Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine Dimers

Al-Bogami, Abdullah Saad; Al-Majid, Abdullah Mohammed; Al-Saad, Mohammed Ali; Mousa, Ahmed Amine; Al-Mazroa, Sara Abdullah; Alkhathlan, Hamad Zaid

doi:10.3390/molecules14062147

Open AccessArticle

Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine Dimers

¹

Department of Chemistry, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia

²

Chemistry Department, Girls College of Education, Riyadh Girls University, Riyadh, Saudi Arabia

^*

Author to whom correspondence should be addressed.

Molecules 2009, 14(6), 2147-2159; https://doi.org/10.3390/molecules14062147

Submission received: 25 April 2009 / Revised: 15 May 2009 / Accepted: 5 June 2009 / Published: 12 June 2009

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Abstract

:

Cyclization of hydrazones derived from 2-acetyl-1-naphthol and 1-acetyl-2-naphthol with triphosgene gave naphtho[1,2-e]-1,3-oxazines, naphtho[2,1-e]-1,3-oxazines or their spiro dimers depending on the molar ratio of triphosgene used for the cyclization.

Keywords:

2-acetyl-1-naphthol; 1-acetyl-2-naphthol; triphosgene; naphthoxazine, spiro naphthoxazine

Introduction

Triphosgene (bis(trichloromethyl)carbonate) has been repeatedly used in the literature for the construction of a variety of heterocyclic systems. It holds an advantage over other similar reagents, such as phosgene and diphosgene, of being a safe and easy to handle solid. Examples of important heterocyclic systems prepared using this reagent include benzothiadiazepines [1], quinazolines [2], diazolidines [3], imidiazolidines [4] and azetidines [5]. We have recently reported the use of triphosgene in the cyclization of hydrazones and Schiff bases of 2-hydroxy- and 2-aminoacetophenones to give 1,3-benzoxazines [6,7], spiro 1,3-benzoxazine dimmers [8], quinazolines and spiro quinazoline dimers [9].

We would like to report here results obtained from the cyclization of hydrazones of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol with triphosgene.

Results and Discussion

Hydrazones of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol were obtained in very good yields from the reaction of these compounds with aromatic hydrazines (Scheme 1, Table 1).

Scheme 1. Synthesis of hydrazones of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol.

i = ArNHNH₂.HCl/EtOH/AcONa/H₂O

Table 1. Hydrazones 1-8.

**Table 1.** Hydrazones **1-8**.
Compound	Ar	Yield (%)
1	Phenyl	92
2	4-ClC₆H₄	82
3	4-BrC₆H₄	79
4	4-CH₃C₆H₄	91
5	Phenyl	75
6	4-ClC₆H₄	80
7	4-BrC₆H₄	68
8	4-CH₃C₆H₄	68

The hydrazones 1-8 show in the their IR spectra absorbances for the C=N group in the 1,614-1,636 cm^-1 range and for the OH and NH groups at about 3,400 cm^-1 and 3,350 cm^-1, respectively. The ¹H-NMR spectra of compounds 1-8 show in each case two distinct doublets which have been assigned to the H₃ and H₄ positions. In the spectra of 1-4 these two doublets appear at δ 7.04-7.16 and δ 7.68-7.76. The lower field signal in this case was assigned to H₃ as it is deshielded by the hydrazone moiety. In contrast, for compounds 5-8, where the two doublets appear at δ 6.80-6.90 and δ 7.63-7.66 the signal at the higher field was assigned to H₃ as in this case this position is shielded by the OH group. It is also worth mentioning here that in the ¹³C-NMR spectra of the above compounds, the methyl group of the hydrazones of the 2-acetyl derivatives 1-4 absorbs at higher fields (δ 12.22-13.04) than those of the 1-acetyl derivatives 5-8 (δ 18.29-18.55). The rest of the spectral data is shown in the Experimental section. Treatment of the hydrazones 1-8 with triphosgene gave the 4-methylenenaphthoxazines 9-16 or the spiro naphthoxazine dimers 17-20, depending on the molar ratio of triphosgene used in the cyclizations (Scheme 2 and Scheme 3, Table 2).

Scheme 2. Reaction of hydrazones 1-4 with triphosgene.

Scheme 3. Reaction of hydrazones 5-8 with triphosgene.

Table 2. 4-Methylenenaphthoxazines 9-16 and spiro naphthoxazine dimmers 17-20.

**Table 2.** 4-Methylenenaphthoxazines **9-16** and spiro naphthoxazine dimmers **17-20**.
Compound	Ar	Yield (%)
9	Phenyl	69
10	4-ClC₆H₄	74
11	4-BrC₆H₄	71
12	4-CH₃C₆H₄	73
13	Phenyl	62
14	4-ClC₆H₄	61
15	4-BrC₆H₄	64
16	4-CH₃C₆H₄	60
17	Phenyl	69
18	4-ClC₆H₄	72
19	4-BrC₆H₄	71
20	4-CH₃C₆H₄	55

These results are in agreement with our previous reports on the reaction of hydrazones of 2-hydroxyacetophenones with triphosgene. It was observed then that the use of 0.5 equivalents of triphosgene gave the 4-methylene-1,3-benzoxazines, while the spiro 1,3-benzoxazine dimers were obtained when 1.0 equivalent of triphosgene was used [8]. The structures of those compounds were established based on X-ray crystal structure and spectroscopic studies [8,9]. As a result, we are showing here partial spectroscopic data for compounds 9-16 (Table 3 and Table 4) and 17-20 (Table 5). In these tables, signals that can be easily attributed to structurally related positions, and with significance to the elucidation of the structures of the new compounds are shown for matter of comparison, while the complete data is given in the experimental section.

