Phosgene, catalytic reaction

Desorption of CO from the surface of such charcoal occurs only at temperatures much higher than those employed in phosgene catalytic synthesis therefore, stage 1 of scheme (371) is irreversible under the usual conditions of the reaction. Kinetic measurements show that the reaction is retarded... 

The release of phosgene and toxic solvent has stimulated the development of novel processes. The BASF process for MDI, that employs high temperatures and pressures to increase the rate of reaction, does not release phosgene. Catalytic routes, via oxidative carbonylation of aniline to methyl A-phenyl carbamate (12), using palladium metal... 

Catalysis. Catalytic properties of the activated carbon surface are useful in both inorganic and organic synthesis. For example, the fumigant sulfuryl fluoride is made by reaction of sulfur dioxide with hydrogen fluoride and fluorine over activated carbon (114). Activated carbon also catalyzes the addition of halogens across a carbon—carbon double bond in the production of a variety of organic haUdes (85) and is used in the production of phosgene... 

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. 

Oxidative carbonylation is not necessarily associated with C - C bond formation. Indeed, heteroatom carbonylation may occur exclusively, as in the oxidative carbonylation of alcohols or phenols to carbonates, of alcohols and amines to carbamates, of aminoalcohols to cyclic carbamates, and of amines to ureas. All these reactions are of particular significance, in view of the possibility to prepare these very important classes of carbonyl compounds through a phosgene-free approach. These carbonylations are usually carried out in the presence of an appropriate oxidant under catalytic conditions (Eqs. 31-33), and in some cases can be promoted not only by transition metals but also by... 

Since both methylation and methoxycarbonylation generate CH30 , both reactions can be conducted in the presence of catalytic amounts of base. This avoids the formation of unwanted inorganic salts as by-products, and the related disposal problems. In principle, the methanol produced can be recycled for the production of DMC. In contrast, methylation with methyl halides or DMS, and carbonyla-tion with phosgene aU generate stoichiometric amounts of inorganic salts. 

A recent patent application describes, in part, a multikilogram scale synthesis of quinapril (Jennings, 2004). The carboxyanhydride of 26 is prepared by treatment with phosgene (Scheme 10.8) (Youssefyeh et al., 1987). This is next coupled with tetrahydroisoquinoline subunit 27 in the presence of catalytic acid. Without isolation of the resultant quinapril t-butyl ester, the reaction solution is treated with acetic acid and anhydrous hydrogen chloride to deprotect the ester. Amorphous quinapril hydrochloride is obtained via treatment with acetonitrile. 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Methyl 4,6-0-benzylidene-3-deoxy-a-D-ribo-hexopyranoside (56) was benzoylated, debenzylidenated, and partially p-toluenesulfon-ylated to 57 this was converted into 58 by reaction with sodium iodide, followed by catalytic reduction. The methanesulfonate of 58 was converted into 59 by reaction with sodium azide in N,N-dimethylformamide, and 59 was converted into 4-azido-3,4,6-trideoxy-a-D-xylo-hexose (60) by acetolysis followed by alkaline hydrolysis. Reduction of 60 with borohydride in methanol afforded 61, which was converted into 62 by successive condensation with acetone, meth-anesulfonylation, and azide exchange. The 4,5-diazido-3,4,5,6-tetra-deoxy-l,2-0-isopropylidene-L-ara/uno-hexitol (62) was reduced with hydrogen in the presence of Raney nickel, the resultant diamine was treated with phosgene in the presence of sodium carbonate, and the product was hydrolyzed under acidic conditions to give 63. The overall yield of 63 from 56 was 4%. The next three reactions (with sodium periodate, the Wittig reaction, and catalytic reduction) were performed without characterization of the intermediate products, and gave (+)-dethiobiotin methyl ester indistinguishable from an authentic sample thereof prepared from (+)-biotin methyl ester. 

Amidines with a more complicated substitution pattern have been prepared from amidines by alkylation—either at nitrogen or at nitrogen substituents. - Variations at these positions have been achieved by heteroarylation, acylation,vinylation or carboxylation with phosgene, thio-phosgene, isocyanide dichlorides or isothiocyanates. Some interesting amidines, e.g. (347)-(3S2) (Scheme 59), have been prepared in this manner. The amidine skeleton can also be varied by halogen-ation, - hydrolysis, isomerization or catalytic hydrogenation or other addition reactions if there are C=—C double bonds present as in (353 equation 173) for example. ... 

This process was elaborated as a heterogeneously catalyzed variation by Asahi Chemicals (Japan) in order to open a new route to diisocyanates, not depending on the use of phosgene [120, 134]. Ethyl phenylcarbamate, which in a first step is obtained by catalytic oxidative carbonylation of aniline, CO, oxygen, and ethanol (eq. (17)), is condensed with aqueous formaldehyde to yield methylene diphenyl diurethane. Thermal decomposition leads to methylene diphenyl diisocyanate (MDI), which is one of the most important intermediates for the industrial manufacture of polyurethanes (eq. (18)). The yields and selectivities of the last reaction step seem to be the main reasons why this process is still inferior to the existing ones. 

Preparation of acid chlorides. The thionyl chloride method of preparing acid chlorides fails with some carboxylic acids (e.g., p-NOjCsHaCOzH) and with all sulfonic acids. Bosshard and co-workers" found that dimethylformamide catalyzes both reactions, either when used as solvent or when employed in catalytic amount in an inert solvent. The reactive, hygroscopic intermediate dimethylformirainium chloride was isolated from one equivalent each of dimethylformamide and thionyl chloride, and also obtained by reaction of dimethylformamide with phosgene, oxalyl chloride, or phosphorus pentachloride. It reacts with an acid with regeneration of dimethylformamide, the catalyst. In one example, 0.3 mole of p-nitrobenzoic acid was heated briefly at 90-95° with 0.315 mole of thionyl chloride and 0.03 mole... 

Under certain conditions, dichloromethane (often the major constituent of chemical paint removers) can be converted into phosgene [238,747]. Tobacco smoke, exhaust gases from oil-fired furnaces or petrol engines, and hot metal surfaces are all reported to have a catalytic effect on the reaction [238] ... 

Manufacture of dichlorine is generally by the electrolysis of brine, although electrolysis of aqueous HCl or catalytic oxidation of dry HCl may be employed [2165]. As mentioned above, complete reaction of the dichlorine must be ensured, as this is an undesirable impurity in the phosgene product [437,1488], particularly where the material is to be used for high specification polycarbonates or isocyanates. 

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