Reagents phosgene

Starting Molecule anhydrous Lysergic acid Reagents Phosgene Diethylamine... 

Phosgenation Reagents Phosgene, Equivalents CAS Reg. No. Source Order No. 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

Acid Chloride Formation. Monoacid chlorides of maleic and fumaric acid are not known. Treatment of maleic anhydride or maleic acid with various reagents such as phosgene [75-44-5] (qv), phthaloyl chloride [88-95-9] phosphoms pentachloride [10026-13-8] or thionyl chloride [7719-09-7] gives 5,5-dichloro-2(5JT)furanone [133565-92-1] (4) (26). Similar conditions convert fumaric acid to fumaryl chloride [627-63-4] (5) (26,27). NoncycHc maleyl chloride [22542-53-6] (6) forms in 11% yield at 220°C in the reaction of one mole of maleic anhydride with six moles of carbon tetrachloride [56-23-5] over an activated carbon [7440-44-4] catalyst (28). 

Reactions. Phosgene interacts with many classes of inorganic and organic reagents. The reactions have been described extensively (10). Reaction with sodium metal takes place at room temperature, but reaction with 2inc requires warming. 

Although POCl is the traditional reagent in the Vilsmeier aldehyde synthesis, phosgene may be employed (27—29). 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared in a variety of substitution reactions. Table 2 shows the rates of substitution compared to thiophene for formylation by phosgene and iV,AT-dimethylfor-mamide, acetylation by acetic anhydride and tin(IV) chloride, and trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235). 

Aryl isothiocyanates can be prepared by the action of thio-phosgene on the arylamine (this reaction fails with naphthyl compounds), by fission of a 5ym-diaryIthiourea with acidic reagents (this reaction involves the loss of half the amine used), and by the decomposition of an ammonium aryldithiocar-bamate (low yields are reported for naphthyl and other compounds).The procedure described here is that of Baxter, Cymerman-Craig, Moyle, and White. ... 

Depending on the reagent ratio, oxalyl chloride reacts with fluorobenzene m the presence of aluminum chloride to afford either 4-fluorobenzoyl chloride or 4,4 -difluorobenzophenone [ii] (equation 22). Phosgene, detected by infrared spectroscopy, is an intermediate. 

Many procedures for the formation of carboxylic acid amides are known in the literature. The most widely practiced method employs carboxylic acid chlorides as the electrophiles which react with the amine in the presence of an acid scavenger. Despite its wide scope, this protocol suffers from several drawbacks. Most notable are the limited stability of many acid chlorides and the need for hazardous reagents for their preparation (thionyl chloride, oxalyl chloride, phosgene etc.) which release corrosive and volatile by-products. Moreover, almost any other functional group in either reaction partner needs to be protected to ensure chemoselective amide formation.2 The procedure outlined above presents a convenient and catalytic alternative to this standard protocol. 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

Isocyanides can be prepared by elimination of water from N-alkylformamides with phosgene and a tertiary amine. Other reagents, among them TsCl in quino-... 

Phosgene can be replaced by a 0.5 molar equivalent of tri-chloromethyl chloroformate. This reagent may be purchased from... 

Trichloromethyl chloroformate has proven effective in the preparation of N-carboxy-a-amino acid anhydrides from amino acids, and various compounds having isocyanate, acid chloride, and chloroformate groups.For example, trichloromethyl chloroformate may be used instead of phosgene in the preparation of 2-tert-butoxycarbonyloxyimino-2-phenylacetonitrile. The use of this reagent is illustrated here by the synthesis of 3-isocyanato-propanoyl chloride from 3-aminopropanoic acid hydrochloride. 

Treatment of a chiral amine with phosgene is the cheapest way to prepare symmetrical ureas [29]. Nevertheless, due to the toxicity and reactivity of that reagent, it can advantageously be replaced by triphosgene [30] or l,l -carbonyldiimidazole [31-34] or other derivatives such as l,l -carbonyldi-2(lH)-pyridinone [35]. This procedure can be extended to thiophosgene (Scheme 1) and its thio-analogues, such as l,l -thiocarbonyldi-2(lH)-pyridinone to produce thioureas [36] chiral diamines can thus be transformed into the corresponding monoureas or monothioureas. 

The general advantage of using carbon tetrachloride or phosgene is that these compounds decompose at the reaction temperature to provide a uniform distribution of active carbon or carbon monoxide and chlorine at the reaction sites over the oxide surface. These reagents are, however, not as convenient to use as a carbon and chlorine mixture in large-scale operations. Besides, phosgene is poisonous. 

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