Benzene with aldehydes

This same oxidation level situation - a disubstituted benzene with aldehyde (ketone) ortho to carbinol ready for cyclisation and dehydration to an isobenzofuran - can be achieved in alternative ways phthalaldehyde can be mono-acetalised, then the remaining aldehyde reduced, or lithiation technology can be utilised, as shown below. 

Reactions with Sahcylaldehydes. Tetraalkyl titanates react in benzene with sahcylaldehyde in a 1 1 or 1 2 molar ratio to give sahcylaldehydotrialkoxy and dialkoxy products, which when heated at reflux seem to undergo a Meewein-Pomidorf reaction to give an aldehyde derived from the alcohol group on the titanate and a reduced titanate complex (37) ... 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

However, addition of (+ )-(7 )-l-methyl-4-(mcthylsulfinyl)benzene, to aldehydes and ketones proceeds with low stereoselectivity. An improvement of the 3-syn diaslereoselectivity was found with the zinc reagent obtained by transmetalation of the lithiated sulfoxide with anhydrous zinc chloride38. An improvement of the stereoselectivity was also attained by exchange of the 4-methylphenyl substituent for a 2-methoxyphenyl or 2-pyridinyl substituent. Thus, the introduction of an additional complexing site into the aromatic part of the sulfoxide reagent enhances the stereoselectivity35. 

On reaction of N-thioformylphenylhydrazine 1533 with aldehydes such as benz-aldehyde (or ketones such as acetophenone) in the presence of TCS 14 in benzene 2,3-dihydro-l,3,4-thiadiazoles such as 1535 are formed in high yields via 1534 [65, 66] (Scheme 9.36). 

Sulphated zirconia catalysts can be acidic or superacidic depending on the method of treatment. A variety of acid-catalysed reactions, referred to earlier in this section, can be carried out with sulphated zirconia. Yadav and Nair (1999) have given a state-of-the art review on this subject. Examples of benzylation of benzene with benzyl chloride / benzyl alcohol, alkylation of o-xylene with. styrene, alkylation of diphenyl oxide with 1-dodecene, isomerization of epoxides to aldehydes, acylation of benzene / chlorobenzene with p-chloro benzoylchloride, etc. are covered in the review. 

A very attractive anionic/anionic/pericyclic/anionic fourfold domino sequence was developed by Kuehne s group, as illustrated in Scheme 2.147 [336]. Herein, on treatment of the enantiopure tryptophane-derived diester 2-644 with a, 3-unsatu-rated aldehydes 2-645 at 70 °C in benzene with benzoic acid and freshly activated... 

In all cases, mixtures of cis and trans diastereoisomers are reported. In terms of experimental observation, it is now possible to prepare 1,3-disubstituted tetrahydro-j8-carbolines and 1-substituted tetrahydro-/3-carbolines of known absolute stereochemistry. For example, if optically active A -benzyltryptophan methyl ester of known chirality reacts with aldehydes in refluxing benzene, the trans derivative is obtained. Arylglycidate was also used in the synthesis instead of aldehydes (78CPB2305). 

The liquid-phase oxidation of acrolein (AL), the reaction products, their routes of formation, reaction in the absence or presence of catalysts such as acetylacetonates (acac) and naphthenates (nap) of transition metals and the influence of reaction factors were discussed in an earlier paper (22). The coordinating state of cobalt acetylacetonate in the earlier stage of the reaction depends on the method of addition to the reaction system (25, 26). The catalyst, Co(acac)2-H20-acrolein, which was synthesized by mixing a solution of Co(acac)2 in benzene with a saturated aqueous solution, decreases the induction period of oxygen uptake and increases the rate of oxygen absorption. The acrolein of the catalyst coordinated with its cobalt through the lone pair of electrons of the aldehyde oxygen. Therefore, it is believed that the coordination of acrolein with a catalyst is necessary to initiate the oxidation reaction (10). 

Oxidative coupling of benzenes with , p- unsaturated aldehydes by... 

OXIDATIVE COUPLING OF BENZENES WITH a, fi- UNSATURATED ALDEHYDES BY Pd(OAc)2/HPMoV /O2 SYSTEM... 

