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Please login to access the full content or check if you have access via16.10.1.1.1.1.2 Method 2: Condensation of 2-Acyl- and 2-Formylbenzoic Acid Derivatives with Hydrazine
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Haider, N.; Holzer, W., Science of Synthesis, (2004) 16, 322.
The synthesis of phthalazin-1(2H)-ones by condensation of 2-acyl- or 2-formylbenzoic acids with hydrazine is one of the oldest areas of phthalazine chemistry and was developed in the 1880s and 1890s.[13,122–130] Employment of 2-acylbenzoic acids 22 leads to 4-substituted phthalazinones 23 (R2 = H) (Scheme 12); reaction with substituted hydrazines yields the corresponding 2-substituted products 23 (R2 ≠ H). From 2-formylbenzoic acids 24, phthalazin-1(2H)-ones 25 and 26 unsubstituted at position 4 are obtained (Scheme 13). In several cases, the former compounds 24 are prepared, in equilibrium with 29, in situ from the appropriate phthalides 27 by bromination and subsequent hydrolysis of the bromo derivatives 28; they are then reacted with hydrazine or substituted hydrazines to give phthalazinones 26, respectively, without isolation (Scheme 14, path A).[131–133] The intermediates 24 are also accessible from the acetophenone derivatives 30 by potassium permanganate oxidation in alkaline medium, and decarboxylation of the resulting 2-oxocarboxylic acids 31 (Scheme 14, path B).[131] If R1 in compound 30 is a methyl group, it is also oxidized leading to the phthalazinones 26 with a carboxylic acid function attached to the benzene moiety.[131] There are only a few examples where the carbonyl atoms in compounds 24 are replaced by equivalent synthons. Thus, phthalazin-1(2H)-one (2) can be obtained in high yield starting from the chloro compound 32,[134] whereas 3-formylphthalonitrile (33) is converted into compound 34 upon heating with hydrazine hydrate in 12 M hydrochloric acid (Scheme 15).[135] 2-Acetylbenzonitrile, with hydrazine hydrate in refluxing methanol, gives 4-methylphthalazin-1(2H)-one; with phenylhydrazine in ethanol the corresponding 4-methyl-2-phenylphthalazin-1(2H)-one is obtained.[136]
Meeeee 88 Meeeeeee ee 8-Meeeeeeeeee Meeee eeee Meeeeeeeee[88,888,888–888]
M8 | M8 | Meeee (%) | ee (°M) | Mee |
---|---|---|---|---|
Me | M | 88 | 888–888 | [888] |
Me | M | 88 | 888–888 | [88] |
Me | M | 88 | 888–888 | [888] |
8-eeeeeee | M | 88 | 888–888 | [888] |
8-eeeee | M | 88 | 888–888 | [888] |
8-eeeeeee | M | 88 | 888–888 | [888] |
8-eeeeeee | M | 88 | 888–888 | [888] |
8-eeeeeee | M | 88 | 888–888 | [888] |
eeeeeee-8-ee | M | 88 | >888 | [888] |
eeeeee-8-eee | M | 88 | 888–888 | [888] |
eeeeeee-8-ee | M | 88 | 888–888 | [888] |
Me | Me | 88 | 888–888 | [888] |
Me | Me | 88 | 888–888 | [888] |
Me | Me | 88 | 888 | [888] |
Me | Me | 88 | 888–888 | [888] |
Me | MM8MM8MM | 88 | 888–888 | [888] |
Me | MM8MM8Me | 88 | 888–888 | [888] |
Meeeee 88 Meeeeeee ee 8-Meeeeeeeeeeee Meeee eeee Meeeeeeee[888,888–888] eee Meeeeeeeeee Meeeeeeeee[888,888]
Meeeee 88 Meeeeeeee ee Meeeeeeeeee Meeeeeeeee-8(8M)-eeee eee Me Meee Meeeeeee 8-Meeeeeeeeeeee Meeee[888–888]
M8 | M8 | Meeee (%) ee 88 eeee 88 | Mee |
---|---|---|---|
8-Me | M | 88 | [888] |
8-Me | M | 88 | [888] |
8-Me | M | 88 | [888] |
8-Me | M | 88 | [888] |
8-MM8 | Me | 88 | [888] |
8-MM8 | Me | 88 | [888] |
8-MM8 | Me | 88 | [888] |
M8 | M8 | Meeee (%) ee 88 eeee 88 | Mee |
---|---|---|---|
8-Me | Me | 88 | [888] |
8-Me | Me | 88 | [888] |
8-MMe | Me | 88 | [888] |
8-MM8Me | Me | 88 | [888] |
8-MM8Me | Me | 88 | [888] |
e M8 ee 88 = Me.
Meeeee 88 Meeeeeeee ee Meeeeeeeee-8(8M)-eeee eeee Meeeee ee Meeeeee Meeeeeee[888,888]
Meeeeeeeeeee Meeeeeeee
8-Meeeeeeeeeeeeeee-8(8M)-eee (88, M8 = Me; M8 = M); Meeeeee Meeeeeeee:[888]
M eeee ee 8-eeeeeeeeeeeeee eeee (88, M8 = Me; 8.8 e, 88.8 eeee) eee 88% eeeeeeeee eeeeeee (8.8 e, 88 eeee) ee MeMM (888 eM) eee eeeeeeee eee 8 e. Meeee eeeeeee, eee eeeeeeeee eeeeeeeeeee eee eeeeeeeee ee eeeeeeeeee, eeeeee eeee MeMM, eee eeeeeeeeeeeeee (MeMM/MMM) ee eeee eeeee eeeeeeee; eeeee: 8.8 e (88%); ee 888–888°M.