Table 3. Partial IR and NMR data for compounds 9-16.

**Table 3.** Partial IR and NMR data for compounds **9-16**.
Compound	IR (cm^-1)		¹H-NMR (ppm)
Compound	C=O	=CH₂	=CH₂	Aromatic
9	1,727	1,620	5.02 (d, J = 2.2 Hz, 1H)	6.80 (d, J = 8.1 Hz, 2H, H_2,6,Ar)
			5.13 (d, J = 2.2 Hz, 1H)	7.61 (d, J = 8.8 Hz, 1H, H₆)
				7.66 (d, J = 8.8 Hz, 1H, H₅)
10	1,732	1,621	5.02 (d, J = 2.2 Hz,1H)	6.78 (d, J = 9.0 Hz, 2H, H_2,6,Ar)
			5.09 (d, J = 2.2 Hz, 1H)	7.23 (d, J = 9.0 Hz,2H, H_3,5,Ar)
				7.67 (d, J = 8.8 Hz, 1H, H₅)
11	1,741	1,621	4.96 (d, J = 2.0 Hz, 1H)	6.73 (d, J = 8.8 Hz, 2H, H_2,6,Ar)
			5.01 (d, J = 2.0 Hz, 1H)	7.24 (d, J = 8.8 Hz, 2H, H_3,5,Ar)
12	1,737	1,612	4.92 (d, J = 2.0 Hz, 1H)	6.71 (d, J = 8.1 Hz, 2H, H_2,6,Ar)
			5.14 (d, J = 2.0 Hz, 1H)	7.02 (d, J = 8.1 Hz, 2H, H_3,5,Ar)
				7.84 (d, J = 8.8 Hz, 1H, H₆)
				7.91 (d, J = 8.8 Hz, 1H, H₅)
13	1,725	1,620	5.04 (d, J = 2.2 Hz, 1H)	6.97 (d, J = 8.8 Hz, 2H, H_2,6,Ar)
			5.15 (d, J = 2.2Hz, 1H)	7.67 (d, J = 8.1 Hz, 1H, H₉)
14	1,732	1,620	5.05 (d, J = 1.5Hz, 1H)	6.84 (d, J = 8.8 Hz, 2H, H_2,6,Ar)
			5.15 (d, J = 1.5 Hz, 1H)	7.23 (d, J = 8.8 Hz, 2H, H_3,5,Ar)
				7.70 (d, J = 8.1 Hz, 1H, H₉)
15	1,733	1,616	5.05 (d, J = 2.2 Hz, 1H)	6.90 (d, J = 8.0 Hz, 2H, H_2,6,Ar)
			5.14 (d, J = 2.2 Hz, 1H)	7.29 (d, J = 8.0 Hz, 2H, H_3,5,Ar)
16	1,741	1,615	5.04 (d, J = 2.2 Hz, 1H)	6.81(d, J = 8.8 Hz, 2H, H_2,6,Ar)
			5.14 (d, J = 2.2 Hz, 1H)	7.08 (d, J = 8.8 Hz, 2H, H_3,5,Ar)
				7.66 (d, J = 8.8 Hz, 1H, H₉)

Table 4. Partial ¹³C-NMR data for 9-16.

**Table 4.** Partial ¹³C-NMR data for **9-16**.
	9	10	11	12	13	14	15	16
C_1,Ar	143.05	143.46	143.35	143.34	143.53	143.48	143.53	142.88
C_2,6,Ar	113.03	115.70	114.89	113.07	113.97	115.33	113.96	114.12
C_3,5,Ar	129.30	132.33	131.99	130.03	129.45	129.44	129.47	129.96
C₂	148.05	147.99	147.35	147.21	148.07	148.01	148.08	148.10
C₄	138.69	138.26	138.54	138.99	138.46	138.30	138.45	138.48
=CH₂	88.60	88.55	88.58	88.97	88.53	88.53	88.54	88.50
C₅ (C₁₀)	122.93	121.48	121.52	121.50	(120.33)	(120.25)	(120.33)	(120.34)
C₆ (C₉)	120.69	120.24	120.73	121.05	(128.12)	(128.23)	(128.13)	(128.10)
C_10b (C_10a)	146.16	144.45	145.60	144.14	(145.29)	(143.95)	(145.29)	(143.53)
C₂	148.05	147.99	147.35	147.21	148.07	148.01	148.08	148.10

Table 5. Partial ¹H and ¹³C-NMR data for the spiro compounds 17- 20.

**Table 5.** Partial ¹H and ¹³C-NMR data for the spiro compounds **17- 20**.
	¹H		¹³C
	CH₃	C_1`	CH₃	C_1`	C_2`	C_12`b	C=O
17	2.12	3.58 (d, J = 14.70 Hz, 1H)	32.15	59.65	85.55	66.06	149.24
		3.69 (d, J = 14.70 Hz, 1H)					149.90
18	2.10	3.49 (d, J = 14.70 Hz, 1H)	32.08	60.07	85.47	66.05	149.01
		3.60 (d, J = 14.70 Hz, 1H)					149.07
19	2.09	3.44 (d, J = 14.70 Hz, 1H)	32.04	60.11	85.41	65.96	148.95
		3.54 (d, J = 14.70 Hz, 1H)					149.15
20	2.51	3.41 (d, J = 14.65 Hz, 1H)	17.20	27.87	97.68	(88.06)*	148.60
		3.54 (d, J = 14.65 Hz, 1H)					149.01

*(C_12'c).

