Reaction with carbamoyl chloride

A variation of this method involves the conversion of the amine into the amine hydrochloride prior to treatment with phosgene. This method has the advantage of producing generally cleaner products by retarding the secondary reaction of the free amine with carbamoyl chloride. 

Reaction of carbamoyl chloride (NH2COCl) with alcohols to yield carbamates [43]. 

The reactivity of A2-thiazolin-5-ones is closely related to the protomeric equilibrium shown in Scheme 127. The nucleophilic activity of the C-5 oxygen atom is clearly demonstrated by its reaction with acetyl chloride, acetic anhydride, benzoyl chloride, methyl or phenyl isocyanate, carbamoyl chloride or phosphorus derivatives in the presence of bases, to give (205-208 Scheme 140). 

The most common reaction of selenolates is the nucleophilic substitution of halide compounds. For the synthesis of selenides 82 the selenolates 80 can be reacted with halides. Nucleophilic selenium species can also be reacted with a variety of other electrophilic compounds. The reaction with acid chlorides, chloroformates, or carbamoyl chlorides leads to the corresponding selenoesters 83 (R" = R ), selenocarbonates 83 (R" = OR ), or selenoamides 83 (R" = NR 2), respectively (Scheme 17).166... 

Scheme 123 Reaction of carbamoyl chlorides with aldehydes.

Effect of Hydrolyzable Chlorine on Activity of Tin Catalysts. The effect of small amounts of hydrolyzable chlorine on the catalytic activity of DBTDL was studied on the model aliphatic system—isocy-anatoethyl methacrylate and n-butanol. The presence of the hydrolyzable chlorine in isocyanate usually decreases the reactivity of isocyanates in the urethane reaction. The results of measurements of the chlorine effect on the change of the rate constant is summarized in Figure 8. It was determined that the very small amounts of the hydrolyzable chlorine, especially in the form of carbamoyl chloride, increased at the beginning the rate constant for the urethane reaction catalyzed by DBTDL and after achieving the maximum at 500 ppm of chlorine the reactivity decreased. This effect was not observed when benzoyl chloride was used in place of carbamoyl chloride. It was assumed that the activation effect of the chlorine was due to the interaction of the carbamoyl chloride with the DBTDL catalyst. In order to understand this effect, the interaction of DBTDL with carbamoyl chloride of hexamethylene diisocyanate (with and without the presence of n-butanol) was studied using the IR technique. Results are summarized in Figure 9. 

According to the process of Campbell and Klingmann (1961) thiolcarbamic acid esters can be prepared with a good yield (90%) by the reaction of carbamoyl chlorides with alkyl mercaptans in solvent-free m ium, in the presence of anhydrous zinc chloride as catalyst. The reaction is the following ... 

With the above plan in mind, we examined the regioselective N-carbamoylation of oxazolidinone (-)-97 with carbamoyl chloride 98 and a combination of n-BuLi and DABCO as bases. In this reaction (-)-97 was treated with n-BuLi in THF at low temperature, and the carbamoyl chloride 98 was added. The mixture was then heated at reflux for 3-4 h, and DABCO (3 eq) was introduced, and reactants were thereafter stirred at reflux for a further 18 hours. The highly crystalline A-carbamoyl oxazolidinone (-)-102 was the end-result it was isolated in 88% yield. Its structure was confirmed by spectroscopic means, and subsequently verified by single crystal X-ray analysis. A second A -acylation with the... 

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. 

Salicylaldehyde and triethyl phosphite upon heating gave, instead of the expected diphosphonate (20), the rearranged phosphate-phosphonate (21). A new method to obtain 1-aminoalkylphosphinic acids (22) has been published it involves addition of bis(trimethylsilyl) phosphonite to Af-trityl imines, followed by hydrolysis. A similar reaction of bis(trimethylsilyl) phosphonite with 1-pyrroline trimer gave 2-pyrrolidinylphosphinic acid in 90% yield. Bis(trimethylsilyl) phosphonite with carbamoyl chlorides and triethylamine gave fair yields of the carbamoylphosphonites (23). ... 

