Hydrazones quaternary

Alkylation of 737 with 738 gave 739 (81USP4252806). Reaction of 2-hydrazinoquinoline with the quaternary salts of N,N-substituted thioamides gave the hydrazones 735 whose cyclization in acetic acid gave triazoloquinolines 736 (80PJC661) (Scheme 127). 

Synthesis of [1,2,3]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pyrimidines A novel approach to [l,2,3]triazolo[l,5-c]pyrimidines is shown in Scheme 55. Batori and Messmer - in the course of their investigations on fused azolium salts - described a synthetic pathway to l,3-disubstituted[l,2,3]triazolo[l,5-c]-pyrimidinium salts <1994JHC1041>. The cyclization was accomplished by transformation of the hydrazone 436. This compound was subjected to an oxidative ring closure by 2,4,4,6-tetrabromo-2,5-cyclohexadienone to give the bicyclic quaternary salt 437 in acceptable yield. 

An unusual one-pot intramolecular sulfoxide alkylation-elimination reaction was found by Gibson et al. <2001SL712>. These authors found that treatment of 459 with potassium bis-trimethylsilylamide resulted in a ring closure to 460 in acceptable yield. Furthermore, Batori and Messmer found an effective method for preparation of [l,2,3]triazolo[l,5- ]pyrimidinium salts <1994JHC1041> oxidative cyclization of hydrazones 461 by 2,4,4,6-tetrabromo-2,5-cyclohexadienone gave rise to the quaternary salts 462. Under certain reaction conditions, the formation of 6-bromo-salts 462 (R6 = Br) was also experienced. As neither the starting compound nor the quaternary triazolopyridinium salt underwent bromination in this position, the authors assumed that this bromination process occurred on one of the intermediates in the course of the above-mentioned cyclization reaction. 

As is depicted in Scheme 1.2.29, the epoxide 128 was synthesized starting from 2,2-dimethyl-l,3-dioxan-5-one RAMP hydrazone (R)-96, which was double-alkylated with methyl iodide at a- and a -positions leading to the trons-dimethylated hydrazone 131 in 79% yield over two steps and excellent stereoselectivity (de, ee > 96%) [68]. The quaternary stereocenter bearing the desired tertiary alcohol function was generated using benzyloxymethyl chloride (BOMCl) as the electrophile to trap the lithiated hydrazone 131, providing the a-quaternary hydrazone 132 in very good yield (92%), excellent diastereomeric and enantiomeric excesses (de, ee > 96%) and with the required cis relationship of the methyl substituents. 

The related benzotriazocinones (317) are obtained by cyclization of dialkylhydrazones (316) and mild thermolysis of the quaternary hydrazones (73CPB2375). The latter undergo ring contraction to diazepines by Stevens rearrangement. 

If an N-substituted hydrazone is used, a quaternary triazolopyridinium salt (13) is the product. Such oxidations have been performed with lead tetraacetate,15 with A/-bromosuccinimide,16 or electrochemically.17... 

By contrast, 3-hydrazino-l,2,4-thiadiazoles (163), which are prepared by ring closure methods, are very sensitive to acids and undergo elimination of sulfur with formation of 5-arylamino-l,2,4-triazoles (164) as indicated in Scheme 61 (63JCS4566). The mechanism of this conversion is not known but presumably involves the attack of a hard nucleophile at the 5-position followed by ring opening, loss of sulfur and recyclization as has been observed with the quaternary salts (77JCS(P1)1791) (see Schemes 22, 23, and 24). Hydrazine (163) reacts with aldehydes to produce hydrazones (165) and with dimethyl malonate to yield pyrazoles (166). Diazonium salts of type (153) have been prepared by the methods... 

Other special injection devices have been applied in combination with derivatization only rarely, if the reaction is carried out directly in the injection port. The method of thermal degradation of quaternary ammonium salts has already been mentioned. This can be performed in a sealed capillary directly in the injection port of the apparatus. The port should then be modified in order that when the reaction is finished, the capillary can be crushed and the products swept into the column. Another method of modification of the injection port in the thermal decomposition of hydrazones by a-ketoglutaric acid is shown in Fig. 4.3 (p.77). 

There is clearly a Fischer indole synthesis in the second step but the first step makes the usut. hydrazone in a most unusual way. The first reaction is diazotization so we have to combine fi diazonium salt with the enolate of the keto-ester. That creates a quaternary centre and the KC H deacylates it to give the aryl hydrazone needed for the Fischer reaction. 

Table 14 Preparation of Aziridines from Oximes (Quaternary Hydrazones) and Grignard Reagents...

The Neber rearrangement involves the base-catalyzed conversion of oxime tosylates, quaternary salts of hydrazones or /V-chloroimines to a-amino ketones via isolable azirine intermediates (equation... 

The sodium salt of the JV-methoxycarbonyl hydrazone rearranges faster than the hydrazone itself or the parent ketone. This method has been used for the construction of vicinal quaternary centers, since the accelerating functionality can simply be removed by Wolff Kischner reduction. For charge-accelerated Claisen rearrangements of related systems see refs 85 and 113— 118. 

Isoquinoline V-imines also have been made only by deprotonation of V-aminoisoquinolinium salts. Just as for the corresponding pyridinium derivatives (see Section II,A,1), the salts 43 can be produced by amination of isoquinoline with hydroxylamine-O-sulfonic acid75 or from V-(2,4-di-nitrophenyl) isoquinolinium chloride (44), 30 31 76 Substituted quaternary amino salts (46) are obtained by cyclization of 2-(2,4-dinitroanilino)-o-styrylaldehyde hydrazones (45) with ethanolic hydrochloric acid, and deprotonation to V-imines is easily effected by alkali. On liberation from the salts by alkali, unsubstituted isoquinoline V-imines dimerize to give... 

Taking advantage of the bulky f-butyl group of methyl )V-((o-bromoacyl)-l -butyl-oxazolidine-4-carboxylate to achieve a 1,3-asymmetric induction in the i- ramolecular alkylation, a series of lactams containing a quaternary chiral center is i. jilable. With S AMP/RAMP chiral auxiliaries, the synthesis of 2-substituted (five, six, and. en membered) lactams is readily achieved." Aldehyde hydrazones of this series undergo iANtereoselective phosphinylation. ... 

Of note, the above methodology has also been extended to the synthesis of a chiral non-racemic 2,2-disubstituted oxetane-3-one, with the generation of a quaternary center firom an a-CH2 unit, by simply exploiting a one-pot double alkylation protocol. Starting firom oxetane-3-one 45, 2,2-dialkylated hydrazone 49 was first obtained with an overall yield of... 

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