It can be seen from Table 3 that there is a noticeable difference in the ¹³C-NMR spectra of 17-19 compared with 20. In the latter compound the CH₃ group and position C_1` absorb at higher fields than those in 17-19, while positions C_2` and C_12`c absorb at lower fields than positions C_2' and C_12'b in 17-19. This might be speculated as a result of the orientation of the aromatic rings in respect to these positions, which needs further studies. In addition, the above results for compounds 17-19 are in close resemblance to these reported for the spiro 1,3-benzoxazine dimmers which might suggest that they have similar steric environment for the 1,3-benzoxazines [8].

The EIMS spectra of the spiro compounds 17-20 did not show the expected molecular ions. They appear to fragment at the spiro junction to give fragments at m/z = M⁺ - ArN₂CO and m/z = M⁺ ‑ ArN₂CO₂. For example, compound 18 shows in its EIMS spectra fragment peaks at m/z 505 and 489, arising from the loss of ClC₆H₄N₂CO and ClC₆H₄N₂CO₂, respectively. This type of fragmentation was previously observed with analogous spiro compounds [8,9].

Finally, it is worth mentioning here that although the formation of the 4-methylene-naphthoxazines 9-16 would be expected to proceed via a similar reaction mechanism to that previously reported for the cyclization of hydrazones of 2-hydroxyacetophenone and acetophenone [6,10], the mechanism for formation of the spiro naphthoxazine dimmers is not clear to us with regards to at what stage does the dimerization occurs to form the final spiro naphthoxazines.

Scheme 4. Proposed mechanism for the formation of the spiro compounds 17-20.

The use of 1.0 equivalents of triphosgene is necessary to form the latter products because in its reactions it gives an equivalent of three moles of phosgene (COCl₂), so the formation of naphthoxazines (where one CO group is introduced) would require only 0.5 equivalent of triphosgene (1.5 equivalent of COCl₂, a slight excess is usually used in these kinds of cyclizations) while the spiro dimers (where two CO groups are introduced) would require double this amount. In Scheme 4, a speculative mechanism for the formation of the spiro products is shown with two pathways; in the first one the dimerization occurs after the formation of the two naphthoxazine nuclei, while in the second one the dimerization takes place before the formation of the second naphthoxazine ring.

Experimental

Melting points are uncorrected. IR spectra were recorded on a Perkin-Elmer 883 spectrophotometer as KBr pellets and expressed as ν in cm^-1. NMR spectra were recorded on JEOL ECP 400 (400 MHz) in CDCl₃ and chemical shifts are expressed as δ in ppm. MS spectra were recorded on Shimadzu QP 5050A GC/MS system.

2-Acetyl-1-naphthol phenylhydrazone (1): To a solution of 2-acetyl-1-naphthol (2.0 g, 10.8 mmol) in ethanol (50 mL) was added a solution of phenylhydrazine hydrochloride (1.9 g, 12.9 mmol) and sodium acetate (1.0 g, 12.2 mmol) in a mixture of ethanol (30 mL) and water (10 mL). The above solution was refluxed for 5 hours and then evaporated under vacuum. The resulting solid was washed with water (50 mL) and then recrystallized from ethanol-chloroform (8:2). Yield 92%, red solid, mp 162°C; IR: 3,410 (OH), 3,334 (NH), 1,620 (C=N); ¹H-NMR: 1.81 (s, 3H), 6.17 (t, J = 7.3 Hz, 1H), 6.46 (d, J = 7.7 Hz, 2H), 6.62 (m, 3H), 6.77 (m, 2H), 6.88 (d, J = 8.8 Hz, 1H), 7.06 (m, 1H), 7.64 (m, 1H); ¹³C-NMR: 13.04, 112.42, 114.49, 117.42, 119.49, 122.49, 123.58, 124.66, 126.51, 126.75, 128.60, 128.84, 133.41, 144.69, 148.03, 154.09; MS: m/z (%) 276 (M⁺, 100), 261 (7), 260 (18), 295 (38), 230 (6), 183 (25), 168 (6), 141 (13), 128 (10), 115 (49), 77 (8); Anal. Calcd. for C₁₈H₁₆N₂O: C, 78.23; H, 5.83; N, 10.13. Found: C, 77.96; H, 5.71; N, 10.28.

2-Acetyl-1-naphthol 4̀-chlorophenylhydrazone (2): This compound was prepared from 2-acetyl-1-naphthol and 4̀-chlorophenylhydrazine using the procedure described for 1. Yield, 82%, brownish solid, mp 175°C; IR: 3,420 (OH), 3,331 (NH), 1,636 (C=N); ¹H-NMR: 2.38 (s, 3H), 6.98 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.32 (m, 2H), 7.49 (m, 2H), 7.73 (m, 1H), 8.40 (m, 1H); ¹³C-NMR: 12.28, 112.67, 114.27, 118.24, 123.22, 123.51, 125.37, 125.67, 127.15, 127.34, 129.49, 134.28, 142.68, 149.27, 155.67; MS: m/z (%) 312 (M+2, 21), 310 (M⁺, 65), 296 (5), 294 (10), 293 (51), 258 (17), 184 (30), 183 (41), 169 (10), 168 (9), 143 (22), 141 (25), 134 (45), 127 (100), 114 (37), 76 (6); Anal. Calcd. for C₁₈H₁₅ClN₂O: C, 69.56; H, 4.86; N, 9.01. Found: C, 69.72; H, 4.77; 8.88.

