Tri-substituted

In brief, suitable hydrolysis of ethyl acetoacetate derivatives will give mono-or di-alkyl substituted acetones or acetic acids. Tri-substituted acetones or acetic acids cannot be obtained moreover, the di-substituted acetones must... 

It follows therefore that ethyl malonate can be used (just as ethyl aceto- acetate) to prepare any mono or di-substituted acetic acid the limitations are identical, namely the substituents must necessarily be alkyl groups (or aryl-alkyl groups such as CjHjCHj), and tri-substituted acetic acids cannot be prepared. Ethyl malonate undergoes no reaction equivalent to the ketonic hydrolysis of ethyl acetoacetate, and the concentration of the alkali used for the hydrolysis is therefore not important. 

Speed manufacturers need only look at the molecules and imagine them without those extra OHs or methylenedioxy ring structures attached to the benzene core. These particular pathways are, however, more uniquely suited for X precursor production because they take advantage of the hindrance that methylenedioxy ring structures and OHs provide on one side of the benzene core. This helps to better assure that mono chloromethylations or bro-minations will occur whereas di- and tri-substitutions are possible on a naked benzene molecule which speed chemists are going to be using (please don t ask). 

Uses ndReactions. Dihydromyrcene is used primarily for manufacture of dihydromyrcenol (25), but there are no known uses for the pseudocitroneUene. Dihydromyrcene can be catalyticaUy hydrated to dihydromyrcenol by a variety of methods (103). Reaction takes place at the more reactive tri-substituted double bond. Reaction of dihydromyrcene with formic acid gives a mixture of the alcohol and the formate ester and hydrolysis of the mixture with base yields dihydromyrcenol (104). The mixture of the alcohol and its formate ester is also a commercially avaUable product known as Dimyrcetol. Sulfuric acid is reported to have advantages over formic acid and hydrogen chloride in that it is less compUcated and gives a higher yield of dihydromyrcenol (105). 

Hypochlorite readily chlorinates phenols to mono-, di-, and tri-substituted compounds (163). In wastewater treatment chlotophenols ate degraded by excess hypochlorite to eliminate off-flavor (164). Hypochlorite converts btomoben2ene to cb1oroben2ene in a biphasic system at pH 7.5—9 using phase-transfer catalysts (165). 

The behaviour under electron impact of IV- and C-trimethylsilylpyrazoles (mono-, di-and tri-substituted) has been studied by Birkofer et al. (740MS 8)347). Loss of a methyl radical followed by loss of HCN is the most common fragmentation feature of these compounds. When more than one trimethylsilyl group is present, a neutral fragment CaHgSi is expelled. Mass spectrometry of pyrazolium salts has been studied by Larsen etal. (8i OMS377, 830MS52). 

This model prediets that tri-substituted and tetra-substituted olefins would also be poor substrates. Thus it was not until 1994 that a study in the epoxidation of higher substituted olefins appeared. Indeed Jaeobsen revealed that tri-substituted olefins, and even tetra-substituted olefins ean be excellent substratesA new model was put forth that encompasses a skewed side-on approach of tri-substituted olefins to the Mn-oxo eomplex. The observation that certain tetrasubstituted olefins undergo epoxidation with good enantioseleetivity suggests that further studies are needed in order to fully understand the transition state geometry of the catalyst and substrate. 

The Nenitzescu reaction generally occurs under relatively mild reaction conditions. Moreover mono-, di-, and tri-substituted quinones react with equal facility. Many enamines including p-aminoacrylonitriles, p-aminoacrylamides, and p-amino-a,p-unsaturated ketones react with quinones to form indole nuclei as well. The mild reaction conditions and the availability of the starting material render it attractive even in those instances where the yield of the product is low. ... 

Relative reactivity of ring-positions based on positional selectivity of polychloro-azines must be regarded with caution because of the unequal activating effects of the chlorine substituents on each other. Also, it should be emphasized that one cannot use the positional selectivity in di- and tri-substitutions to assess relative reactivity of different positions. In such substitutions, the reactivity is determined by a complex combination of activating and deactivating effects which are unequal at the ring-positions (cf. Sections II, E, 1, II, E, 2,c, and II,E,2,e). 

Trichloro-s-triazine also reacts readily with carbon or phosphorus nucleophiles. Diethylmalonate anion forms a mono-derivative under mild conditions and the tri-substitution product (327) under vigorous conditions with excess nucleophile. Nucleophilic attack by the 7r-electrons of ketene diethylacetal to give 254 and of dimethylaniline to give 253 has been mentioned earlier. Two... 

