Ortho amides

A general method for the preparation of 2-hydroxyalkyl-l,4,7-triazacyclodecane macrocycles 202, 203, 204 with a single pendant arm < 1999J(P 1)1211 > through reaction of epoxides has been achieved from the ortho amide derivative l,4,7-triazatricyclo[5.2.1.04 10]decane 40 (Scheme 30) <1999J(P1)1211>. 

Other ortho-acid derivatives which will not be considered in detail in this chapter are the thio ortho esters, amide acetals, ester aminals, and the ortho amides which have the following structures, respectively, RC(SR)3, RC(OR)2-NR2, RC(OR)(NR2)2, and RC—(NR2)3. 

Nitrosation of, 401 Ortho acids, 41-42 Ortho amides, 42 Orthocarbonates, 42 Ortho esters, 41-68 halogenation of acyl groups, 58-60 monocyclic, 51-53 polycyclic, 51... 

Except for the metallic impurities present on the walls of poorly washed glassware, no other transition metal catalyst may be assumed to be present in this experiment. Consequently, the transfer of the dimethylamino group from the ortho amide II to I must be taking place under less energy demanding conditions, where protic acid catalysis suffices to activate the triple carbon to carbon bond. ... 

An ortho amide 78 of propiolic acid has been prepared it readily condenses with acetylacetone (equation 11). Novel A,A-bis(trimethylsilyl)ynamines 80 are obtained by electrophilic amination of lithium acetylides with the hydroxylamine derivative 79 a,b The action of lead tetraacetate on di(alk-l-ynyl)mercury compounds or alk-1-ynyltrimethylstannanes gives highly unstable alk-l-ynyllead triacetates 81 (R = pj. 

Weisman, G. R., Johnson, V., Fiala, R. E. (1980). Tricyclic ortho amides effects of lone-pair orientation upon NMR spectra. Tetrahedron Letters 21(3 ,), 3635-8. 

Yu et al. [143] described the ortho amidation of aromatic and aliphatic oximes under C-H activation. Pd(OAc)2 as a catalyst in combination with Sequiv. of K2S20g as an oxidant was required for the amidation reaction (Scheme 13.98). 

Aromatic ketimines as well as aldimines are viable substrates for ortho amidation, carbamoylation, and sulfamidation. Not only aromatic, but also aliphatic oximes were converted into the amides regioselectively in high yields. It was suggested that the reaction proceeds by the oxidation of the amide to a nitrene species, which then inserts into the ortho-palladated arene. An alternative mechanism, which involves a Pd-nitrene or Pd(IV) species, was also considered for this reaction. 

When the core chromophore is changed to pyrazine (Scheme 30.23, bottom), interaction of enediyne moiety with 1,4-cyclohexadiene proceeds as a cycloaddition [40]. The latter change in reactivity is attributed to the particularly fast formation of an electrophilic triplet state that attacks the jc-bond of 1,4-CHD. In the presence of an ortho-amide functionahty, the same chromophore undergoes either a 7-endo-dig cyclization or photohydration [41]. 

The reaction of trienyl azide 76 was noteworthy as the first reported example of a combined Diels-Alder/Schmidt reaction of any type (see Section 7.7 above). In addition, the isolation of compound 77b represented the first known observation of a bridged lactam from an intramolecular Schmidt reaction (in contrast to the formation of bridged ortho-amide 62 shown in Scheme 7.40). Mechanistically, an endo Diels-Alder leads to 77a and 77b (box at bottom of Scheme 7.43), while an exo transition state leads to 77c (transition state not shown). The formation of fused or bridged lactam depends on antiperiplanar migration of carbon from the equatorially or axially disposed N2 groups in the intermediates shown. 

Carboxyhc acids react with aryl isocyanates, at elevated temperatures to yield anhydrides. The anhydrides subsequently evolve carbon dioxide to yield amines at elevated temperatures (70—72). The aromatic amines are further converted into amides by reaction with excess anhydride. Ortho diacids, such as phthahc acid [88-99-3J, react with aryl isocyanates to yield the corresponding A/-aryl phthalimides (73). Reactions with carboxyhc acids are irreversible and commercially used to prepare polyamides and polyimides, two classes of high performance polymers for high temperature appHcations where chemical resistance is important. Base catalysis is recommended to reduce the formation of substituted urea by-products (74). 

