Synthesis of Carbamate or Urea Compounds

Abstract

The invention pertains to the synthesis of carbamate and urea compounds. In particular the invention is directed to the synthesis of carbamate and urea compounds which may be used in the production of compounds that are used to stabilize nitrocellulose. The method of the invention comprises preparing a carbamate or urea derivative comprising reacting an amine and a carbonate or carbamate in the presence of an ionic liquid.

Claims

1. Method for preparing a carbamate or urea derivative according to formula I, comprising reacting an amine according to formula II and a carbonate or carbamate according to formula III, in the presence of a catalyst ##STR00008## wherein Ar.sup.1 is an aryl that is optionally substituted with one or more halide, alkoxy, alkyl, nitro, sulfonate, ester, amide and/or carboxylate; Ar.sup.2 is Ar.sup.1 or an aryl that is optionally substituted with one or more halide, alkoxy, alkyl, nitro, sulfonate, ester, amide and/or carboxylate; X is an alkoxy, aryloxy or an amine and is optionally substituted with one or more halide, alkoxy, alkyl, nitro, sulfonate, ester, amide and/or carboxylate; and LG is a leaving group.

2. Method according to claim 1, wherein the catalyst comprises an ionic liquid.

3. Method according to claim 2, wherein the ionic liquid comprises a cation and an anion and wherein the cation is a N,N-dialkyl imidazolium, preferably a 1-alkyl-3-methylimidazolium, preferably 1-ethyl-3-methylimidazolium or 1-butyl-3-methylimidazolium (BMIm) and/or the anion is selected from the group consisting of hydroxide, chloride, bromide, iodate, acetate, hexafluorophosphate, tetrafluoroborate and combinations thereof, preferably the anion is a hydroxide or a chloride.

4. Method according to claim 1, wherein the catalyst comprises a non-nucleophilic base, preferably a superbase, more preferably a superbase selected from the group consisting of amidines, phosphazenes and guanidines, even more preferably amidines, most preferably 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

5. Method according to claim 1, wherein Ar.sup.1 is a phenyl, optionally substituted with one or more halide, alkoxy, nitro, sulfonate, ester, amide, carboxylate and Ar.sup.2 is Ar.sup.1 or a phenyl and is optionally substituted with one or more halide, alkoxy, nitro, sulfonate, ester, amide, carboxylate, preferably both Ar.sup.1 and Ar.sup.2 are phenyl such that the amine according to formula II is diphenylamine.

6. Method according to claim 1, wherein X is a C.sub.1-C.sub.4 alkoxy, an C.sub.6-C.sub.10 aryloxy or an amine optionally substituted with one or two C.sub.1-C.sub.4 alkyl groups and LG is X, an alkoxy, an aryloxy, an amine optionally substituted with one or two C.sub.1-C.sub.4 alkyl groups, an amide, a sulfonate such as tosylate, mesylate or nosylate, a halide, a nitrate, a phosphate or a carboxylate, preferably X is methoxy, ethoxy, tert-butoxy, phenoxy, amino or methylamine and/or LG is X, more preferably X and LG are both methoxy or phenoxy.

7. Method according to claim 1, wherein the amine according to formula II and carbonate or carbamate according to formula III are reacted at a temperature of at least 90° C., preferably at least 125° C., more preferably at about 130° C.

8. Method according to claim 1, wherein protonated LG that is also formed by the reaction of the amine according to formula II and the carbonate or carbamate according to formula III is removed during said reaction, preferably by using a membrane or by evaporation.

9. Method according to claim 1, wherein the catalyst is present in less than 50 mol %, more preferably less than 25 mol %, most preferably about 10 mol % with respect to the amine according to formula II.

10. Method according to claim 1, wherein the carbamate or urea derivative according to formula I is further converted into an urea, preferably into Akardite II, typically by reacting the carbamate or urea derivative according to formula I with ammonia or methylamine.

11. Method according to claim 1, wherein at least part of the total amount of the amine according to formula II that is reacted to give the carbamate or urea derivative according to formula I is a recycled product resulting from the conversion as defined in claim 10.

12. Method according to claim 1, wherein the carbamate or urea derivative according to formula I is Akardite II.

Description

EXPERIMENTAL EXAMPLES

[0048] All chemicals were purchased from Sigma Aldrich and used without further purification. Nitrogen gas (N50) was purchased from Air Liquide. Water was obtained by the purification of tap water using a Mili-Q Direct-Q 5. Methylamine was purchased as a solution of 40 wt % in H.sub.2O and 33 wt % in absolute ethanol. Ionic liquid BMImCl was dried in a vacuum stove (Heraeus vacuum oven, Thermo Scientific) at 100° C. for 3 hours and stored under N.sub.2 atmosphere before use. Ace pressure tubes were purchased from Sigma Aldrich and fitted with a Teflex® O-ring, purchased from Eriks. Teflon tape was wrapped around the screw-thread of the pressure tube cap for extra grip. .sup.1H and .sup.13C NMR spectra were recorded on a Bruker Ascend 400 (400 MHz). Mass spectra were recorded on a Finnigan MAT900 using an electrospray ionization technique (ESI-MS), with methanol as the eluent. MS samples were prepared by dissolving a few milligrams of compound in HPLC-grade acetone. IR spectra were recorded on a PelkinElmer Spectrum Two FT-IR spectrometer.

