carboxylic acids by Curtius degradation. Because the reaction of the intermediate acyl azides with alcohols to yield esters is slow, Curtius degradation can be conducted in the presence of alcohols to yield carbamates directly (Entries 4 and 5, Table 14.8). 

Forosamine is an amino sugar component of the antibiotic Lepicidin. Since Le-picidin is sensitive to acid and catalytic hydrogenation, an Fmoc group was selected to protect the amino function. A rather unconventional method was used to introduce it [Scheme 8.94].230 A Curtius rearrangement on the acyl azide derived from carboxylic acid 94.1 proceeded with retention of configuration to give the isocyanate intermediate 94.2 that was trapped with 9-fluorenylmethanol to afford the N-Fmoc derivative 94J in 72% yield. 

In a direct route from carboxylic acids to acyl azides diphenyl phosphorazidate is used probably the reaction passes through a cyclic transition state (Scheme 41). With aromatic and heteroaromatic educts, yields as high as 75% may be obtained. If aliphatic acids are treated under the same conditions, the corresponding azides are, however, immediately transformed into urethanes via isocyanates. Aroyl azides can also be obtained in excellent yields by reaction of carboxylic acids with NaNa and phenyl di-chlorophosphate in the presence of tetrabutylammonium bromide or pyridine (Scheme 41). ... 

Phosgene-free synthesis of isocyanates directly from carboxylic acids and diphenylphos-phonic azide (PhO)2P(0)N3 in combination with proton sponge 1 followed by Curtius rearrangement has been also described222. 

Figure 7 Identification of GW 2433. The biased library comprised a biasing fibrate monomer at Rl. R2 and R3, derived from carboxylic acids and isocyanates, were chosen for diversity by means of experimental design techniques.

The preparation of silica spheres (Scheme 8.1) is straightforward [16], self-assembly of the spheres is well developed [17], and the pore size in the crystals can be readily controlled by selecting the sphere size (the distance from the center of the nanopore projection to the nearest silica sphere surface is 15% of the sphere radius). Surface silanol groups can be directly modified by nucleophilic silylation to introduce a variety of functional groups [18]. Alternatively, silica surface can be first modified with 3-aminopropyltriethoxysilane (Scheme 8.1), followed by treatment with organic molecules carrying electrophilic moieties such as acyl chloride, isocyanate, isothiocyanate, carboxylic acid, sulfonyl chloride [19], or succinimidyl ester [20]. 

The main applications of oxalyl chloride, as described in Chapter 4, are the formation of aryl isocyanates and chloroformates (by reactions with amines and hydroxylic substrates, respectively), and the formation of acyl chlorides from carboxylic acids under very mild conditions. Oxalyl chloride reacts with amides to give acyl isocyanates, and it is used with dimethyl sulfoxide as a mild reagent for the oxidation of alcohols (Swern-type oxidation). It is also used with N,N-dimethylformamide as a mild reagent for chlorination and formylation. Oxalyl chloride is widely used in commercial formulations of speciality polymers, antioxidants, photographic chemicals, X-ray contrasting agents, and chemiluminescent materials. Other physical properties are presented in Chapter 3. 

Without additional reagents Urethans from carboxylic acids via carboxylic acid chlorides, carboxylic acid azides, and isocyanates Shortened Curtins degradation... 

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