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

The preparation of mono- and di-tm-butylcyclopentadienes 1 and 2 starting from monomeric cyclopentadiene was reported first in 1963 [23]. It was noted that the nucleophilic attack of the cyclopentadienide anion on ferf-alkyl halide has to compete with elimination reaction giving isobutene. The yield of the di- and tri-fer/-butylcyclopentadienes 2 and 3 was therefore reported to be modest to low [23, 24], Recently an elegant improvement for this synthesis using phase transfer catalysis was presented (Eq. 1), but the availability of the tri-substituted derivative... 

As one would expect, the tri-substituted eis-trans-2,4-diaryl-3-dimethylaminothietanes (187c,d) were shown by NMR to have all three substituents in pseudoequatorial positions with the remaining hydrogens in axial positions202. 

C—H bonds. Phenol, mono-ortho, and di- and tri-substituted phenolic rings can be monitored between 814-831, 753-794, 820-855, and 912-917 cm-1, respectively. Para-substituted phenolic rings also absorb in the 820-855-cm 1 region. 

Thus unsubstituted (R=H) and substituted (R = alkyl) non-stabilized diyiides 1 react with phenylisocyanate and dicyclohexylcarbodiimide (R NCX), leading to the formation of new monoylide type intermediates. These last ones react in situ with carbonyl compounds through a Wittig type reaction leading respectively to a,)8-unsaturated amides 2 and amidines 3, with a high E stereoselectivity, the double bond being di- or tri-substituted [48,49]. By a similar reactional pathway, diyiides also react with carbonic acid derivatives, with the synthesis as final products of -a,/l-unsaturated esters 4 and acids 5 [50]. 

Intermolecular hydroalkoxylation of 1,1- and 1,3-di-substituted, tri-substituted and tetra-substituted allenes with a range of primary and secondary alcohols, methanol, phenol and propionic acid was catalysed by the system [AuCl(IPr)]/ AgOTf (1 1, 5 mol% each component) at room temperature in toluene, giving excellent conversions to the allylic ethers. Hydroalkoxylation of monosubstituted or trisubstituted allenes led to the selective addition of the alcohol to the less hindered allene terminus and the formation of allylic ethers. A plausible mechanism involves the reaction of the in situ formed cationic (IPr)Au" with the substituted allene to form the tt-allenyl complex 105, which after nucleophilic attack of the alcohol gives the o-alkenyl complex 106, which, in turn, is converted to the product by protonolysis and concomitant regeneration of the cationic active species (IPr)-Au" (Scheme 2.18) [86]. 

The reductive elimination of a variety of )3-substituted sulfones for the preparation of di-and tri-substituted olefins (e.g. 75 to 76) and the use of allyl sulfones as synthetic equivalents of the allyl dianion CH=CH—CHj , has prompted considerable interest in the [1,3]rearrangements of allylic sulfones ". Kocienski has thus reported that while epoxidation of allylic sulfone 74 with MCPBA in CH2CI2 at room temperature afforded the expected product 75, epoxidation in the presence of two equivalents of NaHCOj afforded the isomeric j ,y-epoxysulfone 77. Similar results were obtained with other a-mono- or di-substituted sulfones. On the other hand, the reaction of y-substituted allylic sulfones results in the isomerization of the double bond, only. The following addition-elimination free radical chain mechanism has been suggested (equations 45, 46). In a closely related and simultaneously published investigation, Whitham and coworkers reported the 1,3-rearrangement of a number of acyclic and cyclic allylic p-tolyl sulfones on treatment with either benzoyl peroxide in CCI4 under reflux or with... 

In most cases, pentasubstituted products have not been obtained. Also, with primary amines, the actual isolation of the tris- substituted derivatives has remained rare. 

Firstly, the electronic effect of the substituents would be a dominant factor in the determination of the thermal stability of the thiepins. Thermal stability was found to decrease sharply with decreasing substitution. For example, the tri-substituted benzo-[6]thiepin (16 d) extrudes sulfur only when heated while the non-substituted benzo[ >]-thiepin (4) is readily converted into naphthalene and sulfur at 40 °C with a half-life of 80 min 41 >. 

And finally, Structure 5.2 and Spectrum 5.8 show a classic example of a 1,2,4 tri-substituted benzene ring, (a well known anti-asthma drug, salbutamol). Obviously, the scope for variation in these systems is vast ... 

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