Imines isolation

Gymnodimine, a novel toxic imine isolated from the Foveaux Strait oysters and Gymnodinium sp. In Harmful... 

The resulting achiral iminium cations, with chiral phosphate counteranion, were then enantioselectively reduced using an achiral Hantzsch ester (dihydropyridine) providing enantioenriched amines. During this imine reduction study, one example was shown in which acetophenone and p anisidine [16] were prestirred in the presence of toluene and 4 A molecular sieves [17] for 9h (imine formation), after which the temperature was raised to 35 °C, and the Hantzsch ester (1.4 equiv) and phosphoric acid (TRIP, 5 mol%) were added to give the amine product in 88% ee over an additional 45 h. This is an exciting observation and while not a reductive amination, it is an operational improvement over simple imine reduction which requires imine isolation. 

Reaction conditions imine (1 mmol), p-naphthyl acrylate (2 mmol), p-naphthol (0.1 mmol), 13c (0.1 mmol) in CH2CI2 (0.35 ml) at 30 C for aromatic imines and at 0 6 for aliphatic imines. Isolated yield after column chromatography. 

The reaction probably involves an initial [2+2]-cycloaddition of the aldehyde and the N-sulfinyl compound to produce an adduct 2 [10] which loses sulfur dioxide to yield the N-sulfonyl imine. Isolated yields of the sulfonyl imines shown in Scheme 1 were generally quite good. In the case of the enolizable aldehyde dichloroacetaldehyde, only a low yield of N-sulfonyl imine was produced. An attempt was also made using these same reaction conditions to convert butyraldehyde to the corresponding Af-tosyl imine [6]. However, all that could be isolated here was the bis-sulfonamido acetal. 

Seki, T. et al., Gymnodimine, a novel toxic imine isolated from the Foveanx Strait oysters and Gymnodinium spp., in Harmful and Toxic Algal Blooms, 7th International Conference on Toxic Phytoplankton, Yasumoto, T., Oshima, Y. and Fnknyo, Y. eds., IOC, UNESCO, Sendai, Japan, 1995, pp. 495-498. 

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazole (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methylthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at -78°C and the solution is allowed to warm to room temperature, the deuterolysis affords only dideuterated thiazole (170), with no evidence of any dimeric product. Under these conditions almost complete dianion formation results (169), and the concentration of nonmetalated thiazole is nil. (Scheme 79). This dimerization bears some similitude with the formation of 2-methylthia-zolium anhydrobase dealt with in Chapter DC. Meyers could confirm the independence of the formation of the benzyl-type (172) and the aryl-type... 

Reaction with primary amines (Section 17 10) Isolated product is an imine (Schiff s base) A carbinolamine inter mediate is formed which undergoes de hydration to an imine... 

Reaction with secondary amines (Sec tion 17 11) Isolated product IS an en amine Carbinolamine intermediate can not dehydrate to a stable imine... 

Carbinolamines are formed by nucleophilic addition of an amine to a carbonyl group and are intermediates in the for mation of imines and enamines Carbocation (Section 4 8) Positive ion in which the charge re sides on carbon An example is tert butyl cation (CH3)3C Carbocations are unstable species that though they cannot normally be isolated are believed to be intermediates in certain reactions... 

Like mthenium, amines coordinated to osmium in higher oxidation states such as Os(IV) ate readily deprotonated, as in [Os(en) (NHCH2CH2NH2)] [111614-75-6], This complex is subject to oxidative dehydrogenation to form an imine complex (105). An unusual Os(IV) hydride, [OsH2(en)2] [57345-94-5] has been isolated and characterized. The complexes of aromatic heterocycHc amines such as pyridine, bipytidine, phenanthroline, and terpyridine ate similar to those of mthenium. Examples include [Os(bipy )3 [23648-06-8], [Os(bipy)2acac] [47691-08-7],... 

In the 1,2-dithiole series such imines are readily isolated they can be alkylated or protonated, e.g. (448) (449) (66AHC(7)39). 

Use of mesoionic ring systems for the synthesis of five-membered heterocycles with two or more heteroatoms is relatively restricted because of the few readily accessible systems containing two heteroatoms in the 1,3-dipole. They are particularly suited for the unambiguous synthesis of pyrazoles as the azomethine imine is contained as a masked 1,3-dipole in the sydnone system. An attractive feature of their use is that the precursor to the mesoionic system may be used in the presence of the cyclodehydration agent and the dipolarophile, avoiding the necessity for isolating the mesoionic system. 

