N-acyl hydrazones

N-Acyl-hydrazone werden durch Lithiumalanat zu 1,2-Dialkyl-hydrazinen und Acyl-hydrazinen reduziert3 ... 

Cyclische N-Acyl-hydrazone mit einer cnr/o-Hydrazinocarbonyl-Gruppe ergeben ahnlich den entsprechenden Carbonsaure-hydraziden keine einheitlichen Reduktions-produkte. Im Gegensatz zu den acyclischen Acyl-hydrazonen werden hauptsachlich cyclische Hydrazone gebildet. 5-Oxo-3,4,4-trimethyl-l-phenyl-4,5-dihydro-pyrazol er-gibt z. B. 50% d.Th. 3,4,4-Trimethyl-l-phenyl-4,5-dihydro-pyrazol und 20% d.Th. 5-Hydroxy-3,4,4-trimethyl-1 -phenyl-4,5-dihydro-pyrazoV ... 

Less-common types of C=N derivatives can also be reduced enantioselectively. An interesting example is the hydrogenation of the aromatic N-acyl hydrazones 13 with the Rh-duphos catalyst (Table 34.6 entry 6.1). This reaction was devel-... 

Rhodium diphosphine catalysts can be easily prepared from [Rh(nbd)Cl]2 and a chiral diphosphine, and are suitable for the hydrogenation of imines and N-acyl hydrazones. However, with most imine substrates they exhibit lower activities than the analogous Ir catalysts. The most selective diphosphine ligand is bdppsuif, which is not easily available. Rh-duphos is very selective for the hydrogenation of N-acyl hydrazones and with TOFs up to 1000 h-1 would be active enough for a technical application. Rh-josiphos complexes are the catalysts of choice for the hydrogenation of phosphinyl imines. Recently developed (penta-methylcyclopentyl) Rh-tosylated diamine or amino alcohol complexes are active for the transfer hydrogenation for a variety of C = N functions, and can be an attractive alternative for specific applications. 

Friestad and co-workers recently demonstrated that N-acyl hydrazones were excellent radical acceptors in the presence of a chiral Lewis acid [84], Valerolactam-derived hydrazone 117 proved to be the optimal substrate for enantioselective radical additions. Upon further optimization it was found that Cu(OTf )i and f-bulyl bisoxazoline ligand 96 gave the best yields and ee s (Scheme 31). Interestingly, a mixed solvent system (benzene dichloromethane in a 2 1 ratio, respectively) in the presence of molecular sieves (4 A) were necessary to achieve high yields and selectivities. 

A new synthesis of the pyrazolo[4,3-r ]pyridine core based on an unusual one-step tandem ring closure and rearrangement of bisacetylenic N-acylated hydrazones using aqueous ammonia has been reported (Equation 81 Table 34) <2004T933>. 

Appropriate functionalization of C=N bonds can greatly assist their asymmetic reduction. In particular, the reduction of N-acyl hydrazones with a rhodium complex of the ligand DuPHOS (P13) represents an outstanding example. In this process (Scheme 62) a product of up to 97% e.e. is obtained in high yield. After the reduction, samarium-iodide cleavage of the N—N bond gives the product amine273,274. 

Enantioselective radical addition to N-acyl hydrazone using triethylborane as chain transfer reagent has been reported by Friestad. Enantiomeric excesses up to 95% were obtained in the presence of copper(II)-bisoxazolines Lewis acid (Scheme 51) [115]. 

Figure 2.1 The C C bond disconnection approach to asymmetric amine synthesis and a generalized structure of N acyl hydrazones (1).

Hydrogenation of unfunctionalized C=C Hydrogenation of a- or 8-functionalized C=0 Hydrogenation of aryl ketones Hydrogenation of unfunctionalized C=0 Hydrogenation of N-aryl or cyclic imines Hydrogenation of N-alkyl imines Hydrogenation of N-acyl-hydrazones Epoxidation of allylic alcohols Epoxidation of C=C... 

