Secondary amines phosgene

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. 

Primary cycloaUphatic amines react with phosgene to form isocyanates. Reaction of isocyanates with primary and secondary amines forms ureas. Dehydration of ureas or dehydrosulfuri2ation of thioureas results in carhodiimides. The nucleophilicity that deterrnines rapid amine reactivity with acid chlorides and isocyanates also promotes epoxide ring opening to form hydroxyalkyl- and dihydroxyalkylaniines. Michael addition to acrylonitrile yields stable cyanoethylcycloalkylarnines. 

Alternatively, secondary amine (46) can be treated with phosgene to give (47). This time a catalyst (AlCljjJ is necessary for cyclisation. Notice that cyclisatlon gives only (42) and not the alternative four-membered ring. 

Secondary amines react with phosgene to give carbamoyl chlorides [43] which, on treatment of excess secondary or primary amine or ammonia, yields an asymmetric urea [44-46],... 

Carbamyl chlorides, available by the reaction of phosgene on secondary amines, can react with hydrazines to give good yields of 1,1-dialkylsemi-carbazides [31] (Eq. 24). 

Simple isocyanates containing up to twelve carbon atoms are best prepared by a vapor-phase reaction of phosgene and a primary amine reported in 1950. The reaction occurs without a catalyst at 240-350° to form carbamyl chlorides from which the isocyanates are obtained by refluxing in an inert solvent or by treating with a tertiary amine. Over-all yields range from 58% to 88%. Secondary amines are converted to disubstituted carbamyl chlorides, RjNCOCl. ... 

The acylation of ammonia or primary and secondary amines by chloro-formic esters (chlorocarbonates) is the most general method for the synthesis of urethanes. Chlotoformates are obtained by the action of phosgene on alcohols (method 289) and, without purification, are converted to carbamates by cold concentrated ammonium hydroxide. Over-all yields from primary and secondary alcohols range from 55% to 94%. N-sub-stituted carbamates result in similar yields when primary" or secondary" amines are substituted from ammonia in the reaction. Aqueous sodium hydroxide is sometimes used to neutralize the acid formed. ... 

Asymmetric ureas, N,N dialkylurethanes, and 4,4-dialkylsemicarba-zides are available by this method. In general, the yields are excellent. Carbamyl chlorides are prepared by the action of phosgene on secondary amines (cf. method 411). 

Moreover, these new catalysts may be considered themselves as phosgene derivatives because they are made from phosgene and secondary amines by the scheme depicted below [Scheme 9] ... 

The reaction of phosgene with secondary amines or their hydrochlorides is a well known useful route to carbamoyl chlorides as shown in scheme 119 (Ref. 171). 

The effect of phosgene on a secondary amine R NH (Rj = Mej [1392e], Etj [1286a] or MePh [1392f]) is generally to form the corresponding carbamoyl chloride, according to Equation (10.6) ... 

These products may also be prepared from the reaction of COCi, with the hydrochloride salt of the secondary amine [1451]. In some cases, ureas are formed immediately, for example, in the reactions of piperidine [1652] or 2,2 -bipiperidine [668] with phosgene [1652] ... 

Mixed carbamoyl chloride-isocyanate compounds can be prepared by reaction of phosgene with a material possessing both a primary and a secondary amine function ... 

IV-silyl-substituted secondary amines combine with phosgene, as illustrated in Equation (10.32), to give a carbamoyl chloride [1409]. This proceeds at a faster rate with phosgene... 

Certain secondary amine compounds are commonly used for chemical derivation of isocyanates which, like phosgene, form substituted urea compounds amenable to chromatographic determination. One of the most common of these reagents is 1—(2—pyridyl)-piperazine (PYP) PYP reacts on a one-to-one basis with isocyanate compounds yielding a stable urea derivative which can be quantified specifically and sensitively with reversed phase, high performance liquid chromatography (HPLC) and ultraviolet absorbance detection. 

Isoselenocyanates and selenoamides. Formamides are converted to isoseleno-cyanates by reaction with Se, EtjN, and phosgene in toluene. Selenoamides are obtained" from secondary amines, Se, and 1,1-dihaloalkanes in the presence of NaH in HMPA. An oxidation is involved. 

Ureas and Carbonates. Reagent (1) may be used as a direct replacement for the highly toxic Phosgene in reactions with alcohols and amines. Reaction of (1) with two equivalents of a primary aliphatic or aromatic amine at room temperature rapidly yields a symmetrical urea (eq 9). If only one equivalent of a primary amine is added to (1), then the imidazole-Al-carboxamide (4) is formed (eq 10). These compounds can dissociate into isocyanates and imidazole, even at room temperature, and distillation from the reaction mixture provides a useful synthesis of isocyanates (eq 10).7 Secondary amines react only at one side of (1) at room temperature, again giving the imidazole-Al-carboxamide of type... 

SYNTHESIS The first step involves the s)mthesis of the amino acid 7-benzyl-L-glutamate by a standard Fischer esterification reaction of L-glutamic acid with benzyl alcohol in the presence of strong acid. The amino acid is subsequently converted to the N-carboxyanhydride (NCA) monomer by reaction with phosgene gas, or by reaction with the less hazardous compound triphosgene.The NCA is polymerized by initiation with a variety compounds such as primary and secondary amines, and alkoxides. Typical comonomers include other amino acid NCAs. 

Alkaloids are often rather unstable, e.g., N-oxidation is quite common. In addition to by heat and light, the stability is influenced by solvents (for a review see Baerheim Svendsen and Verpoorte 1983). Halogen-containing solvents are widely used in alkaloid research, and chloroform in particular is one of the most suitable solvents, because of its relatively strong proton donor character. However, these solvents are very active in terms of artifact formation. In chloroform (N-)oxidations occur readily. Also peroxides in ethers may rapidly cause N-oxidations. With dichloromethane, quaternary N-dichlorometho compounds may be formed (Phillipson and Bisset 1972). Similar compounds are formed with minor impurities present in chloroform. Moreover, in chloroform, phosgene is formed, which reacts with the stabilizer ethanol, yielding ethyl chloroformate. This compound may react with secondary amines, causing the formation of ethylcarbamates (Siek et al. 1977). 

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). 

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