Phosgene, reaction with

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

Isocyanate. Lysine has two amino groups in the molecule and dHsocyanate is prepared by reaction with phosgene. Lysine trHsocyanate [69878-18-8] (LTI) is developing on a commercial scale in Japan (244). 

Fatty acid chlorides are very reactive and can be used instead of conventional methods to faciUtate production of amides and esters. lmida2oles are effective recyclable catalysts for the reaction with phosgene (qv) (24). 

Another CNS active agent in this structural class is the tranquilizer-antidepressant caroxazone (52). Its published synthesis begins by reductive aminatiwi of salicylaldehyde and glycinamide to give The synthesis is completed by reaction with phosgene and sodium bicarbonate. ... 

Initially, 50 was converted into the benzoxazinone 51 by reaction with phosgene in the presence of triethylamine and 51 was isolated in 95% yield upon crystallization from methanol. Deprotection of the pMB group from 51 was accomplished with ceric ammonium nitrate (CAN) in aqueous acetonitrile. Efavirenz was isolated in 76% yield after crystallization from EtOAc-heptane (5 95), as shown in Scheme 1.19. There were two issues identified in this route. First, lequiv of ani-saldehyde was generated in this reaction, which could not be cleanly rejected from product 1 by simple crystallization to an acceptable level under the ICH guideline. Anisaldehyde was removed from the organic extract as a bisulfite adduct by washing with aqueous Na2S205 twice, prior to the crystallization of 1. Secondly,... 

Conversion of the amino alcohol 53 to Efavirenz (1) was readily accomplished by reaction with phosgene or phosgene equivalents. The most convenient and economically sound method is to react 53 with phosgene in the absence of base in THF-heptane at 0-25 °C. After aqueous work-up, Efavirenz was crystallized from THF-heptane in excellent yield (93-95%) and purity (>99.5%, >99.5% ee). 

Imidazole, purification of, 48, 45 reaction with phosgene, 48, 44 Imldazole, 1,1 -carbonyldi-, 48, 44 Imidazolium chloride, 48, 46 3-Imino-l-( -tolylsulfonyl)pyrazolidine, from 3-amino-3-pyrazoline sulfate and / -toluenesulfonyl chloride, 48, 9... 

This reaction is typical for the synthesis of sulfonylureas it is mildly exothermic and proceeds smoothly in a variety of inert aprotic solvents. The product is usually obtained in very high yield, as a fine crystalline precipitate. The sulfonyl isocyanates are readily prepared from the substituted benzene sulfonamides by reaction with phosgene, Fig. 3, in the presence of an alkyl isocyanate, for example, butyl isocyanate in an inert solvent at 120 to 140°C according to the general procedure of H. Ulrich and A. A. R. Sayigh (Ref. 3). 

Two other derivatives of toluene are the important explosive trinitrotoluene (TNT) and the polyurethane monomer toluene diisocyanate (TDI). TNT requires complete nitration of toluene. TDI is derived from a mixture of dinitrotoluenes (usually 80% o,p and 20% o,o) by reduction to the diamine and reaction with phosgene to the diisocyanate. TDI is made into flexible foam polyurethanes for cushioning in furniture (35%), transportation (25%), carpet underlay (20%), and bedding (10%). A small amount is used in polyurethane coatings, rigid foams, and elastomers. 

Aniline is condensed with formaldehyde reaction with phosgene gives MDI. 

Ethinamate Ethinamate, 1-ethynylcyclohexanone carbamate (4.3.4), is synthesized by the condensation of acetylene with cyclohexanone and the subsequent transformation of the resnlting carbinol into carbamate by the subsequent reaction with phosgene, and later with ammonia [36,37]. 

Meprobamate Meprobamate, 2-methyl-2-propyl-l,3-propandiol dicarbamate (5.2.2) is synthesized by the reaction of 2-methylvaleraldehyde with two molecules of formaldehyde and the subsequent transformation of the resulting 2-methyl-2-propylpropan-l,3-diol (5.2.1) into the dicarbamate via successive reactions with phosgene and ammonia [48-50]. 

Acetazolamide Acetazolamide is 5-acetamido-l,3,4-thiadiazole-2-sulfonamide (9.7.5). The synthesis of acetazolamide is based on the production of 2-amino-5-mercapto-l,3, 4-thiadiazole (9.7.2), which is synthesized by the reaction of ammonium thiocyanate and hydrazine, forming hydrazino-N,N -( ji-(thiourea) (9.7.1), which cycles into thiazole (9.7.2) upon reaction with phosgene. Acylation of (9.7.2) with acetic anhydride gives 2-acetylamino-5-mercapto-l,3,4-thiadiazol (9.7.3). The obtained product is chlorinated to give 2-acetylamino-5-mercapto-l,3,4-thiadiazol-5-sulfonylchloride (9.7.4), which is transformed into acetazolamide upon reaction with ammonia (9.7.5) [24,25]. 

Methocarbamol Methocarbamol, 3-(2-methoxyphenoxy)-l,2-propanediol-l carbamate (15.3.13), is synthesized by successive reaction with phosgene and then ammonia into 3-(2-methoxyphenoxy)propanediol-1,2 [34,35]. 

Reaction with phosgene yields carbonyl bromide and aluminum chlorobromide ... 

Chlorination of methyl 2,3(l >4//)-quinoxalinedion-5-ylcarboxylate was efficiently achieved by reaction with phosgene in DMF at room temperature in 90% yield <1999JHC1271>. Other procedures using phosphoryl chloride alone or with phosphoms pentachloride or A, A -dimethylaniline decrease remarkably the yields of dichloroquinoxaline. 

The y-amino-p-hydroxy acid derived oxazolidinones 55 are prepared from the corresponding N-unprotected y-amino-p-hydroxy ester derivatives by reaction with phosgene,1119,391 carbonyl diimidazole,[41] or benzyl chloroformate.[86] Alternatively, cyclization is obtained from the N-carbamate protected derivatives, i.e. from the TV-isopropenyloxycarbonyl derivatives under heating,[381 or from the TV-Boc or N-Z derivatives under basic conditions. [68 81 87] By analogy, the p,y-diamino acid analogue is converted into the imidazolidinone 57 by treatment of the unprotected compound with phosgene.[83 88]... 

The cyclization of a-hydrazinohydrazones (653) with ketones has been used for the synthesis of 4-amino-2,3,4,5-tetrahydro-l,2,4-triazines (654), and their reaction with phosgene affords 4-amino-4,5-dihydro-1,2,4-triazin-3-ones (655) (78HC(33)189, pp. 608, 656). 3-Thioxo-l,2,4-triazine-5,6-dione (657) was obtained when oxamohydrazide (656) reacted with thiophosgene (76ACS(B)7l). 

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