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Synthesis of 4-Methylene-1,3-naphthoxazines by the Reaction ofImines with TriphosgeneAbdullah Saad Al-Bogami aa Department of Chemistry , Faculty of Science, King AbdulazizUniversity , North Jeddah , Saudi ArabiaPublished online: 29 Jun 2011.

To cite this article: Abdullah Saad Al-Bogami (2011) Synthesis of 4-Methylene-1,3-naphthoxazinesby the Reaction of Imines with Triphosgene, Synthetic Communications: An InternationalJournal for Rapid Communication of Synthetic Organic Chemistry, 41:19, 2952-2958, DOI:10.1080/00397911.2010.515767

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SYNTHESIS OF 4-METHYLENE-1,3-NAPHTHOXAZINESBY THE REACTION OF IMINES WITH TRIPHOSGENE

Abdullah Saad Al-BogamiDepartment of Chemistry, Faculty of Science, King Abdulaziz University,North Jeddah, Saudi Arabia

GRAPHICAL ABSTRACT

Abstract Reaction of 2-acetyl-1-naphthol with aliphatic amines under microwave irradiation

gave the corresponding imines (Schiff bases), which were treated with triphosgene to give

4-methylene-1,3-naphthoxazines in good yields.

Keywords 2-Acetyl-1-naphthol; amines; imines; microwave irradiation; 1,3-naphthoxa-

zines; triphosgene

INTRODUCTION

Phosgene has long been of tremendous importance to organic chemists for awide variety of synthetic applications (e.g., chloroformylation, carbonylation, chlori-nation, and dehydration). However, because of its highly toxic nature, phosgene gasis difficult to handle safely in the laboratory. Triphosgene [bis(trichloromethyl)carbonate][1] is a stable, crystalline solid that has proved to be a useful substitutefor phosgene.

Triphosgene has been repeatedly used in the literature for the construction of avariety of heterocyclic systems. Examples of important heterocyclic systems preparedusing this reagent include benzothiadiazepines,[2] quinazolines,[3] diazolidines,[4]

imidiazolidines,[5] and azetidines.[6] We have recently reported the use of triphosgenein the cyclization of hydrazones of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol togive naphthoxazine and spiro naphthoxazine.[7]

We report results obtained from the cyclization of imines of 2-acetyl-1-naphthol with triphosgene.

Received April 22, 2010.

Address correspondence to Abdullah Saad Al-Bogami, Department of Chemistry, Faculty of

Science, King Abdulaziz University, P.O. Box 15758, North Jeddah 21454, Saudi Arabia. E-mail:

chem_org@hotmail.com

Synthetic Communications1, 41: 2952–2958, 2011

Copyright # Taylor & Francis Group, LLC

ISSN: 0039-7911 print=1532-2432 online

DOI: 10.1080/00397911.2010.515767

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RESULTS AND DISCUSSION

A series of imines 3 was prepared from the reaction of 2-acetyl-1-naphthol 1with aliphatic amines 2 under microwave irradiation[8–11] (Scheme 1).

Compounds 3a–e (Table 1) show in their infrared (IR) spectra absorbance forthe hydroxyl group at about 3470 cm�1 and C=N at 1620 cm�1, while in the 1HNMR spectra the methyl group appears as a singlet about d¼ 2.50 ppm and thehydroxyl group appears as a broad singlet at 12.50 ppm. The 13C NMR and mass(MS) spectra of these compounds are in agreement with the proposed structures.

Treatment of the imines 3a–e with triphosgene in dichloromethane (DCM) inthe presence of triethylamine gave 4-methylene-1,3-naphthoxazines 4a–e (Scheme 2,Table 2).

Compounds of type 4 show in their IR spectra absorbance for the carbonylgroup at 1737 cm�1, while the exocylic double bond absorbance is at 1620 cm�1.The protons of the latter group appear as two doublets at d¼ 5.05 and 5.09 ppm withcoupling constants of about 2.2Hz in the 1H NMR spectra. Furthermore, the 13CNMR spectra show a distinct absorbance for the exocylic methylene group at about88 ppm, which is in agreement with previous studies on related compounds.[12,13]

Scheme 1. Synthesis of imines 3 under microwave irradiation.

Table 1. Imines 3 derivatives

R Product Yield (%)

N-propyl 3a 91

N-butyl 3b 87

Isobutyl 3c 94

N-hexyl 3d 90

N-heptyl 3e 93

Scheme 2. Reaction of imines 3 with triphosgene.

