Phosgene unsymmetrical

In the ketone method, the central carbon atom is derived from phosgene (qv). A diarylketone is prepared from phosgene and a tertiary arylamine and then condenses with another mole of a tertiary arylamine (same or different) in the presence of phosphoms oxychloride or zinc chloride. The dye is produced directly without an oxidation step. Thus, ethyl violet [2390-59-2] Cl Basic Violet 4 (15), is prepared from 4,4 -bis(diethylamino)benzophenone with diethylaruline in the presence of phosphoms oxychloride. This reaction is very useful for the preparation of unsymmetrical dyes. Condensation of 4,4 -bis(dimethylamino)benzophenone [90-94-8] (Michler s ketone) with AJ-phenjl-l-naphthylamine gives the Victoria Blue B [2580-56-5] Cl Basic Blue 26, which is used for coloring paper and producing ballpoint pen pastes and inks. 

Symmetrical 5,5-dialkyl dithiocarbonates have been obtained by thermal rearrangement of the corresponding (9,5-dialkyl esters in the presence of Aliquat [43]. This procedure is not suitable for the preparation of unsymmetrical 5,5-dialkyl dithiocarbonates, as it has been reported that disproportionation of the products can lead to a mixture of the symmetrical and unsymmetrical esters. Alternatively, they can be prepared by a base-catalysed disproportionation of 5-alkyl-O-methyl dithiocarbonates [44] (Table 4.9). These methods for the synthesis of the 5,5-dialkyl esters are more convenient than the traditional procedures from the thiol and phosgene. 

Alcohols and phenols can be attached to support-bound alcohol linkers as carbonates [467,665,666], although few examples of this have been reported. For the preparation of carbonates, the support-bound alcohol needs to be converted into a reactive carbonic acid derivative by reaction with phosgene or a synthetic equivalent thereof, e.g. disuccinimidyl carbonate [665], carbonyl diimidazole [157], or 4-nitrophenyl chloro-formate [467] (see Section 14.7). The best results are usually obtained with support-bound chloroformates. The resulting intermediate is then treated with an alcohol and a base (DIPEA, DMAP, or DBU), which furnishes the unsymmetrical carbonate. Carbonates are generally more resistant towards nucleophilic cleavage than esters, but are less stable than carbamates. Aryl carbonates are easily cleaved by nucleophiles and are therefore of limited utility as linkers for phenols. 

The intermediate 1,3-diphosphapropenes can be synthesized in a separate reaction of bis(trimethylsilyl)phosphanes with phosgene or isocyanide dichlorides (29, 99), respectively, and can be converted to the unsymmetrically substituted pentadienes with phosphaketene [Eq. (47)]. 

The ethylidene, or unsymmetrical di-halogen substitution products of ethane, are not of much importance, because they do not easily undergo reaction. They are prepared by the reactions just described, viz., from aldehyde by the action of phosphorus penta-chloride, -bromide, or -iodide. Also by the action of phosphorus chlor-bromide, PCl3Br2, or of carbonyl chloride (phosgene), COCI2. They may also be made by the further halogenation of the mono-halogen ethanes ... 

Using this method, the complex [Fe(cp)(CO) j C(0)NHMe ] has been converted into [Fe(cp)(CO) j(CNMe)]Cl, and cis-[Pt(PPh3)j C(0)NHMe Cl] has been used to prepare cj s-[Pt(PPh3)(CNMe)CIj] [635]. In an interesting variation on this procedure, the reaction of phosgene with unsymmetrical carbodiimide adducts of iron has been used to prepare iron(II) complexes containing two different isonitrile ligands at a now chiral centre [636] ... 

Diacyl chlorides can often be either singly or doubly amidated. Carbamoyl chlorides are obtained from phosgene and ammonia or an amine under conditions that must be rigidly adhered to 596 they can then be applied to preparation of aromatic carboxamides by a Friedel-Crafts reaction or to the synthesis of unsymmetrically substituted ureas. 

For instance, methyl isocyanate can be prepared629 by treating diphenylamine with phosgene, which gives diphenylcarbamoyl chloride this can be converted by methylamine into the unsymmetrical urea derivative this 3-methyl-l,l-diphenylurea (226 g), when heated at 240-290°, affords methyl isocyanate (57 g, 100%), b.p. 38-40°, and the distillation residue consists of diphenylamine. 

The failure of cuscohygrine to condense with benzaldehyde, ethyl oxalate and amyl nitrite is hard to accommodate on formula X. Because of the formation of two isomeric hydrazones, and on the erroneous assumptions that base A was di-(a-iV -methylpyrrolidyl)-methane and that methylene di-isonitramine came from a methyl ketone group, Hess and Fink (22) altered Liebermann s formula X so as to represent cuscohygrine as an unsymmetrical di-(JV-methylpyrrolidyl)-propan-2-one (XIII). It has since been found, however, that base A is not identical with di-(a-IV-methyI-pyrrolidyl)-methane prepared by the action of phosgene on pyrrylmagne-sium bromide followed by reduction and methylation (25). Moreover,... 