2-Acetyl-1-naphthol 4̀-bromophenylhydrazone (3): This compound was prepared from 2-acetyl-1-naphthol and 4̀-bromophenylhydrazine using the procedure described for 1. Yield, 79%, brownish solid, mp 182°C; IR: 3,412 (OH), 3,348 (NH), 1,632 (C=N); ¹H-NMR: 2.40 (s, 3H), 6.94 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.8 Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 7.53 (m, 2H), 7.74 (m, 1H), 8.41 (m, 1H); ¹³C-NMR: 12.29, 112.92, 113.20, 118.20, 121.12, 123.32, 123.63, 125.33, 125.38, 127.23, 127.30, 129.70, 134.27, 144.11, 148.52, 155.12; MS: m/z (%) 356 (M+2, 70), 354 (M⁺, 71), 340 (11), 339 (54), 338 (12), 337 (49), 258 (21), 185 (15), 183 (56), 173 (63), 156 (10), 128 (18), 115 (100), 91 (35), 76 (6); Anal. Calcd. for C₁₈H₁₅BrN₂O: C, 60.86; H, 4.25; N, 7.88. Found: C, 60.67; H, 4.15; N, 7.75.

2-Acetyl-1-naphthol 4̀-methylphenylhydrazone (4): This compound was prepared from 2-acetyl-1-naphthol and 4̀-methylphenylhydrazene using the procedure described for 1. Yield, 91% brownish solid, mp 164°C; IR: 3,424 (OH), 3,350 (NH), 1,614 (C=N); ¹H-NMR: 2.01 (s, 3H), 2.19 (s, 3H), 6.76 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 8.1 Hz, 2H), 7.02 (m, 1H), 7.17 (m, 2H), 7.24 (m, 1H), 7.45 (m, 1H), 8.06 (m, 1H); ¹³C-NMR: 12.22, 20.73, 113.03, 113.31, 118.13, 118.42, 123.31, 123.62, 125.01, 125.32, 127.22, 127.49, 130.15, 134.21, 141.96, 148.05, 155.06; MS: m/z (%) 290 (M⁺, 85), 275 (14), 273 (54), 185 (15), 168 (12), 128 (6), 115 (37), 107 (100), 93 (6), 76 (25); Anal. Calcd. for C₁₉H₁₈N₂O: C, 78.59; H, 7.95; N, 12.27. Found: C, 78.38; H, 7.85; N, 12.12.

1-Acetyl-2-naphthol phenylhydrazone (5): This compound was prepared from 1-acetyl-2-naphthol and phenylhydrazine hydrochloride using the procedure described for 1. Yield, 75%, pale yellow solid, mp 125°C; IR: 3,418 (OH), 3,335 (NH), 1,617 (C=N); ¹H-NMR: 2.49 (s, 3H), 6.93 (t, J = 7.3Hz, 1H), 7.12 (d, J = 7.3 Hz, 2H), 7.21 (d, J = 8.8 Hz, 1H), 7.29 (d, J = 7.3 Hz, 2H), 7.33 (m, 1H), 7.44 (m, 1H), 7.79 (d, J = 8.1 Hz, 1H); ¹³C-NMR: 18.41, 113.18, 116.32, 118.64, 121.13, 123.15, 124.52, 126.50, 128.97, 129.26, 129.63, 130.77, 131.66, 144.24, 144.76, 153.43; MS: m/z (%) 276 (M⁺, 69), 260 (21), 259 (100), 184 (22), 169 (6), 141 (9), 128 (7), 115 (28), 93 (33), 77 (9); Anal. Calcd. for C₁₈H₁₆N₂O: C, 78.23, H, 5.73, N, 10.13. Found: C, 78.11; H, 5.73, N, 10.08.

1-Acetyl-2-naphthol 4̀-chlorophenylhydrazone (6): This compound was prepared from 1-acetyl-2-naphthol and 4̀-chlorophenylhydrazine using the procedure described for 1. Yield, 80%, pale yellow solid, mp 154°C; IR: 3,422 (OH), 3,355 (NH), 1,619 (C=N); ¹H-NMR: 2.47 (s, 3H), 7.04 (d, J = 9.2 Hz, 2H), 7.21 (d, J = 9.2 Hz, 2H), 7.24 (d, J = 8.8, 1H), 7.33 (m, 1H), 7.44 (m, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 7.7 Hz, 1H); ¹³C-NMR: 18.42, 114.36, 116.29, 118.57, 123.24, 124.44, 126.60, 129.00, 129.05, 129.30, 129.51, 130.94, 131.65, 142.93, 143.11, 153.30; MS: m/z (%) 312 (M+2, 21), 310 (M⁺, 62), 296 (7), 295 (34), 294 (23), 293 (100), 184 (45), 183 (18), 169 (16), 168 (9), 141 (24), 127 (74), 76 (6); Anal. Calcd. for C₁₈H₁₅ClN₂O: C, 69.56; H, 4.86; N, 9.01. Found: C, 69.42; H, 4.73; N, 9.12.