In addition to (461), Dorn has described the imine (463) isolated from 5-amino-l-methylpyrazole and arenesulfonyl chloride (80CHE1). Upon heating, or in the presence of triethylamine, it undergoes rearrangement to the more stable 5-bis(arylsul-fonamido)pyrazoles (464). 5-Iminopyrazolines (461) react with acyl chlorides at the exocyclic nitrogen atom to afford amidopyrazolium salts (B-76MI40402). 

The addition of diazo compounds generally leads to three membered tings, although in special cases, linear adducts with an intact diazo group [110] or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and aziridines [112,113,114] Aziridines are obtained exclusively on reaction of certain polyfluorinated acyl imines with diazomethane [115]... 

The formation of 88 is postulated to be occurring by the nucleophilic attack of a hydride ion (47), abstracted from the secondary amine, on the a-carbon atom of the iminium salt (89). The resulting carbonium ion (90) then loses a proton to give the imine (91), which could not be separated because of its instability (4H). In the case of 2-methyIhexamethylenimine, however, the corresponding dehydro compound /l -2-methylazacyclo-heptene (92) was isolated. The hydride addition to the iminium ion occurs from the less hindered exo side. 

The Combes reaction has been applied to the preparation of carbazoles related to eJJipticine. In that case, the imine was not formed separately nor purified yet the desired product 57 was isolated in 35%. ... 

The imine (161), obtained from 1-aminopyridinium iodide and potassium carbonate, combines with dimethyl acetylenedicarboxylate yielding in the first place (162) which then with more ester gives dimethyl fumarate and the pyrazolopyridine (163), isolated in 15% yield. A corresponding reaction with isoquinoline imine gave 75% of the primary adduct [(cf. (162)]. ... 

Tliere are few examples for the preparation of imines from A-(l-haloalkyl)azinium halides and primary diamines. Among those reaetions reported, A-(ehlorophenylmethyl)pyridinium ehloride (33k), whieh has not been isolated, reaets with ethane-1,2-diamine and propane-1,3-diamine to afford the eorresponding diimines 72 (Seheme 22, 45-80%) (89JOC4808, 92BSB233). 

Tile chloro derivative 33a (not isolated) interacts with pyridine-2,3-diamine in dichloromethane at room temperature to yield 73 (85%) (93BSB357). A further example deals with the reaction between the salt 39 and benzene-1,2-diamine, which gives an imine 74 (80%) under special experimental conditions (93BSB357). In order for the reaction to work, the salt 39 must be isolated prior to its employment (Section IV,C,8). No traces of the diimines were detected for both cases. However, the experimental conditions were not optimized for this purpose since no more than three equivalents of the diamines were used (Scheme 23). 

Claisen first observed cleavage of the isoxazole ring by the action of reducing agents. He isolated acetylacetone imine (162) by re-... 

A mechanism has been formulated, starting with a condensation to give the imine 4, that can tautomerize to the corresponding enamine 5. The latter can be isolated in some cases, thus supporting the formulated mechanism. A cyclization and subsequent dehydration leads to the imine 6, which tautomerizes to yield the aromatic pyrrole 3 ... 

Sometimes ihe intermediate imine is isolated, but generally it is nol and may even be inferior to direct alkylation (5following sequence for it was desired to acetylate ihe alkylated product as formed, A solution of 50 mmol of an aromatic aldehyde (I) and 50 mmol of aminoaceialdehyde dimethylacetal (2), refluxed 1.5 h in toluene under nitrogen, gave after distillation nearly quantitative yields of the SchifTs base 3 (5d). 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

A number of the purported syntheses of dibenzo[f>,/][l,4]diazocines in the literature have to be revised and the structure of the products corrected.1 Instead of the expected 1,4-diazocine derivatives 1, isoindolobenzimidazoles 2 are actually isolated, the formation of which requires a hydride shift after transannular attack of one imine group onto the other. 

Solladie-Cavallo has recently reported a two-step asymmetric synthesis of dis-ubstituted N-tosylaziridines from (R,R,R,Ss)-(-)-sulfonium salt 2 (derived from Eliel s oxathiane see Section 1.2.1.1) and N-tosyl imines with use of phosphazine base (EtP2) to generate the ylide (Scheme 1.42) [67], Although the diastereoselectiv-ity was highly substrate-dependent, the enantioselectivities obtained were very high (98.7-99.9%). The chiral auxiliary, although used in stoichiometric quantities, could be isolated and reused, but the practicality and scope of this procedure is limited by the use of the strong - as well as expensive and sensitive - phospha-zene base. 

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

---