Aldehydes, preparation from primary

Amidals with a single /i-substituent prepared from primary amides and aldehydes eliminated an equivalent of an amide upon heating to form the enamides642 (equation 47). 

Unsymmetrical secondary amines are readily prepared in good yields by the catalytic reduction of Schiff bases at moderate temperatures in high-or low-pressure equipment. Many examples have been cited. The intermediate imines are prepared from primary amines and aldehydes—very seldom from ketones—and may be used without isolation (cf. method 431). For the preparation of aliphatic amines, e.g., ethyl-w-propylamine and n-butylisoamylamine, a prereduced platinum oxide catalyst is preferred with alcohol as the solvent. Schiff bases from the condensation of aromatic aldehydes with either aromatic or aliphatic amines are more readily prepared and are reduced over a nickel catalyst. In this manner, a large number of N-alkylbenzylamines having halo, hydroxyl, or methoxyl groups on the nucleus have been made. Reductions by means of sodium and alcohol and lithium aluminum hydride have also been described,... 

Methiodide derivatives of 2-alkyl-l-benzyl-2-imidazolines are central to a synthetic route to a-branched ketones (Scheme 3). The addition to the imi-dazolinium salt is sensitive to the nature of the nucleophile, only Grignard reagents prepared from primary alkyl halides giving useful yields. Attempts to reduce the salts, to afford a method for synthesis of aldehydes, virere not successful. 

The alkylation of 3-bromothiophen by allylic alcohols in the presence of Pd(OAc)2 has been studied. Thus, 2-methyl-5-(3-thienyl)pentan-3-one is the major product from reaction between 3-bromothiophen, CH2=CH-CH(OH)CHMe2, Pd(OAc)2, Nal, NaHCOa, and PhsP in HMPT at 130 °C for 8 h. Thienyl aldehydes are similarly prepared from primary alcohols. ... 

The Dess-Martin periodinane ( DMP ) reagent, U,l-tris(acetyloxy)-l,l-dihydro-l,2-benziodoxol-3(l//)-one, has also been used in several complex syntheses for the oxidation of primary or secondary alcohols to aldehydes or ketones, respectively (e.g., M. Nakatsuka, 1990). It is prepared from 2-iodobenzoic add by oxidation with bromic add and acetylation (D.a Dess, 1983). 

Higher nitroalkanes are prepared from lower primary nitroalkanes by a one-pot synthesis (69). Successive condensations with aldehydes and acylating agents are followed by reduction with sodium borohydride. Overall conversions in the 75—80% range are reported. 

Method G Highruiri-selecdvity is also observed in the fluoride-catalyzed reacdonof silyl nitronates v/ith aldehydes. Trialkyl silyl nitronates are prepared in good yield from primary nitroalkanes by consecndve treatment v/ith iithiiim dusopropylamide and trialkylsilyl chloride at -78 C in THF. 

Because the olefin geometry in compound 9 will most certainly have a bearing on the stereochemical outcome of the hydroboration step, a reliable process for the construction of the trans trisubsti-tuted olefin in 9 must be identified. A priori, the powerful and predictable Wittig reaction28 could be used to construct E u, [3-unsaturated ester 10 from aldehyde 11. Reduction of the ethoxycarbonyl grouping in 10, followed by benzylation of the resulting primary alcohol, would then complete the synthesis of 9. Aldehyde 11 is a known substance that can be prepared from 2-furylacetonitrile (12). 

The imines are prepared by 16-12. The enamine salt method has also been used to give good yields of mono a alkylation of a,P-unsaturated ketones. Enamines prepared from aldehydes and butylisobutylamine can be alkylated by simple primary alkyl halides in good yields. N-alkylation in this case is presumably prevented by steric hindrance. 

This is the most common method for the preparation of enamines and usually takes place when an aldehyde or ketone containing an a hydrogen is treated with a secondary amine. The water is usually removed azeotropically or with a drying agent, but molecular sieves can also be used. Stable primary enamines have also been prepared.Enamino-ketones have been prepared from diketones and secondary amines using microwave irradiation on silica gel. ° Secondary amine perchlorates react with aldehydes and ketones to give iminium salts (2, p. 1178). Tertiary amines can only give salts (12). 

Primary amines have been prepared from many aldehydes with at least five carbons and from many ketones by treatment with ammonia and a reducing agent. 

For the addition of an organometailic compound to an imine to give a primary amine, R in RCH=NR would have to be H, and such compounds are seldom stable. However, the conversion has been done, for R = aryl, by the use of the masked reagents (ArCH=N)2S02 [prepared from an aldehyde RCHO and sulfamide (NH2)2S02]. Addition of R"MgX or R"Li to these compounds gives ArCHR"NH2 after hydrolysis. ... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

In general, an aldimine is among the least reactive carbonyl compounds and is by far less reactive than an aldehyde [31-33]. Nevertheless, the Et2Zn-Ni catalytic system is successfully extended to the homoallylation of aldimine. Aldimine prepared in situ from an aldehyde and a primary aromatic amine undergoes the homoallylation smoothly under the essentially identical con-... 

Perhaps the most important recent discovery in catalytic oxidation of alcohols is the use of a catalyst prepared from [Pd(OAc)2] and sulfonated batophenanthroline (see Scheme 8.1 above). This catalyst was found to oxidize primary and secondary, as well as benzylic and allylic alcohols with close to quantitative yields and 90-100 % select vities to the corresponding aldehydes or ketones (Scheme 8.4) [18]. The easy oxidation of non-activated secondary alcohols is particularly noteworthy since in general these are rather unreactive towards O2. 

B. General Oxidation Procedure for Alcohols. A sufficient quantity of a 5% solution of dipyridine chromium (VI) oxide (Note 1) in anhydrous dichloromethane (Note 7) is prepared to provide a sixfold molar ratio of complex to alcohol. This excess is usually required for complete oxidation to the aldehyde. The freshly prepared, pure complex dissolves completely in dichloromethane at 25° at 5% concentration to give a deep red solution, but solutions usually contain small amounts of brown, insoluble material when prepared from crude complex (Note 8). The alcohol, either pure or as a solution in anhydrous methylene chloride, is added to the red solution in one portion with stirring at room temperature or lower. The oxidation of unhindered primary (and secondary) alcohols proceeds to completion within 5 minutes to 15 minutes at 25° with deposition of brownish-black, polymeric, reduced chromium-pyridine products (Note 9). When deposition of reduced chromium compounds is complete (monitoring the reaction by gas chromatography or thin-layer chromatography analysis is helpful), the supernatant liquid is decanted from the (usually tarry) precipitate and the precipitate is rinsed thoroughly with dichloromethane (Note 10). 

Amino-1-fluoro-propylidence)-cyclopentanecarbonitriles (55), i//[CF=C] iso-stere of 2-cyanopyrrolidides, were prepared from 56, an intermediate in the synthesis of 50 (Scheme 19) [65]. A better route was conversion of the primary alcohol (58), another intermediate in the synthesis of 50, to the aldehyde (59) through Swern oxidation followed by treatment with hydroxylamine-O-sulfonicacid (Scheme 10). Both pairs of diastereomer u-55 and 1-55 exhibited inhibitory activity against DPP IV. u-55 and 1-55 also were very stable in buffer (pH 7.6) as assessed by UV-vis spectroscopy over the range of 190-1,100 nm at 30 and 50°C (Scheme 20). 

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