Anilines 4-alkoxy

Alkoxy derivatives of biphenyl can be obtained either from alkoxy-anilines or by coupling with alkoxybenzenes. From diazotized p-bromo-aniline and anisole a 20% yield of 4-bromo-2 -methoxybiphenyl and a 7% yield of 4-bromo-4 -methoxybiphenyl are obtained. In connection with their studies on Cannabis Indica, Ghosh, Pascall, and Todd u prepared the highly substituted biphenyl compound, 2-cyano-5-methyl-2, 5 -dimethoxy-4 -n-amylbiphenyl (VII), in 27% yield from the nitrosoacetyl derivative of 2-cyano-5-methylaniline and 2,5-dimethoxy-n-amylben-zene. 

Hydrogenation of alkoxy anilines takes place over a rhodium catalyst at 60°C and 3.5 atmospheres (Eqn. 17.14). /0> Hydrogenation over a ruthenium catalyst occurs at 80°-90°C and 75-100 atmospheres ofhydrogen. The amount of alkoxy group hydrogenolysis observed under these conditions decreased from about 35% in methanol to about 10% in tert-butyl alcohol. 

The first examples of this kind of material belong to a homologous series of bis-azo-methines (113-114) which have the general structure represented in Table 9 [101]. The materials were prepared by esterification of (/ )-3-methyladipic acid with 4-hy-droxybenzaldehyde to the his-[4-formyl-phenyl] (/ )-3-methyladipate. This was then condensed with the appropriate 4-alkoxy-aniline to give the desired i>is-azomethine dimer. In this homologous series, only the early members (ethoxy, butoxy and hexy-loxy, compounds 113 to 115) showed chiral nematic phases the transition temperatures of these materials are given in Table 9. 

Even polyalkoxy-s-triazines are quite prone to nucleophilic substitution. For example, 2,4,6-trimethoxy-s-triazine (320) is rapidly hydrolyzed (20°, dilute aqueous alkali) to the anion of 4,6-dimethoxy-s-triazin-2(l )-one (331). This reaction is undoubtedly an /S jvr-4r2 reaction and not an aliphatic dealkylation. The latter type occurs with anilines at much higher temperatures (150-200°) and with chloride ion in the reaction of non-basified alcohols with cyanuric chloride at reflux temperatures. The reported dealkylation with methoxide has been shown to be hydrolysis by traces of water present. Several analogous dealkylations by alkoxide ion, reported without evidence for the formation of the dialkyl ether, are all associated with the high reactivity of the alkoxy compounds which ai e, in fact, hydrolyzed by usually tolerable traces of water. Brown ... 

An excellent route to cyclohexylamines is by hydrogenation of the corresponding aniline over rhodium or ruthenium (17,18,19 2 36,63,64). Rhodium has proved especially useful in saturation of alkoxyanilines with minimal hydrogenolysis of the alkoxy function (45), The extent of hydrogenol ysis occurring in saturation of alkoxyanilines depends also on the solvent. Hydrogenolysis of p-methoxyaniline over Ru(OH)2 fell with alcohol solvent in the order methanol (35%) > ethanol (30%) > propanol (26%) > butanol (22%) > isopropanol (16%) > r-butanol (8%) (43). 

The products are (220), probably formed by the dimerization of (219), and the 2-alkoxy-l,2-thiaphosphole derivatives (218). Analogues of the latter are obtained with p-toluenethiol and dialkylamines. The compound (217 R=Ph) is more reactive than (217 R Me ) and will react with aniline on addition of triethylamine even at room temperature, from which the formation of (221) was observed by spectroscopic characterization. Even more reactive is cyclohexylamine which furnishes an analogue of (221) without addition of strong base. ... 

Domino reactions increasingly gain importance in the search for new drugs. Especially appropriate is the use of multi-component reactions in solution combinatorial chemistry. In such a process described by Wessel et al.1231 an alkoxy-nitroenone 48 was treated with different anilines 49 to give ketene-NO-acetals which in the presence of aromatic aldehydes and TfOH are transformed into 50 (scheme 10). The substrate 48 is readily available by oxidation of the nitrosugar 47. 

A striking feature of disperse dye development in recent decades has been the steady growth in bathochromic azo blue dyes to replace the tinctorially weaker and more costly anthraquinone blues. One approach is represented by heavily nuclei-substituted derivatives of N,N-disubstituted 4-aminoazobenzenes, in which electron donor groups (e.g. 2-acylamino-5-alkoxy) are introduced into the aniline coupler residue and acceptor groups (acetyl, cyano or nitro) into the 2,4,6-positions of the diazo component. A PPP-MO study of the mobility of substituent configurations in such systems demonstrated that coplanarity of the two aryl rings could only be maintained if at least one of the 2,6-substituents was cyano. Thus much commercial research effort was directed towards these more bathochromic o-cyano-substituted dyes. 

As in carboxylic esters it is possible to substitute alkoxy groups of Fischer-type carbene complexes by non-carbon nucleophiles, such as other alcohols [73,214,218], enols [219], aliphatic amines [43,64,66,220-224], aniline [79], imines [225], or pyrroles [226]. Strong nucleophiles can also lead to a dealkylation of methoxy-substituted carbene complexes (5 2 at the methyl group, [227]), in the same way as methyl esters can be cleaved by nucleophiles such as iodide. Carbon... 

The Gould-Jacobs reaction is a sequence of the following reactions a. condensation of an aniline 1 with either alkoxy methylenemalonic ester or acyl malonic ester 2 providing the anilidomethylenemalonic ester 3 b. cyclization of 3 to the 4-hydroxy-3-carboalkoxyquinoline 4 c. saponification to form acid 5, and d. decarboxylation to give the 4-hydroxyquinoline 6. 

Many organic chemicals are analyzed by RPC. These include various arylhydroxylamines as the N-hydroxyurea derivative with methyl isocyanate (614) alkyl- and alkoxy-disubstituted azoxybenzenes (6t5), n-alkyl-4-nitrophenylcarbonate esters ranging in length from methyl to octyl (616), 4-nitrophenol in the presence of 4-nitrophenyl phosphate (617), ben-zilic acid, and benactyzine-HCI using ion-pair chromatography (618), as well as aniline and its various metabolites (619), stereoisomers of 4,4 -dihydroxyhydrobenzoin (620), and aldehydes and ketones as the 2,4-dinitrophenylhydrazones (621). The technique has also been used to analyze propellants and hydrazine and 1,1-dimethylhydrazine were quantitita-vely determined (622, 623). 

Boron trifluoride etherate was used in conjunction with the reducing agent borane to rearrange aromatic O-triisopropylsilyl ketoximes to cyclic and acyclic aniline derivatives. The steric hindrance of the substituents on the silicon atom, the size of the aliphatic ring and the presence of alkoxy substituents on the aryl group played important roles in the aniline formation. 

The addition of anilines to styrene oxide was reported to also proceed in the presence of 10mol% 37 affording the corresponding P-amino alcohols 1-5 in yields ranging from 75% to 92% (Scheme 6.37). Additionally, urea derivative 37 (20mol% loading) was found to catalyze the addition of aniline (2.0 equiv.) to ( )-stilbene oxide (92% yield 5.9 d 30°C), the addition of thiophenol (2.0 equiv.) to 2-methoxy styrene oxide (85% 20h rt), and the alcoholysis of 4-methoxy styrene oxide with benzyl alcohol (2.0 equiv.) affording the respective P-alkoxy alcohol (82% 20h rt). 

The reaction follows the same course when one of the alkoxy groups in the starting material is replaced by alkyl. Thus, condensation of aniline (23-4) with EMME... 

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