1-Acetyl-2-naphthol 4̀-bromophenylhydrazone (7): This compound was prepared from 1-acetyl-2-naphthol and 4̀-bromophenylhydrazine using the procedure described for 1. Yield, 68%, yellow solid, mp 153°C; IR: 3,436 (OH), 3,354 (NH), 1,619 (C=N); ¹H-NMR: 2.49 (s, 3H), 7.01 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.4 Hz, 1H), 7.34 (m, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.45 (m, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.78(d, J = 8.4 Hz, 1H); ¹³C-NMR: 18.29, 112.86, 114.66, 116.23, 118.48, 123.14, 124.35, 126.49, 128.90, 129.20, 130.82, 131.54, 132.31, 143.29, 145.04, 153.19; MS: m/z (%) 356 (M+2, 71), 354 (M⁺, 75), 340 (19), 339 (97), 338 (22), 337 (100), 258 (8), 210 (17), 185 (12), 183 (27), 173 (44), 169 (67), 115 (87), 76 (7); Anal. Calcd. for C₁₈H₁₅BrN₂O: C, 60.86; H, 4.25; N, 7.88. Found: C, 60.73; H, 4.38; N, 7.93.

1-Acetyl-2-naphthol 4̀-methylphenylhydrazone (8): This compound was prepared from 1-acetyl-2-naphthol and 4̀-methylphenylhydrazine using the procedure described for 1. Yield, 68%, yellow solid, mp 132 °C; IR: 3,417 (OH), 3,360 (NH), 1,618 (C=N); ¹H-NMR: 2.29 (s, 3H), 2.49 (s, 3H), 7.02 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.8 Hz, 1H), 7.32 (m, 1H), 7.44 (m, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 7.3 Hz, 1H); ¹³C-NMR: 18.55, 20.69, 113.38, 116.22, 118.66, 123.15, 124.51, 126.51, 128.96, 129.24, 130.09, 130.62, 130.81, 131.65, 142.05, 143.11, 153.54; MS: m/z (%) 290 (M⁺, 89), 273 (100), 184 (30), 169 (7), 141 (11), 128 (8), 115 (35), 107 (57), 106 (36), 105 (46), 91 (6), 76 (25); Anal. Calcd. for C₁₉H₁₈N₂O: C, 78.59; H, 7.95; N, 12.27. Found: C, 78.41; H, 7.81; N, 12.18.

4-Methylene-3-(N-phenylamino)-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one (9): To a stirred solution of 0.20 g (0.72 mmol) of 1 and triethylamine (1 mL) in dichloromethane (30 mL) was added dropwise under N₂ atmosphere a solution of 0.5 equivalent (0.12 g, 0.36 mmol) of triphosgene in dichloromethane (10 mL). The mixture was refluxed for 4 hours and then washed with water. The organic layer was dried over magnesium sulfate and evaporated under vacuum. The resulting solid was recrystallized from a mixture of benzene-ethanol (1:1). Yield, 69%, colorless solid, mp 196°C; IR: 3,306 (NH), 1,727 (C=O), 1,620 (=CH₂); ¹H-NMR: 5.02 (d, J = 2.2 Hz, 1H), 5.13 (d, J = 2.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 2H), 7.02 (m, 3H), 7.55 (m, 2H), 7.61 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.83 (m, 1H), 8.20 (m, 1H), 8.33 (bs, 1H); ¹³C-NMR: 88.60, 111.50, 113.03, 120.69, 121.57, 122.93, 125.18, 127.46, 127.89, 128.12, 128.60, 129.30, 134.57, 138.69, 143.05, 146.16, 148.05; MS: m/z (%) 302 (M⁺, 13), 260 (25), 259 (100), 232 (11), 230 (23), 182 (18), 168 (11), 140 (9), 139 (17), 128 (25), 92 (13), 77 (9); Anal. Calcd. for C₁₉H₁₄N₂O₂: C, 75.48; H, 4.67; N, 9.27. Found: C, 75.13; H, 4.50; N, 9.63.

4-Methylene-3-[N-(4̀-chlorophenyl)amino]-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one (10): Prepared from 2 and triphosgene using the procedure described for 9. Yield, 74%, pale yellow solid, mp 182°C; IR: 3,260 (NH), 1,732 (C=O), 1,621 (=CH₂); ¹H-NMR: 5.02 (d, J = 2.2 Hz, 1H), 5.09 (d, J = 2.2 Hz, 1H), 6.57 (bs, 1H), 6.78 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H), 7.59 (m, 3H), 7.67 (d, J = 8.8 Hz, 1H), 7.85 (m, 1H), 8.30 (m, 1H); ¹³C-NMR: 88.55, 111.09, 114.46, 115.70, 120.24, 121.48, 123.03, 125.36, 127.53, 127.70, 128.22, 132.33, 134.68, 138.26, 143.46, 144.45, 147.99; MS: m/z (%) 338 (M+2, 6), 336 (M⁺, 17), 301 (24), 296 (9), 295 (32), 294 (23), 293 (91), 259 (28), 258 (100), 230 (17), 182 (53), 140 (18), 128 (74), 115 (21), 98 (31), 76 (10); Anal. Calcd. for C₁₉H₁₃Cl N₂O₂: C, 67.76; H, 3.89; N, 8.31. Found: C, 67.47; H, 3.71; N, 8.19.

