Amines chlorocarbonylation

A novel application of a phenyl aryldiazosulfone was found by Kessler et al. (1990). l-[4-(7V-Chlorocarbonyl-7V-methylamino)phenyl]-2-(phenylsulfonyl)diazene (6.18) is an acid chloride with a potential diazonio group. The above authors showed that in organic solvents (THF, etc.) this compound reacts easily, as expected, with nucleophiles (HNu), e.g., with aliphatic, aromatic, or heterocyclic amines, with cystine dimethyl ester, or with 4-methoxyphenol at the carbonyl function, yielding... 

Based on the well-known reaction of phenoxazine with phosgene,15 leuco Basic Blue 3 was treated with phosgene to form the stable 10-chlorocarbonyl-3,7-diethylaminophenoxazine (39) which can be isolated and further reacted with alcohol or amine.16... 

Dihydro-1,2,4-oxadiazol-5-ones (74) cannot be 7V-acylated by either chlorocarbonyl isocyanate or trichloroacetyl chloride. However, preparation of 4-chlorocarbonyl compounds (73) can be achieved by cycloaddition of stable nitrile oxides to the C=N double bond of chlorocarbonyl isocyanate <888994, 90ZOR339). Compounds (73) decompose with ammonia, primary amines, or primary amides to isocyanates and (74) (Scheme 26). 

Recently, a new efficient approach for the preparation of 4-alkyl-l,2,4-dithiazolidine-3,5-diones (Dts-amines) 26 was developed by G. Barany and co-workers <2005JA508>. They have shown that Dts-amines 26 can be synthesized directly in a simple and robust reaction of bis(chlorocarbonyl)disulfane with bis(trimethylsilyl)amines that uses the trimethylsilyl group as a large proton to circumvent extant synthetic problems. The reaction occurs in a dry medium with extrusion of two molecules of trimethylchlorosilane (Scheme 39). This simplification and improvement in the synthesis of Dts-amines 26 promises to open new avenues for the application of Dts-based protection strategies. 

Amide should be first transformed to its hydrochloride in order to cut down the formation of a-chloro-jf(-chlorocarbonyl enamines 72,73). The method is very general but the choice of experimental conditions and of the base is critical and yields may vary strongly depending on the case (39). There is also one side-reaction which can hardly be avoided the ynamine already formed reacts with the yet unreacted amide chloride, the a-chloroenamine 70) or even with the tert-amine hydrochloride to form the very stable cyclobutene cyanines and/or allenamidinium salts. These by-products have an interest of their own and will be discussed later. Formation of these salts may strikingly lower the yield of ynamines, but because of their salt character they are not harmfull during the work-up72). 

Under radical conditions tributyltin hydride reduced a-chlorocarbonyl compounds to the corresponding saturated carbonyl derivatives but in the presence of phosphine oxides (HMPA or BU3PO) chemose-lective reduction of the carbonyl group was observed. a-Chloro ketones and aldehydes were reduced with this reagent combination to give good yields of the chlorohydrins. The choice of ligand was important as neither phosphines nor amines were effective substitutes for the phosphine oxides. 

Many amides have been prepared from pyrazinecarboxylic acid chlorides some are listed below with the relevant amines and references 2-chlorocarbonyl [MeNHj/ EtOAc (138) Me NH/EtOAc (138) BujNH etc/EtOAc (138) aniline/EtOAc (138, 1335) other aromatic and heterocyclic amines/EtOAc (138) sulfanilamide/ pyridine (1336) p-(2 -aminoethyl)benzenesulfonamide (1385) p-anisidine/benzene (1334) 4-hydroxypiperidine/benzene chloroform (1386) morpholine/DMF/20° (1387) 2-aminopyrimidine/benzene (1388) glycine/NaOH/ether (1201, cf. 1333, 1360)] 2-chlorocarbonyl-5-methyl [MeNHj/benzene (1337) MejNH/benzene (1337) 4-phenylpiperazine or diethanolamine/benzene-chloroform (1386) 2-chlorocarbonyl-3-phenyl (6-aminopenicillanic acid) (1024) 2-chloro-3-chloro-carbonyl (morpholine/benzene) (838) 2-chloro-5-chlorocarbonyl (NH4OH) (839) 2-chloro-6-chlorocarbonyl (Et2NH/benzene) (870, 1389) 2-chlorocarbonyl-5-hydroxy (aniline/benzene) (1055) 2-chlorocarbonyl-3-methoxy (morpholine/ benzene) (867) 2-chlorocarbonyl-5-methoxy (morpholine/benzene-chloroform) (1386) and 2-(l -chlorocarbonylethyI) (morpholine/benzene) (364). 

In order to develop various new applications of carbamoyl chlorides, we were interested in the synthesis of compounds containing functional groups such as ether oxides of tertiary amines. Thus, we studied and scaled up an improved process for the production of N-chlorocarbonyl morpholine based on a modification of literature data (Ref. 172) [Scheme 120]. 

Dialkyl l-(aminocarbonyl)alkylphosphonates are prepared by coupling amines with dialkyl 1-(alkoxycai bony I )alky I phosphonates," with dialkyl (chlorocarbonyl)methylphospho-... 