Example 1. Synthesis of O-methyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar.SUP.2.═Ar.SUP.1.=pH and X═OMe)

[0049] ##STR00003##

[0050] In a round-bottomed flask (3-neck, 50 ml, fitted with reflux equipment and a valve), the ionic liquid BMImCl (0.5 mmol, 88 mg), diphenyl amine (5.0 mmol, 0.85 g) and anhydrous dimethyl carbonate (5 ml) were mixed under an N.sub.2 atmosphere. The mixture was heated to 130° C. and stirred for 7 hours, while allowing the alcoholic reaction product to escape through the opened valve. It was then cooled to room temperature, the solvent was evaporated and the resulting crude product was purified on a SiO.sub.2 column (the eluent was a mixture of ethyl acetate (EtOAc) and petroleum ether (PetEt):EtOAc/PetEt 10:90). The pure product was obtained as a colorless liquid, which crystallized quickly into a white solid when pressurized air was passed over the liquid. O-methyl-N,N-diphenyl carbamate was obtained in a yield of 80%.

[0051] .sup.1H NMR (CDCl.sub.3): δ 7.40-7.35 (m, 4H, 2 or 3), 7.30-7.22 (m, 6H, 1 and 2 or 3), 3.78 (s, 3H, 6).

[0052] .sup.13C NMR: δ 155.31 (5), 142.59 (4), 128.95 (1, 2, or 3), 126.95 (1, 2, or 3), 126.18 (1, 2, or 3), 53.14 (6).

[0053] (ESI)-MS (calc.): 250.0 (250.3, [M-Na].sup.+) 282.1 (282.3, [M-Na-MeOH].sup.+, 308.0 (308.4, [M-Na-Me.sub.2CO].sup.+, 475.2 (475.6, [M.sub.2-Na].sup.+).

[0054] IR (cm.sup.−1): 3100-3000 (w, C—H stretch, Ph), 2900-3000 (w, C—H stretch, CH.sub.3), 1708 (s, C═O stretch, NC(═O)N), 1588, 1492 and 1439 (m, C═C stretch, Ph).

Example 2. Synthesis of O-ethyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar.SUP.1.═Ar.SUP.2.=pH and X=OEt)

[0055] ##STR00004##

[0056] Example 1 was repeated, only diethyl carbonate (5 ml) was used instead of dimethyl carbonate (5 ml). O-Ethyl-N,N-diphenyl carbamate was obtained in a yield of 57%.

[0057] .sup.1H NMR (CDCl.sub.3): δ 7.39-7.33 (m, 4H, 2 or 3), 7.28-7.20 (m, 6H, 1 and 2 or 3), 4.26 (q, 2H, 6), 1.27 (t, 3H, 7).

[0058] .sup.13C NMR (CDCl.sub.3): δ 154.86 (5), 142.70 (4), 128.87 (1, 2, or 3), 126.98 (1, 2, or 3), 126.01 (1, 2, or 3), 62.06 (6), 14.47 (7).

[0059] (ESI)-MS (calc.): 242.1 (242.3, [M-H].sup.+), 264.1 (264.3, [M-Na].sup.+), 296.1 (296.3, [M-Na-MeOH].sup.+), 322.0 (322.4, [M-Na-Me.sub.2CO].sup.+), 505.2 (505.6, [M.sub.2-Na].sup.+).

[0060] IR (cm.sup.−1): 3100-3000 (w, C—H stretch, Ph), 3000-2900 (w, C—H stretch, CH.sub.2, CH.sub.3), 1715 (s, C═O stretch, NC(═O)O), 1590, 1491 and 1465 (m, C═C stretch, Ph).

Example 3. Synthesis of O-phenyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar.SUP.1.═Ar.SUP.2.=pH and X═OPh)

[0061] ##STR00005##

[0062] Example 1 was repeated, only diphenyl carbonate (7.5 mmol, 1.61 g) was used instead of dimethyl carbonate (5 ml). O-Phenyl-N,N-diphenyl carbamate was obtained in a yield of 9%.

[0063] .sup.1H NMR (CDCl.sub.3): δ 7.439-7.34 (m, 9H), 7.31-7.15 (m, 6H)

[0064] .sup.13C NMR (CDCl.sub.3): δ 153.12 (5), 151.12 (6), 142.28 (4), 129.26 (2 or 8), 129.06 (2 or 8), 126.91 (1 or 9), 126.48 (1 or 9), 125.50 (3), 121.52 (7).