4-Methylene-3-[N-(4̀-bromophenyl)amino]-3,4-dihydro-2H-naphth[2,1-e]1,3-oxazine-2-one (11): Obtained from 3 and triphosgene using the procedure described for 9. Yield, 71%, brownish solid, mp 185°C; IR: 3,281 (NH), 1,741 (C=O), 1,621 (=CH₂); ¹H-NMR: 4.96 (d, J = 2.0 Hz, 1H), 5.01 (d, J = 2.0 Hz, 1H), 6.73 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.54 (m, 4H), 7.83 (m, 1H), 8.17 (m, 1H), 8.69 (bs, 1H); ¹³C-NMR: 88.58, 111.33, 112.06, 114.89, 120.73, 121.52, 122.88, 125.27, 127.53, 127.95, 128.21, 131.99, 134.59, 138.54, 143.35, 145.60, 147.35; MS: m/z (%) 382 (M+2, 12), 380 (M⁺, 13), 354 (12), 340 (16), 339 (74), 337 (72), 301 (44), 259 (36), 258 (100), 230 (26), 182 (58), 128 (74), 115 (33), 91 (43), 76 (11); Anal. Calcd. for C₁₉H₁₃BrN₂O₂: C, 59.86; H, 3.43; N, 7.34. Found: C, 59.73; H, 3.33; N, 7.43.

4-Methylene-3-[N-(4-methylphenyl)amino]-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one (12): Obtained from 4 and triphosgene using the procedure described for 9. Yield, 73%, brownish solid, mp 150°C; IR: 3,260 (NH), 1,737 (C=O), 1,612 (=CH₂); ¹H-NMR: 2.19 (s, 3H), 4.92 (d, J = 2.0 Hz, 1H), 5.14 (d, J = 2.0 Hz, 1H), 6.71 (d, J = 8.1 Hz, 2H), 7.02 (d, J = 8.1 Hz, 2H), 7.69 (m, 2H), 7.84 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 8.04 (m, 1H), 8.17 (m, 1H), 8.67 (bs, 1H); ¹³C-NMR: 20.72, 88.97, 111.70, 113.07, 121.50, 122.80, 125.43, 128.10, 128.43, 128.62, 129.14, 130.03, 134.66, 138.99, 143.34, 144.14, 147.21; MS: m/z (%) 316 (M⁺, 24), 274 (20), 273 (100), 244 (10), 182 (13), 128 (23), 105 (61), 76 (31); Anal. Calcd. for C₂₀H₁₆N₂O₂: C, 75.93; H, 5.10; N, 8.85. Found: C, 75.81; H, 5.15; N, 8.77.

4-Methylene-3-(N-phenylamino)-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one (13): Obtained from 5 and triphosgene using the procedure described for 9. Yield, 62%, colorless solid, mp 166 °C; IR: 3,297 (NH), 1,725 (C=O), 1,620 (=CH₂); ¹H-NMR: 5.04 (d, J = 2.2 Hz, 1H), 5.15 (d, J = 2.2 Hz, 1H), 6.53 (bs, 1H), 6.97 (d, J = 8.8 Hz, 2H), 7.25 (m, 3H), 7.58 (m, 3H), 7.67 (d, J = 8.1 Hz, 1H), 7.84 (m, 1H), 8.32 (m, 1H); ¹³C-NMR: 88.53, 111.24, 113.97, 120.33, 121.90, 122.27, 123.10, 125.23, 127.44, 127.67, 128.12, 129.45, 134.66, 138.46, 143.53, 145.29, 148.07; MS: m/z (%) 302 (M⁺, 7), 258 (100), 182 (16), 128 (5), 115 (7), 92 (5), 77 (6); Anal. Calcd. for C₁₉H₁₄N₂O₂ : C, 75.48; H, 4.67; N, 9.27. Found: C, 75.24; H, 4.71; N, 9.18.

4-Methylene-3-[N-(4-chlorophenyl)amino]-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one (14): Obtained from 6 and triphosgene using the procedure described for 9. Yield, 61%, brownish solid, mp 187°C; IR: 3,260 (NH), 1,732 (C=O), 1,620 (=CH₂); ¹H-NMR: 5.05 (d, J = 1.5 Hz, 1H), 5.15 (d, J = 1.5 Hz, 1H), 6.52 (bs, 1H), 6.84 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.51 (m, 3H), 7.70 (d, J = 8.1 Hz, 1H), 7.86 (m, 1H), 8.31 (m, 1H); ¹³C-NMR: 88.53, 111.10, 115.33, 120.25, 121.87, 123.04, 125.37, 127.22, 127.54, 127.71, 128.23, 129.44, 134.69, 138.30, 143.48, 143.95, 148.01; MS: m/z (%) 338 (M+2, 5), 336 (M⁺, 14), 301 (24), 295 (29), 259 (29), 258 (100), 230 (14), 182 (60), 128 (68), 115 (21), 99 (36), 76 (9); Anal. Calcd. for C₁₉H₁₃Cl N₂O₂: C, 67.76; H, 3.89; N, 8.32. Found: C, 67.59; H, 3.95; N, 8.25.