The reactions of 2-piperidineacetamides with aqueous formaldehyde [68BRP1114397 72JCS(P2)1920] or with A, A-dimethylcarboxamide dialkyl acetals (84EUP104647 85JMC1285) gave perhydro- or 4,4a,5,6,7,8-hexahydro-3/7-pyrido[l,2-c]pyrimidin-3-ones, respectively. Reaction of 1-chlorocarbonyl-2-[l-cyano-l-phenyl-3- [A,A-di(2-propyl)amino]propyl piperidine with ammonium hydroxide or primary amines at 80°C afforded... 

The use of phenoxycarbonyl isocyanate for cyclizing an aminoazole in pyridine is well known (p. 289). This reaction may also be effected by refluxing the reactants in a neutral high-boiling solvent. Chlorocarbonyl isocyanate (review [2929, 3802]) is also a very effective reagent for cyclizing such amines. 

For preparation of compound 193, carbamoylation of 177 by three general methods was smdied extensively (i) the reaction of 177 with isocyanates (Method 1), (ii) the reaction of l-chlorocarbonyl-5-fluorouracil 194 with amines (Method 2), and (iii) the reaction of 177 with carbamoyl chlorides (Method 3). These three methods usually give l-carbamoyl-5-fluoruracils 195 (Scheme 12.34). 3-Carbamoyl-5-fluorouracils are not formed in these reactions. 

The synthesis of cyanurates 215 started with condensation of the corresponding amines with an excess of nitrobiuret 214 (method A, Scheme 33). Subsequent ring closure with diethyl carbonate and sodium ethoxide gave compound 215 in good yields. Similar results could be obtained by the reaction of the same amines with A -chlorocarbonyl isocyanate (method B, Scheme 33) <2002CEJ2288>. 

A wide variety of fluorescent molecular probes have been demonstrated to be suitable for excitation by the He-Cd laser 4-bromomethyl-7-methoxycoumarln has been employed for the detection of carboxylic and phosphoric acids (44,55), 7-chlorocarbonyl-methoxy-4-methylcoumarln for hydroxyl compounds (42), 7-lsothlocya-nato-4-methylcoumarln for amines and amino acids (55), 7-dlazo-4-methyl-coumarln for a variety of aromatic compounds (55), and terbium chelate molecules with long fluorescence lifetimes ( 1 ms) for protein analysis (56). In this study, we examined the utility of l-dlmethylamlnonaphthalene-5-sulfonyl chloride (dansyl chloride) as a sensitive and selective reagent for the determination of biogenic amines and amino acids. 

Thiazopyr (2) is synthesized in a similar fashion. Treatment of the bis-acid chloride 8 in methanoliTHF (1 1) at room temperature for 2.5 h affords the 5-chlorocarbonyl-3-methyl ester selectively [24], which is allowed to react with 2-hydroxyethyl amine to form the corresponding 2-hydroxyethyl amide 9. The hy-droxyethyl amide 9 is subsequently treated with phosphorus pentasulfide and hexamethyl phosphoramide, resulting in sulfurization and cyclization to form the 4,5-dihydrothiazole in thiazopyr (2). 

Simple condensation reactions of cobalticinium hexafluorophosphate activated ester and 1,1 -bis(chlorocarbonyl)cobalticinium chloride with various amines produced new acyclic tripodal, and 1,1 -bis-substituted amide-linked cobalticinium ligands in very good yields. (Schemes 1 and 2). 

More recently, it has been shown that A alkyl and aryl l,2,4-dithiazolidine-3,5-diones (6) can also be accessed directly from the reaction between bis(trimethylsilyl)amines (11) and bis (chlorocarbonyl)disulfane (12) (eq 10). ... 

Regioselective chlorocarbonylation with oxalyl chloride and AICI3 in dichloro-methane at 15 °C of polybenzyl cores 1269 resulting from the CpFe+-induced oc-tabenzylation of durene has been reported [953]. Reaction of the resulting polychlorinated cores with amines and alcohol nucleophiles has opened new rapid synthetic routes toward dendritic materials. 

The chlorocarbonyl functionalized intermediates 1296 usually have limited stability. Under the reaction conditions, they are not isolable and easily eliminate carbon dioxide (in the case of 0-containing nucleophiles, e.g. alcohols or carboxylic acid substrates), or benzyl chloride (in the case of N-dealkylation of tertiary benzyl-amines). 

Herbicidally active l-aryl-4-carbamoyl-tetrazolinones 304 were recently obtained by reacting 1-aryl-tetrazolinones with phosgene in the presence of a solvent at 0-150 °C, and then reacting the resulting (novel) l-aryl-4-chlorocarbonyl-tetrazolinones 303 with amines in the presence of a solvent, and, where appropriate, in the presence of a further basic compound, at —20 to +100 °C [234]. 

In the reaction of chlorocarbonyl isocyanate with secondary amines, allophanoyl chlorides are formed, which are readily dehydrochlorinated to give dialkylaminocarbonyl isocyanate, which dimerizes by a [4+2] cycloaddition reaction to give 481 ". ... 

Thiazolo [3,2-c]pyrimidine-5,7-diones 123 (Ri = R2 = Rs= H, CH3 R4 = H, CH3) were prepared by reaction of N-(chlorocarbonyl) isocyanate with 2-alkylthiazolines 122 (Scheme 54) in acetonitrile containing triethyl amine [80],... 

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