A-Substituted derivatives

In general, condensation takes place at the a-carbon atom, leading to simple cinnamic acids or to their a-substituted derivatives. When possible, the anhydride corresponding to the sodium sail should be the condensing agent. 

C) Acids. Employ oxidation to acids (see 6 above) only if C4H5CHO or a substituted derivative is suspected. Aliphatic aci may be too soluble for ready isolation. 

Thiazoles with Heterocyouc Substituents. Thiazoles with heterocyclic substituents in the 2- or 4-position have been synthesized (Table II-9). Thus thioacetamide (or its a-substituted derivatives) react with bromomethyl heteroarylketones under reflux in alcohol to give the corresponding 2-methyl-4-heteroarylthiazoles heteroaryl groups in the 4-position were 2 -thienyl (213, 692) a-pyrrolyl and 3-method derivatives... 

On the other hand an alkyl side chain on a benzene nng is oxidized on being heated with chromic acid The product is benzoic acid or a substituted derivative of benzoic acid... 

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

In a neutral azole, the apparent rate of formation of an A-substituted derivative depends on the rate of reaction of a given tautomer and on the tautomeric equilibrium constant. For example, with a 3(5)-substituted pyrazole such as (199), which exists as a mixture of two tautomers (199a) and (199b) in equilibrium, the product composition [(200)]/[(201)] is a function of the rate constants Ha and fcs, as well as of the composition of the tautomeric mixture (Scheme 16) <76AHC(Si)l). 

Only the anion (239) is susceptible to C-alkylation in the 4-position. The two other anions (240) and (241) can only give rise to O-and A-substituted derivatives which result in the asymmetry of Scheme 19. 

The Yukawa-Tsuno r values have been measured for the solvolysis reactions fonning benzyl cations and several a-substituted derivatives, 6-3IG charges and bond orders have been calculated for the presumed cationic intermediates. Analyze the data for relationships between r and the structural parameters. (Hint. Plot r versus the bond orders and the charges at C-1, C-2, C-3, and C-4.)... 

Secondary and tertiary amines are naned as A-substituted derivatives of primary fflnines. The parent primary amine is taken to be the one with the longest carbon chain. The prefix N- is added as a locant to identify substituents on the anino nitrogen as needed. 

A/-Methylethylamine (given as CH3NHCH2CH3 in the preceding example) is an A/-substituted derivative of ethanamine it is A/-methyl-ethanamine. 

The A-substituted derivatives of 4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxamides and -3-acetamides and l,6-dimethyl-4-oxo-1,6,7,8-tetrahy-dro-4//-pyrido[l,2-n]pyrimidine-3-carboxamide were prepared by treatment of the appropriate 3-carboxylic acids and acetic acid, first with an alkyl chloroformate in the presence ofNEt3 in CHCI3 below — 10°C, then with an amine (98ACH515). A-Phenethyl and A-[2-(3,4-dimethoxyphenyl)ethyl] derivatives of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetamide were obtained in the reaction of 6-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-acetic acid and phenethylamines in boiling xylene under a H2O separator. Hydrazides of 4-oxo-4//- and 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic acid were prepared from the appropriate ester with H2NNH2 H2O in EtOH. Heating 4-oxo-4//- and 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidine-3-acetic hydrazides in EtOH in the presence of excess Raney Ni afforded fhe appropriafe 4-oxo-6,7,8,9-fefrahydro-4//-pyrido[l,2-n]pyrimidine-3-acefa-mide. In the case of the 4-oxo-4// derivative, in addition to N-N bond... 

The tetrahydro-l,3-oxazines which contain a free A -hydrogen atom can be iV-acylated and A -nitrosated. - Certain A-substituted derivatives of tetrahydro-l,3-oxazin s can also react with acetic anhydride to form A -acetyl derivatives. > Most tetrahydro-l,3-oxazines add methyl iodide to form quaternary... 

C-Nitration does not involve the hydroxyl group but is a reaction with an aliphatic or aromatic hydrocarbon or a substituted derivative to produce such compounds as the nitroparaffins and the nitrotoluenes ... 

The compound is named as a substituted derivative of a deoxy sugar. The group replacing OH determines the configurational description. Any potential ambiguity should be dealt with by the alternative use of the R,S system to specify the modified stereocentre. 

Some interesting differences are found between the reactions of Co(I) and Co—H complexes. For example, [Co (DMG)2py] will react at pH 10-11 with activated olefins to give the -substituted complexes [XCH2CH2Co(DMG)2py)], where X is COOH, COOR, CN, etc. but at pH 7-8, where the complex is present as the hydride, the a-substituted derivatives [CHjCHXCo(DMG)2py] are formed 163, 149). Schrauzer, Weber, and Beckham were able to show that the reactions at higher pH proceeded via the intermediate formation of the 7r-olefin-Co(I) complex 159). The reactions involving Co(I) appear generally to be reversible and the addition of Co—H irreversible (see also Section V,C and VI,B). We can, therefore, write the scheme... 