The reverse reaction is an intramolecular acidolysis of amide group by the o-carboxyhc acid to reform anhydride and amine. This unique feature is the result of an ortho neighboring effect. In contrast, the acylation of an amine with ben2oic anhydride is an irreversible reaction under the same reaction conditions. The poly(amic acid) stmcture (8) can be considered as a class of polyamides. Aromatic polyamides that lack ortho carboxylic groups are very... 

Diphenylamine can be alkylated exclusively in the ortho positions by reacting with an olefin in the presence of aluminum diphenylamide (7), which can be readily obtained by heating DPA with powdered aluminum, or more easily by treating sodium diphenylamide with AIQ. - Ethylene is more reactive than propylene, which in turn is more reactive than isobutylene. Eor a typical reaction, a small amount of the amide is generated in a DPA melt and ethylene is introduced under pressure (5 —30 MPa) at 200—400°C. The absorption of ethylene stops after about 30 min and 2,2 -diethyldiphenylamine is obtained in 95% yield. With propylene only a 25% yield of the 2,2 -diisopropyldiphenylamine is obtained. 

PolybenZimidaZoles. The polyben2imida2oles (PBIs) are generally produced by the high temperature, melt polycondensation reaction of aromatic bis-ortho-diamines and aromatic dicarboxylates (acids, esters, or amides) in a reaction such as that shown in equation 11 to form ben2imida2ole [51-17-2] as the repeating unit. 

The enzyme catalyzes the hydrolysis of an amide bond linkage with water via a covalent enzyme-inhibitor adduct. Benzoxazinones such as 2-ethoxy-4H-3,l-benzoxazin-4-one [41470-88-6] (23) have been shown to completely inactivate the enzyme in a competitive and stoichiometric fashion (Eigure 5). The intermediate (25) is relatively stable compared to the enzyme-substrate adduct due to the electron-donating properties of the ortho substituents. The complex (25) has a half-life of reactivation of 11 hours. 

In some instances the attack of the arene on the nitrilium salt occurs at the ipso carbon rather than the ortho carbon. For example, the Bischler-Napieralski cyclization of phenethyl amide 10 affords a 2 1 mixture of regioisomeric products 11 and 12. The formation of 12 presumably results from attack of the ipso aromatic carbon on the nitrilium salt 13 followed by rearrangement of the spirocyclic carbocation 14 to afford 15, which upon loss of a proton vields product 12. ... 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

Moreover, when carbamino and nitro groups are simultaneously in the ortho position to the triple bond, isomerization occurs only with participation of the amide group (Scheme 125). 

Nucleophilic aromatic substitution of the anthranilic acid derivatives, 72, on ortho-bromonitrobenzene affords the diphenyl-amine, 73. The ester is then saponified and the nitro group reduced to the amine (74). Cyclization of the resulting amino acid by heat affords the lactam (75). Alkylation on the amide nitrogen with 2-dimethylaminoethyl chloride by means of sodium amide affords dibenzepine (76). ... 

The structural feature of ceforanide that is of particular interest is the movement of the C-7 side chain amino moiety from the position a to the amide carbonyl, where it normally resides in ampicillin/cephalexin analogues, to lodgement on a methylene attached to the ortho position on the aromatic ring. 

N-Substituted amides can be prepared by direct attack of isocyanates on aromatic rings.The R group may be alkyl or aryl, but if the latter, dimers and trimers are also obtained. Isothiocyanates similarly give thioamides. The reaction has been carried out intramolecularly both with aralkyl isothiocyanates and acyl isothiocyanates.In the latter case, the product is easily hydrolyzable to a dicarboxylic acid this is a way of putting a carboxyl group on a ring ortho to one already there (34 is... 

Benzylic quaternary ammonium salts, when treated with alkali metal amides, undergo a rearrangement called the Sommelet-Hauser rearrangementSince the product is a benzylic tertiary amine, it can be further alkylated and the product again subjected to the rearrangement. This process can be continued around the ring until an ortho position is blocked. ... 

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