Diazo derivatives, reactions

Only 2-aminothiazole derivatives are reactive enough toward diazonium salts to undergo the diazo-coupling reaction. The azo group fixes exclusively on the 5-position when it is free (Scheme 62) (351). 

Tuduranine, CjgHjgOgN. This member of the aporphine group (p. 306) is the most recent addition to Sinomenium alkaloids and was isolated by Goto from the mother liquors of sinomenine. It is crystalline, has m.p. 125° (with softening at 105°), and yields a sparingly soluble hydrochloride, m.p. 286° (dec.), [a] f — 148° (dilute MeOH), is freely soluble in alkali, and gives feeble ferric chloride and diazo-colour reactions and a fuchsin-red colour with formaldehyde and sulphuric acid. It behaves as a secondary base and yields a diacetyl derivative, m.p. 170°, [a] / — 321-71° (MeOH), which does not form a methiodide, but can be hydrolysed to A -acetyl-tuduranine, m.p. 277°, — 395-24°, and this can be methylated to... 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Oxaestrone has been synthesised from 7-methoxychroman-4-one <96JCS(P1)841>. Formation of the complex chroman-3-one (16) by a Dieckmann reaction and its conversion to the 4-diazo derivative are signifcant steps in the synthesis of the pentacyclic system (17) <96TL5243>. 

Since the regioselectivity of mercuration reactions is often hard to control, recent efforts have focused on the use of Lewis-basic substituents whose role is to direct the approach of the mercuric ion to a specific position. Reaction of the diazo derivative 74 with Hg(OAc)2 leads to mercuration of the naphthalene moiety in the 8-position rather than mercuration of the electron-rich imidazole carbon atoms. 4 Presumably, the diazo-imidazole bidentate moiety coordinates to the mercuric cation, thereby directing substitution at the naphthalene 8-position (Equation (27)). 

Figure 4.31 Reaction of o-tolidine with sodium nitrite in the presence of HC1 yields a highly reactive diazo derivative.

Liebermann-Burchard reaction diazo derivatives nitrated derivative... 

Triazoles (386, R1 = COOMe) were treated with potassium tert-butylate in a mixture of f r/-butanol and benzene for 15-60 min to give (substituted amino)methoxycarbonylmethylenemalonates (387, R1 = COOMe) in 28-54% yields. In the case of the acetyl derivative (386, R = Ph, R1 = COMe), the reaction was carried out in chloroform in the presence of triethylamine at ambient temperature for 8 hr, to give (pheny-lamino)acetylmethylenemalonate (387, R = Ph, R = COMe) in 38% yield. (Phenylamino)acylmethylenemalonates (387, R = Ph,R = COMe, COPh) were also prepared in 62-74% yields when diazo derivatives (388, R1 = COMe, COPh) were heated in benzene for 4-24 hr (80T1821) (Scheme 34). 

The reaction of activated methylene groups with tosyl azide to yield the corresponding diazo derivatives proceeds in high yield [23]. The phase-transfer catalysed reaction is sensitive to the strength of base used the reaction of acetoacetic esters requires relatively mild conditions, otherwise diazoacetic esters are produced (Table 5.41). 

Carbethoxy-4-diazo-l-phenylpyrazol-5-one (22a) (Scheme 88) was synthesized in 76% yield under mild conditions by direct introduction of the diazo group with the azidium salt 293 in sulfuric acid at room temperature [78H(10)199]. The easy introduction of the diazo group probably occurred because the a position of the ester was activated. On the contrary, tosyl azide failed to give the diazo derivative under the same conditions. Diazo transfer with this reagent only takes place under alkaline conditions, but in these reaction conditions, the diazo compound couples with the starting material. 

Padwa and Prein (105,106) applied chiral, but racemic, isomiinchnone dipoles in diastereoselective 1,3-dipolar cycloadditions. The carbonyl ylide related isomiinch-none derivative rac-70 was obtained from the rhodium-catalyzed cyclization of diazo-derivative rac-69 (Scheme 12.24) (105). The reactions of the in situ formed dipole with a series of alkenes was described and in particular the reaction with maleic acid derivatives 71a-c gave rise to reaction with high selectivities. The tetracyclic products 72a-c were all obtained in good yield with high endo/ exo and diastereofacial selectivities. In another paper by the same authors, the reactions of racemic isomilnchnones having an exo-cyclic chirality was described (106). 

The power of chiral C2-symmetric bis(oxazolines) in cyclopropanation reactions has also been exhibited in total synthesis. One example is Corey and co-workers synthesis of sirenin 63 using bis(oxazoline) ligand 8 (Fig. 9.19). They showed that the intramolecular cyclopropanation of diazo derivative 61 proceeded in 77% yield and with 90% ee. Shibasaki and co-workers constructed prostratin 67 through the intermediate cyclopropane 66, also shown in Figure 9.19. Using bis(oxazoline) ligand 64 and copper(I) triflate-derived catalyst, compound 66 was prepared in 70% yield and 92% ee from diazo derivative 65. ... 

Whatever method is used, the replacement of an amino group by fluorine, via a diazo derivative, implies two reaction steps diazotization (to give 1) and dediazoniation (to give 2). The diazo intermediate can be isolated or not depending upon the substrate, the reagents, and the reaction conditions however, some general mechanistic features are common to all cases. 

Reaction of the isobenzopyrylium cation (430) with N2H4 gives (431) (93KGS1475). 1/7-2,3-Benzodiazepines (433) (73JCS(Pl)2543) and analogous thienodiazepines (80JCS(P1)1718) are obtained from electrocyclic reaction of diazo derivatives (432). 

Reaction of pyrido[2,l-6][l,3]thiazine-2,4-dione (105) with p-tosyl azide in the presence of triethylamine in acetonitrile at 0°C gave a 3-diazo derivative (106), which reacted with cyclohexene in the presence of a catalytic amount of rhodium acetate under reflux to yield a spiro derivative (107) [94H(39)219 95H(41)1631]. 

The generation and addition of acyl- and alkoxycarbonylcarbenes to alkenes is usually carried out by using the corresponding diazo derivatives under catalysis of metallic compounds. The metal-catalyzed cyclopropanation reactions with diazo compounds are described in detail by McKervey in Chapter 11, hence dealt with rather briefly in this chapter. The readers who are interested in the preparation of acyl- and alkoxycarbonyl-substi-tuted cyclopropanes are requested to refer also to Chapter 9. 

Azo or diazene compounds possess the —N=N— grouping. Aliphatic azo compounds of the type R—N=N—H appear to be highly unstable and decompose to R—H and nitrogen. Derivatives of the type R—N=N—R are much more stable and can be prepared as mentioned above by oxidation of the corresponding hydrazines. Aromatic azo compounds are available in considerable profusion from diazo coupling reactions (Section 23-IOC) and are of commercial importance as dyes and coloring materials. 

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