Mixtures carbamates

In a 250 ml. conical flask, fitted with an air condenser of wide bore, place 50 g. (51 -5 ml.) of acetonylacetone (see Section V,9, Note 2) and 100 g. of ammonium carbonate (lump form). Heat the mixture in an oil bath at 100° until effervescence stops (60-90 minutes) some ammonium carbonate (or carbamate) sublimes into the condenser and this must be pushed back into the reaction mixture by means of a stout glass rod. Replace the air condenser by a Liebig s condenser with wide bore inner tube and reflux the mixture gently (bath temperature, 115°) for a further 30 minutes dissolve the solid which has sublimed into the condenser in about 5 ml. of hot water and return the solution to the reaction mixture. 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain pro-teaing groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N -deprotection. Only /ert-butyl esters and carbamates ( = Boc) are solvolyzed in this mixture. 

The stream from the reactor consisting of a mixture of urea, unconverted ammonium carbamate, excess water, and NH, is fed into the top of the stripper. The ACES stripper utilizes a ferrite—austenite stainless steel, as do the carbamate condensers. The reactor and scmbber are constmcted with 316 L urea-grade stainless steel. 

Only about 10% of the total urea production is used for amino resins, which thus appear to have a secure source of low cost raw material. Urea is made by the reaction of carbon dioxide and ammonia at high temperature and pressure to yield a mixture of urea and ammonium carbamate the latter is recycled. 

The earliest mention of an ammonium carbonate, salt of hartshorn, appears in English manuscripts of the 14th century. As the name implies, the material was obtained by dry distillation of animal waste such as horn, leather, and hooves. Although many salts have been described in the Hterature for the ternary NH —CO2—H2O system, most, except for ammonium bicarbonate [1066-33-7], NH HCO, ammonium carbonate [506-87-6], (NH 2 02, and ammonium carbamate [1111-78-0], NH4CO2NH2, are mixtures (5,6). 

A. Ethyl N- p-tolylsulfonylmethyl)carhamate,[Carbamic acid, (4 -methyl-phenylsulfonylmethyl)-, ethyl ester]. A solution of 178 g. (1.0 mole) of sodium p-toluenesulfinate (Note 1) in 1 1. of water is placed in a 3-1., three-necked daak, equipped with a condenser, an efficient mechanical stirrer, and a thermometer. After addition of 100 ml. (108 g.) of a 34—37% solution of formaldehyde ca. 1.2-1.4 moles) (Note 2), 107 g. (1.2 moles) of ethyl carbamate (Note 3), and 250 ml. of formic acid (Note 4), the stirred solution is heated to 70°. Soon after this temperature is reached, the reaction mixture becomes turbid by separation of the... 

Ethyl carbamate (J, T. Baker Chemical Company), melting point reported to be 48-50 (but 46-49° was found) was used without purification. The solid was added to the reaction mixture. 

Either the iodo carbamate (96) or the iodo amine salt (94) from above can be converted to the aziridine by refluxing about 2.5 g of the respective product in 100 ml of ethanol which contains 10 ml of water and 10 g of potassium hydroxide for ca. 2 hr. The aziridine is then isolated by pouring the basic reaction mixture into 250 ml water and extracting with 200 ml ether. The ether extract is washed several times with water and dried (MgS04). Evaporation of the ether on a steam bath yields 2j5,3j5-iminocholestane (95, 25-95 %) as a clear oil which solidifies on standing mp 103-105°. This aziridine is not easily crystallized. 

Phenethyl carbamate derivatives 30 have also been employed in Bischler-Napieralski reactions cyclization of these substrates affords 3,4-dihydroisoquinolones 31. These reactions have been conducted using a variety of different promoters including PPA, POCl3, and Tf20. Mixtures of P2O5 and POCI3 appear to afford the best results in some cases. 

To a solution of 2.3 ml of phosphorus oxychloride in 50 ml of dry pyridine is added a solution of 2.2 grams of 3-N-bis((3-chloroethyl)carbamate of estradiol while stirring and at a temperature of about -10°C. The reaction mixture is allowed to stand at about 0°C for I /i hours, whereupon it is hydrolyzed by pouring it into ice-water. The main part of the pyridine is evaporated in vacuo, whereupon the residue is poured into 100 ml of cold 3.5 N hydrochloric acid with stirring. The precipitate thus obtained is isolated and washed with 0.1 N hydrochloric acid and water. 

