From aryl amines

Unexpectedly, Grieco discovered that immonium ions derived from aryl amines and aldehydes do not function as heterodienophiles toward cyclopentadiene, as was found in the case of simple immonium ions, but rather they acted as 2-azadienes leading to a novel synthesis of tetrahy-droquinolines (88TL5855). 

An obvious difficulty arises with this rather elaborate rationale when phosphoramidate and aryl phosphoramidate monoanions are compared for example, the dissimilarity of the dioxan effect yet the identity of product distribution observed in methanol-water competition experiments. Preliminary studies in the author s laboratory have revealed striking differences in the hydrolytic behavior between a series of phosphoramidafes derived from primary aliphatic amines and the above aryl systems. No linear structure-reactivity relationship between the logarithmic rate of hydrolysis of the monoanion species and the pKa of the amine is observed19. Moreover, the rate of hydrolysis of phosphoramidate monoanions derived from aliphatic amines is at least 104 times slower than those formed from aryl amines. In contrast, only a thirtyfold decrease in rate is observed for the corresponding ApKa in the O-phos-phate monoester series. The suspicion that mechanism (1), even with the above proposed modification, is not an accurate description of phosphoramidate monoanion hydrolysis derives some further support from the observation that the monoanion is subject to nucleophilic attack by substituted pyridines al-... 

Grieco PA, Bahsas A (1988) Role reversal in the cyclocondensation of cyclopentadiene with heterodienophiles derived from aryl amines and aldehydes synthesis of novel tetrahydroqui-nolines. Tetrahedron Lett 29 5855-5858... 

Combes Quinoline synthesis Preparation of quinolines from aryl amines and 1,3-diketones. 94... 

According to Teppema and Sebrell [357], the preparation of benzo-thiazoline-2-thiones from aryl amines, sulfur and carbon disulfide is not generally applicable. This has been confirmed by several other authors. Another synthesis, method C, has been worked out starting with o-nitro chloro benzenes. On warming these products in a solution of sodium hydrogen sulfide with slow addition of hydrogen sulfide in the presence of carbon disulfide, near 90% yields of benzothiazoline-2-thiones are obtained. 

Polymer-SK, MeOH, THF, 40°C, 99% yield. This method also cleaves piva-lates from aryl amines and alcohols. 

Quinolines from Aryl-Amines and 1,3-Dicarbonyl Compounds... 

This is most practically carried out via the use of aryl diazonium salts (Ar-N2 Cl ) which are derived from aryl amines(Ar-NH2) which are themselves produced by the catalytic reduction of aryl nitro compounds (Ar-N02). Thus, we would seem to need to put a nitro group para to the original hydroxyl group. We must be aware of phenol s immense reactivity and the subsequent danger of polynitration. To avoid this danger, we treat phenol with dilute nitric acid instead of with concentrated nitric acid and with concentrated sulfuric acid as the catalyst. 

The preparation of radioiodinated arenes from aryl amines by means of the Sandmeyer reaction has proven to be impractical. The unstable diazonium compounds, however, may be converted into stable pyrrolidine triazenes or dialkyltriazenes and used as precursors for labeling. The reaction sequence using pyrrolidine is shown in Pig. 44.8. 

Like carbanions and anions from aryl amines, the anions from phenols have been used in intramolecular to obtain heterocycles by C—C bond formation [87]. One example of this approach is the photostimulated reaction of the phenoxide ion linked with a pendant bromoarene by Al-substi-tuted tetrahydroisoquinoline bridge such as 122. Under this reaction condition, aporphine alkaloid derivatives 123a,b (n=1) were obtained in good yields (Eq. 10.42). This approach was extended for the first time to the synthesis of a homoaporphine alkaloid 123c (w=2) [88]. 

An interesting role reversal is observed in the cyclocondensation of cyclopentadiene with iminium ions derived from aryl amines and aldehydes [5]. The use of aniline as the amine component with formaldehyde and cyclopentadiene in aqueous acetonitrile fails to produce any of the corresponding iV-phenyl-2-azanorbornene 11. Instead, the novel tetrahydroquino-line-based pentacyclic products 12 and 13 are isolated in a near-quantitative yield as a 3.7/1 isomeric ratio ... 

General Conditions for each step and selectivity of m-substituted anilines As previously mentioned, Hauser and Reynolds reported on factors governing the first step of the Conrad-Limpach reaction but they tvere by no means exhaustive. Other than the conditions reported above for the first step, HClAleOH, CHCI3 or CHCI2 (neat or with acid catalyst), PhMe or PhH with removal of water with or without acid catalyst, or EtOH/AcOH/CaS04 were reported to provide the desired enamino-ester from an aryl amine and 3-keto-ester. Hauser and Reynolds also noted that o-nitroaniline and o-nitro-p-methoxyaniline failed to form the desired enamino-ester under conditions which they reported. 

The Knorr quinoline synthesis refers to the formation of a-hydroxyquinolines 4 from P-ketoesters 2 and aryl amines 1. The reaction usually requires heating well above 100°C. However, some cases do exist when the cyclization takes place in the presence of a catalytic amount of mineral acid at temperatures as low as -10 °C. The intermediate anilide 3 undergoes cyclization by dehydration with concentrated sulfuric acid. The reaction is conceptually close to the Doebner-Miller and Gould-Jacobs reactions. ... 

Good yields of 10-aryl-3,6-dinitroacridones were obtained merely by heating 2,2, 4,4 -tetranitrobenzophenone (419) with an excess of the corresponding aryl amines at 125°C. For example, aniline provided 420 in 80% yield (Eq. 38). The reaction is fairly general for meta- and para-substituted anilines, though it proceeds less readily with orf/io-substituted compounds (79JCS(P1)1364). A method of isolation of the intermediate diarylamine in the synthesis of certain 10-aryl-3,6-dinitroacridones from 2,2, 4,4 -tetranitrobenzophenone has also been described (93JCR(M)2779). 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

The preparation of an aryl fluoride—e.g. fluorobenzene 3—starting from an aryl amine—e.g. aniline 1—via an intermediate arenediazonium tetrafluoroborate 2, is called the Schiemann reaction (also called the Balz-Schiemann reaction) The diazotization of aniline 1 in the presence of tetrafluoroborate leads to formation of a benzenediazonium tetrafluoroborate 2 that can be converted into fluorobenzene 3 by thermolysis. 

Independently, Antane reported that arylisonipecotic acids were obtained from aryl bromides in a two-step process involving microwave-assisted palladium-catalyzed amination with ethyl isonipecotate followed by ester hydrolysis with KOH (Scheme 91) [96]. Interestingly, toluene, which is the standard solvent for Buchwald-Hartwig aminations under conventional heating, was used as the sole reaction medium, although it is a very weak... 

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