Example 4. Influence of Reaction Temperature on Formation of O-methyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar.SUP.1.═Ar.SUP.2.=pH and X═OMe)

[0065] To investigate the influence of temperature on the reaction of compounds II and III, experiments according to example 1 were performed, with the only difference that the mixture was heated to different temperatures and stirred for different time periods. The experiments gave the following results. [0066] heated to 90° C. for 24 h: 18% yield [0067] heated to 110° C. for 7 h: 55% yield [0068] heated to 130° C. for 7 h: 80% yield [0069] heated to 130° C. for 16 h: 84% yield

Example 5. Synthesis of N-methyl-N′,N′-diphenylurea (Akardite II)

[0070] ##STR00006##

[0071] A solution of methylamine (MMA) in EtOH/H.sub.2O in a ratio of 3:1 was prepared by mixing 3.5 ml of 33 wt % MMA in EtOH and 10.5 ml of 40 wt % MMA in H.sub.2O. The freshly prepared MMA solution was mixed with O-methyl-N,N-diphenyl carbamate (2.0 mmol, 0.45 g) in a pressure tube (21 ml, fitted with Teflex® O-ring). After sealing the tube, the reaction mixture was heated to 100° C. and stirred until the carbamate was completely consumed. This occurred overnight. The reaction mixture was then cooled to room temperature, and the tube was left open to allow MMA to evaporate. Next, the solvent was evaporated, which turned the reaction mixture into an emulsion. EtOAc was added and the two phases were separated. The aqueous phase was washed with EtOAc. Both EtOAc solutions were combined and the solvent was evaporated. The contents of the resulting liquid were separated using a SiO.sub.2 column (eluent: EtOAc/PetEt 25:75). The AK II fractions were combined and the solvent was evaporated. The remaining solid was washed with PetEt and pure Akardite II was obtained as a white solid in a yield of 17 mg, i.e. 3.8%.

[0072] .sup.1H NMR (CDCl.sub.3): δ 7.36-7.32 (m, 4H, 2 or 3), 7.30-7.20 (m, 6H, 1 and 2 or 3), 4.51 (s, 1H, 6), 2.84 (s, 3H, 7).

[0073] .sup.13C NMR: 156.82 (5), 142.90 (4), 129.37 (1, 2, or 3), 127.42 (1, 2, or 3), 126.12 (1, 2, or 3), 27.48 (7).

[0074] (ESI)-MS (calc.): 227.1 (227.3, [M-H].sup.+), 249.1 (249.3, [M-Na].sup.+), 281.1 (281.3, [M-Na-MeOH].sup.+), 307.1 (307.4, [M-Na-Me.sub.2CO].sup.+), 475.2 (475.6, [M.sub.2-Na].sup.+).

[0075] IR (cm.sup.−1): 3339 (m, N—H stretch, H—NMe), 3100-3000 (w, C—H stretch, Ph), 3000-2900 (w, C—H stretch, CH.sub.3), 1653 (s, C═O stretch, NC(═O)N), 1587, 1486 and 1449 (m, C═C stretch, Ph), 1512 (N—H bend, H—NMe).

Example 6. Synthesis of N-methyl-N′,N′-diphenylurea (Akardite II)

[0076] Example 5 was repeated, only O-ethyl-N,N-diphenyl carbamate (2.0 mmol, 0.48 g) was used instead of O-methyl-N,N-diphenyl carbamate. In this particular example, the carbamate was completely consumed during 12 days of stirring at 100° C. Akardite II was obtained in a yield of 17 mg, i.e. 3.8%.

Example 7. Synthesis of N-methyl-N′,N′-diphenylurea (Akardite II)

[0077] O-Phenyl-N,N-diphenyl carbamate (0.35 mmol, 100 mg) was dissolved in 2 mL of MMA solution, 33 wt % in absolute ethanol. The mixture was stirred at room temperature for 2 days. Next, the solvent was evaporated. The contents of the resulting liquid were separated using a SiO.sub.2 column (eluent: EtOAc/PetEt 25:75). The AK II fractions were combined and the solvent was evaporated. The remaining solid was washed with PetEt and pure Akardite II was obtained as a white solid in a yield of 54 mg, i.e. 68%.

Example 8. Synthesis of N-methyl-N′,N′-diphenylurea (Akardite II)

[0078] Example 7 was repeated, only the reaction mixture was stirred for 5 days instead of 2 days. Akardite II was obtained as a white solid in a yield of 64 mg, i.e. 81%.

Example 9. Synthesis of O-methyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar.SUP.1.═Ar.SUP.2.=pH and X═OMe)

[0079] ##STR00007##

[0080] In a round-bottomed flask (3-neck, 50 ml, fitted with reflux equipment and a valve), ‘superbase’ 1,8-diazabicyclo[5.4.0]undec-7-ene DBU (0.5 mmol, 88 mg), diphenyl amine (5.0 mmol, 0.85 g) and anhydrous dimethyl carbonate (5 ml). The mixture was heated to 130° C. and stirred for 7 hours, while allowing the alcoholic reaction product to escape through the opened valve. It was then cooled to room temperature, the solvent was evaporated and the resulting crude product was purified on a SiO.sub.2 column (the eluent was a mixture of ethyl acetate (EtOAc) and petroleum ether (PetEt):EtOAc/PetEt 10:90). The pure product was obtained as a colorless liquid, which crystallized quickly into a yellowish solid when pressurized air was passed over the liquid. The solid was washed with diethyl ether (Et.sub.2O). O-methyl-N,N-diphenyl carbamate was obtained in a yield of 11%.