The whole is slowly heated to 85°C and stirred at this temperature for 45 minutes. The reaction mixture is cooled and the precipitated product is filtered off. It is washed successively with water and ethanol, dried and crystallized from a mixture of acetic acid and methanol, yielding methyl N-[5(6)-benzoyl-2-benzimidazolyl] carbamate MP 288.5°C. 

A solution of 32 g (030 mol) phosgene in 200 ml benzene is added dropwise at 30°C to a stirred soiution of 53.5 g (032 mol) 3-o-toloxy-13-Pfopanediol in 400 ml benzene. The mixture is stirred for an hour after the addition is completed, and a solution of 39 g of dl-methylaniline in 100 ml benzene is then added, and stirring continued for a half-hour. Ice water (about one-third volume) is then added, and the benzene layer formed is separated and stirred with 500 ml concentrated ammonia at 5°Cfor six hours. The precipitated solid (weighing about 55 g) is recovered and recrystallized from water. The product thus obtained in a yield of about 53 g is 3-(o-toloxy)-2-hydroxypropyl carbamate it is a crystalline solid melting at about 93°C, and having a lower water-solubility and higher oil-solubility than 3-o-toloxy-13-propanediol. 

A mixture of 24.1 g (0.10 mol) of 3-o-methoxyphenoxy-2-hydroxy-1 -propyl carbamate and 6.0 g (0.10 mol) of urea was heated rapidly to the temperature range of 180°C to 200°C, and maintained there for five hours. The reaction melt was poured into 50% ethyl alcohol, from which the product crystallized as a white solid. The crude yield was 18.3 g (82%) melting point 131.5°C to 137 t. Crystallization from water and 95% alcohol gave 9.0 g (40.3%) of pure 5-o-methoxyphenoxymethyl-2-oxazolidone melting point 141°Cto 143. This melting point was not depressed when the material was mixed with an authentic sample. In additional runs acetone was used Instead of ethyl alcohol with equivalent results. 

The mixture was cooled to 7°C, extracted with two 500-oc portions of ice water to remove pyridine hydrochloride, and the benzene solution of 3-o-methoxyphenoxy-2-hy-droxypropyl chlorocarbonate was added to 500 ml of cold concentrated ammonium hydroxide. The mixture was vigorously stirred at 5°C for 6 hours, then the crude white precipitate of 3-o-methoxyphenoxy-2-hydroxypropyl carbamate was filtered off, dissolved in 1,500 ml of hot benzene and completely dried by codistillation of last traces of water with benzene, treated with decolorizing carbon and filtered while hot. On cooling 160 g of product crystallized as white needles melting at 88° to 90°C. 

A solution of 3.1 g of (2-benzoyl-4-chlorophenyl-carbamoylmethyl)carbamic acid benzyl ester in 30 cc of 20% hydrobromic acid in glacial acetic acid was stirred for 45 minutes at room temperature. On addition of 175 cc of anhydrous ether, a gummy solid precipitated. After several minutes the ether solution was decanted. The resultant 5-chloro-2-gly-cylaminobenzophenone was not isolated, but about 155 cc of ether was added to the residue and after chilling in an ice bath, 10% sodium hydroxide was added until the mixture was alkaline. The ether layer was then separated, washed twice with water and dried over sodium sulfate. After filtration, the ether solution was concentrated to dryness in vacuo. The residue was crystallized from benzene to yield 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2(1 H)-one. 

In this context, the enantiomeric pair containing the eutomer of cyclothiazide can be resolved by HPLC on cellulose-derived coated CSPs. Nevertheless, the poor solubility of this compound in solvents compatible with this type of support makes this separation difficult at preparative scale. This operation was achieved with a cellulose carbamate fixed on allylsilica gel using a mixture of toluene/acetone as a mobile phase [59]. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

To a —78 °C solution of (4/C5/ )-2-[(.S )-l-chloro-2-propcnyl]-4,5-dicyclohcxyl-l, 3,2-dioxaborolanc (6) (theoretically 2.0 mmol) in THF are added 0.20 mL (2.0 mmol) of benzaldehydc. The mixture is allowed to reach r.t. overnight and is then treated with 0.30 g (2.0 mmol) of triethanolamine. After stirring for 3 h, 15 mL of sat. aq NH4C1 are added. The phases are separated and the aqueous phase is extracted with three 20-mL portions of diethyl ether. The combined extracts are dried over MgS04 and concentrated. The oily residue is purified by flash chromatography (silica gel, petroleum ether/diethyl ether 6 1) yield 0.26 g (79%) >99% ee [capillary GC of the carbamates obtained with (5 )-(l-isoCyanoethyl)benzene],... 

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