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EXPERIMENTAL

Melting points are uncorrected and were determined on a Gallenkamp melting-point apparatus. Infrared (IR) spectra were recorded on a Perkin-Elmer 883 spectro-photometer as KBr pellets and are expressed as v in cm�1. NMR spectra wererecorded on a Jeol ECP 400 (400MHz) in CDCl3 and are expressed as d in ppm.Mass spectra were recorded on a Shimadzu QP-5050A gas chromatography–massspectrometry (GC=MS) system. Microwave irradiation was carried out in a domesticmicrowave oven [Panasonic model N-N (20002W] output of 1000W. Thin-layerchromatography (TLC) was performed on TLC plates (silica gel 60F245 precoated,20� 20 cm, with an 0.25mm thick).

Table 2. Synthesis of 4-methylene-1,3-naphthoxazines from imines

Reagent Product Yielda (%)

71

68

82

86

81

aYields refer to isolated products.

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Imines 3a–e

General procedure. A solution of the appropriate 2-acetyl-1-naphthol(2.69mmol) and aliphatic amines (2.69mmol) was mixed in an Erlenmeyer flask(100ml). Then the solution was subjected to microwave irradiation in an ordinarydomestic microwave oven at 100W for 1min. The separated solid was then collectedby filtration and recrystallized from methanol.

2-(1-Propylimino-ethyl)-naphthalen-1-ol (3a). This compound was pre-pared from 2-acetyl-1-naphthol and n-propylamine. Yield 91%, yellow powder,mp 101–103 �C; IR: 3445 (OH), 1599 (C=N); 1H NMR: 1.08 (t, 3H), 1.86 (sextet,2H), 2.57 (s, 3H), 3.60 (t, 2H), 6.97 (d, J¼ 8.8Hz, 1H), 7.34–7.63 (m, 4H), 8.77(d, J¼ 8.08Hz, 1H), 12.41 (bs, 1H); 13C NMR: 11.71, 14.93, 22.91, 47.04, 108.89,114.15, 124.82, 125.07, 125.80, 127.11, 129.86, 130.41, 137.48, 171.66, 175.66; MS:m=z (%) 227 (Mþ, 100), 210 (48), 198 (41), 185 (48), 168 (51), 157 (25), 141 (42),128 (25), 115 (78), 99 (22), 89 (17), 69 (17). Anal. calcd. for C15H17NO: C, 78.56;H, 8.35; N, 6.14. Found: C, 78.52; H, 8.23; N, 6.28.

2-(1-Butylimino-ethyl)-naphthalen-1-ol (3b). This compound was pre-pared from 2-acetyl-1-naphthol and n-butylamine. Yield 87%, yellow powder, mp98–99 �C; IR: 3493 (OH), 1625 (C=N); 1H NMR: 0.97 (t, 3H), 1.51 (sextet, 2H),1.76 (quantet, 2H), 2.46 (s, 3H), 3.55 (t, 2H), 6.83 (d, J¼ 9.5Hz, 1H), 7.29–7.59(m, 4H), 8.56 (d, J¼ 8.04Hz, 1H), 12.47 (bs, 1H); 13C NMR: 13.77, 14.72, 20.30,31.55, 45.0, 108.74, 113.78, 124.87, 124.94, 125.79, 127.08, 129.78, 130.59, 137.46,171.56, 174.99; MS: m=z (%) 241 (Mþ, 70), 224 (17), 212 (29), 198 (36), 168 (28),157 (15), 141 (25), 128 (15), 115 (38), 97 (20), 81 (44), 69 (100). Anal. calcd. forC16H19NO: C, 79.63; H, 7.49; N, 6.22. Found: C, 79.55; H, 7.55; N, 6.24.

2-(1-Isobutylimino-ethyl)-naphthalen-1-ol (3c). This compound was pre-pared from 2-acetyl-1-naphthol and isobutylamine. Yield 94%, yellow powder, mp87–89 �C; IR: 3473 (OH), 1589 (C=N); 1H NMR: 1.02 (d, 6H), 2.05 (m, 1H), 2.38(s, 3H), 3.33 (d, 2H), 6.79 (d, J¼ 9.5Hz, 1H), 7.28–7.58 (m, 4H), 8.55 (d, J¼ 8.08Hz,1H); 13C NMR: 14.44, 20.46, 28.95, 52.74, 108.50, 113.26, 124.77, 124.98, 125.79,127.05, 129.69, 130.81, 137.43, 171.11, 175.97; MS: m=z (%) 241 (Mþ, 83), 226(20), 198 (47), 185 (100), 168 (44), 157 (39), 141 (36), 128 (23), 115 (52), 99 (6), 89(9), 69 (21). Anal. calcd. for C16H19NO: C, 79.63; H, 7.49; N, 6.22. Found: C,79.44; H, 7.71; N, 6.20.