4-Methylene-3-[N-(4-bromophenyl)amino]-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one (15): Obtained from 7 and triphosgene using the procedure described for 9. Yield, 64%, colorless solid, mp 203°C; IR: 3,353 (NH), 1,733 (C=O), 1,616 (=CH₂); ¹H-NMR: 5.05 (d, J = 2.2 Hz, 1H), 5.14 (d, J = 2.2 Hz, 1H), 6.53 (bs, 1H), 6.90 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.60 (m, 3H), 7.72 (d, J = 8.8 Hz, 1H), 7.82 (m, 1H), 8.12 (m, 1H); ¹³C-NMR: 88.54, 111.24, 113.96, 116.78, 120.33, 121.90, 125.24, 127.16, 127.45, 127.68, 128.13, 129.47, 134.66, 138.45, 143.53, 145.29, 148.08; MS: m/z (%) 382 (M+2, 18), 380 (M⁺, 16), 301 (35), 259 (30), 258 (100), 230 (35), 210 (18), 184 (49), 182 (48), 139 (45), 126 (69), 115 (72), 101 (35), 76 (19); Anal. Calcd. for C₁₉H₁₃BrN₂O₂: C, 59.86; H, 3.44; N, 7.35. Found: C, 59.98; H, 3.18; N, 7.12.

4-Methylene-3-[N-(4-methylphenyl)amino]-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one (16): Obtained from 8 and triphosgene using the procedure described for 9. Yield 60%, yellowish solid, mp 160°C; IR: 3,245 (NH), 1,741 (C=O), 1,615 (=CH₂); ¹H-NMR: 2.26 (s, 3H), 5.04 (d, J = 2.20 Hz, 1H), 5.14 (d, J = 2.20 Hz, 1H), 6.47 (bs, 1H), 6.81 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 7.58 (m, 3H), 7.66 (d, J = 8.8 Hz, 1H), 7.85 (m, 1H), 8.32 (m, 1H); ¹³C-NMR: 20.71, 88.50, 111.28, 114.12, 120.34, 121.91, 123.10, 125.19, 127.43, 127.67, 128.10, 129.96, 131.73, 134.63, 138.48, 142.88, 143.53, 148.10; MS: m/z (%) 316 (M⁺, 13) 274 (17), 273 (100), 182 (11), 139 (15), 128 (20), 106 (52), 76 (36); Anal. Calcd. for C₂₀H₁₆N₂O₂: C, 75.93; H, 5.10; N, 8.85. Found: C, 75.75; H, 5.22; N, 8.73.

3’-Phenyl-3-(phenylamino)-1’,12’b-dihydro-12`b-methylspiro{4H-naphth[2,1-e]-1,3-oxazine-4,2’ (3’H)- [5H]pyrazolo[1,5-c]naphth[2,1-e]-1,3-oxazine}-2,5’-dione (17): Obtained from 1 and one equivalent of triphosgene using the procedure described for 9. Yield 69%, reddish solid, mp 207 °C; IR: 3,256 (NH), 1,748, 1,755 (2C=O); ¹H-NMR: 2.12 (s, 3H), 3.58 (d, J = 14.70 Hz, 1H), 3.65 (d, J = 14.70 Hz, 1H), 6.72 (m, 4H), 6.97 (m, 4H), 7.11 (m, 5H), 7.58 (m, 5H), 7.91 (m, 2H), 8.40 (m, 2H); ¹³C-NMR: 32.15, 59.65, 66.06, 85.55, 112.48, 112.93, 113.91, 116.47, 116.80, 119.92, 120.36, 121.68, 122.19, 122.23, 124.96, 125.49, 127.55, 127.68, 128.81, 129.19, 133.56, 133.86, 134.09, 141.92, 142.46, 142.78, 143.18, 145.29, 145.42, 145.69, 149.24, 149.90; MS: m/z (%) 471 (M⁺ - C₆H₅N₂CO, 20), 455 (M⁺ - C₆H₅N₂CO₂, 14), 440 (57), 423 (28), 351 (12), 302 (21), 259 (100), 258 (17), 230 (34), 185 (29), 168 (39), 128 (21), 115 (38), 93 (70), 77 (51), 63 (35); Anal. Calcd. for C₃₈H₂₈N₄O₄: C, 75.48; H, 4.66; N, 9.26. Found: C, 75.21; H, 4.71; N, 9.19.

3’-(4-Chlorophenyl)-3-[(4-chlorophenyl)amino]-1’,12’b-dihydro-12’-b-methylspiro{4H-naphth[1,2-e]-1,3-oxazine-4,2’(3’H)-[5H]pyrazolo[1,5-c]naphth[2,1-e]-1,3-oxazine}-2,5’-dione (18): This compound was obtained from 2 and one equivalent of triphosgene using the procedure described for 9. Yield, 72%, mp 267°C; IR: 3,219 (NH), 1,724, 1,753 (2C=O); ¹H-NMR: 2.10 (s, 3H), 3.49 (d, J = 14.70 Hz, 1H), 3.60 (d, J = 14.70 Hz, 1H), 6.35 (m, 3H), 6.65 (m, 4H), 6.93 (m, 4H), 7.66 (m, 5H), 7.82 (m, 2H), 8.40 (m, 2H); ¹³C-NMR: 32.08, 60.07, 66.05, 85.47, 111.88, 114.22, 117.91, 119.62, 121.02, 121.54, 122.16, 122.56, 123.11, 125.25, 125.57, 126.45, 127.18, 127.40, 127.47, 127.66, 127.78, 127.93, 128.81, 128.84, 128.91, 133.47, 134.31, 141.39, 141.81, 143.90, 145.61, 149.61, 149.01, 149.07; MS: m/z (%) 505 (M⁺- ClC₆H₄N₂CO, 22), 489 (M⁺- ClC₆H₄N₂CO₂, 100), 410 (7), 336 (13), 295 (12), 259 (21), 230 (10), 168 (26), 139 (24), 127 (28), 115 (21), 99 (9), 90 (5), 76 (15), 63 (12); Anal. Calcd. for C₃₈H₂₆Cl₂N₄O₄: C, 67.76; H, 3.89; N, 8.32. Found: C, 67.46; H, 3.68; N, 8.54.