In an alternative mechanism [1], it is suggested that the cold stage also involves the reaction of carbamoyl chloride with amine to give isocyanate and amine hydrochloride ... 

Esterification can be carried out using conventional reactions with acid chloride or with acid anhydrides. The etherification of inulin can be done using alkylepoxides as reactant. Carbamoylation reactions using alkyl isocyanate can be performed, obtaining inulin carbamates. 

The ester 870 is prepared by the cross-coupling of the chloroformate 869 with an organotin reagent. Some chloroformates are easily decomposed by a Pd catalyst, and hence the reaction should be carried out by slow addition of the chloroformates. Similarly, the amide 872 is prepared by the reaction of the carbamoyl chloride 871 [742]. The coupling of alkylcopper with ethyl chloroformate catalyzed by Pd affords esters[743]. 

Other unsymmetrical peroxides can be prepared by this reaction by employing other acylating agents, eg, alkyl chloroformates, organosulfonyl chlorides, and carbamoyl chlorides (210). Unsymmetrical and symmetrical di(diacyl peroxides) also are obtained by the reaction of dibasic acid chlorides directiy with peroxycarboxyhc acids or monoacid chlorides directiy with diperoxycarboxyhc acids in the presence of a base (44,187,203). 

Phosgene reacts with a multitude of nitrogen, oxygen, sulfur, and carbon centers. Reaction with primary alkyl and aryl amines yield carbamoyl chlorides which are readily dehydrohalogenated to isocyanates. Secondary amines also form carbamoyl chlorides. 

An interesting illustration of a bielectrophile contributing two heteroatoms to the resultant five-membered ring is the 2-alkyl-2-chloro- (or fluoro-) sulfonylcarbamoyl chlorides (212). With methylhydrazine initial attack by the more basic nitrogen occurred on the carbamoyl chloride, and this was followed by base-induced cyclization to 1,2,3,5-thiatriazolidine derivative (213) (77JCR(S)238, 77JCR(M)2813). Other reactions of this type are discussed in Chapter 4.28. 

The carbamoyl chloride formed may then be decomposed more or less simultaneously with the intial phosgene-amine reaction to produce diisocyanate. A urea may be formed as the result of side reactions. 

The reaction of the enamines 28 and 113 with N,N-dimethyl carbamoyl chloride has been reported to give no isolable -keto amides 63). 

The enamino ketone (49) was reported to give no identifiable products on reaction with N,N-dimethyl carbamoyl chloride 63). However, reaction of (49) with N,N-diethyl carbamoyl chloride in refluxing chlorobenzene gave the N-(3-diethyl-amino-5,5-dimethylcyclohex-2-en-1 -ylidene)pyrrolidinium salt, isolated as the perchlorate. The latter must have been formed as outlined in Scheme I, involving initial O carbamoylation followed by an addition-elimination reaction to give 138 cation which can react with diethylamino anion by a further addition-elimination displacement to give the product 46). 

Reaction of w-methylpiperazine with phosgene affords the carbamoyl chloride (170). Treatment of this intermediate with diethylamine affords the antiparasitic agent diethyl carbamazine (171)... 

Reaction of bis(2-chloroethyl)amine with phosgene affords the corresponding carbamoyl chloride Acylation... 

The ureas, e.g. 28 (R = NMe2), derived from the corresponding 2-(l-arylviny )benzylamines by reaction with (dimethylamino)carbamoyl chloride (Me2NCOCl) in the presence of triethyl-amine, undergo cyclization in refluxing phosphoryl chloride to the 5-aryl-3-(dimethylamino)-l//-2-benzazepin-3-amines. e.g. 29a.84 Prepared similarly are the 3-(4-methylpiperazin-l-yl) compound 29b and the 3-methyl derivative 29c from the corresponding urea and amide, respectively. 

A more highly oxidized derivative of quinazoline forms the heterocyclic moiety of a compound with CNS activity. Condensation of the aminopropylpiperazine 141 with isatoic anhydride gives the anthranilamide 142. Reaction of that amide with phosgene gives directly the heterocyclic ring. (The reaction may proceed by initial formation of the carbamoyl chloride ... 

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

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