2-(1-Hexylimino-ethyl)-naphthalen-1-ol (3d). This compound was pre-pared from 2-acetyl-1-naphthol and n-hexylamine. Yield 90%, yellow needles, mp90–92 �C; IR: 3485 (OH), 1602 (C=N); 1H NMR: 0.90 (t, 3H), 1.30–1.72 (m, 8H),2.50, (s, 3H), 3.62 (t, 2H), 6.75 (d, J¼ 9.5Hz, 1H), 7.33–7.62 (m, 4H), 8.34 (d,J¼ 8.08Hz, 1H), 12.33 (bs,1H); 13CNMR: 14.46, 14.63, 22.85, 26.62, 29.43, 31.40,44.67, 108.31, 112.03, 124.65, 125.80, 126.55, 127.39, 129.88, 131.06, 137.55,172.41, 175.94; MS: m=z (%) 269 (Mþ, 5), 256 (2), 269 (5), 185 (5) 168 (5), 149(17), 137 (6), 97 (27), 81 (40), 69 (83), 57 (100). Anal. calcd. for C18H23NO: C,80.26; H, 8.61; N, 5.20. Found: C, 79.88; H, 7.95; N, 5.36.

2-(1-Heptylimino-ethyl)-naphthalen-1-ol (3e). This compound was pre-pared from 2-acetyl-1-naphthol and n-heptylamine. Yield 93%, yellow needles, mp

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82–85 �C; IR: 3450 (OH), 1603 (C=N); 1H NMR: 0.89 (t, 3H), 1.28–1.33 (m, 8H),1.78 (quintet, 2H), 2.44 (s, 3H), 3.50 (t, 2H), 6.79 (d, J¼ 8.8Hz, 1H), 7.27–7.59(m, 4H), 8.53 (d, J¼ 8.08Hz, 1H), 12.33 (bs, 1H); 13C NMR: 14.19, 14.47, 22.71,27.09, 29.02, 29.62, 31.73, 45.19, 108.46, 113.30, 124.83, 124.98, 125.78, 127.08,129.74, 130.89, 137.49, 171.06, 176.02; MS: m=z (%) 283 (Mþ, 100), 266 (22), 254(14), 212 (42) 198 (44), 185 (34), 168 (21), 157 (10), 141 (12), 115 (12), 69 (2). Anal.calcd. for C19H25NO: C, 80.52; H, 8.89; N, 4.94. Found: C, 80.25; H, 8.95; N, 4.44.

1,3-Naphth-oxazinones (4a–e)

General procedure. A solution of the appropriate imines 3 (3mmol) and1mL of triethylamine in 25mL of dichloromethane was stirred under a nitrogenatmosphere. Triphosgene (1.5mmol) in 10mL of dichloromethane was added drop-wise over a period of 15min. The mixture was stirred at room temperature for 1 hand then refluxed for 3 h. Water was added, the organic layer was separated, andthe aqueous layer was extracted with dichloromethane (30mL). The combinedorganic layers were dried over magnesium sulfate and evaporated to dryness. Theresulting solid was crystallized from ethyl ether.

4-Methylene-3-propyl-3,4-dihydro-naphtho[2,1–e][1,3]oxazine-2-one (4a).This compound was prepared from 3a. Yield 71%, colorless powder, mp 75–76 �C;IR: 1745 (C=O), 1618 (¼CH2);

1H NMR: 1.00 (t, 3H), 1.77 (sextet, 2H), 4.03(t, 2H), 5.05 (d, J¼ 2.2Hz, 1H), 5.09 (d, J¼ 2.2Hz, 1H), 7.58 (d, J¼ 8.8Hz, 1H),7.62–8.37 (m, 5H); 13C NMR: 11.30, 20.93, 44.27, 88.54, 109.49, 121.62, 122.02,122.57, 125.24, 127.67, 128.07, 128.93, 130.21, 137.12, 148.26, 150.55; MS: m=z(%) 253 (Mþ, 27), 170 (100), 142 (6.50), 114 (37), 88 (9), 56 (4). Anal. calcd. forC16H15 NO2: C, 75.57; H, 6.43; N, 5.51. Found: C, 75.30; H, 6.21; N, 5.16.

