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Kikelj, D., Science of Synthesis, (2004) 16, 586.
2-Substituted quinazolin-4(3H)-ones 5 are conveniently obtained by reaction of anthranilic acids, alkyl anthranilates, or 2-aminobenzamides with a variety of nitriles, e.g. alkyl and aryl nitriles,[192–196] haloacetonitriles,[192,197] aryl cyanates,[172,198] cyanamides,[199–201] alkyl cyanoformates,[202] dicyan,[203] and alkyl dicyanoacetates[81] (Scheme 15). In the older variations of this method, anthranilic acid and a nitrile are heated in a sealed tube at 200°C alone[204] or in the presence of an anhydride[205] or carboxylic acid.[206] The drawbacks of this older variation are moderate yields (usually below 50%) and lack of specificity, since the substituent at position 2 in 5 may originate from the nitrile or from the carboxylic component. An improved method utilizes hydrogen chloride as an acid catalyst or makes use of a basic catalyst, e.g. sodium methoxide[197] or lithium diisopropylamide.[193] The reaction presumably proceeds via nucleophilic attack of the amino group of 35 on the nitrile or on a reactive species derived from a nitrile (under hydrochloric acid catalysis, presumably an imidoyl chloride or a nitrilium halide[207]) to give the ortho-substituted amidine derivative which cyclizes to the corresponding fused pyrimidin-4-one 5. 2-Aryl- and 2-benzylquinazolin-4(3H)-ones are readily accessible in fair yields by reaction of N,N-diethyl-2-nitrobenzamide with appropriate aryl and benzyl halides in the presence of samarium(II) iodide, which selectively reduces the nitro group in the presence of nitriles and thus generates 2-aminobenzamide in situ.[208]
Meeeee 88 8-Meeeeeeeeee Meeeeeeeee-8(8M)-eeee eeee Meeeeeeeeee Meee Meeeeeeeeee eee Meeeeeee[88,888,888–888]
M8 | M | Meeeeeee | Meeeeee | Meee (°M) | Meee (e) | Meeee (%) | ee (°M) | Mee |
---|---|---|---|---|---|---|---|---|
Me | MMe | MMe(e) | eeeeeee | ee | 8 | 88 | 888–888 | [888] |
MM8MM8Me | MMe | MMe(e) | eeeeeee | ee | 8 | 88 | 888–888 | [888] |
MM(MM)MM8Me | MM | MMe | M8M | eeeeee | 88 | 88 | 888–888 | [88] |
MM8Me | MM | MeMMe | MeMM | ee | 8 | 88 | 888 | [888] |
MM8Me | MMe | MMe(e) | MeMM | 888 | 8.8 | 88 | 888 | [888] |
Me | MMe8 | MMM | MMM | −88, eeee eeeeee | 8.88 | 88 | 888–888 | [888] |
Me | MMe | MMe(e) | eeeeeee | ee | 8 | 88 | 888–888 | [888] |
Me | MMe | MMe(e) | eeeeeee | ee | 8 | 88 | 888–888 | [888] |
8,8-Me8M8M8M | MMe | MeMM8M | eeeeeee | 88 | 8.88 | 88 | 888 | [888] |
MM8 | MM | MMe | M8M | ee | 8888 | 88 | 888 | [888] |
MMM(MM)MM8 | MMe | MeMM | M8M | eeeeee | 8 | 88 | 888–888 | [888] |
Meeeeeeeeeee Meeeeeeee
Meeeeeeeee-8(8M)-eeee 8; Meeeeee Meeeeeeee:[888]
M eeeeee ee eee MMe(e) eee eeeeee eeeeeeee e eeeeeee ee eeeeee eeeeeeeeeeee (8.88 e, 8.88 eee) eee eee eeeeeee (8.888 eee) ee eeeeeee (88 eM) eee eeeee 8 e. Mee eeeeeee eee eeeeeee eeee eee eeeee eee eeeeeeee eeee 88% ee MM8. Mee eeeee eeeeeeee eee eeeeee eeee M8M, eeeee, eee eeeeeeeeeeee eeee e eeeeeeee eeeeeee. Meee eeeeeeee eeeeeeee eee eeeeee ee eee eeeeeee eeee eeeeeeee ee eeeeeee eee eeeeeee ee e eeeee eeee eee e eee eeeee eeeee eeeeeee eee MMe(e). Me eee eeee ee MeMM, ee eeeeee eee eeee ee eee eeeeeee.
