Alcohols, general condensation

We said esters are condensation products between carboxylic acids and alcohols, but this definition is really too restrictive. In the most general sense, an ester is the condensation product between an alcohol and an acid, not just a carboxylic acid. We saw an example of a nitrate ester earlier in the structure of nitroglycerin. In biochemistry, phosphate esters are one of the most important classes of esters. A phosphate ester is derived from an alcohol and phosphoric acid (H3P04). Again, the acid and alcohol are condensed (under special reaction conditions) to give the ester and a molecule of water. This is shown in Figure 11.53. Phosphate esters form the backbone of DNA and RNA. 

To synthesize a large amount of enantiopure chiral MaNP acid (3), the facile synthesis and enantioresolution of racemic acid 3 were carried out as shown in Fig. 9.9. In general, for enantioresolution of carboxylic acids, chiral synthetic amines or alkaloids have been used. However, we have adopted the following novel strategy using chiral alcohols chiral alcohols are condensed with racemic acid 3 and the diastereomeric esters formed are separated by HPLC on silica gel. 

The most widely used enzymatic bioconversion used in the flavor industry is the condensation of natural acids (generally acetic or other short chain acids) and alcohols (generally ethanol or fusel alcohols) to yield a wide range of esters. It is recognized that enzymes typically are reversible and thus, lipases (or esterases) normally associated with the hydrolysis of esters, can be used to synthesize esters under certain conditions. 

General Synthesis.—High yields of esters are obtained when tri-n-butylstannyl derivatives of alcohols are condensed with aldehydes, and the products treated with A-bromosuccinimide (Scheme 27). In the absence of an aldehyde, dimeric esters (109) are produced via oxidation of the alcohol derivative to the corresponding aldehyde (or ketone), which then condenses as shown. 

PA is a metabolic intermediate in the biosynthetic/degradation pathways of more complex glycerophospholipids. It usually represents less than 1% of total membrane lipids but plays a critical role in signal transduction, due to the xmique ionization properties of its phosphate group (see Chapter 3). Membrane glycerophospholipids are derived from PA by condensation with an organic alcohol (general formula X-OH). Phosphatidylcholine (PC), the most abundant membrane lipid, results from the condensation of choline with PA (Fig. 1.14). 

This preparation was discovered independently by Geuther (1863) and by Frankland and Duppa (1865). The reaction was subsequently investigated in detail and so w idely extended by Claisen that it has become solely a specific example of the more general process known as the Claisen Condensation. Claisen showed that an ester under the influence of sodium ethoxide would not only condense with itself (as in the preparation of ethyl acetoacetate), but also with (i) another ester, (ii) a ketone, if of formula RCHgCOR, (iii) a nitrile, if of formula RCH CN, in each case with the elimination of alcohol. Examples of these modifications are ... 

Knoevenagel reaction. The condensation of an aldehyde with an active methylene compound (usually malonic acid or its derivatives) in the presence of a base is generally called the Knoevenagel reaction. Knoevenagel found that condensations between aldehydes and malonic acid are effectively catalysed by ammonia and by primary and secondary amines in alcoholic solution of the organic amines piperidine was regarded as the best catalyst. 

GENERAL PROCEDURE The Alcoholic alkaline solution is prepared by prolonged stirring of 8.8g (or 4.4g) of KOH pellets in 30mL of alcohol. The alkaline solution is placed in a round-bottom flask provided with a reflux condenser (microwave or conventional systems). Then 4.0g of Safrole (or eugenol) is added and the solution heated."... 

Ary] 2-amino-5-(p-aminophenyl)thia2oles of the general formula 116 were prepared by condensing phenylthiosemicarbazides (115) with either w-bromoacetophenone by refluxing in alcohol for 2 hr (Method A) or with acetophenones and iodine on a steam bath for 8 hr (Method B) Scheme 53 (517), with R = para Me, MeO, Cl, Br, I, NOj, NHj, Ph ortho Me, NOjl or meta Br, I, NO. Yields ranged from 55 to 90% from Method A and 40 to 70% from Method B. 

Manufacturing procedures for producing dye dispersions are generally not disclosed. The principal dispersants in use include long-chain alkyl sulfates, alkaryl sulfonates, fatty amine—ethylene oxide condensates, fatty alcohol—ethylene oxide condensates, naphthalene—formaldehyde—sulfuric acid condensates, and the lignin sulfonic acids. 

Medium Boiling Esters. Esterificatioa of ethyl and propyl alcohols, ethylene glycol, and glycerol with various acids, eg, chloro- or bromoacetic, or pymvic, by the use of a third component such as bensene, toluene, hexane, cyclohexane, or carbon tetrachloride to remove the water produced is quite common. Bensene has been used as a co-solvent ia the preparatioa of methyl pymvate from pymvic acid (101). The preparatioa of ethyl lactate is described as an example of the general procedure (102). A mixture of 1 mol 80% lactic acid and 2.3 mol 95% ethyl alcohol is added to a volume of benzene equal to half that of the alcohol (ca 43 mL), and the resulting mixture is refluxed for several hours. When distilled, the overhead condensate separates iato layers. The lower layer is extracted to recover the benzene and alcohol, and the water is discarded. The upper layer is returned to the column for reflux. After all the water is removed from the reaction mixture, the excess of alcohol and benzene is removed by distillation, and the ester is fractionated to isolate the pure ester. 

The general definition of a condensation reaction is a one that involves product formation by expulsion of water (or other small molecule) as a by-product. By this definition, activation and methylolation are also condensations. In more precise terms the chain-building process should be described as a condensation polymerization, however, in the jargon of the phenolics industry, the term condensation is usually reserved for the chain-building process. This terminology is not necessarily observed in the literature [88]. Many literature reports correctly refer to methylolation as a condensation reaction. The molecular weight development of the phenol alcohol adducts may also be classified as a step-polymerization. 

Aldehydes and ketones with an a hydrogen atom undergo a base-catalyzed carbonyl condensation reaction called the aldol reaction. For example, treatment of acetaldehyde with a base such as sodium ethoxide or sodium hydroxide in a protic solvent leads to rapid and reversible formation of 3-hydroxybutanal, known commonly as aldol (aidehyde + alcohol), hence the general name of the reaction. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

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