Phosgene and triethylamine

Treatment of 2,6-dimethylaniline (121) with phosgene and triethylamine affords the corre-S]ionding isocyanate (122). Condensation of that reactive intermediate with N-isopropylpropyl-cne-1,3-diamine leads to formation of urea 123. This product, recainam (123), acts as membrane Stabilizing agent and thus exhibits both local anesthetic and antiarrhythmic activity [30]. 

Nicotinic acid, conversion to anhydride with phosgene and triethylamine, 47,89... 

Addition of DBU to a solution of 149 in THF induced an elimination reaction accompanied by loss of a molecule of CO2 and provided the unstable amine 150, which was converted in situ into isocyanate 151 by reaction with phosgene and triethylamine. After filtration to remove hydrochloride salts, the solution of 151 was treated with samarium (II) iodide in the presence of lithium chloride. These conditions, which had been previously determined to be optimal for spirooxindole generation on a model system, provided compound 152 as an inseparable 7 1 mixture of diastereoisomers [43]. The major component of this mixture was determined by NOE analysis to have the required configuration, which is consistent with bond formation from the less hindered, convex face of 151 (Scheme 35). 

The diazepine 85 (tetramethyleneurea) has been prepared by a variety of routes. Among these are the treatment of tetramethylene diisocyanate with water,70-72 the rearrangement of the oxime (86) in polyphosphoric acid,73,74 and the reaction of 1,4-diaminobutane with sulfur, methanol, and carbon monoxide at high pressure.75 A novel preparation of 85 involves the reaction of 1,4-diaminobutane with 87 to give the silylated diamine (88). Reaction of 88 with phosgene and triethylamine yielded the bistrimethylsilyldiazepine (89) which was then hydrolyzed in aqueous ethanol to give 85.76... 

Treatment of the amino oxime 156 with phosgene and triethylamine in tetrahydrofuran at — 20°C gives 2-oxo-4,4,5-trimethyl-6-oxa-l,3-diazabi-cyclo[3.1.0]hexane (158) and the oxime 159, presumed to form via the intermediate 7V-oxide 157. ... 

The reagent is generated in toluene solution at—60 from furfuryl alcohol, phosgene, and triethylamine. ... 

With the two molecular systems in hand, we then set out to separate and identify each of the three atropisomers of 47 and 48. After extensive attempts, we found that by using semipreparative thin layer chromatography plates (0.25 mm thick silica, 20 x 20 cm), the rotamers could be separated in excellent yield, although it was necessary to use cold solvents to avoid thermal interconversion of individual atropisomers during the isolation process. The conformations of individual atropisomers were initially tentatively assigned by use of 1- and 2-D low temperature 1H NMR spectroscopy. The initial assignments were then confirmed by reaction with phosgene and triethylamine as discussed below. 

Other reagents are available for introducing the 2-oxo group. Thus, 2-amino-3-pyridyl phenyl ketone, ethyl carbamate, and zinc chloride, fused for 45 min at 230°C, gave a good yield of 4-phenylpyrido[2,3-d ] pyrimidin-2-one (see 3). In addition, 2-ferf-butylamino-3-pyridylphenylketonimine, phosgene, and triethylamine, stirred in cold benzene for 10 min, produced... 

Preparative Methods by the reaction of 2-morpholinoethylamine with Formic Acid in boiling toluene with a water separator, to yield the formamide which is treated either with Phosgene and Triethylamine in CH2CI2 or with Phosphorus Oxychloride and Diisopropylamine.The use of diisopropylamine as base is favored as yields are improved, typically to 68%. Trichloroacetic Anhydride has also been used as an alternative for COCI2, giving a yield of 74%. ... 

To this acid was then added 1 g of 4-ethyl-2,3-dioxo-1-piperazinocarbonyl chloride (from the reaction of N-ethylethylenediamine and diethyl oxalate to give 2,3-dioxo-4-ethyl-piperazine which Is then reacted with phosgene) and the resulting mixture was reacted at 15°C to 20°C for 2 hours. After the reaction, a deposited triethylamine hydrochloride was separated by filtration, and the filtrate was incorporated with 0.4 g of n-butanol to deposit crystals. The deposited crystals were collected by filtration to obtain 1.25 g of white crystals of 6-[ D(—l-Ct-(4-ethyl-2,3-dioxo-1 -piperazinocarbonylaminolphenylacetamido] penicillanic acid. Into a solution of these crystals in 30 ml of tetrahydrofuran was dropped a solution of 0.38 g of a sodium salt of 2-ethyl-hexanoic acid in 10 ml of tetrahydrofuran, upon which white crystals were deposited. The deposited crystals were collected by filtration, sufficiently washed with tetrahydrofuran and then dried to obtain 1.25 g of sodium salt of 6-[D(—)-a-(4-ethyl-2,3-di-0X0-1-piperazinocarbonylaminolphenylacetamido] penicillanic acid, melting point 183°C to 185°C (decomposition), yield 90%. 