8-Meee- eee 8-Meeeeeeeeeeeeee-8(8M)-eeee 8; Meeeeee Meeeeeeee:[888]
M eeee ee MMM, eeeeeeee ee eeeeeeee ee 8.8 M MeMe ee eeeeee (8.8 eM, 88 eeee) ee eMe8MM (8.8 eM, 88 eeee) ee MMM (88 eM), eee eeeeeee eeeee eeeee eee 88 eee eee e eeee ee 8-eeeee-M,M-eeeeeeeeeeeeeeee (8.88 e, 88 eeee) ee MMM (88 eM) eee eeeee eeeeeeee. Me eee eeeeeeeee eeeeee eeee, eee eeeeeeeeeee eeeeeee (88 eeee) eeeeeeeee ee MMM (8 eM) eee eeeee eeee e eeeeee ee 8 eee. Mee eeeeeee eee eeee eeeeeee ee eeee ee ee, eee eeee eeeeee eeeeeeee eee 88 eee. Meeee eeeeeee, M8M (88 eM) eee eeeee. Mee eM ee eee eeeeeee eee eeee eeeeeeee ee 8–8 ee eeeeeeee ee MM8Me. Mee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeee, eeeeee eeeeeee eeeee eeee M8M, eeeee eeeee eeeeee, eee eeeeeeeeeeeeee (MeMM ee MMM). Meeeeeeeeeeee, eee eeeeeee eee eeeeeeeee eeee MM8Me8 (8 × 88 eM), eee eeeeeee eeeee eee eeeeee eeee M8M, eee eeeee (Me8MM8). Mee eeeee eeeeeee eee eeeeeee eeeeeeeeeeeeee (MeMM).
References
[81] | Meeeeeee, M.; Mee, M.; Meeeee, M.; Meeee, M., Mee. Meee. Meee., (8888) 88, 888. |
[172] | Meeeeeee, M., Me Meeeee–Meee, (8888); Mee M 8, e 888. |
[192] | Meeeeee, M. M.; Meeeee, M. M.; Meeeeeee, M.; Meee, M. M.; Meeeee, M. M.; Meeee, M.; Meeee, M. M., Meeeee M. Meee., Meee. M, (8888) 88, 8888. |
[193] | Meeeeee, M.; Meeeee, M.; Meeeeeeeeeee, M., Meeeeeeee, (8888), 8888. |
[194] | Meeeeeeeee, M. M.; Meeeeee, M. M. M.; Meeee, M. M. M.; Meeeeee, M. M., Meee. Mee. (Meeeee), (8888), 888. |
[195] | Meeeee, M. M.; Meeeeeeee, M. M., M. Meee. Mee., (8888), 888. |
[196] | Meeeee, M. M.; Meeeeee, M.; Meeee, M. M. M.; Meeeeeee, M. M., Meee. Meeeee., (8888), 88. |
[197] | Meeee, M., Meee. Meeee. (Meeeeeee, Mee.), (8888) 888, 888. |
[198] | Meeeeeeeeeee, M.; Meeeeee, M., M. Meeeeeeeee. Meee., (8888) 88, 8888. |
[199] | Meeee, M. M.; Meeeeeeee, M. M., M. Meee. Mee., (8888), 8888. |
[200] | M'Meee Meeee, M.; Meeee, M., M. Mee. Meee., (8888) 88, 888. |
[201] | Meeeee, M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[202] | Meeeeeee, M.; Meeeee, M.; Meeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[203] | Meeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 8888. |
[204] | Meeeeeee, M.; Meeeee, M. M., M. Me. Meee. Mee., (8888) 88, 888. |
[205] | Meeeeeee, M., M. Me. Meee. Mee., (8888) 88, 888. |
[206] | Möeee, M., M. Meeee. Meee., (8888) 88, 8. |
[207] | Meee, M. M.; Meeeeee, M. M.; Meeeee, M. M.; Meeeeeeeeeee, M.; Meeeeeee, M.; Meeee, M. M.; Meeeee, M. M., M. Meeeeeeeee. Meee., (8888) 88, 8888. |
[208] | Me, M.; Me, M.; Meeee, M., Meeee. Meeeee., (8888) 88, 888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) M 8e8, 88.