Enantioselective free-radical additions to N-acyl hydrazones mediated by chiral Cu(II) Lewis acids have been demonstrated by Friestad and coworkers [16]. Addition of a variety of alkyl radicals to valerolactam-derived N-acyl hydrazone (54) catalyzed by one equivalent of dehydrated [Cu((S,S)-tBu-box)(H20)2(OTf)](OTf) (55) proceeds with moderate to good yield and high enantioselectivity (Scheme 17.11). Catalytic loadings could be decreased without loss of reactivity, but significant erosion of enantioselectivity was observed. Nevertheless, this methodology represents a viable alternative to classical Strecker and Mannich reactions for asymmetric amine synthesis. 

The Hurd-Mori 1,2,3-thiadiazole synthesis is the reaction of thionyl chloride with the N-acylated or tosylated hydrazone derivatives 1 to provide the 1,2,3-thiadiazole 4 in one simple step. ... 

Hydrazine 835 underwent ring closure with one carbon cyclizing reagents to afford 837 and/or /V-acyl derivatives 836. The N-acyl derivatives underwent cyclization on treatment with phosphorus oxychloride. They were also prepared by the reaction of hydrazones 838 with thionyl chloride (84JHC1565). Compound 835 underwent ring closure with carbon disulfide and ethyl chloroformate to give 839 (Scheme 169). 

Phenyl- und Acyl-hydrazone werden im sauren Milieu in der Regel unter N-N-Spaltung zu Aminen reduziert z. B. ... 

Acyl-hydrazone vom Typ der 3-Oxo-2-methyl-2,3-dihydro-l,2,4-triazine werden im sauren Medium unter Reduktion einer C=N-Doppelbindung im alkalischen unter 1,4-Addition angegriffen2 ... 

Special reactions of hydrazides and azides are illustrated by the conversion of the hydrazide (205) into the azide (206) by nitrous acid (60JOC1950) and thence into the urethane (207) by ethanol (64FES(19)105Q> the conversion of the same azide (206) into the N-alkylamide (208) by ethylamine the formation of the hydrazone (209) from acetaldehyde and the hydrazide (205) and the N- acylation of the hydrazide (205) to give, for example, the formylhydrazide (210) (65FES(20)259>. It is evident that there is an isocyanate intermediate between (206) and (207) such compounds have been isolated sometimes, e.g. (211). Several of the above reactions are involved in some Curtius degradations. 

This molecular motor is an example that illustrates how the changes in configuration can have an influence on the exchanges of dynamic covalent bonds like -C=N- from acyl hydrazones and -S-S- (disulfides). 

Benzy 1-2-methyl- -(Bis-hydrochlo-rid) E16a, 512 (N-Acyl-/N-P-Spaltung), 519 (Hydrazon-Red.)... 

A reduction route similar to that of phenylhydrazones [229] seems to be rather general for azomethine derivatives of hydrazine [229] as it s followed by cyclic and acylic phenylhydrazones, semicarbazones, azines, cyclic hydrazones, and acylated cyclic and acyclic hydrazones [231] under pro tic conditions in DMF, acylated hydrazones of aromatic aldehydes are reduced with saturation of the C=N bond and cleavage of the N-N bond at a more negative potential [232]. The suggestion that the cleavage of the N-N bond precedes the saturation of the azomethine bond is also an essential part of the interpretation of many of the ring contractions of heterocyclic compounds (Chapter 18). 

H.J. Bestmann has prepared the phosphazine of TFAE from 18 and triphenyl phosphine. This compound is hydrolyzed by ZnCl2/H20 to give the parent hydrazone 22 and it can be transformed to the corresponding tris carbonyl compound using HN02 (ref. 41). In analogy to the studies by H. Neuenhoffer, we have N-acylated 22 by acid anhydrides to obtain crude N-acylhydrazones 211 in about 50 % yield (Scheme 46). 

Eine weitere vorteilhafte Moglichkeit zur Synthese mono- und N,N -di-alkylierter Hydrazine besteht in der Hydrierung der Acyl- oder Alkyl-acyl-hydrazone mit anschlieBen-der Hydrolyse (s. S. 244ff.). 

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