3’-(4-Bromophenyl)-3-[(4-bromophenyl)amino]-1’,12’b-dihydro-12’b-methylspiro{4H-naphth[2,1-e]-1,3-oxazine-4,2’(3’H)-[5H]pyrazolo[1,5-e]naphth[2,1-e]-1,3-oxazine}-2,5’-dione (19): Obtained from 3 and one equivalent of triphosgene using the procedure described for 9. Yield, 71%, mp 246 °C; IR: 3,232 (NH), 1,730, 1,745 (2C=O); ¹H-NMR: 2.09 (s, 3H), 3.44 (d, J = 14.70 Hz, 1H), 3.54 (d, J = 14.70 Hz, 1H), 6.28 (m, 3H), 6.60 (m, 3H), 6.85 (m, 2H), 7.04 (m, 2H), 7.52 (m, 6H), 7.78 (m, 2H), 8.34 (m, 2H); ¹³C-NMR: 32.04, 60.11, 65.96, 85.41, 111.75, 113.97, 114.67, 115.87, 117.98, 118.21, 119.56, 121.00, 121.53, 122.16, 122.55, 123.11, 125.31, 127.42, 127.48, 127.69, 127.79, 127.95, 128.94, 131.70, 131.74, 132.05, 133.66, 134.31, 141.78, 141.88, 144.40, 148.95, 149.15; MS: m/z (%) 549 (M⁺- BrC₆H₄N₂CO, 6), 533 (M⁺- BrC₆H₄N₂CO₂, 100), 409 (15), 382 (20), 380 (17), 340 (24), 339 (85), 258 (86), 202 (24), 196 (51), 168 (74), 129 (59), 115 (84), 99 (51), 91 (49), 90 (52), 76 (71), 63 (84); Anal. Calcd. for C₃₈H₂₆Br₂N₄O₄: C, 59.86; H, 3.43; N, 7.34. Found: C, 59.73; H, 3.49; N, 7.42.

3’-(4-Chlorophenyl)-3-[(4-chlorophenyl)amino]-1’,12’b-dihydro-12’b-methylspiro{4H-naphth[1,2-e]-1,3-oxazine-4,2’(3’H)-[5H]pyrazolo[1,54-c]naphth[1,2-e]-1,3-oxazine}-2,5’-dione (20): Obtained from 6 and one equivalent of triphosgene using the procedure described for 9. Yield, 55%; mp 227 °C; IR: 3,338 (NH), 1,730, 1,755 (2C=O); ¹H-NMR: 2.51 (s, 3H), 3.41 (d, J = 14.65 Hz, 1H), 3.54 (d, J = 14.65 Hz, 1H), 7.07 (m, 3H), 7.25 (m, 4H), 7.51 (m, 5H), 8.11 (m, 4H), 8.29 (m, 2H), 8.61 (m, 2H); ¹³C-NMR: 17.20, 27.87, 88.06, 97.68, 114.00, 114.31, 114.46, 115.89, 116.26, 120.55, 123.56, 124.20, 124.87, 125.67, 125.73, 127.89, 128.57, 128.72, 128.87, 128.93, 129.76, 131.21, 131.32, 131.66, 131.77, 131.80, 136.60, 138.88, 143.81, 144.17, 145.50, 147.04, 148.60, 149.01; MS: m/z (%) 505 (M⁺- ClC₆H₄N₂CO, 20), 489 (M⁺- ClC₆H₄N₂CO₂, 100), 410 (7), 336 (21), 319 (15), 295 (21), 293 (44), 258 (31), 230 (14), 139 (29), 127 (44), 115 (35), 75 (20), 63 (16); Anal. Calcd. for C₃₈H₂₆Cl₂N₄O₄: C, 67.76; H, 3.89; N, 8.32. Found: C, 67.53; H, 3.93; N, 8.46.

References

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Sample Availability: Samples of the compounds are available from the authors.

© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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Al-Bogami, A.S.; Al-Majid, A.M.; Al-Saad, M.A.; Mousa, A.A.; Al-Mazroa, S.A.; Alkhathlan, H.Z. Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine Dimers. Molecules 2009, 14, 2147-2159. https://doi.org/10.3390/molecules14062147

AMA Style

Al-Bogami AS, Al-Majid AM, Al-Saad MA, Mousa AA, Al-Mazroa SA, Alkhathlan HZ. Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine Dimers. Molecules. 2009; 14(6):2147-2159. https://doi.org/10.3390/molecules14062147

Chicago/Turabian Style

Al-Bogami, Abdullah Saad, Abdullah Mohammed Al-Majid, Mohammed Ali Al-Saad, Ahmed Amine Mousa, Sara Abdullah Al-Mazroa, and Hamad Zaid Alkhathlan. 2009. "Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine Dimers" Molecules 14, no. 6: 2147-2159. https://doi.org/10.3390/molecules14062147

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Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine Dimers

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