Diesters of phosphoramidic acid are converted to the corresponding isocyanates by phosgene but with A-substituted derivatives the phosphoramidic chlorides are formed. In a similar reaction oxalyl chloride... 

Vertical ionization energies of the two highest molecular orbitals and of orbitals mainly localized on the substituent of a-substituted derivatives of furans, thiophenes, selenophenes, and tellurophenes have been determined.25 Assignments of some of the bands other than the first two in the photoelectron spectra of tellurophene and selenophene are proposed, and the effect of the ring on the orbitals mainly localized on the substituent is briefly discussed. 

Alkenylbenzotriazoles 865 are readily prepared by isomerization of the corresponding allyl derivatives catalyzed by Bu OK. Lithiated compounds 865 are treated with electrophiles to provide a-substituted derivatives 866. Epoxidation of the double bond with ///-chloroperbenzoic acid converts intermediates 866 into oxiranes 867 that can be hydrolyzed to furnish a-hydroxyketones 868 in good yields (Scheme 140) <1996SC2657>. 

However, replacement of a carbon within the shell of C60 by a heteroatom has constituted a daunting task Until recently, there was no mechanism available to do so, and only syntheses from scratch appeared to be up to the challenge.110,771 The first and so far only reported syntheses are for hydroazafullerene C59N+ (55) and its a-substituted derivatives (Scheme 15). The formation of this heterofullerene has been achieved in a remarkable add-catalyzed rearrangement of the opened ketolactam 48 described earlier (Schemes 12 and 15). 

Iodomethyltrialkyltin compounds, R3SnCH2I (from R3SnCl and ICH2ZnI), provide an entry to other functionally substituted organotin compounds. Reaction with nucleophiles such as R10, R1S, R 2N, or R 3P gives further a-substituted derivatives, and carbon nucleophiles can be used to locate the functional groups at more distant positions on the alkyl chain. Some examples are shown in Scheme 3. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

The synthesis of a substituted derivative of 2-keto-l,2,3,4-tetrahydro-dibenzothiophene is discussed in Section VI, D. 

A -Substituted derivatives of cw-2-hydroxy-l-cyclopentanecarboxamide and cis- and tranj-2-hydroxy-l-cyclohexanecarboxamide 128 were transformed with a large excess of l,T-carbonyldiimidazole to oxazinediones 145 (cis, n = 1, 2 irons, n = 2 R = Me, Ph, CHjPh CHaCHaPh) in 40-90% yields. Derivatives with an unsubstituted nitrogen atom could not be isolated (85M857). 

A highly reactive compound containing a neutral divalent carbon with two nonbondmg electrons (ie.,. CR2 or a substitution derivative). The nonbonding electrons can have parallel spins (triplet state) or antiparallel spins (singlet state). The parent species, iCRz, is also known as methylene. A number of carbene derivatives have been used as photoaffinity labels of proteins. Irradiation of 3 -0-(4-benzoyl)benzoyl-ATP will cause 70% inactivation of mitochondrial Fi-ATPase. ... 

O-Alkyl- and O-arylhydroxylamines and their A-substituted derivatives have been the most extensively used reagents for amination of C-nucleophiles (Table 1). O-Methyl hydroxylamine la is the most extensively used O-organylhydroxylamine-type reagent. 

A list of A-mono- and A,A-disubstituted 0-sulfonylhydroxylamines used for amination of ordinary carbanions and enolates are given in Table 3. Except for 3h and 3p, they are 0-(arenesulfonyl)hydroxylamines and their A-substituted derivatives. Methods for the syntheses of various 0-(arenesulfonyl)hydroxylamines have been reported ... 

Piperidine is obtained commercially by the catalytic hydrogenation of pyridine over a nickel catalyst at about 200 C. A-Substituted derivatives are formed by reduction of the corresponding pyridinium salts. 

Azetidin-2-one can be synthesized by treating 1-ethoxy-1-hydroxycy-clopropane with aqueous sodium azide at pH 5.5 (Scheme 8.7a). This type of construction has wider applications and A-substituted derivatives are formed from 1-amino-1-hydroxycyclopropanes in two steps first A-chlorination with tert- miy hypochlorite [2-methylpropan-2-yl chlo-rate(I)], and then treatment with silver ion in acetonitrile (ethanenitrile) to release chloride ion and trigger ring expansion of the tricycle (Scheme 8.7b). 

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