The elimination of hydrogen chloride from chloroformamidine hydrochlorides is another example illustrating the utility of imidoyl halides. Thermolysis of diarylchloroformamidine hydrochlorides PCIV), obtained from N,N -disubstituted thioureas and phosgene, is the best method of synthesis of unsymmetrical carbodiimides (XV) because the generated... 

An early example of benzotriazole utility was the synthesis of a wide range of unsymmetrical tetra-substituted ureas (4) by reaction of 1,1 -carbonylbis-benzotriazole (2), generated in 90% yield from two equivalents of BtH and phosgene, with secondary amines (Scheme 2). The formation of ureas (4) was achieved in two steps via (3), and high yields were reported for both series of compounds (1997JOC4155). 

The groups and Z can be identical or different, thus generating symmetrical or unsymmetrical phosgene equivalents, respectively. 

R-Y-COCl plays the key role in phosgenation reactions that are of a stepwise nature the major part of these processes is COCl (chlorocarbonyl) transfer to R-Y-H generating chloroformates, carbamoyl chlorides, etc. R-Y-COCl is of limited (low) stability and this is the driving force behind its intermediacy in the synthesis of chlorides and isocyanates under elimination conditions (eliminating CO2 and/or HCl), and also determines the character of a reactive substrate in further nucleophilic substitutions to form symmetrical and unsymmetrical substituted carbonic acid derivatives carbonates, carbamates, ureas) or diaryl ketones. Commonly, chloro-formylation and isocyanate formation are independent of the nature of R. Obviously, the reactivity is very different due to the relative basic/nucleophilic ratio. For example, Ar-Cl cannot be prepared through a chloroformate intermediate nor by direct phosgenation, but the reaction does work well in the aliphatic series. 

Phosgene reacts with oximes to form 0-(ch oroformyl) oximes 124, which, on addition of antimony pentachloride, undergo smooth Beckmann rearrangement with loss of carbon dioxide to give the nitrilium salts 125 almost quantitatively [66]. With oxygen or nitrogen nucleophiles, O-(chloroformyl) oximes 124 form symmetrical and unsymmetrical oxalyl derivatives. 

Unsymmetrical carbonates 884 [642] can be synthesized in two steps from N-hydroxy-5-norbornene-2,3-dicarboxamide 881, phosgene, and the appropriate alcohols 883. The activated carbonates 884 are excellent reagents for the introduction of all currently used urethane protecting groups, such as Z, Boc, and Fmoc residues. 

A highly interesting synthetic route for forming intermediates en route to retinal and their analogues involves a palladium-catalyzed transformation of an yne-carbo-nate 888 into an aUenyl enal 889. The carbonate 888 is generated by unsymmetrical carbonylation of propargylic alcohol 886 and silyl enol ether 887 with phosgene [647]. 

Since the addition of amines to isocyanates 1005 can be regarded as the main route for the synthesis of the more challenging N,N -unsymmetrical substituted ureas 1004, isocyanates 1005 are starting reagents in many urea formation reactions. However, it is important to underline, as described in the Section 4.3.1, that isocyanates themselves are toxic and are usually prepared from phosgene [311, 747]. 

The two identical leaving groups (X = Y) in phosgene substitutes 1002 can be consecutively replaced to prepare both symmetrical and unsymmetrical ureas. The selectivity toward the unsymmetrical N,N -disubstituted ureas is critically dependent on the relative reaction rates of the two consecutive nucleophilic substitutions. If the second step is much slower than the first one, the formation of the symmetrical urea is minimized [726]. 

Triphosgene, a safe and stable crystalline solid substitute for phosgene [53, 148], is successfully utilized in the sequential synthesis of unsymmetrical ureas also bearing chiral amino acid derivatives, without any need to purify the intermediates [507]. 

Although numerous methods are available for the preparation of symmetrical and unsymmetrical di- or trisubstituted ureas in good to excellent yields, the only hitherto reported synthesis of unsymmetrical tetrasubstituted ureas involves reaction of a carbamoyl chloride (prepared from a secondary amine and phosgene) with a secondary amine [754]. Moreover, this method, as used more recently [755, 756], suffers from several drawbacks. An excess of amine and/or the use of an acid scavenger (such as pyridine or triethylamine) is required, and the carbamoyl chloride intermediate can be both unstable and difficult to isolate when needed. Moreover, the production of hydrochloric acid prevents the application of this method when acid-sensitive functionalities are present. N,N -Carbonyldibenzotriazole can be utilized to synthesize N,N,N, N -unsymmetrical tetrasubstituted ureas 1023 by a... 

Dimethyldithiocarbonate (DMDTC) 786 represents a mild and safely handled reagent, structurally similar to phosgene, which is useful in the synthesis of ureas (see also Section 4.3.2 Carbamates ). Tables 4.29, 4.30, and 4.31 illustrate various symmetrical and unsymmetrical ureas prepared with DMDTC. 

Unsymmetrical equivalemts of phosgene are less reactive and the rate and selectivity of carbonylation can be conveniently controlled by selecting the nature of the leaving groups and the conditions of consecutive displacements. 

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