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. A method for preparing an N,N-diaryl substituted urea derivative for nitrocellulose stabilization, said method comprising a first step of preparing a carbamate according to formula I, comprising reacting an amine according to formula II and a compound according to formula III, in the presence of a catalyst that comprises an N,N-dialkylimidazolium ionic liquid or a non-nucleophilic base ##STR00008## wherein Ar.sup.1 is an aryl that is optionally substituted with one or more of 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 of halide, alkoxy, alkyl, nitro, sulfonate, ester, amide and/or carboxylate; X is an alkoxy, or an aryloxy and is optionally substituted with one or more of halide, alkoxy, alkyl, nitro, sulfonate, ester, amide and/or carboxylate; and LG is an alkoxy, an aryloxy, an amine that is optionally substituted with one or two C.sub.1-C.sub.4 alkyl groups, an amide, a sulfonate, a halide, a nitrate, a phosphate or a carboxylate; wherein the catalyst is present in less than 50 mol % with respect to the amine according to formula II; and followed by a second step wherein the carbamate according to formula I is reacted with an amine to form said N,N-diaryl substituted urea derivative for nitrocellulose stabilization.

2. The method according to claim 1, wherein the catalyst comprises an N,N-dialkylimidazolium ionic liquid.

3. The 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, and the anion is selected from the group consisting of hydroxide, chloride, bromide, iodate, acetate, hexafluorophosphate, tetrafluoroborate and combinations thereof.

4. The method according to claim 1, wherein the catalyst comprises a non-nucleophilic base.

5. The method according to claim 1, wherein Ar.sup.1 is a phenyl, optionally substituted with one or more of halide, alkoxy, nitro, sulfonate, ester, amide, and carboxylate and Ar.sup.2 is Ar.sup.1 or a phenyl that is optionally substituted with one or more of halide, alkoxy, nitro, sulfonate, ester, amide, and/or carboxylate.

6. The method according to claim 1, wherein X is a C.sub.1-C.sub.4 alkoxy or a C.sub.6-C.sub.10 aryloxy.

7. The method according to claim 1, wherein the amine according to formula II and compound according to formula III are reacted at a temperature of at least 90 C.

8. The method according to claim 1, wherein the reaction between the amine according to formula II and the compound according to formula III also forms a protonated LG product and the protonated LG product is removed during said reaction.

9. The method according to claim 1, wherein the amine reacted with the carbamate according to formula I in the second step is ammonia or methylamine.

10. The method according to claim 1, wherein the carbamate according to formula I is converted into N-methyl-N,N-diphenylurea (Akardite II), wherein Ar.sup.1 and Ar.sup.2 are both phenyl and X is NHMe.

11. The method according to claim 4, wherein the non-nucleophilic base is a superbase selected from the group consisting of amidines, phosphazenes, and guanidines.

12. The method according to claim 3, wherein the cation is 1-ethyl-3-methylimidazolium or 1-butyl-3-methylimidazolium (BMIm).

13. The method according to claim 3, wherein the anion is a hydroxide or a chloride.

14. The method according to claim 5, wherein both Ar.sup.1 and Ar.sup.2 are phenyl such that the amine according to formula II is diphenylamine.

15. The method according to claim 1, wherein the catalyst is present in less than 25 mol % with respect to the amine according to formula II.

16. The method according to claim 1, wherein the catalyst is present in less than 10 mol % with respect to the amine according to formula II.

Description

EXPERIMENTAL EXAMPLES

(1) 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 Ar2Ar1=pH and XOMe)

(2) ##STR00003##

(3) 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%.

(4) .sup.1H NMR (CDCl.sub.3): 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).

(5) .sup.13C NMR: 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).

(6) (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.+).

(7) IR (cm.sup.1): 3100-3000 (w, CH stretch, Ph), 2900-3000 (w, CH stretch, CH.sub.3), 1708 (s, CO stretch, NC(O)N), 1588, 1492 and 1439 (m, CC stretch, Ph).

Example 2

Synthesis of O-ethyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar1Ar2=pH and X=OEt)

(8) ##STR00004##

(9) 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%.

(10) .sup.1H NMR (CDCl.sub.3): 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).

(11) .sup.13C NMR (CDCl.sub.3): 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).

(12) (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.+).

(13) IR (cm.sup.1): 3100-3000 (w, CH stretch, Ph), 3000-2900 (w, CH stretch, CH.sub.2, CH.sub.3), 1715 (s, CO stretch, NC(O)O), 1590, 1491 and 1465 (m, CC stretch, Ph).

Example 3

Synthesis of O-phenyl-N,N-diphenyl Carbamate (Compound I, Wherein Ar1Ar2=pH and XOPh)

(14) ##STR00005##

(15) 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%.

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

(17) .sup.13C NMR (CDCl.sub.3): 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 Ar1Ar2=pH and XOMe)

(18) 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. heated to 90 C. for 24 h: 18% yield heated to 110 C. for 7 h: 55% yield heated to 130 C. for 7 h: 80% yield heated to 130 C. for 16 h: 84% yield

Example 5

Synthesis of N-methyl-N,N-diphenylurea (Akardite II)

(19) ##STR00006##

(20) 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%.

(21) .sup.1H NMR (CDCl.sub.3): 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).

(22) .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).

(23) (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.+).

(24) IR (cm.sup.1): 3339 (m, NH stretch, HNMe), 3100-3000 (w, CH stretch, Ph), 3000-2900 (w, CH stretch, CH.sub.3), 1653 (s, CO stretch, NC(O)N), 1587, 1486 and 1449 (m, CC stretch, Ph), 1512 (NH bend, HNMe).

Example 6

Synthesis of N-methyl-N,N-diphenylurea (Akardite II)

(25) 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)

(26) 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)

(27) 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 Ar1Ar2=pH and XOMe)

(28) ##STR00007##

(29) 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%.