8-Meeeeeeeeeeeeeee-8(8M)-eee (88, M8 = M; M8 = Me): Meeeeee Meeeeeeee[888]
M eeeeeee ee 8-eeeeeeeeeeeee eeee (88, M8 = M; 88 e, 8.888 eee) eee MeMM (888 eM) eee eeeeeee eeee eeeeeeeeeeeeeee (8.8 eM, 8.888 eee) eee eeeeeeee eeeee M8 eee 88 e. Mee eeeeeeeee eeee eee eeeeeeeeeeee ee eeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eeeee ee ee MeMM (88 eM), eeeeeee eeee M8M (88 eM), eee eeeeeeeeeeee. Meeee 88 e, eee eeeeeeeeeeee eeeee eee eeeeeeeee, eeeeee eeee MeMM, eee eee eeeee; eeeee: 88.8 e (88%); ee 888–888°M. Meeeeeeeeeeeeeeee (eeeeeeeeeee; 888 eM) eeeeeeee eeee eeeee eeeeeeee; eeeee: 88.8 e (88%); ee 888.8–888°M.
References
[13] | Meee, M., Mee. Meeee. Meee. Mee., (8888) 88, 8888. |
[121] | Meeeeee, M.; Meeeeeee, M.; Meeee, M.; Meee, M., Meeeeeeeeee, (8888) 88, 8888. |
[122] | Meeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 888. |
[123] | Meeeeeeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 888. |
[124] | Meeeee, M., Meeeee Meeeeee Mee. Meee., (8888) 888, 88. |
[125] | Meeeeeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 8888. |
[126] | Meeeeee, M.; Meeeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 888. |
[127] | Meeeeeeeee, M.; Meeeeeeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 888. |
[128] | Meeeeee, M.; Meeeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 888. |
[129] | eee Meeeeeeeee, M., M. Meeee. Meee., (8888) 88, 888. |
[130] | Meeeeeee, M., Mee. Meeee. Meee. Mee., (8888) 88, 888. |
[131] | Meeeeeee, M.; Meeeeeee, M.; Meeeee, M.; Meeeeeeee, M.; Meeeeeee, M., Meee. Meeee. Meee., (8888) 88, 8888. |
[132] | Meeeeee, M. M.; Meeeeee, M. M. M., M. Me. Meee. Mee., (8888) 88, 8888. |
[133] | Meeeeeee, M.; Meee, M.; Meeeee, M., Mee. Meeee. Me., (8888) 88, 888. |
[134] | Meee Mee., MM 8888888, (8888); Meee. Meeee., (8888) 88, 88888. |
[135] | Meee, M.; Meeee, M.; Mee, M.; Meeeeeee, M.; Meee, M.; Meeee, M., Meee. Meee. Mee. Mee., (8888) 88, 8888. |
[136] | Meeeeeeee, M. M.; eee Meeee, M., Meeeee Meeeeee Mee. Meee., (8888) 888, 888. |
[137] | Meeeeeeee, M.; Meeee, M.; Meee, M.; Meeee, M.; Meeeee, M.; Mee, M., M. Mee. Meee., (8888) 88, 8888. |
[138] | Meeeeeeee, M.; Meeee, M.; Meee, M.; Meeee, M.; Meeeeeee, M.; Meeeee, M.; Mee, M., M. Mee. Meee., (8888) 88, 8888. |
[139] | Meeeeeee, M. M.; Meeeeeeeee, M. M.; Meeeeeee, M. M.; Meeeeee, M. M., Me. Mee. Meee., (8888) 88, 8888; M. Mee. Meee. MMMM (Meee. Meeeee.), (8888) 88, 8888. |
[140] | Meee, M. M.; Meeeee, M. M., M. Meee. Mee., (8888), 8888. |
[141] | M'Meee, M. M.; Meeeeeeeee, M. M., Me. Mee. Meee., (8888) 88, 8888; M. Mee. Meee. MMMM (Meee. Meeeee.), (8888) 88, 8888. |
[142] | Meee, M.; Meeeeeeeeee, M.; Meeeeeeeee, M., Meeeeeeee, (8888) 88, 888. |
[143] | Meeeeeee, M.; Meeeeeeee, M., Meee Mee. Meeee., (8888) 88, 88; Meee. Meeee., (8888) 88, 88888. |
[144] | Meeeeeeeee, M.; Meeeeee, M., Meee. Meee., (8888) 8, 888. |
[145] | Meeeeeee, M. M.; Meeee, M. M.; Meeeeee, M. M. M., M. Meee. Mee., (8888), 8888. |
[146] | Meeeeee, M. M.; Meeeee, M. M.; Meeeeee, M. M.; Meeeeeee, M. M.; Meeeeeeee, M. M., Mee. M. Meee., (8888) 88, 8888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) M 8e, 888.