3-Butyl-4-methylene-3,4-dihydro-naphtho[2,1–e][1,3]oxazine-2-one (4b).This compound was prepared from 3b. Yield 68%, colorless crystals, mp 87–88 �C;IR: 1733 (C=O), 1621 (¼CH2);

1H NMR: 0.99 (t, 3H), 1.46 (sextet, 2H), 1.75 (quan-tet, 2H), 4.00 (t, 2H), 5.02 (d, J¼ 2.2Hz, 1H), 5.09 (d, J¼ 2.2Hz, 1H), 7.60 (d,J¼ 8.8Hz, 1H), 7.64–8.44 (m, 5H); 13C NMR: 13.83, 20.17, 29.68, 42.63, 88.98,109.59, 121.69, 122.12, 122.56, 125.28, 127.70, 128.10, 130.12, 137.17, 148.12,149.44; MS: m=z (%) 267 (Mþ, 21), 212 (13), 198 (9), 184 (9), 170 (100), 142 (5),114 (30). Anal. calcd. for C17H17 NO2: C, 76.83; H, 6.41; N, 5.40. Found: C,76.33; H, 6.81; N, 5.10.

3-Isobutyl-4-methylene-3,4-dihydro-naphtho[2,1–e][1,3]oxazine-2-one(4c). This compound was prepared from 3c.Yield 82%, white powder, mp150–152 �C; IR: 1735 (C=O), 1641 (¼CH2);

1H NMR: 0.99 (d, 6H), 2.28 (m, 1H),3.95 (d, 2H), 5.04 (d, J¼ 2.2Hz, 1H), 5.09 (d, J¼ 2.2Hz, 1H), 7.55–8.20 (m, 5H),8.46 (d, J¼ 9.56Hz, 1H); 13C NMR: 20.10, 27.05, 49.49, 88.34, 109.53, 121.80,122.14, 122.68, 125.28, 127.67, 128.11, 130.24, 137.21, 148.56, 150.70; MS: m=z(%) 267 (Mþ, 10), 214 (6), 170 (100), 114 (20), 56 (5). Anal. calcd. for C17H17

NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 75.98; H, 6.91; N, 5.23.

3-Hexyl-4-methylene-3,4-dihydro-naphtho[2,1–e][1,3]oxazine-2-one (4d).This compound was prepared from 3d. Yield 86%, white powder, mp 91–94 �C; IR:

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1740 (C=O), 1674 (¼CH2);1H NMR: 0.90 (t, 3H), 1.31–1.77 (m, 8H), 4.09 (t, 2H),

5.04 (d, J¼ 2.2Hz, 1H), 5.10 (d, J¼ 2.2Hz, 1H), 7.63 (d, J¼ 9.0Hz, 1H), 7.67–8.47(m, 5H); 13C NMR: 14.10, 22.61, 26.56, 27.59, 31.52, 42.89, 88.56, 109.62, 121.70,122.15, 122.67, 125.30, 127.71, 128.12, 130.23, 137.20, 148.50, 150.67; MS: m=z(%) 295 (Mþ, 18), 214 (6), 170 (100), 114 (20), 56 (8). Anal. calcd. for C19H21

NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.90; H, 7.34; N, 4.20.

3-Heptyl-4-methylene-3,4-dihydro-naphtho[2,1–e][1,3]oxazine-2-one(4e). This compound was prepared from 3e. Yield 81%, yellow powder, mp118–121 �C; IR: 1732 (C=O), 1695 (¼CH2);

1H NMR: 1.19 (t, 3H), 1.28–1.33 (m,10H), 3.92 (t, 2H), 5.04 (d, J¼ 2.2Hz, 1H), 5.12 (d, J¼ 2.2Hz, 1H), 7.70 (d,J¼ 9.0Hz, 1H), 7.75–8.30 (m, 5H); 13C NMR: 8.97, 14.49, 22.59, 26.76, 27.36,28.93, 31.71, 88.56, 110.11, 121.82, 122.34, 125.41, 128.48, 128.81, 130.69, 136.99,148.27, 150.54; MS: m=z (%) 309 (Mþ, 33), 214 (9), 170 (100), 114 (18), 56 (13). Anal.calcd. for C20H23 NO2: C, 77.64; H, 7.49; N, 4.53. Found: C, 77.92; H, 7.11; N, 4.54.

ACKNOWLEDGMENT

The author is thankful to Hamad Z. Alkhathlan, professor of chemistry, KingSaud University, Udaipur, for valuable suggestions and guidance.

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