Dimethyl and diethyl (l-methylpyrrolidin-2-ylidene)malonates (e.g., Scheme 38,467, n = 0, R = R1 = Me, Et R2 = H R4 = Me) and diethyl (l-methyl-l,2-dihydroquinolin-2-ylidene)malonate were obtained in 30-52% yields when l-methylpyrrolidin-2-one and 1-methyl-1,2-dihydroquinolin-2-one were first reacted with phosgene and then with dialkyl malonates in the presence of triethylamine in benzene at 60°C (61CB2278 69JA6683). 

The reaction between a dihydroxy compound (bisphenol) and phosgene, which is performed on an industrial scale, proceeds even at room temperature.The reaction is generally carried out in a biphasic medium consisting of methylene chloride (with dissolved phosgene) and aqueous sodium hydroxide (with dissolved bisphenol sodium salt) and a phase transfer catalyst (e.g.triethylamine).The procedure is termed interfacial polycondensation (see Sect.4.1.2.3 and Examples 4-5,4-12,and 4-13). 

Isocyanides Phosgene in combination with triethylamine has generally been preferred to phosphoryl chloride and triethylamine for dehydration of formamides to isocyanides (1, 857). However, use of phosphoryl chloride in combination with diisopropylamine can give isocyanides in yields comparable to those obtained with phosgene. Even so this new method can fail with some simple alkyl formamides. 

To 20% solution of phosgene in toluene, agitated and cooled to 0°C, are added over 30 min a solution of l-p-fluoro-benzoyl-l-hydroxy-3-N-[N -(2-methoxyphenyl)]piperazinopropane and triethylamine in anhydrous chloroform. It is agitated at ambient temperature for 5 h, cooled to 0°C and the solution saturated with gaseous ammonia. The solution is agitated at ambient temperature for 3 h, filtered and the filtrate dried under reduced pressure, 4-p-fluorophenyl-5-p-(4-o-methoxyphenylpiperazino)ethyl-4-oxazolin-2-one, melting point 154°C (by alcohol) was obtained. 

TTOC Carbonates To a cold solution (0 C) of 23 mmol of phosgene in 12 mL of toluene are added 4 mmol of the appropriate allylic or homoallylic alcohol and 0.43 g (3.3 mmol) of triethylamine. After 2 h at 0 °C, excess phosgene and solvents are removed at reduced pressure. The crude chloroformate is dissolved in 30 mL of benzene and to this solution is added a mixture of 0.4 g (4 mmol) of 3-hydroxy-4-methylthiazolc-2(3//)-thione and 0.43 g (4.3 mmol) of triethylamine in 5 mL of benzene. After 3 h at 20 °C, the solvent is removed under reduced pressure, and the crude TTOC carbonate is purified by chromatography (silica gel, EtOAc/hexane 15 85). The TTOC carbonates are isolated in 60- 65% yield and can be employed in subsequent reactions without purification. 

Since then most isocyanides have become readily available by the transformation (1) -> (2), the method of choice for the preparation of isocyanides. The best dehydrating agents for (1) are phosgene and diphosgene in the presence of triethylamine, and phosphorus oxychloride in the presence of diiso-propylamine. °... 

In general, these two reactions are definitely not suitable for the preparation of appreciable quantities of pure isonitriles indeed, they have been largely replaced by the more widely applicable dehydration method [lc,d,fj. This was first discovered by Hagedorn in 1956 and entails transformation of primary amines into for-mamides, followed by dehydration either with phosgene (or its precursors) and triethylamine, or phosphorus oxychloride and di-wo-propylamine [If]. 

Composites of PANI-NFs, synthesized using a rapid mixing method, with amines have recently been presented as novel materials for phosgene detection [472]. Chemiresistor sensors with nanofibrous PANI films as a sensitive layer, prepared by chemical oxidative polymerization of aniline on Si substrates, which were surface-modified by amino-silane self-assembled monolayers, showed sensitivity to very low concentration (0.5 ppm) of ammonia gas [297]. Ultrafast sensor responses to ammonia gas of the dispersed PANI-CSA nanorods [303] and patterned PANI nanobowl monolayers containing Au nanoparticles [473] have recently been demonstrated. The gas response of the PANI-NTs to a series of chemical vapors such as ammonia, hydrazine, and triethylamine was studied [319,323]. The results indicated that the PANI-NTs show superior performance as chemical sensors. Electrospun isolated PANI-CSA nanofiber sensors of various aliphatic alcohol vapors have been proven to be comparable to or faster than those prepared from PANI-NF mats [474]. An electrochemical method for the detection of ultratrace amount of 2,4,6-trinitrotoluene with synthetic copolypeptide-doped PANI-NFs has recently been reported [475]. PANI-NFs, prepared through the in situ oxidative polymerization method, were used for the detection of aromatic organic compounds [476]. 

---