Like their sulfur counterparts (Section 3.2.4.4.2.), 1 -lithiocyclopropyl selenides 1, as generated by reductive lithiation of bis(selanyl)cyclopropanes 173 with butyllithium in diethyl ether or tetrahydrofuran, react with aldehydes or ketones to give /Lhydroxy selenides 2, which rearrange to cyclobutanones 3 on treatment with p-toluenesulfonic acid in wet benzene.174 175 The method was used in a total synthesis of a-cuparenone.175... 

Isomerization of aifyl ethersAllyl ethers (and methallyl ethers) are isomerized to 1-propenyl ethers when refluxed in benzene with palladium on carbon (4-140 hours). The reaction is compatible with various functional groups (epoxide, aldehyde, hydroxyl). Isolated yields are about 80%. 

Fisher indole synthesis.1 2,3-Disubstituted indoles are formed in 70-90% yield when a ketone phenylhydrazone is treated in benzene with PC13 at 25°. The same indoles are formed when the ketone and phenylhydrazine are treated with PC13. PC15 is less satisfactory than PC13. The method is not applicable to aldehydes. 

Treatment of lithiated (41) with aldehydes (42a-c) at -78 °C and then at room temperature gives the corresponding alcohols (43a-c) in yields up to 80%. When (43a-c) were refluxed in benzene containing a catalytic amount of p-toluenesulfonic acid the 2-substituted furans (44a-c) were formed in good yields. Various 2,3-disubstituted furans were readily prepared by combination of the synthetic methods for 2- and 3-substituted furans (Scheme 9). The synthetic utility of this route is illustrated by the preparation of 2-(3,7-dimethyl-2,6-heptadienyl-3-methylfuran (47), which is a typical 2,3-disubstituted furan occurring in nature, starting from the aldehyde (46) and the acetal (45) (Scheme 10). Table 1 summarizes the 2,3-disubstituted furans synthesized by this route. However, attempts to extend the method to the preparation of 3-acylfurans (48) was unsuccessful because of the formation of the vinyl sulfone (49) via deacylation. 

One of the oldest known thermosetting synthetic polymers is made by condensation of phenols with aldehydes using basic catalysts. The resins that are formed are known as Bakelites. The initial stage is the base-induced reaction of benzenol and methanal to give a (4-hydroxyphenyl)methanol, and this reaction closely resembles an aldol addition and can take place at either the 2-or the 4-position of the benzene ring ... 

The arylation of acetaldehyde enolate by iodobenzene17-128 or p-iodoaniline73 failed, and the reduced products, benzene or aniline were obtained. In the reaction of aldehyde enolates with o-substituted derivatives, however, arylation does occur and in these cases subsequent cyclization reactions usually take place (see Section 2.2.4.2). The special effect of the o-substituents in facilitating reactions with aldehyde enolates is shown by the rare example of simple substitution (i.e. without concomitant cyclization) in equation (34).71... 

Cyclocondensation of dioxygenated 1,3-dienes with aldehydes. In the presence of ZnCl2 in benzene or BP3 etherate in ether, this diene 1 undergoes cyclization with a wide variety of aldehydes to afford 2,3-dihydro-y-pyrones (equation I). The products... 

In basic chemicals, nitrile hydratase and nitrilases have been most successful. Acrylamide from acrylonitrile is now a 30 000 tpy process. In a product tree starting from the addition of HCN to butadiene, nicotinamide (from 3-cyanopyridine, for animal feed), 5-cyanovaleramide (from adiponitrile, for herbicide precursor), and 4-cyanopentanoic acid (from 2-methylglutaronitrile, for l,5-dimethyl-2-piperidone solvent) have been developed. Both the enantioselective addition of HCN to aldehydes with oxynitrilase and the dihydroxylation of substituted benzenes with toluene (or naphthalene) dioxygenase, which are far superior to chemical routes, open up pathways to amino and hydroxy acids, amino alcohols, and diamines in the first case and alkaloids, prostaglandins, and carbohydrate derivatives in the second case. 

Trisubstituted allylic alcohols. A low-valent tantalum prepared by reduction of TaCIs with Zn in DME/benzene adds to alkynes to form a complex that reacts with aldehydes to form (E)-allylic alcohols. The regioselectivity is determined by the bulkiness of the groups on the alkyne and of the R group of the aldehyde. 

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